HOXD10

homeobox D10, the group of HOXL subclass homeoboxes

Basic information

Region (hg38): 2:176108790-176119937

Previous symbols: [ "HOX4", "HOX4D" ]

Links

ENSG00000128710 ∙ NCBI:3236 ∙ OMIM:142984 ∙ HGNC:5133 ∙ Uniprot:P28358 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• congenital vertical talus (Limited), mode of inheritance: AD
• congenital vertical talus (Limited), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Vertical talus, congenital	AD	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Musculoskeletal	15146389; 16450407
One described family was also affected by Charcot-Marie-Tooth disease

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the HOXD10 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the HOXD10 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			3	3	2	8
missense			24	2	2	28
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region			1		1	2
non coding			19	3	11	33
Total	0	0	46	8	15

Variants in HOXD10

This is a list of pathogenic ClinVar variants found in the HOXD10 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
2-176108929-A-G			Likely benign (Mar 29, 2018)
2-176108973-G-T		not specified	Uncertain significance (Dec 16, 2023)
2-176109004-A-G			Benign (Apr 17, 2018)
2-176109013-A-T		not specified	Uncertain significance (Sep 20, 2023)
2-176109074-C-T		not specified	Uncertain significance (Sep 06, 2022)
2-176109075-G-T		not specified	Uncertain significance (Nov 09, 2024)
2-176109079-G-A			Benign (Dec 31, 2019)
2-176109138-T-G		not specified	Uncertain significance (Jul 09, 2024)
2-176116824-C-A		Congenital vertical talus	Uncertain significance (Jan 12, 2018)
2-176116828-C-G		Congenital vertical talus	Uncertain significance (Jan 13, 2018)
2-176116829-C-G		HOXD10-related disorder	Likely benign (Jun 13, 2019)
2-176116850-G-T		not specified	Uncertain significance (Oct 26, 2022)
2-176116868-C-T		not specified	Uncertain significance (Apr 20, 2023)
2-176116920-C-T		Congenital vertical talus	Uncertain significance (Jan 12, 2018)
2-176116927-G-A		not specified	Uncertain significance (Jun 25, 2024)
2-176116928-C-T		not specified	Uncertain significance (Jul 25, 2023)
2-176116949-C-T		Congenital vertical talus	Uncertain significance (Jan 13, 2018)
2-176116958-A-G		not specified	Uncertain significance (Aug 11, 2024)
2-176116963-G-A		not specified	Uncertain significance (Jan 16, 2017)
2-176117011-A-G		not specified	Uncertain significance (May 05, 2023)
2-176117017-G-A		not specified	Uncertain significance (Jun 03, 2024)
2-176117044-G-A			Uncertain significance (Sep 01, 2022)
2-176117053-T-C		not specified	Uncertain significance (May 16, 2024)
2-176117056-A-G		not specified	Uncertain significance (Jan 26, 2023)
2-176117078-C-T		not specified	Uncertain significance (Jan 26, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
HOXD10	protein_coding	protein_coding	ENST00000249501	2	11153

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0629	0.923	125728	0	20	125748	0.0000795

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.0869	192	189	1.02	0.0000102	2263
Missense in Polyphen		70	87.245	0.80234		1088
Synonymous	-1.33	90	75.3	1.19	0.00000489	645
Loss of Function	2.14	4	12.0	0.333	6.12e-7	139

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000119	0.000119
Ashkenazi Jewish	0.00	0.00
East Asian	0.00125	0.000653
Finnish	0.0000924	0.0000462
European (Non-Finnish)	0.0000356	0.0000352
Middle Eastern	0.00125	0.000653
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: 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.
• Disease: DISEASE: 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. {ECO:0000269|PubMed:15146389}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Proteoglycans in cancer - Homo sapiens (human);MicroRNAs in cancer - Homo sapiens (human) (Consensus)

Recessive Scores

• pRec: 0.119

Intolerance Scores

• loftool: 0.333
• rvis_EVS: -0.05
• rvis_percentile_EVS: 50.01

Haploinsufficiency Scores

• pHI: 0.618
• hipred: N
• hipred_score: 0.488
• ghis: 0.414

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.760

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Hoxd10
• Phenotype: reproductive system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); renal/urinary system phenotype; skeleton phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); limbs/digits/tail phenotype; cellular phenotype; muscle phenotype

Gene ontology

• Biological process: single fertilization;skeletal muscle tissue development;adult locomotory behavior;anterior/posterior pattern specification;proximal/distal pattern formation;spinal cord motor neuron cell fate specification;embryonic limb morphogenesis;forelimb morphogenesis;hindlimb morphogenesis;positive regulation of transcription by RNA polymerase II;embryonic skeletal system morphogenesis;peripheral nervous system neuron development;neuromuscular process
• Cellular component: nucleoplasm;cytosol;cytoplasmic ribonucleoprotein granule
• Molecular function: RNA polymerase II regulatory region sequence-specific DNA binding;DNA-binding transcription factor activity, RNA polymerase II-specific;DNA-binding transcription activator activity, RNA polymerase II-specific;chromatin binding