CAPN12
protein-codingcalpain 12, the group of Calpains|EF-hand domain containing
Gene summary
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 a member of the calpain large subunit family. [provided by RefSeq, Jun 2012]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~39.7 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0001071
Submitter: Ambry Genetics
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to CAPN12 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_144691.4. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 1 | 16 | 10 | 27 | ||
| missense | 177 | 11 | 4 | 192 | ||
| nonsense | 2 | 1 | 3 | |||
| start loss | 0 | |||||
| frameshift | 1 | 1 | ||||
| splice donor/acceptor (+/-2bp) | 9 | 9 | ||||
| Total | 0 | 0 | 189 | 29 | 14 | 232 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_653292.2 | 21 | MANE Select | |
| Ensembl | ENSP00000331636.3 | 21 | MANE Select | |
| Ensembl | ENSP00000469217.1 | 3 | Standard | |
| Ensembl | ENSP00000471007.1 | 5 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| capn12 | Danio rerio | Structure: keratinocyte Quality: increased size abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Extracellular matrix organization
- Degradation of the extracellular matrix
Biological Process
- proteolysis
Molecular Function
- calcium-dependent cysteine-type endopeptidase activity
- calcium ion binding
Cellular Component
- cytoplasm
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000328867
- Coding exons
- 21
- Length
- 39718
- Individuals with no LoFs
- 125180
- Homozygous LoFs
- 2
- Heterozygous LoFs
- 566
- Defined
- 125748
- p
- 0.00226
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -1.26 | 510 | 436 | 1.17 | 0.0000279 | 4611 |
| Missense (PolyPhen) | 205 | 178.6 | 1.1478 | 1822 | ||
| Synonymous | -3.03 | 238 | 186 | 1.28 | 0.0000121 | 1453 |
| Loss of Function | -1.09 | 46 | 38.7 | 1.19 | 0.00000166 | 436 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.0048 | 0.0047 | notable |
| Latino/Admixed American | 0.0022 | 0.0022 | notable |
| Ashkenazi Jewish | 0.00071 | 0.00069 | rare |
| East Asian | 0.0021 | 0.0021 | notable |
| Finnish | 0.00098 | 0.00097 | rare |
| European (Non-Finnish) | 0.0014 | 0.0014 | notable |
| South Asian | 0.0059 | 0.0059 | notable |
| Other | 0.0021 | 0.0021 | notable |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Calcium-regulated non-lysosomal thiol-protease. {ECO:0000250}.;
Recessive Scores
- pRec
- 0.118
Intolerance Scores
- LoFtool
- 0.334
- RVIS EVS
- -0.52
- RVIS percentile EVS
- 20.94
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.200
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |