CAPN8

protein-coding

calpain 8, the group of Calpains|EF-hand domain containing

Gene summary

Predicted to enable calcium-dependent cysteine-type endopeptidase activity and identical protein binding activity. Predicted to be involved in proteolysis. Predicted to act upstream of or within calcium-dependent self proteolysis. Predicted to be located in Golgi apparatus. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Jul 2025]

MANE transcript

NM_001143962.2

Inheritance

—

ClinVar variants

U:73B:7

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.73

Max pathogenic AF

—

Genomic locus

chr1:223,538,007-223,665,723

External References & Databases

Ensembl (ENSG00000203697)

Transcript & Mutation Effects

hg38 • Region Span ~127.7 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 CAPN8 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 77

not providedTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001143962.2. 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
missense			72 clinvar	6 clinvar		78
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	73	7	0	80

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 29 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001143962.2	RefSeq	NP_001137434.1	21	MANE Select
ENST00000366872.10	Ensembl	ENSP00000355837.6	21	MANE Select
ENST00000366873.6	Ensembl	ENSP00000355838.2	10	Standard
ENST00000442247.5	Ensembl	ENSP00000409233.1	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
digestion

Molecular Function

calcium-dependent cysteine-type endopeptidase activity
calcium ion binding

Cellular Component

cytoplasm
Golgi apparatus

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000366872
Coding exons: 20
Length: 142088
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	0.844	342	389	0.879	0.0000222	4425
Missense (PolyPhen)		60	79.166	0.7579		860
Synonymous	1.31	137	158	0.867	0.0000100	1297
Loss of Function	1.46	25	34.2	0.730	0.00000146	411

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. Involved in membrane trafficking in the gastric surface mucus cells (pit cells) and may involve the membrane trafficking of mucus cells via interactions with coat protein. Proteolytically cleaves the beta- subunit of coatomer complex (By similarity). {ECO:0000250}.;

Essentials

Essential (CRISPR2): N
Indispensability pred.: N
Indispensability score: 0.0834

Gene Damage Prediction

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