KHDRBS3

Summary

KHDRBS3 (KH RNA binding domain containing, signal transduction associated 3, HGNC:18117) is a protein-coding gene on chromosome 8q24.23, encoding KH domain-containing, RNA-binding, signal transduction-associated protein 3 (O75525). RNA-binding protein that plays a role in the regulation of alternative splicing and influences mRNA splice site selection and exon inclusion.

Enables RNA binding activity; identical protein binding activity; and protein domain specific binding activity. Predicted to be involved in regulation of alternative mRNA splicing, via spliceosome and spermatogenesis. Located in nucleoplasm. Part of protein-containing complex.

Source: NCBI Gene 10656 — RefSeq curated summary.

At a glance

• GWAS associations: 6
• Clinical variants (ClinVar): 60 total
• MANE Select transcript: NM_006558

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18117
Approved symbol	KHDRBS3
Name	KH RNA binding domain containing, signal transduction associated 3
Location	8q24.23
Locus type	gene with protein product
Status	Approved
Aliases	T-STAR, Etle, etoile, SALP, SLM2, SLM-2
Ensembl gene	ENSG00000131773
Ensembl biotype	protein_coding
OMIM	610421
Entrez	10656

Gene structure

Transcript identifiers

Ensembl transcripts: 13 — 6 protein_coding, 3 nonsense_mediated_decay, 3 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000355849, ENST00000517394, ENST00000517859, ENST00000518728, ENST00000519600, ENST00000520981, ENST00000521461, ENST00000522079, ENST00000522433, ENST00000522578, ENST00000524199, ENST00000524282, ENST00000704572

RefSeq mRNA: 1 — MANE Select: NM_006558 NM_006558

CCDS: CCDS6374

Canonical transcript exons

ENST00000355849 — 9 exons

Exon	Start	End
ENSE00000704156	135542654	135542770
ENSE00000704157	135548754	135548900
ENSE00000900471	135521237	135521355
ENSE00001167325	135557448	135557587
ENSE00001217253	135646993	135647610
ENSE00001722982	135457456	135457954
ENSE00003459579	135581878	135582073
ENSE00003522713	135606955	135607037
ENSE00003640102	135645059	135645117

Expression profiles

Bgee: expression breadth ubiquitous, 267 present calls, max score 99.43.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 9.0625 / max 245.8413, expressed in 1288 samples.

FANTOM5 promoters (13 alternative TSS)

Promoter ID	TPM avg	Samples expressed
91233	7.9788	1242
91234	0.4323	205
91232	0.2162	86
91239	0.1038	54
91231	0.0933	33
91242	0.0780	5
91235	0.0448	12
91236	0.0366	8
91238	0.0341	5
91237	0.0145	5

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cortical plate	UBERON:0005343	99.43	gold quality
left testis	UBERON:0004533	98.80	gold quality
right testis	UBERON:0004534	98.78	gold quality
middle temporal gyrus	UBERON:0002771	98.28	gold quality
prefrontal cortex	UBERON:0000451	97.72	gold quality
adult organism	UBERON:0007023	97.48	gold quality
testis	UBERON:0000473	97.31	gold quality
primary visual cortex	UBERON:0002436	97.16	gold quality
Brodmann (1909) area 9	UBERON:0013540	96.98	gold quality
secondary oocyte	CL:0000655	96.80	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	96.79	gold quality
occipital lobe	UBERON:0002021	96.39	gold quality
right frontal lobe	UBERON:0002810	96.19	gold quality
frontal cortex	UBERON:0001870	96.18	gold quality
Brodmann (1909) area 23	UBERON:0013554	96.15	gold quality
neocortex	UBERON:0001950	96.11	gold quality
sperm	CL:0000019	96.04	gold quality
Brodmann (1909) area 46	UBERON:0006483	95.84	gold quality
cerebral cortex	UBERON:0000956	95.80	gold quality
cingulate cortex	UBERON:0003027	95.62	gold quality
male germ cell	CL:0000015	95.57	gold quality
anterior cingulate cortex	UBERON:0009835	95.53	gold quality
orbitofrontal cortex	UBERON:0004167	95.16	gold quality
amygdala	UBERON:0001876	95.14	gold quality
temporal lobe	UBERON:0001871	94.66	gold quality
superior frontal gyrus	UBERON:0002661	94.45	gold quality
CA1 field of hippocampus	UBERON:0003881	94.17	gold quality
telencephalon	UBERON:0001893	94.13	gold quality
parietal lobe	UBERON:0001872	94.04	gold quality
Ammon’s horn	UBERON:0001954	94.00	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 5.

Experiment	Marker?	Max mean expression
E-MTAB-10485	yes	390.54
E-HCAD-25	yes	77.26
E-HCAD-35	yes	69.73
E-GEOD-137537	yes	16.76
E-ANND-3	yes	8.05

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

81 targeting KHDRBS3, 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-513B-5P	99.99	69.96	2150
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-186-5P	99.99	70.83	3707
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-507	99.97	70.11	1915
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-557	99.96	70.01	1640
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
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-144-3P	99.94	73.98	2698
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-7-1-3P	99.91	71.53	4384

Literature-anchored findings (GeneRIF, showing 12)

• SLM-2-dependent VEGF splicing indicates the importance of mRNA splice site selection for glomerular filtration barrier function. (PMID:15901763)
• The T-STAR gene may participate in regulation of telomerase activity in human colon cancer HCT-116 cells in a parallel fashion. (PMID:16810759)
• data implicate hsa-miR-30b, hsa-miR-30d and KHDRBS3 as putative oncogenic target(s) of a novel recurrent medulloblastoma amplicon at 8q24.22-q24.23 (PMID:19584924)
• SerpinB5 interacts with KHDRBS3 and FBXO32, and KHDRBS3 can interact with FBXO32 mRNA. (PMID:21725612)
• Nuclear T-STAR protein expression correlates with HER2 status, hormone receptor negativity and prolonged recurrence free survival in primary breast cancer and decreased cancer cell growth in vitro. (PMID:23923007)
• Sam68 and T-STAR could regulate alternative splicing of some pre-mRNAs by bringing two distant UAA motifs into proximity and looping out regions of the pre-mRNA. (PMID:26758068)
• Down-regulating the KHDRBS3 gene can cause G0/G1 phase arrest and inhibit cell proliferation in CAOV-3 cells. (PMID:28871947)
• High KHDRBS3 expression is associated with enhanced stemness in basal-like breast cancer. (PMID:29356399)
• Molecular biological analysis of 5-FU-resistant gastric cancer organoids; KHDRBS3 contributes to the attainment of features of cancer stem cell. (PMID:33046798)
• KHDRBS3 promotes multi-drug resistance and anchorage-independent growth in colorectal cancer. (PMID:33423358)
• SLM2 Is A Novel Cardiac Splicing Factor Involved in Heart Failure due to Dilated Cardiomyopathy. (PMID:34273561)
• KHDRBS3 promotes paclitaxel resistance and induces glycolysis through modulated MIR17HG/CLDN6 signaling in epithelial ovarian cancer. (PMID:35051418)

Cross-species orthologs

11 orthologs

Organism	Symbol	Gene ID
		ENSDARG00000101020
mus_musculus	Khdrbs3	ENSMUSG00000022332
rattus_norvegicus	Khdrbs3	ENSRNOG00000009539
drosophila_melanogaster	qkr58E-3	FBGN0022984
drosophila_melanogaster	qkr58E-2	FBGN0022985
drosophila_melanogaster	qkr58E-1	FBGN0022986
drosophila_melanogaster	qkr54B	FBGN0022987
drosophila_melanogaster	CG4021	FBGN0034659
drosophila_melanogaster	CG10384	FBGN0034731
drosophila_melanogaster	CG3927	FBGN0034739
drosophila_melanogaster	nsr	FBGN0034740

Paralogs (4): KHDRBS2 (ENSG00000112232), QKI (ENSG00000112531), KHDRBS1 (ENSG00000121774), SF1 (ENSG00000168066)

Protein

Protein identifiers

KH domain-containing, RNA-binding, signal transduction-associated protein 3 — O75525 (reviewed: O75525)

Alternative names: RNA-binding protein T-Star, Sam68-like mammalian protein 2, Sam68-like phosphotyrosine protein

All UniProt accessions (9): A0A994J4I6, A0A994J7I5, E5RG12, E5RHD3, E5RJZ9, O75525, H0YAQ1, H0YAQ3, H0YB45

UniProt curated annotations — full annotation on UniProt →

Function. RNA-binding protein that plays a role in the regulation of alternative splicing and influences mRNA splice site selection and exon inclusion. Binds preferentially to the 5’-[AU]UAAA-3’ motif in vitro. Binds optimally to RNA containing 5’-[AU]UAA-3’ as a bipartite motif spaced by more than 15 nucleotides. Binds poly(A). RNA-binding abilities are down-regulated by tyrosine kinase PTK6. Involved in splice site selection of vascular endothelial growth factor. In vitro regulates CD44 alternative splicing by direct binding to purine-rich exonic enhancer. Can regulate alternative splicing of neurexins NRXN1-3 in the laminin G-like domain 6 containing the evolutionary conserved neurexin alternative spliced segment 4 (AS4) involved in neurexin selective targeting to postsynaptic partners such as neuroligins and LRRTM family members. Targeted, cell-type specific splicing regulation of NRXN1 at AS4 is involved in neuronal glutamatergic synapse function and plasticity. May regulate expression of KHDRBS2/SLIM-1 in defined brain neuron populations by modifying its alternative splicing. Can bind FABP9 mRNA. May play a role as a negative regulator of cell growth. Inhibits cell proliferation. (Microbial infection) Involved in post-transcriptional regulation of HIV-1 gene expression.

Subunit / interactions. Self-associates to form homooligomers; dimerization increases RNA affinity. Interacts with KHDRBS2/SLM-1. Interacts with KHDRBS1/SAM68; heterooligomer formation of KHDRBS family proteins may modulate RNA substrate specificity. Interacts with the splicing regulatory proteins SFRS9, SAFB and YTHDC1. Interacts with HNRPL. Interacts with RBMX, RBMY1A1, p85 subunit of PI3-kinase, SERPINB5. Interacts with SIAH1 which promotes targeting for degradation.

Subcellular location. Nucleus.

Tissue specificity. Ubiquitous with higher expression in testis, skeletal muscle and brain. Expressed in the kidney only in podocytes, the glomerular epithelial cells of the kidney. Strongly expressed after meiosis.

Post-translational modifications. Phosphorylated on tyrosine residues. Isoform 1 C-terminal region is tyrosine-rich, but isoform 2 lacking this C-terminal region is also tyrosine-phosphorylated.

Domain organisation. The proline-rich site binds the SH3 domain of the p85 subunit of PI3-kinase.

Induction. Induced in proteinuric diseases. Down-regulated in immortalized fibroblasts isolated after a proliferative crisis accompanied with massive cell death.

Similarity. Belongs to the KHDRBS family.

Isoforms (2)

UniProt ID	Names	Canonical?
O75525-1	1, SALP-alpha	yes
O75525-2	2, SALP-beta

RefSeq proteins (1): NP_006549* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004087	KH_dom	Domain
IPR032335	Sam68-YY	Domain
IPR032571	Qua1_dom	Domain
IPR036612	KH_dom_type_1_sf	Homologous_superfamily
IPR045071	BBP-like	Family
IPR055256	KH_1_KHDC4/BBP-like	Domain

Pfam: PF16274, PF16568, PF22675

UniProt features (30 total): helix 9, strand 4, region of interest 4, mutagenesis site 3, splice variant 2, turn 2, compositionally biased region 2, chain 1, domain 1, sequence conflict 1, cross-link 1

Structure

Experimental structures (PDB)

5 structures.

PDB	Method	Resolution (Å)
5EL3	X-RAY DIFFRACTION	1.59
5ELT	X-RAY DIFFRACTION	2.13
5ELR	X-RAY DIFFRACTION	2.3
5ELS	X-RAY DIFFRACTION	2.87
5EMO	X-RAY DIFFRACTION	3.03

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O75525-F1	69.45	0.36

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): 4

Mutagenesis-validated functional residues (3):

Position	Phenotype
141	fails to influence alternative splicing of cd44, nrxn2 and nrxn3.
212–251	complete loss of siah1-mediated degradation.
327–346	complete loss of nuclear sublocalization.

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-8849468	PTK6 Regulates Proteins Involved in RNA Processing
R-HSA-162582	Signal Transduction
R-HSA-8848021	Signaling by PTK6
R-HSA-9006927	Signaling by Non-Receptor Tyrosine Kinases

MSigDB gene sets: 179 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_BRAIN_TUMORAL_MACROPHAGE_DN, PEREZ_TP63_TARGETS, GOBP_ALTERNATIVE_MRNA_SPLICING_VIA_SPLICEOSOME, ACEVEDO_NORMAL_TISSUE_ADJACENT_TO_LIVER_TUMOR_DN, BROWNE_HCMV_INFECTION_16HR_UP, ATGTTAA_MIR302C, MODULE_66, BILD_E2F3_ONCOGENIC_SIGNATURE, SCHAEFFER_PROSTATE_DEVELOPMENT_6HR_DN, GOBP_RNA_SPLICING, AAAGGGA_MIR204_MIR211, GOBP_REGULATION_OF_MRNA_SPLICING_VIA_SPLICEOSOME, MODULE_98, JAATINEN_HEMATOPOIETIC_STEM_CELL_UP, HAN_SATB1_TARGETS_DN

GO Biological Process (3): regulation of alternative mRNA splicing, via spliceosome (GO:0000381), mRNA processing (GO:0006397), regulation of mRNA splicing, via spliceosome (GO:0048024)

GO Molecular Function (7): RNA binding (GO:0003723), mRNA binding (GO:0003729), SH3 domain binding (GO:0017124), protein domain specific binding (GO:0019904), identical protein binding (GO:0042802), nucleic acid binding (GO:0003676), protein binding (GO:0005515)

GO Cellular Component (3): nucleus (GO:0005634), nucleoplasm (GO:0005654), protein-containing complex (GO:0032991)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Signaling by PTK6	1
Signaling by Non-Receptor Tyrosine Kinases	1
Signal Transduction	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein binding	2
binding	2
alternative mRNA splicing, via spliceosome	1
regulation of mRNA splicing, via spliceosome	1
RNA processing	1
mRNA metabolic process	1
mRNA splicing, via spliceosome	1
regulation of RNA splicing	1
regulation of mRNA processing	1
nucleic acid binding	1
RNA binding	1
protein domain specific binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
cellular anatomical structure	1
cellular_component	1

Protein interactions and networks

STRING

1094 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
KHDRBS3	SIAH2	O43255	669
KHDRBS3	RBMY1A1	P0DJD3	642
KHDRBS3	PRMT1	Q99873	621
KHDRBS3	SIAH1	Q8IUQ4	594
KHDRBS3	RBMY1D	P0C7P1	593
KHDRBS3	PTK6	Q13882	580
KHDRBS3	SRSF1	Q07955	573
KHDRBS3	MBNL1	Q9NR56	511
KHDRBS3	HNRNPA1	P09651	508
KHDRBS3	RBMXL2	O75526	481
KHDRBS3	SERPINB5	P36952	475
KHDRBS3	SERPINA4	P29622	466
KHDRBS3	NRXN1	Q9ULB1	461
KHDRBS3	YTHDC1	Q96MU7	458
KHDRBS3	LRRC7	Q96NW7	457

IntAct

184 interactions, top by confidence:

A	B	Type	Score
KHDRBS3	KHDRBS2	psi-mi:“MI:0915”(physical association)	0.800
KHDRBS2	KHDRBS3	psi-mi:“MI:0914”(association)	0.800
KHDRBS3	PRPF31	psi-mi:“MI:0915”(physical association)	0.720
KHDRBS3	YTHDC1	psi-mi:“MI:0915”(physical association)	0.720
PRPF31	KHDRBS3	psi-mi:“MI:0915”(physical association)	0.720
KHDRBS3	BAHD1	psi-mi:“MI:0915”(physical association)	0.670
BAHD1	KHDRBS3	psi-mi:“MI:0915”(physical association)	0.670
KHDRBS3	ZNF408	psi-mi:“MI:0915”(physical association)	0.670
KHDRBS3	RBMX	psi-mi:“MI:0915”(physical association)	0.670
KHDRBS3	PRR3	psi-mi:“MI:0915”(physical association)	0.670
KHDRBS1	KHDRBS3	psi-mi:“MI:0914”(association)	0.670
KHDRBS3	KHDRBS1	psi-mi:“MI:0915”(physical association)	0.670
CSNK2A2	PES1	psi-mi:“MI:0914”(association)	0.640
	KHDRBS3	psi-mi:“MI:0915”(physical association)	0.560
KHDRBS3	MARK4	psi-mi:“MI:0915”(physical association)	0.560
INPP5D	KHDRBS3	psi-mi:“MI:0915”(physical association)	0.560
KHDRBS3	DMRT3	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (138): KHDRBS3 (Two-hybrid), KHDRBS3 (Two-hybrid), BAHD1 (Two-hybrid), PRPF31 (Two-hybrid), NCOA5 (Two-hybrid), MARK4 (Two-hybrid), DMRT3 (Two-hybrid), YTHDC1 (Two-hybrid), KHDRBS3 (Affinity Capture-MS), ZNF408 (Two-hybrid), BAHD1 (Two-hybrid), KHDRBS3 (Two-hybrid), RBMX (Two-hybrid), CCDC33 (Two-hybrid), LNX1 (Two-hybrid)

ESM2 similar proteins: B2GV05, B5FXN8, G3V9R8, O08583, O75525, O77768, P07910, P19600, P23588, P52756, P55795, P70333, P97379, P97855, Q08DJ0, Q0VFL7, Q13148, Q13283, Q1RMU5, Q28FB9, Q32LC7, Q3SZF3, Q3T0I4, Q58EA2, Q5R5W2, Q5R9L3, Q5RA82, Q5RB87, Q5RD26, Q5SRX1, Q5VWX1, Q5ZLN5, Q60HC3, Q64012, Q6AY09, Q6GLW1, Q86SE5, Q86V81, Q8BGD9, Q8BTF8

Diamond homologs: G5EFF1, O01367, O74555, O75525, P0CO44, P0CO45, P13230, Q07666, Q08BJ2, Q0VFL3, Q0WLR1, Q12186, Q15637, Q17339, Q32NN2, Q4P0H7, Q4WXV6, Q54BM5, Q5AED9, Q5VWX1, Q5W9D5, Q5W9D6, Q5W9D7, Q60749, Q64213, Q6BSP4, Q6C187, Q6FW77, Q6IRN2, Q6P0D0, Q6P104, Q750X2, Q75GR5, Q7JJZ8, Q8GWR3, Q8GYR4, Q8NIW7, Q8UUW7, Q91V33, Q91XU1

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
SIAH1	“down-regulates quantity by destabilization”	KHDRBS3	polyubiquitination

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 97 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
Processing of Capped Intron-Containing Pre-mRNA	12	17.6×	9e-10
mRNA Polyadenylation	10	15.7×	7e-08
mRNA Splicing - Major Pathway	13	12.7×	3e-09
mRNA Splicing	6	11.8×	8e-04
Metabolism of RNA	9	6.7×	6e-04
Dengue Virus-Host Interactions	7	5.7×	1e-02

GO biological processes:

GO term	Partners	Fold	FDR
regulation of alternative mRNA splicing, via spliceosome	9	27.1×	1e-08
mRNA splicing, via spliceosome	14	15.8×	1e-10
regulation of RNA splicing	5	13.5×	4e-03
mRNA processing	9	8.8×	2e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	43
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2537 predictions. Top by Δscore:

Variant	Effect	Δscore
8:135457951:CAAGG:C	donor_loss	1.0000
8:135457953:AGG:A	donor_loss	1.0000
8:135457955:GTG:G	donor_loss	1.0000
8:135521235:A:AG	acceptor_gain	1.0000
8:135521236:G:GG	acceptor_gain	1.0000
8:135521236:GAA:G	acceptor_gain	1.0000
8:135521354:AG:A	donor_loss	1.0000
8:135521357:T:A	donor_loss	1.0000
8:135548749:TCCAG:T	acceptor_loss	1.0000
8:135548750:CCAG:C	acceptor_loss	1.0000
8:135548752:A:AG	acceptor_gain	1.0000
8:135548752:A:AT	acceptor_loss	1.0000
8:135548752:AG:A	acceptor_gain	1.0000
8:135548753:G:GT	acceptor_gain	1.0000
8:135548753:GG:G	acceptor_gain	1.0000
8:135548753:GGA:G	acceptor_gain	1.0000
8:135548753:GGAA:G	acceptor_gain	1.0000
8:135548858:G:GT	donor_gain	1.0000
8:135548874:G:GT	donor_gain	1.0000
8:135548896:TCCCT:T	donor_gain	1.0000
8:135548901:G:GG	donor_gain	1.0000
8:135557445:TAGG:T	acceptor_loss	1.0000
8:135557446:A:AG	acceptor_gain	1.0000
8:135557446:A:C	acceptor_loss	1.0000
8:135557446:AG:A	acceptor_gain	1.0000
8:135557447:G:GA	acceptor_gain	1.0000
8:135557447:GG:G	acceptor_gain	1.0000
8:135557447:GGA:G	acceptor_gain	1.0000
8:135557447:GGAT:G	acceptor_gain	1.0000
8:135557447:GGATT:G	acceptor_gain	1.0000

AlphaMissense

2231 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:135457892:T:C	L9P	1.000
8:135521327:T:A	V60E	1.000
8:135521333:T:A	I62N	1.000
8:135521333:T:C	I62T	1.000
8:135521333:T:G	I62S	1.000
8:135521335:C:A	P63T	1.000
8:135521335:C:T	P63S	1.000
8:135521336:C:A	P63H	1.000
8:135521336:C:G	P63R	1.000
8:135521347:T:C	F67L	1.000
8:135521349:C:A	F67L	1.000
8:135521349:C:G	F67L	1.000
8:135542654:T:C	F70L	1.000
8:135542655:T:C	F70S	1.000
8:135542655:T:G	F70C	1.000
8:135542656:C:A	F70L	1.000
8:135542656:C:G	F70L	1.000
8:135542657:A:G	N71D	1.000
8:135542659:C:A	N71K	1.000
8:135542659:C:G	N71K	1.000
8:135542660:T:A	F72I	1.000
8:135542660:T:C	F72L	1.000
8:135542660:T:G	F72V	1.000
8:135542661:T:C	F72S	1.000
8:135542661:T:G	F72C	1.000
8:135542662:T:A	F72L	1.000
8:135542662:T:G	F72L	1.000
8:135542664:T:A	V73E	1.000
8:135542666:G:A	G74R	1.000
8:135542666:G:C	G74R	1.000

dbSNP variants (sampled 300 via entrez): RS1000030751 (8:135546959 G>T), RS1000034639 (8:135605833 T>C), RS1000040936 (8:135656913 G>T), RS1000045108 (8:135495042 C>A,G,T), RS1000046442 (8:135580061 C>T), RS1000046565 (8:135563262 G>A,C), RS1000049510 (8:135478594 A>T), RS1000054550 (8:135650136 T>C), RS1000080406 (8:135478959 A>G), RS1000103440 (8:135612413 A>G), RS1000122254 (8:135462917 G>A), RS1000123791 (8:135520828 G>T), RS1000138019 (8:135562947 C>G), RS1000138542 (8:135488419 T>C,G), RS1000180822 (8:135496452 C>T)

Disease associations

OMIM: gene MIM:610421 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST002741_3	Polycystic ovary syndrome	5.000000e-08
GCST004068_2	Venous thromboembolism adjusted for sickle cell variant rs77121243-T	8.000000e-06
GCST004750_20	Squamous cell lung carcinoma	4.000000e-06
GCST005359_15	Disease progression in age-related macular degeneration	8.000000e-06
GCST007576_141	Chronotype	8.000000e-09
GCST011973_2	Colorectal cancer	1.000000e-06

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0008336	disease progression measurement
EFO:0008328	chronotype measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression, increases expression, affects cotreatment, decreases methylation	4
Acetaminophen	increases expression	2
Valproic Acid	increases expression	2
FR900359	increases phosphorylation	1
pirinixic acid	affects binding, decreases expression, increases activity	1
deoxynivalenol	increases expression	1
diethyl maleate	increases expression	1
sodium arsenite	increases expression	1
cobaltous chloride	decreases expression	1
potassium chromate(VI)	decreases expression	1
pentanal	increases expression	1
deguelin	increases expression	1
ICG 001	increases expression	1
abrine	increases expression	1
pyrachlostrobin	increases expression	1
Temozolomide	increases expression	1
Sunitinib	decreases expression	1
Fulvestrant	affects cotreatment, decreases methylation	1
Leflunomide	increases expression	1
Benzo(a)pyrene	decreases methylation	1
Carbamazepine	affects expression	1
Cisplatin	decreases expression	1
Copper	affects binding, decreases expression	1
Disulfiram	affects binding, decreases expression	1
Ivermectin	decreases expression	1
Lead	affects splicing	1
Methotrexate	increases expression	1
Phenobarbital	affects expression	1
Ribonucleotides	affects binding	1
Rotenone	increases expression	1

Clinical trials (associated diseases)

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