• 1
    Haplo
    Score
  • 0
    Triplo
    Score

Gene Facts External Data Attribution

HGNC Symbol
DMRT1 (HGNC:2934) HGNC Entrez Ensembl OMIM UCSC Uniprot GeneReviews LOVD LSDB ClinVar
HGNC Name
doublesex and mab-3 related transcription factor 1
Gene type
protein-coding gene
Locus type
gene with protein product
Previous symbols
No previous names found
Alias symbols
DMT1, CT154
%HI
18.6(Read more about the DECIPHER Haploinsufficiency Index)
pLI
0.74(Read more about gnomAD pLI score)
LOEUF
0.48(Read more about gnomAD LOEUF score)
Cytoband
9p24.3
Genomic Coordinates
GRCh37/hg19: chr9:841697-969090 NCBI Ensembl UCSC
GRCh38/hg38: chr9:841697-969090 NCBI Ensembl UCSC
MANE Select Transcript
NM_021951.3 ENST00000382276.8 (Read more about MANE Select)
Function
Transcription factor that plays a key role in male sex determination and differentiation by controlling testis development and male germ cell proliferation. Plays a central role in spermatogonia by inhibiting meiosis in undifferentiated spermatogonia and promoting mitosis, leading to spermatogonial development and allowing abundant and continuous production of sperm. Acts both as a transcription repressor and activator: prevents meiosis by restricting retinoic acid (RA)-dependent transcription a... (Source: Uniprot)

Dosage Sensitivity Summary (Gene)

Dosage ID:
ISCA-2743
Curation Status:
Complete
Issue Type:
Dosage Curation - Gene
Haploinsufficiency:
Little Evidence for Haploinsufficiency (1)
Triplosensitivity:
No Evidence for Triplosensitivity (0)
Last Evaluated:
11/10/2023

Haploinsufficiency (HI) Score Details

HI Score:
1
HI Evidence Strength:
Little Evidence for Haploinsufficiency (Disclaimer)
HI Disease:
  • Difference of Sexual Development Monarch
HI Evidence:
  • PUBMED: 20685758
    Ledig et al. (2010) report a 103.2kb deletion including exons 1 and 2 of DMRT1 found in a phenotypic female with a 46,XY chromosome complement (patient 44). Inheritance was not reported. DMRT1 deletions were also found in other individuals with gonadal dysgenesis, but these deletions involved additional genes.
  • PUBMED: 22573722
    Ledig et al. (2012) report a 35 kb deletion of exons 3 and 4 of DMRT1 in a phenotypic female patient with ovotesticular disorder of sexual development and a 46,XY karyotype. Inheritance information was not presented. At birth, the patient presented with ambiguous external genitalia. Exam revealed a phallus, bilateral gonad tissue that was interpreted to be dysgenetic ovarian tissue, hemiuterus with left Fallopian tube and right ductus deferens.
  • PUBMED: 23555275
    Lopes et al (2013) reported one 55kb intragenic deletion of DMRT1 overlapping exons 3-4 in a 46,XY chromosomal and phenotypic male with azoospermia. They also report two independent cases with 141kb and 150kb deletions of DRMT1 exons 3-5 and all of DMRT3. Both cases were chromosomal and phenotypic males with azoospermia. Two cases with larger deletions (1.14 MB and 1.94 MB overlapping FOXD4, CBWD1, DOCK8, KANK1, DMRT1, DMRT2, and DMRT3) were also reported in azoospermic males. Inheritance information was not reported. The authors suggest that the lack of sex reversal in these individuals points to variable expressivity in the context of DMRT1 haploinsufficiency, or a possible contribution of the sequence of the undeleted DMRT1 allele (because most studies did not assess the sequence of the undeleted DMRT1 allele).
  • PUBMED: 32741963
    Krausz et al (2020) reported an intragenic deletion in DMRT1, NM_021951.3:c.1_540del, predicted to result in a start loss, in a 46,XY chromosomal and phenotypic male with incomplete spermatogonial arrest and no sperm retrieved after testis biopsy. Inheritance was not determined.
HI Evidence Comments:
DMRT1 is believed to be involved in gonadal development. Segmental deletions in distal 9p have been identified in individuals with gonadal dysgenesis (PMID: 10857744, PMID: 10999792, PMID: 11720880, PMID: 21048976), and DMRT1 has been proposed as a candidate gene for male to female sex reversal. Haploinsufficiency of DMRT1 has been proposed as sufficient for male to female sex reversal (PMID 22573722), but cases of chromosomal and phenotypic males, with DMRT1 deletion and only azoospermia have been reported (PMID 23555275, 32741963). These additional cases suggest variable expressivity and/or the possibility of variants in the undeleted allele of DMRT1 or other genes that modify the phenotypic expression. For discussion of haploinsufficiency of the 9p24.3 region (including DMRT1), please see the linked region (ISCA-46741). Additional evidence: 46,XY chromosomal male with female or ambiguous phenotype: PMID 21340164: Mello et al (2010) reported a noncoding variant c.*12dupT (annotated as 3'UTR+11insT), located within a conserved motif important for mRNA stabilization in a 7 month old 46,XY chromosomal male with gonadal dysgenesis. No parental follow-up or functional studies were conducted. PMID 10857744: Calvari et al (2000) reported a less than 700kb deletion in two phenotypic female sisters with 46,XY karyotypes. The variant was inherited from their 46,XX mother. The extent of the deletion was assessed by YAC/PAC probes and the authors indicated that DRMT1 and DMRT2 lie outside of the deleted region, but that DMRT1 was close to the breakpoint of the deletion. Phenotype unknown: PMID 33726816: Stranneheim et al (2021) reported a nonsense variant in DMRT1, c.257_258delinsAA, p.(Ser86*) in a single individual from a cohort of 3219 rare disease patients assessed by whole genome sequencing. Inheritance was not determined. Phenotype was not provided in the manuscript.

Triplosensitivity (TS) Score Details

TS Score:
0
TS Evidence Strength:
No Evidence for Triplosensitivity (Disclaimer)
TS Evidence Comments:
No evidence was identified supporting or refuting triplosensitivity for this gene.

Genomic View

Select assembly: (NC_000009.11) (NC_000009.12)