HOXD9

Chr 2

homeobox D9

Also known as: HOX4, HOX4C, Hox-4.3, Hox-5.2

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 at 2q31-2q37 chromosome regions. Deletions that removed the entire HOXD gene cluster or 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 1.07
Clinical SummaryHOXD9
Population Constraint (gnomAD)
Low constraint (pLI 0.02) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
64 VUS of 75 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint?
1.07LOEUF
pLI 0.017
Z-score 1.45
OE 0.47 (0.231.07)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?
0.58Z-score
OE missense 0.87 (0.761.00)
147 obs / 168.1 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?
LoF OE?0.47 (0.231.07)
00.351.4
Missense OE?0.87 (0.761.00)
00.61.4
Synonymous OE?1.15
01.21.6
LoF obs/exp: 4 / 8.6Missense obs/exp: 147 / 168.1Syn Z: -0.97

This gene — mechanism propensity

DN
0.6840th %ile
GOF
0.4480th %ile
LOF
0.63top 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

75 submitted variants in ClinVar

Classification Summary

VUS64
Likely Benign3
Benign2
64
VUS
3
Likely Benign
2
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
0
0
0
Likely Pathogenic
0
0
0
0
0
VUS
0
64
0
0
64
Likely Benign
0
3
0
0
3
Benign
0
1
0
1
2
Total0680169

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

View in ClinVar →

22 pathogenic / likely-pathogenic (of 25) ClinVar copy-number / structural variants overlap HOXD9 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →

Protein Context — Lollipop Plot

HOXD9 · 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 →