HOXD12

Chr 2

homeobox D12

Also known as: HOX4H

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, located on different chromosomes, consisting of 9 to 11 genes arranged in tandem. This gene is one of several homeobox HOXD genes located in a cluster on chromosome 2. Deletions that remove the entire HOXD gene cluster or the 5' end of this cluster have been associated with severe limb and genital abnormalities. The exact role of this gene has not been determined. [provided by RefSeq, Jul 2008]

OMIMResearchGenerating clinical summary…
DNmechanismLOEUF 1.53
Clinical SummaryHOXD12
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint?
1.53LOEUF
pLI 0.000
Z-score 0.54
OE 0.79 (0.431.53)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?
-1.34Z-score
OE missense 1.30 (1.161.46)
202 obs / 155.0 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?
LoF OE?0.79 (0.431.53)
00.351.4
Missense OE?1.30 (1.161.46)
00.61.4
Synonymous OE?1.14
01.21.6
LoF obs/exp: 6 / 7.6Missense obs/exp: 202 / 155.0Syn Z: -0.92

This gene — mechanism propensity

DN
0.7131th %ile
GOF
0.3986th %ile
LOF
0.61top 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

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

HOXD12 · 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.

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