MCM2

minichromosome maintenance complex component 2, the group of MCM family|minichromosome maintenance 2-7 complex

Basic information

Region (hg38): 3:127598223-127622436

Previous symbols: [ "CCNL1", "CDCL1" ]

Links

ENSG00000073111 ∙ NCBI:4171 ∙ OMIM:116945 ∙ HGNC:6944 ∙ Uniprot:P49736 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• autosomal dominant nonsyndromic hearing loss 70 (Limited), mode of inheritance: AD
• autosomal dominant nonsyndromic hearing loss (Supportive), mode of inheritance: AD
• autosomal dominant nonsyndromic hearing loss 70 (Strong), mode of inheritance: AD
• nonsyndromic genetic hearing loss (Limited), mode of inheritance: AD
• autosomal dominant nonsyndromic hearing loss 70 (Limited), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Deafness, autosomal dominant 70	AD	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Audiologic/Otolaryngologic	26196677

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the MCM2 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MCM2 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				55	12	67
missense		1	138	14	4	157
nonsense			1			1
start loss			1			1
frameshift						0
inframe indel			4			4
splice donor/acceptor (+/-2bp)		1				1
splice region			4	4	2	10
non coding			3	28	8	39
Total	0	2	147	97	24

Variants in MCM2

This is a list of pathogenic ClinVar variants found in the MCM2 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
3-127598469-G-A			Uncertain significance (May 29, 2023)
3-127598471-C-A			Uncertain significance (Mar 10, 2022)
3-127599299-A-G			Likely benign (Dec 16, 2022)
3-127599302-G-A			Likely benign (Oct 04, 2022)
3-127599326-G-A			Likely benign (Jan 03, 2024)
3-127599344-A-C			Likely benign (Oct 15, 2022)
3-127599350-C-G			Uncertain significance (Nov 15, 2022)
3-127599351-C-G			Uncertain significance (Jun 13, 2024)
3-127599359-G-T			Uncertain significance (Apr 17, 2021)
3-127599363-C-T			Uncertain significance (Dec 31, 2023)
3-127599364-G-C		not specified	Benign/Likely benign (May 12, 2023)
3-127599379-C-T			Uncertain significance (Feb 03, 2023)
3-127599409-G-A			Benign/Likely benign (Jul 31, 2023)
3-127599412-G-C		not specified	Uncertain significance (May 21, 2024)
3-127599427-C-T		not specified	Uncertain significance (Nov 17, 2023)
3-127599437-T-C		MCM2-related disorder	Benign (Jan 02, 2024)
3-127599441-C-T		Autosomal dominant nonsyndromic hearing loss 70	no classifications from unflagged records (Apr 30, 2024)
3-127599442-G-A		not specified	Uncertain significance (Dec 16, 2022)
3-127599455-A-G			Likely benign (May 23, 2018)
3-127599470-C-T		MCM2-related disorder	Likely benign (Dec 01, 2023)
3-127599471-G-A			Uncertain significance (Nov 20, 2022)
3-127599494-G-A			Likely benign (Oct 24, 2023)
3-127599515-T-G		MCM2-related disorder	Benign (Jan 15, 2024)
3-127599518-A-G			Likely benign (Sep 21, 2023)
3-127599524-G-C			Uncertain significance (Dec 22, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
MCM2	protein_coding	protein_coding	ENST00000265056	16	24211

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0000263	1.00	125705	0	43	125748	0.000171

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.68	490	606	0.808	0.0000418	5984
Missense in Polyphen		151	225.96	0.66827		2235
Synonymous	-1.36	268	241	1.11	0.0000169	1786
Loss of Function	3.61	15	39.5	0.380	0.00000213	440

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000387	0.000387
Ashkenazi Jewish	0.0000993	0.0000992
East Asian	0.000327	0.000326
Finnish	0.000185	0.000185
European (Non-Finnish)	0.000160	0.000158
Middle Eastern	0.000327	0.000326
South Asian	0.0000653	0.0000653
Other	0.000493	0.000489

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Acts as component of the MCM2-7 complex (MCM complex) which is the putative replicative helicase essential for 'once per cell cycle' DNA replication initiation and elongation in eukaryotic cells. The active ATPase sites in the MCM2-7 ring are formed through the interaction surfaces of two neighboring subunits such that a critical structure of a conserved arginine finger motif is provided in trans relative to the ATP-binding site of the Walker A box of the adjacent subunit. The six ATPase active sites, however, are likely to contribute differentially to the complex helicase activity. Required for the entry in S phase and for cell division. Plays a role in terminally differentiated hair cells development of the cochlea and induces cells apoptosis. {ECO:0000269|PubMed:26196677, ECO:0000269|PubMed:8175912}.
• Disease: DISEASE: Deafness, autosomal dominant, 70 (DFNA70) [MIM:616968]: A form of non-syndromic sensorineural hearing loss. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information. DFNA70 is characterized by slowly progressive, postlingual hearing impairment. {ECO:0000269|PubMed:26196677}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Cell cycle - Homo sapiens (human);DNA replication - Homo sapiens (human);Cell Cycle;G1 to S cell cycle control;DNA Replication;cdk regulation of dna replication;Activation of ATR in response to replication stress;G2/M Checkpoints;Cell Cycle Checkpoints;Activation of the pre-replicative complex;Unwinding of DNA;Mitotic G1-G1/S phases;Orc1 removal from chromatin;DNA Replication;Switching of origins to a post-replicative state;DNA strand elongation;Synthesis of DNA;S Phase;G1/S Transition;Assembly of the pre-replicative complex;DNA Replication Pre-Initiation;M/G1 Transition;Cell Cycle;Cell Cycle, Mitotic;ATR signaling pathway (Consensus)

Recessive Scores

• pRec: 0.129

Intolerance Scores

• loftool: 0.429
• rvis_EVS: -0.95
• rvis_percentile_EVS: 9.38

Haploinsufficiency Scores

• pHI: 0.994
• hipred: Y
• hipred_score: 0.661
• ghis: 0.679

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.991

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Mcm2
• Phenotype: growth/size/body region phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); endocrine/exocrine gland phenotype; muscle phenotype; cellular phenotype; embryo phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); respiratory system phenotype; hematopoietic system phenotype; normal phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); pigmentation phenotype; neoplasm; digestive/alimentary phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); immune system phenotype

Zebrafish Information Network

• Gene name: mcm2
• Affected structure: pharyngeal arch 3-7
• Phenotype tag: abnormal
• Phenotype quality: aplastic

Gene ontology

• Biological process: G1/S transition of mitotic cell cycle;DNA replication;DNA unwinding involved in DNA replication;DNA replication initiation;nucleosome assembly;apoptotic process;cellular response to interleukin-4;cochlea development;negative regulation of DNA helicase activity
• Cellular component: nuclear chromosome, telomeric region;chromatin;nucleus;nucleoplasm;nuclear origin of replication recognition complex;nucleolus;cytoplasm;microtubule cytoskeleton;MCM complex
• Molecular function: DNA binding;DNA replication origin binding;helicase activity;protein binding;ATP binding;enzyme binding;histone binding;metal ion binding