DMRTA1

Summary

DMRTA1 (DMRT like family A1, HGNC:13826) is a protein-coding gene on chromosome 9p21.3, encoding Doublesex- and mab-3-related transcription factor A1 (Q5VZB9).

Enables sequence-specific double-stranded DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II and sex differentiation. Predicted to act upstream of or within male mating behavior and ovarian follicle development. Predicted to be located in chromatin. Predicted to be active in nucleus.

Source: NCBI Gene 63951 — RefSeq curated summary.

At a glance

• GWAS associations: 33
• Clinical variants (ClinVar): 97 total
• MANE Select transcript: NM_022160

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:13826
Approved symbol	DMRTA1
Name	DMRT like family A1
Location	9p21.3
Locus type	gene with protein product
Status	Approved
Aliases	DMRT4
Ensembl gene	ENSG00000176399
Ensembl biotype	protein_coding
OMIM	614803
Entrez	63951

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000325870

RefSeq mRNA: 1 — MANE Select: NM_022160 NM_022160

CCDS: CCDS6514

Canonical transcript exons

ENST00000325870 — 2 exons

Exon	Start	End
ENSE00001268091	22451064	22455740
ENSE00001268100	22446824	22447732

Expression profiles

Bgee: expression breadth ubiquitous, 131 present calls, max score 79.53.

FANTOM5 (CAGE): breadth broad, TPM avg 1.9172 / max 78.0778, expressed in 583 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
96331	0.7031	175
96332	0.6941	389
96330	0.5200	198

Top tissues by expression

237 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	79.53	gold quality
right lobe of liver	UBERON:0001114	76.68	gold quality
islet of Langerhans	UBERON:0000006	68.71	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	68.20	gold quality
liver	UBERON:0002107	65.74	gold quality
esophagus mucosa	UBERON:0002469	64.90	gold quality
pancreas	UBERON:0001264	64.87	gold quality
lower esophagus mucosa	UBERON:0035834	63.95	gold quality
body of pancreas	UBERON:0001150	63.85	gold quality
esophagus	UBERON:0001043	63.26	gold quality
adult mammalian kidney	UBERON:0000082	62.59	gold quality
body of stomach	UBERON:0001161	61.67	gold quality
minor salivary gland	UBERON:0001830	61.55	gold quality
lower esophagus	UBERON:0013473	61.51	gold quality
lower esophagus muscularis layer	UBERON:0035833	61.46	gold quality
gall bladder	UBERON:0002110	61.32	gold quality
saliva-secreting gland	UBERON:0001044	61.13	gold quality
ganglionic eminence	UBERON:0004023	61.02	gold quality
stomach	UBERON:0000945	59.81	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	59.38	gold quality
mouth mucosa	UBERON:0003729	58.97	gold quality
nasal cavity epithelium	UBERON:0005384	58.57	gold quality
hindlimb stylopod muscle	UBERON:0004252	57.44	gold quality
metanephros cortex	UBERON:0010533	56.94	gold quality
muscle of leg	UBERON:0001383	56.61	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	56.51	gold quality
nasal cavity mucosa	UBERON:0001826	56.40	gold quality
heart right ventricle	UBERON:0002080	56.24	gold quality
mucosa of transverse colon	UBERON:0004991	55.93	gold quality
gastrocnemius	UBERON:0001388	55.90	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.36

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

3 targets.

Target	Regulation
CDKN2A
NCAM1	Activation
NEUROG1	Activation

JASPAR motifs

Motif	Name	Family
MA1707.1	DMRTA1	DMRT factors
MA1707.2	DMRTA1	DMRT factors

JASPAR matrix evidence (PMIDs): PMID:17605809

Upstream regulators (CollecTRI, top): PAX6

miRNA regulators (miRDB)

55 targeting DMRTA1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-4760-3P	99.93	70.50	2385
HSA-MIR-3682-5P	99.93	67.97	1163
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-9902	99.89	69.15	2250
HSA-MIR-137-3P	99.87	74.74	2401
HSA-MIR-4307	99.82	70.45	3374
HSA-MIR-944	99.82	70.85	3042
HSA-MIR-2052	99.79	69.37	2031
HSA-MIR-202-5P	99.78	67.65	991
HSA-MIR-7856-5P	99.75	69.99	2901
HSA-MIR-1200	99.71	70.42	1838
HSA-MIR-33A-3P	99.70	70.27	3362
HSA-MIR-378A-5P	99.65	66.33	1311
HSA-MIR-26A-1-3P	99.64	66.81	788
HSA-MIR-26A-2-3P	99.64	66.82	786
HSA-MIR-4666B	99.64	68.69	1282
HSA-MIR-7152-5P	99.60	69.33	2094
HSA-MIR-3942-3P	99.57	69.03	2854

Literature-anchored findings (GeneRIF, showing 2)

• A genome-wide association study reveals 2 new susceptibility loci for atopic dermatitis, XIRP2 and DMRTA1. (PMID:25865352)
• The DMRTA1-SOX2 positive feedback loop promotes progression and chemotherapy resistance of esophageal squamous cell carcinoma. (PMID:37744275)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
mus_musculus	Dmrta1	ENSMUSG00000043753
rattus_norvegicus	Dmrta1	ENSRNOG00000024093
caenorhabditis_elegans		WBGENE00019521
caenorhabditis_elegans		WBGENE00022060

Paralogs (8): DMRT3 (ENSG00000064218), DMRT1 (ENSG00000137090), DMRTC2 (ENSG00000142025), DMRTA2 (ENSG00000142700), DMRTB1 (ENSG00000143006), DMRT2 (ENSG00000173253), DMRTC1B (ENSG00000184911), DMRTC1 (ENSG00000269502)

Protein

Protein identifiers

Doublesex- and mab-3-related transcription factor A1 — Q5VZB9 (reviewed: Q5VZB9)

All UniProt accessions (1): Q5VZB9

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Nucleus.

Tissue specificity. Expressed in liver, kidney, pancreas, prostate and weakly detected in testis and ovary.

Similarity. Belongs to the DMRT family.

RefSeq proteins (1): NP_071443* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001275	DM_DNA-bd	Domain
IPR005173	DMA	Domain
IPR009060	UBA-like_sf	Homologous_superfamily
IPR026607	DMRT	Family
IPR036407	DM_DNA-bd_sf	Homologous_superfamily
IPR046472	DMRT5_1_DMB_dom	Domain

Pfam: PF00751, PF03474, PF20624

UniProt features (11 total): region of interest 3, sequence conflict 2, compositionally biased region 2, chain 1, domain 1, DNA-binding region 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5VZB9-F1	57.14	0.18

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 106 (showing top): GOBP_BEHAVIOR, CHX10_01, GOBP_OVARIAN_FOLLICLE_DEVELOPMENT, GOBP_REPRODUCTIVE_SYSTEM_DEVELOPMENT, GOBP_REPRODUCTIVE_BEHAVIOR, GOBP_FEMALE_SEX_DIFFERENTIATION, NKX22_01, AFP1_Q6, GOBP_SEX_DIFFERENTIATION, GOBP_DEVELOPMENTAL_PROCESS_INVOLVED_IN_REPRODUCTION, GOBP_DEVELOPMENT_OF_PRIMARY_SEXUAL_CHARACTERISTICS, TAATTA_CHX10_01, ZHOU_INFLAMMATORY_RESPONSE_LIVE_UP, GOMF_SEQUENCE_SPECIFIC_DNA_BINDING, MEISSNER_NPC_HCP_WITH_H3_UNMETHYLATED

GO Biological Process (5): ovarian follicle development (GO:0001541), regulation of transcription by RNA polymerase II (GO:0006357), sex differentiation (GO:0007548), male mating behavior (GO:0060179), regulation of DNA-templated transcription (GO:0006355)

