CAPN2

protein-coding

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

Gene summary

The calpains, calcium-activated neutral proteases, are nonlysosomal, intracellular cysteine proteases. The mammalian calpains include ubiquitous, stomach-specific, and muscle-specific proteins. The ubiquitous enzymes consist of heterodimers with distinct large, catalytic subunits associated with a common small, regulatory subunit. This gene encodes the large subunit of the ubiquitous enzyme, calpain 2. Multiple heterogeneous transcriptional start sites in the 5' UTR have been reported. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2009]

MANE transcript

NM_001748.5

Inheritance

—

ClinVar variants

U:135B:8

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.82

Max pathogenic AF

—

Genomic locus

chr1:223,701,593-223,776,018

External References & Databases

Ensembl (ENSG00000162909)

Transcript & Mutation Effects

hg38 • Region Span ~74.4 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 CAPN2 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 122

not providedTotal: 9

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001748.5. 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	2 clinvar	2 clinvar	5
missense			122 clinvar	2 clinvar	1 clinvar	125
nonsense			1 clinvar			1
start loss						0
frameshift					1 clinvar	1
splice donor/acceptor (+/-2bp)			11 clinvar			11
Total	0	0	135	4	4	143

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 37 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001748.5	RefSeq	NP_001739.3	21	MANE Select
ENST00000295006.6	Ensembl	ENSP00000295006.5	21	MANE Select
NM_001146068.2	RefSeq	NP_001139540.1	21	Standard
ENST00000433674.6	Ensembl	ENSP00000413158.2	21	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

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)

Biological Process

response to hypoxia
blastocyst development
proteolysis
myoblast fusion
female pregnancy

Molecular Function

calcium-dependent cysteine-type endopeptidase activity
calcium ion binding
protein binding
cytoskeletal protein binding
cysteine-type peptidase activity

Cellular Component

chromatin
nucleus
cytoplasm
mitochondrial intermembrane space
lysosome

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000295006
Coding exons: 21
Length: 74426
Individuals with no LoFs: 125528
Homozygous LoFs: 0
Heterozygous LoFs: 220
Defined: 125748
p: 0.000875

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.589	380	414	0.919	0.0000242	4591
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00076	0.00074	rare
Latino/Admixed American	0.00035	0.00035	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.0020	0.0020	notable
Finnish	0.0043	0.0043	notable
European (Non-Finnish)	0.00028	0.00028	rare
South Asian	0.0011	0.0010	notable
Other	0.00065	0.00065	rare

dbNSFP Gene Annotations

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}.;

Recessive Scores

pRec: 0.298

Intolerance Scores

LoFtool: 0.143
RVIS EVS: 0.72
RVIS percentile EVS: 85.83

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.940

Gene Damage Prediction

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