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10 sources retrieved Β· Most recent: April 2026 Β· Index updated 15 days ago
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DMRT2
doublesex and mab-3 related transcription factor 2
Chromosome 9 Β· 9p24.3
NCBI Gene: 10655Ensembl: ENSG00000173253.17HGNC: HGNC:2935UniProt: Q05C20
17PubMed Papers
20Diseases
0Drugs
2Pathogenic Variants
FUNCTIONAL ROLE
Transcription Factor
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
protein bindingregulation of transcription by RNA polymerase IIsex differentiationDNA-binding transcription factor activity, RNA polymerase II-specificDupuytren Contracturetype 2 diabetes mellitusfibroblastic disorderPalmar Fibromatosis
✦AI Summary

DMRT2 is a transcriptional regulator located on chromosome 9 that functions as a DNA-binding transcription factor with dual roles in embryonic development and metabolic regulation. During embryogenesis, DMRT2 acts as a transcriptional activator that directly regulates MYF5 expression through sequence-specific binding to the early epaxial enhancer, playing a critical role in somitogenesis and somite differentiation into sclerotome, dermomyotome, and myotome 1. The gene generates multiple transcript isoforms with distinct coding potential, including bicistronic variants encoding additional polypeptides 1. In the adult kidney, DMRT2 demonstrates antagonistic regulation with transcription factors Hmx2 and Hmx3 to specify intercalated cell subtypes 2. DMRT2 promotes type A intercalated cell differentiation while repressing type B identity through mutually exclusive expression patterns, essential for maintaining systemic acid-base homeostasis 3. Additionally, DMRT2 interacts with the farnesoid X receptor (FXR) in adipose tissue to improve insulin sensitivity and attenuate HDF-induced insulin resistance 4. Clinically, DMRT2 deletions occur in 9p deletion syndrome, which affects diverse developmental and physiological processes 56. The gene's downregulation in insulin-resistant states highlights its metabolic significance beyond developmental functions.

Sources cited
1
DMRT2 generates multiple transcript isoforms including bicistronic variants; location on distal 9p and candidacy for sex reversal investigation
PMID: 10729224
2
DMRT2 directs intercalated cell type A identity through antagonistic interaction with Hmx2/3; CRISPR removal causes IC subtype switching
PMID: 40354537
3
DMRT2 interacts with FXR and improves insulin resistance in adipocytes through positive regulation of FXR transcription activity
PMID: 35250844
4
DMRT2 identified as one of 24 prioritized genes important for majority (83%) of individuals with 9p deletion syndrome
PMID: 40196253
5
DMRT2 promotes type A intercalated cell differentiation while repressing type B identity; mutually exclusive expression with Hmx2 essential for IC subtype specification
PMID: 41051882
6
DMRT2 among 24 genes identified through whole-genome sequencing as important for majority of 9p deletion syndrome cases
PMID: 41137173
Disease Associationsβ“˜20
Dupuytren ContractureOpen Targets
0.43Moderate
type 2 diabetes mellitusOpen Targets
0.42Moderate
fibroblastic disorderOpen Targets
0.35Weak
Palmar FibromatosisOpen Targets
0.33Weak
ankylosing spondylitisOpen Targets
0.31Weak
metabolic syndromeOpen Targets
0.31Weak
fasciitisOpen Targets
0.28Weak
ovarian dysfunctionOpen Targets
0.28Weak
lumbar disc herniationOpen Targets
0.28Weak
Uterine leiomyomaOpen Targets
0.28Weak
androgenetic alopeciaOpen Targets
0.27Weak
ocular hypotensionOpen Targets
0.27Weak
sign or symptomOpen Targets
0.27Weak
Inguinal herniaOpen Targets
0.25Weak
jaw diseaseOpen Targets
0.25Weak
placenta praeviaOpen Targets
0.21Weak
cervical carcinomaOpen Targets
0.20Weak
bone remodeling diseaseOpen Targets
0.20Weak
Abruptio PlacentaeOpen Targets
0.19Weak
response to antihypertensive drugOpen Targets
0.19Weak
Pathogenic Variants2
NM_181872.6(DMRT2):c.129del (p.Asp43fs)Likely pathogenic
See cases|Spondylocostal dysostosis 7, autosomal recessive
β˜…β˜†β˜†β˜†β†’ Residue 43
NM_181872.6(DMRT2):c.1A>T (p.Met1Leu)Pathogenic
not provided
β˜†β˜†β˜†β˜†2026β†’ Residue 1
View on ClinVar β†—
Related Genes
DMRTA1Shared pathway100%DMRTA2Shared pathway100%DMRTB1Shared pathway100%BRD10Co-mentioned in literature100%ZNG1ACo-mentioned in literature100%SRYProtein interaction81%
Tissue Expression6 tissues
Brain
100%
Lung
44%
Heart
15%
Bone Marrow
1%
Ovary
1%
Liver
0%
Gene Interaction Network
Click a node to explore
DMRT2DMRTA1DMRTA2DMRTB1BRD10ZNG1ASRY
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted Β· UniProt Q05C20
View on AlphaFold β†—
Constraintβ“˜
LOEUFβ“˜
1.28LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF0.96 [0.72–1.28]
RankingsWhere DMRT2 stands among ~20K protein-coding genes
  • #14,978of 20,598
    Most Researched17
  • #4,569of 5,498
    Most Pathogenic Variants2
  • #13,481of 17,882
    Most Constrained (LOEUF)1.28
Genes detectedDMRT2
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
The human doublesex-related gene, DMRT2, is homologous to a gene involved in somitogenesis and encodes a potential bicistronic transcript.
PMID: 10729224
Genomics Β· 2000
1.00
2
Dmrt2 and Hmx2 direct intercalated cell diversity in the mammalian kidney through antagonistic and supporting regulatory processes.
PMID: 40354537
Proc Natl Acad Sci U S A Β· 2025
0.90
3
DMRT2 Interacts With FXR and Improves Insulin Resistance in Adipocytes and a Mouse Model.
PMID: 35250844
Front Endocrinol (Lausanne) Β· 2021
0.80
4
Whole-Genome Sequencing Reveals Individual and Cohort Level Insights into Chromosome 9p Syndromes.
PMID: 40196253
medRxiv Β· 2025
0.70
5
linc-ADAIN, a human adipose lincRNA, regulates adipogenesis by modulating KLF5 and IL-8 mRNA stability.
PMID: 38753486
Cell Rep Β· 2024
0.60