GO Molecular Function (8): RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), identical protein binding (GO:0042802), metal ion binding (GO:0046872), sequence-specific double-stranded DNA binding (GO:1990837), DNA binding (GO:0003677), protein binding (GO:0005515), sequence-specific DNA binding (GO:0043565)

GO Cellular Component (2): chromatin (GO:0000785), nucleus (GO:0005634)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
RNA polymerase II transcription regulatory region sequence-specific DNA binding	2
female gonad development	1
anatomical structure development	1
regulation of DNA-templated transcription	1
transcription by RNA polymerase II	1
developmental process involved in reproduction	1
mating behavior	1
DNA-templated transcription	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
cis-regulatory region sequence-specific DNA binding	1
chromatin	1
DNA-binding transcription factor activity	1
regulation of transcription by RNA polymerase II	1
protein binding	1
cation binding	1
double-stranded DNA binding	1
sequence-specific DNA binding	1
nucleic acid binding	1
binding	1
DNA binding	1
chromosome	1
cellular anatomical structure	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

578 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DMRTA1	MTAP	Q13126	546
DMRTA1	AMH	P03971	539
DMRTA1	BSX	Q3C1V8	412
DMRTA1	CDKN2B	P42772	407
DMRTA1	H2AC19	P20670	389
DMRTA1	H2AC20	Q16777	389
DMRTA1	DMRT3	Q9NQL9	388
DMRTA1	ELAVL2	Q12926	379
DMRTA1	FAF1	Q9UNN5	379
DMRTA1	ANOS1	P23352	378
DMRTA1	EMX2	Q04743	345
DMRTA1	ATRX	P46100	342
DMRTA1	EBF2	Q9HAK2	341
DMRTA1	FOXG1	P55315	339
DMRTA1	CCDC38	Q502W7	328

IntAct

13 interactions, top by confidence:

A	B	Type	Score
DMRTA1	WFS1	psi-mi:“MI:0915”(physical association)	0.560
DMRTA1	KIF1B	psi-mi:“MI:0915”(physical association)	0.560
DMRTA1	RNF11	psi-mi:“MI:0915”(physical association)	0.560
HSP90AB1	DMRTA1	psi-mi:“MI:0915”(physical association)	0.400
DMRTA1	ORC5	psi-mi:“MI:0915”(physical association)	0.370
STAT5B	DMRTA1	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (3): DMRTA1 (Affinity Capture-Luminescence), ORC5 (Two-hybrid), STAT5B (Two-hybrid)

ESM2 similar proteins: A0JMA6, A4QNP7, A8TSS9, C0LZJ1, D4A218, F6W2R2, J7FCF0, O42115, O57682, O57685, P32114, P47240, P81068, P83758, Q00288, Q02962, Q19291, Q2I327, Q2MJB4, Q2TAQ8, Q4AE28, Q4V5A3, Q504H8, Q5UU75, Q5VZB9, Q66IK1, Q6DCQ1, Q6F2E3, Q6YHU8, Q6ZPI3, Q71MM5, Q76L87, Q7TST9, Q801F8, Q80WT2, Q86V15, Q8IVH2, Q8JIR6, Q8JJ64, Q90WM5

Diamond homologs: A2A9A2, A2A9I7, A4QNP7, A6QQ94, A8TSS9, B0I1G7, B7ZS42, C0LZJ1, D4A218, F6W2R2, G5EEJ1, J7FCF0, O18214, P23023, P57690, P83758, P85119, Q18248, Q19291, Q2I327, Q2MJB4, Q32LE6, Q3LH63, Q4AE28, Q5UU75, Q5VZB9, Q6YHU8, Q71MM5, Q76L87, Q801F8, Q80WT2, Q8BG36, Q8CFG4, Q8CGW9, Q8IXT2, Q8JIR6, Q90WM5, Q96MA1, Q96SC8, Q9DFI0

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

97 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	84
Likely benign	10
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

314 predictions. Top by Δscore:

Variant	Effect	Δscore
9:22447732:GGT:G	donor_loss	0.9900
9:22451062:A:AG	acceptor_gain	0.9900
9:22451063:G:GG	acceptor_gain	0.9900
9:22447733:G:GG	donor_gain	0.9800
9:22447734:T:A	donor_loss	0.9800
9:22451059:TCCA:T	acceptor_loss	0.9800
9:22451060:CCA:C	acceptor_loss	0.9800
9:22451061:CAG:C	acceptor_loss	0.9800
9:22451062:A:G	acceptor_loss	0.9800
9:22447728:ACAAG:A	donor_gain	0.9700
9:22447731:AG:A	donor_gain	0.9700
9:22447732:GG:G	donor_gain	0.9700
9:22451063:GAAC:G	acceptor_gain	0.9700
9:22447729:CAAG:C	donor_gain	0.9600
9:22447730:AAG:A	donor_gain	0.9600
9:22451063:GAA:G	acceptor_gain	0.9600
9:22451063:GA:G	acceptor_gain	0.9500
9:22451063:GAACA:G	acceptor_gain	0.9500
9:22451346:C:T	donor_gain	0.9400
9:22447510:G:GT	donor_gain	0.9100
9:22451304:G:GT	donor_gain	0.9000
9:22451696:ATC:A	donor_gain	0.8900
9:22451256:G:GT	donor_gain	0.8800
9:22451690:G:GG	donor_gain	0.8600
9:22449418:G:GA	donor_gain	0.8500
9:22449150:C:G	acceptor_gain	0.8400
9:22451260:TG:T	donor_gain	0.8400
9:22451305:A:T	donor_gain	0.8400
9:22447733:G:T	donor_gain	0.8300
9:22451310:A:T	donor_gain	0.8200

AlphaMissense

3188 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:22447363:T:C	C100R	1.000
9:22447404:G:C	K113N	1.000
9:22447404:G:T	K113N	1.000
9:22447411:T:C	C116R	1.000
9:22447441:T:C	C126R	1.000
9:22447464:G:C	Q133H	1.000
9:22447464:G:T	Q133H	1.000
9:22447354:T:A	C97S	0.999
9:22447354:T:C	C97R	0.999
9:22447355:G:C	C97S	0.999
9:22447363:T:A	C100S	0.999
9:22447364:G:C	C100S	0.999
9:22447366:C:A	R101S	0.999
9:22447369:A:G	N102D	0.999
9:22447371:C:A	N102K	0.999
9:22447371:C:G	N102K	0.999
9:22447372:C:G	H103D	0.999
9:22447374:T:A	H103Q	0.999
9:22447374:T:G	H103Q	0.999
9:22447391:T:A	L109H	0.999
9:22447395:G:C	K110N	0.999
9:22447395:G:T	K110N	0.999
9:22447402:A:G	K113E	0.999
9:22447403:A:T	K113M	0.999
9:22447411:T:A	C116S	0.999
9:22447412:G:A	C116Y	0.999
9:22447412:G:C	C116S	0.999
9:22447412:G:T	C116F	0.999
9:22447413:C:G	C116W	0.999
9:22447417:T:A	W118R	0.999

dbSNP variants (sampled 300 via entrez): RS1000519097 (9:22455514 C>T), RS1000658005 (9:22455361 C>A), RS1000666562 (9:22450749 A>G,T), RS1000721470 (9:22450963 G>A,T), RS1001230526 (9:22445566 G>A), RS1001371157 (9:22455776 G>A), RS1001446195 (9:22455979 A>C), RS1001508505 (9:22451244 G>A,T), RS1001669298 (9:22450627 A>C,G), RS1002930335 (9:22449167 A>T), RS1003041528 (9:22454783 G>A), RS1003295785 (9:22447916 T>G), RS1003330519 (9:22447042 C>G,T), RS1003371822 (9:22449447 C>G), RS1003447478 (9:22453428 T>C,G)

Disease associations

OMIM: gene MIM:614803 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

33 associations (top):

Study	Trait	p-value
GCST002198_14	Tuberculosis	8.000000e-06
GCST002726_37	Glucose homeostasis traits	5.000000e-06
GCST002844_4	Atopic dermatitis	1.000000e-08
GCST003400_15	Type 2 diabetes	2.000000e-09
GCST003400_53	Type 2 diabetes	6.000000e-15
GCST003468_10	Chronic lymphocytic leukemia	7.000000e-09
GCST004904_61	Body mass index	6.000000e-18
GCST004904_80	Body mass index	5.000000e-13
GCST005973_37	White blood cell count	2.000000e-12
GCST005977_5	Monocyte count	4.000000e-16
GCST005991_94	Platelet count	8.000000e-19
GCST005997_14	Lymphocyte count	5.000000e-17
GCST006001_24	Hemoglobin A1c levels	1.000000e-15
GCST006002_13	Blood sugar levels	2.000000e-16
GCST006310_4	Post bronchodilator FEV1/FVC ratio in smoking	2.000000e-06
GCST006628_6	Systolic blood pressure	3.000000e-09
GCST007096_142	Pulse pressure	2.000000e-10
GCST007324_83	Adventurousness	4.000000e-09
GCST007325_27	General risk tolerance (MTAG)	4.000000e-08
GCST007707_26	Hypertension	5.000000e-08
GCST007797_48	Asthma onset (childhood vs adult)	3.000000e-07
GCST007798_92	Asthma	8.000000e-08
GCST007800_57	Asthma (childhood onset)	3.000000e-16
GCST007847_42	Type 2 diabetes	5.000000e-13
GCST008295_12	Number of decayed, missing and filled tooth surfaces or use of dentures	3.000000e-11
GCST008306_45	Dentures	2.000000e-11
GCST009391_897	Metabolite levels	3.000000e-06
GCST009963_10	Cataracts (operation)	1.000000e-14
GCST010062_9	Hematological and biochemical traits	7.000000e-07
GCST010703_254	Brain morphology (MOSTest)	5.000000e-14

EFO canonical traits (15, from GWAS)

EFO ID	Trait name
EFO:0006831	acute insulin response measurement
EFO:0004340	body mass index
EFO:0005091	monocyte count
EFO:0004309	platelet count
EFO:0004587	lymphocyte count
EFO:0004541	HbA1c measurement
EFO:0004468	glucose measurement
EFO:0004713	FEV/FVC ratio
EFO:0006335	systolic blood pressure
EFO:0005763	pulse pressure measurement
EFO:0008579	risk-taking behaviour
EFO:0004847	age at onset
EFO:0010078	dentures
EFO:0010441	triacylglycerol 58:7 measurement
EFO:0004346	neuroimaging measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

23 total (human), top 23 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression	2
Silicon Dioxide	increases expression	2
TAK-243	increases sumoylation	1
trichostatin A	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
tobacco tar	decreases expression	1
abrine	increases expression	1
pyrachlostrobin	decreases expression	1
jinfukang	affects cotreatment, increases expression	1
Temozolomide	increases expression	1
Sunitinib	increases expression	1
Air Pollutants	increases abundance, increases expression	1
Benzo(a)pyrene	decreases methylation	1
Cadmium	decreases expression, increases abundance	1
Cisplatin	affects cotreatment, increases expression	1
Estradiol	decreases expression	1
Paraquat	increases expression	1
Rotenone	decreases expression	1
Smoke	decreases expression	1
Aflatoxin B1	decreases methylation	1
Cadmium Chloride	decreases expression, increases abundance	1
Acrylamide	decreases expression	1
Particulate Matter	increases abundance, increases expression	1

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.