MCC

MCC regulator of WNT signaling pathway, the group of EF-hand domain containing

Basic information

Region (hg38): 5:113022105-113488823

Links

ENSG00000171444 ∙ NCBI:4163 ∙ OMIM:159350 ∙ HGNC:6935 ∙ Uniprot:P23508 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

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

• Inborn genetic diseases (82 variants)
• not provided (21 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MCC 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				7	2	9
missense			60	6	1	67
nonsense						0
start loss						0
frameshift						0
inframe indel					1	1
splice donor/acceptor (+/-2bp)						0
splice region					2	2
non coding			22		1	23
Total	0	0	82	13	5

Variants in MCC

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

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

Position	Type	Phenotype	Significance	ClinVar
5-113027325-G-T		not specified	Uncertain significance (Sep 20, 2023)
5-113027360-C-T		not specified	Uncertain significance (Dec 27, 2023)
5-113027396-T-C		not specified	Uncertain significance (Aug 13, 2021)
5-113027411-A-G			Uncertain significance (-)
5-113027426-T-C		not specified	Uncertain significance (Mar 17, 2023)
5-113028959-C-T		not specified	Uncertain significance (May 15, 2023)
5-113028992-T-A			Benign (Jul 15, 2018)
5-113029001-T-C		not specified	Uncertain significance (Oct 05, 2023)
5-113029012-A-G		not specified	Uncertain significance (Feb 02, 2022)
5-113029018-C-T		not specified	Uncertain significance (Mar 16, 2022)
5-113029022-C-G		not specified	Uncertain significance (Dec 20, 2021)
5-113029027-T-C		not specified	Uncertain significance (Dec 19, 2022)
5-113043533-C-T		not specified	Uncertain significance (Aug 28, 2023)
5-113043541-G-A			Likely benign (Jul 06, 2018)
5-113043549-A-G		not specified	Uncertain significance (Jul 12, 2023)
5-113043555-C-A		not specified	Uncertain significance (Nov 15, 2021)
5-113043570-C-T		not specified	Uncertain significance (Aug 12, 2022)
5-113043585-T-A		not specified	Uncertain significance (Dec 12, 2023)
5-113043587-A-C		not specified	Uncertain significance (May 24, 2023)
5-113043591-C-T		not specified	Uncertain significance (Aug 16, 2021)
5-113043623-G-A		Carcinoma of colon	Pathogenic (Mar 15, 1991)
5-113049094-T-A		not specified	Uncertain significance (Feb 16, 2023)
5-113049220-C-T		not specified	Uncertain significance (Aug 17, 2021)
5-113049223-G-A		not specified	Uncertain significance (Jun 03, 2022)
5-113049244-G-T		not specified	Uncertain significance (Jun 22, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
MCC	protein_coding	protein_coding	ENST00000408903	19	466732

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
4.66e-16	0.977	125368	3	377	125748	0.00151

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.881	660	599	1.10	0.0000354	6689
Missense in Polyphen		316	306.14	1.0322		3599
Synonymous	-2.95	300	242	1.24	0.0000150	1954
Loss of Function	2.52	33	52.7	0.626	0.00000296	571

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000741	0.000741
Ashkenazi Jewish	0.000199	0.000198
East Asian	0.000744	0.000707
Finnish	0.0000464	0.0000462
European (Non-Finnish)	0.000266	0.000264
Middle Eastern	0.000744	0.000707
South Asian	0.0101	0.0101
Other	0.000991	0.000978

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Candidate for the putative colorectal tumor suppressor gene located at 5q21. Suppresses cell proliferation and the Wnt/b- catenin pathway in colorectal cancer cells. Inhibits DNA binding of b-catenin/TCF/LEF transcription factors. Involved in cell migration independently of RAC1, CDC42 and p21-activated kinase (PAK) activation (PubMed:18591935, PubMed:19555689, PubMed:22480440). Represses the beta-catenin pathway (canonical Wnt signaling pathway) in a CCAR2-dependent manner by sequestering CCAR2 to the cytoplasm, thereby impairing its ability to inhibit SIRT1 which is involved in the deacetylation and negative regulation of beta-catenin (CTNB1) transcriptional activity (PubMed:24824780). {ECO:0000269|PubMed:18591935, ECO:0000269|PubMed:19555689, ECO:0000269|PubMed:22480440, ECO:0000269|PubMed:24824780}.
• Pathway: TNFalpha (Consensus)

Recessive Scores

• pRec: 0.110

Intolerance Scores

• loftool: 0.838
• rvis_EVS: -1.43
• rvis_percentile_EVS: 4.04

Haploinsufficiency Scores

• pHI: 0.693
• hipred: N
• hipred_score: 0.492
• ghis: 0.507

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.653

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Mcc
• Phenotype: normal phenotype

Zebrafish Information Network

• Gene name: mcc
• Affected structure: head
• Phenotype tag: abnormal
• Phenotype quality: malformed

Gene ontology

• Biological process: signal transduction;negative regulation of epithelial cell migration;Wnt signaling pathway;establishment of protein localization;negative regulation of epithelial cell proliferation;negative regulation of canonical Wnt signaling pathway
• Cellular component: nucleus;nucleoplasm;cytoplasm;cytosol;plasma membrane;lamellipodium
• Molecular function: protein binding;signaling receptor activity