DIRAS3

Summary

DIRAS3 (DIRAS family GTPase 3, HGNC:687) is a protein-coding gene on chromosome 1p31.3, encoding GTP-binding protein Di-Ras3 (O95661).

This gene encodes a member of the ras superfamily. This gene is imprinted gene with monoallelic expression of the paternal allele which is associated with growth suppression. The encoded protein acts as a tumor suppressor whose function is abrogated in many ovarian and breast cancers. This protein may also play a role autophagy in certain cancer cells by regulating the autophagosome initiation complex.

Source: NCBI Gene 9077 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 25 total
• Dosage sensitivity (ClinGen): haploinsufficiency no evidence, triplosensitivity no evidence
• MANE Select transcript: NM_004675

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:687
Approved symbol	DIRAS3
Name	DIRAS family GTPase 3
Location	1p31.3
Locus type	gene with protein product
Status	Approved
Aliases	NOEY2
Ensembl gene	ENSG00000162595
Ensembl biotype	protein_coding
OMIM	605193
Entrez	9077

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 5 protein_coding

ENST00000370981, ENST00000646789, ENST00000691269, ENST00000693623, ENST00000903449

RefSeq mRNA: 1 — MANE Select: NM_004675 NM_004675

CCDS: CCDS641

Canonical transcript exons

ENST00000646789 — 2 exons

Exon	Start	End
ENSE00001454045	68045962	68047362
ENSE00003822354	68050548	68050627

Expression profiles

Bgee: expression breadth ubiquitous, 208 present calls, max score 95.14.

FANTOM5 (CAGE): breadth broad, TPM avg 5.1351 / max 508.2565, expressed in 716 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
12771	3.7765	563
12769	0.5050	159
12770	0.2738	112
12773	0.2416	105
12772	0.2343	98
12774	0.1039	39

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
adenohypophysis	UBERON:0002196	95.14	gold quality
pituitary gland	UBERON:0000007	95.07	gold quality
hypothalamus	UBERON:0001898	94.34	gold quality
nucleus accumbens	UBERON:0001882	93.60	gold quality
left ovary	UBERON:0002119	93.60	gold quality
right ovary	UBERON:0002118	91.87	gold quality
ovary	UBERON:0000992	91.33	gold quality
oocyte	CL:0000023	88.18	gold quality
apex of heart	UBERON:0002098	88.11	gold quality
body of pancreas	UBERON:0001150	86.74	gold quality
germinal epithelium of ovary	UBERON:0001304	86.31	gold quality
right adrenal gland cortex	UBERON:0035827	85.20	gold quality
left adrenal gland	UBERON:0001234	84.83	gold quality
left adrenal gland cortex	UBERON:0035825	84.58	gold quality
right adrenal gland	UBERON:0001233	84.49	gold quality
secondary oocyte	CL:0000655	84.11	gold quality
pancreas	UBERON:0001264	84.06	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	83.73	gold quality
calcaneal tendon	UBERON:0003701	83.54	gold quality
adrenal cortex	UBERON:0001235	83.43	gold quality
islet of Langerhans	UBERON:0000006	83.34	gold quality
mucosa of stomach	UBERON:0001199	82.81	gold quality
adrenal gland	UBERON:0002369	82.76	gold quality
amygdala	UBERON:0001876	81.53	gold quality
gall bladder	UBERON:0002110	81.52	gold quality
adrenal tissue	UBERON:0018303	81.31	gold quality
caudate nucleus	UBERON:0001873	80.95	gold quality
heart right ventricle	UBERON:0002080	80.63	gold quality
putamen	UBERON:0001874	80.33	gold quality
heart left ventricle	UBERON:0002084	78.88	gold quality

Single-cell (SCXA)

Detected in 7 experiment(s), a significant marker in 6.

Experiment	Marker?	Max mean expression
E-MTAB-8559	yes	1608.45
E-MTAB-5061	yes	9.86
E-MTAB-7249	yes	4.57
E-GEOD-81608	yes	4.44
E-HCAD-31	yes	3.69
E-ENAD-27	no	3.90
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): E2F1, E2F2, E2F3, E2F4, E2F5, HDAC9, STAT3

miRNA regulators (miRDB)

48 targeting DIRAS3, 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-6833-3P	100.00	70.63	3197
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-221-3P	99.86	71.56	1329
HSA-MIR-222-3P	99.86	71.35	1337
HSA-MIR-4307	99.82	70.45	3374
HSA-MIR-4668-5P	99.79	70.58	3782
HSA-MIR-4677-5P	99.70	70.09	1940
HSA-MIR-548M	99.70	68.87	1749
HSA-MIR-379-3P	99.69	69.60	1524
HSA-MIR-411-3P	99.69	69.63	1524
HSA-MIR-10393-5P	99.65	68.01	1368
HSA-MIR-7156-5P	99.64	68.81	1369
HSA-MIR-105-5P	99.54	69.24	2060
HSA-MIR-7853-5P	99.54	69.30	2055
HSA-MIR-12123	99.52	71.79	2990
HSA-MIR-4452	99.50	68.45	1493
HSA-MIR-4273	99.45	67.93	1206
HSA-MIR-3606-5P	99.31	69.67	1168
HSA-MIR-888-5P	99.30	70.15	1855
HSA-MIR-548V	99.29	69.47	1157
HSA-MIR-3191-5P	99.24	66.52	1722
HSA-MIR-664A-3P	99.22	71.08	2696

Functional genomics

ClinGen dosage: haploinsufficiency 0 (no evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• A link between NOEY2 loss expression and the spreading mechanism of breast cancer may possibly exist. (PMID:12485503)
• ARHI inhibits cell growth, and loss of its expression in cells may contribute to the development of breast and ovarian cancers (PMID:12771940)
• Hypermethylation of CpG island II in the promoter region of ARHI is associated with the complete loss of ARHI expression in breast cancer cells. (PMID:12874023)
• ARHI may have a role in development and progression of ductal breast carcinoma in situ (PMID:14506155)
• Association between STAT3 and ARHI as well as the functional inhibition of STAT3 transcriptional activity by ARHI suggests a novel mechanism through which a putative tumor suppressor gene can inhibit STAT3 activity in breast and ovarian cancers. (PMID:16061651)
• Down-regulation of ARHI gene is associated with breast cancer (PMID:16158053)
• Down-regulation of ARHI due to loss of heterozygosity and promoter methylation is associated with ovarian cancers (PMID:18286529)
• DIRAS3 is a novel, prognostically relevant candidate gene that is frequently methylated and silenced in oligodendroglial tumors with 1p deletion. (PMID:18302158)
• provide evidences that ARHI downregulated in HCCs could play a role in liver cancer via acting as a tumor suppressor gene, which mainly was triggered by the epigenetic events in HCC specimens (PMID:18612997)
• ARHI can induce autophagic cell death, but can also promote tumor dormancy in the presence of factors that promote survival in the cancer microenvironment. (PMID:19033662)
• Data show that ARHI could compete for Ran-importin binding and induce disruption of importin-binding to cargo proteins, including STAT3. (PMID:19435463)
• The presence of NOEY2 mutations in human breast cancer and early-stage lesions indicates that NOEY2 mutations may be partly associated with breast tumourigenesis. (PMID:19482475)
• ARHI represents a modulator of cancer cell proliferation and may play an important role in the development of pancreatic cancer. (PMID:19639215)
• Loss of heterozygosity at 1p31 (including ARHI) did not correlate with the mitotic activity index nor provide prognostic information. (PMID:19759414)
• These data highlighted an important role for ARHI in controlling hepatocellular carcinoma growth and angiogenesis. (PMID:21093415)
• Data show that ARHI re-expression induces autophagic cell death in breast cancer cells and enhances the inhibitory effects of paclitaxel by promoting autophagy, apoptosis, and G2/M cell cycle arrest. (PMID:21244707)
• ARHI expression is present in the endometrium and up-regulated in ectopic endometrium, whereas in the ectopic endometrium of patients with malignant endometriosis its expression is often negative. (PMID:21602127)
• ARHI has a critical and previously uncharacterized role in the regulation of ovarian cancer cell migration. (PMID:21643014)
• ARHI has pro-apoptotic effects on HCC cells, which is associated with the inactivation of both Akt and NF-kappaB survival pathways. (PMID:21933150)
• The level of ARHI mRNA was significantly lower in aggressive compared with non-aggressive prostate cancer tissue samples (PMID:22117988)
• downregulation of ARHI may play an important role both in the pathogenesis and aggravation of gastric cancer. ARHI gene CpG island methylation is a potential molecular basis of its downregulation. (PMID:22427032)
• ARHI expression is downregulated in human gastric cancer and it may be a novel tumor suppressive target for gastric cancer therapy. (PMID:22497484)
• The consequence of complex formation is a DiRas3-mediated recruitment and anchorage of C-RAF to components of the membrane skeleton, suppression of C-RAF/B-RAF heterodimerization, and inhibition of C-RAF kinase activity. (PMID:22605333)
• DiRas3 interacts with C-RAF and downregulates MEK1 activity to restrict cell migration. (PMID:23157514)
• overexpression of ARHI gene might be associated with the inhibition of lung cancer cell growth, proliferation and invasion, and the promotion of apoptosis. (PMID:23247805)
• ARHI acts as a tumor suppressor by downregulating the NFkappaB signaling pathway, which results in the inhibition of cell proliferation, apoptosis and the cell cycle in the pancreatic tumor PANC-1 cell line (PMID:23447002)
• acetylated STAT3 bound to the ARHI promoter and recruited DNA methyltransferase 1 for genetic modification. (PMID:23604529)
• Expression of JMJD2A in infiltrating duct carcinoma is higher than in fibroadenoma, and is associated with ARHI, p53 and ER (PMID:23678541)
• Results indicate that the aplysia ras homolog member I (ARHI) 3’UTR was a direct target of miR-221 in breast cancer MCF-7 cells. (PMID:23801152)
• Imprinted chromatin around DIRAS3 regulates alternative splicing of GNG12-AS1, a long noncoding RNA. (PMID:23871723)
• Loss of ARHI expression is associated with glioma. (PMID:24458808)
• The silence of ARHI expression in vitro seems to accelerate the malignant transformation of healthy ovarian cells by restraining apoptosis and autophagy. (PMID:24476894)
• ARHI is required for autophagy-meditated cancer cell arrest and ARHI inhibits signaling through PI3K/AKT and Ras/MAP by enhancing internalization and degradation of the epidermal growth factor receptor. (PMID:24769729)
• suggest that DIRAS3 not only regulates the autophagosome initiation complex, but induces autophagy in dormant, nutrient-deprived ovarian cancer cells that remain after conventional chemotherapy, facilitating their survival (PMID:24879154)
• EZH2-‘‘induced H3K27me3 is associated with epigenetic repression of the ARHI tumor-suppressor gene in epithelial ovarian cancer (PMID:25077680)
• JMJD2A-dependent silencing of Sp1 in advanced breast cancer promotes metastasis by downregulation of DIRAS3. (PMID:25193278)
• ARHI competes with RanGTPase and interacts with importin beta via basic-acidic patch interaction, which leads to inhibition of STAT3 translocation. (PMID:25499977)
• Letter: ARHI suppresses pancreatic cancer by regulating ERK 1/2 signaling. (PMID:25675421)
• study reports somatic mutation of ARHI gene in hepatocellular carcinoma (HCC), however, only one ARHI mutation was detected; data indicate that somatic mutation in ARHI may be rare in HCCs and suggest that somatic mutational events in ARHI may not contribute to development of HCCs (PMID:26143066)
• ARHI mRNA and protein expression is markedly decreased in osteosarcoma MG-63 cells lines. Overexpression of ARHI inhibits cell viability and proliferation. (PMID:26165148)

Cross-species orthologs

0 orthologs

Paralogs (35): RALA (ENSG00000006451), REM1 (ENSG00000088320), RASL10A (ENSG00000100276), RASD2 (ENSG00000100302), RASL12 (ENSG00000103710), RHEB (ENSG00000106615), RASD1 (ENSG00000108551), RERGL (ENSG00000111404), RAP1A (ENSG00000116473), RASL11A (ENSG00000122035), RAP2C (ENSG00000123728), RAP2A (ENSG00000125249), RRAS (ENSG00000126458), RAP1B (ENSG00000127314), RASL11B (ENSG00000128045), KRAS (ENSG00000133703), RRAS2 (ENSG00000133818), RERG (ENSG00000134533), REM2 (ENSG00000139890), RIT1 (ENSG00000143622), RALB (ENSG00000144118), RIT2 (ENSG00000152214), MRAS (ENSG00000158186), GEM (ENSG00000164949), DIRAS2 (ENSG00000165023), RRAD (ENSG00000166592), RHEBL1 (ENSG00000167550), NKIRAS2 (ENSG00000168256), HRAS (ENSG00000174775), DIRAS1 (ENSG00000176490), RAP2B (ENSG00000181467), ERAS (ENSG00000187682), NKIRAS1 (ENSG00000197885), NRAS (ENSG00000213281), RASL10B (ENSG00000270885)

Protein

Protein identifiers

GTP-binding protein Di-Ras3 — O95661 (reviewed: O95661)

Alternative names: Distinct subgroup of the Ras family member 3, Rho-related GTP-binding protein RhoI

All UniProt accessions (1): O95661

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Cell membrane.

Tissue specificity. Expressed in normal ovarian and breast epithelial cells but not in ovarian and breast cancers.

Similarity. Belongs to the small GTPase superfamily. Di-Ras family.

RefSeq proteins (1): NP_004666* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001806	Small_GTPase	Family
IPR005225	Small_GTP-bd	Domain
IPR020849	Small_GTPase_Ras-type	Family
IPR027417	P-loop_NTPase	Homologous_superfamily

Pfam: PF00071

UniProt features (11 total): binding site 5, chain 1, propeptide 1, helix 1, short sequence motif 1, modified residue 1, lipid moiety-binding region 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
6NAZ	X-RAY DIFFRACTION	3.08

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O95661-F1	73.19	0.43

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (5): 44–51; 63–69; 91–95; 152–155; 182–183

Post-translational modifications (2): 226, 226

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 87 (showing top): GOBP_REGULATION_OF_PHOSPHORYLATION, GOBP_REGULATION_OF_TRANSFERASE_ACTIVITY, MODULE_66, GOBP_GENOMIC_IMPRINTING, GOBP_CELLULAR_PROCESS_INVOLVED_IN_REPRODUCTION_IN_MULTICELLULAR_ORGANISM, GOBP_DEVELOPMENTAL_PROCESS_INVOLVED_IN_REPRODUCTION, PIEPOLI_LGI1_TARGETS_UP, GOBP_REGULATION_OF_PROTEIN_SERINE_THREONINE_KINASE_ACTIVITY, GOBP_CHROMATIN_REMODELING, GOBP_SMALL_GTPASE_MEDIATED_SIGNAL_TRANSDUCTION, ACEVEDO_METHYLATED_IN_LIVER_CANCER_DN, GOBP_EPIGENETIC_REGULATION_OF_GENE_EXPRESSION, GOBP_REGULATION_OF_PHOSPHORUS_METABOLIC_PROCESS, BLALOCK_ALZHEIMERS_DISEASE_DN, KAN_RESPONSE_TO_ARSENIC_TRIOXIDE

GO Biological Process (4): regulation of cyclin-dependent protein serine/threonine kinase activity (GO:0000079), small GTPase-mediated signal transduction (GO:0007264), genomic imprinting (GO:0071514), signal transduction (GO:0007165)

GO Molecular Function (5): GTPase activity (GO:0003924), GTP binding (GO:0005525), GDP binding (GO:0019003), nucleotide binding (GO:0000166), protein binding (GO:0005515)

GO Cellular Component (2): plasma membrane (GO:0005886), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
guanyl ribonucleotide binding	2
cyclin-dependent protein serine/threonine kinase activity	1
regulation of protein serine/threonine kinase activity	1
intracellular signaling cassette	1
germ cell development	1
epigenetic programming of gene expression	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
ribonucleoside triphosphate phosphatase activity	1
purine ribonucleoside triphosphate binding	1
anion binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
binding	1
membrane	1
cell periphery	1
cellular anatomical structure	1

Protein interactions and networks

STRING

2325 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DIRAS3	RASSF1	Q9NS23	612
DIRAS3	MEST	Q5EB52	603
DIRAS3	FAM50B	Q9Y247	571
DIRAS3	PLAGL1	Q9UM63	565
DIRAS3	PIK3C3	Q8NEB9	529
DIRAS3	STAT3	P40763	525
DIRAS3	PEG3	P78418	522
DIRAS3	NAP1L5	Q96NT1	513
DIRAS3	PIK3CB	P42338	508
DIRAS3	PEG10	Q86TG7	452
DIRAS3	SGCE	O43556	448
DIRAS3	NNAT	Q16517	441
DIRAS3	TG	P01266	437
DIRAS3	ZDBF2	Q9HCK1	428
DIRAS3	PIK3CA	P42336	423

IntAct

22 interactions, top by confidence:

A	B	Type	Score
DIRAS3	MEOX2	psi-mi:“MI:0915”(physical association)	0.560
DIRAS3	MTIF2	psi-mi:“MI:0914”(association)	0.530
DIRAS3	DCAF10	psi-mi:“MI:0914”(association)	0.530
DIRAS3	STAT3	psi-mi:“MI:0915”(physical association)	0.460
STAT3	DIRAS3	psi-mi:“MI:0403”(colocalization)	0.460
APC	DIRAS3	psi-mi:“MI:0915”(physical association)	0.370
BAG4	DIRAS3	psi-mi:“MI:0915”(physical association)	0.370
BRMS1	DIRAS3	psi-mi:“MI:0915”(physical association)	0.370
DIRAS3	CHEK2	psi-mi:“MI:0915”(physical association)	0.370
DIRAS3	FGFR4	psi-mi:“MI:0915”(physical association)	0.370
KRAS	DIRAS3	psi-mi:“MI:0915”(physical association)	0.370
PALB2	DIRAS3	psi-mi:“MI:0915”(physical association)	0.370
PPM1D	DIRAS3	psi-mi:“MI:0915”(physical association)	0.370
PTPN1	DIRAS3	psi-mi:“MI:0915”(physical association)	0.370
TGFB1	DIRAS3	psi-mi:“MI:0915”(physical association)	0.370
WT1	DIRAS3	psi-mi:“MI:0915”(physical association)	0.370
DIRAS3	CBX6	psi-mi:“MI:0914”(association)	0.350
DIRAS3	MEOX2	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (278): MTIF2 (Affinity Capture-MS), SLC30A1 (Affinity Capture-MS), RAP1GDS1 (Affinity Capture-MS), RNF19B (Affinity Capture-MS), HECTD1 (Affinity Capture-MS), MDM2 (Affinity Capture-MS), RHOA (Affinity Capture-MS), DCAF10 (Affinity Capture-MS), FEZ2 (Affinity Capture-MS), DIRAS3 (Synthetic Growth Defect), DIRAS3 (Two-hybrid), DIRAS3 (Two-hybrid), DIRAS3 (Two-hybrid), DIRAS3 (Two-hybrid), DIRAS3 (Two-hybrid)

ESM2 similar proteins: A2YEQ6, O35963, O74536, O95661, O95755, P25378, P35283, P35284, P51156, P52198, P97950, Q00246, Q02723, Q06AU4, Q08AT1, Q08E00, Q09178, Q14088, Q20365, Q29RR0, Q3SXC5, Q3UHC2, Q504M8, Q53S08, Q5H913, Q5JT25, Q5R615, Q5U1Y1, Q5ZHV1, Q62120, Q62689, Q64008, Q69XM7, Q6IQ22, Q75R65, Q7SZ59, Q7TN89, Q7Z444, Q8C0V7, Q8CAM5

Diamond homologs: A5A6J7, A6NIZ1, A8NU18, B3M185, B3NZR4, B4GFJ8, B4HKC7, B4JFU8, B4LY29, B4NJ72, B4PUP5, C4YKT4, G4MZY8, O42277, O42785, O95057, O95661, P01111, P01112, P01116, P01117, P01119, P03967, P05774, P08556, P08642, P08644, P08645, P08646, P0CY32, P10114, P10301, P12825, P13856, P15064, P18613, P20171, P22123, P22278, P22279

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 16 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.

GO biological processes:

GO term	Partners	Fold	FDR
negative regulation of cell population proliferation	6	15.8×	5e-04
positive regulation of gene expression	5	12.1×	4e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	20
Likely benign	4
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

381 predictions. Top by Δscore:

Variant	Effect	Δscore
1:68047360:CCC:C	acceptor_gain	1.0000
1:68047361:CCC:C	acceptor_gain	1.0000
1:68047361:CC:C	acceptor_gain	0.9900
1:68047362:CC:C	acceptor_gain	0.9900
1:68047363:C:CC	acceptor_gain	0.9900
1:68047363:CT:C	acceptor_loss	0.9900
1:68050543:CTTA:C	donor_loss	0.9900
1:68050544:TTA:T	donor_loss	0.9900
1:68050545:TA:T	donor_loss	0.9900
1:68050547:C:CG	donor_loss	0.9900
1:68051460:CGAGG:C	donor_gain	0.9900
1:68047359:ACCC:A	acceptor_gain	0.9800
1:68047360:CCCC:C	acceptor_gain	0.9800
1:68047363:C:T	acceptor_gain	0.9800
1:68049695:T:TA	donor_gain	0.9800
1:68050547:CCTTT:C	donor_gain	0.9800
1:68051468:T:A	donor_gain	0.9800
1:68051557:T:A	donor_gain	0.9800
1:68047358:GACCC:G	acceptor_gain	0.9700
1:68050546:A:AC	donor_gain	0.9700
1:68050547:C:CC	donor_gain	0.9700
1:68050004:C:CT	donor_gain	0.9600
1:68051385:T:TA	donor_gain	0.9600
1:68049990:TCC:T	donor_gain	0.9500
1:68051385:TC:T	donor_gain	0.9500
1:68051438:AG:A	donor_gain	0.9500
1:68050005:C:CT	donor_gain	0.9400
1:68050547:CCT:C	donor_gain	0.9400
1:68047272:T:TG	acceptor_gain	0.9300
1:68049767:G:A	donor_gain	0.9300

AlphaMissense

1507 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:68046962:G:C	F112L	0.985
1:68046962:G:T	F112L	0.985
1:68046964:A:G	F112L	0.985
1:68046767:G:C	F177L	0.974
1:68046767:G:T	F177L	0.974
1:68046769:A:G	F177L	0.974
1:68046949:A:G	S117P	0.969
1:68046960:A:T	V113D	0.965
1:68046840:T:A	K153I	0.964
1:68047148:T:A	K50N	0.958
1:68047148:T:G	K50N	0.958
1:68046884:T:A	K138N	0.956
1:68046884:T:G	K138N	0.956
1:68047149:T:A	K50I	0.956
1:68046967:C:G	A111P	0.953
1:68046722:G:C	F192L	0.952
1:68046722:G:T	F192L	0.952
1:68046724:A:G	F192L	0.952
1:68047152:C:A	G49V	0.949
1:68046849:A:T	V150E	0.944
1:68047179:A:T	V40D	0.943
1:68046781:A:G	W173R	0.942
1:68046781:A:T	W173R	0.942
1:68046839:T:A	K153N	0.942
1:68046839:T:G	K153N	0.942
1:68046952:A:C	Y116D	0.941
1:68046842:A:C	N152K	0.939
1:68046842:A:T	N152K	0.939
1:68046846:C:T	G151D	0.938
1:68047145:A:C	S51R	0.936

dbSNP variants (sampled 300 via entrez): RS1000528542 (1:68051750 C>T), RS1001024243 (1:68045946 A>C), RS1001432543 (1:68051611 G>A,T), RS1001883580 (1:68051856 G>A), RS1001962077 (1:68051373 TAAAC>T), RS1002328663 (1:68052324 A>G), RS1002783210 (1:68048616 T>C), RS1003439256 (1:68049098 A>G), RS1003485174 (1:68048241 G>T), RS1004842930 (1:68051284 T>C), RS1005132291 (1:68051598 C>A,T), RS1005229485 (1:68050229 ATTAC>A), RS1005305521 (1:68049037 C>T), RS1005727209 (1:68050206 C>T), RS1006743988 (1:68050521 C>T)

Disease associations

OMIM: gene MIM:605193 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression	5
sodium arsenite	increases expression, decreases expression	3
bisphenol A	increases expression	2
Benzo(a)pyrene	affects methylation, decreases expression, decreases methylation	2
Estradiol	affects expression, increases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Silicon Dioxide	decreases expression, increases expression	2
aristolochic acid I	decreases expression	1
methyleugenol	decreases expression	1
terbufos	increases methylation	1
trichostatin A	increases expression	1
arsenite	increases methylation	1
butyraldehyde	decreases expression	1
CGP 52608	affects binding, increases reaction	1
2-palmitoylglycerol	increases expression	1
entinostat	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
archazolid B	decreases expression	1
(+)-JQ1 compound	decreases expression	1
Temozolomide	decreases expression	1
Sunitinib	decreases expression	1
Arsenic Trioxide	decreases expression	1
Acetaminophen	decreases expression	1
Air Pollutants	affects methylation, increases abundance	1
Ethanol	increases expression	1
Fonofos	increases methylation	1
Nickel	decreases expression	1
Nitrogen Dioxide	affects methylation, increases abundance	1
Parathion	increases methylation	1

Clinical trials (associated diseases)

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