DMRT1

Chr 9

doublesex and mab-3 related transcription factor 1

Also known as: CT154, DMT1

NCBI Gene: 1761ENSG00000137090UniProt: Q9Y5R6

This gene is found in a cluster with two other members of the gene family, having in common a zinc finger-like DNA-binding motif (DM domain). The DM domain is an ancient, conserved component of the vertebrate sex-determining pathway that is also a key regulator of male development in flies and nematodes. This gene exhibits a gonad-specific and sexually dimorphic expression pattern. Defective testicular development and XY feminization occur when this gene is hemizygous. [provided by RefSeq, Jul 2008]

Primary Disease Associations & Inheritance

UniProtTesticular germ cell tumor
UniProt46,XY sex reversal 4
367
ClinVar variants
124
Pathogenic / LP
0.74
pLI score
0
Active trials
Clinical Summary— DMRT1
⚡
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.74) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
124 Pathogenic / Likely Pathogenic· 102 VUS of 367 total submissions
Some data sources returned errors (1)

clinvar: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esummary.fcgi

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.48LOEUF
pLI 0.739
Z-score 2.85
OE 0.15 (0.06–0.48)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
-0.44Z-score
OE missense 1.08 (0.97–1.21)
234 obs / 215.9 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.15 (0.06–0.48)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.08 (0.97–1.21)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.48
0≤1.21.6
LoF obs/exp: 2 / 13.2Missense obs/exp: 234 / 215.9Syn Z: -3.60

ClinVar Variant Classifications

367 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic108
Likely Pathogenic16
VUS102
Likely Benign30
Benign37
Conflicting2
108
Pathogenic
16
Likely Pathogenic
102
VUS
30
Likely Benign
37
Benign
2
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
108
0
108
Likely Pathogenic
2
6
8
0
16
VUS
0
69
33
0
102
Likely Benign
0
2
9
19
30
Benign
0
3
26
8
37
Conflicting
—2
Total28018427295

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

View in ClinVar →

Protein Context — Lollipop Plot

DMRT1 · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Sex determination and maintenance: the role of DMRT1 and FOXL2.
Huang S et al.·Asian J Androl
2017Review
Systematic molecular analyses for 115 karyotypically normal men with isolated non-obstructive azoospermia.
Muranishi Y et al.·Hum Reprod
2024
Unveiling the roles of Sertoli cells lineage differentiation in reproductive development and disorders: a review.
Gao Y et al.·Front Endocrinol (Lausanne)
2024Review
Genes promoting and disturbing testis development.
Barrionuevo FJ et al.·Histol Histopathol
2012Review
Whole-genome sequencing reveals individual and cohort level insights into chromosome 9p syndromes.
Wang Y et al.·Genome Med
2025Cohort
Functional assessment of DMRT1 variants and their pathogenicity for isolated male infertility.
Emich J et al.·Fertil Steril
2023Functional
Approach to the Virilizing Girl at Puberty.
Santi M et al.·J Clin Endocrinol Metab
2021Review
Impact of iron deficiency on therapeutic outcomes in colorectal cancer patients: a single-center cohort study.
Luo Y et al.·J Transl Med
2025Cohort
Genomics of sexual cell fate transdifferentiation in the mouse gonad.
Murphy MW et al.·G3 (Bethesda)
2022Functional
Familial DMRT1-related non-obstructive azoospermia: a case report.
Severi G et al.·J Assist Reprod Genet
2024Case report
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Integrated Analysis of Testicular Histology, Sperm Quality, and Gene Expression (TGFB2, DMRT1) in Rooster Semen (Gallus gallus domesticus).
Ivershina A et al.·Animals (Basel)
2026🔓 Open Access
Sex-specific functional evolution of Dmrt1 in African clawed frogs (Xenopus), and the importance of genetic tipping points in developmental biology.
Kukoly LM et al.·PLoS Genet
2026🔓 Open AccessFunctional
Sexual Dimorphic Expression of Dmrt1 in Adult Japanese Gecko (Gekko japonicus).
Ping J et al.·Sex Dev
2025
Transposable Element-Mediated Cis-Regulation Drives the Evolution of dmrt1 as a Candidate Master Sex-Determining Gene in Black Carp.
Guo J et al.·Mol Biol Evol
2025🔓 Open Access
Gene Duplication, Translocation, and Molecular Evolution of Dmrt1 and Related Sex-Determining Genes in Anurans.
Shinde SS et al.·Biomolecules
2025🔓 Open Access
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools