CAPN15

Chr 16AR

calpain 15

Also known as: OGIN, SOLH

NCBI Gene: 6650ENSG00000103326UniProt: O75808

This gene encodes a protein containing zinc-finger-like repeats and a calpain-like protease domain. The encoded protein may function as a transcription factor, RNA-binding protein, or in protein-protein interactions during visual system development. [provided by RefSeq, Jul 2008]

Primary Disease Associations & Inheritance

Oculogastrointestinal neurodevelopmental syndromeMIM #619318
AR
0
Active trials
56
Pathogenic / LP
435
ClinVar variants
4
Pubs (1 yr)
1.8
Missense Z
0.32
LOEUF· LoF intolerant
Clinical Summary— CAPN15
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.97). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
56 Pathogenic / Likely Pathogenic· 276 VUS of 435 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
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.
0.32LOEUF
pLI 0.969
Z-score 4.97
OE 0.17 (0.10–0.32)
Highly constrained

Highly LoF-intolerant (top ~10% 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.
1.77Z-score
OE missense 0.81 (0.76–0.87)
578 obs / 711.0 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 (0.10–0.32)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.81 (0.76–0.87)
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.1.31
0≤1.21.6
LoF obs/exp: 7 / 41.6Missense obs/exp: 578 / 711.0Syn Z: -4.46

ClinVar Variant Classifications

435 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic53
Likely Pathogenic3
VUS276
Likely Benign87
Benign14
Conflicting2
53
Pathogenic
3
Likely Pathogenic
276
VUS
87
Likely Benign
14
Benign
2
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
1
4
48
0
53
Likely Pathogenic
1
1
1
0
3
VUS
0
254
22
0
276
Likely Benign
0
21
6
60
87
Benign
0
1
5
8
14
Conflicting
—2
Total22818268435

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

View in ClinVar →

Protein Context — Lollipop Plot

CAPN15 · protein map & ClinVar variants

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

Gene2Phenotype Curations

CAPN15-related oculogastrointestinal neurodevelopmental syndrome

strong
ARLoss Of FunctionAbsent Gene Product, Altered Gene Product Structure
Dev. Disorders
G2P ↗
splice donor variantframeshift variantmissense variantintron variantwhole partial gene duplication

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Landmark / reviewRecent case evidence
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 4 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 4 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