CAPN10

Chr 2

calpain 10

Also known as: CANP10, NIDDM1

CAPN10 encodes calpain-10, a calcium-regulated cysteine protease that catalyzes limited proteolysis of substrates involved in cytoskeletal remodeling and signal transduction, and may play a role in insulin-stimulated glucose uptake. Mutations cause noninsulin-dependent diabetes mellitus type 1, which typically has adult onset and involves metabolic dysfunction. This gene shows no constraint against loss-of-function variants in the general population.

Summary from RefSeq, OMIM, UniProt
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Primary Disease Associations & Inheritance

{Diabetes mellitus, noninsulin-dependent 1}MIM #601283
UniProtType 2 diabetes mellitus 1
0
Active trials
12
Pubs (1 yr)
106
P/LP submissions
0%
P/LP missense
1.00
LOEUF
LOF
Mechanism· G2P
Clinical SummaryCAPN10
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
104 unique Pathogenic / Likely Pathogenic· 135 VUS of 305 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.00LOEUF
pLI 0.000
Z-score 1.56
OE 0.71 (0.511.00)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
1.17Z-score
OE missense 0.84 (0.770.92)
357 obs / 424.7 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.71 (0.511.00)
00.351.4
Missense OE0.84 (0.770.92)
00.61.4
Synonymous OE1.06
01.21.6
LoF obs/exp: 24 / 33.8Missense obs/exp: 357 / 424.7Syn Z: -0.70
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
limitedCAPN10-related intellectual developmental disorderLOFAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.6551th %ile
GOF
0.6737th %ile
LOF
0.2678th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

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

ClinVar Variant Classifications

305 submitted variants in ClinVar

Classification Summary

Pathogenic95
Likely Pathogenic9
VUS135
Likely Benign30
Benign14
95
Pathogenic
9
Likely Pathogenic
135
VUS
30
Likely Benign
14
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
3
0
92
0
95
Likely Pathogenic
0
0
9
0
9
VUS
1
120
12
2
135
Likely Benign
0
14
1
15
30
Benign
0
7
2
5
14
Total414111622283

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

View in ClinVar →

Protein Context — Lollipop Plot

CAPN10 · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
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