URI1

Summary

URI1 (URI1 prefoldin like chaperone, HGNC:13236) is a protein-coding gene on chromosome 19q12, encoding Unconventional prefoldin RPB5 interactor 1 (O94763). Involved in gene transcription regulation. It is a common-essential gene (DepMap: required in 95.7% of cancer cell lines).

This gene encodes member of the prefoldin family of molecular chaperones. The encoded protein functions as a scaffolding protein and plays roles in ubiquitination and transcription, in part though interactions with the RNA polymerase II subunit RPB5. This gene may play a role in multiple malignancies including ovarian cancer and hepatocellular carcinoma. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene, and a pseudogene of this gene is located on the long arm of chromosome 22.

Source: NCBI Gene 8725 — RefSeq curated summary.

At a glance

• GWAS associations: 5
• Clinical variants (ClinVar): 104 total
• Cancer dependency (DepMap): dependent in 95.7% of screened cell lines (common-essential)
• MANE Select transcript: NM_003796

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:13236
Approved symbol	URI1
Name	URI1 prefoldin like chaperone
Location	19q12
Locus type	gene with protein product
Status	Approved
Aliases	RMP, NNX3, FLJ10575, URI, PPP1R19
Ensembl gene	ENSG00000105176
Ensembl biotype	protein_coding
OMIM	603494
Entrez	8725

Gene structure

Transcript identifiers

Ensembl transcripts: 17 — 12 protein_coding, 3 protein_coding_CDS_not_defined, 2 nonsense_mediated_decay

ENST00000360605, ENST00000392271, ENST00000570564, ENST00000570704, ENST00000573052, ENST00000574110, ENST00000574176, ENST00000574233, ENST00000574666, ENST00000574766, ENST00000575242, ENST00000576442, ENST00000585655, ENST00000909804, ENST00000909805, ENST00000909806, ENST00000926067

RefSeq mRNA: 2 — MANE Select: NM_003796 NM_001252641, NM_003796

CCDS: CCDS12420, CCDS58658

Canonical transcript exons

ENST00000392271 — 11 exons

Exon	Start	End
ENSE00003461488	29971193	29971227
ENSE00003464814	30009005	30009353
ENSE00003487363	30005361	30005452
ENSE00003489869	30007470	30007638
ENSE00003500455	30012285	30012531
ENSE00003509247	29942239	29942664
ENSE00003570189	30011094	30011236
ENSE00003570879	29986282	29986417
ENSE00003597886	30005651	30005708
ENSE00003615214	29985223	29985301
ENSE00003684182	30014887	30016612

Expression profiles

Bgee: expression breadth ubiquitous, 292 present calls, max score 98.05.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 35.9045 / max 553.9949, expressed in 1818 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
175012	29.9634	1817
175014	5.1497	1636
175013	0.7423	441
175011	0.0226	3
175018	0.0224	2
175019	0.0041	1

Top tissues by expression

295 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
adrenal tissue	UBERON:0018303	98.05	gold quality
calcaneal tendon	UBERON:0003701	97.94	gold quality
left testis	UBERON:0004533	96.66	gold quality
right testis	UBERON:0004534	96.62	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	96.45	gold quality
rectum	UBERON:0001052	95.88	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	95.72	gold quality
parotid gland	UBERON:0001831	95.55	gold quality
left ovary	UBERON:0002119	95.55	gold quality
ventricular zone	UBERON:0003053	95.54	gold quality
spinal cord	UBERON:0002240	95.51	gold quality
testis	UBERON:0000473	95.48	gold quality
islet of Langerhans	UBERON:0000006	95.42	gold quality
muscle of leg	UBERON:0001383	95.42	gold quality
gastrocnemius	UBERON:0001388	95.40	gold quality
tendon	UBERON:0000043	95.22	gold quality
endocervix	UBERON:0000458	95.20	gold quality
corpus callosum	UBERON:0002336	95.14	gold quality
skin of abdomen	UBERON:0001416	95.04	gold quality
right ovary	UBERON:0002118	95.00	gold quality
body of pancreas	UBERON:0001150	94.98	gold quality
colonic epithelium	UBERON:0000397	94.96	gold quality
medial globus pallidus	UBERON:0002477	94.93	gold quality
muscle organ	UBERON:0001630	94.81	gold quality
right adrenal gland cortex	UBERON:0035827	94.77	gold quality
adrenal gland	UBERON:0002369	94.76	gold quality
ectocervix	UBERON:0012249	94.72	gold quality
pancreas	UBERON:0001264	94.68	gold quality
middle frontal gyrus	UBERON:0002702	94.65	gold quality
left adrenal gland	UBERON:0001234	94.56	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.97

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

1 targets.

Target	Regulation
AR	Repression

Upstream regulators (CollecTRI, top): AR

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 95.7% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 17)

• a component of a signaling pathway that coordinates nutrient availability with gene expression (PMID:14615539)
• Data show that URI and PP1gamma are components of an S6K1-regulated mitochondrial pathway dedicated to oppose sustained S6K1 survival signaling and to ensure that the threshold for apoptosis is set based on nutrient and growth factor availability. (PMID:17936702)
• Is part of an RNA polymerase II-associated complex with possible chaperone activity. (PMID:19450687)
• Data show that URI is an “addicting” oncogene selectively required for the survival of ovarian cancer cells with increased URI copy number. (PMID:21397856)
• Data show that while Art-27 can bind AR directly, URI is bound to chromatin prior to hormone-dependent recruitment of AR, suggesting a role for URI in modulating AR recruitment to target genes. (PMID:21730289)
• Higher level of URI/RMP expression in high-grade endometrioid adenocarcinomas compared to tissues of adjacent endometrium or gland suggests a diagnostic and possibly, a prognostic value of URI/RMP in endometrioid adenocarcinoma. (PMID:24228101)
• URI may have an important role in the development of multiple myeloma and chemotherapeutic resistance through activation of the IL-6/STAT3 pathway. (PMID:24625985)
• Results show that URI expression is essential for hepatocarcinogenesis and associated with poor survival. (PMID:25453901)
• High URI1 expression is associated with epithelial ovarian cancer. (PMID:25527175)
• RMP status in tumors may be a useful marker in estimating prognosis in patients with hepatocellular carcinoma and in assisting in the selection of patients who are likely to benefit from adjuvant TACE to prevent relapse. (PMID:25605019)
• These findings suggest that URI1 has properties of a ’non-oncogene’ that supports the oncogenic phenotype of those cancer cells that have evolved a dependency on this molecular chaperone system for survival (PMID:27105489)
• This work uncovers that URI-regulated OGT confers c-MYC-dependent survival functions in response to glucose fluctuations. (PMID:27505673)
• Amplification of 19q12 CCNE1/URI was found in 10.4% (28/270) and was significantly associated with type II endometrial cancer (EC) high grade, advanced FIGO stage, and aberrant tumor supressor p53 expression. (PMID:27582547)
• that KAP1 phosphorylation is decreased following recruitment of PP2A by URI. (PMID:27780869)
• Collectively, these findings indicate that RMP promotes Epithelial-mesenchymal transition and hepatocellular carcinoma metastasis through NF-kappaB/CSN2/Snail pathway. These results suggest that RMP and p65 may serve as potential candidates of the targets in the treatment of metastatic hepatocellular carcinoma. (PMID:28423737)
• HBx and c-MYC are involved in URI1 expression in HCC-B. URI1 expression may play important roles in the development and progression of HCC-B because HBx and c-MYC are well-known oncogenic factors in the virus and host (PMID:31739577)
• URI1 suppresses irradiation-induced reactive oxygen species (ROS) by activating autophagy in hepatocellular carcinoma cells. (PMID:34421352)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	uri1	ENSDARG00000026664
mus_musculus	Uri1	ENSMUSG00000030421
rattus_norvegicus	Uri1	ENSRNOG00000014463
drosophila_melanogaster	uri	FBGN0035025

Protein

Protein identifiers

Unconventional prefoldin RPB5 interactor 1 — O94763 (reviewed: O94763)

Alternative names: Protein NNX3, Protein phosphatase 1 regulatory subunit 19, RNA polymerase II subunit 5-mediating protein

All UniProt accessions (9): O94763, I3L0K5, I3L104, I3L130, I3L280, I3L2V7, I3L467, I3NI51, K7EQZ9

UniProt curated annotations — full annotation on UniProt →

Function. Involved in gene transcription regulation. Acts as a transcriptional repressor in concert with the corepressor UXT to regulate androgen receptor (AR) transcription. May act as a tumor suppressor to repress AR-mediated gene transcription and to inhibit anchorage-independent growth in prostate cancer cells. Required for cell survival in ovarian cancer cells. Together with UXT, associates with chromatin to the NKX3-1 promoter region. Antagonizes transcriptional modulation via hepatitis B virus X protein. Plays a central role in maintaining S6K1 signaling and BAD phosphorylation under normal growth conditions thereby protecting cells from potential deleterious effects of sustained S6K1 signaling. The URI1-PPP1CC complex acts as a central component of a negative feedback mechanism that counteracts excessive S6K1 survival signaling to BAD in response to growth factors. Mediates inhibition of PPP1CC phosphatase activity in mitochondria. Coordinates the regulation of nutrient-sensitive gene expression availability in a mTOR-dependent manner. Seems to be a scaffolding protein able to assemble a prefoldin-like complex that contains PFDs and proteins with roles in transcription and ubiquitination.

Subunit / interactions. Homodimer. Component of the PAQosome complex which is responsible for the biogenesis of several protein complexes and which consists of R2TP complex members RUVBL1, RUVBL2, RPAP3 and PIH1D1, URI complex members PFDN2, PFDN6, PDRG1, UXT and URI1 as well as ASDURF, POLR2E and DNAAF10/WDR92. Interacts with POLR2E/RPB5, RUVBL2 and RUVBL1. Interacts with PFDN2, PFDN4 and STAP1; the interactions are phosphorylation-dependent and occur in a growth-dependent manner in the mitochondrion. Interacts with UXT. Interacts with PPP1CC; the interaction is phosphorylation-dependent and occurs in a growth factor-dependent manner. Interacts (via the middle C-terminal region) with GTF2F1 and GTF2F2. Interacts with DMAP1. Interacts with TSC1 and TSC2. Interacts with PRPF8 and EFTUD2 in a ZNHIT2-dependent manner.

Subcellular location. Nucleus. Cytoplasm. Mitochondrion. Cell projection. Dendrite.

Tissue specificity. Ubiquitous. Expressed in ovarian cancers (at protein level). Expressed strongly in skeletal muscle. Expressed weakly in brain, heart, pancreas and in prostate epithelial cells.

Post-translational modifications. Phosphorylated. Phosphorylation occurs essentially on serine residues. Phosphorylation occurs in response to androgen treatment in prostate cancer cells in a mTOR-dependent manner. Phosphorylated; hyperhosphorylated in mitochondria in a mTORC-dependent signaling pathway. Phosphorylated at Ser-372 by RPS6KB1 in a growth factor- and rapamycin-dependent manner. S6K1-mediated mitochondrial phosphorylation at Ser-372 disrupts the URI1-PPP1CC complex in the mitochondrion, relieves PPP1CC phosphatase inhibition activity and hence engages a negative feedback diminishing RPS6KB1 kinase activity, preventing sustained S6K1-dependent signaling.

Similarity. Belongs to the RNA polymerase II subunit 5-mediating protein family.

Isoforms (4)

UniProt ID	Names	Canonical?
O94763-1	1	yes
O94763-2	2
O94763-3	3
O94763-4	4

RefSeq proteins (2): NP_001239570, NP_003787* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004127	Prefoldin_subunit_alpha	Family
IPR009053	Prefoldin	Homologous_superfamily
IPR052255	RNA_pol_II_subunit5-mediator	Family

Pfam: PF02996

UniProt features (25 total): sequence conflict 5, compositionally biased region 5, region of interest 4, modified residue 4, splice variant 4, chain 1, sequence variant 1, mutagenesis site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O94763-F1	62.85	0.23

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 (4): 1, 372, 373, 442

Mutagenesis-validated functional residues (1):

Position	Phenotype
372	does not lead to dissociation of the uri1-ppp1cc complex. enhances phosphorylation of rps6kb1 after igf1 stimulation. co

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 280 (showing top): GOBP_INTRINSIC_APOPTOTIC_SIGNALING_PATHWAY_IN_RESPONSE_TO_DNA_DAMAGE_BY_P53_CLASS_MEDIATOR, MORF_MBD4, GOBP_REGULATION_OF_PHOSPHATASE_ACTIVITY, GOBP_CELLULAR_RESPONSE_TO_LIPID, GOBP_NEGATIVE_REGULATION_OF_HYDROLASE_ACTIVITY, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, GOBP_GROWTH, MITSIADES_RESPONSE_TO_APLIDIN_DN, MORF_PSMC2, AGGCACT_MIR5153P, GOBP_NEGATIVE_REGULATION_OF_INTRACELLULAR_SIGNAL_TRANSDUCTION, GOBP_REGULATION_OF_HYDROLASE_ACTIVITY, GOBP_NEGATIVE_REGULATION_OF_INTRINSIC_APOPTOTIC_SIGNALING_PATHWAY

