DLX5

Chr 7ARAD

distal-less homeobox 5

The protein is a homeobox transcription factor that regulates bone development by activating genes essential for osteoblast differentiation and chondrogenesis. Mutations cause split-hand/split-foot malformation, typically involving limb defects present at birth, and follow an autosomal dominant inheritance pattern. The gene shows moderate intolerance to loss-of-function variants (LOEUF 0.68), consistent with its role in developmental processes.

OMIMResearchSummary from RefSeq, UniProt
MultiplemechanismAR/ADLOEUF 0.682 OMIM phenotypes
Clinical SummaryDLX5
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.26) despite low pLI — interpret in context.
📋
ClinVar Variants
29 unique Pathogenic / Likely Pathogenic· 56 VUS of 119 total submissions
Some data sources returned errors (1)

ncbi: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esearch.fcgi

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.68LOEUF
pLI 0.218
Z-score 2.30
OE 0.26 (0.120.68)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.04Z-score
OE missense 0.99 (0.871.13)
166 obs / 167.4 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.26 (0.120.68)
00.351.4
Missense OE0.99 (0.871.13)
00.61.4
Synonymous OE1.19
01.21.6
LoF obs/exp: 3 / 11.4Missense obs/exp: 166 / 167.4Syn Z: -1.29
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
limitedDLX5-related split-hand and foot malformationOTHERAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.6259th %ile
GOF
0.2796th %ile
LOF
0.68top 10%

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Literature Evidence

LOFMutations of the DLX5 (distal-less) transcription factor-encoding gene in chromosome 7 cause SHFM through haploinsufficiency, but the vast majority of cases result from heterozygous chromosomal aberrations of the region without mutating the DLX5 gene.PMID:27821526

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

ClinVar Variant Classifications

119 submitted variants in ClinVar

Classification Summary

Pathogenic22
Likely Pathogenic7
VUS56
Likely Benign18
Benign9
Conflicting1
22
Pathogenic
7
Likely Pathogenic
56
VUS
18
Likely Benign
9
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
2
2
18
0
22
Likely Pathogenic
2
3
2
0
7
VUS
6
44
5
1
56
Likely Benign
0
3
4
11
18
Benign
0
0
7
2
9
Conflicting
1
Total10523614113

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

View in ClinVar →

Protein Context — Lollipop Plot

DLX5 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