Persius/hicric huggingface dataset:
QDPR
QDPR (quinoid dihydropteridine reductase) is a human gene that produces the enzyme quinoid dihydropteridine reductase. This enzyme is part of the pathway that recycles a substance called tetrahydrobiopterin, also known as BH4. Tetrahydrobiopterin works with an enzyme called phenylalanine hydroxylase to process a substance called phenylalanine. Phenylalanine is an amino acid (a building block of proteins) that is obtained through the diet; it is found in all proteins and in some artificial sweeteners. When tetrahydrobiopterin interacts with phenylalanine hydroxylase, tetrahydrobiopterin is altered and must be recycled to a usable form. The regeneration of this substance is critical for the proper processing of several other amino acids in the body. Tetrahydrobiopterin also helps produce certain chemicals in the brain called neurotransmitters, which transmit signals between nerve cells.
The QDPR gene is located on the short (p) arm of chromosome 4 at position 15.31, from base pair 17,164,291 to base pair 17,189,981.
In melanocytic cells QDPR gene expression may be regulated by MITF.

# Related conditions
Mutations in the QDPR gene are a common cause of tetrahydrobiopterin deficiency. More than 30 disorder-causing mutations in this gene have been identified, including aberrant splicing, amino acid substitutions, insertions, or premature terminations. These mutations completely, or almost completely, inactivate quinoid dihydropteridine reductase, which prevents the normal recycling of tetrahydrobiopterin. In the absence of usable tetrahydrobiopterin, the body cannot process phenylalanine correctly. As a result, phenylalanine from the diet builds up in the bloodstream and other tissues and can lead to brain damage. Neurotransmitters in the brain are also affected, resulting in delayed development, seizures, movement disorders, and other symptoms.
In addition, a reduction in the activity of quinoid dihydropteridine reductase may cause calcium to build up abnormally in certain parts of the brain, resulting in damage to nerve cells.
RAC2
Rac2 (Ras-related C3 botulinum toxin substrate 2) is a small (~21 kDa) signaling G protein (to be specific, a GTPase), and is a member of the Rac subfamily of the family Rho family of GTPases. It is encoded by the gene RAC2.
Members of Rho family of GTPases appear to regulate a diverse array of cellular events, including the control of cell growth, cytoskeletal reorganization, and the activation of protein kinases.

# Interactions
Rac2 has been shown to interact with ARHGDIA and Nitric oxide synthase 2A.
RAG1
Recombination activating gene 1 also known as RAG-1 is a protein that in humans is encoded by the RAG1 gene.
The protein encoded by this gene is involved in activation of immunoglobulin V-D-J recombination. The encoded protein is involved in recognition of the DNA substrate, but stable binding and cleavage activity also requires RAG2. The RAG-1/2 complex recognizes the Recombination Signal Sequence (RSS) that flank the V, D and J regions in the gene that codes for the constant region of both the heavy chain and light chain in an antibody. The complex binds to the Recombination Signal Sequences and nicks the DNA. This leads to the removal of the RSS  and the eventual binding of the V D and J sequences.  Defects in this gene can be the cause of several diseases.
Because of these effects, Rag1 deletion is used in mouse models of disease to impair  and  maturation, and functionally deletes mature T and B cells from the immune system.
RALB
Ras-related protein Ral-B (RalB) is a protein that in humans is encoded by the RALB gene on chromosome 2.  This protein is one of two paralogs of the Ral protein, the other being RalA, and part of the Ras GTPase family. RalA functions as a molecular switch to activate a number of biological processes, majorly cell division and transport, via signaling pathways. Its biological role thus implicates it in many cancers.

# Structure
The Ral isoforms share an 80% overall match in amino acid sequence and 100% match in their effector-binding region. The two isoforms mainly differ in the C-terminal hypervariable region, which contains multiple sites for post-translational modification, leading to diverging subcellular localization and biological function. For example, phosphorylation of Serine 194 on RalA by the kinase Aurora A results in the relocation of RalA to the inner mitochondrial membrane, where RalA helps carry out mitochondrial fission; whereas phosphorylation of Serine 198 on RalB by the kinase PKC results in the relocation of RalB to other internal membranes and activation of its tumorigenic function.

# Function
RalB is one of two proteins in the Ral family, which is itself a subfamily within the Ras family of small GTPases. As a Ras GTPase, RalB functions as a molecular switch that becomes active when bound to GTP and inactive when bound to GDP. RalB can be activated by RalGEFs and, in turn, activate effectors in signal transduction pathways leading to biological outcomes. For instance, RalB interacts with two components of the exocyst, Exo84 and Sec5, to promote autophagosome assembly, secretory vesicle trafficking, and tethering. Other downstream biological functions include exocytosis, receptor-mediated endocytosis, tight junction biogenesis, filopodia formation, mitochondrial fission, and cytokinesis.
While the above functions appear to be shared between the two Ral isoforms, their differential subcellular localizations result in their differing involvement in certain biological processes. In particular, RalB is more involved in apoptosis and cell motility. Moreover, RalB specifically interacts with Exo84 to assemble the beclin-1VPS34 autophagy initiation complex, and with Sec5 to activate the innate immune response via the Tank-binding kinase 1 (TBK1).

# Clinical significance
Ral proteins have been associated with the progression of several cancers, including bladder cancer and prostate cancer. Though the exact mechanisms remain unclear, studies reveal that RalB promotes tumor invasion and metastasis. As a result, inhibition of RalB inhibits further progression of cancer. In addition, RalB regulates p53 levels in a K-Ras-independent manner during cancer development. RalB also promotes cell survival during infection by double-stranded DNA viruses by activating TBK1 to carry out an immune response.

# Interactions
RalB has been shown to interact with:
- CDC42,
- EXOC8,
- RALBP1, and
- Sec5.
RBM3
Putative RNA-binding protein 3 is a protein that in humans is encoded by the RBM3 gene.

# Function
This gene is a member of the glycine-rich RNA-binding protein family and encodes a protein with one RNA recognition motif (RRM) domain. Expression of this gene is induced by cold shock and low oxygen tension. A pseudogene exists on chromosome 1. Alternate transcriptional splice variants, encoding different isoforms, have been characterized.
RBM3 is cold-induced RNA binding protein and is involved in mRNA biogenesis exerts anti-apoptotic effects. According to antibody-based profiling and transcriptomics analysis, RBM3 protein is present in all analysed human tissues and based on confocal microscopy mainly localised to the nucleoplasm.

# Clinical significance
RBM3 is a proto-oncogene that is associated with tumor progression and metastasis and is a potential cancer biomarker. Based on patient survival data, high levels of RBM3 protein in tumor cells is a favourable prognostic biomarker in colorectal cancer.
RBMX
Heterogeneous nuclear ribonucleoprotein G is a protein that in humans is encoded by the RBMX gene.

# Function
This gene belongs to the RBMY gene family which includes candidate Y chromosome spermatogenesis genes. This gene, an active X chromosome homolog of the Y chromosome RBMY gene, is widely expressed whereas the RBMY gene evolved a male-specific function in spermatogenesis. Pseudogenes of this gene, found on chromosomes 1, 4, 9, 11, and 6, were likely derived by retrotransposition from the original gene. Alternatively spliced transcript variants encoding different isoforms have been identified but their biological nature has not been determined.

# Interactions
RBMX has been shown to interact with SFRS10 and CDC5L.

# Model organisms
Model organisms have been used in the study of RBMX function. A conditional knockout mouse line called Rbmxtm2b(KOMP)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
RBP1
Retinol binding protein 1, cellular, also known as RBP1, is a protein that in humans is encoded by the RBP1 gene.

# Function
RBP1 is the carrier protein involved in the transport of retinol (vitamin A alcohol) from the liver storage site to peripheral tissue. Vitamin A is a fat-soluble vitamin necessary for growth, reproduction, differentiation of epithelial tissues, and vision. The gene harbors four exons encoding 24, 59, 33, and 16 amino acid residues, respectively. The second intervening sequence alone occupies 19 kb of the 21 kb of the gene.

# Clinical significance
Cellular retinol-binding protein-1 (CRBP-1) contributes to the maintenance of the differentiative state of endometrial cells through the regulation of bioavailability of retinol.  On the converse, loss of CRBP-1 is associated with development of endometrial cancer.
RBP3
Retinol-binding protein 3, interstitial (RBP3), also known as IRBP is a protein that in humans is encoded by the RBP3 gene.  RBP3 orthologs  have been identified in most eutherians except tenrecs and armadillos.

# Function
The inter-photoreceptor retinoid-binding protein is a large glycoprotein known to bind retinoids and found primarily in the interphotoreceptor matrix of the retina between the retinal pigment epithelium and the photoreceptor cells. It is thought to transport retinoids between the retinal pigment epithelium and the photoreceptors, a critical role in the visual process.

# Gene
The human IRBP gene is approximately 9.5 kbp in length and consists of four exons separated by three introns. The introns are 1.6-1.9 kbp long. The gene is transcribed by photoreceptor and retinoblastoma cells into an approximately 4.3-kilobase mRNA that is translated and processed into a glycosylated protein of 135,000 Da.

# Structure
The amino acid sequence of human IRBP can be divided into four contiguous homology domains with 33-38% identity, suggesting a series of gene duplication events. In the gene, the boundaries of these domains are not defined by exon-intron junctions, as might have been expected. The first three homology domains and part of the fourth are all encoded by the first large exon, which is 3,180 base pairs long. The remainder of the fourth domain is encoded in the last three exons, which are 191, 143, and approximately 740 base pairs long, respectively.

# Application
The rbp3 gene is commonly used in animals as a nuclear DNA phylogenetic marker. The exon 1 has first been used in a pioneer study to provide evidence for monophyly of Chiroptera. Then, it has been used to infer the phylogeny of  placental mammal orders, and of the major clades of Rodentia, Macroscelidea, and Primates. RBP3 is also useful at lower taxonomic levels, e.g., in muroid rodents and Malagasy primates, at the phylogeography level in Geomys and Apodemus rodents, and even for carnivora species identification purposes.
Note that the RBP3 intron 1 has also been used to investigate the platyrrhine primates phylogenetics.
RCC1
Regulator of chromosome condensation 1, also known as RCC1, Ran guanine nucleotide exchange factor and RanGEF, is the name for a human gene and protein.
RCC1 also functions as a guanine nucleotide exchange factor for Ran GTPase.

# Interactions
RCC1 has been shown to interact with RANBP3 and Ran (biology).
REC8
Meiotic recombination protein REC8 homolog is a protein that in humans is encoded by the REC8 gene.
Rec8 is a meiosis-specific component of the cohesin complex that binds sister chromatids in preparation for the two divisions of meiosis. Rec8 is sequentially removed from sister chromatids. It is removed from the arms of chromosomes in the first division - separating homologous chromosomes from each other. However, Rec8 is maintained at centromeres so that sister chromatids are kept joined until anaphase of meiosis II, at which point removal of remaining cohesin leads to the separation of sister chromatids.

# Function
This gene encodes a member of the kleisin family of SMC (structural maintenance of chromosome) protein partners. The protein localizes to the axial elements of chromosomes during meiosis in both oocytes and spermatocytes. REC8 protein appears to participate with other cohesins STAG3, SMC1 and SMC3 in sister chromatid cohesion throughout the whole meiotic process in human oocytes.  In the mouse, the homologous protein is a key component of the meiotic cohesion complex, which regulates sister chromatid cohesion and recombination between homologous chromosomes. Multiple alternatively spliced variants, encoding the same protein, have been found for this gene.
Rec8 remains in complex with SMC proteins until anaphase, where it is degraded by Separase once the spindle assembly checkpoint is bypassed. Unlike the other Kleisin family member, Scc1, Rec8 must be phosphorylated prior to degradation. Prior to anaphase, Rec8 is protected from phosphorylation by Protein Phosphatase 2 (PP2A-B56) in mouse.  PP2A is recruited to cohesin by Shugoshin 2 (Sgo2; SGOL2 in yeast). Bypass of the spindle assembly checkpoint activates Separase, which then degrades phosphorylated Rec8 and untethers Cohesin from sister chromatids, allowing for segregation of chromosomes.

# Interactions
REC8 has been shown to interact with SMC3.
REV1
DNA repair protein REV1 is a protein that in humans is encoded by the REV1 gene. 
This gene encodes a protein with similarity to the S. cerevisiae mutagenesis protein Rev1. The Rev1 proteins contain a BRCT domain, which is important in protein-protein interactions. A suggested role for the human Rev1-like protein is as a scaffold that recruits DNA polymerases involved in translesion synthesis (TLS) of damaged DNA. Two alternatively spliced transcript variants that encode different proteins have been found. Rev1 is a Y family DNA polymerase; it is sometimes referred to as a deoxycytidyl transferase because it only inserts deoxycytidine (dC) across from lesions. Whether G, A, T, C, or an abasic site, Rev1 will always add a C. Rev1 has the ability to always add a C, because it uses an arginine as a template which complements well with C. Yet it is believed that Rev1 rarely uses its polymerase activity; rather it is thought that Rev1's primary role is as a protein landing pad, whereby it helps direct the recruitment of TLS proteins, especially Pol  (Rev3/Rev7).

# Interactions
REV1 has been shown to interact with MAD2L2. It is believed that Rev1 may interact with PCNA, once ubiquitylated due to a lesion, and help recruit Pol  (Rev3/Rev7) a B family polymerase involved in TLS.
RFC2
Replication factor C subunit 2 is a protein that in humans is encoded by the RFC2 gene.

# Function
The elongation of primed DNA templates by DNA polymerase delta and epsilon requires the action of the accessory proteins, proliferating cell nuclear antigen (PCNA) and replication factor C (RFC). RFC, also called activator 1, is a protein complex consisting of five distinct subunits of 145, 40, 38, 37, and 36.5 kD. This gene encodes the 40 kD subunit, which has been shown to be responsible for binding ATP. Deletion of this gene has been associated with Williams syndrome. Alternatively spliced transcript variants encoding distinct isoforms have been described.

# Interactions
RFC2 has been shown to interact with BRD4, CHTF18, PCNA, RFC4 and RFC5.
RFX1
MHC class II regulatory factor RFX1 is a protein that, in humans, is encoded by the RFX1 gene located on the short arm of chromosome 19.

# Structure
The RFX1 gene is a member of the regulatory factor X (RFX) gene family, which encodes transcription factors that contain five conserved domains including a highly conserved, centrally located, winged helix DNA binding domain as well as a dimerization domain located in the C-terminal region of the sequence. Apart from the five conserved domains, the RFX proteins diverge significantly. The DNA binding and dimerization domains of the RFX family proteins show no similarities to the other domains with the same functions in other proteins.

# Species distribution
The RFX protein family is conserved in S. pombe, S. cerevisiae, C. elegans, mice and humans. There are seven known RFX proteins in humans, five in mice, and one in C. elegans as well as one in each of the two species of yeast.

# Function
The protein encoded by this gene is structurally related to regulatory factors X2, X3, X4, and X5. It is a transcriptional activator that can bind DNA as a monomer or as a heterodimer with RFX family members X2, X3, and X5, but not with X4. This protein binds to the Xboxes of MHC class II genes and is essential for their expression.  Also, it can bind to an inverted repeat that is required for expression of hepatitis B virus genes. The RFX proteins were originally cloned and characterized due to their high affinity for a cis-acting promoter sequence, called the Xbox, found in all MHC class II genes.
Levels of mRNA encoding this protein as well as RFX2 and RFX3 are found to be consistently elevated in the testis and are variable in other tissues throughout the body.
RFX1 contains a C-terminal sequence with no apparent homology to other RFX proteins. This C-terminal tail contains an acidic region that is thought to aid in crossing the nuclear membrane. Two major functions are hypothesized to this exist for this domain: a contribution to the nuclear localization signal (NLS) as well as the contradictory down-regulation of DNA binding as well as nuclear association. These two functions were originally identified through sequence mutations and translational fusions with gfp (green fluorescent protein) and remain to be confirmed.

# Interactions
RFX1 has been shown to interact with Abl gene.
RFX6
Regulatory factor X, 6 also known as DNA-binding protein RFX6 is a protein that in humans is encoded by the RFX6 gene.

# Function
The nuclear protein encoded by this gene is a member of the regulatory factor X (RFX) family of transcription factors. Studies in mice suggest that this gene is specifically required for the differentiation of islet cells for the production of insulin, but not for the differentiation of pancreatic polypeptide-producing cells. It regulates the transcription factors involved in beta-cell maturation and function, thus, restricting the expression of the beta-cell differentiation and specification genes.

# Clinical significance
Mutations in this gene are associated with Mitchell-Riley syndrome, which is characterized by neonatal diabetes with pancreatic hypoplasia, duodenal and jejunal atresia, and gall bladder agenesis.
RGS2
Regulator of G-protein signaling 2 is a protein that in humans is encoded by the RGS2 gene. It is part of a larger family of RGS proteins that control signalling through G-protein coupled receptors (GPCR).

# Function
RGS2 is thought to have protective effects against myocardial hypertrophy as well as atrial arrhythmias. Increased stimulation of Gs coupled 1-adrenergic receptors and Gq coupled 1-adrenergic receptors in the heart can result in cardiac hypertrophy. In the case of Gq protein coupled receptor (GqPCR) mediated hypertrophy, Gq will activate the intracellular affectors phospholipase C and rho guanine nucleotide exchange factor to stimulate cell processes which lead to cardiomyocyte hypertrophy. RGS2 functions as a GTPase Activating Protein (GAP) which acts to increase the natural GTPase activity of the G subunit.  By increasing the GTPase activity of the G subunit, RGS2 promotes GTP hydrolysis back to GDP, thus converting the G subunit back to its inactive state and reducing its signalling ability. Both GsPCR and GqPCR activation can contribute to cardiac hypertrophy via activation of MAP Kinases as well. RGS2 has been shown to decrease phosphorylation of those MAP kinases and therefore decrease their activation in response to Gs signalling.
In the case of GsPCR mediated hypertrophy, the main mechanism by which signalling contributes to hypertrophy is through the G subunit; Gs signalling by itself is not sufficient.  Nevertheless, RGS2 has been shown to inhibit Gs mediated hypertrophy. The mechanism of how RGS2 regulates increased G signalling is not well understood, apart from the fact that it is unrelated to RGS2s GAP function. A deficiency in RGS2 has been linked with increased cardiac hypertrophy in mice. RGS2 deficient hearts appear normal until confronted with an increased workload, to which they respond readily with increased Gq signalling and hypertrophy.
Gs subunits increase adenyl cyclase activity, which in turn leads to cAMP accumulation in the myocyte nucleus to trigger hypertrophy. RGS2 regulates the effects of increased Gs signalling through its GAP function. Stimulation of GsPCRs  not only leads to hypertrophy but it has also been shown to selectively induce higher expression levels of RGS2 which in turn, protects against hypertrophy, providing a mechanism for maintaining homeostatic conditions.
There has also been some evidence of a role of RGS2 in atrial arrhythmias where RGS2 deficient mice exhibited prolonged and greater susceptibility to electrically induced atrial fibrillation. This was attributed to a decrease in RGS2s inhibitory effects on Gq coupled M3 muscarinic receptor signalling, resulting in increased Gq activity. The M3 muscarinic receptor normally activates delayed rectifier potassium channels in the atria, thus increased Gq activity is thought to result in an altered potassium flux, a decreased refractory period, increased chance of current re-entry and inappropriate contraction.

# Interactions
RGS2 has been shown to interact with PRKG1 and ADCY5.
RGS4
Regulator of G protein signaling 4 also known as RGP4 is a protein that in humans is encoded by the RGS4 gene. RGP4 regulates G protein signaling.

# Function
Regulator of G protein signalling (RGS) family members are regulatory molecules that act as GTPase activating proteins (GAPs) for G alpha subunits of heterotrimeric G proteins. RGS proteins are able to deactivate G protein subunits of the Gi alpha, Go alpha and Gq alpha subtypes. They drive G proteins into their inactive GDP-bound forms. Regulator of G protein signaling 4 belongs to this family. All RGS proteins share a conserved 120-amino acid sequence termed the RGS domain which conveys GAP activity. Regulator of G protein signaling 4 protein is 37% identical to RGS1 and 97% identical to rat Rgs4. This protein negatively regulates signaling upstream or at the level of the heterotrimeric G protein and is localized in the cytoplasm.

# Clinical significance
A number of studies associate the RGS4 gene with schizophrenia, while some fail to detect an association.
RGS4 is also of interest as one of the three main RGS proteins (along with RGS9 and RGS17) involved in terminating signalling by the mu opioid receptor, and may be important in the development of tolerance to opioid drugs.

# Inhibitors
- cyclic peptides
- CCG-4986

# Interactions
RGS4 has been shown to interact with:
- COPB2,
- ERBB3,  and
- GNAQ.
RGS5
Regulator of G-protein signaling 5 is a protein that in humans is encoded by the RGS5 gene.
The regulator of G protein signaling (RGS) proteins are signal transduction molecules that have structural homology to SST2 of Saccharomyces cerevisiae and EGL-10 of Caenorhabditis elegans. Multiple genes homologous to SST2 are present in higher eukaryotes. RGS proteins are involved in the regulation of heterotrimeric G proteins by acting as GTPase activators.

# Interactions
RGS5 has been shown to interact with GNAO1, GNAI2 and GNAI3.