CAPN14

protein-coding

calpain 14, the group of Calpains|EF-hand domain containing

Gene summary

Calpains are a family of cytosolic calcium-activated cysteine proteases involved in a variety of cellular processes including apoptosis, cell division, modulation of integrin-cytoskeletal interactions, and synaptic plasticity (Dear et al., 2000 [PubMed 10964513]). CAPN14 belongs to the calpain large subunit family.[supplied by OMIM, Mar 2008]

MANE transcript

NM_001145122.2

Inheritance

—

ClinVar variants

U:123B:13

Top phenotype

Amyotrophic lateral sclerosis

gnomAD constraint

pLI —, LoF o/e 0.84

Max pathogenic AF

—

Genomic locus

chr2:31,173,056-31,233,858

External References & Databases

Ensembl (ENSG00000214711)

Transcript & Mutation Effects

hg38 • Region Span ~60.8 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 CAPN14 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 132

not providedTotal: 3

Amyotrophic lateral sclerosisTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001145122.2. 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	1 clinvar	2
missense			123 clinvar	11 clinvar		134
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	123	12	1	136

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_001145122.2	RefSeq	NP_001138594.1	21	MANE Select
ENST00000403897.4	Ensembl	ENSP00000385247.3	21	MANE Select
NM_001321270.2	RefSeq	NP_001308199.1	18	Standard
ENST00000398824.6	Ensembl	ENSP00000381805.2	4	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Extracellular matrix organization
Degradation of the extracellular matrix

Biological Process

proteolysis

Molecular Function

calcium-dependent cysteine-type endopeptidase activity
calcium ion binding

Cellular Component

cytoplasm

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000403897
Coding exons: 21
Length: 60801
Individuals with no LoFs: 0
Homozygous LoFs: 0
Heterozygous LoFs: 0
Defined: 0
p: 0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.13	299	359	0.832	0.0000195	4480
Missense (PolyPhen)		101	121.48	0.83141		1635
Synonymous	1.36	124	145	0.856	0.00000813	1269
Loss of Function	0.959	36	42.8	0.842	0.00000201	497

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0	0.0	absent
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Calcium-regulated non-lysosomal thiol-protease. {ECO:0000250}.;

Intolerance Scores

RVIS EVS: 2.66
RVIS percentile EVS: 98.84

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.0977

Gene Damage Prediction

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