DLX6

Chr 7

distal-less homeobox 6

NCBI Gene: 1750ENSG00000006377UniProt: P56179

This gene encodes a member of a homeobox transcription factor gene family similiar to the Drosophila distal-less gene. This family is comprised of at least 6 different members that encode proteins with roles in forebrain and craniofacial development. This gene is in a tail-to-tail configuration with another member of the family on the long arm of chromosome 7. [provided by RefSeq, Jul 2008]

141
ClinVar variants
19
Pathogenic / LP
0.92
pLI score· haploinsufficient
0
Active trials
Clinical Summary— DLX6
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.92). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
19 Pathogenic / Likely Pathogenic· 81 VUS of 141 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.38LOEUF
pLI 0.921
Z-score 3.02
OE 0.08 (0.03–0.38)
Highly constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
1.17Z-score
OE missense 0.73 (0.62–0.85)
105 obs / 144.6 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.08 (0.03–0.38)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.73 (0.62–0.85)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.38
0≤1.21.6
LoF obs/exp: 1 / 12.5Missense obs/exp: 105 / 144.6Syn Z: -2.27

ClinVar Variant Classifications

141 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic17
Likely Pathogenic2
VUS81
Likely Benign29
Benign11
Conflicting1
17
Pathogenic
2
Likely Pathogenic
81
VUS
29
Likely Benign
11
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
17
0
17
Likely Pathogenic
0
0
2
0
2
VUS
0
39
42
0
81
Likely Benign
0
2
5
22
29
Benign
0
0
8
3
11
Conflicting
—1
Total0417425141

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

View in ClinVar →

Protein Context — Lollipop Plot

DLX6 · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Genetic regulatory pathways of split-hand/foot malformation.
Kantaputra PN et al.·Clin Genet
2019Review
The key role of DLX6 in nasopharyngeal carcinoma: metastasis, angiogenesis and tumor immune mechanism.
Yang H et al.·Front Immunol
2025Functional
LncRNA DLX6-AS1/miR-129-5p/DLK1 axis aggravates stemness of osteosarcoma through Wnt signaling.
Zhang RM et al.·Biochem Biophys Res Commun
2018
Expression of lncRNA DLX6-AS1 in patients with hepatic carcinoma and its prognostic value.
Lin Y et al.·Biotechnol Genet Eng Rev
2024Cohort
Serum DLX6-AS1 and miR-141-3p as early diagnostic biomarkers and regulators of delayed fracture healing (DFH).
Zhang M et al.·J Orthop Surg Res
2025
Expression analysis and mutation detection of DLX5 and DLX6 in autism.
Nakashima N et al.·Brain Dev
2010
Association between lncRNAs in plasma exosomes and diabetic retinopathy.
Ye Q et al.·Front Endocrinol (Lausanne)
2022
cAMP-response element binding protein mediates podocyte injury in diabetic nephropathy by targeting lncRNA DLX6-AS1.
Zheng W et al.·Metabolism
2022
Long non-coding RNA DLX6-AS1 mediates proliferation, invasion and apoptosis of endometrial cancer cells by recruiting p300/E2F1 in DLX6 promoter region.
Zhao H et al.·J Cell Mol Med
2020
Long non-coding RNA DLX6-AS1 aggravates hepatocellular carcinoma carcinogenesis by modulating miR-203a/MMP-2 pathway.
Zhang L et al.·Biomed Pharmacother
2017
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools