HOXD10

Chr 2AD

homeobox D10

Also known as: HOX4, HOX4D, HOX4E, Hox-4.4

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]

OMIMResearchGenerating clinical summary…
DNmechanismADLOEUF 0.762 OMIM phenotypes
Clinical SummaryHOXD10
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.33) despite low pLI — interpret in context.
📋
ClinVar Variants
1 unique Pathogenic / Likely Pathogenic· 72 VUS of 102 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint?
0.76LOEUF
pLI 0.063
Z-score 2.14
OE 0.33 (0.160.76)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?
-0.09Z-score
OE missense 1.02 (0.901.15)
192 obs / 188.6 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?
LoF OE?0.33 (0.160.76)
00.351.4
Missense OE?1.02 (0.901.15)
00.61.4
Synonymous OE?1.19
01.21.6
LoF obs/exp: 4 / 12.0Missense obs/exp: 192 / 188.6Syn Z: -1.33

This gene — mechanism propensity

DN
0.7326th %ile
GOF
0.4677th %ile
LOF
0.51top 25%

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

102 submitted variants in ClinVar

Classification Summary

Pathogenic1
VUS72
Likely Benign6
Benign16
Conflicting5
1
Pathogenic
72
VUS
6
Likely Benign
16
Benign
5
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
1
0
0
1
Likely Pathogenic
0
0
0
0
0
VUS
1
53
15
3
72
Likely Benign
0
0
3
3
6
Benign
0
2
12
2
16
Conflicting
5
Total156308100

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

30 pathogenic / likely-pathogenic (of 31) ClinVar copy-number / structural variants overlap HOXD10 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →

Protein Context — Lollipop Plot

HOXD10 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →