DLX3

Chr 17AD

distal-less homeobox 3

Also known as: AI4, TDO

NCBI Gene: 1747UniProt: O60479

Many vertebrate homeo box-containing genes have been identified on the basis of their sequence similarity with Drosophila developmental genes. Members of the Dlx gene family contain a homeobox that is related to that of Distal-less (Dll), a gene expressed in the head and limbs of the developing fruit fly. The Distal-less (Dlx) family of genes comprises at least 6 different members, DLX1-DLX6. Trichodentoosseous syndrome (TDO), an autosomal dominant condition, has been correlated with DLX3 gene mutation. This gene is located in a tail-to-tail configuration with another member of the gene family on the long arm of chromosome 17. Mutations in this gene have been associated with the autosomal dominant conditions trichodentoosseous syndrome and amelogenesis imperfecta with taurodontism. [provided by RefSeq, Jul 2008]

Primary Disease Associations & Inheritance

Amelogenesis imperfecta, type IVMIM #104510
AD
Trichodontoosseous syndromeMIM #190320
AD
UniProtTrichodentoosseous syndrome
0
Active trials
0
ClinVar variants
0
Pathogenic / LP
1.0
Missense Z
0.97
LOEUF
6
Pubs (2 yr)
Clinical Summary— DLX3
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
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.
0.97LOEUF
pLI 0.003
Z-score 1.65
OE 0.49 (0.27–0.97)
Tolerant

Typical tolerance to LoF variation

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.
0.96Z-score
OE missense 0.79 (0.69–0.92)
134 obs / 169.0 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.0.49 (0.27–0.97)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.79 (0.69–0.92)
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.0.91
0≤1.21.6
LoF obs/exp: 6 / 12.2Missense obs/exp: 134 / 169.0Syn Z: 0.66

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

DLX3 · 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

Amelogenesis imperfecta, type IV

MIM #104510

Molecular basis of disorder known

Autosomal dominant

Trichodontoosseous syndrome

MIM #190320

Molecular basis of disorder known

Autosomal dominant
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Novel DLX3 variant identified in a family with tricho-dento-osseous syndrome.
Liu H et al.·Arch Oral Biol
2022
Association between malocclusions and amelogenesis imperfecta genotype and phenotype: A systematic review.
Broutin A et al.·Int Orthod
2023Review
The homeoprotein DLX3 and tumor suppressor p53 co-regulate cell cycle progression and squamous tumor growth.
Palazzo E et al.·Oncogene
2016
A heterozygous missense variant in DLX3 leads to uterine leiomyomas and pregnancy losses in a consanguineous Iranian family.
Saboori-Darabi S et al.·Gene
2023
Novel DLX3 variants in amelogenesis imperfecta with attenuated tricho-dento-osseous syndrome.
Whitehouse LLE et al.·Oral Dis
2019
Woolly hair in tricho-dento-osseous syndrome.
Perandones-González H et al.·Pediatr Dermatol
2023Case report
Dlx3 transcriptional regulation of osteoblast differentiation: temporal recruitment of Msx2, Dlx3, and Dlx5 homeodomain proteins to chromatin of the osteocalcin gene.
Hassan MQ et al.·Mol Cell Biol
2004
COADREADx: A comprehensive algorithmic dissection of colorectal cancer unravels salient biomarkers and actionable insights into its discrete progression.
Palaniappan A et al.·PeerJ
2024
Developmental biology and genetics of dental malformations.
Hu JC et al.·Orthod Craniofac Res
2007Review
DLX3 c.561_562delCT mutation causes attenuated phenotype of tricho-dento-osseous syndrome.
Wright JT et al.·Am J Med Genet A
2008
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.

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External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients