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10 sources retrieved Β· Most recent: April 2026 Β· Index updated 15 days ago
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DMRT1
doublesex and mab-3 related transcription factor 1
Chromosome 9 Β· 9p24.3
NCBI Gene: 1761Ensembl: ENSG00000137090.12HGNC: HGNC:2934UniProt: H3BN61
49PubMed Papers
22Diseases
0Drugs
9Pathogenic Variants
FUNCTIONAL ROLE
Transcription Factor
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
sequence-specific double-stranded DNA bindingidentical protein bindingnucleusSertoli cell differentiationneurodegenerative diseaseuterine fibroidtesticular carcinomaTesticular Germ Cell Tumor
✦AI Summary

DMRT1 (doublesex and mab-3 related transcription factor 1) is a critical transcriptional regulator that plays essential roles in sex determination, gonadal development, and germ cell biology. In mammalian development, DMRT1 functions as a key factor in testis determination by working alongside SRY to upregulate SOX9 expression in supporting cells, thereby initiating the testicular genetic cascade 1. The protein acts as a pioneer transcription factor with unique DNA-binding properties, capable of accessing closed chr9 and collaborating with SOX9 to maintain and reprogram sexual cell fate 2. DMRT1 is crucial for germline commitment, promoting epigenetic resetting through global enrichment of 5-hydroxymethylcytosine and demethylation at DMRT1 binding sites 3. Beyond embryonic development, DMRT1 maintains adult gonadal identity through a regulatory relationship with FOXL2, with disruption potentially causing sex reversal even in adulthood 4. Clinically, DMRT1 haploinsufficiency is associated with 46,XY disorders of sex development and complete gonadal dysgenesis in humans 2. The gene is also implicated in chromosome 9 deletion syndromes, where it represents one of 24 critical genes affecting the majority of patients 5. Environmental toxins can disrupt DMRT1 expression, contributing to spermatogenesis disorders 6.

Sources cited
1
DMRT1 is required alongside SRY for testis determination by upregulating SOX9 in supporting cells
PMID: 37847154
2
DMRT1 functions as a pioneer transcription factor with unique DNA-binding properties and collaborates with SOX9
PMID: 34515237
3
DMRT1 promotes germline commitment through epigenetic resetting and global 5-hydroxymethylcytosine enrichment
PMID: 37709822
4
DMRT1 maintains adult gonadal identity in relationship with FOXL2, with disruption causing potential sex reversal
PMID: 28091399
5
DMRT1 is one of 24 critical genes in chromosome 9p deletion syndromes affecting majority of patients
PMID: 40196253
6
Environmental toxins can disrupt DMRT1 expression contributing to spermatogenesis disorders
PMID: 39295530
Disease Associationsβ“˜22
neurodegenerative diseaseOpen Targets
0.53Moderate
uterine fibroidOpen Targets
0.49Moderate
testicular carcinomaOpen Targets
0.49Moderate
Testicular Germ Cell TumorOpen Targets
0.46Moderate
Uterine leiomyomaOpen Targets
0.45Moderate
male infertility with azoospermia or oligozoospermia due to single gene mutationOpen Targets
0.37Weak
male infertilityOpen Targets
0.37Weak
uterine benign neoplasmOpen Targets
0.35Weak
Testicular Non-Seminomatous Germ Cell TumorOpen Targets
0.33Weak
testicular neoplasmOpen Targets
0.33Weak
tonsillitisOpen Targets
0.32Weak
azoospermiaOpen Targets
0.32Weak
46,XY sex reversal 4Open Targets
0.31Weak
otosclerosisOpen Targets
0.31Weak
autoimmune thyroid diseaseOpen Targets
0.30Weak
basal cell carcinomaOpen Targets
0.25Weak
Increased total eosinophil countOpen Targets
0.24Weak
skin cancerOpen Targets
0.20Weak
skin neoplasmOpen Targets
0.14Weak
non-melanoma skin carcinomaOpen Targets
0.14Weak
46,XY sex reversal 4UniProt
Testicular germ cell tumorUniProt
Pathogenic Variants9
NM_021951.3(DMRT1):c.879C>G (p.Tyr293Ter)Likely pathogenic
Male infertility
β˜…β˜†β˜†β˜†2024β†’ Residue 293
NM_021951.3(DMRT1):c.968-11_977delLikely pathogenic
Male infertility
β˜…β˜†β˜†β˜†2024
NM_021951.3(DMRT1):c.146dup (p.Ser50fs)Likely pathogenic
Male infertility
β˜…β˜†β˜†β˜†2024β†’ Residue 50
NM_021951.3(DMRT1):c.315C>G (p.Cys105Trp)Likely pathogenic
not provided
β˜…β˜†β˜†β˜†2024β†’ Residue 105
NM_021951.3(DMRT1):c.425C>T (p.Ala142Val)Likely pathogenic
Male infertility with azoospermia or oligozoospermia due to single gene mutation
β˜…β˜†β˜†β˜†2023β†’ Residue 142
NM_021951.3(DMRT1):c.395G>A (p.Gly132Asp)Likely pathogenic
Male infertility with azoospermia or oligozoospermia due to single gene mutation
β˜…β˜†β˜†β˜†2023β†’ Residue 132
NM_021951.3(DMRT1):c.982A>G (p.Ser328Gly)Likely pathogenic
Male infertility with azoospermia or oligozoospermia due to single gene mutation
β˜…β˜†β˜†β˜†2023β†’ Residue 328
NM_021951.3(DMRT1):c.344T>A (p.Met115Lys)Likely pathogenic
Non-obstructive azoospermia
β˜…β˜†β˜†β˜†2021β†’ Residue 115
NM_021951.3(DMRT1):c.332G>T (p.Arg111Met)Likely pathogenic
46,XY sex reversal 4
β˜…β˜†β˜†β˜†2017β†’ Residue 111
View on ClinVar β†—
Related Genes
NR5A1Protein interaction95%SOX9Protein interaction92%KANK1Protein interaction92%DHHProtein interaction90%SOX3Protein interaction89%GATA4Protein interaction86%
Tissue Expression6 tissues
Brain
100%
Bone Marrow
22%
Lung
0%
Heart
0%
Liver
0%
Ovary
0%
Gene Interaction Network
Click a node to explore
DMRT1NR5A1SOX9KANK1DHHSOX3GATA4
PROTEIN STRUCTURE
Preparing viewer…
PDB4YJ0 Β· 3.81 Γ… Β· X-ray
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
0.43Moderately Constrained
pLIβ“˜
1.00Intolerant
Observed/Expected LoF0.23 [0.13–0.43]
RankingsWhere DMRT1 stands among ~20K protein-coding genes
  • #8,934of 20,598
    Most Researched49
  • #2,970of 5,498
    Most Pathogenic Variants9
  • #2,329of 17,882
    Most Constrained (LOEUF)0.43 Β· top quartile
Genes detectedDMRT1
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
Cellular Iron Metabolism and Regulation.
PMID: 31456203
Adv Exp Med Biol Β· 2019
1.00
2
DMRT1 regulates human germline commitment.
PMID: 37709822
Nat Cell Biol Β· 2023
0.90
3
Short Chain Chlorinated Paraffins Impaired Spermatogenesis Process in Mice via Inhibiting Ξ±-KG/TET Enzyme Activity.
PMID: 39295530
Environ Sci Technol Β· 2024
0.80
4
PMID: 37847154
Elife Β· 2023
0.70
5
Non-transferrin-bound iron transporters.
PMID: 30316781
Free Radic Biol Med Β· 2019
0.60