MCTP2

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

Basic information

Region (hg38): 15:94231538-94483952

Links

ENSG00000140563 ∙ NCBI:55784 ∙ OMIM:616297 ∙ HGNC:25636 ∙ Uniprot:Q6DN12 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• congenital heart defects, multiple types (Limited), mode of inheritance: AD

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the MCTP2 gene.

• Inborn_genetic_diseases (151 variants)
• not_provided (49 variants)
• MCTP2-related_disorder (36 variants)
• not_specified (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MCTP2 gene is commonly pathogenic or not. These statistics are base on transcript: NM_001385001.1. Only rare variants are included in the table.

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.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				21	8	29
missense			150	13	5	168
nonsense			3	1		4
start loss						0
frameshift			1	1		2
splice donor/acceptor (+/-2bp)			1	1		2
Total	0	0	155	37	13

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
MCTP2	protein_coding	protein_coding	ENST00000357742	22	248866

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
6.03e-52	2.98e-11	124871	1	876	125748	0.00349

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-1.42	572	484	1.18	0.0000270	5777
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00407	0.00407
Ashkenazi Jewish	0.000105	0.0000992
East Asian	0.0138	0.0136
Finnish	0.00725	0.00714
European (Non-Finnish)	0.00183	0.00177
Middle Eastern	0.0138	0.0136
South Asian	0.00513	0.00508
Other	0.00274	0.00261

dbNSFP

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

Haploinsufficiency Scores

• pHI: 0.113
• hipred: N
• hipred_score: 0.197
• ghis: 0.527

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.116

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Mctp2

Gene ontology

• Biological process: multicellular organism development;calcium-mediated signaling;regulation of neurotransmitter secretion
• Cellular component: nucleoplasm;cytosol;membrane;integral component of membrane;synaptic vesicle membrane
• Molecular function: calcium ion binding;calcium-dependent phospholipid binding