MCM6

minichromosome maintenance complex component 6, the group of MCM family|minichromosome maintenance 2-7 complex

Basic information

Region (hg38): 2:135839625-135876443

Links

ENSG00000076003 ∙ NCBI:4175 ∙ OMIM:601806 ∙ HGNC:6949 ∙ Uniprot:Q14566 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Lactose intolerance, adult type; Lactase persistence	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	Biochemical; Gastrointestinal	7543318; 9481112; 11788828; 12915462; 15114531; 16041375; 15928901; 16019716; 17120047; 17159977; 18179885

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the MCM6 gene.

• Inborn genetic diseases (29 variants)
• Nonpersistence of intestinal lactase (5 variants)
• not provided (4 variants)
• not specified (1 variants)
• Lactase persistence (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MCM6 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				1	2	3
missense			31	1	1	33
nonsense			1			1
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region					1	1
non coding						0
Total	0	0	32	2	3

Variants in MCM6

This is a list of pathogenic ClinVar variants found in the MCM6 region.

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

Position	Type	Phenotype	Significance	ClinVar
2-135840873-A-G		not specified • Lactase persistence	Benign (-)
2-135840878-T-C		not specified	Uncertain significance (Jun 28, 2023)
2-135844550-G-A		not specified	Uncertain significance (Feb 15, 2023)
2-135844558-C-T		not specified	Uncertain significance (Oct 25, 2023)
2-135844562-G-A		not specified	Uncertain significance (Oct 25, 2023)
2-135844618-T-C		not specified	Uncertain significance (Feb 10, 2022)
2-135844626-G-A			Benign (Dec 31, 2019)
2-135844679-C-T		not specified	Uncertain significance (Apr 06, 2023)
2-135846225-GGT-G		MCM6-related disorder	Likely benign (Mar 14, 2019)
2-135846246-C-T		not specified	Likely benign (Feb 15, 2023)
2-135848085-A-C		not specified	Uncertain significance (Feb 05, 2024)
2-135848085-A-G		not specified	Uncertain significance (Dec 15, 2023)
2-135848112-T-C		not specified	Uncertain significance (Sep 07, 2022)
2-135848134-G-A		not specified	Uncertain significance (Oct 12, 2022)
2-135851073-G-C		Lactase persistence	association (Nov 20, 2018)
2-135851076-G-A		Lactase persistence	association (Jan 26, 2021)
2-135851079-A-G		Lactase persistence	Uncertain significance (-)
2-135851081-A-C		Lactase persistence	association (Nov 20, 2018)
2-135851176-C-G		Lactase persistence	association (Jun 16, 2015)
2-135851421-C-T		not specified	Uncertain significance (Feb 28, 2024)
2-135851464-G-A		Nonpersistence of intestinal lactase	Uncertain significance (Feb 08, 2021)
2-135851521-G-A		Nonpersistence of intestinal lactase	Uncertain significance (Jan 11, 2024)
2-135852842-T-C		not specified	Uncertain significance (Oct 25, 2022)
2-135852855-T-C		not specified	Uncertain significance (Aug 12, 2021)
2-135852888-T-C		Nonpersistence of intestinal lactase	Uncertain significance (Aug 07, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
MCM6	protein_coding	protein_coding	ENST00000264156	17	36801

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.978	0.0217	125733	0	14	125747	0.0000557

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.07	390	454	0.859	0.0000245	5387
Missense in Polyphen		111	171.04	0.64898		1991
Synonymous	0.764	147	159	0.923	0.00000817	1572
Loss of Function	5.05	7	42.6	0.164	0.00000247	504

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000181	0.000181
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.000139	0.000139
European (Non-Finnish)	0.0000441	0.0000439
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

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. {ECO:0000269|PubMed:9305914}.
• Pathway: Cell cycle - Homo sapiens (human);DNA replication - Homo sapiens (human);Cell Cycle;Retinoblastoma (RB) in Cancer;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 (Consensus)

Recessive Scores

• pRec: 0.206

Intolerance Scores

• loftool: 0.480
• rvis_EVS: -0.57
• rvis_percentile_EVS: 18.9

Haploinsufficiency Scores

• pHI: 0.981
• hipred: Y
• hipred_score: 0.831
• ghis: 0.697

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.546

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Mcm6
• Phenotype: cellular phenotype; growth/size/body region phenotype; neoplasm; hematopoietic system 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)

Gene ontology

• Biological process: G1/S transition of mitotic cell cycle;DNA replication;DNA unwinding involved in DNA replication;DNA replication initiation
• Cellular component: nuclear chromosome, telomeric region;nucleus;nucleoplasm;MCM complex
• Molecular function: single-stranded DNA binding;ATP-dependent DNA helicase activity;protein binding;ATP binding;identical protein binding