PIN4
gene geneOn this page
Also known as PAR14PAR17EPVH
Summary
PIN4 (peptidylprolyl cis/trans isomerase, NIMA-interacting 4, HGNC:8992) is a protein-coding gene on chromosome Xq13.1, encoding Peptidyl-prolyl cis-trans isomerase NIMA-interacting 4 (Q9Y237). Isoform 1 is involved as a ribosomal RNA processing factor in ribosome biogenesis.
This gene encodes a member of the parvulin subfamily of the peptidyl-prolyl cis/trans isomerase protein family. The encoded protein catalyzes the isomerization of peptidylprolyl bonds, and may play a role in the cell cycle, chromatin remodeling, and/or ribosome biogenesis. The encoded protein may play an additional role in the mitochondria.
Source: NCBI Gene 5303 — RefSeq curated summary.
At a glance
- GWAS associations: 2
- Clinical variants (ClinVar): 42 total
- Druggable target: yes
- MANE Select transcript:
NM_006223
Identifiers
Gene identifiers
| Field | Value |
|---|---|
| HGNC ID | HGNC:8992 |
| Approved symbol | PIN4 |
| Name | peptidylprolyl cis/trans isomerase, NIMA-interacting 4 |
| Location | Xq13.1 |
| Locus type | gene with protein product |
| Status | Approved |
| Aliases | PAR14, PAR17, EPVH |
| Ensembl gene | ENSG00000102309 |
| Ensembl biotype | protein_coding |
| OMIM | 300252 |
| Entrez | 5303 |
Gene structure
Transcript identifiers
Ensembl transcripts: 10 — 8 protein_coding, 2 nonsense_mediated_decay
ENST00000218432, ENST00000373662, ENST00000373669, ENST00000423432, ENST00000439980, ENST00000446576, ENST00000496835, ENST00000652108, ENST00000664196, ENST00000913143
RefSeq mRNA: 2 — MANE Select: NM_006223
NM_001170747, NM_006223
CCDS: CCDS14417, CCDS55447
Canonical transcript exons
ENST00000373669 — 4 exons
| Exon | Start | End |
|---|---|---|
| ENSE00000672615 | 72186461 | 72186534 |
| ENSE00000672618 | 72196785 | 72196904 |
| ENSE00001461195 | 72197368 | 72198340 |
| ENSE00002064549 | 72181757 | 72181828 |
Expression profiles
Bgee: expression breadth ubiquitous, 290 present calls, max score 98.84.
FANTOM5 (CAGE): breadth ubiquitous, TPM avg 13.1235 / max 775.5929, expressed in 1737 samples.
FANTOM5 promoters (2 alternative TSS)
| Promoter ID | TPM avg | Samples expressed |
|---|---|---|
| 196725 | 12.8166 | 1731 |
| 196724 | 0.3069 | 132 |
Top tissues by expression
295 total, by Bgee expression score (0-100, higher = more expressed):
| Tissue | Anatomy ID | Expression score | Quality |
|---|---|---|---|
| tendon of biceps brachii | UBERON:0008188 | 98.84 | gold quality |
| cervix squamous epithelium | UBERON:0006922 | 98.81 | gold quality |
| tongue squamous epithelium | UBERON:0006919 | 98.03 | gold quality |
| squamous epithelium | UBERON:0006914 | 97.97 | gold quality |
| gingival epithelium | UBERON:0001949 | 97.91 | gold quality |
| amniotic fluid | UBERON:0000173 | 97.85 | gold quality |
| esophagus squamous epithelium | UBERON:0006920 | 97.83 | gold quality |
| germinal epithelium of ovary | UBERON:0001304 | 97.66 | gold quality |
| buccal mucosa cell | CL:0002336 | 97.62 | gold quality |
| hair follicle | UBERON:0002073 | 97.37 | gold quality |
| epithelial cell of pancreas | CL:0000083 | 97.22 | gold quality |
| pancreatic ductal cell | CL:0002079 | 97.04 | gold quality |
| palpebral conjunctiva | UBERON:0001812 | 96.91 | gold quality |
| epithelium of esophagus | UBERON:0001976 | 96.66 | gold quality |
| nephron tubule | UBERON:0001231 | 96.45 | gold quality |
| parietal pleura | UBERON:0002400 | 96.19 | gold quality |
| sperm | CL:0000019 | 96.16 | gold quality |
| gingiva | UBERON:0001828 | 96.09 | gold quality |
| pleura | UBERON:0000977 | 95.99 | gold quality |
| epithelium of nasopharynx | UBERON:0001951 | 95.94 | gold quality |
| medial globus pallidus | UBERON:0002477 | 95.91 | gold quality |
| visceral pleura | UBERON:0002401 | 95.89 | gold quality |
| male germ cell | CL:0000015 | 95.86 | gold quality |
| cervix epithelium | UBERON:0004801 | 95.51 | gold quality |
| Brodmann (1909) area 23 | UBERON:0013554 | 95.23 | gold quality |
| globus pallidus | UBERON:0001875 | 95.22 | gold quality |
| skeletal muscle tissue of biceps brachii | UBERON:0004502 | 94.98 | gold quality |
| biceps brachii | UBERON:0001507 | 94.67 | gold quality |
| kidney epithelium | UBERON:0004819 | 94.54 | gold quality |
| skeletal muscle tissue of rectus abdominis | UBERON:0004511 | 94.47 | gold quality |
Single-cell (SCXA)
Detected in 1 experiment(s), a significant marker in 1.
| Experiment | Marker? | Max mean expression |
|---|---|---|
| E-ANND-3 | yes | 9.25 |
Regulation
Is transcription factor: no
miRNA regulators (miRDB)
35 targeting PIN4, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):
| miRNA | Max score | Avg score | miRNA target_count |
|---|---|---|---|
| HSA-MIR-186-5P | 99.99 | 70.83 | 3707 |
| HSA-MIR-4282 | 99.99 | 75.36 | 6408 |
| HSA-MIR-4267 | 99.96 | 66.53 | 2368 |
| HSA-MIR-590-3P | 99.96 | 74.34 | 6478 |
| HSA-MIR-141-3P | 99.94 | 72.79 | 2421 |
| HSA-MIR-200A-3P | 99.94 | 72.68 | 2420 |
| HSA-MIR-627-3P | 99.90 | 71.42 | 3316 |
| HSA-MIR-380-3P | 99.89 | 70.18 | 1978 |
| HSA-MIR-30A-3P | 99.87 | 69.74 | 2928 |
| HSA-MIR-30D-3P | 99.87 | 69.92 | 2917 |
| HSA-MIR-30E-3P | 99.87 | 69.68 | 2942 |
| HSA-MIR-5582-3P | 99.86 | 72.48 | 4221 |
| HSA-MIR-4729 | 99.69 | 72.18 | 4233 |
| HSA-MIR-6757-3P | 99.63 | 66.88 | 1089 |
| HSA-MIR-4499 | 99.62 | 67.29 | 1470 |
| HSA-MIR-7106-5P | 99.53 | 67.47 | 3574 |
| HSA-MIR-3123 | 99.47 | 67.15 | 2693 |
| HSA-MIR-766-5P | 99.47 | 67.91 | 2225 |
| HSA-MIR-6505-3P | 99.34 | 67.39 | 1071 |
| HSA-MIR-219A-1-3P | 98.91 | 67.87 | 639 |
| HSA-MIR-4680-3P | 98.64 | 68.60 | 2093 |
| HSA-MIR-4691-5P | 98.41 | 66.77 | 1343 |
| HSA-MIR-6792-3P | 98.41 | 66.86 | 1359 |
| HSA-MIR-6818-5P | 97.50 | 67.10 | 1167 |
| HSA-MIR-6831-3P | 97.49 | 69.29 | 505 |
| HSA-MIR-148B-5P | 97.29 | 66.30 | 992 |
| HSA-MIR-6874-3P | 97.29 | 66.34 | 975 |
| HSA-MIR-3192-5P | 96.98 | 65.76 | 1926 |
| HSA-MIR-6857-3P | 96.70 | 65.43 | 915 |
| HSA-MIR-5702 | 96.68 | 68.21 | 958 |
Literature-anchored findings (GeneRIF, showing 9)
- The N-terminal basic domain of human parvulin hPar14 is responsible for the entry to the nucleus and high-affinity DNA-binding. (PMID:12144781)
- subcellular localization and DNA binding properties of hPar14 are regulated by phosphorylation of the N-terminal domain (PMID:12860119)
- Identification of a longer Parvulin isoform (Par17) that has an extension at the 5’ end including a 75 bp extended open reading frame. (PMID:16522211)
- Data indicate the association of Par14 with insulin receptor substrate 1 (IRS-1) in human HepG2 cells overexpressing both as well as endogenously in the mouse liver. (PMID:23720771)
- Data indicate that Pin1 prolyl isomerase active site cysteine, Cys113, is highly susceptible to oxidation. (PMID:25595659)
- Par14 can be described as an endogenous non-histone chromatin protein, which binds DNA in vivo (PMID:25645591)
- Ca(2+)/Calmodulin binding to the N-terminal of Par17 causes steric hindrance of the Par17 active site, thus interfering with the Par17/tubulin interaction. (PMID:25940090)
- Numerous other proteins in addition to PIN1 are endowed with PPIase activity. These include other members of the parvulin family to which PIN1 belongs, such as PIN4, as well as several cyclophilins and FK506-binding proteins…This review will discuss studies providing evidence for multiple roles of PIN1 and other PPIases in glioblastoma and medulloblastoma, the most frequent adult and pediatric primary brain tumors. (PMID:30314361)
- Par14 interacts with the androgen receptor, augmenting both its transcriptional activity and prostate cancer proliferation. (PMID:36583514)
Cross-species orthologs
5 orthologs
| Organism | Symbol | Gene ID |
|---|---|---|
| danio_rerio | pin4 | ENSDARG00000004527 |
| mus_musculus | Pin4 | ENSMUSG00000079480 |
| rattus_norvegicus | Pin4 | ENSRNOG00000050051 |
| drosophila_melanogaster | CG11858 | FBGN0039305 |
| caenorhabditis_elegans | WBGENE00012996 |
Paralogs (1): PIN1 (ENSG00000127445)
Protein
Protein identifiers
Peptidyl-prolyl cis-trans isomerase NIMA-interacting 4 — Q9Y237 (reviewed: Q9Y237)
Alternative names: Parvulin-14, Parvulin-17, Peptidyl-prolyl cis-trans isomerase Pin4, Peptidyl-prolyl cis/trans isomerase EPVH, Rotamase Pin4
All UniProt accessions (7): Q9Y237, A0A494C021, D6RFY5, H0Y4T6, H0Y610, H0Y8P6, J3KMW3
UniProt curated annotations — full annotation on UniProt →
Function. Isoform 1 is involved as a ribosomal RNA processing factor in ribosome biogenesis. Binds to tightly bent AT-rich stretches of double-stranded DNA. Isoform 2 binds to double-stranded DNA.
Subunit / interactions. Isoform 1 is found in pre-ribosomal ribonucleoprotein (pre-rRNP) complexes.
Subcellular location. Nucleus. Nucleolus. Cytoplasm. Cytoskeleton. Spindle. Cytoplasm Mitochondrion. Mitochondrion matrix.
Tissue specificity. Isoform 2 is much more stable than isoform 1 (at protein level). Ubiquitous. Isoform 1 and isoform 2 are expressed in kidney, liver, blood vessel, brain, mammary gland, skeletal muscle, small intestine and submandibularis. Isoform 1 transcripts are much more abundant than isoform 2 in each tissue analyzed.
Post-translational modifications. Phosphorylated. Isoform 1 phosphorylation occurs both in the nucleus and the cytoplasm. Isoform 1 phosphorylation at Ser-19 does not affect its PPIase activity but is required for nuclear localization, and the dephosphorylation is a prerequisite for the binding to DNA. The unphosphorylated isoform 1 associates with the pre-rRNP complexes in the nucleus. Isoform 2 is sumoylated with SUMO2 and SUMO3.
Domain organisation. The PPIase domain enhances mitochondrial targeting.
Miscellaneous. The first 25 amino acids are sufficient for mitochondrial targeting.
Similarity. Belongs to the PpiC/parvulin rotamase family. PIN4 subfamily.
Isoforms (3)
| UniProt ID | Names | Canonical? |
|---|---|---|
| Q9Y237-1 | 1 | yes |
| Q9Y237-2 | 2 | |
| Q9Y237-3 | 3 |
RefSeq proteins (2): NP_001164218, NP_006214* (*=MANE)
Domains & families (InterPro)
| ID | Name | Type |
|---|---|---|
| IPR000297 | PPIase_PpiC | Domain |
| IPR043323 | PIN4 | Family |
| IPR046357 | PPIase_dom_sf | Homologous_superfamily |
Pfam: PF13616
Catalyzed reactions (Rhea), 1 shown:
- [protein]-peptidylproline (omega=180) = [protein]-peptidylproline (omega=0) (RHEA:16237)
UniProt features (23 total): strand 5, helix 4, region of interest 3, mutagenesis site 2, sequence variant 2, splice variant 2, chain 1, domain 1, turn 1, compositionally biased region 1, modified residue 1
Structure
Experimental structures (PDB)
5 structures.
| PDB | Method | Resolution (Å) |
|---|---|---|
| 3UI4 | X-RAY DIFFRACTION | 0.8 |
| 3UI6 | X-RAY DIFFRACTION | 0.89 |
| 3UI5 | X-RAY DIFFRACTION | 1.4 |
| 1EQ3 | SOLUTION NMR | |
| 1FJD | SOLUTION NMR |
Predicted structure (AlphaFold)
| Model | pLDDT | Fraction very-high |
|---|---|---|
| AF-Q9Y237-F1 | 80.28 | 0.33 |
Functional residue map
Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.
Post-translational modifications (1): 19
Mutagenesis-validated functional residues (2):
| Position | Phenotype |
|---|---|
| 19 | does not abolish nuclear localization and reduces dna-binding ability. |
| 19 | abolishes phosphorylation and strongly reduces nuclear localization. |
Function
Pathways and Gene Ontology
Reactome pathways
0 pathways
MSigDB gene sets: 107 (showing top):
GSE18804_SPLEEN_MACROPHAGE_VS_TUMORAL_MACROPHAGE_UP, GOBP_RIBOSOME_BIOGENESIS, MULLIGHAN_NPM1_SIGNATURE_3_UP, ONKEN_UVEAL_MELANOMA_UP, BLALOCK_ALZHEIMERS_DISEASE_UP, TIEN_INTESTINE_PROBIOTICS_24HR_UP, SPIELMAN_LYMPHOBLAST_EUROPEAN_VS_ASIAN_UP, GOBP_RIBONUCLEOPROTEIN_COMPLEX_BIOGENESIS, GOCC_SPINDLE, GOCC_PRERIBOSOME, GOCC_MITOCHONDRIAL_MATRIX, GOCC_NUCLEOLUS, GOCC_RIBONUCLEOPROTEIN_COMPLEX, GOMF_CIS_TRANS_ISOMERASE_ACTIVITY, RHEIN_ALL_GLUCOCORTICOID_THERAPY_DN
GO Biological Process (1): rRNA processing (GO:0006364)
GO Molecular Function (7): DNA binding (GO:0003677), bent DNA binding (GO:0003681), double-stranded DNA binding (GO:0003690), RNA binding (GO:0003723), peptidyl-prolyl cis-trans isomerase activity (GO:0003755), protein binding (GO:0005515), isomerase activity (GO:0016853)
