CAPN1

Chr 11AR

calpain 1

Also known as: CANP, CANP1, CANPL1, SPG76, muCANP, muCL

NCBI Gene: 823ENSG00000014216UniProt: P07384

The calpains, calcium-activated neutral proteases, are nonlysosomal, intracellular cysteine proteases. The mammalian calpains include ubiquitous, stomach-specific, and muscle-specific proteins. The ubiquitous enzymes consist of heterodimers with distinct large, catalytic subunits associated with a common small, regulatory subunit. This gene encodes the large subunit of the ubiquitous enzyme, calpain 1. Several transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Nov 2010]

Primary Disease Associations & Inheritance

Spastic paraplegia 76, autosomal recessiveMIM #616907
AR
375
ClinVar variants
59
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— CAPN1
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
59 Pathogenic / Likely Pathogenic· 163 VUS of 375 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
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.
0.71LOEUF
pLI 0.000
Z-score 3.16
OE 0.50 (0.36–0.71)
Tolerant

Typical tolerance to LoF variation

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.
1.68Z-score
OE missense 0.78 (0.72–0.85)
369 obs / 471.9 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.0.50 (0.36–0.71)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.78 (0.72–0.85)
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.0.77
0≤1.21.6
LoF obs/exp: 23 / 46.1Missense obs/exp: 369 / 471.9Syn Z: 2.48

ClinVar Variant Classifications

375 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic40
Likely Pathogenic19
VUS163
Likely Benign115
Benign33
Conflicting5
40
Pathogenic
19
Likely Pathogenic
163
VUS
115
Likely Benign
33
Benign
5
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
17
4
19
0
40
Likely Pathogenic
7
1
11
0
19
VUS
0
149
14
0
163
Likely Benign
0
10
49
56
115
Benign
0
2
23
8
33
Conflicting
—5
Total2416611664375

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

View in ClinVar →

Protein Context — Lollipop Plot

CAPN1 · 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 1; CAPN1
MIM #114220 · *

Spastic paraplegia 76, autosomal recessive

MIM #616907

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Hereditary ataxias and paraparesias: clinical and genetic update.
Parodi L et al.·Curr Opin Neurol
2018Review
Spastic paraplegia type 76 due to novel CAPN1 mutations: three case reports with literature review.
Zhu Z et al.·Neurogenetics
2023Review
Two novel homozygous mutations of CAPN1 in Chinese patients with hereditary spastic paraplegia and literatures review.
Peng F et al.·Orphanet J Rare Dis
2019Review
Generalized myokymia, or neuromyotonia, or both in dogs with or without spinocerebellar ataxia.
Vanhaesebrouck A et al.·J Vet Intern Med
2023
Increasing involvement of CAPN1 variants in spastic ataxias and phenotype-genotype correlations.
Méreaux JL et al.·Neurogenetics
2021
Structure-based design of pan-coronavirus inhibitors targeting host cathepsin L and calpain-1.
Xie X et al.·Signal Transduct Target Ther
2024
CAPN1 promotes malignant behavior and erlotinib resistance mediated by phosphorylation of c-Met and PIK3R2 via degrading PTPN1 in lung adenocarcinoma.
Chen Y et al.·Thorac Cancer
2020
Whole genome sequencing analysis in primary lateral sclerosis (PLS) patients reveals mutations in neurological diseases-causing genes.
Manini A et al.·J Neurol
2025Cohort
CAPN1 is a novel biomaker of patients with AML based on comprehensive analysis.
Wang H et al.·Biotechnol Genet Eng Rev
2024Cohort
Cisplatin-induced pyroptosis is mediated via the CAPN1/CAPN2-BAK/BAX-caspase-9-caspase-3-GSDME axis in esophageal cancer.
Li RY et al.·Chem Biol Interact
2022
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Loss-of-function variants in the CAPN1 activator CD99L2 cause X-linked spastic ataxia.
Menden B et al.·Nat Commun
2026🔓 Open Access
Single-Nucleotide Polymorphisms in Calpastatin (CAST) and Micro-Calpain (CAPN1) Genes Influencing Meat Tenderness in Crossbred Beef Cattle in Thailand.
Thaloengsakdadech T et al.·Vet Sci
2026🔓 Open Access
Spinal overexpression of CAPN1 in CaMKII neurons mediates paclitaxel-induced neuropathic pain via NCS-1-TRPV4 signaling.
Zhang YN et al.·Mol Pain
2026🔓 Open Access
Engineered exosomal miR140 modulates mitophagy of chondrocytes through targeting CAPN1 to alleviate osteoarthritis.
Liu Y et al.·Sci China Life Sci
2025
Expression profiles of the Tau-associated genes GSk3β, CAPN1, and CDK5R1 in the brain cortex of aged female cynomolgus monkeys with cognitive impairment.
Darusman HS et al.·Open Vet J
2025🔓 Open Access
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