HOXD10
protein-codinghomeobox D10, the group of HOXL subclass homeoboxes
Gene summary
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. [provided by RefSeq, Jul 2008]
- HOX4
- HOX4D
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~11.1 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AD
Disease ID:MONDO:0008652
Submitter: Ambry Genetics
Inheritance Pattern: AD
Disease ID:MONDO:0008652
Submitter: Labcorp Genetics (formerly Invitae)
Inheritance Pattern: AD
Disease ID:MONDO:0008652
Submitter: PanelApp Australia
Clinical Genomic Database (CGD)
Manifestation: Musculoskeletal
Intervention: General
Rationale: 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
Comments: One described family was also affected by Charcot-Marie-Tooth disease
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to HOXD10 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_002148.4. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 3 | 4 | 2 | 9 | ||
| missense | 1 | 52 | 4 | 2 | 59 | |
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 1 | 0 | 57 | 8 | 4 | 70 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_002139.2 | 2 | MANE Select | |
| Ensembl | ENSP00000249501.4 | 2 | MANE Select | |
| Ensembl | ENSP00000802502.1 | 2 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Proteoglycans in cancer - Homo sapiens (human)
- MicroRNAs in cancer - Homo sapiens (human)
Biological Process
- single fertilization
- skeletal muscle tissue development
- adult locomotory behavior
- anterior/posterior pattern specification
- proximal/distal pattern formation
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
Cellular Component
- nucleoplasm
- cytosol
- cytoplasmic ribonucleoprotein granule
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000249501
- Coding exons
- 2
- Length
- 11153
- Individuals with no LoFs
- 125728
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 20
- Defined
- 125748
- p
- 0.0000795
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.0869 | 192 | 189 | 1.02 | 0.0000102 | 2263 |
| Missense (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 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000062 | 0.000062 | rare |
| Latino/Admixed American | 0.000058 | 0.000058 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.0013 | 0.00065 | notable |
| Finnish | 0.000092 | 0.000046 | rare |
| European (Non-Finnish) | 0.000036 | 0.000035 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- 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.;
Recessive Scores
- pRec
- 0.119
Intolerance Scores
- LoFtool
- 0.333
- RVIS EVS
- -0.05
- RVIS percentile EVS
- 50.01
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.760
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |