MCMDC2

Summary

MCMDC2 (minichromosome maintenance domain containing 2, HGNC:26368) is a protein-coding gene on chromosome 8q13.1, encoding Minichromosome maintenance domain-containing protein 2 (Q4G0Z9). Plays an important role in meiotic recombination and associated DNA double-strand break repair.

Predicted to enable ATP binding activity and DNA binding activity. Predicted to be involved in double-strand break repair via break-induced replication. Predicted to act upstream of or within meiosis I cell cycle process; oogenesis; and spermatogenesis. Predicted to be active in nucleus.

Source: NCBI Gene 157777 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 86 total — 1 pathogenic, 2 likely-pathogenic
• MANE Select transcript: NM_173518

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26368
Approved symbol	MCMDC2
Name	minichromosome maintenance domain containing 2
Location	8q13.1
Locus type	gene with protein product
Status	Approved
Aliases	FLJ25692
Ensembl gene	ENSG00000178460
Ensembl biotype	protein_coding
OMIM	617545
Entrez	157777

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 7 protein_coding, 2 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000313616, ENST00000396592, ENST00000415737, ENST00000422365, ENST00000428734, ENST00000469823, ENST00000492775, ENST00000872355, ENST00000872356, ENST00000941704

RefSeq mRNA: 3 — MANE Select: NM_173518 NM_001136160, NM_001136161, NM_173518

CCDS: CCDS47868, CCDS47869, CCDS6197

Canonical transcript exons

ENST00000422365 — 15 exons

Exon	Start	End
ENSE00001323192	66874326	66874456
ENSE00001650950	66870771	66870831
ENSE00001691818	66919003	66922048
ENSE00003458470	66878574	66878696
ENSE00003460116	66877349	66877544
ENSE00003477125	66880849	66880974
ENSE00003487945	66890865	66891070
ENSE00003488940	66878815	66878919
ENSE00003514908	66905226	66905335
ENSE00003532281	66883757	66883994
ENSE00003534313	66896780	66896959
ENSE00003558926	66901206	66901348
ENSE00003559429	66874053	66874234
ENSE00003664437	66874527	66874586
ENSE00003678269	66896170	66896336

Expression profiles

Bgee: expression breadth ubiquitous, 157 present calls, max score 83.05.

FANTOM5 (CAGE): breadth broad, TPM avg 0.8598 / max 55.9345, expressed in 492 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
89225	0.8598	492

Top tissues by expression

243 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	83.05	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	79.65	gold quality
right testis	UBERON:0004534	75.83	gold quality
left testis	UBERON:0004533	75.48	gold quality
testis	UBERON:0000473	75.09	gold quality
cortical plate	UBERON:0005343	73.48	gold quality
hindlimb stylopod muscle	UBERON:0004252	67.34	gold quality
muscle of leg	UBERON:0001383	65.64	gold quality
gastrocnemius	UBERON:0001388	65.22	gold quality
ventricular zone	UBERON:0003053	64.45	gold quality
right adrenal gland	UBERON:0001233	63.96	gold quality
cerebellar hemisphere	UBERON:0002245	63.51	gold quality
cerebellar cortex	UBERON:0002129	63.48	gold quality
ganglionic eminence	UBERON:0004023	63.21	gold quality
right adrenal gland cortex	UBERON:0035827	63.21	gold quality
rectum	UBERON:0001052	63.20	gold quality
islet of Langerhans	UBERON:0000006	62.78	gold quality
left adrenal gland	UBERON:0001234	62.70	gold quality
left adrenal gland cortex	UBERON:0035825	62.19	gold quality
right hemisphere of cerebellum	UBERON:0014890	62.01	gold quality
cerebellum	UBERON:0002037	61.83	gold quality
heart left ventricle	UBERON:0002084	61.29	gold quality
adrenal gland	UBERON:0002369	61.20	gold quality
adrenal tissue	UBERON:0018303	61.09	gold quality
adrenal cortex	UBERON:0001235	60.85	gold quality
right uterine tube	UBERON:0001302	60.76	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	60.66	gold quality
right atrium auricular region	UBERON:0006631	60.66	gold quality
cardiac ventricle	UBERON:0002082	60.62	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	60.46	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.76
E-MTAB-8060	no	30.69

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): E2F1

miRNA regulators (miRDB)

140 targeting MCMDC2, 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-3613-3P	100.00	76.36	7965
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AD-5P	99.94	71.23	3502
HSA-MIR-548AE-5P	99.94	71.23	3502
HSA-MIR-548AK	99.94	71.24	3488
HSA-MIR-548AM-5P	99.94	71.24	3488
HSA-MIR-548AP-5P	99.94	71.14	3489
HSA-MIR-548AQ-5P	99.94	71.34	3426
HSA-MIR-548AR-5P	99.94	71.28	3515
HSA-MIR-548AS-5P	99.94	71.22	3482
HSA-MIR-548AU-5P	99.94	71.24	3488
HSA-MIR-548AY-5P	99.94	71.23	3502
HSA-MIR-548B-5P	99.94	71.23	3502
HSA-MIR-548BB-5P	99.94	71.27	3509
HSA-MIR-548C-5P	99.94	71.24	3488
HSA-MIR-548D-5P	99.94	71.23	3502
HSA-MIR-548H-5P	99.94	71.24	3488

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	MCMDC2	ENSDARG00000106560
mus_musculus	Mcmdc2	ENSMUSG00000046101
rattus_norvegicus	Mcmdc2	ENSRNOG00000021702

Paralogs (8): MCM2 (ENSG00000073111), MCM6 (ENSG00000076003), MCM5 (ENSG00000100297), MCM4 (ENSG00000104738), MCM9 (ENSG00000111877), MCM3 (ENSG00000112118), MCM8 (ENSG00000125885), MCM7 (ENSG00000166508)

Protein

Protein identifiers

Minichromosome maintenance domain-containing protein 2 — Q4G0Z9 (reviewed: Q4G0Z9)

All UniProt accessions (5): Q4G0Z9, B4DXX4, F8WCM6, F8WDR8, G3XAN3

UniProt curated annotations — full annotation on UniProt →

Function. Plays an important role in meiotic recombination and associated DNA double-strand break repair.

Isoforms (4)

UniProt ID	Names	Canonical?
Q4G0Z9-1	1	yes
Q4G0Z9-2	2
Q4G0Z9-3	3
Q4G0Z9-4	4

RefSeq proteins (3): NP_001129632, NP_001129633, NP_775789* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR031327	MCM	Family
IPR041562	MCM_lid	Domain
IPR058769	MCMDC2_N	Domain

Pfam: PF17855, PF26063

UniProt features (17 total): sequence conflict 5, splice variant 4, sequence variant 3, short sequence motif 2, chain 1, domain 1, modified residue 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q4G0Z9-F1	86.00	0.56

Functional residue map

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

Post-translational modifications (1): 292

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 77 (showing top): GOBP_MEIOTIC_CHROMOSOME_SEGREGATION, GOBP_CHROMOSOME_ORGANIZATION, GOBP_OOGENESIS, GOBP_MALE_GAMETE_GENERATION, GOBP_SYNAPTONEMAL_COMPLEX_ORGANIZATION, GOBP_ORGANELLE_FISSION, GOBP_DNA_DAMAGE_RESPONSE, GOBP_CELLULAR_PROCESS_INVOLVED_IN_REPRODUCTION_IN_MULTICELLULAR_ORGANISM, GOBP_CHROMOSOME_ORGANIZATION_INVOLVED_IN_MEIOTIC_CELL_CYCLE, GOBP_FEMALE_GAMETE_GENERATION, GOBP_DEVELOPMENTAL_PROCESS_INVOLVED_IN_REPRODUCTION, GOBP_HOMOLOGOUS_CHROMOSOME_SEGREGATION, GOBP_MEIOTIC_CELL_CYCLE_PROCESS, GOBP_PROTEIN_DNA_COMPLEX_ORGANIZATION, GOBP_RECOMBINATIONAL_REPAIR

GO Biological Process (10): double-strand break repair via break-induced replication (GO:0000727), synaptonemal complex assembly (GO:0007130), spermatogenesis (GO:0007283), late meiotic recombination nodule assembly (GO:0042140), oogenesis (GO:0048477), double-strand break repair involved in meiotic recombination (GO:1990918), DNA repair (GO:0006281), DNA damage response (GO:0006974), meiotic recombination nodule assembly (GO:0007146), meiotic cell cycle (GO:0051321)

GO Molecular Function (3): DNA binding (GO:0003677), ATP binding (GO:0005524), protein binding (GO:0005515)

GO Cellular Component (1): nucleus (GO:0005634)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
double-strand break repair via homologous recombination	1
homologous chromosome pairing at meiosis	1
cellular component assembly	1
chromosome organization involved in meiotic cell cycle	1
synaptonemal complex organization	1
developmental process involved in reproduction	1
male gamete generation	1
meiotic recombination nodule assembly	1
germ cell development	1
female gamete generation	1
double-strand break repair	1
reciprocal meiotic recombination	1
meiotic cell cycle process	1
DNA metabolic process	1
DNA damage response	1
cellular response to stress	1
meiotic DNA recombinase assembly	1
cell cycle	1
sexual reproduction	1
reproductive process	1
meiotic nuclear division	1
nucleic acid binding	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
binding	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

1238 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MCMDC2	MSH4	O15457	579
MCMDC2	MCM9	Q9NXL9	553
MCMDC2	SHOC1	Q5VXU9	542
MCMDC2	A0A494C100	A0A494C100	496
MCMDC2	MCM8	Q9UJA3	493
MCMDC2	GINS4	Q9BRT9	483
MCMDC2	TEX11	Q8IYF3	462
MCMDC2	HORMAD1	Q86X24	456
MCMDC2	SYCP1	Q15431	456
MCMDC2	C14orf39	Q8N1H7	454
MCMDC2	SPO11	Q9Y5K1	452
MCMDC2	RNF212	Q495C1	440
MCMDC2	REC8	O95072	440
MCMDC2	ORC3	Q9UBD5	432
MCMDC2	ORC5	O43913	429

IntAct

4 interactions, top by confidence:

A	B	Type	Score
MCMDC2	LXN	psi-mi:“MI:0915”(physical association)	0.560
LXN	MCMDC2	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (3): MCMDC2 (Affinity Capture-MS), MCMDC2 (Two-hybrid), MCMDC2 (Cross-Linking-MS (XL-MS))

ESM2 similar proteins: A0JM23, A0JMU5, D3ZVK1, E1BPX4, E9PXF8, E9Q956, G5EF51, P0CI65, P49717, P57075, P81128, P83509, Q008S8, Q0V9Q6, Q16K67, Q1RMS6, Q32NG0, Q32NR9, Q3EBC8, Q3V3E1, Q4G0Z9, Q5N870, Q5R6Y2, Q5XI14, Q5ZL91, Q66IW8, Q692V3, Q6AZT7, Q6DIR8, Q6NTN5, Q6P2P2, Q6P2S7, Q6P5D8, Q6ZS30, Q7TQK1, Q7Z392, Q7Z494, Q80VJ4, Q8BGG7, Q8C0L9

Diamond homologs: E9Q956, Q4G0Z9, Q5XI14

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	2
Uncertain significance	63
Likely benign	2
Benign	4

Top pathogenic / likely-pathogenic (3)

Variant ID	HGVS	Classification
1328953	NM_173518.5(MCMDC2):c.1795C>T (p.Arg599Ter)	Pathogenic
2690955	NM_173518.5(MCMDC2):c.1363C>T (p.Gln455Ter)	Likely pathogenic
2690956	NM_173518.5(MCMDC2):c.1767T>A (p.Tyr589Ter)	Likely pathogenic

SpliceAI

2265 predictions. Top by Δscore:

Variant	Effect	Δscore
8:66870832:G:C	donor_loss	1.0000
8:66874457:G:GG	donor_gain	1.0000
8:66878687:G:GG	donor_gain	1.0000
8:66878813:A:G	acceptor_gain	1.0000
8:66880847:A:AG	acceptor_gain	1.0000
8:66880848:G:GG	acceptor_gain	1.0000
8:66883755:A:AG	acceptor_gain	1.0000
8:66883756:G:GA	acceptor_gain	1.0000
8:66883976:A:AG	donor_gain	1.0000
8:66896168:A:AG	acceptor_gain	1.0000
8:66896169:G:GG	acceptor_gain	1.0000
8:66896333:GATG:G	donor_gain	1.0000
8:66870832:G:GG	donor_gain	0.9900
8:66874251:T:A	donor_loss	0.9900
8:66874587:G:GG	donor_gain	0.9900
8:66878569:TTCA:T	acceptor_loss	0.9900
8:66878570:TCA:T	acceptor_loss	0.9900
8:66878572:A:AG	acceptor_gain	0.9900
8:66878572:A:T	acceptor_loss	0.9900
8:66878572:AG:A	acceptor_gain	0.9900
8:66878573:G:A	acceptor_loss	0.9900
8:66878573:G:GG	acceptor_gain	0.9900
8:66878573:GG:G	acceptor_gain	0.9900
8:66878685:GA:G	donor_gain	0.9900
8:66878694:GTG:G	donor_gain	0.9900
8:66878695:TGGTA:T	donor_loss	0.9900
8:66878697:G:T	donor_loss	0.9900
8:66878698:T:G	donor_loss	0.9900
8:66878814:G:GG	acceptor_gain	0.9900
8:66880841:A:AG	acceptor_gain	0.9900

AlphaMissense

4459 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:66896265:T:A	W459R	0.993
8:66896265:T:C	W459R	0.993
8:66877514:T:C	C151R	0.990
8:66878642:T:C	C184R	0.990
8:66883906:A:C	S329R	0.989
8:66883908:T:A	S329R	0.989
8:66883908:T:G	S329R	0.989
8:66877508:T:C	F149L	0.988
8:66877510:T:A	F149L	0.988
8:66877510:T:G	F149L	0.988
8:66883816:T:A	W299R	0.987
8:66883816:T:C	W299R	0.987
8:66901288:G:C	R570P	0.987
8:66905284:G:C	D610H	0.987
8:66890878:A:C	S363R	0.986
8:66890880:C:A	S363R	0.986
8:66890880:C:G	S363R	0.986
8:66905285:A:C	D610A	0.986
8:66877509:T:C	F149S	0.985
8:66877502:G:C	A147P	0.984
8:66878686:A:C	R198S	0.984
8:66878686:A:T	R198S	0.984
8:66874181:T:C	L14P	0.983
8:66878606:G:C	A172P	0.982
8:66905242:G:C	A596P	0.982
8:66877514:T:A	C151S	0.981
8:66877515:G:C	C151S	0.981
8:66877529:T:C	C156R	0.981
8:66905285:A:T	D610V	0.981
8:66919090:T:C	L656P	0.981

dbSNP variants (sampled 300 via entrez): RS1000009447 (8:66889827 C>T), RS1000152728 (8:66907767 T>A,C), RS1000402023 (8:66920797 C>G,T), RS1000408237 (8:66885069 C>G,T), RS1000430736 (8:66886216 G>A), RS1000604903 (8:66899976 A>C), RS1000654281 (8:66892609 G>A), RS1000732974 (8:66884541 T>C), RS1000761841 (8:66893713 A>G), RS1000906707 (8:66880035 G>A), RS1000961223 (8:66890928 T>G), RS1000973083 (8:66887130 A>G), RS1001022916 (8:66898783 T>C), RS1001023937 (8:66907067 C>G), RS1001032726 (8:66899171 T>G)

Disease associations

OMIM: gene MIM:617545 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): azoospermia (MONDO:0100459)

Orphanet (1): Male infertility with azoospermia or oligozoospermia due to single gene mutation (Orphanet:399805)

HPO phenotypes

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

GWAS associations

0 associations (top):

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D053713	Azoospermia	C12.100.500.430.380; C12.100.750.700.380; C12.200.294.430.380

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

15 total (human), top 15 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases expression, increases methylation	2
propionaldehyde	increases expression	1
perfluorooctanoic acid	increases expression	1
perfluorooctane sulfonic acid	increases expression	1
perfluoro-n-nonanoic acid	increases expression	1
erucylphospho-N,N,N-trimethylpropylammonium	increases expression	1
ICG 001	increases 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
Estradiol	affects cotreatment, decreases expression	1
Formaldehyde	decreases expression	1
Methotrexate	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Aflatoxin B1	decreases methylation	1
Aflatoxin M1	decreases expression	1
Asbestos, Crocidolite	decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT02307994	PHASE4	UNKNOWN	Clinical Research on Effectiveness and Safety of Treatment of Severe Oligospermia or Azoospermia With uFSH
NCT02275169	PHASE3	UNKNOWN	FSH Treatment for Non-obstructive Azoospermic Patients
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
NCT02041910	PHASE1/PHASE2	UNKNOWN	Testicular Injection of Autologous Stem Cells for Treatment of Patients With Azoospermia
NCT00282477	Not specified	UNKNOWN	Trial to Evaluate Erectile Function, Fertility and Sperm Count in Male Cyclists Compared to Age Matched Controls
NCT00484081	Not specified	COMPLETED	Microdissection Testicular Sperm Extraction (MicroTESE) and IVF-ICSI Outcome in Non-Obstructive Azoospermia (NOA)
NCT00548977	Not specified	COMPLETED	Genetic Studies Spermatogenic Failure
NCT01375062	Not specified	COMPLETED	Obtaining Undifferentiated Cells From Testis Biopsy
NCT01509482	Not specified	COMPLETED	Insulin Resistance in Idiopathic Oligospermia and Azoospermia
NCT02008799	Not specified	UNKNOWN	Intra Testicular Artery Injection of Bone Marrow Stem Cell in Management of Azoospermia
NCT02339272	Not specified	COMPLETED	Study of Synapsis and Recombination in Male Meiosis and the Implications in Infertility
NCT02414295	Not specified	COMPLETED	Sperm Production in Kleinfelter Syndrome Patients After Mesenchymal Stem Cell Injection
NCT02418832	Not specified	RECRUITING	Testis Needle Aspiration of Sperm in Men With Azoospermia
NCT02617173	Not specified	UNKNOWN	The Effect of Low Electrical Current on Testicular Spermatocyte Count
NCT02773498	Not specified	TERMINATED	Comparison of Medical Results of Testicular Sperm Extraction by Conventional Surgery and Microsurgical Track
NCT03497728	Not specified	TERMINATED	Detection of Microdeletions in the Azoospermia Factor (AZF) Regions in Infertile Male Patients
NCT04675164	Not specified	COMPLETED	Laser Assisted Sperm Selection of Viable Immotile Testicular Sperm in Azoospermic Infertile Men
NCT05479474	Not specified	RECRUITING	Platelet Rich Plasma Testis Treatment for Infertile Men
NCT05628987	Not specified	RECRUITING	The Association of Gut Microbiota and Spermatogenic Dysfunction
NCT05866484	Not specified	COMPLETED	Testicular Sperm Aspiration (TESA) vs. Microfluidic Sperm Separation (MSS)
NCT06524258	Not specified	COMPLETED	Testicular Elastography for Microscopic Testicular Sperm Extraction
NCT06841328	Not specified	RECRUITING	Fertility Enhancement Through Regenerative Treatment in Ovaries and Testes
NCT06941922	Not specified	RECRUITING	Testicular Evaluation of Azoospermia Using Micro-Ultrasound
NCT07074015	Not specified	RECRUITING	IntelliWell: An AI-Assisted Imaging Platform for Detection and Location of Ultra-Rare Testicular Sperm in Surgical Specimens
NCT07357701	Not specified	RECRUITING	Identifying Genome Variants in Non-Obstructive Azoospermia (NOA) or Primary Ovarian Insufficiency (POI)
NCT07542626	Not specified	RECRUITING	Fertility Restoration With Autografting of Cryopreserved Immature Testicular Tissue