CLCA2
protein-codingchloride channel accessory 2, the group of Chloride channel accessory
Gene summary
This gene encodes a member of the calcium-activated chloride channel regulator (CLCR) family of proteins. Members of this family regulate the transport of chloride across the plasma membrane. The encoded protein is autoproteolytically processed to generate N- and C- terminal fragments. Expression of this gene is upregulated by the tumor suppressor protein p53 in response to DNA damage. In breast cancer, expression of this gene is downregulated and the encoded protein may inhibit migration and invasion while promoting mesenchymal-to-epithelial transition in cancer cell lines. [provided by RefSeq, Sep 2016]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~32.4 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AD
Disease ID:MONDO:0000992
Submitter: Genomics England PanelApp
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to CLCA2 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_006536.7. 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 | 2 | 2 | 5 | ||
| missense | 145 | 8 | 153 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 147 | 10 | 2 | 159 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_006527.1 | 14 | MANE Select | |
| Ensembl | ENSP00000359596.4 | 14 | MANE Select | |
| Ensembl | ENSP00000809746.1 | 14 | Standard | |
| RefSeq | XP_011540750.1 | 11 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Renin secretion - Homo sapiens (human)
- Pancreatic secretion - Homo sapiens (human)
- Stimuli-sensing channels
- Ion channel transport
- p73 transcription factor network
Biological Process
- proteolysis
- cell adhesion
- ion transmembrane transport
- chloride transmembrane transport
Molecular Function
- metalloendopeptidase activity
- intracellular calcium activated chloride channel activity
- chloride channel activity
- ligand-gated ion channel activity
- metal ion binding
Cellular Component
- extracellular region
- nucleus
- cytosol
- plasma membrane
- integral component of plasma membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000370565
- Coding exons
- 14
- Length
- 32473
- Individuals with no LoFs
- 125577
- Homozygous LoFs
- 1
- Heterozygous LoFs
- 170
- Defined
- 125748
- p
- 0.000680
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.373 | 469 | 492 | 0.953 | 0.0000236 | 6191 |
| Missense (PolyPhen) | 139 | 160.23 | 0.8675 | 2086 | ||
| Synonymous | -1.76 | 204 | 174 | 1.17 | 0.00000840 | 1819 |
| Loss of Function | 0.0804 | 43 | 43.6 | 0.987 | 0.00000254 | 490 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.0010 | 0.0010 | notable |
| Latino/Admixed American | 0.00057 | 0.00055 | rare |
| Ashkenazi Jewish | 0.000099 | 0.000099 | rare |
| East Asian | 0.00038 | 0.00038 | rare |
| Finnish | 0.000092 | 0.000092 | rare |
| European (Non-Finnish) | 0.00087 | 0.00086 | rare |
| South Asian | 0.00079 | 0.00075 | rare |
| Other | 0.00066 | 0.00065 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Plays a role in modulating chloride current across the plasma membrane in a calcium-dependent manner, and cell adhesion. Involved in basal cell adhesion and/or stratification of squamous epithelia. May act as a tumor suppressor in breast and colorectal cancer. Plays a key role for cell adhesion in the beginning stages of lung metastasis via the binding to ITGB4. {ECO:0000269|PubMed:10554024, ECO:0000269|PubMed:11320086, ECO:0000269|PubMed:11445004, ECO:0000269|PubMed:15707651, ECO:0000269|PubMed:16158324}.;
Recessive Scores
- pRec
- 0.157
Intolerance Scores
- LoFtool
- 0.966
- RVIS EVS
- -0.04
- RVIS percentile EVS
- 50.54
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.0361
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | High |
| Cancer | Medium | Medium | Medium |