Persius/hicric huggingface dataset:
HDAC1
Histone deacetylase 1 (HDAC1) is an enzyme that in humans is encoded by the HDAC1 gene.

# Function
Histone acetylation and deacetylation, catalyzed by multisubunit complexes, play a key role in the regulation of eukaryotic gene expression. The protein encoded by this gene belongs to the histone deacetylase/acuc/apha family and is a component of the histone deacetylase complex. It also interacts with retinoblastoma tumor-suppressor protein and this complex is a key element in the control of cell proliferation and differentiation. Together with metastasis-associated protein-2 MTA2, it deacetylates p53 and modulates its effect on cell growth and apoptosis.

# Model organisms
Model organisms have been used in the study of HDAC1 function. A conditional knockout mouse line, called Hdac1tm1a(EUCOMM)Wtsi was generated as part of the International Knockout Mouse Consortium program  a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists  at the Wellcome Trust Sanger Institute. 
Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion. Twenty five tests were carried out and two phenotypes were reported. A reduced number of homozygous mutant embryos were identified during gestation, and none survived until weaning. The remaining tests were carried out on heterozygous mutant adult mice, and no significant abnormalities were observed in these animals.

# Interactions
HDAC1 has been shown to interact with:
- Androgen receptor,
- BCL6,
- BTG2, 
- BUB1B,
- BUB1,
- BUB3,
- CBFA2T3,
- CDC20,
- CDH1,
- CHD3,
- CHD4,
- COUP-TFII,
- CTBP1,
- DDX17,
- DDX5,
- DNMT3A,
- DNMT3L,
- Death-associated protein 6,
- EED,
- EVI1,
- EZH2,
- FKBP3,
- GATA1,
- HMG20B,
- HSPA4,
- HUS1,
- Histone deacetylase 2,
- Homeobox protein TGIF1,
- Host cell factor C1,
- IFRD1,
- IKZF1,
- ING1,
- MBD3,
- MIER1,
- MLL,
- MTA1,
- MTA2,
- Mad1,
- Mdm2,
- Methyl-CpG-binding domain protein 2,
- Mothers against decapentaplegic homolog 2,
- MyoD,
- NFKB1,
- Nuclear receptor co-repressor 2,
- P21, 
- PCNA,
- PHF21A,
- Prohibitin,
- Promyelocytic leukemia protein,
- RAD9A,
- RBBP4,
- RBBP7,
- RCOR1,
- RELA,
- RFC1,
- Retinoblastoma protein,
- Retinoblastoma-like protein 1,
- Retinoblastoma-like protein 2,
- SAP30,
- SATB1,
- SIN3A,
- SIN3B,
- SPEN,
- SUDS3,
- SUV39H1,
- Sp1 transcription factor,
- TOP2A,
- TOP2B,  and
- Zinc finger and BTB domain-containing protein 16.
HDAC4
Histone deacetylase 4, also known as HDAC4, is a protein that in humans is encoded by the HDAC4 gene.

# Function
Histones play a critical role in transcriptional regulation, cell cycle progression, and developmental events. Histone acetylation/deacetylation alters chromosome structure and affects transcription factor access to DNA. The protein encoded by this gene belongs to class II of the histone deacetylase/acuc/apha family. It possesses histone deacetylase activity and represses transcription when tethered to a promoter. This protein does not bind DNA directly but through transcription factors MEF2C and MEF2D. It seems to interact in a multiprotein complex with RbAp48 and HDAC3.  Furthermore, HDAC4 is required for TGFbeta1-induced myofibroblastic differentiation.

# Clinical significance
Studies have shown that HDAC4 regulates bone and muscle development.  Harvard University researchers also concluded that it promotes healthy vision: Reduced levels of the protein led to the death of the rod photoreceptors and bipolar cells in the retinas of mice.

# Interactions
HDAC4 has been shown to interact with:
- BCL6,
- BTG2, 
- CBX5,
- GATA1,
- HDAC3,
- MAPK1,
- MAPK3,
- MEF2C,
- Myocyte-specific enhancer factor 2A,
- Nuclear receptor co-repressor 1,
- Nuclear receptor co-repressor 2,
- Testicular receptor 2,
- YWHAB,
- YWHAE, and
- Zinc finger and BTB domain-containing protein 16.
HDAC6
Histone deacetylase 6 is an enzyme that in humans is encoded by the HDAC6 gene.

# Function
Histones play a critical role in transcriptional regulation, cell cycle progression, and developmental events. Histone acetylation/deacetylation alters chromatin structure and affects transcription. The protein encoded by this gene belongs to class II of the histone deacetylase/acuc/apha family. It contains an internal duplication of two catalytic domains that appear to function independently of each other. This protein possesses histone deacetylase activity and represses transcription.

# Clinical relevance
Mutations in this gene have been associated to Alzheimer's disease.
Over expression of this protein correlates with tumorigenesis and cell survival. HDAC6 also encourages metastasis of cancer cells.

# Functions
Retracts the Cilium of the cell, which is necessary prior to mitosis of the cell.
HDAC also encourages cell motility and catalyzes -tubulin deacetylation. as a result the enzyme also encourages cancer cell metastasis.
HDAC6 also affects transcription and translation by regulating the heat-shock protein 90 (Hsp90) and stress granules (SGs), respectively.
HDAC6 is also known to bond with high affinity to ubiquitinated proteins. HDAC6 is also required in the formation of SG (Stress granule proteins and is instrumental in SG formation; pharmacological inhibition or genetic removal of HDAC6 abolished SG formation.

# Interactions
HDAC6 has been shown to interact with HDAC11 and Zinc finger and BTB domain-containing protein 16.
HDAC6 interacts with SG (Stress granule) protein G3BP1.
HDAC8
Histone deacetylase 8 is an enzyme that in humans is encoded by the HDAC8 gene.

# Function
Histones play a critical role in transcriptional regulation, cell cycle progression, and developmental events. Histone acetylation / deacetylation alters chromosome structure and affects transcription factor access to DNA. The protein encoded by this gene belongs to class I of the histone deacetylase/acuc/apha family. It has histone deacetylase activity and represses transcription when tethered to a promoter.
Histone deacetylase 8 is involved in skull morphogenesis and metabolic control of the ERR-alpha / PGC1-alpha transcriptional complex.

# Clinical significance
HDAC8 has been linked to number of disease states notably to acute myeloid leukemia and is related to actin cytoskeleton in smooth muscle cells. siRNA targeting HDAC8 showed anticancer effects. Inhibition of HDAC8 induced apoptosis has been observed in T cell lymphomas. In addition the HDAC8 enzyme has been implicated in the pathogenesis of neuroblastoma. Therefore, there has been interest in developing HDAC8 selective inhibitors.

# Interactions
- ERR-alpha.
HECW2
HECT, C2 and WW domain containing E3 ubiquitin protein ligase 2 is a protein that in humans is encoded by the HECW2 gene.

# Model organisms
Model organisms have been used in the study of HECW2 function. A conditional knockout mouse line called Hecw2tm1a(EUCOMM)Wtsi was generated at the Wellcome Trust Sanger Institute. Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion. Additional screens performed:  - In-depth immunological phenotyping

# Clinical significance
Mutations in the HECW2 gene have been associated to epilepsy and intellectual disability. These mutations affect one copy of the HECW2 gene and are believed to change the function of the HECW2 protein.
HERC5
Probable E3 ubiquitin-protein ligase HERC5 is an enzyme that in humans is encoded by the HERC5 gene.
This gene is a member of the HERC family of ubiquitin ligases and encodes a protein with a HECT domain and five RCC1 repeats. Pro-inflammatory cytokines upregulate expression of this gene in endothelial cells. The protein localizes to the cytoplasm and perinuclear region and functions as an interferon-induced E3 protein ligase that mediates ISGylation of protein targets. The gene lies in a cluster of HERC family genes on chromosome 4. HERC5 has been shown to exhibit antiviral activity towards HIV-1, influenza A virus and human papillomavirus.

# Interactions
HERC5 has been shown to interact with NME2 and Cyclin E1.
HESX1
Homeobox expressed in ES cells 1, also known as homeobox protein ANF, is a homeobox protein that in humans is encoded by the HESX1 gene.
Expression of HEX1 and HESX1 marks the anterior visceral endoderm of the embryo. The AVE is an extra-embryonic tissue, key to the establishment of the anterior-posterior body axis.

# Clinical significance
Mutations in the HESX1 gene are associated with some cases of septo-optic dysplasia or Pickardt-Fahlbusch syndrome.
HIF3A
Hypoxia-inducible factor 3 alpha is a protein that in humans is encoded by the HIF3A gene.

# Function
The protein encoded by this gene is the alpha-3 subunit of one of several alpha/beta-subunit heterodimeric transcription factors that regulate many adaptive responses to low oxygen tension (hypoxia). The alpha-3 subunit lacks the transactivation domain found in factors containing either the alpha-1 or alpha-2 subunits. It is thought that factors containing the alpha-3 subunit are negative regulators of hypoxia-inducible gene expression. At least three transcript variants encoding three different isoforms have been found for this gene.
In rats, it plays a negative role in the adaptation to hypoxia, because the inhibition of HIF-3 expression leads to an increase in physical endurance.

# Clinical significance
DNA methylation in the introns of HIF3A is associated with BMI an adiposity.
HKDC1
Hexokinase domain containing 1 (HKDC1) is an enzyme which in humans is encoded by the HKDC1 gene on chromosome 10. It is a recently discovered hexokinase isoform that likely phosphorylates glucose in maternal metabolism during pregnancy.

# Structure
The HKDC1 gene is oriented in a head-to-tail arrangement next to the HK1 gene on chromosome 10. This arrangement, along with its amino acid sequence similarity to HK1, suggests that HKDC1 and HK1 derived from the same precursor via a tandem gene duplication event. The similarity between HKDC1 and HK1 may have obscured its discovery in earlier screens for vertebrate hexokinases. Unlike the HK2 pseudogene, HKDC1 contains an intact open reading frame of 917 residues and is conserved across animal species, indicating that it encodes a functional protein. Moreover, the encoded protein contains conserved glucose-binding sites in its N- and C-terminal domains as well as an ATP-binding site in its C-terminal domain, indicating that its C-terminal is capable of hexokinase activity.

# Function
As the recently identified fifth isoform of hexokinase, HKDC1 catalyzes the rate-limiting and first obligatory step of glucose metabolism, which is the ATP-dependent phosphorylation of glucose to G6P. Though its particular biological function remains unclear, HKDC1 has been suggested to play a more major role in glucose metabolism during pregnancy, as the mother would need to provide enough energy for both herself and the fetus. HKDC1 is ubiquitously expressed, with the highest levels of expression in pharynx, thymus, colon, esophagus, and eye tissue.

# Clinical Significance

## Cancer
Compared to the other hexokinases, HKDC1 was dramatically overexpressed in cancer tissues, indicating that this isoform might play an important and different role in cancer growth. Further experiments clarifying this role will be required for developing HKDC1 as a therapeutic target.

## Gestational hyperglycemia
Several regulatory variants, including various enhancers, targeting HKDC1 expression have been associated with gestational hyperglycemia in pregnant women. Considering that maternal glucose levels during pregnancy impact the both fetal and later health outcomes, a greater understanding of the genetic mechanisms underlying  maternal glycemia during pregnancy may help identify and aid such women at risk.
HLA-E
HLA class I histocompatibility antigen, alpha chain E (HLA-E) also known as MHC class I antigen E is a protein that in humans is encoded by the HLA-E gene. The human HLA-E is a non-classical MHC class I molecule that is characterized by a limited polymorphism and a lower cell surface expression than its classical paralogues. The functional homolog in mice is called Qa-1b, officially known as H2-T23.

# Structure
Like other MHC class I molecules, HLA-E is a heterodimer consisting of an  heavy chain and a light chain (-2 microglobulin). The heavy chain is approximately 45 kDa and anchored in the membrane. The HLA-E gene contains 8 exons. Exon one encodes the signal peptide, exons 2 and 3 encode the 1 and 2 domains, which both bind the peptide, exon 4 encodes the 3 domain, exon 5 encodes the transmembrane domain, and exons 6 and 7 encode the cytoplasmic tail.

# Function
HLA-E has a very specialized role in cell recognition by natural killer cells (NK cells). HLA-E binds a restricted subset of peptides derived from signal peptides of classical MHC class I molecules, namely HLA-A, B, C, G. These peptides are released from the membrane of the endoplasmic reticulum (ER) by the signal peptide peptidase and trimmed by the cytosolic proteasome. Upon transport into the ER lumen by the transporter associated with antigen processing (TAP), these peptides bind to a peptide binding groove on the HLA-E molecule. This allows HLA-E to assemble correctly and to be expressed on the cell surface. NK cells recognize the HLA-E+peptide complex using the heterodimeric receptor CD94/NKG2A/B/C. When CD94/NKG2A or CD94/NKG2B is engaged, it produces an inhibitory effect on the cytotoxic activity of the NK cell to prevent cell lysis. However, binding of HLA-E to CD94/NKG2C results in NK cell activation. This interaction has been shown to trigger expansion of NK cell subsets in antiviral responses.
HLA-G
HLA-G histocompatibility antigen, class I, G, also known as human leukocyte antigen G (HLA-G), is a protein that in humans is encoded by the HLA-G gene.
HLA-G belongs to the HLA nonclassical class I heavy chain paralogues. This class I molecule is a heterodimer consisting of a heavy chain and a light chain (beta-2 microglobulin). The heavy chain is anchored in the membrane. HLA-G is expressed on fetal derived placental cells. The heavy chain is approximately 45 kDa and its gene contains 8 exons. Exon one encodes the leader peptide, exons 2 and 3 encode the alpha1 and alpha2 domain, which both bind the peptide, exon 4 encodes the alpha3 domain, exon 5 encodes the transmembrane region, and exon 6 encodes the cytoplasmic tail. Exon 7 and 8 are not translated due to a stop codon present in exon 6.

# Function
HLA-G may play a role in immune tolerance in pregnancy, being expressed in the placenta by extravillous trophoblast cells (EVT), while the classical MHC class I genes (HLA-A and HLA-B) are not. As HLA-G was first identified in placenta samples, many studies have evaluated its role in pregnancy disorders, such as preeclampsia and recurrent pregnancy loss. its downregulation is related to HLA-A and -B downregulation results in protection from cytotoxic T cell responses, but would in theory result in a missing self response by natural killer cells. HLA-G is a ligand for NK cell inhibitory receptor KIR2DL4, and therefore expression of this HLA by the trophoblast defends it against NK cell-mediated death.
However, a large family with several members bearing only "null" HLA-G alleles has been found. None of these homozygous subjects have pregnancy or birth difficulties; nor do they present immunodeficiencies, autoimmune diseases, or tumors. It is striking that this "null" allele (HLA-G*01:05N), while it is quite frequent in some populations, like in Iranians, it is almost absent in some Amerindian populations. Also, some higher primates do not show all MHC-G isoforms. In addition, Cercopithecinae middle-sized Old World monkeys do not bear full MHC-G molecules since all of these monkeys present stop codons at MHC-G DNA. All of these anomalies must be studied.
The presence of soluble HLA-G (sHLA-G) in embryos is associated with better pregnancy rates. In order to optimize pregnancy rates, there is significant evidence that a morphological scoring system is the best strategy for the selection of embryos. However, presence of soluble HLA-G might be considered as a second parameter if a choice has to be made between embryos of morphologically equal quality.

# Interactions
HLA-G has been shown to interact with CD8A.
HLA E
Major histocompatibility complex, class I, E, also known as HLA-E, is a human gene.
HLA-E belongs to the HLA class I heavy chain paralogues. This class I molecule is a heterodimer consisting of a heavy chain and a light chain (beta-2 microglobulin). The heavy chain is anchored in the membrane. HLA-E binds a restricted subset of peptides derived from the leader peptides of other class I molecules. The heavy chain is approximately 45 kDa and its gene contains 8 exons. Exon one encodes the leader peptide, exons 2 and 3 encode the alpha1 and alpha2 domains, which both bind the peptide, exon 4 encodes the alpha3 domain, exon 5 encodes the transmembrane region, and exons 6 and 7 encode the cytoplasmic tail.
HLA-E is a protein that is a member of the HLA family. It is one of a family of molecules known as MHC class Ib and has a very specialized role in cell recognition by NK cells (Natural Killer). HLA-E is very highly conserved and presents a small repertoire of peptides of various origins. HLA-E is expressed ubiquitously. The primary peptides HLA-E binds are derived from the leader sequence of other HLA class Ia molecules, such as HLA-A, B, C, G.These proteins bind to the Peptide binding groove of the HLA-E molecule, and this allows it to be expressed on  on the surface. NK cells recognise bound HLA-E+Peptide combination using the heterodimeric inhibitory receptor CD94/NKG2A or the activating receptor NKG2C/CD94 . When CD94/NKG2A is stimulated, it produces an inhibitory effect on the cytotoxic activity of the NK cell to prevent cell lysis.
A number of viruses have evolved to express proteins that inhibit the expression of MHC I molecules on cell surface of cells they infect, thereby preventing Antigen presentation that would allow the Immune system to recognise infection. NK cells therefore identify cells that are exhibiting such characteristics of viral infection.
HLA E is also reported to interact with the T-cell receptor. HLA-E presents a peptide (VMAPRTLIL) derived from the UL40 protein from cytomegalovirus. This peptide is highly similar to the leader peptides derived from other HLA molecules and acts as a surrogate "leader peptide" and interacts with CD94/NKG2 receptors. This engagement relays into an overall inhibitory effect on NK-cell meditated cytotoxicity.
HMGA1
High-mobility group protein HMG-I/HMG-Y is a protein that in humans is encoded by the HMGA1 gene.

# Function
This gene encodes a non-histone chromatin protein involved in many cellular processes, including regulation of inducible gene transcription, DNA replication, heterochromatin organization,  integration of retroviruses into chromosomes, and the metastatic progression of cancer cells.
HMGA1 proteins are quite small (~10-12 kDa) and basic molecules, and consist of three AT-hooks with the RGRP (Arg-Gly-Arg-Pro) core  motif, a novel cross-linking domain located between the second and third AT-hook, and a C-terminal acidic tail characteristic for the HMG family comprising HMGA, HMGB and HMGN proteins.
HMGA1-GFP fusion proteins are highly dynamic in vivo (determined using FRAP analysis), but in contrast also show nanomolar affinity to AT-rich DNA in vitro (determined biochemically), which might be explained due to the extensive post-transcriptional modifications in vivo. HMGA1 preferentially binds to the minor groove of AT-rich regions in double-stranded DNA using its AT-hooks. It has little secondary structure in solution but assumes distinct conformations when bound to substrates such as DNA or other proteins. HMGA1 proteins have high amounts of diverse posttranslational modifications and are located mainly in the nucleus, especially in heterochromatin, but also in mitochondria and the cytoplasm.
Recently it has been shown that HMGA1 proteins, HMGA1a and HMGA1b, can cross-link DNA fibers in vitro and can induce chromatin clustering in vivo suggesting a structural role of HMGA1 proteins in heterochromatin organization.
At least seven transcript variants encoding two different isoforms (HMGA1a, HMGA1b) have been found for this gene. The splice variant HMGA1c with only two AT hooks and no acidic tail is in discussion to be a real member of the HMGA family.
Mice lacking their variant of HMGA1, i.e., Hmga1-/- mice, are diabetic, show a cardiac hypertrophy and express low levels of the insulin receptor.

# Interactions
HMGA1 has been shown to interact with CEBPB and Sp1 transcription factor.
HMOX1
HMOX1 (heme oxygenase (decycling) 1) is a human gene that encodes for the enzyme heme oxygenase 1 (EC 1.14.99.3). Heme oxygenase mediates the first step of heme catabolism, it cleaves heme to form biliverdin.
Heme oxygenase, an essential enzyme in heme catabolism, cleaves heme to form biliverdin, carbon monoxide, and ferrous iron. The biliverdin is subsequently converted to bilirubin by biliverdin reductase. Heme oxygenase activity is induced by its substrate heme and by various nonheme substances. Heme oxygenase occurs as 2 isozymes, an inducible heme oxygenase-1 and a constitutive heme oxygenase-2. HMOX1 and HMOX2 belong to the heme oxygenase family.
The HMOX gene is located on the long (q) arm of chromosome 22 at position 12.3, from base pair 34,101,636 to base pair 34,114,748.

# Related conditions
- Heme oxygenase-1 deficiency

# Anti-inflammatory effect
The ability of oxygenase 1 to catabolize free heme and produce carbon monoxide (CO) gives its anti-inflammatory properties by  up-regulation of interleukin 10 (IL-10) and interleukin 1 receptor antagonist (IL-1RA) expression.
HNRPD
Heterogeneous nuclear ribonucleoprotein D0 (HNRNPD) also known as AU-rich element RNA-binding protein 1 (AUF1) is a protein that in humans is encoded by the HNRNPD gene. Alternative splicing of this gene results in four transcript variants.

# Function
This gene belongs to the subfamily of ubiquitously expressed heterogeneous nuclear ribonucleoproteins (hnRNPs). The hnRNPs are nucleic acid binding proteins and they complex with heterogeneous nuclear RNA (hnRNA). The interaction sites on the RNA are frequently biased towards particular sequence motifs. These proteins are associated with pre-mRNAs in the nucleus and appear to influence pre-mRNA processing and other aspects of mRNA metabolism and transport. While all of the hnRNPs are present in the nucleus, some seem to shuttle between the nucleus and the cytoplasm. The hnRNP proteins have distinct nucleic acid binding properties. The protein encoded by this gene has two repeats of quasi-RRM domains that bind to RNAs. It localizes to both the nucleus and the cytoplasm. This protein is implicated in the regulation of mRNA stability.

# Interactions
HNRPD has been shown to interact with SAFB and Hsp27. AUF1 also has been reported to interact with mRNAs such as Mef2c mRNA.