DMRTC2

Summary

DMRTC2 (DMRT like family C2, HGNC:13911) is a protein-coding gene on chromosome 19q13.2, encoding Doublesex- and mab-3-related transcription factor C2 (Q8IXT2). May be involved in sexual development.

Enables sequence-specific double-stranded DNA binding activity. Predicted to be involved in cell differentiation; regulation of transcription by RNA polymerase II; and sex differentiation. Predicted to act upstream of or within heterochromatin organization; male meiosis I; and spermatid nucleus elongation. Predicted to be located in chromatin. Predicted to be active in nucleus.

Source: NCBI Gene 63946 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 53 total
• MANE Select transcript: NM_001040283

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:13911
Approved symbol	DMRTC2
Name	DMRT like family C2
Location	19q13.2
Locus type	gene with protein product
Status	Approved
Aliases	DMRT7
Ensembl gene	ENSG00000142025
Ensembl biotype	protein_coding
OMIM	614806
Entrez	63946

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 5 protein_coding, 1 retained_intron, 1 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000269945, ENST00000596258, ENST00000596660, ENST00000596827, ENST00000599022, ENST00000600017, ENST00000601660, ENST00000602098

RefSeq mRNA: 1 — MANE Select: NM_001040283 NM_001040283

CCDS: CCDS33034

Canonical transcript exons

ENST00000269945 — 9 exons

Exon	Start	End
ENSE00000951884	41850312	41850372
ENSE00000951885	41850526	41850700
ENSE00001164354	41851584	41852333
ENSE00001309323	41848795	41848975
ENSE00003010493	41845042	41845101
ENSE00003536888	41847736	41847881
ENSE00003537970	41848452	41848528
ENSE00003546094	41847425	41847652
ENSE00003613975	41849130	41849256

Expression profiles

Bgee: expression breadth broad, 53 present calls, max score 94.35.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.1005 / max 114.5756, expressed in 3 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
176071	0.0680	3
176069	0.0189	3
176070	0.0136	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right testis	UBERON:0004534	94.35	gold quality
left testis	UBERON:0004533	93.50	gold quality
testis	UBERON:0000473	91.33	gold quality
sperm	CL:0000019	87.08	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	86.38	gold quality
secondary oocyte	CL:0000655	84.42	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	82.60	gold quality
oocyte	CL:0000023	73.86	gold quality
adult organism	UBERON:0007023	72.47	gold quality
buccal mucosa cell	CL:0002336	59.25	gold quality
tibialis anterior	UBERON:0001385	55.01	silver quality
cardiac muscle of right atrium	UBERON:0003379	54.34	gold quality
left ventricle myocardium	UBERON:0006566	54.23	gold quality
kidney epithelium	UBERON:0004819	53.93	gold quality
epithelial cell of pancreas	CL:0000083	53.84	gold quality
upper arm skin	UBERON:0004263	53.52	gold quality
blood	UBERON:0000178	53.45	gold quality
pancreatic ductal cell	CL:0002079	53.33	silver quality
deltoid	UBERON:0001476	51.16	gold quality
myocardium	UBERON:0002349	50.25	gold quality
quadriceps femoris	UBERON:0001377	48.89	gold quality
vastus lateralis	UBERON:0001379	48.00	gold quality
ileal mucosa	UBERON:0000331	47.44	silver quality
colonic epithelium	UBERON:0000397	47.03	gold quality
nasal cavity epithelium	UBERON:0005384	47.03	gold quality
upper leg skin	UBERON:0004262	43.71	silver quality
bone marrow	UBERON:0002371	43.69	gold quality
layer of synovial tissue	UBERON:0007616	43.55	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	43.37	gold quality
muscle tissue	UBERON:0002385	41.85	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	2.78

Regulation

Is transcription factor: yes

JASPAR motifs

Motif	Name	Family
MA1479.1	DMRTC2	DMRT factors
MA1479.2	DMRTC2	DMRT factors

JASPAR matrix evidence (PMIDs): PMID:25215497

miRNA regulators (miRDB)

26 targeting DMRTC2, 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-4668-3P	100.00	68.74	2635
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-3529-3P	99.90	73.55	3045
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-1343-3P	99.89	66.78	1815
HSA-MIR-6783-3P	99.89	67.92	2059
HSA-MIR-6857-5P	99.87	65.32	985
HSA-MIR-6752-3P	99.72	66.71	1587
HSA-MIR-4524A-3P	99.72	66.85	2406
HSA-MIR-4743-3P	99.62	68.12	2095
HSA-MIR-5693	99.24	66.67	1106
HSA-MIR-4520-2-3P	99.14	69.28	1009
HSA-MIR-4999-3P	99.11	65.55	424
HSA-MIR-3117-5P	99.04	67.93	618
HSA-MIR-500A-5P	98.76	69.13	1241
HSA-MIR-6804-3P	98.72	64.82	852
HSA-MIR-1261	98.62	68.10	896
HSA-MIR-5581-3P	98.55	70.31	1161
HSA-MIR-4450	98.26	68.35	725
HSA-MIR-6773-3P	98.17	65.51	1213
HSA-MIR-7850-5P	98.12	67.28	1111
HSA-MIR-6841-5P	97.19	67.29	409
HSA-MIR-215-3P	97.02	68.01	1209
HSA-MIR-711	96.60	65.75	528

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
mus_musculus	Dmrtc2	ENSMUSG00000011349
rattus_norvegicus	Dmrtc2	ENSRNOG00000020109
caenorhabditis_elegans		WBGENE00019521
caenorhabditis_elegans		WBGENE00022060

Paralogs (8): DMRT3 (ENSG00000064218), DMRT1 (ENSG00000137090), DMRTA2 (ENSG00000142700), DMRTB1 (ENSG00000143006), DMRT2 (ENSG00000173253), DMRTA1 (ENSG00000176399), DMRTC1B (ENSG00000184911), DMRTC1 (ENSG00000269502)

Protein

Protein identifiers

Doublesex- and mab-3-related transcription factor C2 — Q8IXT2 (reviewed: Q8IXT2)

All UniProt accessions (5): Q8IXT2, B4DX56, M0QZH7, M0R1Z9, M0R2D7

UniProt curated annotations — full annotation on UniProt →

Function. May be involved in sexual development.

Subcellular location. Nucleus.

Tissue specificity. Expressed in testis and pancreas.

Miscellaneous. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.

Similarity. Belongs to the DMRT family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q8IXT2-1	1	yes
Q8IXT2-2	2

RefSeq proteins (1): NP_001035373* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001275	DM_DNA-bd	Domain
IPR026607	DMRT	Family
IPR031577	DMRT-C1/C2_C	Domain
IPR036407	DM_DNA-bd_sf	Homologous_superfamily

Pfam: PF00751, PF15791

UniProt features (8 total): region of interest 2, splice variant 2, sequence conflict 2, chain 1, DNA-binding region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8IXT2-F1	60.70	0.20

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 61 (showing top): GOBP_MALE_GAMETE_GENERATION, GOBP_ORGANELLE_FISSION, GOBP_NUCLEUS_ORGANIZATION, GOBP_MALE_MEIOSIS_I, GOBP_CELLULAR_PROCESS_INVOLVED_IN_REPRODUCTION_IN_MULTICELLULAR_ORGANISM, GOBP_SPERMATID_NUCLEUS_DIFFERENTIATION, GOBP_SEX_DIFFERENTIATION, GOBP_DEVELOPMENTAL_PROCESS_INVOLVED_IN_REPRODUCTION, GOBP_MEIOTIC_CELL_CYCLE_PROCESS, GOBP_HETEROCHROMATIN_ORGANIZATION, AGCTCCT_MIR28, GOBP_MEIOTIC_CELL_CYCLE, GOCC_SEX_CHROMOSOME, LEIN_CEREBELLUM_MARKERS, GOCC_XY_BODY

GO Biological Process (7): male meiosis I (GO:0007141), spermatid nucleus elongation (GO:0007290), sex differentiation (GO:0007548), heterochromatin organization (GO:0070828), regulation of DNA-templated transcription (GO:0006355), regulation of transcription by RNA polymerase II (GO:0006357), cell differentiation (GO:0030154)

GO Molecular Function (6): 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), sequence-specific DNA binding (GO:0043565)

GO Cellular Component (3): chromatin (GO:0000785), XY body (GO:0001741), nucleus (GO:0005634)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
meiosis I	1
male meiotic nuclear division	1
male gamete generation	1
meiotic cell cycle	1
nucleus organization	1
spermatid nucleus differentiation	1
developmental process involved in reproduction	1
chromatin organization	1
DNA-templated transcription	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
regulation of DNA-templated transcription	1
transcription by RNA polymerase II	1
cellular developmental process	1
chromatin	1
RNA polymerase II transcription regulatory region sequence-specific DNA binding	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
DNA binding	1
chromosome	1
cellular anatomical structure	1
sex chromosome	1
condensed chromatin of inactivated sex chromosome	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

566 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DMRTC2	LYPD4	Q6UWN0	571
DMRTC2	C10orf120	Q5SQS8	513
DMRTC2	SOX30	O94993	483
DMRTC2	NCAPH	Q15003	479
DMRTC2	C5orf47	Q569G3	477
DMRTC2	IQCF1	Q8N6M8	459
DMRTC2	CCDC27	Q2M243	444
DMRTC2	CCDC83	Q8IWF9	441
DMRTC2	PKMYT1	Q99640	424
DMRTC2	CDADC1	Q9BWV3	421
DMRTC2	RCHY1	Q96PM5	398
DMRTC2	ACCSL	Q4AC99	394
DMRTC2	RBBP8NL	Q8NC74	393
DMRTC2	SAXO1	Q8IYX7	386
DMRTC2	DEFB112	Q30KQ8	384

IntAct

3 interactions, top by confidence:

A	B	Type	Score
IRF9	DMRTC2	psi-mi:“MI:0915”(physical association)	0.370
TXNRD1	DMRTC2	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (3): DMRTC2 (Proximity Label-MS), DMRTC2 (Two-hybrid), TXNRD1 (Two-hybrid)

ESM2 similar proteins: A0A5F9ZHS7, A1YGK1, A2T7E6, A8MZG2, O08574, O43593, O60393, O75593, O88621, O95231, P0C1T1, P0CG20, P20428, P97609, Q04667, Q17QR5, Q2KIS6, Q2M1V0, Q2T9Q7, Q32LE6, Q497V6, Q5JUK2, Q5M844, Q5RJB0, Q5TGS1, Q61645, Q61657, Q6ZMY3, Q6ZN32, Q6ZNG2, Q7RTU1, Q8BZW2, Q8CGW9, Q8IWN7, Q8IXT2, Q8IZ20, Q8N1L9, Q8N7G0, Q8N944, Q8N9Y4

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

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	47
Likely benign	5
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1180 predictions. Top by Δscore:

Variant	Effect	Δscore
19:41847420:CCTA:C	acceptor_loss	1.0000
19:41847421:CTA:C	acceptor_loss	1.0000
19:41847423:A:AG	acceptor_gain	1.0000
19:41847423:AG:A	acceptor_loss	1.0000
19:41847424:G:GA	acceptor_gain	1.0000
19:41847424:G:GC	acceptor_loss	1.0000
19:41847424:GATCC:G	acceptor_gain	1.0000
19:41847649:TCCT:T	donor_gain	1.0000
19:41847651:CT:C	donor_gain	1.0000
19:41847651:CTG:C	donor_loss	1.0000
19:41847653:G:GG	donor_gain	1.0000
19:41847653:GTG:G	donor_loss	1.0000
19:41847654:TGAG:T	donor_loss	1.0000
19:41848450:A:AG	acceptor_gain	1.0000
19:41848450:AGCT:A	acceptor_gain	1.0000
19:41848451:G:GG	acceptor_gain	1.0000
19:41848451:GCTG:G	acceptor_gain	1.0000
19:41850381:A:T	donor_gain	1.0000
19:41850384:G:GT	donor_gain	1.0000
19:41850448:G:GT	donor_gain	1.0000
19:41847416:T:TA	acceptor_gain	0.9900
19:41847424:GA:G	acceptor_gain	0.9900
19:41847424:GAT:G	acceptor_gain	0.9900
19:41847424:GATC:G	acceptor_gain	0.9900
19:41847648:ATCCT:A	donor_gain	0.9900
19:41847650:CCT:C	donor_gain	0.9900
19:41847657:G:GG	donor_gain	0.9900
19:41847734:AG:A	acceptor_gain	0.9900
19:41847735:GG:G	acceptor_gain	0.9900
19:41847735:GGGA:G	acceptor_gain	0.9900

AlphaMissense

2325 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:41847561:T:A	C45S	0.999
19:41847561:T:C	C45R	0.999
19:41847562:G:C	C45S	0.999
19:41847572:T:A	H48Q	0.999
19:41847572:T:G	H48Q	0.999
19:41847615:T:C	F63L	0.999
19:41847617:C:A	F63L	0.999
19:41847617:C:G	F63L	0.999
19:41847552:T:C	C42R	0.998
19:41847565:G:C	R46P	0.998
19:41847639:T:C	C71R	0.998
19:41847593:G:C	K55N	0.997
19:41847593:G:T	K55N	0.997
19:41847602:G:C	K58N	0.997
19:41847602:G:T	K58N	0.997
19:41847609:T:C	C61R	0.997
19:41847615:T:A	F63I	0.997
19:41847615:T:G	F63V	0.997
19:41847616:T:C	F63S	0.997
19:41847616:T:G	F63C	0.997
19:41847630:T:C	C68R	0.997
19:41847639:T:A	C71S	0.997
19:41847640:G:C	C71S	0.997
19:41847740:C:A	R77S	0.997
19:41847754:G:A	M81I	0.997
19:41847754:G:C	M81I	0.997
19:41847754:G:T	M81I	0.997
19:41847552:T:A	C42S	0.996
19:41847553:G:A	C42Y	0.996
19:41847553:G:C	C42S	0.996

dbSNP variants (sampled 300 via entrez): RS1000189887 (19:41847796 A>G), RS1000560049 (19:41845743 C>G), RS1003742123 (19:41844359 C>T), RS1004270385 (19:41850172 A>C,G), RS1004332060 (19:41844100 A>T), RS1004380739 (19:41844317 G>A,T), RS1004643641 (19:41848490 C>A,T), RS1005010048 (19:41848737 C>T), RS1005306364 (19:41851349 G>A,T), RS1005363391 (19:41844920 C>T), RS1005687063 (19:41851576 G>A,C), RS1007721871 (19:41846121 G>T), RS1008061142 (19:41852822 G>A), RS1008438100 (19:41849152 C>G,T), RS1008723125 (19:41847890 C>A,T)

Disease associations

OMIM: gene MIM:614806 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST010703_14	Brain morphology (MOSTest)	1.000000e-09

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
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

7 total (human), top 7 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Resveratrol	decreases expression, affects cotreatment	2
bisphenol A	affects cotreatment, decreases methylation	1
Temozolomide	affects response to substance	1
Fulvestrant	affects cotreatment, decreases methylation	1
Carmustine	affects response to substance	1
Copper	affects cotreatment, decreases expression	1
Plant Extracts	affects cotreatment, decreases expression	1

Cellosaurus cell lines

2 cell lines: 2 embryonic stem cell

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_A1A1	SEES3-1V human DMRTC2, clone1	Embryonic stem cell	Male
CVCL_A1A2	SEES3-1V human DMRTC2, clone2	Embryonic stem cell	Male

Clinical trials (associated diseases)

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