GO Cellular Component (10): nucleus (GO:0005634), nucleoplasm (GO:0005654), chromosome (GO:0005694), nucleolus (GO:0005730), cytoplasm (GO:0005737), mitochondrial matrix (GO:0005759), spindle (GO:0005819), preribosome (GO:0030684), mitochondrion (GO:0005739), cytoskeleton (GO:0005856)
GO top-level categories
Rollup of top GO terms by namespace:
| Category | Terms |
|---|---|
| intracellular membraneless organelle | 4 |
| nucleic acid binding | 2 |
| DNA binding | 2 |
| intracellular membrane-bounded organelle | 2 |
| nuclear lumen | 2 |
| cellular anatomical structure | 2 |
| RNA processing | 1 |
| rRNA metabolic process | 1 |
| ribosome biogenesis | 1 |
| cis-trans isomerase activity | 1 |
| catalytic activity, acting on a protein | 1 |
| binding | 1 |
| catalytic activity | 1 |
| intracellular anatomical structure | 1 |
| mitochondrion | 1 |
| intracellular organelle lumen | 1 |
| microtubule cytoskeleton | 1 |
| ribonucleoprotein complex | 1 |
| cytoplasm | 1 |
Protein interactions and networks
STRING
2873 interactions, top by confidence (×1000):
| Protein A | Protein B | Partner UniProt | Score |
|---|---|---|---|
| PIN4 | FKBP1A | P20071 | 803 |
| PIN4 | EPRS1 | P07814 | 724 |
| PIN4 | NKTR | P30414 | 667 |
| PIN4 | PLK1 | P53350 | 552 |
| PIN4 | NR1I2 | O75469 | 542 |
| PIN4 | GLRX5 | Q86SX6 | 530 |
| PIN4 | PPIG | Q13427 | 498 |
| PIN4 | CLK1 | P49759 | 497 |
| PIN4 | AMACR | Q9UHK6 | 473 |
| PIN4 | F2R | P25116 | 472 |
| PIN4 | PIN1 | Q13526 | 463 |
| PIN4 | NUCLEOLIN | P19338 | 459 |
| PIN4 | CLIC2 | O15247 | 444 |
| PIN4 | RPS19 | P39019 | 437 |
| PIN4 | POLR2A | P24928 | 431 |
IntAct
44 interactions, top by confidence:
| A | B | Type | Score |
|---|---|---|---|
| FAM9B | PIN4 | psi-mi:“MI:0915”(physical association) | 0.670 |
| PIN4 | ZBTB9 | psi-mi:“MI:0915”(physical association) | 0.670 |
| PIN4 | CEP72 | psi-mi:“MI:0915”(physical association) | 0.670 |
| PIN4 | FAM9B | psi-mi:“MI:0915”(physical association) | 0.670 |
| CEP72 | PIN4 | psi-mi:“MI:0915”(physical association) | 0.670 |
| ERH | SNRPD3 | psi-mi:“MI:0914”(association) | 0.580 |
| PIN4 | MAGEA11 | psi-mi:“MI:0915”(physical association) | 0.560 |
| PIN4 | PNMA1 | psi-mi:“MI:0915”(physical association) | 0.560 |
| FATE1 | PIN4 | psi-mi:“MI:0915”(physical association) | 0.560 |
| MAGEA11 | PIN4 | psi-mi:“MI:0915”(physical association) | 0.560 |
| PIN4 | FATE1 | psi-mi:“MI:0915”(physical association) | 0.560 |
| EGFR | PIN4 | psi-mi:“MI:0915”(physical association) | 0.550 |
| PIN4 | EGFR | psi-mi:“MI:0915”(physical association) | 0.550 |
| GNAT3 | psi-mi:“MI:0915”(physical association) | 0.400 | |
| PIN4 | CHST15 | psi-mi:“MI:0915”(physical association) | 0.400 |
| PIN4 | E7 | psi-mi:“MI:0915”(physical association) | 0.370 |
| ERBB2 | PIN4 | psi-mi:“MI:0915”(physical association) | 0.370 |
| ERBB3 | PIN4 | psi-mi:“MI:0915”(physical association) | 0.370 |
