CAPN6

Chr X

calpain 6

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

NCBI Gene: 827ENSG00000077274UniProt: Q9Y6Q1

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]

137
ClinVar variants
76
Pathogenic / LP
0.82
pLI score
0
Active trials
Clinical Summary— CAPN6
⚡
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.82) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
76 Pathogenic / Likely Pathogenic· 48 VUS of 137 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
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?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
1.52Z-score
OE missense 0.73 (0.65–0.83)
187 obs / 255.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.17 (0.08–0.39)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.73 (0.65–0.83)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.14
0≤1.21.6
LoF obs/exp: 4 / 23.2Missense obs/exp: 187 / 255.2Syn Z: -0.99

ClinVar Variant Classifications

137 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic72
Likely Pathogenic4
VUS48
Likely Benign1
Benign12
72
Pathogenic
4
Likely Pathogenic
48
VUS
1
Likely Benign
12
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
1
0
71
0
72
Likely Pathogenic
0
1
3
0
4
VUS
0
40
8
0
48
Likely Benign
0
0
0
1
1
Benign
0
1
9
2
12
Total142913137

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

View in ClinVar →

Protein Context — Lollipop Plot

CAPN6 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
CALPAIN 6; CAPN6
MIM #300146 · *
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Calpain-6 confers atherogenicity to macrophages by dysregulating pre-mRNA splicing.
Miyazaki T et al.·J Clin Invest
2016
Potential Link Between a Disruptive CAPN6 Variant and Neurodevelopmental Disorders.
Calì F et al.·Int J Mol Sci
2026Case report
Increased expression of calpain 6 in uterine sarcomas and carcinosarcomas: an immunohistochemical analysis.
Lee SJ et al.·Int J Gynecol Cancer
2007
Gene expression patterns associated with tumor-infiltrating CD4+ and CD8+ T cells in invasive breast carcinomas.
Wang Z et al.·Hum Immunol
2021
Transcriptomics and Prognosis Analysis to Identify Critical Biomarkers in Invasive Breast Carcinoma.
Wu J et al.·Technol Cancer Res Treat
2020
Functional study of 14-3-3 protein epsilon (YWHAE) in keratinocytes: microarray integrating bioinformatics approaches.
Yin SJ et al.·J Biomol Struct Dyn
2020Functional
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools