DMRTA2

Chr 1

DMRT like family A2

Also known as: DMRT5

NCBI Gene: 63950 ENSG00000142700 UniProt: Q96SC8 OMIM: 614804

DMRTA2 encodes a transcription factor that binds DNA and regulates gene expression, with predicted roles in nervous system development and sexual differentiation. Mutations cause autosomal dominant intellectual disability with developmental delay, and the gene is highly constrained against loss-of-function variants (pLI 0.92, LOEUF 0.38). The condition primarily affects neurodevelopment with onset in early childhood.

OMIM ResearchSummary from RefSeq, UniProt

Enables sequence-specific double-stranded DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II and sex differentiation. Predicted to act upstream of or within several processes, including nervous system development; positive regulation of neuroblast proliferation; and stem cell fate specification. Predicted to be located in chromatin. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.38

Clinical Summary— DMRTA2

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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.

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ClinVar Variants

85 VUS of 92 total submissions

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?

0.38LOEUF

pLI 0.916

Z-score 2.61

OE 0.00 (0.00–0.38)

Highly constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

1.40Z-score

OE missense 0.72 (0.63–0.83)

141 obs / 196.3 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.00 (0.00–0.38)

0≤0.351.4

Missense OE?0.72 (0.63–0.83)

0≤0.61.4

Synonymous OE?1.15

0≤1.21.6

LoF obs/exp: 0 / 8.0Missense obs/exp: 141 / 196.3Syn Z: -1.13

This gene — mechanism propensity

0.3991th %ile

GOF

0.3293th %ile

LOF

0.81top 5%

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

LOFprediction above median · LOEUF 0.38

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

92 submitted variants in ClinVar

ClinVar

Classification Summary

VUS85

Likely Benign2

Benign3

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	85	0	85
Likely Benign	2	0	2
Benign	1	2	3
Total	88	2	90

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

View in ClinVar →

7 pathogenic / likely-pathogenic (of 12) ClinVar copy-number / structural variants overlap DMRTA2 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →