Persius/hicric huggingface dataset:
PHLDA1
Pleckstrin homology-like domain family A member 1 (PHLDA1) is a protein that in humans is encoded by the PHLDA1 gene.
This gene encodes an evolutionarily conserved proline-histidine rich nuclear protein. The encoded protein may play an important role in the anti-apoptotic effects of insulin-like growth factor-1.

# Interactions
PHLDA1 has been shown to interact with RPL14, EIF3D and PABPC4.
PHOX2B
Paired-like homeobox 2b (PHOX2B), also known as neuroblastoma Phox (NBPhox), is a protein that in humans is encoded by the PHOX2B gene located on chromosome 4.
It codes for a homeodomain transcription factor. It is expressed exclusively in the nervous system, in most neurons that control the viscera (cardiovascular, digestive and respiratory systems). It is also required for their differentiation.

# Pathology
Mutations in human PHOX2B cause a rare disease of the visceral nervous system (dysautonomia): congenital central hypoventilation syndrome (associated with respiratory arrests during sleep and, occasionally, wakefulness), Hirschsprung's disease (partial agenesis of the enteric nervous system), ROHHAD, and tumours of the sympathetic ganglia.
In most people, Exon 3 of the gene contains a sequence of 20 polyalanine repeats. An increase in the number of repeats is associated with congenital central hypoventilation syndrome. There may also be other pathogenic mutations further along the gene.
PI4K2A
Phosphatidylinositol 4-kinase 2-alpha is an enzyme that in humans is encoded by the PI4K2A gene.

# Classification
This gene encodes a phosphatidylinositol 4-kinase which catalyzes phosphorylation of phosphatidylinositol at the D-4 position, yielding phosphatidylinositol 4-phosphate (PI4P). Besides the fact, that PI4P serves as a precursor for other important phosphoinositides, such as phosphatidylinositol 4,5-bisphosphate, PI4P is an essential molecule in the cellular signaling and trafficking especially in the Golgi apparatus and the trans Golgi network.
Phosphatidylinositol 4-kinases are evolutionary conserved among eukaryotes and include four human isoforms
- phosphatidylinositol 4-kinase alpha (PI4KA)
- phosphatidylinositol 4-kinase beta (PI4KB)
- phosphatidylinositol 4-kinase 2-alpha (PI4K2A)
- phosphatidylinositol 4-kinase 2-beta (PI4K2B)

# Function
Phosphatidylinositol 4-kinase 2-alpha (PI4K2A) is the most abundant phosphatidylinositol 4-kinase in human cells and is responsible for the synthesis of approximately 50% of the total PI4P within the cell. PI4K2A is associated mainly with the membranes of the trans Golgi network and early and late endosomes; its membrane association is achieved by a heavy palmitoylation within a specific cysteine-rich motif. Besides the synthesis of phosphatidylinositol 4,5-bisphosphate, PI4K2A is involved in various cell processes including membrane trafficking, regulation of endosomal sorting promoting target protein recruitment to endosomes or trans Golgi network, or signal transduction. Particularly, it regulates e.g. targeting of clathrin adaptor complexes to the Golgi apparatus, EGFR signaling, or the Wnt signaling pathway.

# Clinical significance
Dysfunction of PI4K2A may contribute to tumour growth, spastic paraplegia, Gaucher's disease, or Alzheimer's disease.

# Structure
PI4K2A is composed of a proline-rich N-terminal region and a kinase domain located C-terminally. The proline-rich N-terminal region contains physiologically important binding sites for a ubiquitin ligase Itch  and clathrin adaptor complex 3, but is likely disordered and dispensable for the kinase activity. The kinase domain can be divided into N-terminal and C-terminal lobes with the ATP binding groove and putative phosphatidylinositol binding pocket in between. The C-lobe of the kinase domain contains an additional lateral hydrophobic pocket with no distinct function assigned yet.
PIEZO1
Piezo1 is a mechanosensitive ion channel protein that in humans is encoded by the gene PIEZO1.  Piezo1 and its close homolog piezo2 were cloned in 2010, using an siRNA-based screen for mechanosensitive ion channels.

# Structure and function
PIEZO1 (this gene) and PIEZO2 share 47% identity with each other and they have no similarity to any other protein and contain no known protein domains. They are predicted to have 24-36 transmembrane domains, depending on the prediction algorithm used. In the original publication the authors were careful not to call the piezo proteins ion channels, but a more recent study by the same lab convincingly demonstrated that indeed piezo1 is the pore forming subunit of a mechanosensitive channel.

# Tissue distribution
Piezo1 is expressed in the lungs, bladder and skin, where mechanosensation has important biological roles. Unlike Piezo2 which is highly expressed in sensory dorsal root ganglia, piezo1 is not expressed in sensory neurons.

# Clinical significance
Piezo1 is also found in red blood cells, and gain of function mutations in the channels are associated with hereditary xerocytosis or stomatocytosis. Piezo1 channels are pivotal integrators in vascular biology.
An allele of Piezo1, E756del, results in a gain-of-function mutation, resulting in dehydrated RBCs and conveying resistance to Plasmodium. This allele has been demonstrated in vitro to prevent cerebral malaria infection. 

# Ligands
- Yoda1  (small molecule agonist)
PIEZO2
Piezo-type mechanosensitive ion channel component 2 is a protein that in humans is encoded by the PIEZO2 gene.

# Function
Piezos are large transmembrane proteins conserved among various species, all having between 24 and 36 predicted transmembrane domains. 'Piezo' comes from the Greek 'piesi,' meaning 'pressure.' The PIEZO2 protein has a role in rapidly adapting mechanically activated (MA) currents in somatosensory neurons.

# Pathology
- Gain-of-function mutations in the mechanically activated ion channel PIEZO2 cause a subtype of Distal Arthrogryposis.
- Recent studies show that the congenital atrophy in PIEZO2 leads to not having self perception of extremities, and so the distortion in the response to touch (where the response was linked to an emotional response rather than a physical one). It was performed with two patients who would not be able to attempt to coordinate their movements without visually doing it, nor could they know where their extremities were at.
- PIEZO2 mutations link Gordon syndrome (distal arthrogryposis type 3), Marden-Walker syndrome and Arthrogryposis (Distal Arthrogryposis Type 5).
PIK3R1
Phosphatidylinositol 3-kinase regulatory subunit alpha is an enzyme that in humans is encoded by the PIK3R1 gene.

# Function
Phosphatidylinositol 3-kinase phosphorylates the inositol ring of phosphatidylinositol at the 3-prime position. The enzyme comprises a 110 kD catalytic subunit and a regulatory subunit of either 85, 55, or 50 kD. This gene encodes the 85 kD regulatory subunit. Phosphatidylinositol 3-kinase plays an important role in the metabolic actions of insulin, and a mutation in this gene has been associated with insulin resistance. Alternative splicing of this gene results in three transcript variants encoding different isoforms.

# Clinical significance
Mutations in PIK3R1 are implicated in cases of                 breast cancer            .
Mutations in PIK3R1 are associated to                 SHORT syndrome            .

# Interactions
PIK3R1 has been shown to interact with:
- ADAM12,
- BCAR1,
- CBLB,
- CD117,
- CD28,
- CD7,
- CENTG1,
- CBL,
- EPHA2,
- EPOR,
- ERBB3,
- EZR,
- FCGR2A,
- GAB1,
- GAB2,
- Grb2,
- HRAS,
- IRS1
- IRS2,
- IL1R1,
- JAK2,
- KHDRBS1,
- LTK,
- LAT,
- LCP2,
- PIK3CD,
- PTK2,
- SHB,
- TUBA1B,
- TYRO3,
- VAV1, and
- WAS.
PLAGL2
Zinc finger protein PLAGL2 is a protein that in humans is encoded by the PLAGL2 gene.
Zinc finger protein PLAGL2 is a zinc finger protein that recognizes DNA and/or RNA.
The gene has seen in gliomas to suppress cellular differentiation and thus encourage cells to become more stem cell like. Such plasticity is seen in glioma cells, together with the ignorance to differentiation factors.
PLSCR3
Phospholipid scramblase 3 is an enzyme that in humans is encoded by the PLSCR3 gene  (abbreviated to PLS3 in this section). Like the other phospholipid scramblase family members (PLS1, PLS2, PLS4), PLS3 is a type II plasma membrane protein that is rich in proline and integral in apoptosis, or programmed cell death. The regulation of apoptosis is critical for both cell development and tissue homeostasis 
Although phospholipid scramblase is thought to exist in all eukaryotic cells, PLS3 is a protein that is novel to the mitochondria. This is very important because mitochondria are central in the apoptotic cell pathway. This newly found member of the scramblase family is "responsible for phospholipid translocation between two lipid compartments,"  the inner mitochondrial membrane and the outer membrane. Further experimental evidence suggests that the mechanism and effectors of PLS3's enzymatic activity are rather nuanced.

# Effect on mitochondrial cardiolipin
Cardiolipin is a mitochondrion-specific phospholipid found in both the mitochondrial inner and outer membranes Many studies speculate that cardiolipin is a likely player in mitochondrial apoptosis. In a study done by R Lee et al., it was found that during apoptosis, cardiolipin in the outer membrane of the mitochondria increased from 10% to 30% saturation. Finding that cardiolipin concentration in the outer mitochondrial membrane increased during apoptosis (as well as knowing the function that PLS3 plays in mitochondrial apoptotic effects) clued Lee in to the fact that PLS3 may have effects on this cardiolipin membrane redistribution. Lees study looked into the consequences of cardiolipin redistribution in the mitochondria and found that cardiolipin plays a critical role in proteins that are involved with oxidative respiration (such as ATP synthase), which in turn affects ATP production. In Lee's experiment determining the effect of cardiolipin deprivation on cells, he studied an infected yeast mutant that lacked a cardiolipin creating enzyme, and found that although it was viable, the yeast was "moderately deficient in mitochondrial energy transforming machinery."
It was subsequently deduced that PLS3 is an effector for the redistribution of cardiolipin from the inner to outer mitochondrial membrane. Thus, when PLS3 flips cardiolipin across the inner to outer membrane of the mitochondria, the oxidative phosphorylation induced is greatly disturbed. It was deduced experimentally that a lack of proper oxidative phosphorylation is directly linked with mitochondrial apoptosis. Thus, this PLS3-induced redistribution of cardiolipin during apoptosis has major effects on mitochondrial function.

# Summary
Although the results of the experiments above are very intriguing and shed light on what was once a mystery, there have been only a few experiments that have targeted PSL3. And, furthermore, in a majority of the experiments and studies that were reviewed, it is evident that there is some doubt in the experimental findings
PLXNA2
Plexin-A2 is a protein that in humans is coded by the PLXNA2 gene.
This gene encodes a member of the plexin-A family of semaphorin co-receptors. Semaphorins are a large family of secreted or membrane-bound proteins that mediate repulsive effects on axon pathfinding during nervous system development. A subset of semaphorins are recognized by plexin-A/neuropilin transmembrane receptor complexes, triggering a cellular signal transduction cascade that leads to axon repulsion. This plexin-A family member is thought to transduce signals from semaphorin-3A and -3C.
In some studies, the PLXNA2 gene is associated with schizophrenia. and anxiety.
PLXNB1
Plexin B1 is a protein of the plexin family that in humans is encoded by the PLXNB1 gene.

# Function
Within neural tissues, the plexin family serves as transmembrane receptors for Semaphorins. Outside of neural tissues, Plexin B1 is implicated in the control of cell migration.

# Interactions
PLXNB1 has been shown to interact with ARHGEF12, Rnd1 and ARHGEF11.
PNPLA3
Patatin-like phospholipase domain-containing protein 3 (PNPLA3) also known as adiponutrin (ADPN), acylglycerol O-acyltransferase or calcium-independent phospholipase A2-epsilon (iPLA2-epsilon)  is an enzyme that in humans is encoded by the PNPLA3 gene.

# Function
Adiponutrin is a triacylglycerol lipase that mediates triacylglycerol hydrolysis in adipocytes. The encoded protein, which appears to be membrane bound, may be involved in the balance of energy usage/storage in adipocytes.

# Genomics
The gene is located on the long arm of chromosome 22 at band 13.31 (22q13.31). It lies on the Watson (plus) strand and is 40,750 bases in length.
Upstream of the gene putaive binding sites for several transcription factors have been identified. These include PPAR-gamma, POU2F1, and POU2F2. If any of these transcriptions factors are actually involved in the regulation of this gene is not known at present.

# Biochemistry
The recommended name for the gene product is patatin-like phospholipase domain-containing protein 3. It is a Single-pass type II membrane protein and is a multifunctional enzyme with both triacylglycerol lipase and acylglycerol O-acyltransferase activities.  It is involved in the triacylglycerol hydrolysis in adipocytes and may play a role in energy metabolism.
The mature protein is 481 amino acids in length and the predicted molecular weight is 52.865 kiloDaltons (kDa). Two the isoforms have been described but the functional significance - if any - of these forms is not known.

# Clinical relevance
An association between alcoholic liver disease in caucasians and variations in this gene has been confirmed.
Gut 2012;61:150-159 doi:10.1136/gutjnl-2011-301239, Genetic determinants of alcoholic liver disease, Felix Stickel,Jochen Hampe.
POLR1E
DNA-directed RNA polymerase I subunit RPA49 is an enzyme that in humans is encoded by the POLR1E gene.

# Model organisms
Model organisms have been used in the study of POLR1E function. A conditional knockout mouse line, called Polr1etm1a(KOMP)Wtsi was generated as part of the International Knockout Mouse Consortium programa 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 seven tests were carried out on mutant mice and two significant abnormalities were observed.  No homozygous mutant embryos were identified during gestation, and therefore none survived until weaning. The remaining tests were carried out on heterozygous mutant adult mice; no additional significant abnormalities were observed in these animals.

# Interactions
POLR1E has been shown to interact with CD3EAP and POLR1C.
POLR2B
DNA-directed RNA polymerase II subunit RPB2 is an enzyme that in humans is encoded by the POLR2B gene.
This gene encodes the second largest subunit of RNA polymerase II, the polymerase responsible for synthesizing messenger RNA in eukaryotes. This subunit, in combination with at least two other polymerase subunits, forms a structure within the polymerase that maintains contact in the active site of the enzyme between the DNA template and the newly synthesized RNA.

# Interactions
POLR2B has been shown to interact with POLR2C, POLR2E, POLR2H and POLR2L.
POLR2E
DNA-directed RNA polymerases I, II, and III subunit RPABC1 is a protein that in humans is encoded by the POLR2E gene.
This gene encodes the fifth largest subunit of RNA polymerase II, the polymerase responsible for synthesizing messenger RNA in eukaryotes. This subunit is shared by the other two DNA-directed RNA polymerases and is present in two-fold molar excess over the other polymerase subunits. An interaction between this subunit and a hepatitis virus transactivating protein has been demonstrated, suggesting that interaction between transcriptional activators and the polymerase can occur through this subunit. A pseudogene is located on chromosome 11.

# Interactions
POLR2E has been shown to interact with TAF15, POLR2C, POLR2G, POLR2H, POLR2A, POLR2B, POLR2L and GTF2F2.
POLR2G
DNA-directed RNA polymerase II subunit RPB7 is an enzyme that in humans is encoded by the POLR2G gene.
This gene encodes the seventh largest subunit of RNA polymerase II, the polymerase responsible for synthesizing messenger RNA in eukaryotes. In yeast, the association of this subunit with the polymerase under suboptimal growth conditions indicates it may play a role in regulating polymerase function.

# Interactions
POLR2G has been shown to interact with TAF15, POLR2C, POLR2H and POLR2E.
POLR2H
DNA-directed RNA polymerases I, II, and III subunit RPABC3 is a protein that in humans is encoded by the POLR2H gene.
This gene encodes one of the essential subunits of RNA polymerase II that is shared by the other two eukaryotic DNA-directed RNA polymerases, I and III.

# Interactions
POLR2H has been shown to interact with POLR2C, POLR2G, POLR2A, POLR2B and POLR2E.
POLR2L
DNA-directed RNA polymerases I, II, and III subunit RPABC5 is a protein that in humans is encoded by the POLR2L gene.

# Function
This gene encodes a subunit of RNA polymerase II, the polymerase responsible for synthesizing messenger RNA in eukaryotes. The product of this gene contains four conserved cysteines characteristic of an atypical zinc-binding domain. Like its counterpart in yeast, this subunit may be shared by the other two DNA-directed RNA polymerases.

# Interactions
POLR2L has been shown to interact with POLR2C, POLR2A, POLR2B and POLR2E.
POLR3F
DNA-directed RNA polymerase III subunit RPC6 is an enzyme that in humans is encoded by the POLR3F gene.

# Function
The protein encoded by this gene is one of more than a dozen subunits forming eukaryotic RNA polymerase III (RNA Pol III), which transcribes 5S ribosomal RNA and tRNA genes. This protein has been shown to bind both TFIIIB90 and TBP, two subunits of RNA polymerase III transcription initiation factor IIIB (TFIIIB). Unlike most of the other RNA Pol III subunits, the encoded protein is unique to this polymerase.

# Model organisms
Model organisms have been used in the study of POLR3F function. A conditional knockout mouse line called Polr3ftm1a(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
POM121
Nuclear envelope pore membrane protein POM 121 is a protein that in humans is encoded by the POM121 gene. Alternatively spliced variants that encode different protein isoforms have been described but the full-length nature of only one has been determined.

# Function
The nuclear envelope creates distinct nuclear and cytoplasmic compartments in eukaryotic cells. It consists of two concentric membranes perforated by nuclear pores, large protein complexes that form aqueous channels to regulate the flow of macromolecules between the nucleus and the cytoplasm. These complexes are composed of at least 100 different polypeptide subunits, many of which belong to the nucleoporin family. This gene encodes a member of the FG-repeat-containing nucleoporins. The protein encoded by this gene is an integral membrane protein that localizes to the central spoke ring complex and participates in anchoring the nuclear pore complex to the nuclear envelope.
Antibodies against this protein can be used to identify the nuclear envelope in immunofluorescence experiments.
POPDC2
Popeye domain-containing protein 2 is a protein that in humans is encoded by the POPDC2 gene.

# Structure
This gene encodes a member of the POP family of proteins which contain three putative transmembrane domains. This membrane associated protein is predominantly expressed in skeletal and cardiac muscle. The Popeye domain, which is located in the cytoplasmic part of the protein displays limited sequence homology to other proteins, while sequence conservation amongst Popeye proteins is high and amounts to approximately 40%60%.

# Function
The bacterial CAP or CRP proteins are the closest related non-Popdcproteins. CRP proteins function as cyclic nucleotide-regulated transcription factors that modulate the expression of genes encoding enzymes involved in carbohydrate metabolism. The cyclic AMP-binding domains of these proteins display approximately 25% identity and 60% similarity to the Popeye domain. Significant structural similarity is evident between the Popeye domain and cAMP binding domains of eukaryotic protein kinase A (PKA) and HCN channels.

# Ligands
The Popeye domain binds cyclic nucleotides and has a binding affinity (IC50) for cAMP of 120 nM, which is comparable to the affinities reported for PKA (100 nM) and HCN4 (240 nM). One of the interacting proteins is the two-pore potassium (K2P) channel TREK-1. In the presence of Popdc proteins, TREK-1 current is increased. This increase was based on an enhanced membrane representation of TREK-1, suggesting a modulation of channel trafficking by Popdc proteins.

# Animal studies
Genetic inactivation of Popdc2 in mice resulted in bradyarrhythmia, which is strictly stress-dependent. At rest a normal ECG was observed. Gene inactivation in the zebrafish also causes a cardiac arrhythmia phenotype and defective skeletal muscle development.
POU3F2
POU domain, class 3, transcription factor 2 is a protein that in humans is encoded by the POU3F2 gene.

# Function
N-Oct-3 is a protein belonging to a large family of transcription factors that bind to the octameric DNA sequence ATGCAAAT. Most of these proteins share a highly homologous region, referred to as the POU domain, which occurs in several mammalian transcription factors, including the octamer-binding proteins Oct1 (POU2F1; MIM 164175) and Oct2 (POU2F2; MIM 164176), and the pituitary protein Pit1 (PIT1; MIM 173110). Class III POU genes are expressed predominantly in the CNS. It is likely that CNS-specific transcription factors such as these play an important role in mammalian neurogenesis by regulating their diverse patterns of gene expression.

# Disease linkage
The POU3F2 protein associates with the Bipolar disorder. It is involved in the neocortex development in mice, and is linked to a single nucletide polymorphism, Rs1906252, that is associated with a cognitive phenotype: processing information speed.
Chromosome 6q16.1 deletions resulting in loss of one copy of POU3F2 have been shown to cause a human syndrome of susceptibility to obesity and variable levels of developmental delay and Intellectual Disability.

# Interactions
POU3F2 has been shown to interact with PQBP1.
POU3F4
POU domain, class 3, transcription factor 4 is a protein that in humans is encoded by the POU3F4 gene found on the X chromosome.
POU3F4 is involved in the patterning of the neural tube and both the paraventricular and supraoptic nuclei of the hypothalamus in the developing embryo. During development, POU3F4 is also expressed in the mesenchyme of the periotic bone surrounding the inner ear. A knockout mice model displayed that alteration to the POU3F4 gene interrupted this mesenchymal cell differentiation in the superior semicircular canal. The deformities observed in mice were similar to those in humans with X-linked non-syndromic deafness (DFN-3).

# Clinical significance
Genetic testing on various persons has confirmed that mutations of the POU3F4 gene cause X-linked non-syndromic deafness (DFN-3). These known mutations include:
- Missense mutation causing the substitution of amino acid glycine for glutamic acid at position 216
- A deletion of the POU3F4 gene and 530 more kilobases upstream
- An amino acid substitution of serine for leucine (S228L) in POU3F4
- Frameshift truncation and extension mutations at the POU3F4 C-terminus
Physical anomalies caused by POU3F4 mutations that have been recognized by high resolution computed tomography (HRCT) and magnetic resonance imaging (MRI) include absence of the central axis of the cochlea, an abnormally wide lateral internal auditory canal and a thickened stapes footplate. These anomalies are associated with X-linked non-syndromic deafness.