Persius/hicric huggingface dataset:
POU4F1
POU domain, class 4, transcription factor 1 (POU4F1) also known as brain-specific homeobox/POU domain protein 3A (BRN3A), homeobox/POU domain protein RDC-1 or Oct-T1 is a protein that in humans is encoded by the POU4F1 gene.
BRN3A (POU4F1) is a class IV POU domain-containing transcription factor highly expressed in the developing peripheral sensory nervous system (dorsal root ganglia, trigeminal ganglion, and hindbrain sensory ganglia), certain regions of the central nervous system, retinal neurons called ganglion cells, and in cells of the B- and T-lymphocytic lineages.

# Discovery
Brn3a was initially discovered in mice based on homology to the prototypal POU transcription factors Pit1 (Pituitary-specific positive transcription factor 1, Pou1f1), Oct1 (Pou2f1), and the Caenorhabditis elegans factor Unc86, and named Brn3. When multiple members of the Brn3 gene class were discovered, it was renamed Brn3.0 and Brn3a by different groups of researchers.  Subsequently, the gene was systematically renamed Pou4f1 in mice and POU4F1 in humans.  The protein product is still frequently referred to as Brn3a.

# Function
In addition to sensory neurons, in rodents and birds (and presumably humans) Brn3a is expressed in multiple sites in the central nervous system, including the spinal cord, midbrain superior colliculus, red nucleus, nucleus ambiguus, inferior olivary nucleus, habenula, and retina.
Mice with null mutations ("knockouts") in Brn3a die at birth, due to developmental defects in the nucleus ambiguus, which is essential for respiration.
Brn3a is a transcription factor which acts in development by regulating downstream "target" genes.  Microarrays have been used to determine many genes downstream of Brn3a in peripheral sensory neurons.
In the sensory neurons Brn3a is co-expressed with the LIM domain transcription factor ISL1 or Islet1, and has many downstream targets in common with Isl1. Pou4f1/Isl1 double mutant mice show strong epistatic effects in regulation of many downstream genes in the sensory neurons of double mutant mouse embryos.
Although the homozygous Brn3a null mutation is lethal at birth in mice, Brn3a null heterozygotes have no known phenotype. i.e. the Brn3a null mutation is completely recessive.  This can be explained by gene dosage compensation due to autoregulation, in which expression of the remaining copy of the Pou4f1 gene is increased in heterozygotes, leading to near-normal expression of its downstream targets. The combination of homozygote lethality and dosage compensation in heterozygotes may explain why POU4F1 mutations have not been identified in any human disease, whereas diseases are associated with several other members of the POU domain transcription factor class.

# Interactions
POU4F1 has been shown to interact with Estrogen receptor alpha, RIT2 and Ewing sarcoma breakpoint region 1.
PPP1CA
Serine/threonine-protein phosphatase PP1-alpha catalytic subunit is an enzyme that in humans is encoded by the PPP1CA gene.

# Function
The protein encoded by this gene is one of the three catalytic subunits of protein phosphatase 1 (PP1). PP1 is a serine/threonine specific protein phosphatase known to be involved in the regulation of a variety of cellular processes, such as cell division, glycogen metabolism, muscle contractility, protein synthesis, and HIV-1 viral transcription. Increased PP1 activity has been observed in the end stage of heart failure. Studies in both human and mice suggest that PP1 is an important regulator of cardiac function. Mouse studies also suggest that PP1 functions as a suppressor of learning and memory. Three alternatively spliced transcript variants encoding different isoforms have been found for this gene.

# Interactive pathway map
Click on genes, proteins and metabolites below to link to respective articles.
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# Interactions
PPP1CA has been shown to interact with:
- AKAP11,
- BCL2-like 1,
- BCL2L2,
- BRCA1,
- CDC5L,
- Host cell factor C1,
- KvLQT1,
- LMTK2,
- PHACTR3,
- PPP1R15A,
- PPP1R8,
- PPP1R9B,
- Protein kinase R,  and
- SMARCB1.
PPP1CB
Serine/threonine-protein phosphatase PP1-beta catalytic subunit is an enzyme that in humans is encoded by the PPP1CB gene.
The protein encoded by this gene is one of the three catalytic subunits of protein phosphatase 1 (PP1). PP1 is a serine/threonine specific protein phosphatase known to be involved in the regulation of a variety of cellular processes, such as cell division, glycogen metabolism, muscle contractility, protein synthesis, and HIV-1 viral transcription. Mouse studies suggest that PP1 functions as a suppressor of learning and memory. Two alternatively spliced transcript variants encoding distinct isoforms have been observed.

# Interactions
PPP1CB has been shown to interact with PPP1R15A, Nucleolin, SMARCB1 and PPP1R9B.
PPP1R8
Nuclear inhibitor of protein phosphatase 1 is an enzyme that in humans is encoded by the PPP1R8 gene.
This gene, through alternative splicing, encodes three different isoforms. Two of the protein isoforms encoded by this gene are specific inhibitors of type 1 serine/threonine protein phosphatases and can bind but not cleave RNA. The third protein isoform lacks the phosphatase inhibitory function but is a single-strand endoribonuclease comparable to RNase E of E. coli. This isoform requires magnesium for its function and cleaves specific sites in A+U-rich regions of RNA.

# Interactions
PPP1R8 has been shown to interact with PPP1CA, Histone deacetylase 2, SF3B1 EED  and the EZH2 domain of PRC2.
PPP2CB
Serine/threonine-protein phosphatase 2A catalytic subunit beta isoform is an enzyme that in humans is encoded by the PPP2CB gene.

# Function
This gene encodes the phosphatase 2A catalytic subunit. Protein phosphatase 2A is one of the four major Ser/Thr phosphatases, and it is implicated in the negative control of cell growth and division. It consists of a common heteromeric core enzyme, which is composed of a catalytic subunit and a constant regulatory subunit, that associates with a variety of regulatory subunits. This gene encodes a beta isoform of the catalytic subunit. Two transcript variants encoding the same protein have been identified for this gene.

# Interactions
PPP2CB has been shown to interact with TLX1, PPP2R1B and PPP2R1A.
PPP2R4
Serine/threonine-protein phosphatase 2A regulatory subunit B' is an enzyme that in humans is encoded by the PPP2R4 gene.
Protein phosphatase 2A is one of the four major Ser/Thr phosphatases and is implicated in the negative control of cell growth and division. Protein phosphatase 2A holoenzymes are heterotrimeric proteins composed of a structural subunit A, a catalytic subunit C, and a regulatory subunit B. The regulatory subunit is encoded by a diverse set of genes that have been grouped into the B/PR55, B'/PR61, and B/PR72 families. These different regulatory subunits confer distinct enzymatic specificities and intracellular localizations to the holozenzyme. The product of this gene belongs to the B' family. This gene encodes a specific phosphotyrosyl phosphatase activator of the dimeric form of protein phosphatase 2A. Alternative splicing results in multiple transcript variants encoding different isoforms.

# Interactions
PPP2R4 has been shown to interact with PPP2R3A, CCNG1 and Janus kinase 2.
PRIMA1
Proline-rich membrane anchor 1, also known as PRiMA, is a protein that in humans is encoded by the PRIMA1 gene.

# Function
PRiMA functions to organize acetylcholinesterase (AChE) into tetramers, and to anchor AChE at neural cell membranes. This is accomplished by the proline rich anchor domain (PRAD) of PRIMA1 which anchors the tetramer of AChE into the plasma membrane of neural cells and myocytes. The PRAD interacts with the C-terminal T-peptide of AChE.
PRiMA plays a role in targeting AChE to the cell surface and, in neuroblastoma cells, PRiMA the limiting factor of such targeting. In both mice and humans, PRiMA exists as two alternative splice variants that differ in their cytoplasmic regions.

# Clinical significance
The severity of neurogenerative diseases, such as Alzheimers, can be related to the degradation of AChE.
PRKAB1
5'-AMP-activated protein kinase subunit beta-1 is an enzyme that in humans is encoded by the PRKAB1 gene.
The protein encoded by this gene is a regulatory subunit of the AMP-activated protein kinase (AMPK). AMPK is a heterotrimer consisting of an alpha catalytic subunit, and non-catalytic beta and gamma subunits. AMPK is an important energy-sensing enzyme that monitors cellular energy status. In response to cellular metabolic stresses, AMPK is activated, and thus phosphorylates and inactivates acetyl-CoA carboxylase (ACC) and beta-hydroxy beta-methylglutaryl-CoA reductase (HMGCR), key enzymes involved in regulating de novo biosynthesis of fatty acid and cholesterol. This subunit may be a positive regulator of AMPK activity. The myristoylation and phosphorylation of this subunit have been shown to affect the enzyme activity and cellular localization of AMPK. This subunit may also serve as an adaptor molecule mediating the association of the AMPK complex.

# Model organisms
Model organisms have been used in the study of PRKAB1 function. A conditional knockout mouse line, called Prkab1tm1a(KOMP)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.
Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion. Twenty five tests were carried out on mutant mice and four significant abnormalities were observed. Homozygous mutant males displayed impaired glucose tolerance. Animals of both sex had increased circulating bilirubin levels, increased IgG3 levels, and a number of atypical haematology parameters.

# Interactions
PRKAB1 has been shown to interact with PRKAG2 and PRKAG1.
The 5'-AMP-activated protein kinase beta subunit interaction domain (AMPKBI) is a conserved domain found in the beta subunit of the 5-AMP-activated protein kinase complex, and its yeast homologues Sip1 (SNF1-interacting protein 1), Sip2 (SNF1-interacting protein 2) and Gal83 (galactose metabolism 83), which are found in the SNF1 (sucrose non-fermenting) kinase complex. This region is sufficient for interaction of this subunit with the kinase complex, but is not solely responsible for the interaction, and the interaction partner is not known.
PRKAB2
5'-AMP-activated protein kinase subunit beta-2 is an enzyme that in humans is encoded by the PRKAB2 gene.
The protein encoded by this gene is a regulatory subunit of the AMP-activated protein kinase (AMPK). AMPK is a heterotrimer consisting of an alpha catalytic subunit, and non-catalytic beta and gamma subunits. AMPK is an important energy-sensing enzyme that monitors cellular energy status. In response to cellular metabolic stresses, AMPK is activated, and thus phosphorylates and inactivates acetyl-CoA carboxylase (ACC) and beta-hydroxy beta-methylglutaryl-CoA reductase (HMGCR), key enzymes involved in regulating de novo biosynthesis of fatty acid and cholesterol. This subunit may be a positive regulator of AMPK activity. It is highly expressed in skeletal muscle and thus may have tissue-specific roles.

# Related gene problems
- 1q21.1 deletion syndrome
- 1q21.1 duplication syndrome

# Interactions
PRKAB2 has been shown to interact with PRKAG2 and PRKAG1.
Research on the genes CHD1L and PRKAB2 within lymphoblast cells lead to the conclusion that anomalies appear with the 1q21.1 deletion syndrome:
- CHD1L is an enzyme which is involved in untangling the chromatids and the DNA repair system. With 1q21.1 deletion syndrome a disturbance occurs, which leads to increased DNA breaks. The role of CHD1L is similar to that of helicase with the Werner syndrome
- PRKAB2 is involved in maintaining the energy level of cells. With 1q21.1-deletion syndrome this function was attenuated.
PRKACB
cAMP-dependent protein kinase catalytic subunit beta is an enzyme that in humans is encoded by the PRKACB gene.
cAMP is a signaling molecule important for a variety of cellular functions. cAMP exerts its effects by activating the protein kinase A (PKA), which transduces the signal through phosphorylation of different target proteins. The inactive holoenzyme of PKA is a tetramer composed of two regulatory and two catalytic subunits. cAMP causes the dissociation of the inactive holoenzyme into a dimer of regulatory subunits bound to four cAMP and two free monomeric catalytic subunits. Four different regulatory subunits and three catalytic subunits of PKA have been identified in humans. The protein encoded by this gene is a member of the serine/threonine protein kinase family and is a catalytic subunit of PKA. Three alternatively spliced transcript variants encoding distinct isoforms have been observed.

# Interactions
PRKACB has been shown to interact with Ryanodine receptor 2 and Low affinity nerve growth factor receptor.
PRKCB1
Protein kinase C beta type is an enzyme that in humans is encoded by the PRKCB gene.
Protein kinase C (PKC) is a family of serine- and threonine-specific protein kinases that can be activated by calcium and second messenger diacylglycerol. PKC family members phosphorylate a wide variety of protein targets and are known to be involved in diverse cellular signaling pathways. PKC family members also serve as major receptors for phorbol esters, a class of tumor promoters. Each member of the PKC family has a specific expression profile and is believed to play a distinct role in cells. The protein encoded by this gene is one of the PKC family members. This protein kinase has been reported to be involved in many different cellular functions, such as B cell activation, apoptosis induction, endothelial cell proliferation, and intestinal sugar absorption. Studies in mice also suggest that this kinase may also regulate neuronal functions and correlate fear-induced conflict behavior after stress. Alternatively spliced transcript variants encoding distinct isoforms have been reported. This gene could be associated with autism.

# Interactions
PRKCB1 has been shown to interact with RIPK4, beta adrenergic receptor kinase, PDLIM5 and GNB2L1.
PRPF31
PRP31 pre-mRNA processing factor 31 homolog (S. cerevisiae), also known as PRPF31, is a protein which in humans is encoded by the PRPF31 gene.

# Function
PRPF31 is the gene coding for the splicing factor hPRP31. It is essential for the formation of the spliceosome hPRP31 is associated with the U4/U6 di-snRNP and interacts with another splicing factor, hPRP6, to form the U4/U6-U5 tri-snRNP. It has been shown that when hPRP31 is knocked down by RNAi, U4/U6 di-snRNPs accumulate in the Cajal bodies and the U4/U6-U5 tri-snRNP cannot form.
PRPF31 is recruited to introns following the attachment of U4 and U6 RNAs and the 15.5K protein NHP2L1. The addition of PRPF31 is crucial for the transition of the spliceosomal complex to the activated state.

# Clinical significance
A mutation in PRPF31 is one of 4 known mutations in splicing factors which are known to cause retinitis pigmentosa. The first mutation in PRPF31 was discovered by Vithana et al. in 2001. Retinitis pigmentosa (RP) is a clinically and genetically heterogeneous group of retinal dystrophies characterized by a progressive degeneration of photoreceptors, eventually resulting in severe visual impairment.

# Inheritance
Mutations in PRPF31 are inherited in an autosomal dominant manner, accounting for 2.5% of cases of autosomal dominant retinitis pigmentosa (adRP) in a mixed UK population. However, the inheritance pattern of PRPF31 mutations is atypical of dominant inheritance, showing the phenomenon of partial penetrance, whereby a dominant mutations appear to "skip" generations. This is thought to be due to the presence of two wild type alleles, a high-expressivity allele and a low-expressivity allele. If a patient has a mutant allele and a high-expressivity allele, they do not show disease phenotype. If a patient has a mutant allele and a low-expressivity allele, the residual level of protein falls beneath the threahold for normal function, and so they do show disease phenotype. The inheritance pattern of PRPF31 can therefore be thought of as a variation of haploinsufficiency. This variant of haploinsufficiency is only seen in two other human diseases: Erythropoietic protoporphyria, caused by mutations in the FECH gene; and hereditary elliptocytosis, caused by mutations in the spectrin gene.
PRSS56
Putative serine protease 56 (PRSS56) is a serine protease that has been implicated in human eye development.

# Genomics
The gene is located on long arm of chromosome 2 (2q37.1). The encoded protein is 603 amino acid residues in length with a predicted molecular weight of 64 597 Daltons.
The protein contains a peptidase S1 domain and possesses trypsin like serine protease activity.

# Clinical
Mutations in this gene are a cause of autosomal recessive posterior microphthalmos. The clinical features of this condition include extreme hyperopia due to short axial length with essentially normal anterior segment, steep corneal curvatures, shallow anterior chamber, thick lenses and thickened scleral walls. The palpebral fissures appear narrow because of relatively deep set eyes. Visual acuity is mildly to moderately reduced, and anisometropic or strabismic amblyopia is common. The fundus of the eye shows crowded optical discs, tortuous vessels and an abnormal foveal avascular zone.

# Disease Model
Mice homozygous for an ENU induced mutation show increased intraocular pressure, reduction in eye axial length, and narrow iridocorneal angles. Eyes from individuals with angle-closure glaucoma (ACG) often have a modestly decreased axial length, shallow anterior chamber and relatively large lens, features that predispose to angle closure. Homozygous mice model ACG.
PTPN12
Tyrosine-protein phosphatase non-receptor type 12 is an enzyme that in humans is encoded by the PTPN12 gene.
The protein encoded by this gene is a member of the protein tyrosine phosphatase (PTP) family. PTPs are known to be signaling molecules that regulate a variety of cellular processes including cell growth, differentiation, mitotic cycle, and oncogenic transformation. This PTP contains a C-terminal PEST motif, which serves as a proteinprotein interaction domain, and may be related to protein intracellular half-life. This PTP was found to bind and dephosphorylate the product of oncogene c-ABL, thus may play a role in oncogenesis. This PTP was shown to interact with, and dephosphorylate, various of cytoskeleton and cell adhesion molecules, such as p130 (Cas), CAKbeta/PTK2B, PSTPIP1, and paxillin, which suggested its regulatory roles in controlling cell shape and mobility.

# Interactions
PTPN12 has been shown to interact with BCAR1, Grb2, PSTPIP1, TGFB1I1, Paxillin and SHC1.
PTPN22
Protein tyrosine phosphatase, non-receptor type 22 (lymphoid), also known as PTPN22, is a protein that in humans is encoded by the PTPN22 gene. This gene can be expressed in different forms. PTPN22 affects the responsiveness of T and B cell receptors, and mutations are associated with increases or decreases in risks of autoimmune diseases.

# Molecular biology
The gene is located on the short arm of Chromosome 1 near the centromere (1p13.2) on the Crick (minus) strand. It is 57,898  bases in length and encodes a protein of 807 amino acids (molecular weight 91,705 Da). There are 24 exons in the gene and 21 transcript variants encoding 10 distinct proteins are known. The proteins are located in the cytoplasm.

# Function
This gene encodes a protein tyrosine phosphatase which is expressed primarily in lymphoid tissues. This enzyme is involved in several signalling pathways associated with the immune response.  Based on models of the murine phosphatase, structural identification, and human genetics the phosphatase forms complexes with C-src tyrosine kinase (Csk), associated with the control of Src family members. The mutation Arg620Trp disrupts binding to Csk, alters the responsiveness of T and B cell receptors, and is associated with autoimmune diseases. There are other suggestions that the phosphatase regulates CBL function in the T cell receptor signaling pathway. Other interactions are likely.

# Disease association
The common 1858T (rs2476601) Arg620Trp nonsynonymous single nucleotide polymorphism located in the PTPN22 gene has been associated with autoimmune disorders, including an increased risk of Type 1 Diabetes, rheumatoid arthritis, Systemic Lupus Erythematosus, Vitiligo and Graves' disease, but a decreased risk of Crohn's disease.
A recent study suggests that the mutation does not, on a population basis, reduce life span. The mutation may be conserved in human evolution because it may provide a hyper-immune response to infectious disease.
Mutations in PTPN22 are over-represented in breast cancer.
PTPRN2
Receptor-type tyrosine-protein phosphatase N2 (R-PTP-N2) also known as islet cell autoantigen-related protein (ICAAR) and phogrin is an enzyme that in humans is encoded by the PTPRN2 gene. PTPRN and PTPRN2 (this gene) are both found to be major autoantigens associated with insulin-dependent diabetes mellitus.

# Function
Due to a close similarity in the gene sequences, the protein encoded by this gene has traditionally been considered a member of the protein tyrosine phosphatase (PTP) family. PTPs are known to be signaling molecules that regulate a variety of cellular processes including cell growth, differentiation, mitotic cycle, and oncogenic transformation. However, recent research has shown that the PTPRN2 mouse homolog, known as phogrin, dephosphorylates the lipid phosphatidylinositol rather than tyrosine. Specifically, phogrin was shown to act upon phosphatidylinositol 3-phosphate and Phosphatidylinositol 4,5-diphosphate, whereas it has never been observed acting upon tyrosine. PTPRN2 should, therefore, be more accurately considered a PIPase rather than a PTPase. Phosphorylated forms of phosphatidylinositol (PI) are called phosphoinositides and play important roles in lipid signaling, cell signaling and membrane trafficking.
The protein produced by PTPRN2 possesses an extracellular region, a single transmembrane region, and a single intracellular catalytic domain, and thus represents a receptor-type PTP. The catalytic domain of this PTP is most closely related to PTPRN, also known as IA-2.

# Gene
Three alternatively spliced transcript variants of this gene, which encode distinct proteins, have been reported.

# Interactions
PTPRN2 has been shown to interact with: CKAP5, SPTBN4, and UBQLN4.

# Clinical significance
R-PTP-N2 functions as an autoantigen in diabetes mellitus type 1.