DLX4

Chr 17AD

distal-less homeobox 4

Also known as: BP1, DLX7, DLX8, DLX9, OFC15

The DLX4 protein is a homeobox transcription factor that functions in palatogenesis during embryonic development and may act as a repressor of beta-globin gene expression. Mutations cause orofacial cleft 15, inherited in an autosomal dominant pattern. The pathogenic mechanism likely involves disrupted transcriptional regulation of genes required for normal palatal development.

Summary from RefSeq, OMIM, UniProt
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Primary Disease Associations & Inheritance

?Orofacial cleft 15MIM #616788
AD
UniProtNon-syndromic orofacial cleft 15
0
Active trials
4
Pubs (1 yr)
0
P/LP submissions
P/LP missense
1.07
LOEUF
Multiple*
Mechanism· predicted
Clinical SummaryDLX4
Population Constraint (gnomAD)
Low constraint (pLI 0.02) — loss-of-function variants are relatively tolerated in the population.
Some data sources returned errors (1)

ensembl: TimeoutError: The operation was aborted due to timeout

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
-0.02Z-score
OE missense 1.00 (0.871.16)
128 obs / 127.4 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.47 (0.231.07)
00.351.4
Missense OE1.00 (0.871.16)
00.61.4
Synonymous OE0.94
01.21.6
LoF obs/exp: 4 / 8.6Missense obs/exp: 128 / 127.4Syn Z: 0.40
DN
0.6938th %ile
GOF
0.4183th %ile
LOF
0.54top 25%

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and loss-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

DNprediction above median
LOF1 literature citation

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.

Literature Evidence

LOFWild-type human DLX4, but not mutant DLX4_c.546delG, could activate two murine Dlx conserved regulatory elements, implying that the mutation caused haploinsufficiency.PMID:25954033

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

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

DLX4 · 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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Clinical Literature
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