CAPN6

protein-coding

calpain 6, the group of Calpains|C2 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 highly expressed in the placenta. Its C-terminal region lacks any homology to the calmodulin-like domain of other calpains. The protein lacks critical active site residues and thus is suggested to be proteolytically inactive. The protein may play a role in tumor formation by inhibiting apoptosis and promoting angiogenesis. [provided by RefSeq, Nov 2009]

MANE transcript

NM_014289.4

Inheritance

—

ClinVar variants

P:2U:103B:3

Top phenotype

Prostate cancer

gnomAD constraint

pLI —, LoF o/e 0.17

Max pathogenic AF

—

Genomic locus

chrX:111,245,099-111,270,483

External References & Databases

Ensembl (ENSG00000077274)

Transcript & Mutation Effects

hg38 • Region Span ~25.4 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 CAPN6 variants in ClinVar

5 Conditions Cataloged

not specifiedTotal: 41

not providedTotal: 4

Prostate cancerTotal: 1

Essential tremorTotal: 1

Neurodevelopmental delayTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_014289.4. 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			12 clinvar	1 clinvar	2 clinvar	15
missense		1 clinvar	76 clinvar			77
nonsense			9 clinvar			9
start loss						0
frameshift	1 clinvar					1
splice donor/acceptor (+/-2bp)			6 clinvar			6
Total	1	1	103	1	2	108

Highest pathogenic variant AF is 0.0000018216446

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 6 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_014289.4	RefSeq	NP_055104.2	12	MANE Select
ENST00000324068.2	Ensembl	ENSP00000317214.1	12	MANE Select
ENST00000932651.1	Ensembl	ENSP00000602710.1	10	Standard
ENST00000932651.2	Ensembl	ENSP00000602710.1	10	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

microtubule bundle formation
proteolysis
regulation of cytoskeleton organization

Molecular Function

calcium-dependent cysteine-type endopeptidase activity
microtubule binding

Cellular Component

cytoplasm
cytosol
spindle microtubule
perinuclear region of cytoplasm

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000324068
Coding exons: 12
Length: 25421
Individuals with no LoFs: 125732
Homozygous LoFs: 3
Heterozygous LoFs: 7
Defined: 125742
p: 0.0000398

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.52	187	255	0.733	0.0000199	4254
Missense (PolyPhen)		67	110.49	0.6064		1647
Synonymous	-0.991	97	85.4	1.14	0.00000593	1195
Loss of Function	3.70	4	23.2	0.172	0.00000176	381

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0.00014	0.000099	rare
East Asian	0	0.0	absent
Finnish	0.00013	0.000092	rare
European (Non-Finnish)	0.000086	0.000062	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Microtubule-stabilizing protein that may be involved in the regulation of microtubule dynamics and cytoskeletal organization. May act as a regulator of RAC1 activity through interaction with ARHGEF2 to control lamellipodial formation and cell mobility. Does not seem to have protease activity as it has lost the active site residues (By similarity). {ECO:0000250, ECO:0000269|PubMed:17210638}.;

Recessive Scores

pRec: 0.147

Intolerance Scores

LoFtool: 0.138
RVIS EVS: 0.13
RVIS percentile EVS: 63.2

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.165

Gene Damage Prediction

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