CAPN2

calpain 2, the group of Calpains|EF-hand domain containing

Basic information

Region (hg38): 1:223701592-223776018

Links

ENSG00000162909 ∙ NCBI:824 ∙ OMIM:114230 ∙ HGNC:1479 ∙ Uniprot:P17655 ∙ 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 CAPN2 gene.

• Inborn genetic diseases (40 variants)
• not provided (7 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CAPN2 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				2	2	4
missense			39	2	1	42
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding					1	1
Total	0	0	39	4	4

Variants in CAPN2

This is a list of pathogenic ClinVar variants found in the CAPN2 region.

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

Position	Type	Phenotype	Significance	ClinVar
1-223712675-G-C		not specified	Uncertain significance (Jul 12, 2023)
1-223712678-A-C		not specified	Uncertain significance (Mar 16, 2022)
1-223712703-C-A		not specified	Uncertain significance (Feb 07, 2023)
1-223712723-T-C		not specified	Uncertain significance (Mar 06, 2023)
1-223712784-C-T			Benign (Apr 04, 2018)
1-223712807-C-T		not specified	Uncertain significance (Aug 02, 2023)
1-223712833-C-A		not specified	Uncertain significance (Jun 22, 2021)
1-223712855-G-A		not specified	Uncertain significance (Aug 17, 2022)
1-223712873-C-CCACGGTAGGAAGCG			Benign (Aug 17, 2018)
1-223717790-T-C		not specified	Uncertain significance (Jun 12, 2023)
1-223744135-A-G		not specified	Uncertain significance (Jun 29, 2023)
1-223744192-A-G		not specified	Uncertain significance (Aug 12, 2021)
1-223744208-T-C		not specified	Uncertain significance (Dec 15, 2023)
1-223745429-G-A			Likely benign (Aug 05, 2018)
1-223745433-A-G		not specified	Uncertain significance (Dec 13, 2023)
1-223747004-G-A		not specified	Uncertain significance (Jul 20, 2021)
1-223747016-G-T		not specified	Uncertain significance (Oct 25, 2023)
1-223747021-A-G			Likely benign (May 01, 2022)
1-223747038-C-G		not specified	Uncertain significance (Jan 11, 2023)
1-223747049-G-A		not specified	Uncertain significance (Dec 21, 2023)
1-223750924-G-C		not specified	Uncertain significance (Jan 23, 2023)
1-223750926-A-G		not specified	Uncertain significance (Mar 07, 2023)
1-223750935-C-G		not specified	Uncertain significance (Dec 19, 2023)
1-223750973-C-A		not specified	Uncertain significance (Nov 21, 2022)
1-223752029-A-G		not specified	Uncertain significance (Jan 12, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CAPN2	protein_coding	protein_coding	ENST00000295006	21	74426

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
3.52e-22	0.0295	125528	0	220	125748	0.000875

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.589	380	414	0.919	0.0000242	4591
Missense in Polyphen		152	159.5	0.953		1737
Synonymous	-0.413	176	169	1.04	0.0000105	1299
Loss of Function	1.15	38	46.4	0.818	0.00000250	494

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00111	0.00109
Ashkenazi Jewish	0.00	0.00
East Asian	0.00198	0.00196
Finnish	0.00430	0.00431
European (Non-Finnish)	0.000285	0.000281
Middle Eastern	0.00198	0.00196
South Asian	0.00106	0.00101
Other	0.000652	0.000652

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Calcium-regulated non-lysosomal thiol-protease which catalyzes limited proteolysis of substrates involved in cytoskeletal remodeling and signal transduction. Proteolytically cleaves MYOC at 'Arg-226' (PubMed:17650508). Proteolytically cleaves CPEB3 following neuronal stimulation which abolishes CPEB3 translational repressor activity, leading to translation of CPEB3 target mRNAs (By similarity). {ECO:0000250|UniProtKB:O08529, ECO:0000269|PubMed:17650508}.
• Pathway: Focal adhesion - Homo sapiens (human);Protein processing in endoplasmic reticulum - Homo sapiens (human);Alzheimer,s disease - Homo sapiens (human);Necroptosis - Homo sapiens (human);Apoptosis - Homo sapiens (human);Cellular senescence - Homo sapiens (human);Integrin-mediated Cell Adhesion;Alzheimers Disease;Focal Adhesion;VEGFA-VEGFR2 Signaling Pathway;Deregulated CDK5 triggers multiple neurodegenerative pathways in Alzheimer,s disease models;Neurodegenerative Diseases;Disease;role of mef2d in t-cell apoptosis;mcalpain and friends in cell motility;Extracellular matrix organization;ErbB1 downstream signaling;Degradation of the extracellular matrix;Signaling events mediated by focal adhesion kinase (Consensus)

Recessive Scores

• pRec: 0.298

Intolerance Scores

• loftool: 0.143
• rvis_EVS: 0.72
• rvis_percentile_EVS: 85.83

Haploinsufficiency Scores

• pHI: 0.212
• hipred: Y
• hipred_score: 0.606
• ghis: 0.485

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.940

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Capn2
• Phenotype: embryo 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); normal phenotype; reproductive system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan)

Gene ontology

• Biological process: response to hypoxia;blastocyst development;proteolysis;myoblast fusion;female pregnancy;positive regulation of cardiac muscle cell apoptotic process;protein autoprocessing;regulation of interleukin-6 production;cellular response to interferon-beta;response to hydrogen peroxide;behavioral response to pain;regulation of cytoskeleton organization;proteolysis involved in cellular protein catabolic process;cellular response to lipopolysaccharide;cellular response to amino acid stimulus;positive regulation of neuron death;positive regulation of myoblast fusion;positive regulation of phosphatidylcholine biosynthetic process
• Cellular component: chromatin;nucleus;cytoplasm;mitochondrial intermembrane space;lysosome;endoplasmic reticulum;Golgi apparatus;cytosol;plasma membrane;focal adhesion;external side of plasma membrane;dendrite;cortical actin cytoskeleton;pseudopodium;neuronal cell body;membrane raft;extracellular exosome;perinuclear endoplasmic reticulum
• Molecular function: calcium-dependent cysteine-type endopeptidase activity;calcium ion binding;protein binding;cytoskeletal protein binding;cysteine-type peptidase activity;enzyme binding;protein heterodimerization activity