DMRT3

Chr 9

doublesex and mab-3 related transcription factor 3

Also known as: DMRTA3

NCBI Gene: 58524ENSG00000064218UniProt: Q9NQL9OMIM: 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.

OMIMResearchSummary from RefSeq, UniProt
DNmechanismLOEUF 1.17
Clinical Summary— DMRT3
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
56 unique Pathogenic / Likely Pathogenic· 118 VUS of 200 total submissions
Explore recent and relevant literature in Research Assistant →

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 OE0.69 (0.42–1.17)
0≤0.351.4
Missense OE1.30 (1.18–1.42)
0≤0.61.4
Synonymous OE1.24
0≤1.21.6
LoF obs/exp: 10 / 14.5Missense obs/exp: 335 / 258.5Syn Z: -2.09
DN
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.

ClinVar Variant Classifications

200 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic50
Likely Pathogenic6
VUS118
Likely Benign11
Benign7
50
Pathogenic
6
Likely Pathogenic
118
VUS
11
Likely Benign
7
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
50
0
50
Likely Pathogenic
0
1
5
0
6
VUS
0
100
18
0
118
Likely Benign
0
7
0
4
11
Benign
0
4
0
3
7
Total0112737192

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

View in ClinVar →

Protein Context — Lollipop Plot

DMRT3 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Adult spinal Dmrt3 neurons receive direct somatosensory inputs from ipsi- and contralateral primary afferents and from brainstem motor nuclei
Vieillard J et al.·J Comp Neurol
2023
Comprehensive Analysis of DMRT3 as a Potential Biomarker Associated with the Immune Infiltration in a Pan-Cancer Analysis and Validation in Lung Adenocarcinoma
Yang D et al.·Cancers (Basel)
2022
Single Cell Transcriptomic Analysis of Spinal Dmrt3 Neurons in Zebrafish and Mouse Identifies Distinct Subtypes and Reveal Novel Subpopulations Within the dI6 Domain
Iglesias González AB et al.·Front Cell Neurosci
2021Functional
Genomic analysis of gaits and racing performance of the French trotter
Ricard A et al.·J Anim Breed Genet
2021
Genome-wide identification and comparative analysis of Dmrt genes in echinoderms
Wang Q et al.·Sci Rep
2023
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients