DLX2

Chr 2

distal-less homeobox 2

Also known as: TES-1, TES1

NCBI Gene: 1746 ENSG00000115844 UniProt: Q07687 OMIM: 126255

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. The DLX proteins are postulated to play a role in forebrain and craniofacial development. This gene is located in a tail-to-tail configuration with another member of the gene family on the long arm of chromosome 2. [provided by RefSeq, Jul 2008]

OMIM Research

OMIM ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.25

Clinical Summary— DLX2

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Population Constraint (gnomAD)

Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.98). One damaged copy is likely sufficient to cause disease.

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ClinVar Variants

44 VUS of 49 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.25LOEUF

pLI 0.978

Z-score 3.18

OE 0.00 (0.00–0.25)

Highly constrained

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

Missense Constraint?

0.95Z-score

OE missense 0.80 (0.70–0.92)

141 obs / 176.5 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.00 (0.00–0.25)

0≤0.351.4

Missense OE?0.80 (0.70–0.92)

0≤0.61.4

Synonymous OE?0.96

0≤1.21.6

LoF obs/exp: 0 / 11.8Missense obs/exp: 141 / 176.5Syn Z: 0.28

This gene — mechanism propensity

0.4587th %ile

GOF

0.2298th %ile

LOF

0.87top 5%

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

LOFprediction above median · LOEUF 0.25

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

49 submitted variants in ClinVar

ClinVar

Classification Summary

VUS44

Likely Benign1

Benign2

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Synonymous	Total
Pathogenic	0	0	0
Likely Pathogenic	0	0	0
VUS	44	0	44
Likely Benign	0	1	1
Benign	0	2	2
Total	44	3	47

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

View in ClinVar →

20 pathogenic / likely-pathogenic (of 23) ClinVar copy-number / structural variants overlap DLX2 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →