MCC

protein-coding

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

Gene summary

This gene is a candidate colorectal tumor suppressor gene that is thought to negatively regulate cell cycle progression. The orthologous gene in the mouse expresses a phosphoprotein associated with the plasma membrane and membrane organelles, and overexpression of the mouse protein inhibits entry into S phase. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

MANE transcript

NM_001085377.2

Inheritance

—

ClinVar variants

P:2U:183B:16

Top phenotype

Carcinoma of colon

gnomAD constraint

pLI —, LoF o/e 0.63

Max pathogenic AF

—

Genomic locus

chr5:113,022,106-113,488,823

External References & Databases

Ensembl (ENSG00000171444)

Transcript & Mutation Effects

hg38 • Region Span ~466.7 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 MCC variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 248

not providedTotal: 23

Carcinoma of colonTotal: 2

Prostate cancerTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001085377.2. 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	7 clinvar	2 clinvar	10
missense	2 clinvar		180 clinvar	6 clinvar	1 clinvar	189
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	2	0	183	13	3	201

Highest pathogenic variant AF is 0.000013010088

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 9 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001085377.2	RefSeq	NP_001078846.2	19	MANE Select
ENST00000408903.7	Ensembl	ENSP00000386227.3	19	MANE Select
NM_002387.3	RefSeq	NP_002378.2	17	Standard
ENST00000302475.9	Ensembl	ENSP00000305617.4	17	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
mcc	Danio rerio	Structure: head Quality: malformed abnormal

Gene / Model

Organism

Observed Phenotype

mcc

Danio rerio

Structure: head

Quality: malformed

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

TNFalpha

Biological Process

signal transduction
negative regulation of epithelial cell migration
Wnt signaling pathway
establishment of protein localization
negative regulation of epithelial cell proliferation

Molecular Function

protein binding
signaling receptor activity

Cellular Component

nucleus
nucleoplasm
cytoplasm
cytosol
plasma membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000408903
Coding exons: 19
Length: 466732
Individuals with no LoFs: 125368
Homozygous LoFs: 3
Heterozygous LoFs: 377
Defined: 125748
p: 0.00151

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.881	660	599	1.10	0.0000354	6689
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00025	0.00025	rare
Latino/Admixed American	0.00049	0.00049	rare
Ashkenazi Jewish	0.00020	0.00020	rare
East Asian	0.00074	0.00071	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.00027	0.00026	rare
South Asian	0.010	0.010	notable
Other	0.00099	0.00098	rare

dbNSFP Gene Annotations

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}.;

Recessive Scores

pRec: 0.110

Intolerance Scores

LoFtool: 0.838
RVIS EVS: -1.43
RVIS percentile EVS: 4.04

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.653

Gene Damage Prediction

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