GO Biological Process (10): negative regulation of transcription by RNA polymerase II (GO:0000122), regulation of cell growth (GO:0001558), regulation of transcription by RNA polymerase II (GO:0006357), response to virus (GO:0009615), negative regulation of phosphatase activity (GO:0010923), intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator (GO:0042771), protein stabilization (GO:0050821), cellular response to growth factor stimulus (GO:0071363), cellular response to steroid hormone stimulus (GO:0071383), negative regulation of intrinsic apoptotic signaling pathway (GO:2001243)

GO Molecular Function (7): RNA polymerase II complex binding (GO:0000993), chromatin binding (GO:0003682), transcription corepressor activity (GO:0003714), protein phosphatase inhibitor activity (GO:0004864), phosphatase inhibitor activity (GO:0019212), phosphoprotein binding (GO:0051219), protein binding (GO:0005515)

GO Cellular Component (10): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), mitochondrion (GO:0005739), cytosol (GO:0005829), dendrite (GO:0030425), protein folding chaperone complex (GO:0101031), RPAP3/R2TP/prefoldin-like complex (GO:1990062), protein-containing complex (GO:0032991), cell projection (GO:0042995)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
transcription by RNA polymerase II	2
negative regulation of DNA-templated transcription	2
phosphatase activity	2
binding	2
intracellular membrane-bounded organelle	2
cytoplasm	2
regulation of transcription by RNA polymerase II	1
cell growth	1
regulation of growth	1
regulation of cellular component organization	1
regulation of DNA-templated transcription	1
response to other organism	1
regulation of phosphatase activity	1
negative regulation of dephosphorylation	1
negative regulation of hydrolase activity	1
intrinsic apoptotic signaling pathway in response to DNA damage	1
intrinsic apoptotic signaling pathway by p53 class mediator	1
regulation of protein stability	1
response to growth factor	1
cellular response to endogenous stimulus	1
cellular response to hormone stimulus	1
response to steroid hormone	1
cellular response to lipid	1
intrinsic apoptotic signaling pathway	1
negative regulation of intracellular signal transduction	1
negative regulation of apoptotic signaling pathway	1
regulation of intrinsic apoptotic signaling pathway	1
RNA polymerase core enzyme binding	1
transcription coregulator activity	1
phosphoprotein phosphatase activity	1
phosphatase inhibitor activity	1
protein phosphatase regulator activity	1
enzyme inhibitor activity	1
phosphatase regulator activity	1
protein binding	1
nuclear lumen	1
intracellular anatomical structure	1
neuron projection	1
dendritic tree	1

Protein interactions and networks

STRING

1156 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
URI1	POLR2E	P19388	997
URI1	PFDN2	Q9UHV9	966
URI1	UXT	Q9UBK9	889
URI1	PFDN4	Q9NQP4	868
URI1	RUVBL1	P82276	830
URI1	PFDN6	O15212	830
URI1	TENT4A	Q5XG87	822
URI1	PPP1CC	P36873	772
URI1	PDRG1	Q9NUG6	755
URI1	RUVBL2	Q9Y230	735
URI1	DNAAF10	Q96MX6	710
URI1	RBP5	P82980	685
URI1	ASDURF	L0R819	640
URI1	RPAP3	Q9H6T3	608
URI1	CRABP1	P29762	600

IntAct

184 interactions, top by confidence:

A	B	Type	Score
NPHP1	NPHP4	psi-mi:“MI:2364”(proximity)	0.930
URI1	PPP1CC	psi-mi:“MI:0915”(physical association)	0.910
PPP1CC	URI1	psi-mi:“MI:0915”(physical association)	0.910
POLR2E	POLR3A	psi-mi:“MI:0914”(association)	0.870
RUVBL1	ZNHIT1	psi-mi:“MI:0914”(association)	0.860
POLR2E	URI1	psi-mi:“MI:0915”(physical association)	0.850
URI1	POLR2E	psi-mi:“MI:0914”(association)	0.850
MED9	MED19	psi-mi:“MI:0914”(association)	0.790
PPP1CB	CCDC85C	psi-mi:“MI:0914”(association)	0.750
PPP1CC	CCDC85C	psi-mi:“MI:0914”(association)	0.740
PPP1CC	CCDC85C	psi-mi:“MI:2364”(proximity)	0.740
PFDN2	URI1	psi-mi:“MI:0915”(physical association)	0.740
DPF2	ARID1A	psi-mi:“MI:0914”(association)	0.730
POLR2E	MED19	psi-mi:“MI:0914”(association)	0.730
PFDN4	PFDN6	psi-mi:“MI:0914”(association)	0.730
POLR3E	POLR3A	psi-mi:“MI:0914”(association)	0.730
POLR2J	POLR2D	psi-mi:“MI:0914”(association)	0.730
RPRD1B	POLR2D	psi-mi:“MI:0914”(association)	0.730
URI1	GTF2F2	psi-mi:“MI:0915”(physical association)	0.700
GTF2F2	URI1	psi-mi:“MI:0915”(physical association)	0.700

BioGRID (313): URI1 (Affinity Capture-MS), URI1 (Affinity Capture-MS), URI1 (Affinity Capture-MS), URI1 (Affinity Capture-MS), URI1 (Affinity Capture-MS), URI1 (Affinity Capture-MS), URI1 (Co-fractionation), URI1 (Co-fractionation), URI1 (Affinity Capture-MS), URI1 (Reconstituted Complex), URI1 (Synthetic Growth Defect), URI1 (Synthetic Lethality), URI1 (Affinity Capture-MS), URI1 (Proximity Label-MS), URI1 (Proximity Label-MS)

ESM2 similar proteins: A0A1L8HTT5, A0A2R6W1B1, A2XC52, A6QR44, B9F4I8, F4I9G2, F4JSE7, O88566, O94763, P35922, P53349, P55265, Q06787, Q13233, Q1EQW7, Q2R2B1, Q3UDK1, Q3ULM0, Q53NI2, Q5E9N5, Q5EAH9, Q5QLS7, Q62925, Q63505, Q651A1, Q6PHZ5, Q7T3U0, Q7TN31, Q80Z10, Q80ZW0, Q86UB2, Q8CBX9, Q8CDG3, Q8CF97, Q8CFE5, Q8H8C6, Q8IPH9, Q8IVF5, Q8K284, Q8N9B5

Diamond homologs: O94763, Q3B7M7, Q3TLD5, Q54HG4, Q9W148

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
RPS6KB1	“down-regulates activity”	URI1	phosphorylation
URI1	“form complex”	“URI1 prefoldin co-chaperone”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 137 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
RNA Polymerase III Chain Elongation	11	80.2×	4e-17
FGFR2 mutant receptor activation	9	78.8×	9e-15
Signaling by FGFR2 IIIa TM	10	69.1×	2e-15
Abortive elongation of HIV-1 transcript in the absence of Tat	11	62.8×	3e-16
RNA Polymerase III Transcription Termination	11	62.8×	3e-16
RNA Polymerase III Transcription Initiation From Type 2 Promoter	12	58.3×	6e-17
RNA Polymerase III Transcription Initiation From Type 1 Promoter	12	56.3×	6e-17
RNA Polymerase III Transcription Initiation From Type 3 Promoter	12	56.3×	6e-17

GO biological processes:

GO term	Partners	Fold	FDR
transcription elongation by RNA polymerase II	6	22.4×	3e-05
positive regulation of transcription elongation by RNA polymerase II	7	17.7×	2e-05
protein dephosphorylation	6	11.2×	1e-03
protein folding	12	10.4×	5e-07
protein stabilization	15	8.4×	2e-07
transcription by RNA polymerase II	12	7.1×	2e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

104 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	75
Likely benign	8
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

2448 predictions. Top by Δscore:

Variant	Effect	Δscore
19:29986386:GGCT:G	donor_gain	1.0000
19:29986387:GCTG:G	donor_gain	1.0000
19:29986414:GAAC:G	donor_gain	1.0000
19:29986418:G:GG	donor_gain	1.0000
19:30005351:ATT:A	acceptor_gain	1.0000
19:30005358:CAGA:C	acceptor_loss	1.0000
19:30005359:A:AG	acceptor_gain	1.0000
19:30005359:A:C	acceptor_loss	1.0000
19:30005360:G:GC	acceptor_gain	1.0000
19:30005360:GAT:G	acceptor_gain	1.0000
19:30005360:GATGT:G	acceptor_gain	1.0000
19:30005448:GCGAT:G	donor_gain	1.0000
19:30005449:CGAT:C	donor_gain	1.0000
19:30005450:GAT:G	donor_gain	1.0000
19:30005450:GATG:G	donor_gain	1.0000
19:30005450:GATGT:G	donor_loss	1.0000
19:30005451:AT:A	donor_gain	1.0000
19:30005451:ATG:A	donor_loss	1.0000
19:30005452:TG:T	donor_loss	1.0000
19:30005453:G:GA	donor_loss	1.0000
19:30005453:G:GG	donor_gain	1.0000
19:30005454:T:A	donor_loss	1.0000
19:30005455:GAGTA:G	donor_loss	1.0000
19:30005637:T:TA	acceptor_gain	1.0000
19:30005642:A:AG	acceptor_gain	1.0000
19:30005643:A:G	acceptor_gain	1.0000
19:30005644:A:AG	acceptor_gain	1.0000
19:30005645:A:G	acceptor_gain	1.0000
19:30005646:A:G	acceptor_gain	1.0000
19:30005646:ACCAG:A	acceptor_gain	1.0000

AlphaMissense

3564 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:29985264:T:C	L65P	0.999
19:29986343:T:A	V98D	0.999
19:29986363:T:C	F105L	0.999
19:29986365:T:A	F105L	0.999
19:29986365:T:G	F105L	0.999
19:29986387:G:C	A113P	0.999
19:29986409:G:C	R120P	0.999
19:29942645:T:C	L33P	0.998
19:29985252:T:C	L61P	0.998
19:29986319:T:C	L90P	0.998
19:29986337:T:A	V96D	0.998
19:29986351:G:A	G101R	0.998
19:29986351:G:C	G101R	0.998
19:29986352:G:A	G101E	0.998
19:29986352:G:T	G101V	0.998
19:29986364:T:C	F105S	0.998
19:30011101:T:C	I348T	0.998
19:29985252:T:A	L61H	0.997
19:29985264:T:A	L65H	0.997
19:29986313:G:A	G88E	0.997
19:29986319:T:A	L90H	0.997
19:29986351:G:T	G101W	0.997
19:29986388:C:A	A113D	0.997
19:30005424:T:C	F144S	0.997
19:30011125:T:C	L356S	0.997
19:30011130:T:C	F358L	0.997
19:30011132:C:A	F358L	0.997
19:30011132:C:G	F358L	0.997
19:29986301:C:A	A84D	0.996
19:29986332:T:A	N94K	0.996

dbSNP variants (sampled 300 via entrez): RS1000065555 (19:29949043 C>T), RS1000077917 (19:29921895 T>C), RS1000098431 (19:30006864 C>T), RS1000122017 (19:29964031 C>T), RS1000129826 (19:29921693 T>A), RS1000248730 (19:29975723 C>T), RS1000269644 (19:30014317 G>A), RS1000272170 (19:29957766 G>A), RS1000307226 (19:29991489 C>A,G), RS1000308398 (19:29937663 G>A), RS1000330252 (19:30013768 A>G), RS1000334215 (19:29946252 A>G), RS1000352660 (19:30013659 C>G), RS1000384950 (19:29975893 G>A), RS1000457708 (19:29982917 C>A,T)

Disease associations

OMIM: gene MIM:603494 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST004070_18	Cerebrospinal P-tau181p levels	9.000000e-06
GCST005951_21	Body mass index	4.000000e-09
GCST005951_22	Body mass index	2.000000e-08
GCST006426_6	Serum urate levels in chronic kidney disease	5.000000e-08
GCST007094_2	Diastolic blood pressure	3.000000e-10

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004763	p-tau measurement
EFO:0004340	body mass index
EFO:0004531	urate measurement
EFO:0006336	diastolic blood pressure

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

35 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression, increases methylation	4
Cisplatin	affects response to substance, decreases response to substance	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	2
aristolochic acid I	decreases expression	1
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	affects cotreatment, increases methylation	1
methylparaben	increases expression	1
cobaltous chloride	increases expression	1
coumarin	affects phosphorylation	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
nutlin 3	affects cotreatment, increases secretion	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
Temozolomide	increases expression	1
Sunitinib	increases expression	1
Arsenic Trioxide	increases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Leflunomide	decreases expression	1
Caffeine	affects phosphorylation	1
Dactinomycin	affects cotreatment, increases secretion	1
Doxorubicin	affects response to substance	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Formaldehyde	decreases expression	1
Methyl Methanesulfonate	decreases expression	1
Quercetin	decreases phosphorylation	1
Rotenone	decreases expression	1
Silicon Dioxide	decreases expression	1
Tretinoin	decreases expression	1

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.