DMRT1 doublesex and mab-3 related transcription factor 1 [Homo sapiens (human)] - Gene

Summary

Official Symbol: DMRT1provided by HGNC
Official Full Name: doublesex and mab-3 related transcription factor 1provided by HGNC
Primary source: HGNC:HGNC:2934
See related: Ensembl:ENSG00000137090 MIM:602424; AllianceGenome:HGNC:2934
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: DMT1; CT154
Summary: 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]
Expression: Restricted expression toward testis (RPKM 15.0) See more
Orthologs: mouse all
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Genomic context

Location:: 9p24.3

Exon count:: 7

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	9	NC_000009.12 (841697..969090)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	9	NC_060933.1 (842204..970359)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	9	NC_000009.11 (841697..969090)

Chromosome 9 - NC_000009.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

DMRT1 regulates human germline commitment.
Title: DMRT1 regulates human germline commitment.
Functional assessment of DMRT1 variants and their pathogenicity for isolated male infertility.
Title: Functional assessment of DMRT1 variants and their pathogenicity for isolated male infertility.
Report differential expression of DMRT1 in normal human spermatogenesis, testicular mixed germ cell-sex cord stromal tumor, spermatocytic tumor, and seminoma.
Title: Protein expression of the transcription factors DMRT1, TCLF5, and OCT4 in selected germ cell neoplasms of the testis.
DMRT1 is required for testicular differentiation in humans. DMRT1 repression results in alterations in expression of key genes involved in gonadal development. Repression of DMRT1 results in focal dysgenesis in the human fetal testis
Title: DMRT1 repression using a novel approach to genetic manipulation induces testicular dysgenesis in human fetal gonads.
DMRT1 might influence sex-specific patterns of childhood asthma, and its expression in testis tissue and lung macrophages suggests a potential involvement in hormone or immune cell regulation.
Title: Doublesex and mab-3 related transcription factor 1 (DMRT1) is a sex-specific genetic determinant of childhood-onset asthma and is expressed in testis and macrophages.
The results suggest a role of changes in DMRT1 dosage in non-obstructive azoospermia potentially also through a process of gene misregulation, even though DMRT1 deleterious variants seem to be rare.
Title: Rare double sex and mab-3-related transcription factor 1 regulatory variants in severe spermatogenic failure.
The role of DMT1 in mitochondrial iron acquisition by immunofluorescence with mitochondrial markers in cells and isolated mitochondria, as well as flow cytometric quantification of DMT1-positive mitochondria from an inducible expression system.
Title: Mitochondria represent another locale for the divalent metal transporter 1 (DMT1).
These show that DMRT proteins use a unique binding interaction, inserting two adjacent antiparallel recognition helices into a widened DNA major groove to make base-specific contacts.
Title: An ancient protein-DNA interaction underlying metazoan sex determination.
Point mutations of DMRT1 may be rarely associated with male infertility.
Title: DMRT1 mutations are rarely associated with male infertility.
The combined results indicate that DMRT1 loss-of-function mutations are a risk factor and potential genetic cause of human spermatogenic failure
Title: Human spermatogenic failure purges deleterious mutation load from the autosomes and both sex chromosomes, including the gene DMRT1.

Submit: New GeneRIF Correction See all GeneRIFs (22)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Copy number response

Description
Copy number response Triplosensitivity No evidence available (Last evaluated 2023-11-10) ClinGen Genome Curation Page Haploinsufficency Little evidence for dosage pathogenicity (Last evaluated 2023-11-10) ClinGen Genome Curation PagePubMed

EBI GWAS Catalog

Description
A second independent locus within DMRT1 is associated with testicular germ cell tumor susceptibility. EBI GWAS Catalog EBI GWAS CatalogPubMed
Common genetic variation and antidepressant efficacy in major depressive disorder: a meta-analysis of three genome-wide pharmacogenetic studies. EBI GWAS Catalog EBI GWAS CatalogPubMed
Identification of nine new susceptibility loci for testicular cancer, including variants near DAZL and PRDM14. EBI GWAS Catalog EBI GWAS CatalogPubMed
Meta-analysis identifies four new loci associated with testicular germ cell tumor. EBI GWAS Catalog EBI GWAS CatalogPubMed
Novel genetic loci identified for the pathophysiology of childhood obesity in the Hispanic population. EBI GWAS Catalog EBI GWAS CatalogPubMed
Variants near DMRT1, TERT and ATF7IP are associated with testicular germ cell cancer. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables DNA-binding transcription activator activity, RNA polymerase II-specific	IEA Inferred from Electronic Annotation more info
enables DNA-binding transcription factor activity, RNA polymerase II-specific	IBA Inferred from Biological aspect of Ancestor more info
enables DNA-binding transcription factor activity, RNA polymerase II-specific	ISA Inferred from Sequence Alignment more info
enables RNA polymerase II cis-regulatory region sequence-specific DNA binding	IBA Inferred from Biological aspect of Ancestor more info
enables chromatin binding	IEA Inferred from Electronic Annotation more info
enables cis-regulatory region sequence-specific DNA binding	ISS Inferred from Sequence or Structural Similarity more info
enables identical protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables metal ion binding	IEA Inferred from Electronic Annotation more info
enables sequence-specific double-stranded DNA binding	IDA Inferred from Direct Assay more info	PubMed

Process	Evidence Code	Pubs
involved_in Sertoli cell development	IEA Inferred from Electronic Annotation more info
involved_in Sertoli cell differentiation	ISS Inferred from Sequence or Structural Similarity more info
involved_in cell morphogenesis	IEA Inferred from Electronic Annotation more info
involved_in germ cell migration	IEA Inferred from Electronic Annotation more info
involved_in intracellular signal transduction	IEA Inferred from Electronic Annotation more info
involved_in male germ cell proliferation	ISS Inferred from Sequence or Structural Similarity more info
involved_in male sex determination	ISS Inferred from Sequence or Structural Similarity more info
involved_in male sex differentiation	ISS Inferred from Sequence or Structural Similarity more info
involved_in meiosis I	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of meiotic nuclear division	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of transcription by RNA polymerase II	ISS Inferred from Sequence or Structural Similarity more info
involved_in oocyte development	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of male gonad development	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of meiosis I	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of mitotic nuclear division	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of transcription by RNA polymerase II	ISS Inferred from Sequence or Structural Similarity more info
involved_in regulation of nodal signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in regulation of transcription by RNA polymerase II	IBA Inferred from Biological aspect of Ancestor more info
involved_in sex differentiation	IBA Inferred from Biological aspect of Ancestor more info
involved_in spermatogenesis	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
located_in chromatin	ISA Inferred from Sequence Alignment more info
located_in cytoplasm	IEA Inferred from Electronic Annotation more info
located_in female germ cell nucleus	IEA Inferred from Electronic Annotation more info
is_active_in nucleus	IBA Inferred from Biological aspect of Ancestor more info
located_in nucleus	IDA Inferred from Direct Assay more info	PubMed
located_in nucleus	ISS Inferred from Sequence or Structural Similarity more info

General protein information

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Preferred Names: doublesex- and mab-3-related transcription factor 1

Names: DM domain expressed in testis 1; DM domain expressed in testis protein 1

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_009221.1 RefSeqGene

Range

5008..132401

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001363767.1 → NP_001350696.1 doublesex- and mab-3-related transcription factor 1 isoform 2

Status: REVIEWED

Source sequence(s)

AL136365

Consensus CDS

CCDS87636.1

UniProtKB/TrEMBL

H3BN61

Conserved Domains (1) summary

pfam12374
Location:3 → 44

Dmrt1; Double-sex mab3 related transcription factor 1
NM_021951.3 → NP_068770.2 doublesex- and mab-3-related transcription factor 1 isoform 1

See identical proteins and their annotated locations for NP_068770.2

Status: REVIEWED

Source sequence(s)

AF130728, BC040847, BG202785

Consensus CDS

CCDS6442.1

UniProtKB/Swiss-Prot

B2R913, Q6T1H8, Q6T1H9, Q8IW77, Q9Y5R6

Related

ENSP00000371711.3, ENST00000382276.8

Conserved Domains (2) summary

pfam00751
Location:72 → 118

DM; DM DNA binding domain

pfam12374
Location:130 → 202

Dmrt1; Double-sex mab3 related transcription factor 1

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000009.12 Reference GRCh38.p14 Primary Assembly

Range

841697..969090

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_006716732.2 → XP_006716795.1 doublesex- and mab-3-related transcription factor 1 isoform X3

Conserved Domains (2) summary

pfam00751
Location:72 → 118

DM; DM DNA binding domain

pfam12374
Location:130 → 202

Dmrt1; Double-sex mab3 related transcription factor 1
XM_011517770.2 → XP_011516072.2 doublesex- and mab-3-related transcription factor 1 isoform X1
XM_011517771.2 → XP_011516073.2 doublesex- and mab-3-related transcription factor 1 isoform X2

UniProtKB/TrEMBL

H3BN61

Related

ENSP00000454701.1, ENST00000569227.1
XM_011517773.4 → XP_011516075.1 doublesex- and mab-3-related transcription factor 1 isoform X1

Conserved Domains (1) summary

pfam12374
Location:1 → 44

Dmrt1; Double-sex mab3 related transcription factor 1

Alternate T2T-CHM13v2.0

Genomic

NC_060933.1 Alternate T2T-CHM13v2.0

Range

842204..970359

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_054362229.1 → XP_054218204.1 doublesex- and mab-3-related transcription factor 1 isoform X3
XM_054362227.1 → XP_054218202.1 doublesex- and mab-3-related transcription factor 1 isoform X1
XM_054362228.1 → XP_054218203.1 doublesex- and mab-3-related transcription factor 1 isoform X2

UniProtKB/TrEMBL

H3BN61
XM_054362230.1 → XP_054218205.1 doublesex- and mab-3-related transcription factor 1 isoform X1