| ERBB4 | PIN4 | psi-mi:“MI:0915”(physical association) | 0.370 |
BioGRID (86): PIN4 (Two-hybrid), PNMA1 (Two-hybrid), CEP72 (Two-hybrid), FATE1 (Two-hybrid), FAM9B (Two-hybrid), ZBTB9 (Two-hybrid), PIN4 (Affinity Capture-RNA), CCT5 (Co-fractionation), DYNC1H1 (Co-fractionation), MARS (Co-fractionation), PIN4 (Co-fractionation), PIN4 (Co-fractionation), PIN4 (Co-fractionation), CHST15 (Affinity Capture-MS), FRMD1 (Two-hybrid)
ESM2 similar proteins: A0JNJ5, A6QPY8, B5KFL3, F1Q749, F1RRT2, F8RP11, O43100, O43102, O60832, O88600, P02600, P02606, P05977, P08590, P09541, P09542, P12829, P16409, P17209, P34932, P85100, Q12906, Q15147, Q28BT8, Q2TFN9, Q4I665, Q4WJM6, Q503Y7, Q5B5W1, Q5R495, Q5R887, Q5RDM4, Q5ZJH9, Q5ZLF0, Q5ZLN5, Q61316, Q66T82, Q6GL57, Q6P4K8, Q6P848
Diamond homologs: A1VYV6, A4IKU2, A5I7R3, A5N4J2, A6QI23, A6QPY8, A6U2U4, A7FPK5, A7GJD2, A7X3U8, A8YY10, B1IGZ5, B1KTE0, B1YK87, B5KFL3, B9DY54, C1FNE4, C3KW94, C5D6L9, O74448, P0ABZ6, P0ABZ7, P0ABZ8, P0ABZ9, P0C2B5, P0DMT5, P24327, P40415, P44092, P56112, P60747, P60748, P60749, P60750, Q02473, Q02VE3, Q03GD4, Q03QE1, Q07YK0, Q0HLT0
SIGNOR signaling
4 interactions.
| A | Effect | B | Mechanism |
|---|---|---|---|
| CSNK2A1 | “down-regulates activity” | PIN4 | phosphorylation |
| PIN4 | up-regulates | “Ribosome biogenesis” | |
| PIN4 | up-regulates | rRNA_transcription | |
| PIN4 | “up-regulates activity” | IRS1 | isomerization |
Enriched among interaction partners
Reactome pathways and GO biological processes over-represented among this gene’s 31 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.
Reactome pathways:
| Pathway | Partners | Fold | FDR |
|---|---|---|---|
| RAF/MAP kinase cascade | 5 | 13.3× | 6e-04 |
Disease & clinical
Clinical variants and AI predictions
ClinVar
42 variants total. Per-class counts are floors (≥ shown; pagination cap):
| Classification | Count (floor) |
|---|---|
| Pathogenic | 0 |
| Likely pathogenic | 0 |
| Uncertain significance | 19 |
| Likely benign | 0 |
| Benign | 0 |
Top pathogenic / likely-pathogenic (0)
SpliceAI
1750 predictions. Top by Δscore:
| Variant | Effect | Δscore |
|---|---|---|
| X:72186457:AAAG:A | acceptor_gain | 1.0000 |
| X:72186457:AAAGG:A | acceptor_gain | 1.0000 |
| X:72186531:AAAG:A | donor_loss | 1.0000 |
| X:72186535:G:A | donor_loss | 1.0000 |
| X:72186536:T:A | donor_loss | 1.0000 |
| X:72195195:GA:G | donor_gain | 1.0000 |
| X:72196780:TGCA:T | acceptor_loss | 1.0000 |
| X:72196781:GCAG:G | acceptor_loss | 1.0000 |
| X:72196783:A:AG | acceptor_gain | 1.0000 |
| X:72196784:G:GG | acceptor_gain | 1.0000 |
| X:72196784:GGTC:G | acceptor_gain | 1.0000 |
| X:72196784:GGTCA:G | acceptor_gain | 1.0000 |
| X:72196902:GGG:G | donor_gain | 1.0000 |
| X:72196903:GG:G | donor_gain | 1.0000 |
| X:72196903:GGG:G | donor_gain | 1.0000 |
| X:72196904:GG:G | donor_gain | 1.0000 |
| X:72196904:GGT:G | donor_loss | 1.0000 |
| X:72196905:G:T | donor_loss | 1.0000 |
| X:72196906:T:TC | donor_loss | 1.0000 |
| X:72238841:TACCT:T | donor_loss | 1.0000 |
| X:72272768:TTGCC:T | acceptor_gain | 1.0000 |
| X:72272769:TGCC:T | acceptor_gain | 1.0000 |
| X:72272770:GCC:G | acceptor_gain | 1.0000 |
| X:72272771:CC:C | acceptor_gain | 1.0000 |
| X:72272771:CCC:C | acceptor_gain | 1.0000 |
| X:72272772:CC:C | acceptor_gain | 1.0000 |
| X:72272773:C:CC | acceptor_gain | 1.0000 |
| X:72272773:C:T | acceptor_gain | 1.0000 |
| X:72272774:T:A | acceptor_loss | 1.0000 |
| X:72273228:TTACC:T | donor_loss | 1.0000 |
AlphaMissense
870 scored. Top likely-pathogenic:
| Variant | Protein change | am_pathogenicity |
|---|---|---|
| X:72196795:T:A | I43N | 1.000 |
| X:72196801:G:A | C45Y | 1.000 |
| X:72196802:T:G | C45W | 1.000 |
| X:72197423:C:A | A98E | 1.000 |
| X:72197477:T:A | V116D | 1.000 |
| X:72197483:C:T | T118I | 1.000 |
| X:72197488:T:C | F120L | 1.000 |
| X:72197490:T:A | F120L | 1.000 |
| X:72197490:T:G | F120L | 1.000 |
| X:72197491:G:A | G121R | 1.000 |
| X:72197491:G:C | G121R | 1.000 |
| X:72197492:G:A | G121E | 1.000 |
| X:72197492:G:T | G121V | 1.000 |
| X:72197504:T:A | I125N | 1.000 |
| X:72196786:T:A | V40D | 0.999 |
| X:72196789:G:C | R41T | 0.999 |
| X:72196789:G:T | R41I | 0.999 |
| X:72196791:C:A | H42N | 0.999 |
| X:72196791:C:G | H42D | 0.999 |
| X:72196792:A:G | H42R | 0.999 |
| X:72196793:C:A | H42Q | 0.999 |
| X:72196793:C:G | H42Q | 0.999 |
| X:72196795:T:C | I43T | 0.999 |
| X:72196795:T:G | I43S | 0.999 |
| X:72196798:T:C | L44P | 0.999 |
| X:72196800:T:C | C45R | 0.999 |
| X:72196827:G:C | A54P | 0.999 |
| X:72196828:C:A | A54D | 0.999 |
| X:72196840:T:C | L58S | 0.999 |
| X:72196857:T:C | F64L | 0.999 |
dbSNP variants (sampled 300 via entrez): RS1000086952 (X:72190739 G>A), RS1000098291 (X:72186776 C>T), RS1000307391 (X:72231737 A>G), RS1000381258 (X:72222482 C>T), RS1000526361 (X:72252008 C>T), RS1000603897 (X:72199285 A>C), RS1000648071 (X:72215339 A>G), RS1000698302 (X:72238274 C>T), RS1000732667 (X:72226010 T>C), RS1000749566 (X:72212739 G>A,T), RS1000835180 (X:72186466 G>T), RS1000901144 (X:72188718 C>G), RS1000902268 (X:72261095 C>T), RS1000957922 (X:72216201 C>G,T), RS1000976185 (X:72213325 C>G)
Disease associations
OMIM: gene MIM:300252 | disease phenotypes:
GenCC curated gene-disease
Mondo (0):
Orphanet (0):
HPO phenotypes
0 total (0 of 0 shown, HPO-id order):
GWAS associations
2 associations (top):
| Study | Trait | p-value |
|---|---|---|
| GCST005790_47 | Rosacea symptom severity | 7.000000e-06 |
| GCST012466_5 | Autism spectrum disorder | 6.000000e-06 |
EFO canonical traits (1, from GWAS)
| EFO ID | Trait name |
|---|---|
| EFO:0009180 | rosacea severity measurement |
Drugs & pharmacology
Drug and pharmacology data
Is drug target: yes
ChEMBL targets (1): CHEMBL4923 (SINGLE PROTEIN)
PharmGKB: 1 entry (VIP=true, CPIC=false)
ChEMBL bioactivities
1 potent at pChembl≥5 of 4 total, top 1 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).
