HOXC10

Summary

HOXC10 (homeobox C10, HGNC:5122) is a protein-coding gene on chromosome 12q13.13, encoding Homeobox protein Hox-C10 (Q9NYD6). Sequence-specific transcription factor which is part of a developmental regulatory system that provides cells with specific positional identities on the anterior-posterior axis. It is a selective cancer dependency (DepMap: 11.9% of cell lines).

This gene belongs to the homeobox family of genes. The homeobox genes encode a highly conserved family of transcription factors that play an important role in morphogenesis in all multicellular organisms. Mammals possess four similar homeobox gene clusters, HOXA, HOXB, HOXC and HOXD, which are located on different chromosomes and consist of 9 to 11 genes arranged in tandem. This gene is one of several homeobox HOXC genes located in a cluster on chromosome 12. The protein level is controlled during cell differentiation and proliferation, which may indicate this protein has a role in origin activation.

Source: NCBI Gene 3226 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 35 total
• Cancer dependency (DepMap): dependent in 11.9% of screened cell lines
• MANE Select transcript: NM_017409

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:5122
Approved symbol	HOXC10
Name	homeobox C10
Location	12q13.13
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000180818
Ensembl biotype	protein_coding
OMIM	605560
Entrez	3226

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 3 protein_coding_CDS_not_defined, 2 protein_coding

ENST00000303460, ENST00000511575, ENST00000513413, ENST00000514415, ENST00000515593

RefSeq mRNA: 1 — MANE Select: NM_017409 NM_017409

CCDS: CCDS8868

Canonical transcript exons

ENST00000303460 — 2 exons

Exon	Start	End
ENSE00001151643	53989169	53990279
ENSE00001151648	53985146	53986010

Expression profiles

Bgee: expression breadth ubiquitous, 166 present calls, max score 96.48.

FANTOM5 (CAGE): breadth broad, TPM avg 6.4444 / max 408.3216, expressed in 609 samples.

FANTOM5 promoters (11 alternative TSS)

Promoter ID	TPM avg	Samples expressed
125830	1.7339	455
125833	1.4650	290
125842	1.2844	379
125840	0.6757	289
125841	0.2729	152
125831	0.2708	158
125829	0.2690	178
125835	0.2082	112
125839	0.1596	65
125834	0.0593	20

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
gastrocnemius	UBERON:0001388	96.48	gold quality
muscle of leg	UBERON:0001383	95.85	gold quality
buccal mucosa cell	CL:0002336	93.66	gold quality
metanephros cortex	UBERON:0010533	92.96	gold quality
renal medulla	UBERON:0000362	92.66	gold quality
popliteal artery	UBERON:0002250	92.46	gold quality
tibial artery	UBERON:0007610	92.43	gold quality
tibialis anterior	UBERON:0001385	92.32	gold quality
muscle organ	UBERON:0001630	91.96	gold quality
adult mammalian kidney	UBERON:0000082	91.55	gold quality
quadriceps femoris	UBERON:0001377	91.54	gold quality
vastus lateralis	UBERON:0001379	91.23	gold quality
calcaneal tendon	UBERON:0003701	89.31	gold quality
skin of leg	UBERON:0001511	88.62	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	87.35	gold quality
kidney	UBERON:0002113	87.27	gold quality
skin of abdomen	UBERON:0001416	86.71	gold quality
saphenous vein	UBERON:0007318	85.96	gold quality
zone of skin	UBERON:0000014	85.89	gold quality
subcutaneous adipose tissue	UBERON:0002190	85.58	gold quality
cortex of kidney	UBERON:0001225	84.61	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	83.51	gold quality
synovial joint	UBERON:0002217	82.78	gold quality
tendon	UBERON:0000043	82.21	gold quality
layer of synovial tissue	UBERON:0007616	81.40	gold quality
metanephros	UBERON:0000081	78.79	gold quality
skin of hip	UBERON:0001554	78.13	gold quality
triceps brachii	UBERON:0001509	77.31	gold quality
cartilage tissue	UBERON:0002418	76.85	gold quality
kidney epithelium	UBERON:0004819	76.52	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-GEOD-75367	yes	49.30
E-HCAD-10	yes	42.62
E-ANND-3	yes	4.25
E-MTAB-10290	no	92.02

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

2 targets.

Target	Regulation
HOXB8	Repression
LAMB2	Activation

JASPAR motifs

Motif	Name	Family
MA0905.1	HOXC10	HOX
MA0905.2	HOXC10	HOX

JASPAR matrix evidence (PMIDs): PMID:18585359

Upstream regulators (CollecTRI, top): ESR1, ESR2, KMT2A, KMT2B, PITX1

miRNA regulators (miRDB)

135 targeting HOXC10, 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-4533	100.00	69.48	2758
HSA-MIR-12118	100.00	65.88	1270
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-4673	100.00	66.64	1490
HSA-MIR-33A-5P	99.99	68.62	1055
HSA-MIR-33B-5P	99.99	68.58	1062
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-6891-5P	99.98	66.53	1372
HSA-MIR-3173-3P	99.98	66.49	1217
HSA-MIR-4645-5P	99.98	65.81	1284
HSA-MIR-103A-3P	99.98	69.14	1595
HSA-MIR-107	99.98	69.14	1595
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-6888-3P	99.97	65.95	1170
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-3605-5P	99.96	67.12	932
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-515-5P	99.92	69.82	2343
HSA-MIR-519E-5P	99.92	69.62	2358
HSA-MIR-329-3P	99.91	66.56	1234
HSA-MIR-362-3P	99.91	66.38	1267
HSA-MIR-3529-3P	99.90	73.55	3045
HSA-MIR-7162-3P	99.89	68.16	1682
HSA-MIR-129-5P	99.88	70.26	3273
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-MIR-12119	99.87	68.35	1653
HSA-MIR-221-3P	99.86	71.56	1329

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 11.9% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 34)

• Early mitotic dedgradation of the homeoprotein HOXC10 is potentially linked to cell cycle progression. (PMID:12853486)
• Cervical cancer cells with high endogenous levels of HOXC10 were less invasive after short hairpin RNA-mediated knockdown of HOXC10 expression; findings support a key role for the HOXC10 homeobox protein in cervical cancer progression (PMID:17974957)
• Data demonstrate that HOXC10 is a gene that may discriminate between amnion-derived mesenchymal stem cells (MSCs) and decidua-derived MSCs. (PMID:19522674)
• Reduced HOXC10 in vitro and in xenografts resulted in decreased apoptosis and caused antiestrogen resistance. (PMID:24670685)
• This study investigates the role and clinical implication of HOXC10 in human thyroid cancer. (PMID:26279264)
• HOXC9 and HOXC10 may play an important role in the development of obesity, adverse fat distribution, and subsequent alterations in whole-body metabolism and adipose tissue function. (PMID:26647900)
• These results indicated that HOXC10 might be a diagnostic marker for osteosarcoma and could be a potential molecular target for the therapy of osteosarcoma (PMID:28474998)
• that HOXC10 decreased the MSC osteogenic differentiation potential (PMID:28605223)
• Furthermore, our results showed that ectopic expression of HOXC10 could reverse inhibition of metastasis by overexpressed miR-136 in GC-9811P cells. Our findings provide new insights into the role of miR-136 in the gastric cancer-specific peritoneal metastasis and implicate the potential application of miR-136 in gastric cancer peritoneal metastasis therapy. (PMID:28656883)
• HOXC10 directly binds to the PD-L2 and TDO2 promoter regions thus stimulating proliferation, invasion and induction of immunosuppressive gene expression in glioma. (PMID:29676849)
• HOXC10 may promote invasion and migration of gastric cancer cells by regulating ATM/NF-kappaB signaling pathway. (PMID:29753747)
• Overexpression of HOXC10 promotes glioblastoma cell progression to a poor prognosis via the PI3K/AKT signalling pathway (PMID:29768063)
• Our study revealed a new mechanism mediated by CHD7 for its role in promoting HOXC10 expression and contribute to mammary oncogenesis. (PMID:30343692)
• Data showed that lncHOXC-AS3 was required for osteogenesis in BM-MSCs by enhancing HOXC10 expression. (PMID:30353595)
• Protein arginine methyltransferase 5 (PRMT5) and WD repeat domain 5 (WDR5), both of which regulate histone post-translational modifications, were required for HOXC10-mediated VEGFA upregulation. Importantly, a significant correlation between HOXC10 levels and VEGFA expression was observed in a cohort of human gliomas. (PMID:30429891)
• High HOXC10 expression is associated with Recurrence in Gastric Cancer. (PMID:30673899)
• HOXC10 expression is upregulated in gastric cancer through DNA demethylation, and HOXC10 overexpression increases proliferation and migration of gastric cancer cells. (PMID:31115563)
• HOXC10 promotes cell migration, invasion, and tumor growth in gastric carcinoma cells through upregulating proinflammatory cytokines. (PMID:31552684)
• MircoRNA-129-5p suppresses the development of glioma by targeting HOXC10. (PMID:32111444)
• Interleukin 1beta-mediated HOXC10 Overexpression Promotes Hepatocellular Carcinoma Metastasis by Upregulating PDPK1 and VASP. (PMID:32206125)
• A Deregulated HOX Gene Axis Confers an Epigenetic Vulnerability in KRAS-Mutant Lung Cancers. (PMID:32243838)
• MiR-129-5p induces cell cycle arrest through modulating HOXC10/Cyclin D1 to inhibit gastric cancer progression. (PMID:32356314)
• MiR-129-5p Restrains Apatinib Resistance in Human Gastric Cancer Cells Via Downregulating HOXC10. (PMID:32552008)
• HOXC10 upregulation confers resistance to chemoradiotherapy in ESCC tumor cells and predicts poor prognosis. (PMID:32587398)
• The lncRNA HMS recruits RNA-binding protein HuR to stabilize the 3’-UTR of HOXC10 mRNA. (PMID:34302808)
• Identification of cis-HOX-HOXC10 axis as a therapeutic target for colorectal tumor-initiating cells without APC mutations. (PMID:34320348)
• Transcription factor HOXC10 activates the expression of MTFR2 to regulate the proliferation, invasion and migration of colorectal cancer cells. (PMID:34523692)
• HOXC6/8/10/13 predict poor prognosis and associate with immune infiltrations in glioblastoma. (PMID:34763232)
• [The effect of HOXC10 gene on biological behaviors of glioma cells and mechanism in tumor microenvironment]. (PMID:35316872)
• HOXC10 indicates poor survival outcome in gastric cancer and promotes G1/S cell cycle transition through transcriptional repression of p21. (PMID:36264773)
• m[6]A-modified HOXC10 promotes HNSCC progression via co-activation of ADAM17/EGFR and Wnt/beta-catenin signaling. (PMID:38063205)
• Pan-cancer analysis of homeodomain-containing gene C10 and its carcinogenesis in lung adenocarcinoma. (PMID:38154103)
• HOXC10 promotes hypertrophic scar fibroblast fibrosis through the regulation of STMN2 and the TGF-beta/Smad signaling pathway. (PMID:39152325)
• The HOXC10/NOD1/ERK axis drives osteolytic bone metastasis of pan-KRAS-mutant lung cancer. (PMID:39191757)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	hoxc10a	ENSDARG00000070348
mus_musculus	Hoxc10	ENSMUSG00000022484
rattus_norvegicus	Hoxc10	ENSRNOG00000016149

Paralogs (42): HOXA11 (ENSG00000005073), HOXC8 (ENSG00000037965), HOXA1 (ENSG00000105991), HOXA2 (ENSG00000105996), HOXA3 (ENSG00000105997), HOXA5 (ENSG00000106004), HOXA6 (ENSG00000106006), HOXA13 (ENSG00000106031), TLX1 (ENSG00000107807), HOXB6 (ENSG00000108511), TLX2 (ENSG00000115297), HOXB8 (ENSG00000120068), HOXB5 (ENSG00000120075), HOXB3 (ENSG00000120093), HOXB1 (ENSG00000120094), HOXA7 (ENSG00000122592), HOXC13 (ENSG00000123364), HOXC11 (ENSG00000123388), HOXC12 (ENSG00000123407), HOXD1 (ENSG00000128645), HOXD3 (ENSG00000128652), HOXD9 (ENSG00000128709), HOXD10 (ENSG00000128710), HOXD11 (ENSG00000128713), HOXD13 (ENSG00000128714), PDX1 (ENSG00000139515), HOXB13 (ENSG00000159184), TLX3 (ENSG00000164438), HOXD4 (ENSG00000170166), HOXD12 (ENSG00000170178), HOXB9 (ENSG00000170689), HOXC5 (ENSG00000172789), HOXB2 (ENSG00000173917), HOXD8 (ENSG00000175879), GSX2 (ENSG00000180613), HOXC9 (ENSG00000180806), HOXB4 (ENSG00000182742), HOXA4 (ENSG00000197576), HOXC6 (ENSG00000197757), HOXC4 (ENSG00000198353)

Protein

Protein identifiers

Homeobox protein Hox-C10 — Q9NYD6 (reviewed: Q9NYD6)

Alternative names: Homeobox protein Hox-3I

All UniProt accessions (3): Q9NYD6, D6RAG4, Q53XI4

UniProt curated annotations — full annotation on UniProt →

Function. Sequence-specific transcription factor which is part of a developmental regulatory system that provides cells with specific positional identities on the anterior-posterior axis.

Subcellular location. Nucleus.

Similarity. Belongs to the Abd-B homeobox family.

RefSeq proteins (1): NP_059105* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001356	HD	Domain
IPR009057	Homeodomain-like_sf	Homologous_superfamily
IPR017970	Homeobox_CS	Conserved_site
IPR020479	HD_metazoa	Domain
IPR046333	HXA10/ABDB-like	Family

Pfam: PF00046

UniProt features (14 total): cross-link 3, sequence conflict 3, region of interest 2, compositionally biased region 2, modified residue 2, chain 1, DNA-binding region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NYD6-F1	61.04	0.21

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 (5): 254, 8, 189, 106, 195

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 187 (showing top): ATF_B, GOBP_SPINAL_CORD_DEVELOPMENT, RNGTGGGC_UNKNOWN, E2F_Q4, E2F_Q4_01, E2F4DP1_01, GOBP_SKELETAL_SYSTEM_DEVELOPMENT, XU_GH1_AUTOCRINE_TARGETS_UP, LFA1_Q6, GOZGIT_ESR1_TARGETS_DN, GOBP_NEUROGENESIS, CREBP1_Q2, TGACCTY_ERR1_Q2, FOXO4_01, AP2_Q3

GO Biological Process (11): skeletal system development (GO:0001501), regulation of transcription by RNA polymerase II (GO:0006357), positive regulation of cell population proliferation (GO:0008284), anterior/posterior pattern specification (GO:0009952), proximal/distal pattern formation (GO:0009954), spinal cord motor neuron cell fate specification (GO:0021520), embryonic limb morphogenesis (GO:0030326), positive regulation of transcription by RNA polymerase II (GO:0045944), neuromuscular process (GO:0050905), negative regulation of cold-induced thermogenesis (GO:0120163), regulation of DNA-templated transcription (GO:0006355)

GO Molecular Function (7): RNA polymerase II transcription regulatory region sequence-specific DNA binding (GO:0000977), RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), DNA-binding transcription activator activity, RNA polymerase II-specific (GO:0001228), sequence-specific double-stranded DNA binding (GO:1990837), DNA binding (GO:0003677), protein binding (GO:0005515)

GO Cellular Component (4): chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654), nuclear body (GO:0016604)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
RNA polymerase II transcription regulatory region sequence-specific DNA binding	3
transcription by RNA polymerase II	2
regionalization	2
regulation of transcription by RNA polymerase II	2
cellular anatomical structure	2
system development	1
regulation of DNA-templated transcription	1
cell population proliferation	1
regulation of cell population proliferation	1
positive regulation of cellular process	1
spinal cord motor neuron differentiation	1
neuron fate specification	1
limb morphogenesis	1
embryonic appendage morphogenesis	1
positive regulation of DNA-templated transcription	1
nervous system process	1
negative regulation of multicellular organismal process	1
cold-induced thermogenesis	1
regulation of cold-induced thermogenesis	1
DNA-templated transcription	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
transcription cis-regulatory region binding	1
cis-regulatory region sequence-specific DNA binding	1
chromatin	1
DNA-binding transcription factor activity	1
DNA-binding transcription factor activity, RNA polymerase II-specific	1
DNA-binding transcription activator activity	1
positive regulation of transcription by RNA polymerase II	1
double-stranded DNA binding	1
sequence-specific DNA binding	1
nucleic acid binding	1
binding	1
chromosome	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
nucleoplasm	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

676 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
HOXC10	TBX4	P57082	902
HOXC10	TBX5	Q99593	782
HOXC10	TBX6	O95947	678
HOXC10	TBX3	O15119	599
HOXC10	SALL4	Q9UJQ4	566
HOXC10	DUX4L2	P0CJ85	562
HOXC10	TBX2	Q13207	556
HOXC10	TBR1	Q16650	517
HOXC10	PRMT5	O14744	515
HOXC10	HOXC13	P31276	514
HOXC10	PROP1	O75360	507
HOXC10	GAPDH	P00354	502
HOXC10	HOXB13	Q92826	489
HOXC10	TBX1	O43435	476
HOXC10	XRCC6	P12956	447

IntAct

12 interactions, top by confidence:

A	B	Type	Score
EGFR	GAPDH	psi-mi:“MI:0914”(association)	0.790
HOXC10	USP21	psi-mi:“MI:0915”(physical association)	0.560
YWHAG	HOXC10	psi-mi:“MI:0915”(physical association)	0.370
NUP205	HOXC10	psi-mi:“MI:0915”(physical association)	0.370
HOXC10	TRMU	psi-mi:“MI:0914”(association)	0.350
BMI1	MEIS3P1	psi-mi:“MI:0914”(association)	0.350
S100A2	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
S100P	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
USP21	HOXC10	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (22): HOXC10 (Affinity Capture-RNA), HOXC10 (Affinity Capture-MS), SNX15 (Affinity Capture-MS), TRMU (Affinity Capture-MS), MAPK14 (Affinity Capture-MS), MAPK9 (Affinity Capture-MS), HOXC10 (Affinity Capture-RNA), HOXC10 (Affinity Capture-MS), HOXC10 (Two-hybrid), HOXC10 (Affinity Capture-MS), SNX15 (Affinity Capture-MS), MAPK9 (Affinity Capture-MS), MAPK14 (Affinity Capture-MS), TRMU (Affinity Capture-MS), HOXC10 (Affinity Capture-MS)

ESM2 similar proteins: A1YFT7, A2D5V0, A2D635, A2T6F8, A2T7D1, G3X9P6, O42502, O57374, P09092, P21711, P24342, P28358, P28359, P31257, P31263, P42583, P79724, Q08820, Q15699, Q1ECY2, Q1KKS8, Q1KKT0, Q1KKV1, Q1KKV4, Q1KKZ4, Q1KKZ6, Q6JIY4, Q6JIY5, Q6NSW7, Q8AWY2, Q8JJ26, Q90469, Q90470, Q91685, Q91926, Q9DDU1, Q9DDU2, Q9H9S0, Q9IA13, Q9IA14

Diamond homologs: A1YFT7, A2D5V0, A2D635, A2T6F8, A2T7D1, A2T7H7, B5DFK3, O42502, O42503, O42506, O43248, P09013, P09014, P09023, P09025, P09067, P09079, P09087, P09631, P09632, P09633, P10179, P14838, P15861, P17481, P17482, P17509, P18863, P18866, P20615, P23459, P23813, P24340, P24341, P24342, P28356, P28357, P28358, P28359, P31257

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
HOXC10	“up-regulates quantity by expression”	LAMB2	“transcriptional regulation”

Disease & clinical

Cancer significance

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	35
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

263 predictions. Top by Δscore:

Variant	Effect	Δscore
12:53986006:GAAAG:G	donor_gain	1.0000
12:53986007:AAAGG:A	donor_loss	1.0000
12:53986008:AAGGT:A	donor_loss	1.0000
12:53986009:AGGTA:A	donor_loss	1.0000
12:53986011:G:C	donor_loss	1.0000
12:53986011:G:GG	donor_gain	1.0000
12:53986011:GT:G	donor_loss	1.0000
12:53986012:T:G	donor_loss	1.0000
12:53986008:AAG:A	donor_gain	0.9900
12:53986009:AG:A	donor_gain	0.9900
12:53986010:GG:G	donor_gain	0.9900
12:53989167:A:AG	acceptor_gain	0.9900
12:53989167:AGAG:A	acceptor_gain	0.9900
12:53989168:G:GG	acceptor_gain	0.9900
12:53989168:GA:G	acceptor_gain	0.9900
12:53989168:GAGG:G	acceptor_gain	0.9900
12:53989168:GAGGA:G	acceptor_gain	0.9900
12:53986007:AAAG:A	donor_gain	0.9600
12:53989166:CAG:C	acceptor_gain	0.9500
12:53989167:AGA:A	acceptor_gain	0.9500
12:53989168:GAG:G	acceptor_gain	0.9500
12:53986517:G:A	acceptor_gain	0.9300
12:53989163:TAACA:T	acceptor_loss	0.9100
12:53989167:A:T	acceptor_loss	0.9100
12:53989168:G:GA	acceptor_loss	0.9100
12:53989164:A:AG	acceptor_gain	0.8500
12:53986682:ATGTT:A	donor_gain	0.8400
12:53986495:C:CA	acceptor_gain	0.8300
12:53986516:T:TA	acceptor_gain	0.8200
12:53986684:GTT:G	donor_gain	0.8200

AlphaMissense

2256 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:53989201:T:A	W262R	1.000
12:53989201:T:C	W262R	1.000
12:53989223:G:C	R269T	1.000
12:53989223:G:T	R269M	1.000
12:53989224:G:C	R269S	1.000
12:53989224:G:T	R269S	1.000
12:53989225:A:G	K270E	1.000
12:53989227:G:C	K270N	1.000
12:53989227:G:T	K270N	1.000
12:53989228:A:G	K271E	1.000
12:53989231:A:G	R272G	1.000
12:53989232:G:C	R272T	1.000
12:53989232:G:T	R272M	1.000
12:53989233:G:C	R272S	1.000
12:53989233:G:T	R272S	1.000
12:53989238:C:A	P274H	1.000
12:53989240:T:A	Y275N	1.000
12:53989240:T:C	Y275H	1.000
12:53989240:T:G	Y275D	1.000
12:53989241:A:C	Y275S	1.000
12:53989241:A:G	Y275C	1.000
12:53989244:C:T	T276I	1.000
12:53989246:A:G	K277E	1.000
12:53989248:A:C	K277N	1.000
12:53989248:A:T	K277N	1.000
12:53989253:A:C	Q279P	1.000
12:53989253:A:G	Q279R	1.000
12:53989254:G:C	Q279H	1.000
12:53989254:G:T	Q279H	1.000
12:53989259:T:C	L281P	1.000

dbSNP variants (sampled 300 via entrez): RS1000637790 (12:53990067 A>G), RS1000665051 (12:53984568 A>T), RS1000946141 (12:53985009 C>T), RS1001329145 (12:53987430 G>A), RS1001611641 (12:53987902 C>A), RS1001899322 (12:53984434 A>T), RS1002005271 (12:53983785 G>A), RS1002563878 (12:53988069 G>C), RS1003031493 (12:53988247 T>C,G), RS1004363277 (12:53987611 C>G), RS1004401810 (12:53988720 C>G,T), RS1005367411 (12:53986367 G>A), RS1005460234 (12:53986595 G>A,C), RS1005636605 (12:53989540 A>G), RS1005665014 (12:53990247 A>C,T)

Disease associations

OMIM: gene MIM:605560 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST005956_70	Waist-to-hip ratio adjusted for BMI	4.000000e-13
GCST005957_6	Waist-to-hip ratio adjusted for BMI (age <50)	6.000000e-06
GCST005958_9	Waist-to-hip ratio adjusted for BMI (age >50)	1.000000e-08
GCST005962_20	Waist-to-hip ratio adjusted for BMI x sex x age interaction (4df test)	7.000000e-13

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0008007	age at assessment
EFO:0008343	sex interaction measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

29 total (human), top 29 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Nickel	decreases expression	2
Valproic Acid	affects expression, decreases methylation	2
FR900359	increases phosphorylation	1
urushiol	decreases expression	1
apocarotenal	increases expression	1
beta-lapachone	increases expression	1
arsenite	increases methylation	1
nickel sulfate	increases expression	1
coumarin	decreases phosphorylation	1
CGP 52608	affects binding, increases reaction	1
abrine	increases expression	1
Grape Seed Proanthocyanidins	affects cotreatment, decreases expression	1
(+)-JQ1 compound	decreases expression	1
theaflavin-3,3’-digallate	affects expression	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Catechin	affects cotreatment, decreases expression	1
Cisplatin	increases expression	1
Estradiol	decreases expression	1
Gallic Acid	decreases expression	1
Methylcholanthrene	increases expression	1
Testosterone	decreases expression	1
Tetrachlorodibenzodioxin	affects binding, increases reaction	1
Tretinoin	decreases expression	1
Zinc	decreases expression	1
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	1
Aflatoxin B1	decreases methylation	1
Antirheumatic Agents	increases expression	1
beta Carotene	increases expression	1
Lactic Acid	increases expression	1

Clinical trials (associated diseases)

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