DMC1

Summary

DMC1 (DNA meiotic recombinase 1, HGNC:2927) is a protein-coding gene on chromosome 22q13.1, encoding Meiotic recombination protein DMC1/LIM15 homolog (Q14565). Participates in meiotic recombination, specifically in homologous strand assimilation, which is required for the resolution of meiotic double-strand breaks.

This gene encodes a member of the superfamily of recombinases (also called DNA strand-exchange proteins). Recombinases are important for repairing double-strand DNA breaks during mitosis and meiosis. This protein, which is evolutionarily conserved, is reported to be essential for meiotic homologous recombination and may thus play an important role in generating diversity of genetic information. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 11144 — RefSeq curated summary.

At a glance

• Gene–disease (curated): primary ovarian failure (Strong, GenCC) — +2 more curated relationships
• Clinical variants (ClinVar): 44 total — 2 pathogenic, 3 likely-pathogenic
• MANE Select transcript: NM_007068

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2927
Approved symbol	DMC1
Name	DNA meiotic recombinase 1
Location	22q13.1
Locus type	gene with protein product
Status	Approved
Aliases	LIM15
Ensembl gene	ENSG00000100206
Ensembl biotype	protein_coding
OMIM	602721
Entrez	11144

Gene structure

Transcript identifiers

Ensembl transcripts: 20 — 18 protein_coding, 1 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000216024, ENST00000415483, ENST00000428462, ENST00000439567, ENST00000464842, ENST00000478820, ENST00000899118, ENST00000911572, ENST00000911573, ENST00000911574, ENST00000911575, ENST00000911576, ENST00000911577, ENST00000911578, ENST00000911579, ENST00000911580, ENST00000957688, ENST00000957689, ENST00000957690, ENST00000957691

RefSeq mRNA: 3 — MANE Select: NM_007068 NM_001278208, NM_001363017, NM_007068

CCDS: CCDS13973, CCDS63477

Canonical transcript exons

ENST00000216024 — 14 exons

Exon	Start	End
ENSE00000654376	38521608	38521724
ENSE00000654377	38537592	38537652
ENSE00000654379	38538539	38538612
ENSE00000654381	38539321	38539412
ENSE00000654382	38549925	38549997
ENSE00001948236	38570043	38570183
ENSE00003479349	38568206	38568289
ENSE00003547276	38552666	38552707
ENSE00003548937	38567583	38567627
ENSE00003599462	38566590	38566736
ENSE00003604674	38562287	38562369
ENSE00003663453	38555357	38555409
ENSE00003786185	38538295	38538409
ENSE00003843247	38518948	38520089

Expression profiles

Bgee: expression breadth ubiquitous, 171 present calls, max score 91.17.

FANTOM5 (CAGE): breadth broad, TPM avg 2.4424 / max 74.8983, expressed in 830 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
194196	2.0124	772
194195	0.4300	241

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
buccal mucosa cell	CL:0002336	91.17	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	84.01	gold quality
right testis	UBERON:0004534	81.58	gold quality
left testis	UBERON:0004533	79.89	gold quality
testis	UBERON:0000473	78.98	gold quality
ventricular zone	UBERON:0003053	77.33	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	77.12	gold quality
calcaneal tendon	UBERON:0003701	75.29	gold quality
ganglionic eminence	UBERON:0004023	73.51	gold quality
hindlimb stylopod muscle	UBERON:0004252	71.84	gold quality
gingival epithelium	UBERON:0001949	71.38	gold quality
secondary oocyte	CL:0000655	69.69	gold quality
superficial temporal artery	UBERON:0001614	69.45	gold quality
cerebellar vermis	UBERON:0004720	69.25	silver quality
tonsil	UBERON:0002372	69.19	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	68.80	gold quality
oocyte	CL:0000023	68.57	gold quality
gingiva	UBERON:0001828	68.51	gold quality
descending thoracic aorta	UBERON:0002345	68.06	gold quality
colonic epithelium	UBERON:0000397	67.75	gold quality
deltoid	UBERON:0001476	67.74	silver quality
bone marrow	UBERON:0002371	67.74	gold quality
lymph node	UBERON:0000029	67.65	gold quality
tendon	UBERON:0000043	67.26	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	67.24	gold quality
cardia of stomach	UBERON:0001162	67.01	gold quality
pylorus	UBERON:0001166	66.93	gold quality
vena cava	UBERON:0004087	66.85	gold quality
pericardium	UBERON:0002407	66.84	gold quality
ventral tegmental area	UBERON:0002691	66.81	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.12

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

57 targeting DMC1, 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-5011-5P	100.00	83.46	5820
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-9718	99.94	68.91	918
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-345-3P	99.89	70.23	1421
HSA-MIR-576-5P	99.84	70.46	2582
HSA-MIR-5010-3P	99.83	70.60	2357
HSA-MIR-548AZ-5P	99.83	69.94	3230
HSA-MIR-548T-5P	99.83	69.91	3220
HSA-MIR-3121-3P	99.82	71.96	3630
HSA-MIR-577	99.78	69.13	2479
HSA-MIR-3680-3P	99.75	72.51	3095
HSA-MIR-5580-3P	99.70	69.41	2052
HSA-MIR-466	99.67	70.85	2863
HSA-MIR-670-5P	99.67	69.94	1565
HSA-MIR-587	99.64	70.86	2611
HSA-MIR-802	99.61	67.70	1254
HSA-MIR-1290	99.59	69.90	2079
HSA-MIR-24-3P	99.59	69.97	1934
HSA-MIR-3609	99.52	69.89	2587
HSA-MIR-548AH-5P	99.52	69.73	2626
HSA-MIR-4672	99.50	71.58	2893

Literature-anchored findings (GeneRIF, showing 35)

• p53 might be involved in homologous recombination and/or checkpoint function by directly binding to DMC1 protein to repress genomic instability in meiotic germ cells (PMID:14764457)
• The monomeric structure of the Dmc1 protein closely resembled those of the human and archaeal Rad51 proteins. We found another hydrogen bonding interaction at the polymer interface. (PMID:15125839)
• hDmc1-mediated DNA recombination initiates through the nucleation of hDmc1 onto ssDNA to form a helical nucleoprotein filament (PMID:15164066)
• N-terminal domain of DMC1 is required for the formation of the octamer, which may support the proper DNA binding activity of the DMC1 protein. (PMID:15917243)
• activation of hDmc1 is mediated through conformational changes induced by free Ca2+ ion binding to a protein site that is distinct from the Mg2+.ATP-binding center (PMID:15917244)
• BRCA2 binds the meiosis-specific recombinase DMC1 and define the primary DMC1 interaction site to a 26 amino-acid region (PMID:17541404)
• Hop2/Mnd1 greatly stimulates Dmc1 to promote synaptic complex formation on long duplex DNAs (PMID:17639081)
• Data show that DMC1 mutations may be one explanation for premature ovarian failure. (PMID:18166824)
• The interaction of DMC1 and the homologue of the large subunit of CAF-1 is reported. (PMID:18355319)
• Results indicate that Rad51 and Dmc1 filaments are essentially identical with respect to several structural parameters, including persistence length, helical pitch, filament diameter, DNA base pairs per helical turn and helical handedness. (PMID:18535008)
• Biochemical analyses revealed that the human DMC1-M200V variant had reduced stability, and was moderately defective in catalyzing in vitro recombination reactions. (PMID:18566005)
• Reversibility, equilibration, and fidelity of strand exchange reaction between short oligonucleotides promoted by RecA protein from escherichia coli and human Rad51 and Dmc1 proteins. (PMID:19004837)
• DMC1-I37N polymorphism may be a source of improper meiotic recombination, causing meiotic defects in humans (PMID:19076215)
• the Dmc1 filament formed on single-stranded DNA has a mass per unit length expected from approximately 6.5 subunits per turn (PMID:20600108)
• D-loops in a human DMC1-driven reaction are substantially more resistant to dissociation by branch-migration proteins such as RAD54 than those formed by RAD51. (PMID:21151113)
• RAD51AP1 foci colocalize with a subset of DMC1 foci in spermatocytes. (PMID:21307306)
• RAD51-associated protein 1 (RAD51AP1) interacts with the meiotic recombinase DMC1 through a conserved motif. (PMID:21903585)
• The results suggested that PSF may function as an activator for the meiosis-specific recombinase DMC1. (PMID:22156371)
• conserved lysine in the Walker A motif of hDMC1 is critical for ATP binding. (PMID:23182424)
• results suggested mutations in the coding sequence of DMC1 are not associated with premature ovarian failure in Chinese women (PMID:23265958)
• truncated DMC1 octamers further stack with alternate polarity into a filament (PMID:23545642)
• In contrast to RAD51, stabilization of the presynaptic filament via ATP hydrolysis attenuation is insufficient for enhancement of the DMC1-catalyzed recombination reaction. (PMID:26088134)
• Dmc1 can reject divergent DNA sequences while bypassing a few mismatches in the DNA sequence. (PMID:26709229)
• BRCA2 protein stimulates DMC1-mediated DNA strand exchange between RPA-ssDNA complexes and duplex DNA, thus identifying BRCA2 as a mediator of DMC1 recombination function. (PMID:26976601)
• Data indicate that ahomologous pairing by DMC1 protein or RAD51 recombinase in chromatin containing nucleosome-depleted double-stranded DNA (dsDNA) regions. (PMID:27052786)
• To the best of our knowledge, this is the first report identifying DMC1 as the causative gene for human non-obstructive azoospermia and premature ovarian insufficiency. (PMID:29331980)
• In this study, we created a mouse model of a putative infertility allele, DMC1M200V. DMC1 encodes a RecA homolog essential for meiotic recombination and fertility in mice..we found that Dmc1M200V/M200V male and female mice are fully fertile and do not exhibit any gonadal abnormalities (PMID:30085085)
• Identification of fidelity-governing factors in human recombinases DMC1 and RAD51 from cryo-EM structures. (PMID:33446654)
• A pathogenic DMC1 frameshift mutation causes nonobstructive azoospermia but not primary ovarian insufficiency in humans. (PMID:34515795)
• Mechanisms of distinctive mismatch tolerance between Rad51 and Dmc1 in homologous recombination. (PMID:34871438)
• Can PCNA and LIM15 gene expression levels predict sperm retrieval success in men with non-obstructive azoospermia? (PMID:35570072)
• Recent advances in functional conservation and divergence of recombinase RAD51 and DMC1. (PMID:35729697)
• MiR-4284 inhibits sensitivity to paclitaxel in human ovarian carcinoma SKOV3ip1 and HeyA8 cells by targeting DMC1. (PMID:35946537)
• FIGNL1 AAA+ ATPase remodels RAD51 and DMC1 filaments in pre-meiotic DNA replication and meiotic recombination. (PMID:37891173)
• Positive and negative regulators of RAD51/DMC1 in homologous recombination and DNA replication. (PMID:38142595)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	dmc1	ENSDARG00000055883
mus_musculus	Dmc1	ENSMUSG00000022429
rattus_norvegicus	Dmc1	ENSRNOG00000013807

Paralogs (6): RAD51 (ENSG00000051180), RAD51C (ENSG00000108384), XRCC3 (ENSG00000126215), RAD51B (ENSG00000182185), RAD51D (ENSG00000185379), XRCC2 (ENSG00000196584)

Protein

Protein identifiers

Meiotic recombination protein DMC1/LIM15 homolog — Q14565 (reviewed: Q14565)

All UniProt accessions (3): Q14565, B0QYE0, B0QYE1

UniProt curated annotations — full annotation on UniProt →

Function. Participates in meiotic recombination, specifically in homologous strand assimilation, which is required for the resolution of meiotic double-strand breaks.

Subunit / interactions. Double stacked ring-shaped homooctamer. Interacts with BRCA2. Interacts with the MND1-PSMC3IP heterodimer. Interacts with RAD51AP1; the interaction is direct and stimulates DMC1-mediated homologous recombination.

Subcellular location. Nucleus. Chromosome.

Similarity. Belongs to the RecA family. DMC1 subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
Q14565-1	1	yes
Q14565-2	2

RefSeq proteins (3): NP_001265137, NP_001349946, NP_008999* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003593	AAA+_ATPase	Domain
IPR010995	DNA_repair_Rad51/TF_NusA_a-hlx	Homologous_superfamily
IPR011940	Dmc1	Family
IPR013632	Rad51_C	Domain
IPR016467	DNA_recomb/repair_RecA-like	Family
IPR020587	RecA_monomer-monomer_interface	Domain
IPR020588	RecA_ATP-bd	Domain
IPR027417	P-loop_NTPase	Homologous_superfamily

Pfam: PF08423, PF14520

UniProt features (55 total): helix 16, strand 14, binding site 9, mutagenesis site 6, turn 4, sequence variant 2, sequence conflict 2, chain 1, splice variant 1

Structure

Experimental structures (PDB)

10 structures.

PDB	Method	Resolution (Å)
6R3P	X-RAY DIFFRACTION	2.05
4HYY	X-RAY DIFFRACTION	2.6
1V5W	X-RAY DIFFRACTION	3.2
7CGY	ELECTRON MICROSCOPY	3.2
7C9C	ELECTRON MICROSCOPY	3.33
7C99	ELECTRON MICROSCOPY	3.36
8R2G	X-RAY DIFFRACTION	3.45
8QQE	X-RAY DIFFRACTION	3.46
7C98	ELECTRON MICROSCOPY	3.47
2ZJB	X-RAY DIFFRACTION	3.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q14565-F1	90.82	0.85

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (9): 126–133; 230; 230; 233; 236; 236; 242; 242; 311

Mutagenesis-validated functional residues (6):

Position	Phenotype
230	abolishes binding to ssdna or dsdna.
233	abolishes binding to ssdna.
236	abolishes binding to ssdna or dsdna.
242	abolishes binding to ssdna or dsdna.
258	decreases octamer stability.
311	abolishes binding to ssdna.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-912446	Meiotic recombination

MSigDB gene sets: 160 (showing top): AHRARNT_01, GOBP_MEIOTIC_CHROMOSOME_SEGREGATION, REACTOME_MEIOTIC_RECOMBINATION, GOBP_CHROMOSOME_ORGANIZATION, GOBP_OOGENESIS, GOBP_MALE_GAMETE_GENERATION, KAUFFMANN_DNA_REPAIR_GENES, CAGCTG_AP4_Q5, GOBP_ANATOMICAL_STRUCTURE_MATURATION, GOBP_OVARIAN_FOLLICLE_DEVELOPMENT, GOBP_ORGANELLE_FISSION, SHETH_LIVER_CANCER_VS_TXNIP_LOSS_PAM2, GOBP_REPRODUCTIVE_SYSTEM_DEVELOPMENT, BLALOCK_ALZHEIMERS_DISEASE_UP, GOBP_CELL_MATURATION

GO Biological Process (19): DNA recombinase assembly (GO:0000730), ovarian follicle development (GO:0001541), oocyte maturation (GO:0001556), mitotic recombination (GO:0006312), homologous chromosome pairing at meiosis (GO:0007129), reciprocal meiotic recombination (GO:0007131), male meiosis I (GO:0007141), spermatogenesis (GO:0007283), spermatid development (GO:0007286), female gamete generation (GO:0007292), DNA strand invasion (GO:0042148), meiotic cell cycle (GO:0051321), chromosome organization involved in meiotic cell cycle (GO:0070192), double-strand break repair involved in meiotic recombination (GO:1990918), double-strand break repair via homologous recombination (GO:0000724), DNA metabolic process (GO:0006259), DNA repair (GO:0006281), gamete generation (GO:0007276), oogenesis (GO:0048477)

GO Molecular Function (12): DNA strand exchange activity (GO:0000150), DNA binding (GO:0003677), double-stranded DNA binding (GO:0003690), single-stranded DNA binding (GO:0003697), ATP binding (GO:0005524), ATP-dependent activity, acting on DNA (GO:0008094), identical protein binding (GO:0042802), ATP-dependent DNA damage sensor activity (GO:0140664), nucleotide binding (GO:0000166), protein binding (GO:0005515), ATP hydrolysis activity (GO:0016887), catalytic activity, acting on DNA (GO:0140097)

GO Cellular Component (7): chromosome, telomeric region (GO:0000781), condensed nuclear chromosome (GO:0000794), lateral element (GO:0000800), nucleus (GO:0005634), nucleoplasm (GO:0005654), chromosome (GO:0005694), site of double-strand break (GO:0035861)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Meiosis	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
DNA recombination	3
meiotic cell cycle process	3
developmental process involved in reproduction	2
meiosis I	2
male gamete generation	2
meiotic cell cycle	2
germ cell development	2
DNA metabolic process	2
sexual reproduction	2
double-strand break repair	2
catalytic activity, acting on DNA	2
DNA binding	2
ATP-dependent activity	2
cellular anatomical structure	2
double-strand break repair via synthesis-dependent strand annealing	1
protein-DNA complex assembly	1
DNA repair complex assembly	1
female gonad development	1
anatomical structure development	1
cell maturation	1
oocyte development	1
homologous chromosome segregation	1
chromosome organization involved in meiotic cell cycle	1
reciprocal homologous recombination	1
male meiotic nuclear division	1
spermatid differentiation	1
gamete generation	1
cell cycle	1
reproductive process	1
meiotic nuclear division	1
chromosome organization	1
reciprocal meiotic recombination	1
recombinational repair	1
nucleic acid metabolic process	1
DNA damage response	1
multicellular organismal reproductive process	1
female gamete generation	1
nucleic acid binding	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1

Protein interactions and networks

STRING

2446 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DMC1	SPO11	Q9Y5K1	716
DMC1	SYCP3	Q8IZU3	636
DMC1	SYCP1	Q15431	627
DMC1	MSH4	O15457	607
DMC1	PSMC3IP	Q9P2W1	593
DMC1	REC8	O95072	575
DMC1	KASH5	Q8N6L0	575
DMC1	TEX11	Q8IYF3	571
DMC1	RAD51	Q06609	549
DMC1	HORMAD1	Q86X24	549
DMC1	MND1	Q9BWT6	524
DMC1	MEIOB	Q8N635	518
DMC1	PRDM9	Q9NQV7	510
DMC1	POLM	Q9NP87	498
DMC1	RAD52	P43351	494

IntAct

89 interactions, top by confidence:

A	B	Type	Score
BRCA2	RAD51	psi-mi:“MI:0914”(association)	0.980
DMC1	NIF3L1	psi-mi:“MI:0915”(physical association)	0.810
NIF3L1	DMC1	psi-mi:“MI:0915”(physical association)	0.810
SDCBP	DMC1	psi-mi:“MI:0915”(physical association)	0.780
PSMA3	DMC1	psi-mi:“MI:0915”(physical association)	0.780
GORASP2	DMC1	psi-mi:“MI:0915”(physical association)	0.780
DMC1	SDCBP	psi-mi:“MI:0915”(physical association)	0.780
DMC1	PSMA3	psi-mi:“MI:0915”(physical association)	0.780
DMC1	GORASP2	psi-mi:“MI:0915”(physical association)	0.780
BRCA2	DMC1	psi-mi:“MI:0407”(direct interaction)	0.760

BioGRID (66): DMC1 (Two-hybrid), DMC1 (Two-hybrid), DMC1 (Two-hybrid), DMC1 (Two-hybrid), GORASP2 (Two-hybrid), NIF3L1 (Two-hybrid), KCTD17 (Two-hybrid), POTEF (Affinity Capture-MS), ACTA1 (Affinity Capture-MS), RAD51 (Affinity Capture-MS), RFWD2 (Affinity Capture-MS), SVIP (Affinity Capture-MS), DMC1 (Affinity Capture-MS), RAD51 (Two-hybrid), KCTD17 (Two-hybrid)

ESM2 similar proteins: A2SR54, A3CWU4, A4FWV5, A4YCN4, A5UMW0, A6VGG2, A8AB83, A9AA90, B8BM09, O27436, O42634, O73948, O77507, O93748, P0CW58, P0CW59, P25453, P37383, P37384, P50265, P70099, P94102, Q06609, Q08297, Q12UG7, Q14565, Q27297, Q2KJ94, Q2NE95, Q39009, Q40134, Q46A31, Q49593, Q4JAT5, Q61880, Q67EU8, Q6L126, Q7EAG4, Q7GBF7, Q7GBF8

Diamond homologs: A2SR54, A3CWU4, A3CXI2, A3MXX9, A4FWV5, A4WN87, A4YCN4, A5UMW0, A6VGG2, A8AB83, A9AA90, B0R7Y4, B1YC14, B8BM09, B8D610, C3MRI1, C3MY77, C3MZK6, C3N7M8, C3NFU5, C4KIT6, O27436, O29269, O42634, O58001, O73948, O74036, O77507, O93748, P0CW58, P0CW59, P0CW91, P0CW92, P25301, P25453, P25454, P36601, P37383, P37384, P50265

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
DMC1	“up-regulates activity”	SYCP3	binding
DMC1	“up-regulates activity”	Synaptonemal_complex	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	3
Uncertain significance	30
Likely benign	1
Benign	1

Top pathogenic / likely-pathogenic (5)

Variant ID	HGVS	Classification
1328944	NM_007068.4(DMC1):c.364A>G (p.Thr122Ala)	Pathogenic
1328945	NM_007068.4(DMC1):c.860C>A (p.Pro287His)	Pathogenic
3629598	NM_007068.4(DMC1):c.164C>T (p.Thr55Ile)	Likely pathogenic
3629599	NM_007068.4(DMC1):c.490A>G (p.Thr164Ala)	Likely pathogenic
3629600	NM_007068.4(DMC1):c.581A>G (p.Tyr194Cys)	Likely pathogenic

SpliceAI

0 predictions. Top by Δscore:

AlphaMissense

2240 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
22:38521623:G:T	A313D	1.000
22:38521628:T:A	R311S	1.000
22:38521628:T:G	R311S	1.000
22:38521629:C:G	R311T	1.000
22:38521676:A:C	H295Q	1.000
22:38521676:A:T	H295Q	1.000
22:38521678:G:C	H295D	1.000
22:38521692:C:T	G290E	1.000
22:38521695:C:T	G289E	1.000
22:38521696:C:A	G289W	1.000
22:38521696:C:G	G289R	1.000
22:38521696:C:T	G289R	1.000
22:38537624:A:C	N268K	1.000
22:38537624:A:T	N268K	1.000
22:38538354:A:G	L239S	1.000
22:38538400:A:G	S224P	1.000
22:38552689:G:A	T133I	1.000
22:38552692:T:A	K132I	1.000
22:38552693:T:G	K132Q	1.000
22:38552695:C:T	G131E	1.000
22:38552703:A:C	F128L	1.000
22:38552703:A:T	F128L	1.000
22:38552705:A:G	F128L	1.000
22:38555359:C:T	G126E	1.000
22:38520042:C:T	G334E	0.999
22:38520043:C:G	G334R	0.999
22:38520043:C:T	G334R	0.999
22:38520067:C:G	A326P	0.999
22:38521624:C:G	A313P	0.999
22:38521629:C:A	R311I	0.999

dbSNP variants (sampled 300 via entrez): RS1000021132 (22:38558809 C>T), RS1000026804 (22:38544478 G>A), RS1000097479 (22:38552183 T>G), RS1000099582 (22:38518381 G>A), RS1000132675 (22:38509007 C>T), RS1000137685 (22:38517367 G>A), RS1000212795 (22:38524366 C>A,T), RS1000248111 (22:38524137 C>G,T), RS1000389926 (22:38530853 C>T), RS1000469291 (22:38518911 C>A), RS1000475627 (22:38510214 G>A), RS1000525982 (22:38510447 T>G), RS1000721606 (22:38532680 T>C), RS1000731986 (22:38538362 A>C), RS1000735862 (22:38570287 G>A,C)

Disease associations

OMIM: gene MIM:602721 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
primary ovarian failure	Strong	Autosomal recessive
azoospermia	Strong	Autosomal recessive
spermatogenic failure	Limited	Autosomal recessive

Mondo (3): azoospermia (MONDO:0100459), primary ovarian failure (MONDO:0005387), spermatogenic failure (MONDO:0004983)

Orphanet (1): NON RARE IN EUROPE: Primary ovarian failure (Orphanet:619)

HPO phenotypes

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

GWAS associations

0 associations (top):

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D053713	Azoospermia	C12.100.500.430.380; C12.100.750.700.380; C12.200.294.430.380
D016649	Primary Ovarian Insufficiency	C12.050.351.500.056.630.750; C12.100.250.056.630.750; C19.391.630.750

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

31 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Cadmium Chloride	decreases expression, increases abundance, increases expression	2
fluorene-9-bisphenol	increases expression	1
myristicin	decreases expression	1
chlorophyllin	decreases reaction, increases expression	1
bromoacetate	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
sodium arsenite	decreases expression	1
zinc chromate	decreases expression, increases abundance	1
chromium hexavalent ion	decreases expression, increases abundance	1
CGP 52608	affects binding, increases reaction	1
chloropicrin	increases expression	1
2-palmitoylglycerol	increases expression	1
entinostat	increases expression	1
erucylphospho-N,N,N-trimethylpropylammonium	increases expression	1
ICG 001	increases expression	1
abrine	decreases expression	1
incobotulinumtoxinA	decreases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	increases expression	1
Temozolomide	decreases expression	1
Sunitinib	increases expression	1
Air Pollutants	increases abundance, increases expression	1
Benzo(a)pyrene	increases expression, decreases reaction	1
Cadmium	decreases expression, increases abundance	1
Dichlorodiphenyl Dichloroethylene	increases expression	1
Tobacco Smoke Pollution	decreases expression	1
Tretinoin	decreases expression	1
Valproic Acid	affects expression	1
Aflatoxin B1	increases methylation	1
Asbestos, Crocidolite	decreases expression	1
Antirheumatic Agents	decreases expression	1

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B8EQ	Abcam HCT 116 DMC1 KO	Cancer cell line	Male
CVCL_B8UU	Abcam MCF-7 DMC1 KO	Cancer cell line	Female
CVCL_B9GZ	Abcam A-549 DMC1 KO	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00417066	PHASE4	COMPLETED	Flexible GnRH Antagonist vs Flare up GnRH Agonist Protocol in Poor Responders
NCT00732693	PHASE4	COMPLETED	Evaluation of Physiologic and Standard Sex Steroid Replacement Regimens in Women With Premature Ovarian Failure
NCT00837616	PHASE4	COMPLETED	Estrogen Dosing in Turner Syndrome: Pharmacology and Metabolism
NCT01853501	PHASE4	UNKNOWN	Effects of ADSC Therapy in Women With POF
NCT02783937	PHASE4	COMPLETED	Filgrastim for Premature Ovarian Insufficiency
NCT03535480	PHASE4	UNKNOWN	Autologous Bone Marrow Stem Cell Ovarian Transplantation to Restore Ovarian Function in Premature Ovarian Failure
NCT02307994	PHASE4	UNKNOWN	Clinical Research on Effectiveness and Safety of Treatment of Severe Oligospermia or Azoospermia With uFSH
NCT00140998	PHASE3	COMPLETED	Estrogen Treatment (Oral vs. Patches) in Turner Syndrome
NCT02275169	PHASE3	UNKNOWN	FSH Treatment for Non-obstructive Azoospermic Patients
NCT00001951	PHASE2	COMPLETED	Hormone Replacement in Young Women With Premature Ovarian Failure
NCT00370019	PHASE2	WITHDRAWN	Effects of an Estrogen Replacement Therapy Skin Patch on Ovulation in Women With Premature Ovarian Failure
NCT00429494	PHASE2	COMPLETED	GnRH Analogue for Ovarian Function Preservation in Hematopoietic Stem Cell Transplantation Patients
NCT03816852	PHASE2	SUSPENDED	The Safety and Efficiency Study of Mesenchymal Stem Cell (19#iSCLife®-POI) in Premature Ovarian Insufficiency
NCT04536467	PHASE2	UNKNOWN	Prevention of Chemotherapy-Induced Ovarian Failure With Goserelin in Premenopausal Lymphoma Patients
NCT06117982	PHASE2	COMPLETED	The Impact of Granulocyte Colony Stimulating Factor on Premature Ovarian Insufficiency
NCT02544191	PHASE2	UNKNOWN	GnRHa Combined With hCG and hMG for Treatment of Patients With Non-obstructive Azoospermia
NCT03762967	PHASE2	UNKNOWN	Autologous Adipose-Derived Adult Stromal Vascular Cell Administration for Male Patients With Infertility
NCT02912104	PHASE1	COMPLETED	A Therapeutic Trial of Human Amniotic Epithelial Cells Transplantation for Primary Ovarian Failure
NCT03178695	PHASE1	COMPLETED	Inovium Ovarian Rejuvenation Trials
NCT04815213	PHASE1	ACTIVE_NOT_RECRUITING	The Use of Expandeded Mesenchymal Stromal Cells (MSC) in Premature Ovarian Failure (POF) in Adult Humans
NCT05138367	PHASE1	COMPLETED	Effects of UCA-PSCs in Women With POF
NCT06132542	PHASE1	UNKNOWN	Autologous ADMSC Transplantation in Patients With POI
NCT00948857	PHASE2/PHASE3	TERMINATED	Dehydroepiandrosterone (DHEA) Treatment and Premature Ovarian Failure (POF)
NCT04031456	PHASE2/PHASE3	RECRUITING	Autologous PRP Infusion May Restore Ovarian Function and May Promote Folliculogenesis in POI Patients
NCT02043743	PHASE1/PHASE2	UNKNOWN	Autologous Stem Cells Transplantation in Patients With Idiopathic and Drug Induced Premature Ovarian Failure
NCT02062931	PHASE1/PHASE2	UNKNOWN	Autologous Mesenchymal Stem Cells Transplantation In Women With Premature Ovarian Failure
NCT02151890	PHASE1/PHASE2	COMPLETED	Pregnancy After Stem Cell Transplantation in Premature Ovarian Failure
NCT02372474	PHASE1/PHASE2	COMPLETED	It is a Real The First Baby Of Autologous Stem Cell Therapy in Premature Ovarian Failure
NCT02603744	PHASE1/PHASE2	UNKNOWN	Autologous Adipose Derived Mesenchymal Stromal Cells Transplantation in Women With Premature Ovarian Failure (POF)
NCT02644447	PHASE1/PHASE2	COMPLETED	Transplantation of HUC-MSCs With Injectable Collagen Scaffold for POF
NCT03069209	PHASE1/PHASE2	UNKNOWN	Autologous Bone Marrow-Derived Stem Cell Transplantation in Patients With Premature Ovarian Failure (POF)
NCT03985462	PHASE1/PHASE2	WITHDRAWN	Very Small Embryonic-like Stem Cells for Ovary
NCT04009473	PHASE1/PHASE2	UNKNOWN	Stem Cell Therapy and Growth Factor Ovarian in Vitro Activation
NCT04071574	PHASE1/PHASE2	COMPLETED	Comparative Study on the Efficacy of Ovarian Stimulation Protocols on the Success Rate of ICSI in Female Infertility
NCT04922398	PHASE1/PHASE2	UNKNOWN	Ovarian Injection of PRP (Platelet -Rich Plasma) Vs Normal Saline in Premature Ovarian Insufficiency
NCT05462379	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Autologous Heterotopic Fresh Ovarian Graft in Woman With LACC Eligible for Pelvic Radiotherapy Treatment.
NCT06202547	PHASE1/PHASE2	UNKNOWN	Intra-ovarian Injection of MSC-EVs in Idiopathic Premature Ovarian Failure
NCT01129947	EARLY_PHASE1	WITHDRAWN	The Use of DHEA in Women With Premature Ovarian Failure
NCT05522634	EARLY_PHASE1	UNKNOWN	A Clinical Study of Chinese Herbal Compound TJAOA101 in the Treatment of Premature Ovarian Insufficiency
NCT07308327	EARLY_PHASE1	ACTIVE_NOT_RECRUITING	The Influence of Gut Microbiota on Ovarian Function: A Single-center, Randomized,Double Blind, Parallel-controlled, Exploratory Clinical Trial