DMRT3

Chr 9

doublesex and mab-3 related transcription factor 3

NCBI Gene: 58524 ENSG00000064218 UniProt: Q9NQL9 OMIM: 614754

Encodes a transcription factor that regulates spinal cord interneuron specification and development of locomotor circuits controlling coordinated limb movements and gait. Mutations cause autosomal recessive developmental and epileptic encephalopathy-52 with abnormal gait and movement disorders. This gene is highly constrained against loss-of-function variants, indicating that biallelic mutations likely represent severe disruptions to normal protein function.

OMIM ResearchSummary from RefSeq, UniProt

Probable transcription factor that plays a role in configuring the spinal circuits controlling stride in vertebrates. Involved in neuronal specification within specific subdivision of spinal cord neurons and in the development of a coordinated locomotor network controlling limb movements. May regulate transcription during sexual development (By similarity)

OMIM ResearchGenerating clinical summary…

DNmechanismLOEUF 1.17

Clinical Summary— DMRT3

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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?

1.17LOEUF

pLI 0.000

Z-score 1.09

OE 0.69 (0.42–1.17)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-1.69Z-score

OE missense 1.30 (1.18–1.42)

335 obs / 258.5 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.69 (0.42–1.17)

0≤0.351.4

Missense OE?1.30 (1.18–1.42)

0≤0.61.4

Synonymous OE?1.24

0≤1.21.6

LoF obs/exp: 10 / 14.5Missense obs/exp: 335 / 258.5Syn Z: -2.09

This gene — mechanism propensity

0.6647th %ile

GOF

0.3789th %ile

LOF

0.49top 25%

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

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.

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