CASTOR1

Summary

CASTOR1 (cytosolic arginine sensor for mTORC1 subunit 1, HGNC:34423) is a protein-coding gene on chromosome 22q12.2, encoding Cytosolic arginine sensor for mTORC1 subunit 1 (Q8WTX7). Functions as an intracellular arginine sensor within the amino acid-sensing branch of the TORC1 signaling pathway.

Enables several functions, including arginine binding activity; identical protein binding activity; and protein sequestering activity. Involved in cellular response to L-arginine; cellular response to amino acid starvation; and regulation of TORC1 signaling. Located in GATOR2 complex and cytosol.

Source: NCBI Gene 652968 — RefSeq curated summary.

At a glance

• GWAS associations: 12
• Clinical variants (ClinVar): 57 total
• MANE Select transcript: NM_001037666

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:34423
Approved symbol	CASTOR1
Name	cytosolic arginine sensor for mTORC1 subunit 1
Location	22q12.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000239282
Ensembl biotype	protein_coding
OMIM	617034
Entrez	652968

Gene structure

Transcript identifiers

Ensembl transcripts: 19 — 7 protein_coding, 5 nonsense_mediated_decay, 4 retained_intron, 3 protein_coding_CDS_not_defined

ENST00000404953, ENST00000407689, ENST00000415484, ENST00000421236, ENST00000425691, ENST00000440704, ENST00000440839, ENST00000459785, ENST00000463795, ENST00000464854, ENST00000471480, ENST00000492159, ENST00000497605, ENST00000498572, ENST00000865127, ENST00000865128, ENST00000865129, ENST00000955196, ENST00000955197

RefSeq mRNA: 1 — MANE Select: NM_001037666 NM_001037666

CCDS: CCDS43001

Canonical transcript exons

ENST00000407689 — 9 exons

Exon	Start	End
ENSE00001323420	30285117	30285688
ENSE00003469025	30286016	30286098
ENSE00003492012	30288706	30288776
ENSE00003513398	30286263	30286376
ENSE00003641385	30287373	30287560
ENSE00003671727	30287155	30287287
ENSE00003686137	30286825	30286948
ENSE00003687398	30285832	30285926
ENSE00003899410	30289385	30289505

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 96.75.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 2.5292 / max 27.0833, expressed in 1303 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
193613	3.6797	1224
193614	1.9930	1151
193615	0.5361	311

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
lower esophagus mucosa	UBERON:0035834	96.75	gold quality
esophagus mucosa	UBERON:0002469	93.01	gold quality
vagina	UBERON:0000996	91.56	gold quality
esophagus	UBERON:0001043	89.36	gold quality
ectocervix	UBERON:0012249	89.14	gold quality
tibial nerve	UBERON:0001323	88.71	gold quality
right ovary	UBERON:0002118	88.37	gold quality
apex of heart	UBERON:0002098	88.00	gold quality
placenta	UBERON:0001987	87.48	gold quality
right lung	UBERON:0002167	87.24	gold quality
mucosa of stomach	UBERON:0001199	86.62	gold quality
right lobe of thyroid gland	UBERON:0001119	86.61	gold quality
uterine cervix	UBERON:0000002	86.53	gold quality
left lobe of thyroid gland	UBERON:0001120	86.49	gold quality
right testis	UBERON:0004534	85.84	gold quality
thyroid gland	UBERON:0002046	85.71	gold quality
left ovary	UBERON:0002119	85.71	gold quality
temporal lobe	UBERON:0001871	85.65	gold quality
amygdala	UBERON:0001876	85.58	gold quality
prostate gland	UBERON:0002367	85.52	gold quality
lower esophagus	UBERON:0013473	85.41	gold quality
ovary	UBERON:0000992	85.39	gold quality
lower esophagus muscularis layer	UBERON:0035833	85.38	gold quality
putamen	UBERON:0001874	85.33	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	85.14	gold quality
endocervix	UBERON:0000458	84.91	gold quality
left testis	UBERON:0004533	84.88	gold quality
left uterine tube	UBERON:0001303	84.74	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	84.71	gold quality
testis	UBERON:0000473	84.61	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

22 targeting CASTOR1, 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-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-6079	99.84	68.54	1170
HSA-MIR-1827	99.63	68.57	3265
HSA-MIR-671-5P	99.52	67.11	1277
HSA-MIR-1207-5P	99.49	69.11	2983
HSA-MIR-4441	99.49	66.56	3216
HSA-MIR-21-5P	99.46	70.54	1035
HSA-MIR-6882-5P	99.35	71.13	1206
HSA-MIR-520A-5P	99.35	66.72	1632
HSA-MIR-525-5P	99.35	66.85	1615
HSA-MIR-4763-3P	99.10	67.83	2649
HSA-MIR-4477A	98.83	69.75	2952
HSA-MIR-6846-5P	98.81	65.86	1121
HSA-MIR-6848-5P	98.81	65.49	1126
HSA-MIR-224-5P	98.33	70.12	1256
HSA-MIR-211-3P	98.14	66.77	1052
HSA-MIR-6801-3P	98.04	64.64	805
HSA-MIR-6810-3P	97.96	64.57	1023
HSA-MIR-27B-5P	97.34	66.55	549

Literature-anchored findings (GeneRIF, showing 8)

• This genome wide association study identified a new rheumatoid arthritis susceptibility locus mapping to 22q12 in the GATSL3 gene. (PMID:24449572)
• Study establishes the CASTOR1 homodimer and CASTOR1-CASTOR2 heterodimer as arginine sensors for the mTORC1 pathway. (PMID:26972053)
• 1.8 A crystal structure of arginine-bound CASTOR1 (PMID:27487210)
• these findings demonstrated that CASTOR1 inhibits the tumorigenesis of lung adenocarcinoma cells and might serve as a potential therapeutic target or prognostic marker for human patients with lung adenocarcinoma. (PMID:30132978)
• Report crystal structures of arginine sensor CASTOR1 in arginine-bound and ligand free states at 2.05A and 2.8A, respectively. Structural comparison of CASTOR1 between two states reveals near identical conformations, except in two loop regions. It indicates CASTOR1 does not undergo large conformational change during arginine binding. (PMID:30503338)
• the KSHV-encoded miRNA miR-K4-5p, and probably miR-K1-5p, directly targeted CASTOR1 to inhibit its expression. Knockdown of miR-K1-5p and -K4-5p restored CASTOR1 expression and thereby attenuated mTORC1 activation. (PMID:31305263)
• The binding free energy calculations revealed that Nalpha-acetyl-arginine, citrulline, and norarginine have sufficient binding affinity with CASTOR1 to compete with arginine. The hydrogen bond analysis revealed that norarginine, Nalpha-acetyl-arginine and D-arginine have proficient H-bonds that can facilitate their entering the narrow binding pocket. (PMID:31659101)
• RNF167 activates mTORC1 and promotes tumorigenesis by targeting CASTOR1 for ubiquitination and degradation. (PMID:33594058)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Castor1	ENSMUSG00000020424
rattus_norvegicus	Castor1	ENSRNOG00000006740

Paralogs (1): CASTOR2 (ENSG00000274070)

Protein

Protein identifiers

Cytosolic arginine sensor for mTORC1 subunit 1 — Q8WTX7 (reviewed: Q8WTX7)

Alternative names: Cellular arginine sensor for mTORC1 protein 1, GATS-like protein 3

All UniProt accessions (6): Q8WTX7, B7WPJ3, F2Z2C1, F2Z3I9, F8WD52, H7C2U7

UniProt curated annotations — full annotation on UniProt →

Function. Functions as an intracellular arginine sensor within the amino acid-sensing branch of the TORC1 signaling pathway. As a homodimer or a heterodimer with CASTOR2, binds and inhibits the GATOR subcomplex GATOR2 and thereby mTORC1. Binding of arginine to CASTOR1 allosterically disrupts the interaction of CASTOR1-containing dimers with GATOR2 which can in turn activate mTORC1 and the TORC1 signaling pathway.

Subunit / interactions. Forms homodimers and heterodimers with CASTOR2. Interacts with the GATOR2 complex which is composed of MIOS, SEC13, SEH1L, WDR24 and WDR59; the interaction is negatively regulated by arginine. Interacts with TM4SF5; the interaction is positively regulated by leucine and is negatively regulated by arginine.

Subcellular location. Cytoplasm. Cytosol.

Tissue specificity. Widely expressed.

Post-translational modifications. Phosphorylation at Ser-14 by AKT1, promoting the interaction between CASTOR1 and RNF167. Ubiquitinated by RNF167 via ‘Lys-29’-polyubiquitination, leading to its degradation, releasing the GATOR2 complex. Ubiquitination by RNF167 is promoted by phosphorylation at Ser-14 by AKT1.

Domain organisation. Based on x-ray crystallography data, the protein would be constituted of 4 tandem ACT domains instead of the 2 predicted from the sequence.

Similarity. Belongs to the GATS family.

RefSeq proteins (1): NP_001032755* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR026249	CASTOR_fam	Family
IPR027795	CASTOR_ACT_dom	Domain
IPR040778	CASTOR1_N	Domain
IPR045865	ACT-like_dom_sf	Homologous_superfamily
IPR049479	CASTOR1_ACT-like	Domain
IPR051719	CASTOR_mTORC1	Family

Pfam: PF13840, PF18700, PF21389

UniProt features (73 total): mutagenesis site 26, strand 17, helix 16, turn 5, binding site 4, domain 2, chain 1, sequence conflict 1, modified residue 1

Structure

Experimental structures (PDB)

10 structures.

PDB	Method	Resolution (Å)
5I2C	X-RAY DIFFRACTION	1.8
5GT7	X-RAY DIFFRACTION	2.05
5GV2	X-RAY DIFFRACTION	2.06
5GS9	X-RAY DIFFRACTION	2.5
5GT8	X-RAY DIFFRACTION	2.8
9KP4	X-RAY DIFFRACTION	3.08
9DX2	ELECTRON MICROSCOPY	3.4
9LWF	ELECTRON MICROSCOPY	3.41
9OTI	ELECTRON MICROSCOPY	3.5
9LVK	ELECTRON MICROSCOPY	3.59

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8WTX7-F1	88.84	0.77

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 (4): 111–112; 274; 280–281; 300–304

Post-translational modifications (1): 14

Mutagenesis-validated functional residues (26):

Position	Phenotype
61	in 3kr mutant; abolished ubiquitination by rnf167; when associated with r-96 and r-213.
90	no effect on interaction with the gator2 complex.
96	no effect on interaction with the gator2 complex.
96	in 3kr mutant; abolished ubiquitination by rnf167; when associated with r-61 and r-213.
99	no effect on interaction with the gator2 complex.
108–110	loss of arginine-binding. constitutively interacts with the gator2 complex.
111	loss of arginine-binding. constitutively interacts with the gator2 complex. constitutively inhibits the torc1 signaling
113	no effect on interaction with the gator2 complex.
118–119	no effect on arginine-binding. no effect on homodimerization. loss of interaction with the gator2 complex which constitu
121	no effect on arginine-binding. no effect on homodimerization. loss of interaction with the gator2 complex which constitu
126	decreased arginine-binding. constitutively interacts with the gator2 complex.
175	decreased arginine-binding. constitutively interacts with the gator2 complex.
202	no effect on arginine-binding. loss of homodimerization. decreased interaction with the gator2 complex which constitutiv
207	no effect on arginine-binding. loss of homodimerization. decreased interaction with the gator2 complex which constitutiv
213	in 3kr mutant; abolished ubiquitination by rnf167; when associated with r-61 and r-96.
261	no effect on arginine-binding. no effect on homodimerization. loss of interaction with the gator2 complex.
264	no effect on interaction with the gator2 complex.
276	decreased arginine-binding. constitutively interacts with the gator2 complex.
277	decreased arginine-binding. constitutively interacts with the gator2 complex.
278	decreased arginine-binding. constitutively interacts with the gator2 complex.
280	loss of arginine-binding. constitutively inhibits the torc1 signaling pathway.
292	no effect on arginine-binding. no effect on homodimerization. loss of interaction with the gator2 complex.
302	no effect on interaction with the gator2 complex.
304	loss of arginine-binding. constitutively interacts with the gator2 complex. constitutively inhibits the torc1 signaling
14	abolished phosphorylation by akt1, leading to decreased interaction with rnf167 and subsequent ubiquitination.

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-9639288	Amino acids regulate mTORC1
R-HSA-2262752	Cellular responses to stress
R-HSA-8953897	Cellular responses to stimuli
R-HSA-9711097	Cellular response to starvation

MSigDB gene sets: 90 (showing top): GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_RESPONSE_TO_ACID_CHEMICAL, GOBP_POSITIVE_REGULATION_OF_TOR_SIGNALING, GOBP_CELLULAR_RESPONSE_TO_ACID_CHEMICAL, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, GOBP_NEGATIVE_REGULATION_OF_INTRACELLULAR_SIGNAL_TRANSDUCTION, GOBP_NEGATIVE_REGULATION_OF_TOR_SIGNALING, GOBP_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, GOBP_CELLULAR_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_POSITIVE_REGULATION_OF_INTRACELLULAR_SIGNAL_TRANSDUCTION, GOBP_CELLULAR_RESPONSE_TO_STARVATION, GOBP_TOR_SIGNALING, GOBP_RESPONSE_TO_STARVATION, GOMF_AMINO_ACID_BINDING, GOMF_ORGANIC_ACID_BINDING

GO Biological Process (6): cellular response to amino acid starvation (GO:0034198), cellular response to L-arginine (GO:1903577), negative regulation of TORC1 signaling (GO:1904262), positive regulation of TORC1 signaling (GO:1904263), cellular response to nutrient levels (GO:0031669), protein K6-linked ubiquitination (GO:0085020)

GO Molecular Function (5): arginine binding (GO:0034618), identical protein binding (GO:0042802), molecular sensor activity (GO:0140299), protein sequestering activity (GO:0140311), protein binding (GO:0005515)

GO Cellular Component (3): cytosol (GO:0005829), cytoplasm (GO:0005737), GATOR2 complex (GO:0061700)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Cellular response to starvation	1
Cellular responses to stimuli	1
Cellular responses to stress	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
TORC1 signaling	2
regulation of TORC1 signaling	2
protein binding	2
cellular anatomical structure	2
cellular response to starvation	1
response to amino acid starvation	1
cellular response to amino acid stimulus	1
cellular response to nitrogen compound	1
cellular response to oxygen-containing compound	1
response to L-arginine	1
negative regulation of TOR signaling	1
positive regulation of TOR signaling	1
response to nutrient levels	1
cellular response to stimulus	1
protein polyubiquitination	1
amino acid binding	1
carboxylic acid binding	1
cation binding	1
molecular function regulator activity	1
molecular sequestering activity	1
binding	1
cytoplasm	1
intracellular anatomical structure	1
protein-containing complex	1
Seh1-associated complex	1

Protein interactions and networks

STRING

454 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CASTOR1	SLC38A9	Q8NBW4	876
CASTOR1	SAMTOR	Q1RMZ1	764
CASTOR1	SESN2	P58004	723
CASTOR1	SEH1L	Q96EE3	719
CASTOR1	RRAGC	Q9HB90	669
CASTOR1	RRAGA	Q7L523	663
CASTOR1	MIOS	Q9NXC5	640
CASTOR1	WDR59	Q6PJI9	626
CASTOR1	RRAGB	Q5VZM2	609
CASTOR1	EFNA5	P52803	605
CASTOR1	WDR24	Q96S15	602
CASTOR1	SESN1	Q9Y6P5	588
CASTOR1	RRAGD	Q9NQL2	582
CASTOR1	RHEB	Q15382	581
CASTOR1	NPRL2	Q8WTW4	572

IntAct

57 interactions, top by confidence:

A	B	Type	Score
ZC2HC1A	CASTOR1	psi-mi:“MI:0915”(physical association)	0.830
CASTOR1	ZC2HC1A	psi-mi:“MI:0915”(physical association)	0.830
IFIT2	IFIT3	psi-mi:“MI:0914”(association)	0.780
CASTOR1	CASTOR1	psi-mi:“MI:0915”(physical association)	0.770
CASTOR1	CASTOR1	psi-mi:“MI:0914”(association)	0.770
CASTOR1	CASTOR2	psi-mi:“MI:0914”(association)	0.710
CASTOR1	MIOS	psi-mi:“MI:0915”(physical association)	0.710
CASTOR1	CASTOR2	psi-mi:“MI:0915”(physical association)	0.710
CASTOR2	CASTOR1	psi-mi:“MI:0915”(physical association)	0.710
CASTOR1	WDR59	psi-mi:“MI:0915”(physical association)	0.710
WDR24	CASTOR1	psi-mi:“MI:0914”(association)	0.690
	CASTOR1	psi-mi:“MI:0407”(direct interaction)	0.680

BioGRID (45): GATSL3 (Two-hybrid), GATSL3 (Two-hybrid), GATSL2 (Affinity Capture-MS), MIOS (Affinity Capture-MS), WDR24 (Affinity Capture-MS), ZC2HC1A (Affinity Capture-MS), WDR59 (Affinity Capture-MS), GATSL3 (Affinity Capture-Western), GATSL3 (Affinity Capture-Western), MIOS (Affinity Capture-Western), GATSL3 (Affinity Capture-Western), GATSL2 (Affinity Capture-Western), GATSL3 (Affinity Capture-Western), GATSL2 (Reconstituted Complex), GATSL3 (Reconstituted Complex)

ESM2 similar proteins: A0A0C2S258, A0A0C2WKN7, A0A0D1DNX1, A0A0U5GNT1, A0A1C8AX29, A0A1D5AG16, A0A1L9WLI9, A0A1U8QK63, A0A1U9YHZ6, A0A2I1C3U2, A0A2I1D2M7, A0A2L0VXR0, A0A2V5GUR2, A0A397HQN2, A0A3S7WQS5, A0A6S6QR11, A8PRN6, B6JWC1, B7STY2, I1RV23, I1S489, M2XHU6, O13284, P0CI62, P38675, P39058, P9WEK5, P9WEU7, Q00681, Q00706, Q0CCX5, Q0V8A3, Q2HFL8, Q2TXG3, Q3AUM0, Q4WD44, Q4WD45, Q4WMJ9, Q5AV00, Q5AV07

Diamond homologs: A6NHX0, Q0V8A3, Q5BJZ0, Q5R9D1, Q63ZZ8, Q6DDW7, Q8CAB8, Q8NAP1, Q8WTX7, Q9CWQ8

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
CASTOR1	“form complex”	“CASTOR1-CASTOR2 arginine binding complex”	binding
CASTOR1	“form complex”	“CASTOR1-GATOR2 arginine binding complex”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 14 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
Amino acids regulate mTORC1	5	100.2×	5e-08

GO biological processes:

GO term	Partners	Fold	FDR
negative regulation of TORC1 signaling	5	135.0×	1e-08

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	44
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1452 predictions. Top by Δscore:

Variant	Effect	Δscore
22:30285827:CTCA:C	donor_loss	1.0000
22:30285829:CA:C	donor_loss	1.0000
22:30285830:A:AC	donor_gain	1.0000
22:30285830:ACCAG:A	donor_loss	1.0000
22:30285831:C:CT	donor_gain	1.0000
22:30285924:CAT:C	acceptor_gain	1.0000
22:30285927:C:CC	acceptor_gain	1.0000
22:30285933:G:C	acceptor_gain	1.0000
22:30285933:G:GC	acceptor_gain	1.0000
22:30286099:C:CA	acceptor_loss	1.0000
22:30286099:C:CC	acceptor_gain	1.0000
22:30286261:A:AC	donor_gain	1.0000
22:30286262:C:CC	donor_gain	1.0000
22:30287149:CCTCA:C	donor_loss	1.0000
22:30287150:CTCAC:C	donor_loss	1.0000
22:30287151:TCA:T	donor_loss	1.0000
22:30287152:CA:C	donor_loss	1.0000
22:30287154:CCATG:C	donor_gain	1.0000
22:30287191:C:A	donor_gain	1.0000
22:30287294:C:CT	acceptor_gain	1.0000
22:30287369:TCACC:T	donor_loss	1.0000
22:30287370:CACCA:C	donor_loss	1.0000
22:30287371:A:AC	donor_gain	1.0000
22:30287371:AC:A	donor_gain	1.0000
22:30287372:C:CA	donor_gain	1.0000
22:30287372:C:T	donor_loss	1.0000
22:30287372:CC:C	donor_gain	1.0000
22:30287372:CCAGG:C	donor_gain	1.0000
22:30287556:CAGCT:C	acceptor_gain	1.0000
22:30287557:AGCT:A	acceptor_gain	1.0000

AlphaMissense

2141 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
22:30285856:G:C	S299R	1.000
22:30285856:G:T	S299R	1.000
22:30285858:T:G	S299R	1.000
22:30285833:A:G	L307P	0.999
22:30285850:G:C	F301L	0.999
22:30285850:G:T	F301L	0.999
22:30285852:A:G	F301L	0.999
22:30285857:C:A	S299I	0.999
22:30286017:A:C	F275L	0.999
22:30286017:A:T	F275L	0.999
22:30286019:A:G	F275L	0.999
22:30286055:A:G	W263R	0.999
22:30286055:A:T	W263R	0.999
22:30286287:A:T	V240D	0.999
22:30287374:A:G	L124P	0.999
22:30287443:A:T	V101D	0.999
22:30287519:A:G	W76R	0.999
22:30287519:A:T	W76R	0.999
22:30288761:G:C	S43R	0.999
22:30288761:G:T	S43R	0.999
22:30288763:T:G	S43R	0.999
22:30285836:G:T	A306D	0.998
22:30285842:T:A	D304V	0.998
22:30285854:G:A	T300I	0.998
22:30285867:A:C	Y296D	0.998
22:30286018:A:C	F275C	0.998
22:30286018:A:G	F275S	0.998
22:30286293:G:A	S238F	0.998
22:30286293:G:T	S238Y	0.998
22:30286294:A:G	S238P	0.998

dbSNP variants (sampled 300 via entrez): RS1000389680 (22:30287670 G>A,T), RS1000404870 (22:30286064 C>T), RS1000404940 (22:30287955 G>A), RS1001116980 (22:30290587 T>A), RS1002474096 (22:30287610 C>A), RS1003141495 (22:30290435 C>G), RS1003738696 (22:30289208 G>A), RS1004280178 (22:30291329 A>G), RS1004315699 (22:30288936 C>A), RS1005201958 (22:30285399 C>T), RS1005254006 (22:30290060 G>A), RS1005314615 (22:30289610 G>A), RS1006039038 (22:30289883 T>C), RS1006825804 (22:30289394 C>T), RS1007708977 (22:30291399 G>A)

Disease associations

OMIM: gene MIM:617034 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

12 associations (top):

Study	Trait	p-value
GCST002323_8	Rheumatoid arthritis	7.000000e-09
GCST005194_253	Coronary artery disease	1.000000e-07
GCST005851_15	Delirium	1.000000e-06
GCST010866_174	Coronary artery disease	4.000000e-10
GCST011365_115	Myocardial infarction	8.000000e-07
GCST012228_566	Waist-hip index	3.000000e-08
GCST012228_567	Waist-hip index	2.000000e-08
GCST012230_206	Waist-to-hip ratio adjusted for BMI	3.000000e-08
GCST90020024_821	A body shape index	9.000000e-09
GCST90020025_1783	Waist-to-hip ratio adjusted for BMI	2.000000e-08
GCST90020027_402	Waist-hip index	2.000000e-08
GCST90020029_170	Waist circumference adjusted for body mass index	5.000000e-09

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0007789	BMI-adjusted waist circumference

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

19 total (human), top 19 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Arsenic	affects methylation, decreases expression, increases abundance	2
Cisplatin	affects expression, affects cotreatment, increases expression	2
Estradiol	decreases reaction, increases expression, affects cotreatment, decreases expression	2
Particulate Matter	decreases expression, increases abundance, increases expression	2
pirinixic acid	decreases expression, increases activity, affects binding	1
sodium arsenate	decreases expression, increases abundance	1
trichostatin A	affects expression	1
jinfukang	affects cotreatment, increases expression	1
Decitabine	affects expression	1
Sunitinib	decreases expression	1
Zoledronic Acid	increases expression	1
Air Pollutants	decreases expression, increases abundance	1
Calcitriol	affects cotreatment, increases expression	1
Testosterone	affects cotreatment, increases expression	1
Tobacco Smoke Pollution	decreases expression	1
Valproic Acid	affects expression	1
Okadaic Acid	decreases expression	1
Lactic Acid	decreases expression	1
S-Nitrosoglutathione	decreases expression	1

Clinical trials (associated diseases)

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