| pChembl | Type | Value | Unit | Molecule |
|---|---|---|---|---|
| 5.82 | IC50 | 1500 | nM | CHEMBL2409076 |
PubChem BioAssay actives
1 with measured affinity, of 8 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.
| Compound | Assay | Type | Value | Unit |
|---|---|---|---|---|
| ethyl 2-[13-(2-ethoxy-2-oxoethyl)-5,7,12,14-tetraoxo-6,13-diazatetracyclo[6.6.2.04,16.011,15]hexadeca-1(15),2,4(16),8,10-pentaen-6-yl]acetate | 761671: Inhibition of Par14 (unknown origin) | ic50 | 1.5000 | uM |
CTD chemical–gene interactions
38 total (human), top 30 by PubMed support.
| Chemical | Actions (top 5) | PubMed papers |
|---|---|---|
| Valproic Acid | affects expression, increases expression | 3 |
| bisphenol A | affects cotreatment, decreases methylation, increases expression | 2 |
| sodium arsenite | affects methylation, affects cotreatment, increases expression | 2 |
| Benzo(a)pyrene | affects methylation, decreases expression, increases methylation | 2 |
| Cyclosporine | decreases expression | 2 |
| Aflatoxin B1 | decreases methylation, increases methylation | 2 |
| bisphenol F | increases expression | 1 |
| dicrotophos | decreases expression | 1 |
| methylmercuric chloride | decreases expression | 1 |
| terbufos | increases methylation | 1 |
| tris(1,3-dichloro-2-propyl)phosphate | decreases expression | 1 |
| potassium chromate(VI) | decreases expression | 1 |
| nutlin 3 | affects cotreatment, increases secretion | 1 |
| ICG 001 | decreases expression | 1 |
| bisphenol B | increases expression | 1 |
| abrine | decreases expression | 1 |
| bisphenol S | increases expression | 1 |
| MT19c compound | increases expression | 1 |
| bisphenol AF | increases expression | 1 |
| Temozolomide | decreases expression | 1 |
| Fulvestrant | affects cotreatment, decreases methylation | 1 |
| Acetaminophen | decreases expression | 1 |
| Arsenic | affects methylation | 1 |
| Cannabidiol | decreases expression | 1 |
| Dactinomycin | affects cotreatment, increases secretion | 1 |
| Fonofos | increases methylation | 1 |
| Ivermectin | decreases expression | 1 |
| Methyl Methanesulfonate | increases expression | 1 |
| Parathion | increases methylation | 1 |
| Ribonucleotides | affects binding | 1 |
ChEMBL screening assays
7 unique, capped per target: 7 binding
Representative assays (with source publication via chembl_document):
| Assay ID | Type | Description | Source paper |
|---|---|---|---|
| CHEMBL2410563 | Binding | Inhibition of Par14 (unknown origin) | Pin1 inhibitors: Pitfalls, progress and cellular pharmacology. — Bioorg Med Chem Lett |
Clinical trials (associated diseases)
0 trials via MONDO — disease-level, not drug-specific.
Related Atlas pages
No linked Atlas pages yet — the cross-entity mesh grows as the corpus expands.