CAPN9

protein-coding

calpain 9, the group of Calpains|EF-hand domain containing

Gene summary

Calpains are ubiquitous, well-conserved family of calcium-dependent, cysteine proteases. The calpain proteins are heterodimers consisting of an invariant small subunit and variable large subunits. The large subunit possesses a cysteine protease domain, and both subunits possess calcium-binding domains. Calpains have been implicated in neurodegenerative processes, as their activation can be triggered by calcium influx and oxidative stress. The protein encoded by this gene is expressed predominantly in stomach and small intestine and may have specialized functions in the digestive tract. This gene is thought to be associated with gastric cancer. Multiple alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

MANE transcript

NM_006615.3

Inheritance

—

ClinVar variants

U:109B:7

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.87

Max pathogenic AF

—

Genomic locus

chr1:230,747,384-230,802,003

External References & Databases

Ensembl (ENSG00000135773)

Transcript & Mutation Effects

hg38 • Region Span ~54.6 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 CAPN9 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 103

not providedTotal: 4

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_006615.3. 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		3
missense			102 clinvar	5 clinvar		107
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			6 clinvar			6
Total	0	0	109	7	0	116

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 28 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_006615.3	RefSeq	NP_006606.1	20	MANE Select
ENST00000271971.7	Ensembl	ENSP00000271971.2	20	MANE Select
NM_001319676.2	RefSeq	NP_001306605.1	18	Standard
NM_016452.3	RefSeq	NP_057536.1	19	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Integrin-mediated Cell Adhesion
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

cellular_component
cytoplasm

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000271971
Coding exons: 20
Length: 54620
Individuals with no LoFs: 122465
Homozygous LoFs: 99
Heterozygous LoFs: 3184
Defined: 125748
p: 0.0131

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.0997	408	402	1.01	0.0000238	4580
Missense (PolyPhen)		169	165.9	1.0187		1856
Synonymous	0.678	151	162	0.932	0.0000104	1275
Loss of Function	0.808	37	42.7	0.867	0.00000227	458

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0081	0.0079	notable
Latino/Admixed American	0.0063	0.0063	notable
Ashkenazi Jewish	0.00070	0.00069	rare
East Asian	0.083	0.082	notable
Finnish	0.00023	0.00023	rare
European (Non-Finnish)	0.0038	0.0037	notable
South Asian	0.033	0.033	notable
Other	0.011	0.010	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Calcium-regulated non-lysosomal thiol-protease.;

Recessive Scores

pRec: 0.0901

Intolerance Scores

LoFtool: 0.126
RVIS EVS: 1.12
RVIS percentile EVS: 92.1

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.162

Gene Damage Prediction

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