CAPN6

Chr X

calpain 6

Also known as: CANPX, CAPNX, CalpM, DJ914P14.1

NCBI Gene: 827 ENSG00000077274 UniProt: Q9Y6Q1 OMIM: 300146

CAPN6 encodes a proteolytically inactive member of the calcium-dependent cysteine protease family that functions as a microtubule-stabilizing protein and regulates cytoskeletal organization and cell mobility through RAC1 signaling pathways. The gene is highly constrained against loss-of-function variants, but specific disease associations and inheritance patterns have not been established in the provided data.

OMIM ResearchSummary from RefSeq, UniProt

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]

OMIM ResearchGenerating clinical summary…

LOEUF 0.39

Clinical Summary— CAPN6

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Population Constraint (gnomAD)

Moderately constrained gene (pLI 0.82) — some intolerance to loss-of-function variants.

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ClinVar Variants

3 unique Pathogenic / Likely Pathogenic· 40 VUS of 119 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.39LOEUF

pLI 0.819

Z-score 3.70

OE 0.17 (0.08–0.39)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

1.52Z-score

OE missense 0.73 (0.65–0.83)

187 obs / 255.2 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.17 (0.08–0.39)

0≤0.351.4

Missense OE?0.73 (0.65–0.83)

0≤0.61.4

Synonymous OE?1.14

0≤1.21.6

LoF obs/exp: 4 / 23.2Missense obs/exp: 187 / 255.2Syn Z: -0.99

ClinVar Variant Classifications

119 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic2

Likely Pathogenic1

VUS40

Likely Benign1

Benign12

Pathogenic

Likely Pathogenic

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	1	0	1	0	2
Likely Pathogenic	0	1	0	0	1
VUS	0	40	0	0	40
Likely Benign	0	0	0	1	1
Benign	0	1	9	2	12
Total	1	42	10	3	56

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

72 pathogenic / likely-pathogenic (of 81) ClinVar copy-number / structural variants overlap CAPN6 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →