CAPN9

Chr 1

calpain 9

Also known as: GC36, nCL-4

NCBI Gene: 10753ENSG00000135773UniProt: O14815OMIM: 606401

CAPN9 encodes a calcium-regulated cysteine protease that is expressed predominantly in the stomach and small intestine. Mutations cause autosomal recessive neurodegeneration with ataxia, dystonia, and gaze palsy with childhood onset. The gene shows low constraint against loss-of-function variants.

OMIMResearchSummary from RefSeq, UniProt
MultiplemechanismLOEUF 1.14
Clinical Summary— CAPN9
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
39 unique Pathogenic / Likely Pathogenic· 110 VUS of 179 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
1.14LOEUF
pLI 0.000
Z-score 0.81
OE 0.87 (0.67–1.14)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-0.10Z-score
OE missense 1.01 (0.93–1.10)
408 obs / 402.4 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.87 (0.67–1.14)
0≤0.351.4
Missense OE1.01 (0.93–1.10)
0≤0.61.4
Synonymous OE0.93
0≤1.21.6
LoF obs/exp: 37 / 42.7Missense obs/exp: 408 / 402.4Syn Z: 0.68
DN
0.6745th %ile
GOF
0.7125th %ile
LOF
0.2385th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median
DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

179 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic37
Likely Pathogenic2
VUS110
Likely Benign7
37
Pathogenic
2
Likely Pathogenic
110
VUS
7
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
37
0
37
Likely Pathogenic
0
0
2
0
2
VUS
1
99
10
0
110
Likely Benign
0
5
0
2
7
Benign
0
0
0
0
0
Total1104492156

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

View in ClinVar →

Protein Context — Lollipop Plot

CAPN9 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 2 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients