MCTP2

protein-coding

multiple C2 and transmembrane domain containing 2, the group of Multiple C2 and transmembrane domain containing

Gene summary

Enables calcium ion binding activity. Predicted to be involved in regulation of neurotransmitter secretion. Located in cytosol; membrane; and nucleoplasm. [provided by Alliance of Genome Resources, Jul 2025]

MANE transcript

NM_001385001.1

Inheritance

ClinVar variants

U:178B:52

Top phenotype

Inborn genetic diseases

gnomAD constraint

pLI —, LoF o/e 1.34

Max pathogenic AF

—

Genomic locus

chr15:94,231,538-94,483,952

External References & Databases

Ensembl (ENSG00000140563)

Transcript & Mutation Effects

hg38 • Region Span ~252.4 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

congenital heart defects, multiple typesLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0000119

Submitter: Ambry Genetics

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to MCTP2 variants in ClinVar

4 Conditions Cataloged

Inborn genetic diseasesTotal: 163

not providedTotal: 54

MCTP2-related disorderTotal: 38

not specifiedTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001385001.1. 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			2 clinvar	22 clinvar	8 clinvar	32
missense			168 clinvar	14 clinvar	5 clinvar	187
nonsense			5 clinvar	1 clinvar		6
start loss						0
frameshift			1 clinvar	1 clinvar		2
splice donor/acceptor (+/-2bp)			2 clinvar	1 clinvar		3
Total	0	0	178	39	13	230

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 46 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001385001.1	RefSeq	NP_001371930.1	22	MANE Select
ENST00000357742.10	Ensembl	ENSP00000350377.4	22	MANE Select
NM_001159643.2	RefSeq	NP_001153115.1	20	Standard
NM_001159644.2	RefSeq	NP_001153116.1	9	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

multicellular organism development
calcium-mediated signaling
regulation of neurotransmitter secretion

Molecular Function

calcium ion binding
calcium-dependent phospholipid binding

Cellular Component

nucleoplasm
cytosol
membrane
integral component of membrane
synaptic vesicle membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000357742
Coding exons: 22
Length: 248866
Individuals with no LoFs: 124871
Homozygous LoFs: 1
Heterozygous LoFs: 876
Defined: 125748
p: 0.00349

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-1.42	572	484	1.18	0.0000270	5777
Missense (PolyPhen)		157	124.31	1.263		1524
Synonymous	-0.498	192	183	1.05	0.0000103	1631
Loss of Function	-2.23	68	50.8	1.34	0.00000289	591

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0021	0.0021	notable
Latino/Admixed American	0.0020	0.0019	notable
Ashkenazi Jewish	0.00010	0.000099	rare
East Asian	0.014	0.014	notable
Finnish	0.0073	0.0071	notable
European (Non-Finnish)	0.0018	0.0018	notable
South Asian	0.0051	0.0051	notable
Other	0.0027	0.0026	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Might play a role in the development of cardiac outflow tract. {ECO:0000269|PubMed:23773997}.;
Disease: DISEASE: Note=Heterozygosity for a 2.2-Mb deletion at chromosome 15q26.2, encompassing MCTP2, has been identified in a 10-year-old girl and her 3-year-old half brother, who had both coarctation of the aorta associated with dysmorphic features and ventricular septal defects. An intragenic MCTP2 duplication, leading to premature truncation (F697X) within the first transmembrane region of the protein, has also been observed in a male patient with a non-syndromic complex cardiac malformation involving coarctation, hypoplastic left heart, mitral atresia, bicuspid aortic valve and muscular ventricular septal defect. Although the link between left ventricular outflow tract malformations and MCTP2 could not be established, it has been proposed that defects in the MCTP2 gene may contribute to phenotype. This hypothesis is supported by the observation that Xenopus laevis embryos treated with MCTP2 morpholinos show no evidence of endocardial cushion formation at any level of the developing outflow tract (PubMed:23773997). {ECO:0000269|PubMed:23773997}.;

Recessive Scores

pRec: 0.0958

Intolerance Scores

LoFtool: 0.999
RVIS EVS: -0.19
RVIS percentile EVS: 39.31

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.116

Gene Damage Prediction

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