DLX1

Chr 2

distal-less homeobox 1

NCBI Gene: 1745 ENSG00000144355 UniProt: P56177 OMIM: 600029

This gene encodes a member of a homeobox transcription factor gene family similiar to the Drosophila distal-less gene. The encoded protein is localized to the nucleus where it may function as a transcriptional regulator of signals from multiple TGF-{beta} superfamily members. The encoded protein may play a role in the control of craniofacial patterning and the differentiation and survival of inhibitory neurons in the forebrain. This gene is located in a tail-to-tail configuration with another member of the family on the long arm of chromosome 2. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Jul 2008]

OMIM Research

OMIM ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.29

Clinical Summary— DLX1

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Population Constraint (gnomAD)

Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.96). One damaged copy is likely sufficient to cause disease.

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ClinVar Variants

23 VUS of 27 total submissions

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Clinical Trials

1 active or recruiting trial — potential therapeutic options may be available

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.29LOEUF

pLI 0.962

Z-score 2.96

OE 0.00 (0.00–0.29)

Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?

1.82Z-score

OE missense 0.57 (0.47–0.69)

80 obs / 140.6 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.00 (0.00–0.29)

0≤0.351.4

Missense OE?0.57 (0.47–0.69)

0≤0.61.4

Synonymous OE?1.34

0≤1.21.6

LoF obs/exp: 0 / 10.2Missense obs/exp: 80 / 140.6Syn Z: -2.06

This gene — mechanism propensity

0.3793th %ile

GOF

0.2099th %ile

LOF

0.89top 5%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.29

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

27 submitted variants in ClinVar

ClinVar

Classification Summary

VUS23

Likely Benign1

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Total
Pathogenic	0	0
Likely Pathogenic	0	0
VUS	23	23
Likely Benign	1	1
Benign	0	0
Total	24	24

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

View in ClinVar →

21 pathogenic / likely-pathogenic (of 24) ClinVar copy-number / structural variants overlap DLX1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →