HOXD10

Summary

HOXD10 (homeobox D10, HGNC:5133) is a protein-coding gene on chromosome 2q31.1, encoding Homeobox protein Hox-D10 (P28358). Sequence-specific transcription factor which is part of a developmental regulatory system that provides cells with specific positional identities on the anterior-posterior axis.

This gene is a member of the Abd-B homeobox family and encodes a protein with a homeobox DNA-binding domain. It is included in a cluster of homeobox D genes located on chromosome 2. The encoded nuclear protein functions as a sequence-specific transcription factor that is expressed in the developing limb buds and is involved in differentiation and limb development. Mutations in this gene have been associated with Wilm’s tumor and congenital vertical talus (also known as “rocker-bottom foot” deformity or congenital convex pes valgus) and/or a foot deformity resembling that seen in Charcot-Marie-Tooth disease.

Source: NCBI Gene 3236 — RefSeq curated summary.

At a glance

• Gene–disease (curated): congenital vertical talus (Limited, GenCC)
• GWAS associations: 5
• Clinical variants (ClinVar): 102 total — 1 pathogenic
• Phenotypes (HPO): 5
• MANE Select transcript: NM_002148

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:5133
Approved symbol	HOXD10
Name	homeobox D10
Location	2q31.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000128710
Ensembl biotype	protein_coding
OMIM	142984
Entrez	3236

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 2 protein_coding_CDS_not_defined, 1 protein_coding

ENST00000249501, ENST00000490088, ENST00000549469

RefSeq mRNA: 1 — MANE Select: NM_002148 NM_002148

CCDS: CCDS2266

Canonical transcript exons

ENST00000249501 — 2 exons

Exon	Start	End
ENSE00000882912	176116778	176117578
ENSE00001816717	176118954	176119937

Expression profiles

Bgee: expression breadth ubiquitous, 133 present calls, max score 96.34.

FANTOM5 (CAGE): breadth broad, TPM avg 1.5019 / max 130.4827, expressed in 255 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
23832	0.7328	175
23835	0.3832	126
23836	0.1458	64
23830	0.0933	32
23837	0.0612	32
23834	0.0316	19
23833	0.0271	11
23831	0.0268	9

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
renal medulla	UBERON:0000362	96.34	gold quality
decidua	UBERON:0002450	95.91	gold quality
body of uterus	UBERON:0009853	95.85	gold quality
urethra	UBERON:0000057	95.57	gold quality
stromal cell of endometrium	CL:0002255	94.38	gold quality
calcaneal tendon	UBERON:0003701	92.51	gold quality
metanephros cortex	UBERON:0010533	91.97	gold quality
vagina	UBERON:0000996	91.90	gold quality
myometrium	UBERON:0001296	91.58	gold quality
endometrium	UBERON:0001295	90.42	gold quality
buccal mucosa cell	CL:0002336	90.40	gold quality
uterus	UBERON:0000995	89.84	gold quality
muscle layer of sigmoid colon	UBERON:0035805	89.63	gold quality
ectocervix	UBERON:0012249	89.56	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	88.68	gold quality
tendon of biceps brachii	UBERON:0008188	88.52	gold quality
tendon	UBERON:0000043	87.73	gold quality
prostate gland	UBERON:0002367	85.63	gold quality
sigmoid colon	UBERON:0001159	85.10	gold quality
endocervix	UBERON:0000458	84.13	gold quality
kidney	UBERON:0002113	83.91	gold quality
germinal epithelium of ovary	UBERON:0001304	83.34	gold quality
adult mammalian kidney	UBERON:0000082	83.30	gold quality
cortex of kidney	UBERON:0001225	83.22	gold quality
mammalian vulva	UBERON:0000997	82.81	gold quality
seminal vesicle	UBERON:0000998	81.77	gold quality
female reproductive system	UBERON:0000474	80.47	gold quality
metanephros	UBERON:0000081	79.50	gold quality
adult organism	UBERON:0007023	76.79	gold quality
uterine cervix	UBERON:0000002	76.68	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.80

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

5 targets.

Target	Regulation
HOXC5
IGFBP3
LILRB1
REN	Activation
ROCK2

JASPAR motifs

Motif	Name	Family
MA1506.1	HOXD10	HOX
MA1506.2	HOXD10	HOX

JASPAR matrix evidence (PMIDs): PMID:18585359

Upstream regulators (CollecTRI, top): EZH2, POU2F1

miRNA regulators (miRDB)

71 targeting HOXD10, 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-190A-3P	100.00	80.35	5520
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-432-3P	100.00	67.86	705
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-3134	100.00	66.43	777
HSA-MIR-1193	100.00	65.93	529
HSA-MIR-6759-5P	99.99	66.54	785
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-25-3P	99.98	74.60	1817
HSA-MIR-363-3P	99.98	74.72	1821
HSA-MIR-367-3P	99.98	74.83	1819
HSA-MIR-103A-3P	99.98	69.14	1595
HSA-MIR-107	99.98	69.14	1595
HSA-MIR-1229-3P	99.97	66.49	906
HSA-MIR-6793-5P	99.97	65.95	758
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-23C	99.95	73.92	3192
HSA-MIR-767-5P	99.95	70.85	993
HSA-MIR-218-5P	99.93	72.22	2103
HSA-MIR-3529-3P	99.90	73.55	3045
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-137-3P	99.87	74.74	2401
HSA-MIR-579-3P	99.86	71.66	3628
HSA-MIR-664B-3P	99.84	71.65	3590

Literature-anchored findings (GeneRIF, showing 34)

• results indicate a role for HoxD10 in maintaining a nonangiogenic state in the endothelium (PMID:12466126)
• Missense Mutation in HOXD10 is associated with congenital vertical talus and Charcot-Marie-Tooth disease (PMID:15146389)
• An autosomal-dominant-inherited mutation in a HOXD10 gene with complete penetrance is found in all members of a pedigree with congenital vertical talus. (PMID:15368082)
• No evidence was found of linkage near the HOXD gene cluster on chromosome 2q, suggesting genes other than HOXD10 are responsible for idiopathic clubfoot. (PMID:17417092)
• Pak1 is a target of miR-7 and that HoxD10 plays a regulatory role in modifying the expression of miR-7. (PMID:18922890)
• miR-10b induced glioma cell invasion by modulating tumor invasion factors MMP-14 and uPAR expression via the direct target HOXD10 (PMID:21419107)
• HoxD10 potentially functions as a tumor suppressor that is inactivated through promoter hypermethylation in gastric cancer. (PMID:22160393)
• Suggest that miR-10b can stimulate the upregulation of RhoC and AKT phosphorylation through targeting HOXD10, thus promoting cell invasion in gastric tumors. (PMID:22293682)
• TBX1 can alter TGF-beta/BMP, an important signaling pathway, through interacting with HOXD10. Above findings may shed light on the mechanism of TBX1 mutations leading to renal malformations found in patients carrying a 22q11 deletion. (PMID:22842189)
• downregulation of HOXD10 expression by miR-10b overexpression may induce an increase of pro-metastatic gene products, such as MMP14 and RHOC, and contribute to the acquisition of metastatic phenotypes in epithelial ovarian cancer cells (PMID:23670532)
• It is a member of the HOX gene family. HOX genes are the main regulatory genes that directly influence organogenesis and maintain the function of differentiated tissues (PMID:24219032)
• miR-23a was upregulated in glioma. This overexpression promoted glioma cell invasion, probably by modulating MMP-14 via directly inhibiting the expression of HOXD10. (PMID:24305689)
• KLF4 and HOXD10 were identified as direct targets of miR-10b in bladder cancer cells (PMID:24573354)
• HOXD10 expression varies by stage of disease and produces differential effects in head and neck squamous cell carcinoma. (PMID:25010866)
• Downregulation of the HOXD10 gene expression was associated with breast cancer. (PMID:25081374)
• POU2F1 activity regulates HOXD10 and HOXD11 gene expression in head and neck squamous cell carcinoma, promoting a proliferative and invasive phenotype. (PMID:25301728)
• These results suggested that HOXD10 may be a putative suppressor gene and can act as a prognostic marker and potentially a novel therapeutic target for cholangiocellular carcinoma. (PMID:26260613)
• Low HOXD10 promotes migration and invasion in gastric cancer. (PMID:26311318)
• By treating LECs with VEGF-C156S and analyzing subsequent changes in gene expression, we identified several ‘immediate early’ transcription factors that showed a rapid transient upregulation VEGFR-3 stimulation. these results reveal an important and unanticipated role of HOXD10 in the regulation of VEGFR-3 signaling in lymphatic endothelial cells, and in the control of lymphangiogenesis and permeability. (PMID:27199372)
• Knock down of the dickkopf WNT signaling pathway inhibitor 2 (DKK2) resulted in a significant suppression of HOXD10, HOXD11 and HOXD13 while over-expression of DKK2 and stimulation with factors of the WNT signaling pathway. (PMID:27363011)
• High expression of HOXD10 is associated with laryngeal squamous cell carcinoma. (PMID:27658780)
• our data suggest that the loss of HoxD10 function is common and may thus result in a progressive phenotype in PCa. HoxD10 may function as a biomarker that differentiates patients with BCR disease from the ones that are not after radical prostatectomy, implicating its potential as a therapeutic target. (PMID:28231752)
• Knockdown of HOXD10 in renal cells also resulted in increased resistance to colistin cytotoxicity. (PMID:28335481)
• Results show that HOXD10 is frequently methylated in human hepatocellular carcinoma (HCC), and the expression of HOXD10 is regulated by promoter region methylation. HOXD10 suppresses HCC cell growth both in vitro and in vivo. HOXD10 suppresses human HCC by inhibiting ERK signaling. (PMID:29075359)
• Results show that HOXD10 promoter is hypermethylated in papillary thyroid cancer (PTC) tissues and its mRNA expression decreased. Moreover, the hypermethylation of HOXD10 was associated with invasion of the primary tumor. Further data provide evidence that the epigenetic suppression of the HOXD10 gene may play a role in the tumorigenesis of PTC. (PMID:29115628)
• MiR-10b could regulate the proliferation, colony formation, cell cycle and apoptosis of acute myeloid leukemia cells through targeting HOXD10 (PMID:30468483)
• The results indicated that completely different sets of transcription factors coregulate HOXA4 and HOXD10 (but not HOXA9) and their expression-correlated genes. (PMID:30552679)
• HOXD10 was suppressed in colon adenocarcinoma cells, which down-regulated RHOC/AKT/MAPK pathway. (PMID:30683109)
• Homeobox D10, a tumor suppressor, inhibits the proliferation and migration of esophageal squamous cell carcinoma. (PMID:30938888)
• Downregulation of microRNA-92b-3p suppresses proliferation, migration, and invasion of gastric cancer SGC-7901 cells by targeting Homeobox D10. (PMID:31106881)
• Circ_0000317/microRNA-520g/HOXD10 axis affects the biological characteristics of colorectal cancer. (PMID:34292663)
• Upregulation of homeobox D10 expression suppresses invasion and migration of clear cell renal cell carcinoma through targeting of E-cadherin. (PMID:34825321)
• Circ_0077109 sponges miR-139-5p and upregulates HOXD10 in trophoblast cells as potential mechanism for preeclampsia progression. (PMID:35964231)
• Joint-specific regulation of homeobox D10 expression in rheumatoid arthritis fibroblast-like synoviocytes. (PMID:38829908)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	hoxd10a	ENSDARG00000057859
mus_musculus	Hoxd10	ENSMUSG00000050368
rattus_norvegicus	Hoxd10	ENSRNOG00000001581

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), 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), HOXC10 (ENSG00000180818), HOXB4 (ENSG00000182742), HOXA4 (ENSG00000197576), HOXC6 (ENSG00000197757), HOXC4 (ENSG00000198353)

Protein

Protein identifiers

Homeobox protein Hox-D10 — P28358 (reviewed: P28358)

Alternative names: Homeobox protein Hox-4D, Homeobox protein Hox-4E

All UniProt accessions (1): P28358

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.

Tissue specificity. Strongly expressed in the adult male and female urogenital tracts.

Disease relevance. Vertical talus, congenital (CVT) [MIM:192950] A rare malformation characterized by vertical orientation of the talus with a rigid dorsal dislocation of the navicular, equinus deformity of the calcaneus, abduction deformity of the forefoot, and contracture of the soft tissues of the hind- and mid-foot. This condition is usually associated with multiple other congenital deformities and only rarely is an isolated deformity with familial occurrence. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the Abd-B homeobox family.

RefSeq proteins (1): NP_002139* (*=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 (9 total): compositionally biased region 2, modified residue 2, chain 1, DNA-binding region 1, region of interest 1, sequence variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P28358-F1	60.05	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 (2): 238, 239

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 242 (showing top): GOBP_SPINAL_CORD_DEVELOPMENT, RNGTGGGC_UNKNOWN, GOBP_SINGLE_FERTILIZATION, RRAGTTGT_UNKNOWN, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOBP_MUSCLE_TISSUE_DEVELOPMENT, GOBP_BEHAVIOR, PAX4_01, GOBP_SKELETAL_SYSTEM_DEVELOPMENT, GOBP_HINDLIMB_MORPHOGENESIS, GOBP_EMBRYONIC_SKELETAL_SYSTEM_DEVELOPMENT, GOBP_ADULT_BEHAVIOR, GOBP_EMBRYONIC_SKELETAL_SYSTEM_MORPHOGENESIS, GOBP_NEUROGENESIS, RACCACAR_AML_Q6

GO Biological Process (18): regulation of transcription by RNA polymerase II (GO:0006357), single fertilization (GO:0007338), skeletal muscle tissue development (GO:0007519), adult locomotory behavior (GO:0008344), 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), forelimb morphogenesis (GO:0035136), hindlimb morphogenesis (GO:0035137), negative regulation of cell cycle (GO:0045786), embryonic skeletal system morphogenesis (GO:0048704), peripheral nervous system neuron development (GO:0048935), neuromuscular process (GO:0050905), skeletal system development (GO:0001501), regulation of DNA-templated transcription (GO:0006355), regulation of gene expression (GO:0010468), positive regulation of transcription by RNA polymerase II (GO:0045944)

GO Molecular Function (9): 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), chromatin binding (GO:0003682), sequence-specific double-stranded DNA binding (GO:1990837), RNA polymerase II transcription regulatory region sequence-specific DNA binding (GO:0000977), DNA binding (GO:0003677), DNA-binding transcription factor activity (GO:0003700), protein binding (GO:0005515)

GO Cellular Component (6): chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytosol (GO:0005829), transcription repressor complex (GO:0017053), cytoplasmic ribonucleoprotein granule (GO:0036464)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
limb morphogenesis	3
RNA polymerase II transcription regulatory region sequence-specific DNA binding	3
cellular anatomical structure	3
regulation of DNA-templated transcription	2
transcription by RNA polymerase II	2
regionalization	2
regulation of transcription by RNA polymerase II	2
binding	2
transcription cis-regulatory region binding	2
cytoplasm	2
fertilization	1
striated muscle tissue development	1
skeletal muscle organ development	1
locomotory behavior	1
adult behavior	1
spinal cord motor neuron differentiation	1
neuron fate specification	1
embryonic appendage morphogenesis	1
cell cycle	1
negative regulation of cellular process	1
regulation of cell cycle	1
embryonic organ morphogenesis	1
skeletal system morphogenesis	1
embryonic skeletal system development	1
neuron development	1
peripheral nervous system neuron differentiation	1
nervous system process	1
system development	1
DNA-templated transcription	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
gene expression	1
regulation of macromolecule biosynthetic process	1
positive regulation of DNA-templated transcription	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

Protein interactions and networks

STRING

1194 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
HOXD10	RHOC	P08134	819
HOXD10	SHH	Q15465	682
HOXD10	MEIS1	O00470	667
HOXD10	EVX2	Q03828	601
HOXD10	HOXD13	P35453	600
HOXD10	HOXD3	P31249	598
HOXD10	HOXD11	P31277	576
HOXD10	HOXD1	Q9GZZ0	575
HOXD10	SUZ12	Q15022	571
HOXD10	HOXD12	P35452	527
HOXD10	HOXA3	O43365	507
HOXD10	HOXA4	Q00056	493
HOXD10	HOXA9	P31269	491
HOXD10	HOXA5	P20719	490
HOXD10	HOXA6	P31267	460

IntAct

38 interactions, top by confidence:

A	B	Type	Score
HOXD10	SERPINB4	psi-mi:“MI:0915”(physical association)	0.590
GEMIN2	HOXD10	psi-mi:“MI:0915”(physical association)	0.560
HOXD10	COPS3	psi-mi:“MI:0915”(physical association)	0.560
HOXD10	PIAS1	psi-mi:“MI:0915”(physical association)	0.560
HOXD10	RASSF1	psi-mi:“MI:0915”(physical association)	0.560
HOXD10	SKIC8	psi-mi:“MI:0915”(physical association)	0.560
HOXD10	MPND	psi-mi:“MI:0915”(physical association)	0.560
HOXD10	RNF183	psi-mi:“MI:0915”(physical association)	0.560
GMNN	HOXD10	psi-mi:“MI:0407”(direct interaction)	0.440
HOXD10		psi-mi:“MI:0915”(physical association)	0.370

BioGRID (13): SERPINB4 (Affinity Capture-MS), S100A7 (Affinity Capture-MS), SERPINB4 (Affinity Capture-MS), RCHY1 (PCA), HOXD10 (Two-hybrid), HOXD10 (Reconstituted Complex), SERPINB4 (Affinity Capture-MS), HOXD10 (Affinity Capture-MS), RNF114 (Affinity Capture-MS), KLHL21 (Affinity Capture-MS), NPW (Affinity Capture-MS), HOXD10 (Reconstituted Complex), HOXD10 (Reconstituted Complex)

ESM2 similar proteins: A0A087WRU1, A0JNH1, A2RUB1, A6QNQ6, B0S6S9, B1WC58, D3Z987, D3ZJ47, E1BC15, O60673, P28358, P28359, P56716, P70347, Q0P5X5, Q0VAV2, Q0VBV7, Q15468, Q2M2Z5, Q3UXL4, Q3V089, Q49A88, Q569L8, Q5BQN8, Q5CZC0, Q5QGS0, Q5T1N1, Q5VWN6, Q60988, Q61493, Q62924, Q6ZP01, Q6ZU52, Q6ZVD7, Q80U59, Q80WQ8, Q86WS4, Q86YC2, Q8CB14, Q8IUR6

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

3 interactions.

A	Effect	B	Mechanism
POU2F1	“up-regulates quantity by expression”	HOXD10	“transcriptional regulation”
HMGB1	“up-regulates activity”	HOXD10	binding
HOXD10	“up-regulates activity”	MEIS1	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	72
Likely benign	5
Benign	16

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
14878	NM_002148.4(HOXD10):c.956T>A (p.Met319Lys)	Pathogenic

SpliceAI

242 predictions. Top by Δscore:

Variant	Effect	Δscore
2:176108904:CA:C	acceptor_loss	1.0000
2:176108905:A:AG	acceptor_gain	1.0000
2:176108905:AG:A	acceptor_loss	1.0000
2:176108905:AGTT:A	acceptor_gain	1.0000
2:176108906:G:GG	acceptor_gain	1.0000
2:176108906:GT:G	acceptor_gain	1.0000
2:176108906:GTT:G	acceptor_gain	1.0000
2:176108906:GTTG:G	acceptor_gain	1.0000
2:176108906:GTTGC:G	acceptor_gain	1.0000
2:176108897:T:TA	acceptor_gain	0.9900
2:176117570:A:T	donor_gain	0.9900
2:176117988:GT:G	donor_gain	0.9900
2:176108901:TTGCA:T	acceptor_gain	0.9800
2:176108902:T:TA	acceptor_gain	0.9800
2:176108902:TGCAG:T	acceptor_gain	0.9800
2:176108903:GCAG:G	acceptor_gain	0.9800
2:176108904:CAG:C	acceptor_gain	0.9800
2:176108905:AGTTG:A	acceptor_gain	0.9800
2:176108906:G:T	acceptor_gain	0.9800
2:176118943:A:AG	acceptor_gain	0.9800
2:176109114:A:AG	donor_gain	0.9700
2:176109115:G:GG	donor_gain	0.9700
2:176118952:A:AG	acceptor_gain	0.9700
2:176118953:G:GG	acceptor_gain	0.9700
2:176117575:AAAG:A	donor_loss	0.9600
2:176117577:AG:A	donor_loss	0.9600
2:176117578:GG:G	donor_loss	0.9600
2:176117579:G:T	donor_loss	0.9600
2:176118952:AGAG:A	acceptor_gain	0.9600
2:176118953:GAGG:G	acceptor_gain	0.9600

AlphaMissense

2270 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:176118986:T:A	W260R	1.000
2:176118986:T:C	W260R	1.000
2:176118988:G:C	W260C	1.000
2:176118988:G:T	W260C	1.000
2:176119008:G:C	R267T	1.000
2:176119008:G:T	R267I	1.000
2:176119009:A:C	R267S	1.000
2:176119009:A:T	R267S	1.000
2:176119010:A:G	K268E	1.000
2:176119012:G:C	K268N	1.000
2:176119012:G:T	K268N	1.000
2:176119013:A:G	K269E	1.000
2:176119015:G:C	K269N	1.000
2:176119015:G:T	K269N	1.000
2:176119016:A:G	R270G	1.000
2:176119016:A:T	R270W	1.000
2:176119017:G:C	R270T	1.000
2:176119017:G:T	R270M	1.000
2:176119018:G:C	R270S	1.000
2:176119018:G:T	R270S	1.000
2:176119023:C:A	P272H	1.000
2:176119025:T:A	Y273N	1.000
2:176119025:T:C	Y273H	1.000
2:176119025:T:G	Y273D	1.000
2:176119026:A:C	Y273S	1.000
2:176119026:A:G	Y273C	1.000
2:176119029:C:T	T274I	1.000
2:176119031:A:G	K275E	1.000
2:176119033:G:C	K275N	1.000
2:176119033:G:T	K275N	1.000

dbSNP variants (sampled 300 via entrez): RS1000296037 (2:176119903 G>A,T), RS1001404199 (2:176118627 A>C,G), RS1001473603 (2:176119826 C>G), RS1001911703 (2:176114954 C>T), RS1002040804 (2:176119435 G>A,C,T), RS1002945775 (2:176118190 C>G), RS1003537507 (2:176116716 C>A,G,T), RS1003693324 (2:176117973 C>A,T), RS1004058500 (2:176116568 G>A), RS1005043379 (2:176116488 G>A,C,T), RS1005115612 (2:176116336 C>A,G,T), RS1006117920 (2:176114914 C>A,G), RS1006190198 (2:176119460 TATATAA>T), RS1006567401 (2:176119064 T>C), RS1008075854 (2:176118620 G>A,C)

Disease associations

OMIM: gene MIM:142984 | disease phenotypes: MIM:192950

GenCC curated gene-disease

Disease	Classification	Inheritance
congenital vertical talus	Limited	Autosomal dominant

Mondo (1): congenital vertical talus (MONDO:0008652)

Orphanet (1): Congenital vertical talus (Orphanet:178382)

HPO phenotypes

5 total (5 of 5 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0001369	Arthritis
HP:0001838	Rocker bottom foot
HP:0001848	Calcaneovalgus deformity
HP:0008138	Equinus calcaneus

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST002337_4	Amyotrophic lateral sclerosis (sporadic)	1.000000e-06
GCST006661_148	Male-pattern baldness	3.000000e-18
GCST007876_9	Estimated glomerular filtration rate	1.000000e-14
GCST007877_2	Creatinine levels	1.000000e-08
GCST90016670_10	Kidney volume	4.000000e-08

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

21 total (human), top 21 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Aflatoxin B1	decreases methylation	2
propionaldehyde	increases expression	1
arsenite	increases methylation	1
butyraldehyde	increases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1
pentanal	increases expression	1
jinfukang	affects cotreatment, decreases expression	1
(+)-JQ1 compound	decreases expression	1
Sorafenib	affects cotreatment, decreases reaction, increases expression	1
Ropivacaine	affects cotreatment, decreases reaction, increases expression	1
Aldehydes	increases expression	1
Benzo(a)pyrene	affects methylation, decreases methylation	1
Cadmium	decreases expression	1
Cisplatin	affects cotreatment, decreases expression	1
Estradiol	affects expression, increases reaction	1
Formaldehyde	increases expression	1
Lipopolysaccharides	increases expression, affects response to substance	1
Silver	decreases expression	1
Tetrachlorodibenzodioxin	increases expression	1
Tretinoin	increases expression	1
Valproic Acid	increases expression	1

Cellosaurus cell lines

3 cell lines: 3 embryonic stem cell

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_A3A8	SEES3-1V human HOXD10, clone1	Embryonic stem cell	Male
CVCL_A3A9	SEES3-1V human HOXD10, clone2	Embryonic stem cell	Male
CVCL_A3B0	SEES3-1V human HOXD10, clone3	Embryonic stem cell	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00916903	Not specified	TERMINATED	Genetic Disease Gene Identification