Major histocompatibility complex class III gene family
MHC class III region encodes for other immune components, such as complement components (e.g., C2, C4, factor B) and some that encode cytokines (e.g., TNF-) and also HSPs. They are mainly known from their genes because their gene cluster is present between those of class I and class II. The gene cluster was discovered in between class I and class II genes on the short (p) arm  of human chromosome 6. It was later found that it contains many genes for different signalling molecules such as tumour necrosis factors (TNFs) and heat shock proteins. More than 60 MHC class III genes are described, which is about 28% of the total MHC genes (224).
MHC class III genes are located on chromosome 6 (6p21.3) in humans. It covers 700 kb and contains 61 genes. The gene cluster is the most gene-dense region of the human genome. They are basically similar with those of other animals. The functions of many genes are yet unknown. Many retroelements such as human endogenous retrovirus (HERV) and Alu elements are located in the cluster. The region containing genes G11/C4/Z/CYP21/X/Y, varying in size from 142 to 214 kb, is known as the most complex gene cluster in the human genome.
MHC class III genes are similar in humans, mouse, frog (Xenopus tropicalis), and gray short-tailed opossum, but not all genes are common. For example, human NCR3, MIC and MCCD1 are absent in mouse. Human NCR3 and LST1 are absent in opossum. However, birds (chicken and quail) have only a single gene, which codes for a complement component gene (C4). In fishes, the genes are distributed in different chromosomes.

# Major histocompatibility complex class III genes
Gene ID: 177 is AGER advanced glycosylation end-product specific receptor on 6p21.32: "The advanced glycosylation end product (AGE) receptor encoded by this gene is a member of the immunoglobulin superfamily of cell surface receptors. It is a multiligand receptor, and besides AGE, interacts with other molecules implicated in homeostasis, development, and inflammation, and certain diseases, such as diabetes and Alzheimer's disease. Many alternatively spliced transcript variants encoding different isoforms, as well as non-protein-coding variants, have been described for this gene (PMID:18089847)."
- NP_001127.1 advanced glycosylation end product-specific receptor isoform 1 precursor: "Transcript Variant: This variant (1, also known as RAGE) represents the predominant transcript, and encodes isoform 1." Conserved Domains (3) summary: smart00410 Location: 24  117 IG_like; Immunoglobulin like, pfam08205 Location: 124  219 C2-set_2; CD80-like C2-set immunoglobulin domain, and pfam13927 Location: 239  304 Ig_3; Immunoglobulin domain.
- NP_001193858.1 advanced glycosylation end product-specific receptor isoform 2 precursor: "Transcript Variant: This variant (2, also known as RAGE_v5) uses an alternate in-frame donor splice site at an internal coding exon compared to variant 1. This results in a longer isoform (2) containing an additional protein segment compared to isoform 1." Conserved Domains (4) summary: cd00096 Location: 34  111 Ig; Immunoglobulin domain, smart00408 Location: 267  322 IGc2; Immunoglobulin C-2 Type, smart00410 Location: 260  331 IG_like; Immunoglobulin like, pfam08205 Location: 124  235 C2-set_2; CD80-like C2-set immunoglobulin domain.
- NP_001193861.1 advanced glycosylation end product-specific receptor isoform 3 precursor: "Transcript Variant: This variant (3, also known as RAGE_v4) uses alternate in-frame acceptor and donor splice sites at two internal coding exons compared to variant 1. This results in a shorter isoform (2) missing two internal protein segments compared to isoform 1." Conserved Domains (4) summary: smart00408 Location: 237  292 IGc2; Immunoglobulin C-2 Type, smart00410 Location: 230  301 IG_like; Immunoglobulin like, pfam08205 Location: 110  205 C2-set_2; CD80-like C2-set immunoglobulin domain, and pfam13895 Location: 23  103 Ig_2; Immunoglobulin domain.
- NP_001193863.1 advanced glycosylation end product-specific receptor isoform 4 precursor: "Transcript Variant: This variant (4, also known as RAGE_v6) lacks the penultimate coding exon, and uses alternate donor splice sites at two internal coding exons compared to variant 1. This results in a frame-shift and a shorter isoform (4) with a distinct C-terminus compared to isoform 1." Conserved Domains (4) summary: cd00096 Location: 34  111 Ig; Immunoglobulin domain, smart00408 Location: 267  322 IGc2; Immunoglobulin C-2 Type, smart00410 Location: 260  331 IG_like; Immunoglobulin like, and pfam08205 Location: 124  235 C2-set_2; CD80-like C2-set immunoglobulin domain.
- NP_001193865.1 advanced glycosylation end product-specific receptor isoform 5 precursor: "Transcript Variant: This variant (5, also known as RAGE_v9) lacks the penultimate coding exon, and uses alternate acceptor and donor splice sites at two internal coding exons compared to variant 1. This results in a frame-shift and a shorter isoform (5) with a distinct C-terminus compared to isoform 1." Conserved Domains (4) summary: cd00096 Location: 34  111 Ig; Immunoglobulin domain, smart00408 Location: 251  275 IGc2; Immunoglobulin C-2 Type, smart00410 Location: 24  117 IG_like; Immunoglobulin like, pfam08205 Location: 124  219 C2-set_2; CD80-like C2-set immunoglobulin domain.
- NP_001193869.1 advanced glycosylation end product-specific receptor isoform 6 precursor: "Transcript Variant: This variant (6, also known as RAGE_v1) lacks the penultimate coding exon, and uses an alternate donor splice site at another coding exon compared to variant 1. This results in a frame-shift and a shorter isoform (6, also known as esRAGE and soluble RAGE) with a distinct C-terminus compared to isoform 1. This isoform lacks the transmembrane and intracellular domains, is secreted (PMID:18089847), and thought to function as a decoy receptor that inhibits RAGE signaling, and thus prevent the pathological progression of some pathologic conditions, such as Alzheimer's disease (PMID:18431028). Variants 6 and 9 encode the same isoform." Conserved Domains (4) summary: cd00096 Location: 34  111 Ig; Immunoglobulin domain, smart00408 Location: 251  306 IGc2; Immunoglobulin C-2 Type, smart00410 Location: 244  315 IG_like; Immunoglobulin like, and pfam08205 Location: 124  219 C2-set_2; CD80-like C2-set immunoglobulin domain.
- NP_001193883.1 advanced glycosylation end product-specific receptor isoform 8 precursor: "Transcript Variant: This variant (8, also known as RAGE_v8) lacks two internal coding exons, and uses an alternate donor splice site at another coding exon compared to variant 1. This results in a frame-shift, and a shorter isoform (8) with a distinct C-terminus compared to isoform 1." Conserved Domains (4) summary: cd00096 Location: 34  111 Ig; Immunoglobulin domain, smart00408 Location: 251  276 IGc2; Immunoglobulin C-2 Type, smart00410 Location: 24  117 IG_like; Immunoglobulin like, and pfam08205 Location: 124  219 C2-set_2; CD80-like C2-set immunoglobulin domain.
- NP_001193895.1 advanced glycosylation end product-specific receptor isoform 6 precursor: "Transcript Variant: This variant (9, also known as RAGE_v10) lacks the penultimate coding exon, and uses alternate splice sites at other exons at the 3' end compared to variant 1. This results in a frame-shift and a shorter isoform (6, also known as esRAGE and soluble RAGE) with a distinct C-terminus compared to isoform 1. Variants 6 and 9 encode the same isoform." Conserved Domains (4) summary: cd00096 Location: 34  111 Ig; Immunoglobulin domain, smart00408 Location: 251  306 IGc2; Immunoglobulin C-2 Type, smart00410 Location: 244  315 IG_like; Immunoglobulin like, and pfam08205 Location: 124  219 C2-set_2; CD80-like C2-set immunoglobulin domain.
- NP_751947.1 advanced glycosylation end product-specific receptor isoform 7 precursor: "Transcript Variant: This variant (7, also known as RAGE_v16) uses alternate splice sites at several internal coding exons compared to variant 1. This results in a frame-shift and a shorter isoform (7, also known as hRAGEsec) with a distinct C-terminus compared to isoform 1." Conserved Domains (4) summary: smart00410 Location: 24  103 IG_like; Immunoglobulin like, pfam08205 Location: 110  205 C2-set_2; CD80-like C2-set immunoglobulin domain, pfam13895 Location: 23  103 Ig_2; Immunoglobulin domain, and cl11960 Location: 237  260 Ig; Immunoglobulin domain.
- XP_016865817.1 advanced glycosylation end product-specific receptor isoform X1, Conserved Domains (4) summary: smart00408 Location: 298  323 IGc2; Immunoglobulin C-2 Type, smart00410 Location: 55  148 IG_like; Immunoglobulin like, pfam08205 Location: 155  266 C2-set_2; CD80-like C2-set immunoglobulin domain, and pfam13895 Location: 54  148 Ig_2; Immunoglobulin domain.
Gene ID: 578 is BAK1 BCL2 antagonist/killer 1 on 6p21.31: "The protein encoded by this gene belongs to the BCL2 protein family. BCL2 family members form oligomers or heterodimers and act as anti- or pro-apoptotic regulators that are involved in a wide variety of cellular activities. This protein localizes to mitochondria, and functions to induce apoptosis. It interacts with and accelerates the opening of the mitochondrial voltage-dependent anion channel, which leads to a loss in membrane potential and the release of cytochrome c. This protein also interacts with the tumor suppressor P53 after exposure to cell stress."
Gene ID: 629 is CFB complement factor B on 6p21.33: "This gene encodes complement factor B, a component of the alternative pathway of complement activation. Factor B circulates in the blood as a single chain polypeptide. Upon activation of the alternative pathway, it is cleaved by complement factor D yielding the noncatalytic chain Ba and the catalytic subunit Bb. The active subunit Bb is a serine protease which associates with C3b to form the alternative pathway C3 convertase. Bb is involved in the proliferation of preactivated B lymphocytes, while Ba inhibits their proliferation. This gene localizes to the major histocompatibility complex (MHC) class III region on chromosome 6. This cluster includes several genes involved in regulation of the immune reaction. Polymorphisms in this gene are associated with a reduced risk of age-related macular degeneration. The polyadenylation site of this gene is 421 bp from the 5' end of the gene for complement component 2."
- NP_001701.2 complement factor B preproprotein.
Gene ID: 717 is C2 complement C2 on 6p21.33: "Component C2 is a serum glycoprotein that functions as part of the classical pathway of the complement system. Activated C1 cleaves C2 into C2a and C2b. The serine proteinase C2a then combines with complement factor 4b to create the C3 or C5 convertase. Deficiency of C2 has been reported to associated with certain autoimmune diseases and SNPs in this gene have been associated with altered susceptibility to age-related macular degeneration. This gene localizes within the class III region of the MHC on the short arm of chromosome 6. Alternative splicing results in multiple transcript variants encoding distinct isoforms. Additional transcript variants have been described in publications but their full-length sequence has not been determined."
- NP_000054.2 complement C2 isoform 1 preproprotein: "Transcript Variant: This variant (1) encodes the longest isoform (1)."
- NP_001139375.1 complement C2 isoform 2 precursor: "Transcript Variant: This variant (2) lacks two in-frame exons in the 5' coding region, compared to variant 1, that results in an isoform (2) with a shorter N-terminus that lacks one of two SUSHI repeat domains, compared to isoform 1."
- NP_001171534.1 complement C2 isoform 3: "Transcript Variant: This variant (3) has an alternate 5' sequence and lacks an in-frame internal segment, as compared to variant 1. The resulting isoform (3) is shorter; it has a distinct N-terminus and lacks an internal segment, as compared to isoform 1."
- NP_001269386.1 complement C2 isoform 4: "Transcript Variant: This variant (4) represents use of an alternate promoter and has multiple differences in the coding region compared to variant 1. The resulting protein (isoform 4) has a distinct N-terminus and is shorter than isoform 1."
- NP_001269387.1 complement C2 isoform 5: "Transcript Variant: This variant (5) differs in the 5' UTR, lacks a portion of the 5' coding region, and initiates translation at an alternate start codon, compared to variant 1. The encoded isoform (5) has a shorter and distinct N-terminus compared to isoform 1."
- NP_001269388.1 complement C2 isoform 6 precursor: "Transcript Variant: This variant (6) uses an alternate 3' exon structure, and thus differs in the 3' coding region and 3' UTR compared to variant 1. It encodes isoform 6 which is shorter and has a distinct C-terminus, compared to isoform 1."
Gene ID: 720 is C4A complement C4A (Rodgers blood group) aka MHC class III region complement on 6p21.33: "This gene encodes the acidic form of complement factor 4, part of the classical activation pathway. The protein is expressed as a single chain precursor which is proteolytically cleaved into a trimer of alpha, beta, and gamma chains prior to secretion. The trimer provides a surface for interaction between the antigen-antibody complex and other complement components. The alpha chain is cleaved to release C4 anaphylatoxin, an antimicrobial peptide and a mediator of local inflammation. Deficiency of this protein is associated with systemic lupus erythematosus and type I diabetes mellitus. This gene localizes to the major histocompatibility complex (MHC) class III region on chromosome 6. Varying haplotypes of this gene cluster exist, such that individuals may have 1, 2, or 3 copies of this gene. Two transcript variants encoding different isoforms have been found for this gene."
- NP_001239133.1 complement C4-A isoform 2 preproprotein: "Transcript Variant: This variant (2) lacks an alternate in-frame segment compared to variant 1. The resulting isoform (2) has the same N- and C-termini but is shorter compared to isoform 1."
- NP_009224.2 complement C4-A isoform 1 preproprotein: "Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1)."
Gene ID: 721 is C4B complement C4B (Chido blood group) on 6p21.33: "This gene encodes the basic form of complement factor 4, part of the classical activation pathway. The protein is expressed as a single chain precursor which is proteolytically cleaved into a trimer of alpha, beta, and gamma chains prior to secretion. The trimer provides a surface for interaction between the antigen-antibody complex and other complement components. The alpha chain may be cleaved to release C4 anaphylatoxin, a mediator of local inflammation. Deficiency of this protein is associated with systemic lupus erythematosus. This gene localizes to the major histocompatibility complex (MHC) class III region on chromosome 6. Varying haplotypes of this gene cluster exist, such that individuals may have 1, 2, or 3 copies of this gene. In addition, this gene exists as a long form and a short form due to the presence or absence of a 6.4 kb endogenous HERV-K retrovirus in intron 9."
- NP_001002029.3 complement C4-B preproprotein.
Gene ID: 780 is DDR1 discoidin domain receptor tyrosine kinase 1 on 6p21.33: "Receptor tyrosine kinases play a key role in the communication of cells with their microenvironment. These kinases are involved in the regulation of cell growth, differentiation and metabolism. The protein encoded by this gene belongs to a subfamily of tyrosine kinase receptors with homology to Dictyostelium discoideum protein discoidin I in their extracellular domain, and that are activated by various types of collagen. Expression of this protein is restricted to epithelial cells, particularly in the kidney, lung, gastrointestinal tract, and brain. In addition, it has been shown to be significantly overexpressed in several human tumors. Alternatively spliced transcript variants encoding different isoforms have been described for this gene."
- NP_001189450.1 epithelial discoidin domain-containing receptor 1 isoform 4 precursor: "Transcript Variant: This variant (4) is missing an internal coding exon compared to variant 1. This results in a frame-shift, and early translation termination, rendering this transcript a candidate for nonsense-mediated mRNA decay (NMD). However, the encoded isoform (4, also known as DDR1d) is represented as it has been detected in vivo in several colon carcinoma cell lines (PMID:11344127). This isoform is truncated and lacks the catalytic tyrosine kinase domain, therefore, most likely lacks intrinsic tyrosine kinase activity. It may function in some other regulatory capacity."
- NP_001189451.1 epithelial discoidin domain-containing receptor 1 isoform 5 precursor: "Transcript Variant: This variant (5) is missing an internal coding exon, and uses an alternate acceptor splice site at one of the coding exons compared to variant 1. This results in localized frame-shift, and a shorter isoform (5, also known as DDR1e) compared to isoform 1. This isoform lacks the ATP binding site, therefore, most likely lacks intrinsic tyrosine kinase activity. It may function in some other regulatory capacity."
- NP_001189452.1 epithelial discoidin domain-containing receptor 1 isoform 6 precursor: "Transcript Variant: This variant (6) contains an alternate 5' terminal exon compared to variant 1. This results in translation initiation from an in-frame upstream start codon, and a longer isoform (6) with a distinct N-terminus compared to isoform 1."
- NP_001284581.1 epithelial discoidin domain-containing receptor 1 isoform 1 precursor: "Transcript Variant: This variant (7) differs in the 5' UTR compared to variant 1. It encodes isoform 1 (also known as DDR1a). Variants 1, 7, and 8 encode the same isoform (1)."
- NP_001284582.1 epithelial discoidin domain-containing receptor 1 isoform 1 precursor: "Transcript Variant: This variant (8) differs in the 5' UTR compared to variant 1. It encodes isoform 1 (also known as DDR1a). Variants 1, 7, and 8 encode the same isoform (1)."
- NP_001284583.1 epithelial discoidin domain-containing receptor 1 isoform 2 precursor: "Transcript Variant: This variant (9) contains an additional in-frame coding exon and differs in the 5' UTR compared to variant 1, resulting in a longer isoform (2, also known as DDR1b) with a 37 aa protein segment not found in isoform 1. Variants 2 and 9 encode the same isoform (2)."
- NP_001945.3 epithelial discoidin domain-containing receptor 1 isoform 1 precursor: "Transcript Variant: This variant (1) represents the predominant transcript, and encodes isoform 1 (also known as DDR1a). Variants 1, 7, and 8 encode the same isoform (1)."
- NP_054699.2 epithelial discoidin domain-containing receptor 1 isoform 2 precursor: "Transcript Variant: This variant (2) contains an additional in-frame coding exon compared to variant 1, resulting in a longer isoform (2, also known as DDR1b) with a 37 aa protein segment not found in isoform 1. Variants 2 and 9 encode the same isoform (2)."
- NP_054700.2 epithelial discoidin domain-containing receptor 1 isoform 3 precursor: "Transcript Variant: This variant (3) contains an additional in-frame coding exon, and uses an alternate in-frame acceptor splice site at one of the coding exons compared to variant 1. This results in the longest isoform (3, also known as DDR1c) with additional protein segments not found in isoform 1."
Gene ID: 1041 is CDSN corneodesmosin on 6p21.33: "This gene encodes a protein found in corneodesmosomes, which localize to human epidermis and other cornified squamous epithelia. The encoded protein undergoes a series of cleavages during corneocyte maturation. This gene is highly polymorphic in human populations, and variation has been associated with skin diseases such as psoriasis, hypotrichosis and peeling skin syndrome. The gene is located in the major histocompatibility complex (MHC) class I region on chromosome 6."
- NP_001255.4 corneodesmosin precursor.
Gene ID: 1192 is CLIC1 chloride intracellular channel 1 on 6p21.33: "Chloride channels are a diverse group of proteins that regulate fundamental cellular processes including stabilization of cell membrane potential, transepithelial transport, maintenance of intracellular pH, and regulation of cell volume. Chloride intracellular channel 1 is a member of the p64 family; the protein localizes principally to the cell nucleus and exhibits both nuclear and plasma membrane chloride ion channel activity."
- NP_001274522.1 chloride intracellular channel protein 1: "Transcript Variant: This variant (1) represents the longest transcript. Variants 1, 2 and 3 encode the same protein."
- NP_001274523.1 chloride intracellular channel protein 1: "Transcript Variant: This variant (3) has an alternate exon in the 5' UTR compared to variant 1. Variants 1, 2 and 3 encode the same protein."
- NP_001279.2 chloride intracellular channel protein 1: "Transcript Variant: This variant (2) has an alternate exon in the 5' UTR compared to variant 1. Variants 1, 2 and 3 encode the same protein."
Gene ID: 1432 is MAPK14 mitogen-activated protein kinase 14 on 6p21.31: "The protein encoded by this gene is a member of the MAP kinase family. MAP kinases act as an integration point for multiple biochemical signals, and are involved in a wide variety of cellular processes such as proliferation, differentiation, transcription regulation and development. This kinase is activated by various environmental stresses and proinflammatory cytokines. The activation requires its phosphorylation by MAP kinase kinases (MKKs), or its autophosphorylation triggered by the interaction of MAP3K7IP1/TAB1 protein with this kinase. The substrates of this kinase include transcription regulator ATF2, MEF2C, and MAX, cell cycle regulator CDC25B, and tumor suppressor p53, which suggest the roles of this kinase in stress related transcription and cell cycle regulation, as well as in genotoxic stress response. Four alternatively spliced transcript variants of this gene encoding distinct isoforms have been reported."
- NP_001306.1 mitogen-activated protein kinase 14 isoform 1: "Transcript Variant: This variant (1) encodes the longest isoform (1)  STKc_p38alpha; Catalytic domain of the Serine/Threonine Kinase, p38alpha Mitogen-Activated Protein Kinase (also called MAPK14)."
- NP_620581.1 mitogen-activated protein kinase 14 isoform 2: "Transcript Variant: This variant (2) contains a different segment within the coding region when compared to variant 1. The translation frame remains the same, and the resulting isoform 2 has an internal segment different from that of isoform 1."
- NP_620582.1 mitogen-activated protein kinase 14 isoform 3: "Transcript Variant: This variant (3) contains a different internal segment within the coding region, and a different 3' coding region as well as a different 3' UTR, when compared to variant 1. It thus encodes an isoform that has a different internal segment, and a distinct C-terminus, as compared to isoform 1."
- NP_620583.1 mitogen-activated protein kinase 14 isoform 4: "Transcript Variant: This variant (4) contains a different internal segment when compared to variant 1. It thus encodes an isoform that has a different and shorter internal segment, as compared to isoform 1."
Gene ID: 1460 is CSNK2B casein kinase 2 beta on 6p21.33: "This gene encodes the beta subunit of casein kinase II, a ubiquitous protein kinase which regulates metabolic pathways, signal transduction, transcription, translation, and replication. The enzyme is composed of three subunits, alpha, alpha prime and beta, which form a tetrameric holoenzyme. The alpha and alpha prime subunits are catalytic, while the beta subunit serves regulatory functions. The enzyme localizes to the endoplasmic reticulum and the Golgi apparatus. Two transcript variants encoding different isoforms have been found for this gene."
- NP_001269314.1 casein kinase II subunit beta isoform 2: "Transcript Variant: This variant (2) uses an alternate in-frame splice junction in the 3' coding sequence compared to variant 1. The resulting isoform (2) has the same N- and C-termini but is shorter compared to isoform 1."
- NP_001311.3 casein kinase II subunit beta isoform 1: "Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1)."
Gene ID: 1589 is CYP21A2 cytochrome P450 family 21 subfamily A member 2 on 6p21.33: "This gene encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. This protein localizes to the endoplasmic reticulum and hydroxylates steroids at the 21 position. Its activity is required for the synthesis of steroid hormones including cortisol and aldosterone. Mutations in this gene cause congenital adrenal hyperplasia. A related pseudogene is located near this gene; gene conversion events involving the functional gene and the pseudogene are thought to account for many cases of steroid 21-hydroxylase deficiency. Two transcript variants encoding different isoforms have been found for this gene."
- NP_000491.4 steroid 21-hydroxylase isoform a: "Transcript Variant: This variant (1) encodes the longer isoform (a)."
- NP_001122062.3 steroid 21-hydroxylase isoform b: "Transcript Variant: This variant (2) lacks an alternate in-frame exon compared to variant 1. The resulting isoform (b) has the same N- and C-termini but is shorter compared to isoform a."
- NP_001355072.1  steroid 21-hydroxylase isoform c: "Transcript Variant: This variant (3), as well as variant 4, encodes isoform c."
- NP_001355073.1  steroid 21-hydroxylase isoform c: "Transcript Variant: This variant (4), as well as variant 3, encodes isoform c."
Gene ID: 1797 is DXO decapping exoribonuclease aka DOM3Z on 6p21.33: "This gene localizes to the major histocompatibility complex (MHC) class III region on chromosome 6. The function of its protein product is unknown, but its ubiquitous expression and conservation in both simple and complex eukaryotes suggests that this may be a housekeeping gene."
- NP_001358134.1 decapping and exoribonuclease protein isoform 1: "Transcript Variant: This variant (1) represents the longest transcript. Both variants 1 and 3 encode the same protein."
- NP_001358135.1 decapping and exoribonuclease protein isoform 1: "Transcript Variant: This variant (2) differs in the 5' UTR compared to variant 1. Both variants 1 and 3 encode the same protein."
- NP_005501.2 decapping and exoribonuclease protein isoform 2.
Gene ID: 2289 is FKBP5 FKBP prolyl isomerase 5 on 6p21.31: "The protein encoded by this gene is a member of the immunophilin protein family, which play a role in immunoregulation and basic cellular processes involving protein folding and trafficking. This encoded protein is a cis-trans prolyl isomerase that binds to the immunosuppressants FK506 and rapamycin. It is thought to mediate calcineurin inhibition. It also interacts functionally with mature hetero-oligomeric progesterone receptor complexes along with the 90 kDa heat shock protein and P23 protein. This gene has been found to have multiple polyadenylation sites. Alternative splicing results in multiple transcript variants."
- NP_001139247.1 peptidyl-prolyl cis-trans isomerase FKBP5 isoform 1: "Transcript Variant: This variant (2) differs in the 5' UTR compared to variant 1. Variants 1, 2 and 3 encode the same isoform (1)."
- NP_001139248.1 peptidyl-prolyl cis-trans isomerase FKBP5 isoform 1: "Transcript Variant: This variant (3) differs in the 5' UTR compared to variant 1. Variants 1, 2 and 3 encode the same isoform (1)."
- NP_001139249.1 peptidyl-prolyl cis-trans isomerase FKBP5 isoform 2: "Transcript Variant: This variant (4) has multiple differences in the coding region and 3' UTR compared to variant 1 which result in a frameshift. The resulting protein (isoform 2) is shorter and has a distinct C-terminus compared to isoform 1."
- NP_004108.1 peptidyl-prolyl cis-trans isomerase FKBP5 isoform 1: "Transcript Variant: This variant (1) represents the shortest transcript and encodes the longer isoform (1). Variants 1, 2 and 3 encode the same isoform (1)."
Gene ID: 2914 is GRM4 glutamate metabotropic receptor 4 on 6p21.31: "L-glutamate is the major excitatory neurotransmitter in the central nervous system and activates both ionotropic and metabotropic glutamate receptors. Glutamatergic neurotransmission is involved in most aspects of normal brain function and can be perturbed in many neuropathologic conditions. The metabotropic glutamate receptors are a family of G protein-coupled receptors, that have been divided into 3 groups on the basis of sequence homology, putative signal transduction mechanisms, and pharmacologic properties. Group I includes GRM1 and GRM5 and these receptors have been shown to activate phospholipase C. Group II includes GRM2 and GRM3 while Group III includes GRM4, GRM6, GRM7 and GRM8. Group II and III receptors are linked to the inhibition of the cyclic AMP cascade but differ in their agonist selectivities. Several transcript variants encoding different isoforms have been found for this gene."
- NP_000832.1 metabotropic glutamate receptor 4 isoform 1 precursor: "Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (1)."
- NP_001243738.1 metabotropic glutamate receptor 4 isoform 2: "Transcript Variant: This variant (2) differs in the 5' UTR and coding sequence, and lacks an alternate in-frame exon compared to variant 1. The resulting isoform (2) has a shorter and distinct N-terminus and lacks an alternate internal segment compared to isoform 1."
- NP_001243740.1 metabotropic glutamate receptor 4 isoform 4 precursor: "Transcript Variant: This variant (4) lacks an alternate in-frame exon compared to variant 1. The resulting isoform (4) has the same N- and C-termini but is shorter compared to isoform 1."
- NP_001243741.1 metabotropic glutamate receptor 4 isoform 5: "Transcript Variant: This variant (5) differs in the 5' UTR and coding sequence compared to variant 1. The resulting isoform (5) has a shorter and distinct N-terminus compared to isoform 1."
- NP_001243742.1 metabotropic glutamate receptor 4 isoform 6: "Transcript Variant: This variant (6) differs in the 5' UTR and coding sequence compared to variant 1. The resulting isoform (6) has a shorter and distinct N-terminus compared to isoform 1."
- NP_001269776.1 metabotropic glutamate receptor 4 isoform 8: "Transcript Variant: This variant (8) uses an alternate 5' structure and thus differs in the 5' UTR and 5' coding region compared to variant 1. These differences cause translation initiation at a downstream AUG and result in an isoform (8) with a shorter N-terminus, compared to isoform 1."
Gene ID: 4295 is MLN motilin on 6p21.31: "This gene encodes a small peptide hormone that is secreted by cells of the small intestine to regulate gastrointestinal contractions and motility. Proteolytic processing of the secreted protein produces the mature peptide and a byproduct referred to as motilin-associated peptide (MAP). Three transcript variants encoding different preproprotein isoforms but the same mature peptide have been found for this gene."
- NP_001035198.1 promotilin isoform 2 preproprotein: "Transcript Variant: This variant (2) uses an alternate in-frame splice site in the 3' coding region, compared to variant 1, resulting in a shorter preproprotein (isoform 2) but not affecting the mature peptide."
- NP_001171627.1 promotilin isoform 3 preproprotein: "Transcript Variant: This variant (3) uses an alternate in-frame splice junction at the 3' end of an exon compared to variant 1. The resulting isoform (3) has the same N- and C-termini but is shorter compared to isoform 1."
- NP_002409.1 promotilin isoform 1 preproprotein: "ranscript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (1)."
Gene ID: 4439 is MSH5 mutS homolog 5 on 6p21.33: "This gene encodes a member of the mutS family of proteins that are involved in DNA mismatch repair and meiotic recombination. This protein is similar to a Saccharomyces cerevisiae protein that participates in segregation fidelity and crossing-over events during meiosis. This protein plays a role in promoting ionizing radiation-induced apoptosis. This protein forms hetero-oligomers with another member of this family, mutS homolog 4. Polymorphisms in this gene have been linked to various human diseases, including IgA deficiency, common variable immunodeficiency, and premature ovarian failure. Alternative splicing results multiple transcript variants. Read-through transcription also exists between this gene and the downstream chromosome 6 open reading frame 26 (C6orf26) gene."
- NP_002432.1 mutS protein homolog 5 isoform c: "Transcript Variant: This variant (3) differs in the 5' UTR and uses alternate in-frame splice sites in both the central and 3' coding regions, compared to variant 1, resulting in an isoform (c) that is longer than isoform a. Both variants 3 and 4 encode the same isoform."
- NP_079535.4 mutS protein homolog 5 isoform a: "Transcript Variant: This variant (1) represents the shortest transcript and encodes the shortest isoform (a)."
- NP_751897.1 mutS protein homolog 5 isoform b: "Transcript Variant: This variant (2) uses alternate in-frame splice sites in both the central and 3' coding regions, compared to variant 1, resulting in an isoform (b) that is longer than isoform a."
- NP_751898.1 mutS protein homolog 5 isoform c: "Transcript Variant: This variant (4) uses alternate in-frame splice sites in both the central and 3' coding regions, compared to variant 1, resulting in an isoform (c) that is longer than isoform a. Both variants 3 and 4 encode the same isoform."
Gene ID: 4736 is RPL10A ribosomal protein L10a on 6p21.31: "Ribosomes, the organelles that catalyze protein synthesis, consist of a small 40S subunit and a large 60S subunit. Together these subunits are composed of 4 RNA species and approximately 80 structurally distinct proteins. This gene encodes a ribosomal protein that is a component of the 60S subunit. The protein belongs to the L1P family of ribosomal proteins. It is located in the cytoplasm. The expression of this gene is downregulated in the thymus by cyclosporin-A (CsA), an immunosuppressive drug. Studies in mice have shown that the expression of the ribosomal protein L10a gene is downregulated in neural precursor cells during development. This gene previously was referred to as NEDD6 (neural precursor cell expressed, developmentally downregulated 6), but it has been renamed RPL10A (ribosomal protein 10a). As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed through the genome."
Gene ID: 4758 is NEU1 neuraminidase 1 on 6p21.33: "The protein encoded by this gene is a lysosomal enzyme that cleaves terminal sialic acid residues from substrates such as glycoproteins and glycolipids. In the lysosome, this enzyme is part of a heterotrimeric complex together with beta-galactosidase and cathepsin A (the latter is also referred to as 'protective protein'). Mutations in this gene can lead to sialidosis, a lysosomal storage disease that can be type 1 (cherry red spot-myoclonus syndrome or normosomatic type), which is late-onset, or type 2 (the dysmorphic type), which occurs at an earlier age with increased severity."
- NP_000425.1 sialidase-1 precursor.
Gene ID: 4855 is NOTCH4 notch receptor 4 on 6p21.32: "This gene encodes a member of the NOTCH family of proteins. Members of this Type I transmembrane protein family share structural characteristics including an extracellular domain consisting of multiple epidermal growth factor-like (EGF) repeats, and an intracellular domain consisting of multiple different domain types. Notch signaling is an evolutionarily conserved intercellular signaling pathway that regulates interactions between physically adjacent cells through binding of Notch family receptors to their cognate ligands. The encoded preproprotein is proteolytically processed in the trans-Golgi network to generate two polypeptide chains that heterodimerize to form the mature cell-surface receptor. This receptor may play a role in vascular, renal and hepatic development. Mutations in this gene may be associated with schizophrenia. Alternative splicing results in multiple transcript variants, at least one of which encodes an isoform that is proteolytically processed."
- NP_004548.3 neurogenic locus notch homolog protein 4 preproprotein: "Transcript Variant: This variant (1) represents the longest transcript and encodes the protein."
Gene ID: 5460 is POU5F1 POU class 5 homeobox 1 on 6p21.33: "This gene encodes a transcription factor containing a POU homeodomain that plays a key role in embryonic development and stem cell pluripotency. Aberrant expression of this gene in adult tissues is associated with tumorigenesis. This gene can participate in a translocation with the Ewing's sarcoma gene on chromosome 21, which also leads to tumor formation. Alternative splicing, as well as usage of alternative AUG and non-AUG translation initiation codons, results in multiple isoforms. One of the AUG start codons is polymorphic in human populations. Related pseudogenes have been identified on chromosomes 1, 3, 8, 10, and 12."
- NP_001167002.1 POU domain, class 5, transcription factor 1 isoform 2: "Transcript Variant: This variant (3) differs in the 5' UTR, lacks a portion of the 5' coding region, and initiates translation at a downstream in-frame non-AUG (CUG) start codon, compared to variant 1. The resulting isoform (2, also known as OCT4B-190) is shorter at the N-terminus, compared to isoform 1. Variants 2 and 3 encode the same isoform (2). This variant may encode an additional isoform through the use of an alternative downstream AUG start codon. Use of alternate start codons and the non-AUG start codon is described in PMID:19489092."
- NP_001272915.1 POU domain, class 5, transcription factor 1 isoform 4: "Transcript Variant: This variant (4, also known as OCT4B1) contains multiple differences in the 5' UTR and the 5' coding region, compared to variant 1, and initiates translation at a downstream in-frame AUG start codon. The resulting isoform (4, also known as OCT4B-164) is shorter at the N-terminus, compared to isoform 1."
- NP_001272916.1 POU domain, class 5, transcription factor 1 isoform 3: "Transcript Variant: This variant (5, also known as OCT4B) differs in the 5' UTR, lacks a portion of the 5' coding region, and initiates translation at an alternate AUG start codon, compared to variant 1. The resulting isoform (3, also known as OCT4B-265) is shorter and has a distinct N-terminus, compared to isoform 1. This variant represents an allele of variant 2 that contains an AUG start codon that is polymorphic in human populations (see rs3130932). This variant may encode additional isoforms through the use of alternative downstream AUG and non-AUG start codons, as described in PMID:19489092."
- NP_002692.2 POU domain, class 5, transcription factor 1 isoform 1: "Transcript Variant: This variant (1, also known as OCT4A) represents the shortest transcript and encodes the longest isoform (1)."
- NP_976034.4 POU domain, class 5, transcription factor 1 isoform 2: "Transcript Variant: This variant (2, also known as OCT4B) differs in the 5' UTR, lacks a portion of the 5' coding region, and initiates translation at a downstream in-frame non-AUG (CUG) start codon, compared to variant 1. The resulting isoform (2, also known as OCT4B-190) is shorter at the N-terminus, compared to isoform 1. Variants 2 and 3 encode the same isoform (2). This variant may encode additional isoforms through the use of an alternative downstream AUG start codon, as well as an alternative upstream AUG start codon, which is polymorphic in human populations (AGG allele represented in this RefSeq; see rs3130932). Use of alternate start codons and the non-AUG start codon is described in PMID:19489092."
Gene ID: 5514 is PPP1R10 protein phosphatase 1 regulatory subunit 10 aka MHC class I region proline-rich protein CAT53 on 6p21.33: "This gene encodes a protein phosphatase 1 binding protein. The encoded protein plays a role in many cellular processes including cell cycle progression, DNA repair and apoptosis by regulating the activity of protein phosphatase 1. This gene lies within the major histocompatibility complex class I region on chromosome 6, and alternatively spliced transcript variants have been observed for this gene."
- NP_001363124.1 serine/threonine-protein phosphatase 1 regulatory subunit 10: "Transcript Variant: This variant (3) represents the longest transcript. Variants 1 and 3 both encode the same protein."
- NP_002705.2 serine/threonine-protein phosphatase 1 regulatory subunit 10 .
Gene ID: 5603 is MAPK13 mitogen-activated protein kinase 13 on 6p21.31: "This gene encodes a member of the mitogen-activated protein (MAP) kinase family. MAP kinases act as an integration point for multiple biochemical signals, and are involved in a wide variety of cellular processes such as proliferation, differentiation, transcription regulation and development. The encoded protein is a p38 MAP kinase and is activated by proinflammatory cytokines and cellular stress. Substrates of the encoded protein include the transcription factor ATF2 and the microtubule dynamics regulator stathmin. Alternatively spliced transcript variants have been observed for this gene."
- NP_002745.1  mitogen-activated protein kinase 13: "Transcript Variant: This variant (1) represents the longer transcript and is protein-coding."
Gene ID: 6204 is RPS10 ribosomal protein S10 on 6p21.31: "Ribosomes, the organelles that catalyze protein synthesis, consist of a small 40S subunit and a large 60S subunit. Together these subunits are composed of 4 RNA species and approximately 80 structurally distinct proteins. This gene encodes a ribosomal protein that is a component of the 40S subunit. The protein belongs to the S10E family of ribosomal proteins. It is located in the cytoplasm. Variable expression of this gene in colorectal cancers compared to adjacent normal tissues has been observed, although no correlation between the level of expression and the severity of the disease has been found. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed through the genome. Alternate splicing results in multiple transcript variants that encode the same protein. Naturally occurring read-through transcription occurs between this locus and the neighboring locus NUDT3 (nudix (nucleoside diphosphate linked moiety X)-type motif 3)."
- NP_001005.1 40S ribosomal protein S10: "Transcript Variant: This variant (2) differs in the 5' UTR compared to variant 1. Variants 1, 2 and 3 encode the same protein."
- NP_001190174.1 40S ribosomal protein S10: "Transcript Variant: This variant (1) represents the longer transcript. Variants 1, 2 and 3 encode the same protein."
- NP_001191020.1 40S ribosomal protein S10: "Transcript Variant: This variant (3) differs in the 5' UTR compared to variant 1. Variants 1, 2 and 3 encode the same protein."
Gene ID: 6631 is SNRPC small nuclear ribonucleoprotein polypeptide C on 6p21.31: "This gene encodes one of the specific protein components of the U1 small nuclear ribonucleoprotein (snRNP) particle required for the formation of the spliceosome. The encoded protein participates in the processing of nuclear precursor messenger RNA splicing. snRNP particles are attacked by autoantibodies frequently produced by patients with connective tissue diseases. The genome contains several pseudogenes of this functional gene. Alternative splicing results in a non-coding transcript variant."
- NP_003084.1 U1 small nuclear ribonucleoprotein C: "Transcript Variant: This variant (1) represents the longer transcript."
Gene ID: 6732 is SRPK1 SRSF protein kinase 1 on 6p21.31: "This gene encodes a serine/arginine protein kinase specific for the SR (serine/arginine-rich domain) family of splicing factors. The protein localizes to the nucleus and the cytoplasm. It is thought to play a role in regulation of both constitutive and alternative splicing by regulating intracellular localization of splicing factors. Alternative splicing of this gene results in multiple transcript variants. Additional alternatively spliced transcript variants have been described for this gene, but their full length nature have not been determined."
- NP_003128.3 SRSF protein kinase 1: "Transcript Variant: This variant (1) represents the shorter transcript."
Gene ID: 6882 is TAF11 TATA-box binding protein associated factor 11 on 6p21.31: "Initiation of transcription by RNA polymerase II requires the activities of more than 70 polypeptides. The protein that coordinates these activities is transcription factor IID (TFIID), which binds to the core promoter to position the polymerase properly, serves as the scaffold for assembly of the remainder of the transcription complex, and acts as a channel for regulatory signals. TFIID is composed of the TATA-binding protein (TBP) and a group of evolutionarily conserved proteins known as TBP-associated factors or TAFs. TAFs may participate in basal transcription, serve as coactivators, function in promoter recognition or modify general transcription factors (GTFs) to facilitate complex assembly and transcription initiation. This gene encodes a small subunit of TFIID that is present in all TFIID complexes and interacts with TBP. This subunit also interacts with another small subunit, TAF13, to form a heterodimer with a structure similar to the histone core structure. Two transcript variants encoding different isoforms have been found for this gene."
- NP_001257417.1 transcription initiation factor TFIID subunit 11 isoform 2: "Transcript Variant: This variant (2) lacks an alternate coding exon compared to variant 1, that causes a frameshift. The resulting isoform (2) has a shorter and distinct C-terminus compared to isoform 1."
- NP_005634.1 transcription initiation factor TFIID subunit 11 isoform 1: "Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1)."
Gene ID: 6941 is TCF19 transcription factor 19 on 6p21.33: "This gene encodes a protein that contains a PHD-type zinc finger domain and likely functions as a transcription factor. The encoded protein plays a role proliferation and apoptosis of pancreatic beta cells. Alternative splicing results in multiple transcript variants."
- NP_001070979.1 transcription factor 19: "Transcript Variant: This variant (2) uses an alternate splice site in the 5' UTR compared to variant 1. Variants 1, 2, and 3 encode the same protein."
- NP_001305837.1 transcription factor 19: "Transcript Variant: This variant (3) lacks an alternate segment in the 5' UTR compared to variant 1. Variants 1, 2, and 3 encode the same protein."
- NP_009040.2 transcription factor 19: "Transcript Variant: This variant (1) represents the longest transcript. Variants 1, 2, and 3 encode the same protein."
Gene ID: 6954 is TCP11 t-complex 11 on 6p21.31.
- NP_001248746.2 T-complex protein 11 homolog isoform 3: "Transcript Variant: This variant (3) uses an alternate splice site in the 5' coding region, but maintains the reading frame, compared to variant 1. The encoded isoform (3) is shorter than isoform 1."
- NP_001248747.1 T-complex protein 11 homolog isoform 4: "Transcript Variant: This variant (4) lacks an exon in the 5' coding region, but maintains the reading frame, compared to variant 1. The encoded isoform (4) is shorter than isoform 1."
- NP_001248748.1 T-complex protein 11 homolog isoform 5: "Transcript Variant: This variant (5) lacks an exon and uses an alternate splice site in the 5' coding region, but maintains the reading frame, compared to variant 1. The encoded isoform (5) is shorter than isoform 1."
- NP_001248749.1 T-complex protein 11 homolog isoform 6: "Transcript Variant: This variant (6) differs in the 5' UTR, includes an alternate internal exon in the 5' region and initiates translation at a downstream, in-frame start codon, compared to variant 1. Variants 6 and 7 encode the same isoform (6), which has a shorter N-terminus compared to isoform 1."
- NP_001248750.1 T-complex protein 11 homolog isoform 6: "Transcript Variant: This variant (7) has multiple differences, including the use of a downstream, in-frame start codon, compared to variant 1. Variants 6 and 7 encode the same isoform (6), which has a shorter N-terminus compared to isoform 1."
- NP_001353252.1 T-complex protein 11 homolog isoform 6 .
- NP_001353253.1 T-complex protein 11 homolog isoform 2 .
- NP_001353254.1 T-complex protein 11 homolog isoform 7 .
- NP_001353255.1 T-complex protein 11 homolog isoform 8 .
- NP_001353256.1 T-complex protein 11 homolog isoform 9 .
- NP_001353257.1 T-complex protein 11 homolog isoform 9 .
- NP_001353258.1 T-complex protein 11 homolog isoform 9 .
- NP_001353259.1 T-complex protein 11 homolog isoform 10 .
- NP_001353260.1 T-complex protein 11 homolog isoform 11 .
- NP_001353261.1 T-complex protein 11 homolog isoform 12 .
- NP_001357616.1 T-complex protein 11 homolog isoform 1: "Transcript Variant: This variant (1) encodes the longest isoform (1)."
- NP_061149.1 T-complex protein 11 homolog isoform 2: "Transcript Variant: This variant (2) has multiple differences, including the use of an alternate start codon, compared to variant 1. The encoded isoform (2) is shorter and has a distinct N-terminus, compared to isoform 1."
Gene ID: 7148 is TNXB tenascin XB on 6p21.33-p21.32: "This gene encodes a member of the tenascin family of extracellular matrix glycoproteins. The tenascins have anti-adhesive effects, as opposed to fibronectin which is adhesive. This protein is thought to function in matrix maturation during wound healing, and its deficiency has been associated with the connective tissue disorder Ehlers-Danlos syndrome. This gene localizes to the major histocompatibility complex (MHC) class III region on chromosome 6. It is one of four genes in this cluster which have been duplicated. The duplicated copy of this gene is incomplete and is a pseudogene which is transcribed but does not encode a protein. The structure of this gene is unusual in that it overlaps the CREBL1 and CYP21A2 genes at its 5' and 3' ends, respectively. Multiple transcript variants encoding different isoforms have been found for this gene."
- NP_001352205.1 tenascin-X isoform 3 precursor: "Transcript Variant: This variant (3) represents the longest transcript and encodes the longest isoform (3). It should be noted that the exon combination of this variant lacks full-length transcript support in human; it is predicted based on a combination of partial human and homologous transcript alignments."
- NP_061978.6 tenascin-X isoform 1 precursor: "Transcript Variant: This variant (XB) uses an alternate in-frame splice junction compared to variant 3. The resulting isoform (1) has the same N- and C-termini but is shorter compared to isoform 3. It should be noted that the exon combination of this variant lacks full-length transcript support in human; it is predicted based on a combination of partial human and homologous transcript alignments."
- NP_115859.2 tenascin-X isoform 2: "Transcript Variant: This variant (XB-S) is transcribed from a cryptic internal promoter sequence and is substantially shorter than variant 3 at the 5' end. It encodes isoform 2, which is identical to the C-terminus of the full-length protein, isoform 3."
Gene ID: 7287 is TULP1 TUB like protein 1 on 6p21.31: "This gene encodes a member of the tubby-like gene family (TULPs). Members of this family have been identified in plants, vertebrates, and invertebrates. TULP proteins share a conserved C-terminal region of approximately 200 amino acid residues. The protein encoded by this gene is thought to play a role in the physiology of photoreceptors. Mutations in this gene are associated with recessive juvenile retinitis pigmentosa and Leber congenital amaurosis-15."
- NP_001276324.1 tubby-related protein 1 isoform 2: "Transcript Variant: This variant (2) lacks an alternate in-frame exon in the 5' coding region, compared to variant 1. It encodes isoform 2, which lacks an internal segment and is shorter than isoform 1."
- NP_003313.3 tubby-related protein 1 isoform 1: "Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1)."
Gene ID: 7407 is VARS1 valyl-tRNA synthetase 1 on 6p21.33: "Aminoacyl-tRNA synthetases catalyze the aminoacylation of tRNA by their cognate amino acid. Because of their central role in linking amino acids with nucleotide triplets contained in tRNAs, aminoacyl-tRNA synthetases are thought to be among the first proteins that appeared in evolution. The protein encoded by this gene belongs to class-I aminoacyl-tRNA synthetase family and is located in the class III region of the major histocompatibility complex."
Gene ID: 7629 is ZNF76 zinc finger protein 76 on 6p21.31.
- NP_001278961.1 zinc finger protein 76 isoform 2: "Transcript Variant: This variant (2) lacks an alternate in-frame exon compared to variant 1. The resulting isoform (2) has the same N- and C-termini but is shorter compared to isoform 1."
- NP_003418.2 zinc finger protein 76 isoform 1: "Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1)."
Gene ID: 7936 is NELFE negative elongation factor complex member E aka major histocompatibility complex gene RD on 6p21.33: "The protein encoded by this gene is part of a complex termed negative elongation factor (NELF) which represses RNA polymerase II transcript elongation. This protein bears similarity to nuclear RNA-binding proteins; however, it has not been demonstrated that this protein binds RNA. The protein contains a tract of alternating basic and acidic residues, largely arginine (R) and aspartic acid (D). The gene localizes to the major histocompatibility complex (MHC) class III region on chromosome 6."
- NP_002895.3 negative elongation factor E.
Gene ID: 7940 is LST1 leukocyte specific transcript 1 on 6p21.33: "The protein encoded by this gene is a membrane protein that can inhibit the proliferation of lymphocytes. Expression of this gene is enhanced by lipopolysaccharide, interferon-gamma, and bacteria. Several transcript variants encoding different isoforms have been found for this gene."
- NP_001160010.1 leukocyte-specific transcript 1 protein isoform 6: "Transcript Variant: This variant (6) lacks an alternate in-frame exon in the 5' coding region, compared to variant 1, resulting in an isoform (6) that is shorter than isoform 1. The 5' UTR of this variant is incomplete because the transcripts supporting this CDS exon combination lack a complete 5' UTR, and alternative splicing choices exist further upstream."
- NP_009092.3 leukocyte-specific transcript 1 protein isoform 1: "Transcript Variant: This variant (1) encodes the longest isoform (1). The 5' UTR of this variant is incomplete because the transcripts supporting this CDS exon combination lack a complete 5' UTR, and alternative splicing choices exist further upstream."
- NP_995309.2 leukocyte-specific transcript 1 protein isoform 2: "Transcript Variant: This variant (2) includes an additional exon in the 5' UTR and lacks an internal exon that causes a frameshift in the 3' coding region, compared to variant 1. The encoded isoform (2) has a distinct C-terminus and is shorter than isoform 1."
- NP_995310.2 leukocyte-specific transcript 1 protein isoform 3: "Transcript Variant: This variant (3) includes an additional exon in the 5' UTR, lacks an alternate in-frame exon in the 5' coding region, and uses an alternate in-frame splice site in the 3' coding region, compared to variant 1. The encoded isoform (3) is shorter than isoform 1."
- NP_995311.2 leukocyte-specific transcript 1 protein isoform 4: "Transcript Variant: This variant (4) includes an additional exon in the 5' UTR and uses an alternate in-frame splice site in the 3' coding region, compared to variant 1. The encoded isoform (4) is shorter than isoform 1."
- NP_995312.2 leukocyte-specific transcript 1 protein isoform 5: "Transcript Variant: This variant (5) lacks an alternate exon in the central coding region and uses an alternate splice site that causes a frameshift in the 3' coding region, compared to variant 1. The encoded isoform (5) has a distinct C-terminus and is shorter than isoform 1. The 5' UTR of this variant is incomplete because the transcripts supporting this CDS exon combination lack a complete 5' UTR, and alternative splicing choices exist further upstream."
Gene ID: 8449 is DHX16 DEAH-box helicase 16 on 6p21.33: "DEAD box proteins, characterized by the conserved motif Asp-Glu-Ala-Asp (DEAD), are putative RNA helicases. They are implicated in a number of cellular processes involving alteration of RNA secondary structure such as translation initiation, nuclear and mitochondrial splicing, and ribosome and spliceosome assembly. Based on their distribution patterns, some members of this family are believed to be involved in embryogenesis, spermatogenesis, and cellular growth and division. This gene encodes a DEAD box protein, which is a functional homolog of fission yeast Prp8 protein involved in cell cycle progression. This gene is mapped to the MHC region on chromosome 6p21.3, a region where many malignant, genetic and autoimmune disease genes are linked. Three transcript variants encoding different isoforms have been found for this gene."
- NP_001157711.1 pre-mRNA-splicing factor ATP-dependent RNA helicase DHX16 isoform 2: "Transcript Variant: This variant (2) differs in the 5' UTR and coding sequence compared to variant 1. The resulting isoform (2) has a shorter and distinct N-terminus compared to isoform 1."
- NP_001350444.1 pre-mRNA-splicing factor ATP-dependent RNA helicase DHX16 isoform 3: "Transcript Variant: This variant (3) contains an alternate exon compared to variant 1. The resulting isoform (3) has a shorter and distinct N-terminus compared to isoform 1."
- NP_003578.2 pre-mRNA-splicing factor ATP-dependent RNA helicase DHX16 isoform 1: "Transcript Variant: This variant (1) encodes the longest isoform (1)."
Gene ID: 8859 is STK19 serine/threonine kinase 19 aka MHC class III HLA-RP1 on 6p21.33: "This gene encodes a serine/threonine kinase which localizes predominantly to the nucleus. Its specific function is unknown; it is possible that phosphorylation of this protein is involved in transcriptional regulation. This gene localizes to the major histocompatibility complex (MHC) class III region on chromosome 6 and expresses two transcript variants."
- NP_004188.1 serine/threonine-protein kinase 19 isoform 1: "Transcript Variant: This variant (1) uses an alternate splice site in the coding region, compared to variant 2. It encodes isoform 1 which is shorter compared to isoform 2. Although isoforms 1 and 2 differ in the kinase domain, it appears that there is no difference in kinase activity between isoforms 1 and 2."
- NP_115830.1 serine/threonine-protein kinase 19 isoform 2: "Transcript Variant: This variant (2) represents the longest transcript and encodes the longest isoform (2). Although isoforms 1 and 2 differ in the kinase domain, it appears that there is no difference in kinase activity between isoforms 1 and 2."
Gene ID: 8870 is IER3 immediate early response 3 on 6p21.33: "This gene functions in the protection of cells from Fas- or tumor necrosis factor type alpha-induced apoptosis. Partially degraded and unspliced transcripts are found after virus infection in vitro, but these transcripts are not found in vivo and do not generate a valid protein."
Gene ID: 9656 is MDC1 mediator of DNA damage checkpoint 1 on 6p21.33: "The protein encoded by this gene contains an N-terminal forkhead domain, two BRCA1 C-terminal (BRCT) motifs and a central domain with 13 repetitions of an approximately 41-amino acid sequence. The encoded protein is required to activate the intra-S phase and G2/M phase cell cycle checkpoints in response to DNA damage. This nuclear protein interacts with phosphorylated histone H2AX near sites of DNA double-strand breaks through its BRCT motifs, and facilitates recruitment of the ATM kinase and meiotic recombination 11 protein complex to DNA damage foci."
Gene ID: 10211 is FLOT1 flotillin 1 on 6p21.33: "This gene encodes an protein that localizes to the caveolae, which are small domains on the inner cell membranes. This protein plays a role in vesicle trafficking and cell morphology. Alternative splicing results in multiple transcript variants."
- NP_001305804.1 flotillin-1 isoform 2: "Transcript Variant: This variant (2) lacks an alternate in-frame exon compared to variant 1. The encoded isoform (2) is shorter than isoform 1."
- NP_005794.1 flotillin-1 isoform 1: "Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1)."
Gene ID: 259197 is NCR3 natural cytotoxicity triggering receptor 3 on 6p21.33: "The protein encoded by this gene is a natural cytotoxicity receptor (NCR) that may aid NK cells in the lysis of tumor cells. The encoded protein interacts with CD3-zeta (CD247), a T-cell receptor. A single nucleotide polymorphism in the 5' untranslated region of this gene has been associated with mild malaria suceptibility. Three transcript variants encoding different isoforms have been found for this gene."
- NP_001138938.1 natural cytotoxicity triggering receptor 3 isoform b: "Transcript Variant: This variant (2) uses an alternate splice site in the 3' coding region compared to variant 1, that results in a frameshift. It encodes isoform b, which has a shorter and distinct C-terminus compared to isoform a."
- NP_001138939.1 natural cytotoxicity triggering receptor 3 isoform c: "Transcript Variant: This variant (3) uses an alternate splice site in the 3' coding region compared to variant 1, that results in a frameshift. It encodes isoform c, which has a shorter and distinct C-terminus compared to isoform a."
- NP_667341.1 natural cytotoxicity triggering receptor 3 isoform a precursor: "Transcript Variant: This variant (1) encodes the longest isoform (a).  Ig; Immunoglobulin domain".

# Hypotheses
- Downstream core promoters may work as transcription factors even as their complements or inverses.
- In addition to the DNA binding sequences listed above, the transcription factors that can open up and attach through the local epigenome need to be known and specified.