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GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 15 days ago
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DMRT3
doublesex and mab-3 related transcription factor 3
Chromosome 9 Β· 9p24.3
NCBI Gene: 58524Ensembl: ENSG00000064218.6HGNC: HGNC:13909UniProt: Q9NQL9
17PubMed Papers
20Diseases
0Drugs
1Pathogenic Variants
FUNCTIONAL ROLE
Transcription Factor
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
protein bindingsequence-specific double-stranded DNA bindingRNA polymerase II cis-regulatory region sequence-specific DNA bindingDNA-binding transcription factor activity, RNA polymerase II-specificneurodegenerative diseaseprimary ovarian insufficiencymale reproductive organ cancersynovium disorder
✦AI Summary

DMRT3 is a transcription factor located on chromosome 9 that functions primarily in configuring spinal circuits controlling locomotor coordination. In vertebrates, DMRT3 is expressed in spinal cord interneurons and plays a critical role in developing coordinated limb movement networks 1. A specific missense mutation (Ser301STOP) in DMRT3 causes the 'gaited' phenotype in horses, enabling comfortable ambling and pacing gaits, with this allele showing high frequency in gaited breeds and harness racing horses 12. Beyond locomotion, DMRT3 participates in sexual differentiation through regulation of estrogen receptor 1 (ESR1) expression. In disorders of sex development (DSDs), mutations in DMRT3 interact with OAS3 to prevent ESR1 mRNA degradation, causing 46,XY sex reversal and hypospadias 3. Recent evidence indicates DMRT3 transcriptionally regulates the lncRNA OIP5-AS1, which promotes pyroptosis in bronchial epithelial cells during asthma by stabilizing YAP mRNA 4. Clinically, DMRT3 deletion is associated with 9p deletion syndrome, affecting 83% of individuals with this condition 56. A deletion of a DMRT3 enhancer element has been linked to spastic cerebral palsy pathogenesis through impaired forebrain development and gait coordination 7. Additionally, DMRT3 shows aberrant expression in multiple cancer types, correlating with poor prognosis and potential chemoresistance 8.

Sources cited
1
DMRT3 Ser301STOP mutation causes gaitedness in horses; expressed in spinal cord interneurons and important for limb movement coordination
PMID: 27505236
2
DMRT3 mutations (A>C at position 878) found in Indian horse and donkey breeds; major impact on gaitedness at high frequency in gaited breeds
PMID: 37149793
3
DMRT3 mutations interact with OAS3 to regulate ESR1 expression in human sexual differentiation; involved in disorders of sex development
PMID: 32553473
4
DMRT3 transcriptionally upregulates lncRNA OIP5-AS1, which promotes pyroptosis in asthma through EIF4A3/YAP axis
PMID: 39287912
5
DMRT3 is one of 24 genes identified as important for majority (83%) of individuals with 9p deletion syndrome
PMID: 40196253
6
DMRT3 identified as important gene in 9p deletion syndrome through whole-genome sequencing and spatial transcriptomics
PMID: 41137173
7
DMRT3 enhancer deletion linked to spastic cerebral palsy pathogenesis; DMRT3 expressed in developing forebrain and spinal interneurons as locomotion coordinator
PMID: 29305858
8
DMRT3 aberrantly expressed in pan-cancer; high expression associated with poor overall survival in multiple cancer types; may promote tumorigenesis
PMID: 36551704
Disease Associationsβ“˜20
neurodegenerative diseaseOpen Targets
0.48Moderate
primary ovarian insufficiencyOpen Targets
0.27Weak
male reproductive organ cancerOpen Targets
0.19Weak
synovium disorderOpen Targets
0.11Weak
Uterine leiomyomaOpen Targets
0.10Suggestive
uterine fibroidOpen Targets
0.09Suggestive
cancerOpen Targets
0.07Suggestive
neoplasmOpen Targets
0.07Suggestive
Dupuytren ContractureOpen Targets
0.06Suggestive
otosclerosisOpen Targets
0.05Suggestive
infantile-onset generalized dyskinesia with orofacial involvementOpen Targets
0.05Suggestive
ankylosing spondylitisOpen Targets
0.05Suggestive
biliary tract diseaseOpen Targets
0.05Suggestive
Increased total eosinophil countOpen Targets
0.05Suggestive
Primary lateral sclerosisOpen Targets
0.05Suggestive
fibroblastic disorderOpen Targets
0.05Suggestive
familial amyotrophic lateral sclerosisOpen Targets
0.05Suggestive
Autosomal recessive cerebellar ataxia - saccadic intrusionOpen Targets
0.04Suggestive
juvenile primary lateral sclerosisOpen Targets
0.04Suggestive
Palmar FibromatosisOpen Targets
0.04Suggestive
Pathogenic Variants1
NM_021240.4(DMRT3):c.1327C>T (p.Pro443Ser)Likely pathogenic
Premature ovarian failure
β˜…β˜†β˜†β˜†2020β†’ Residue 443
View on ClinVar β†—
Related Genes
ZNG1ACo-mentioned in literature100%BRD10Co-mentioned in literature100%PLPP6Co-mentioned in literature67%DMRTA1Shared pathway50%DMRTA2Shared pathway50%DMRTB1Shared pathway50%
Tissue Expression6 tissues
Brain
100%
Bone Marrow
3%
Lung
3%
Liver
0%
Heart
0%
Ovary
0%
Gene Interaction Network
Click a node to explore
DMRT3ZNG1ABRD10PLPP6DMRTA1DMRTA2DMRTB1
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted Β· UniProt Q9NQL9
View on AlphaFold β†—
Constraintβ“˜
LOEUFβ“˜
1.27LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF0.93 [0.69–1.27]
RankingsWhere DMRT3 stands among ~20K protein-coding genes
  • #14,979of 20,598
    Most Researched17
  • #5,410of 5,498
    Most Pathogenic Variants1
  • #13,426of 17,882
    Most Constrained (LOEUF)1.27
Genes detectedDMRT3
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
Identification and characterization of single nucleotide polymorphisms in
PMID: 37149793
Anim Biotechnol Β· 2023
1.00
2
Whole-Genome Sequencing Reveals Individual and Cohort Level Insights into Chromosome 9p Syndromes.
PMID: 40196253
medRxiv Β· 2025
0.90
3
Comprehensive Analysis of DMRT3 as a Potential Biomarker Associated with the Immune Infiltration in a Pan-Cancer Analysis and Validation in Lung Adenocarcinoma.
PMID: 36551704
Cancers (Basel) Β· 2022
0.80
4
The origin of ambling horses.
PMID: 27505236
Curr Biol Β· 2016
0.70
5
New findings in disorders of sex development: role of DMRT3 and OAS3.
PMID: 32532494
Fertil Steril Β· 2020
0.60