DMRT1
Doublesex and mab-3 related transcription factor 1
Gene Information Card
| Symbol | DMRT1 |
|---|---|
| Full Name | Doublesex and mab-3 related transcription factor 1 |
| Gene Type | protein-coding |
| Chromosomal Location | 9p24.3 |
| NCBI Gene ID | 1761 ncbi.nlm.nih.gov/gene/1761 |
| Ensembl ID | ENSG00000136997 |
| UniProt ID | Q9Y5R6 |
| OMIM ID | 602424 |
| HGNC ID | 2934 |
| Aliases | DMT1, DMRT1a, DMRT1b, CT93, testis-specific transcription factor |
Description
DMRT1 (Doublesex and mab-3 related transcription factor 1) is a protein-coding gene located on chromosome 9p24.3. It encodes a transcription factor containing a DM domain, which is critical for male sex determination and testicular development. DMRT1 is expressed predominantly in the testis and plays a key role in Sertoli cell differentiation and maintenance of male germ cells. Loss-of-function mutations are associated with 46,XY disorders of sex development (DSD), including complete gonadal dysgenesis. The gene is also implicated in certain cancers, such as testicular germ cell tumors.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| 46,XY complete gonadal dysgenesis | Loss-of-function mutations in DMRT1 impair testis determination, leading to failure of testicular development and female external genitalia in 46,XY individuals. | OMIM #602424; ClinVar; PMID: 10615123 |
| Testicular germ cell tumor | Somatic deletions and reduced expression of DMRT1 are observed in testicular germ cell tumors, suggesting a tumor suppressor role. | COSMIC; PMID: 20062063 |
| 46,XY partial gonadal dysgenesis | Missense or splice-site variants in DMRT1 can cause partial testicular development, resulting in ambiguous genitalia. | ClinVar; PMID: 21712856 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 38.2 | High |
| Ovary | 0.3 | Not detected |
| Prostate | 0.1 | Not detected |
| Skin | 0.1 | Not detected |
| Brain | 0.0 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Sertoli cells (primary) | 45.0 | High expression; key for testis development |
| NTERA-2 (testicular embryonal carcinoma) | 12.5 | Moderate expression; model for germ cell tumors |
| HeLa | 0.0 | No expression |
| HEK293 | 0.0 | No expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.259C>T (p.Arg87*) | Nonsense | Rare | Loss of function; truncates protein; associated with 46,XY gonadal dysgenesis |
| c.346G>A (p.Gly116Arg) | Missense | Rare | Loss of function; disrupts DNA binding; partial gonadal dysgenesis |
| c.1A>G (p.Met1?) | Start loss | Very rare | Loss of function; no protein translation; complete gonadal dysgenesis |
| Deletion of 9p24.3 (including DMRT1) | Copy number loss | Rare | Haploinsufficiency; associated with 46,XY DSD and intellectual disability |
Mutation functional classification
Loss of Function (LOF)
Nonsense, frameshift, start-loss, and missense variants that impair DNA binding or protein stability lead to loss of DMRT1 function, causing 46,XY disorders of sex development.
Gain of Function (GOF)
No gain-of-function mutations have been reported for DMRT1.
Dominant Negative (DN)
No dominant-negative mutations have been characterized for DMRT1.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Sex determination (REACT: R-HSA-1470244)
• Transcriptional regulation of testis development (REACT: R-HSA-9623433)
Protein Summary
The DMRT1 protein (UniProt Q9Y5R6) is a 373-amino acid transcription factor containing a DM domain (residues 27–78) that binds DNA as a dimer. It is localized to the nucleus and regulates genes involved in male sex determination, including SOX9 and FGF9. DMRT1 is essential for Sertoli cell differentiation and maintenance of spermatogonial stem cells. The protein is highly expressed in adult testis and is absent in most other tissues. Structural studies show that the DM domain recognizes DNA sequences with a conserved A/T-rich core.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| DMRT1 Knockout HEK293 Cell Line | EDJ-KQ50241 | Human | 1761 | Details Get a Quote |
| DMRT1 Knockout HeLa Cell Line | EDJ-KQ53097 | Human | 1761 | Details Get a Quote |
| DMRT1 Knockout A-549 Cell Line | EDJ-KQ61570 | Human | 1761 | Details Get a Quote |
| DMRT1 Knockout HCT 116 Cell Line | EDJ-KQ70060 | Human | 1761 | Details Get a Quote |
