MCM5

minichromosome maintenance complex component 5, the group of minichromosome maintenance 2-7 complex|MCM family

Basic information

Region (hg38): 22:35400134-35425431

Previous symbols: [ "CDC46" ]

Links

ENSG00000100297 ∙ NCBI:4174 ∙ OMIM:602696 ∙ HGNC:6948 ∙ Uniprot:P33992 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Meier-Gorlin syndrome 8 (Limited), mode of inheritance: Unknown

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Meier-Gorlin syndrome 8	AR	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	Craniofacial; Genitourinary; Musculoskeletal	28198391

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the MCM5 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MCM5 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	71	12	84
missense			177	8	3	188
nonsense			2			2
start loss						0
frameshift			3			3
inframe indel			1			1
splice donor/acceptor (+/-2bp)			1			1
splice region			10	15	2	27
non coding			4	36	6	46
Total	0	0	189	115	21

Variants in MCM5

This is a list of pathogenic ClinVar variants found in the MCM5 region.

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

Position	Type	Phenotype	Significance	ClinVar
22-35400444-G-A			Likely benign (Apr 09, 2023)
22-35400451-G-A			Uncertain significance (Jan 06, 2024)
22-35400474-C-T			Likely benign (May 15, 2023)
22-35400476-A-G		not specified	Uncertain significance (Sep 12, 2023)
22-35400477-C-T			Likely benign (Jan 18, 2022)
22-35400480-C-T			Likely benign (Jan 29, 2024)
22-35400500-C-T			Uncertain significance (Mar 31, 2023)
22-35400501-C-A			Likely benign (Jul 14, 2022)
22-35400517-C-G			Uncertain significance (Dec 06, 2022)
22-35400521-A-C		not specified	Uncertain significance (Nov 28, 2023)
22-35400525-G-T			Likely benign (Nov 06, 2023)
22-35400549-G-A			Likely benign (Feb 22, 2023)
22-35400554-T-G			Uncertain significance (Sep 30, 2022)
22-35400566-G-T			Uncertain significance (Jul 19, 2022)
22-35400570-GGGC-G			Uncertain significance (Jul 11, 2022)
22-35400579-C-T			Likely benign (Jun 15, 2023)
22-35400589-T-C		not specified	Uncertain significance (Nov 14, 2023)
22-35400593-C-T		not specified	Uncertain significance (May 23, 2023)
22-35400612-C-T			Benign (Jan 29, 2024)
22-35400613-T-C			Likely benign (May 13, 2022)
22-35400614-C-T			Likely benign (Sep 24, 2021)
22-35400615-C-T			Likely benign (Mar 06, 2022)
22-35400621-G-T			Likely benign (Nov 30, 2022)
22-35400624-C-T			Likely benign (Nov 15, 2023)
22-35403192-A-G			Benign (Jan 26, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
MCM5	protein_coding	protein_coding	ENST00000216122	16	25368

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.000593	0.999	125717	0	31	125748	0.000123

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.16	409	481	0.851	0.0000305	4806
Missense in Polyphen		114	174.6	0.65293		1668
Synonymous	-0.739	204	191	1.07	0.0000122	1455
Loss of Function	3.56	12	34.6	0.347	0.00000189	386

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000388	0.000387
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000544	0.0000544
Finnish	0.0000463	0.0000462
European (Non-Finnish)	0.000143	0.000141
Middle Eastern	0.0000544	0.0000544
South Asian	0.0000980	0.0000980
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 (By similarity). Interacts with MCMBP. {ECO:0000250}.
• Disease: DISEASE: Meier-Gorlin syndrome 8 (MGORS8) [MIM:617564]: A form of Meier-Gorlin syndrome, a syndrome characterized by bilateral microtia, aplasia/hypoplasia of the patellae, and severe intrauterine and postnatal growth retardation with short stature and poor weight gain. Additional clinical findings include anomalies of cranial sutures, microcephaly, apparently low-set and simple ears, microstomia, full lips, highly arched or cleft palate, micrognathia, genitourinary tract anomalies, and various skeletal anomalies. While almost all cases have primordial dwarfism with substantial prenatal and postnatal growth retardation, not all cases have microcephaly, and microtia and absent/hypoplastic patella are absent in some. Despite the presence of microcephaly, intellect is usually normal. MGORS8 inheritance is autosomal recessive. {ECO:0000269|PubMed:28198391}. 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;TNFalpha;Cell Cycle, Mitotic (Consensus)

Recessive Scores

• pRec: 0.190

Intolerance Scores

• loftool: 0.624
• rvis_EVS: -0.44
• rvis_percentile_EVS: 24.63

Haploinsufficiency Scores

• pHI: 0.972
• hipred: Y
• hipred_score: 0.731
• ghis: 0.655

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.987

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Mcm5
• 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)

Zebrafish Information Network

• Gene name: mcm5
• Affected structure: whole organism
• Phenotype tag: abnormal
• Phenotype quality: dwarf-like

Gene ontology

• Biological process: G1/S transition of mitotic cell cycle;DNA replication;DNA replication initiation
• Cellular component: nuclear chromosome, telomeric region;nucleus;nucleoplasm;cytosol;membrane;MCM complex
• Molecular function: DNA replication origin binding;helicase activity;protein binding;ATP binding