SART1

Summary

SART1 (spliceosome associated factor 1, recruiter of U4/U6.U5 tri-snRNP, HGNC:10538) is a protein-coding gene on chromosome 11q13.1, encoding U4/U6.U5 tri-snRNP-associated protein 1 (O43290). Plays a role in mRNA splicing as a component of the U4/U6-U5 tri-snRNP, one of the building blocks of the spliceosome. It is a common-essential gene (DepMap: required in 98.7% of cancer cell lines).

This gene encodes two proteins, the SART1(800) protein expressed in the nucleus of the majority of proliferating cells, and the SART1(259) protein expressed in the cytosol of epithelial cancers. The SART1(259) protein is translated by the mechanism of -1 frameshifting during posttranscriptional regulation; its full-length sequence is not published yet. The two encoded proteins are thought to be involved in the regulation of proliferation. Both proteins have tumor-rejection antigens. The SART1(259) protein possesses tumor epitopes capable of inducing HLA-A2402-restricted cytotoxic T lymphocytes in cancer patients. This SART1(259) antigen may be useful in specific immunotherapy for cancer patients and may serve as a paradigmatic tool for the diagnosis and treatment of patients with atopy. The SART1(259) protein is found to be essential for the recruitment of the tri-snRNP to the pre-spliceosome in the spliceosome assembly pathway.

Source: NCBI Gene 9092 — RefSeq curated summary.

At a glance

• GWAS associations: 6
• Clinical variants (ClinVar): 154 total
• Cancer dependency (DepMap): dependent in 98.7% of screened cell lines (common-essential)
• MANE Select transcript: NM_005146

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10538
Approved symbol	SART1
Name	spliceosome associated factor 1, recruiter of U4/U6.U5 tri-snRNP
Location	11q13.1
Locus type	gene with protein product
Status	Approved
Aliases	Ara1, Snu66, SNRNP110, HAF
Ensembl gene	ENSG00000175467
Ensembl biotype	protein_coding
OMIM	605941
Entrez	9092

Gene structure

Transcript identifiers

Ensembl transcripts: 15 — 8 protein_coding, 5 retained_intron, 1 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000312397, ENST00000528137, ENST00000528573, ENST00000529532, ENST00000529580, ENST00000530251, ENST00000532333, ENST00000533386, ENST00000872360, ENST00000923550, ENST00000923551, ENST00000923552, ENST00000972145, ENST00000972146, ENST00000972147

RefSeq mRNA: 1 — MANE Select: NM_005146 NM_005146

CCDS: CCDS31611

Canonical transcript exons

ENST00000312397 — 20 exons

Exon	Start	End
ENSE00001190115	65967471	65967586
ENSE00001190123	65967259	65967383
ENSE00001190131	65966350	65966556
ENSE00001190177	65961734	65962093
ENSE00001506283	65966076	65966218
ENSE00001622819	65979012	65980137
ENSE00001670851	65977764	65977899
ENSE00001716420	65976395	65976568
ENSE00001739580	65976656	65976766
ENSE00002411458	65967679	65967821
ENSE00002485504	65965092	65965218
ENSE00003492986	65964074	65964131
ENSE00003507195	65977563	65977653
ENSE00003573782	65965887	65965986
ENSE00003578323	65978600	65978689
ENSE00003587487	65964515	65964570
ENSE00003590491	65978793	65978914
ENSE00003592407	65977014	65977101
ENSE00003690299	65965702	65965779
ENSE00003691276	65965342	65965447

Expression profiles

Bgee: expression breadth ubiquitous, 292 present calls, max score 96.59.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 36.0161 / max 271.3708, expressed in 1822 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
115256	36.0161	1822

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
tendon of biceps brachii	UBERON:0008188	96.59	gold quality
lower esophagus mucosa	UBERON:0035834	96.31	gold quality
apex of heart	UBERON:0002098	96.08	gold quality
granulocyte	CL:0000094	96.06	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	95.88	gold quality
ectocervix	UBERON:0012249	95.56	gold quality
mucosa of transverse colon	UBERON:0004991	95.54	gold quality
adenohypophysis	UBERON:0002196	95.53	gold quality
endocervix	UBERON:0000458	95.50	gold quality
right lobe of thyroid gland	UBERON:0001119	95.42	gold quality
skin of leg	UBERON:0001511	95.38	gold quality
body of uterus	UBERON:0009853	95.37	gold quality
left uterine tube	UBERON:0001303	95.31	gold quality
right ovary	UBERON:0002118	95.29	gold quality
left lobe of thyroid gland	UBERON:0001120	95.11	gold quality
skin of abdomen	UBERON:0001416	95.02	gold quality
left ovary	UBERON:0002119	95.00	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	94.94	gold quality
tibial nerve	UBERON:0001323	94.88	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	94.86	gold quality
stromal cell of endometrium	CL:0002255	94.85	gold quality
muscle layer of sigmoid colon	UBERON:0035805	94.85	gold quality
spleen	UBERON:0002106	94.84	gold quality
lower esophagus muscularis layer	UBERON:0035833	94.69	gold quality
lower esophagus	UBERON:0013473	94.68	gold quality
hindlimb stylopod muscle	UBERON:0004252	94.57	gold quality
left testis	UBERON:0004533	94.52	gold quality
ascending aorta	UBERON:0001496	94.45	gold quality
thoracic aorta	UBERON:0001515	94.39	gold quality
popliteal artery	UBERON:0002250	94.38	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.37
E-GEOD-110499	no	62.04

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

47 targeting SART1, 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-12118	100.00	65.88	1270
HSA-MIR-6891-5P	99.98	66.53	1372
HSA-MIR-3173-3P	99.98	66.49	1217
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-1236-3P	99.94	68.04	1695
HSA-MIR-106A-5P	99.90	73.94	2683
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-17-5P	99.89	73.83	2665
HSA-MIR-106B-5P	99.88	74.72	2795
HSA-MIR-20A-5P	99.88	74.76	2769
HSA-MIR-20B-5P	99.88	74.01	2621
HSA-MIR-519D-3P	99.88	73.97	2607
HSA-MIR-526B-3P	99.88	74.06	2587
HSA-MIR-93-5P	99.88	73.98	2606
HSA-MIR-6844	99.82	70.69	2423
HSA-MIR-4517	99.76	69.19	1867
HSA-MIR-29B-2-5P	99.67	68.98	1726
HSA-MIR-561-3P	99.64	70.90	3647
HSA-MIR-6848-3P	99.64	66.49	885
HSA-MIR-7106-5P	99.53	67.47	3574
HSA-MIR-4437	99.52	65.29	1266
HSA-MIR-7159-3P	99.51	70.17	1920
HSA-MIR-766-5P	99.47	67.91	2225
HSA-MIR-582-5P	99.47	70.79	2635
HSA-MIR-4251	99.40	69.19	3363
HSA-MIR-6843-3P	99.26	66.42	915
HSA-MIR-939-3P	98.97	65.07	2347
HSA-MIR-1304-5P	98.90	68.58	1054
HSA-MIR-6889-3P	98.84	67.35	1198
HSA-MIR-4451	98.82	68.17	1455

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 98.7% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 9)

• p110, a novel human U6 snRNP protein and U4/U6 snRNP recycling factor (PMID:12032085)
• hypothesize that polymorphic variation within the SART-1 gene may account for individuals developing atopy (PMID:12189166)
• hypoxia-associated factor (HAF), also known as SART1, a protein expressed in proliferating cells, binds and ubiquitinates HIF-1alpha in vitro, and both binding and E3 ligase activity are mediated by HAF amino acids 654 to 800 (PMID:18838541)
• This study identifies SART1 as a previously unidentified regulator of c-FLIP and drug-induced activation of caspase-8. (PMID:22027693)
• SART1 exerts its anti-Hepatitis C virus action through direct transcriptional regulation for some Interferon stimulating genes and alternative splicing for others. (PMID:25481564)
• Data indicate that mutant VHL can protect HIF1alpha from SART1-dependent degradation in normoxic conditions, but this protection is lost in hypoxic settings, favoring hypoxia-dependent ccRCC proliferation. (PMID:25915846)
• SART1 has a role in IFN-mediated anti-Hepatitis B virus response (PMID:28077916)
• Patients with clear cell renal carcinoma with high HAF transcript or protein levels showed significantly decreased overall survival compared with those with low HAF. Functional study shows that HAF promotes neurofibromin ubiquitination and degradation independently of oxygen and pVHL, resulting in Ras-ERK pathway activation. (PMID:30705246)
• Suppressing Sart1 to modulate macrophage polarization by siRNA-loaded liposomes: a promising therapeutic strategy for pulmonary fibrosis. (PMID:33391530)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
mus_musculus	Sart1	ENSMUSG00000039148
rattus_norvegicus	Sart1	ENSRNOG00000020475
drosophila_melanogaster	CG6686	FBGN0032388
caenorhabditis_elegans		WBGENE00017605

Protein

Protein identifiers

U4/U6.U5 tri-snRNP-associated protein 1 — O43290 (reviewed: O43290)

Alternative names: SNU66 homolog, Squamous cell carcinoma antigen recognized by T-cells 1, U4/U6.U5 tri-snRNP-associated 110 kDa protein

All UniProt accessions (2): E9PQI8, O43290

UniProt curated annotations — full annotation on UniProt →

Function. Plays a role in mRNA splicing as a component of the U4/U6-U5 tri-snRNP, one of the building blocks of the spliceosome. May also bind to DNA.

Subunit / interactions. Identified in the spliceosome C complex. Component of the U4/U6-U5 tri-snRNP complex composed of the U4, U6 and U5 snRNAs and at least PRPF3, PRPF4, PRPF6, PRPF8, PRPF31, SNRNP200, TXNL4A, SNRNP40, DDX23, CD2BP2, PPIH, SNU13, EFTUD2, SART1 and USP39. Interacts with UBL5. Interacts with IVNS1ABP (via Kelch repeats).

Subcellular location. Nucleus.

Tissue specificity. Ubiquitously expressed.

Post-translational modifications. Sumoylated with SUMO2.

Similarity. Belongs to the SNU66/SART1 family.

Isoforms (1)

UniProt ID	Names	Canonical?
O43290-1	1, 125 kDa	yes

RefSeq proteins (1): NP_005137* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR005011	SNU66/SART1	Family
IPR045347	HIND	Conserved_site

Pfam: PF03343, PF19252

UniProt features (71 total): cross-link 23, modified residue 17, helix 12, region of interest 4, sequence variant 3, strand 3, compositionally biased region 3, coiled-coil region 2, sequence conflict 2, chain 1, turn 1

Structure

Experimental structures (PDB)

26 structures.

PDB	Method	Resolution (Å)
4PYU	X-RAY DIFFRACTION	2
8H6L	ELECTRON MICROSCOPY	2.6
8H6K	ELECTRON MICROSCOPY	2.7
6QW6	ELECTRON MICROSCOPY	2.92
8Q7N	ELECTRON MICROSCOPY	3.1
8QOZ	ELECTRON MICROSCOPY	3.1
8QPE	ELECTRON MICROSCOPY	3.1
8H6E	ELECTRON MICROSCOPY	3.2
8H6J	ELECTRON MICROSCOPY	3.25
6QX9	ELECTRON MICROSCOPY	3.28
8Y6O	ELECTRON MICROSCOPY	3.38
8QP8	ELECTRON MICROSCOPY	3.5
8QPA	ELECTRON MICROSCOPY	3.7
8QPB	ELECTRON MICROSCOPY	3.7
6AHD	ELECTRON MICROSCOPY	3.8
8QP9	ELECTRON MICROSCOPY	4.1
8QZS	ELECTRON MICROSCOPY	4.1
8QPK	ELECTRON MICROSCOPY	4.2
8R09	ELECTRON MICROSCOPY	4.3
8R0B	ELECTRON MICROSCOPY	4.4
5O9Z	ELECTRON MICROSCOPY	4.5
8QO9	ELECTRON MICROSCOPY	5.29
8R0A	ELECTRON MICROSCOPY	5.8
8R08	ELECTRON MICROSCOPY	6.1
8RM5	ELECTRON MICROSCOPY	6.9
8QXD	ELECTRON MICROSCOPY	9.6

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O43290-F1	64.28	0.04

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 (40): 189, 321, 348, 392, 430, 448, 474, 486, 521, 591, 596, 598, 621, 695, 761, 764, 789, 125, 133, 141 …

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-72163	mRNA Splicing - Major Pathway
R-HSA-72172	mRNA Splicing
R-HSA-72203	Processing of Capped Intron-Containing Pre-mRNA
R-HSA-8953854	Metabolism of RNA

MSigDB gene sets: 170 (showing top): GOBP_REGULATION_OF_CELL_ACTIVATION, GOBP_RIBOSOME_BIOGENESIS, GOBP_POSITIVE_REGULATION_OF_HEMOPOIESIS, MORF_UBE2I, chr11q13, GOBP_POSITIVE_REGULATION_OF_CELL_ADHESION, GOBP_CELL_CELL_ADHESION, GOBP_REGULATION_OF_LEUKOCYTE_DIFFERENTIATION, CATRRAGC_UNKNOWN, GOBP_REGULATION_OF_HEMOPOIESIS, GOBP_SPLICEOSOMAL_TRI_SNRNP_COMPLEX_ASSEMBLY, GOBP_POSITIVE_REGULATION_OF_CELL_DIFFERENTIATION, BLALOCK_ALZHEIMERS_DISEASE_UP, REACTOME_PROCESSING_OF_CAPPED_INTRON_CONTAINING_PRE_MRNA, GOBP_POSITIVE_REGULATION_OF_CELL_ACTIVATION

GO Biological Process (7): spliceosomal snRNP assembly (GO:0000387), mRNA splicing, via spliceosome (GO:0000398), maturation of 5S rRNA (GO:0000481), mRNA cis splicing, via spliceosome (GO:0045292), positive regulation of cytotoxic T cell differentiation (GO:0045585), mRNA processing (GO:0006397), RNA splicing (GO:0008380)

GO Molecular Function (2): RNA binding (GO:0003723), protein binding (GO:0005515)

GO Cellular Component (11): nucleus (GO:0005634), nucleoplasm (GO:0005654), spliceosomal complex (GO:0005681), cytoplasm (GO:0005737), Golgi apparatus (GO:0005794), cytosol (GO:0005829), Cajal body (GO:0015030), nuclear speck (GO:0016607), U4/U6 x U5 tri-snRNP complex (GO:0046540), U2-type precatalytic spliceosome (GO:0071005), catalytic step 2 spliceosome (GO:0071013)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
mRNA Splicing	1
Processing of Capped Intron-Containing Pre-mRNA	1
Metabolism of RNA	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
mRNA splicing, via spliceosome	2
RNA processing	2
intracellular membrane-bounded organelle	2
cytoplasm	2
nuclear ribonucleoprotein granule	2
U5 snRNP	2
protein-RNA complex assembly	1
RNA splicing, via transesterification reactions with bulged adenosine as nucleophile	1
mRNA processing	1
rRNA processing	1
cytotoxic T cell differentiation	1
positive regulation of T cell differentiation	1
regulation of cytotoxic T cell differentiation	1
mRNA metabolic process	1
nucleic acid binding	1
binding	1
nuclear lumen	1
nuclear protein-containing complex	1
ribonucleoprotein complex	1
intracellular anatomical structure	1
endomembrane system	1
U4/U6 snRNP	1
spliceosomal tri-snRNP complex	1
U2-type spliceosomal complex	1
U1 snRNP	1
U2 snRNP	1
U4/U6 x U5 tri-snRNP complex	1
precatalytic spliceosome	1
Prp19 complex	1
spliceosomal complex	1
catalytic complex	1

Protein interactions and networks

STRING

2666 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SART1	PRPF3	O43395	912
SART1	DSE	Q9UL01	884
SART1	SNRNP200	O75643	868
SART1	PRPF6	O94906	834
SART1	MAGEC1	O60732	810
SART1	PRPF31	Q8WWY3	797
SART1	UBL5	Q9BZL1	786
SART1	MFAP1	P55081	784
SART1	ZMAT2	Q96NC0	783
SART1	PRPF8	Q6P2Q9	772
SART1	PRPF38A	Q8NAV1	742
SART1	DDX23	Q9BUQ8	725
SART1	SLC39A7	Q92504	697
SART1	EFTUD2	Q15029	676
SART1	HIF1A	Q16665	652

IntAct

205 interactions, top by confidence:

A	B	Type	Score
SNRPF	GEMIN2	psi-mi:“MI:0914”(association)	0.910
SNRPE	GEMIN2	psi-mi:“MI:0914”(association)	0.770
PRPF6	SART1	psi-mi:“MI:0915”(physical association)	0.750
SART1	PRPF6	psi-mi:“MI:0915”(physical association)	0.750
SART1	PRPF6	psi-mi:“MI:0914”(association)	0.750
PRPF6	SART1	psi-mi:“MI:0914”(association)	0.750
H2AX	PPM1G	psi-mi:“MI:0914”(association)	0.730
PRPF3	PRPF4	psi-mi:“MI:0914”(association)	0.730
PRPF3	SART1	psi-mi:“MI:0915”(physical association)	0.720
SART1	PRPF3	psi-mi:“MI:0915”(physical association)	0.720
SART1	PRPF3	psi-mi:“MI:0914”(association)	0.720
EPN1	PHGDH	psi-mi:“MI:0914”(association)	0.710
SNRPD2	GEMIN2	psi-mi:“MI:0914”(association)	0.710
SNRPG	GEMIN2	psi-mi:“MI:0914”(association)	0.710
UBL5	SART1	psi-mi:“MI:0914”(association)	0.670
SART1	UBL5	psi-mi:“MI:0915”(physical association)	0.670
NCBP2	KPNA3	psi-mi:“MI:0914”(association)	0.640
CAMKV	AP3B1	psi-mi:“MI:0914”(association)	0.640
PRPF8	PRPF4	psi-mi:“MI:0914”(association)	0.640
SF3B1	SAP18	psi-mi:“MI:0914”(association)	0.640
SNRNP40	PRPF4	psi-mi:“MI:0914”(association)	0.640
DDX23	PRPF4	psi-mi:“MI:0914”(association)	0.640
SNRPB	SART1	psi-mi:“MI:0914”(association)	0.640

BioGRID (479): SART1 (Two-hybrid), SART1 (Affinity Capture-Western), SART1 (Affinity Capture-MS), SART1 (Affinity Capture-MS), SART1 (Affinity Capture-MS), SART1 (Affinity Capture-MS), SART1 (Affinity Capture-MS), SART1 (Biochemical Activity), SART1 (Affinity Capture-MS), SART1 (Affinity Capture-MS), SART1 (Affinity Capture-MS), SART1 (Affinity Capture-MS), SART1 (Affinity Capture-MS), EFTUD2 (Co-fractionation), PABPC1 (Co-fractionation)

ESM2 similar proteins: A0JNI5, A2AJT4, A2AQ19, A4IFB1, B1H1X4, D3ZTQ1, O43290, P35269, Q05519, Q12872, Q13435, Q3THK3, Q3UJB0, Q3UQU0, Q3USH5, Q4V7C9, Q53F19, Q568R1, Q5EA53, Q5HZB6, Q5PQQ2, Q5R539, Q5RAD5, Q5XIW8, Q5ZM19, Q66I22, Q6AY96, Q6DDA4, Q6GLZ8, Q6INH5, Q6ZPZ3, Q8BZR9, Q8CFC7, Q8K194, Q8N2M8, Q8N5F7, Q8TF01, Q8VHI6, Q8WVK2, Q923D5

Diamond homologs: O43290, Q12420, Q5XIW8, Q9Z315, O94538, Q9LFE0

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
SART1	“form complex”	“U4/U6.U5 snRNP complex”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 194 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
Metabolism of non-coding RNA	8	34.3×	2e-09
mRNA Splicing - Minor Pathway	18	27.2×	6e-20
mRNA Splicing	34	25.2×	5e-37
mRNA Splicing - Major Pathway	61	22.5×	3e-66
Processing of Capped Intron-Containing Pre-mRNA	37	20.5×	6e-37
mRNA Polyadenylation	32	19.0×	2e-30
RNA Polymerase II Transcription Termination	11	16.3×	3e-09
mRNA 3’-end processing	12	16.0×	5e-10

GO biological processes:

GO term	Partners	Fold	FDR
RNA splicing, via transesterification reactions	13	46.9×	6e-17
spliceosomal complex assembly	13	45.2×	8e-17
U2-type prespliceosome assembly	11	39.7×	2e-13
spliceosomal tri-snRNP complex assembly	6	39.0×	6e-07
mRNA cis splicing, via spliceosome	6	34.4×	1e-06
spliceosomal snRNP assembly	10	33.6×	3e-11
negative regulation of mRNA splicing, via spliceosome	7	31.0×	2e-07
mRNA splicing, via spliceosome	53	28.1×	2e-60

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	119
Likely benign	5
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2802 predictions. Top by Δscore:

Variant	Effect	Δscore
11:65962090:GCCG:G	donor_gain	1.0000
11:65962093:GGTG:G	donor_loss	1.0000
11:65962094:G:GG	donor_gain	1.0000
11:65962099:G:GT	donor_gain	1.0000
11:65964124:GAGAC:G	donor_gain	1.0000
11:65964127:ACTAA:A	donor_gain	1.0000
11:65964128:CTAA:C	donor_gain	1.0000
11:65964129:TAA:T	donor_gain	1.0000
11:65964129:TAAG:T	donor_loss	1.0000
11:65964130:AA:A	donor_gain	1.0000
11:65964131:AGT:A	donor_loss	1.0000
11:65964132:G:GG	donor_gain	1.0000
11:65964136:G:GG	donor_gain	1.0000
11:65964513:A:AG	acceptor_gain	1.0000
11:65964514:G:GG	acceptor_gain	1.0000
11:65964514:GC:G	acceptor_gain	1.0000
11:65964569:GG:G	donor_gain	1.0000
11:65964570:GG:G	donor_gain	1.0000
11:65965090:A:AG	acceptor_gain	1.0000
11:65965090:A:T	acceptor_loss	1.0000
11:65965090:AGAG:A	acceptor_gain	1.0000
11:65965091:G:GC	acceptor_loss	1.0000
11:65965091:G:GG	acceptor_gain	1.0000
11:65965091:GA:G	acceptor_gain	1.0000
11:65965091:GAGG:G	acceptor_gain	1.0000
11:65965091:GAGGC:G	acceptor_gain	1.0000
11:65965192:G:GT	donor_gain	1.0000
11:65965214:C:G	donor_gain	1.0000
11:65965216:GGG:G	donor_gain	1.0000
11:65965217:GG:G	donor_gain	1.0000

AlphaMissense

5191 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:65965197:G:C	R178P	1.000
11:65976497:T:C	F559L	1.000
11:65976499:C:A	F559L	1.000
11:65976499:C:G	F559L	1.000
11:65977819:T:C	F698L	1.000
11:65977821:C:A	F698L	1.000
11:65977821:C:G	F698L	1.000
11:65977850:T:A	V708D	1.000
11:65977856:T:A	I710N	1.000
11:65977856:T:G	I710S	1.000
11:65977861:T:G	Y712D	1.000
11:65977867:G:C	D714H	1.000
11:65977876:G:C	G717R	1.000
11:65977877:G:A	G717D	1.000
11:65977877:G:T	G717V	1.000
11:65977880:G:C	R718P	1.000
11:65977886:T:A	L720H	1.000
11:65977886:T:C	L720P	1.000
11:65977894:A:G	K723E	1.000
11:65977896:G:C	K723N	1.000
11:65977896:G:T	K723N	1.000
11:65977897:G:A	E724K	1.000
11:65978600:G:C	A725P	1.000
11:65978601:C:A	A725D	1.000
11:65978603:T:A	F726I	1.000
11:65978603:T:C	F726L	1.000
11:65978603:T:G	F726V	1.000
11:65978604:T:C	F726S	1.000
11:65978604:T:G	F726C	1.000
11:65978605:C:A	F726L	1.000

dbSNP variants (sampled 300 via entrez): RS1000007881 (11:65973065 T>C), RS1000072033 (11:65976218 G>A), RS1000349464 (11:65962950 A>G), RS1000397229 (11:65973955 G>A,T), RS1000451701 (11:65960615 C>G,T), RS1000505266 (11:65960822 A>C), RS1000680293 (11:65967055 G>A), RS1000818564 (11:65964150 G>A,T), RS1000886850 (11:65962727 G>T), RS1001115572 (11:65970567 G>A), RS1001170471 (11:65963656 A>G), RS1001354051 (11:65976949 A>G,T), RS1001415790 (11:65965834 C>T), RS1001599262 (11:65962205 C>G,T), RS1001750945 (11:65968818 C>G,T)

Disease associations

OMIM: gene MIM:605941 | 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
GCST002481_8	Acne (severe)	3.000000e-11
GCST007294_7	Body fat distribution (trunk fat ratio)	8.000000e-12
GCST007294_75	Body fat distribution (trunk fat ratio)	1.000000e-07
GCST007295_158	Body fat distribution (leg fat ratio)	8.000000e-06
GCST007295_48	Body fat distribution (leg fat ratio)	3.000000e-09
GCST008103_21	Bipolar disorder	2.000000e-08

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004341	body fat distribution

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases abundance, increases expression, affects cotreatment	3
Air Pollutants	affects expression, increases abundance, increases expression	2
Arsenic	affects methylation, affects cotreatment, increases abundance, increases expression	2
Cadmium Chloride	increases abundance, increases expression	2
FR900359	affects phosphorylation	1
TAK-243	decreases sumoylation	1
triphenyl phosphate	affects expression	1
bisphenol A	increases expression	1
deoxynivalenol	increases expression	1
lead acetate	increases expression	1
methylparaben	increases expression	1
pyrrolidine dithiocarbamic acid	affects cotreatment, decreases expression, decreases reaction	1
manganese chloride	affects cotreatment, increases abundance, increases expression	1
ochratoxin A	decreases expression	1
benzo(e)pyrene	decreases methylation	1
aflatoxin B2	increases methylation	1
cupric chloride	increases expression	1
coumarin	increases phosphorylation	1
perfluoro-n-nonanoic acid	decreases expression	1
abrine	increases expression	1
bisphenol S	affects expression	1
Resveratrol	affects cotreatment, increases expression	1
Sunitinib	increases expression	1
Arsenic Trioxide	increases expression	1
Benzo(a)pyrene	decreases expression	1
Cadmium	increases abundance, increases expression	1
Caffeine	affects phosphorylation	1
Cisplatin	decreases expression	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Ivermectin	decreases expression	1

Clinical trials (associated diseases)

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