CMA1
protein-codingchymase 1, the group of Granule associated serine proteases of immune defence
Gene summary
This gene encodes a chymotryptic serine proteinase that belongs to the peptidase family S1. It is expressed in mast cells and is thought to function in the degradation of the extracellular matrix, the regulation of submucosal gland secretion, and the generation of vasoactive peptides. In the heart and blood vessels, this protein, rather than angiotensin converting enzyme, is largely responsible for converting angiotensin I to the vasoactive peptide angiotensin II. Alternative splicing results in multiple variants. [provided by RefSeq, Apr 2015]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~2.9 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to CMA1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001836.5. 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 | 1 | 2 | |||
| missense | 41 | 2 | 43 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 43 | 3 | 0 | 46 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001827.1 | 5 | MANE Select | |
| Ensembl | ENSP00000250378.3 | 5 | MANE Select | |
| RefSeq | NP_001295012.1 | 3 | Standard | |
| Ensembl | ENSP00000206446.4 | 3 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Agents Acting on the Renin-Angiotensin System Pathway, Pharmacodynamics
- Renin-angiotensin system - Homo sapiens (human)
- ACE Inhibitor Pathway, Pharmacodynamics
- Lung fibrosis
- ACE Inhibitor Pathway
Biological Process
- angiotensin maturation
- extracellular matrix disassembly
- midbrain development
- basement membrane disassembly
- positive regulation of angiogenesis
Molecular Function
- endopeptidase activity
- serine-type endopeptidase activity
- serine-type peptidase activity
- peptide binding
Cellular Component
- extracellular region
- extracellular space
- cytoplasm
- secretory granule
- collagen-containing extracellular matrix
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000250378
- Coding exons
- 5
- Length
- 2913
- Individuals with no LoFs
- 125014
- Homozygous LoFs
- 4
- Heterozygous LoFs
- 714
- Defined
- 125732
- p
- 0.00286
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -1.75 | 201 | 142 | 1.41 | 0.00000782 | 1589 |
| Missense (PolyPhen) | 76 | 51.795 | 1.4673 | 604 | ||
| Synonymous | -1.90 | 74 | 55.9 | 1.32 | 0.00000300 | 519 |
| Loss of Function | -0.806 | 11 | 8.47 | 1.30 | 3.56e-7 | 112 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.0050 | 0.0050 | notable |
| Latino/Admixed American | 0.0010 | 0.0010 | notable |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.031 | 0.031 | notable |
| Finnish | 0.000092 | 0.000092 | rare |
| European (Non-Finnish) | 0.000080 | 0.000079 | rare |
| South Asian | 0.00039 | 0.00039 | rare |
| Other | 0.0015 | 0.0015 | notable |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Major secreted protease of mast cells with suspected roles in vasoactive peptide generation, extracellular matrix degradation, and regulation of gland secretion.;
Recessive Scores
- pRec
- 0.626
Intolerance Scores
- LoFtool
- 0.477
- RVIS EVS
- 0.2
- RVIS percentile EVS
- 67.19
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.138
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |