MCMDC2

protein-coding

minichromosome maintenance domain containing 2, the group of MCM family

Gene summary

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. [provided by Alliance of Genome Resources, Jul 2025]

Previous symbols:

C8orf45

MANE transcript

NM_173518.5

Inheritance

—

ClinVar variants

P:3U:68B:5

Top phenotype

Male infertility with azoospermia or oligozoospermia due to single gene mutation

gnomAD constraint

pLI —, LoF o/e 0.61

Max pathogenic AF

—

Genomic locus

chr8:66,870,749-66,922,048

External References & Databases

Ensembl (ENSG00000178460)

Transcript & Mutation Effects

hg38 • Region Span ~51.3 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to MCMDC2 variants in ClinVar

5 Conditions Cataloged

not specifiedTotal: 65

not providedTotal: 4

Male infertility with azoospermia or oligozoospermia due to single gene mutationTotal: 2

AzoospermiaTotal: 1

See casesTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_173518.5. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous					1 clinvar	1
missense			66 clinvar	2 clinvar	2 clinvar	70
nonsense	1 clinvar	2 clinvar	1 clinvar			4
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)						0
Total	1	2	68	2	3	76

Highest pathogenic variant AF is 0.00018465654

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 25 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_173518.5	RefSeq	NP_775789.3	14	MANE Select
ENST00000422365.7	Ensembl	ENSP00000413632.2	14	MANE Select
NM_001136160.2	RefSeq	NP_001129632.1	13	Standard
NM_001136161.2	RefSeq	NP_001129633.1	12	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

DNA replication initiation
synaptonemal complex assembly
spermatogenesis
late meiotic recombination nodule assembly
oogenesis

Molecular Function

DNA binding
ATP binding

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000422365
Coding exons: 14
Length: 51300
Individuals with no LoFs: 125555
Homozygous LoFs: 0
Heterozygous LoFs: 187
Defined: 125742
p: 0.000744

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.07	269	323	0.833	0.0000151	4422
Missense (PolyPhen)		79	98.935	0.7985		1319
Synonymous	0.935	103	116	0.890	0.00000535	1309
Loss of Function	1.97	18	29.5	0.610	0.00000137	430

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00031	0.00025	rare
Latino/Admixed American	0.00036	0.00029	rare
Ashkenazi Jewish	0.0017	0.0017	notable
East Asian	0	0.0	absent
Finnish	0.0029	0.0029	notable
European (Non-Finnish)	0.00078	0.00074	rare
South Asian	0.00014	0.00013	rare
Other	0.0010	0.00098	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Plays an important role in meiotic recombination and associated DNA double-strand break repair. {ECO:0000250|UniProtKB:E9Q956}.;

Intolerance Scores

RVIS EVS: 1.16
RVIS percentile EVS: 92.59

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N

Gene Damage Prediction

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