DMRT1

doublesex and mab-3 related transcription factor 1

Basic information

Region (hg38): 9:841690-969090

Links

ENSG00000137090 ∙ NCBI:1761 ∙ OMIM:602424 ∙ HGNC:2934 ∙ Uniprot:Q9Y5R6 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• 46,XX disorder of sex development (Limited), mode of inheritance: AD
• 46,XY disorder of sex development (Strong), mode of inheritance: AD

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the DMRT1 gene.

• not_provided (53 variants)
• not_specified (48 variants)
• Male_infertility_with_azoospermia_or_oligozoospermia_due_to_single_gene_mutation (3 variants)
• Male_infertility (3 variants)
• Non-obstructive_azoospermia (2 variants)
• Pure_gonadal_dysgenesis_46,XY (1 variants)
• See_cases (1 variants)
• 46,XY_sex_reversal_4 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the DMRT1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000021951.3. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				13	6	19
missense		6	62	4	1	73
nonsense		1				1
start loss						0
frameshift		2				2
splice donor/acceptor (+/-2bp)		1				1
Total	0	10	62	17	7

Highest pathogenic variant AF is 0.00000433676

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
DMRT1	protein_coding	protein_coding	ENST00000382276	5	127401

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.739	0.261	124932	0	814	125746	0.00324

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.438	234	216	1.08	0.0000108	2416
Missense in Polyphen		59	69.432	0.84975		845
Synonymous	-3.60	134	90.4	1.48	0.00000486	749
Loss of Function	2.85	2	13.2	0.152	5.69e-7	158

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00406	0.00386
Ashkenazi Jewish	0.00202	0.00199
East Asian	0.00266	0.00261
Finnish	0.0138	0.0131
European (Non-Finnish)	0.00297	0.00288
Middle Eastern	0.00266	0.00261
South Asian	0.000722	0.000719
Other	0.00372	0.00359

dbNSFP

Source: dbNSFP

• Function: 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 and repressing STRA8 expression and promotes spermatogonial development by activating spermatogonial differentiation genes, such as SOHLH1. Also plays a key role in postnatal sex maintenance by maintaining testis determination and preventing feminization: represses transcription of female promoting genes such as FOXL2 and activates male-specific genes. May act as a tumor suppressor. May also play a minor role in oogenesis (By similarity). {ECO:0000250}.
• Disease: DISEASE: Testicular germ cell tumor (TGCT) [MIM:273300]: A common malignancy in males representing 95% of all testicular neoplasms. TGCTs have various pathologic subtypes including: unclassified intratubular germ cell neoplasia, seminoma (including cases with syncytiotrophoblastic cells), spermatocytic seminoma, embryonal carcinoma, yolk sac tumor, choriocarcinoma, and teratoma. {ECO:0000269|PubMed:20543847}. Note=The disease may be caused by mutations affecting the gene represented in this entry.; DISEASE: 46,XY sex reversal 4 (SRXY4) [MIM:154230]: A condition characterized by male-to-female sex reversal in the presence of a normal 46,XY karyotype. Patients display complete or partial gonadal dysgenesis and a chromosome 9p deletion. {ECO:0000269|PubMed:21048976, ECO:0000269|PubMed:9490411, ECO:0000269|PubMed:9718346}. Note=The disease may be caused by mutations affecting the gene represented in this entry.

Intolerance Scores

• loftool: 0.0628
• rvis_EVS: -0.42
• rvis_percentile_EVS: 25.56

Haploinsufficiency Scores

• pHI: 0.452
• hipred: Y
• hipred_score: 0.597
• ghis: 0.401

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.935

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Dmrt1
• Phenotype: reproductive system phenotype; endocrine/exocrine gland phenotype

Zebrafish Information Network

• Gene name: dmrt1
• Affected structure: spermatogonium
• Phenotype tag: abnormal
• Phenotype quality: decreased amount

Gene ontology

• Biological process: negative regulation of transcription by RNA polymerase II;cell morphogenesis;male germ cell proliferation;spermatogenesis;germ cell migration;male sex determination;intracellular signal transduction;negative regulation of meiotic nuclear division;positive regulation of mitotic nuclear division;positive regulation of transcription by RNA polymerase II;male sex differentiation;oocyte development;Sertoli cell differentiation;Sertoli cell development;positive regulation of meiosis I;regulation of nodal signaling pathway;positive regulation of male gonad development
• Cellular component: nucleus;cytoplasm
• Molecular function: RNA polymerase II regulatory region sequence-specific DNA binding;DNA-binding transcription factor activity, RNA polymerase II-specific;proximal promoter sequence-specific DNA binding;DNA-binding transcription activator activity, RNA polymerase II-specific;chromatin binding;identical protein binding;protein homodimerization activity;metal ion binding;protein heterodimerization activity