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GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 15 days ago
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CAPN15
calpain 15
Chromosome 16 Β· 16p13.3
NCBI Gene: 6650Ensembl: ENSG00000103326.13HGNC: HGNC:11182UniProt: O75808
36PubMed Papers
21Diseases
0Drugs
7Pathogenic Variants
FUNCTIONAL ROLE
Protease
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
cell adhesioncysteine-type peptidase activityprotein bindingcytoplasmoculogastrointestinal-neurodevelopmental syndromemicrophthalmiacolobomaAbnormality of the skeletal system
✦AI Summary

CAPN15 encodes calpain 15, an intracellular cysteine protease belonging to the non-classical small optic lobe (SOL) family of calpains that plays critical roles in vertebrate development 1. The protein exhibits calcium-dependent cysteine-type endopeptidase activity and demonstrates a preference for cleavage at basic residues, particularly lysine 2. CAPN15 is widely expressed throughout the brain and central nervous system, with strongest expression during early development that decreases postnatally 1. In adult mice, expression is particularly prominent in neurons involved in plasticity such as the hippocampus, lateral amygdala, and Purkinje neurons 3. Loss of CAPN15 function is associated with oculogastrointestinal neurodevelopmental syndrome (OGIN), a rare autosomal recessive disorder characterized by developmental eye anomalies including microphthalmia and coloboma, growth deficits, developmental delay, and hearing loss 1. Recent studies have expanded the phenotypic spectrum to include Dandy-Walker malformation and cerebellar anomalies 4. Complete knockout mice exhibit smaller brains with particularly affected thalamus and hippocampal subregions 3, while conditional knockout studies demonstrate roles in adult behavior including self-grooming, motor performance, and fear conditioning 5. The protein appears to have distinct functions in brain development versus adult brain function.

Sources cited
1
CAPN15 belongs to the SOL family of calpains, is widely expressed in brain/CNS during development, and loss causes eye defects and neurodevelopmental disorders
PMID: 32885237
2
CAPN15 shows preference for cleavage at basic residues, particularly lysine
PMID: 40238785
3
CAPN15 is expressed in adult brain regions involved in plasticity and knockout mice have smaller brains with affected thalamus and hippocampus
PMID: 33951504
4
CAPN15 variants are associated with Dandy-Walker malformation, expanding the phenotypic spectrum
PMID: 37596828
5
CAPN15 conditional knockout affects adult behaviors including self-grooming, motor performance, and fear conditioning
PMID: 37598906
Disease Associationsβ“˜21
oculogastrointestinal-neurodevelopmental syndromeOpen Targets
0.72Strong
microphthalmiaOpen Targets
0.50Moderate
colobomaOpen Targets
0.48Moderate
Abnormality of the skeletal systemOpen Targets
0.06Suggestive
Isolated anophthalmia - microphthalmiaOpen Targets
0.06Suggestive
microphthalmia, isolated, with colobomaOpen Targets
0.06Suggestive
ovarian dysfunctionOpen Targets
0.05Suggestive
early-onset non-syndromic cataractOpen Targets
0.05Suggestive
congenital primary aphakiaOpen Targets
0.04Suggestive
microphthalmia, isolated, with coloboma 10Open Targets
0.04Suggestive
Microphthalmia - ankyloblepharon - intellectual disabilityOpen Targets
0.04Suggestive
Microphthalmia - cataractOpen Targets
0.04Suggestive
microphthalmia, isolated, with cataract 1Open Targets
0.04Suggestive
cataract 9 multiple typesOpen Targets
0.04Suggestive
Cataract-microcornea syndromeOpen Targets
0.04Suggestive
anterior segment dysgenesis 7Open Targets
0.04Suggestive
Congenital cataract microcornea with corneal opacityOpen Targets
0.04Suggestive
Posterior polar cataractOpen Targets
0.04Suggestive
Familial ocular anterior segment mesenchymal dysgenesisOpen Targets
0.04Suggestive
autosomal dominant keratitisOpen Targets
0.04Suggestive
Oculogastrointestinal neurodevelopmental syndromeUniProt
Pathogenic Variants7
NM_005632.3(CAPN15):c.1003del (p.Ser335fs)Likely pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 335
NM_005632.3(CAPN15):c.1957G>A (p.Gly653Ser)Likely pathogenic
Oculogastrointestinal-neurodevelopmental syndrome
β˜…β˜†β˜†β˜†2024β†’ Residue 653
NM_005632.3(CAPN15):c.2398C>T (p.Arg800Trp)Pathogenic
Oculogastrointestinal-neurodevelopmental syndrome
β˜†β˜†β˜†β˜†2021β†’ Residue 800
NM_005632.3(CAPN15):c.3083G>A (p.Arg1028Lys)Pathogenic
Oculogastrointestinal-neurodevelopmental syndrome
β˜†β˜†β˜†β˜†2021β†’ Residue 1028
NM_005632.3(CAPN15):c.2904+1_2905-45delPathogenic
Oculogastrointestinal-neurodevelopmental syndrome
β˜†β˜†β˜†β˜†2021
NM_005632.3(CAPN15):c.2159C>T (p.Ser720Phe)Pathogenic
Oculogastrointestinal-neurodevelopmental syndrome
β˜†β˜†β˜†β˜†2021β†’ Residue 720
NM_005632.3(CAPN15):c.2905G>A (p.Gly969Ser)Pathogenic
Oculogastrointestinal-neurodevelopmental syndrome
β˜†β˜†β˜†β˜†2021β†’ Residue 969
View on ClinVar β†—
Related Genes
CAPNS1Protein interaction78%HABP2Shared pathway67%LMLNShared pathway67%TINAGShared pathway67%CIROPShared pathway50%PCDH18Shared pathway50%
Tissue Expression6 tissues
Liver
100%
Lung
84%
Ovary
65%
Bone Marrow
57%
Brain
11%
Heart
10%
Gene Interaction Network
Click a node to explore
CAPN15CAPNS1HABP2LMLNTINAGCIROPPCDH18
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted Β· UniProt O75808
View on AlphaFold β†—
Constraintβ“˜
LOEUFβ“˜
0.97LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF0.77 [0.62–0.97]
RankingsWhere CAPN15 stands among ~20K protein-coding genes
  • #10,744of 20,598
    Most Researched36
  • #3,239of 5,498
    Most Pathogenic Variants7
  • #9,265of 17,882
    Most Constrained (LOEUF)0.97
Genes detectedCAPN15
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
circRARS synergises with IGF2BP3 to regulate RNA methylation recognition to promote tumour progression in renal cell carcinoma.
PMID: 38073586
Clin Transl Med Β· 2023
1.00
2
Identifying putative substrates of Calpain-15 in neurodevelopment.
PMID: 40238785
PLoS One Β· 2025
0.90
3
MRI of Capn15 Knockout Mice and Analysis of Capn 15 Distribution Reveal Possible Roles in Brain Development and Plasticity.
PMID: 33951504
Neuroscience Β· 2021
0.80
4
Behavioral characterization of Capn15 conditional knockout mice.
PMID: 37598906
Behav Brain Res Β· 2023
0.70
5
Novel association of Dandy-Walker malformation with CAPN15 variants expands the phenotype of oculogastrointestinal neurodevelopmental syndrome.
PMID: 37596828
Am J Med Genet A Β· 2023
0.60