CLCA1
protein-codingchloride channel accessory 1, the group of Chloride channel accessory
Gene summary
This gene encodes a member of the calcium sensitive chloride conductance protein family. To date, all members of this gene family map to the same region on chromosome 1p31-p22 and share a high degree of homology in size, sequence, and predicted structure, but differ significantly in their tissue distributions. The encoded protein is expressed as a precursor protein that is processed into two cell-surface-associated subunits, although the site at which the precursor is cleaved has not been precisely determined. The encoded protein may be involved in mediating calcium-activated chloride conductance in the intestine. [provided by RefSeq, Jul 2008]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~31.9 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 CLCA1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001285.4. 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 | 0 | |||||
| missense | 101 | 11 | 4 | 116 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 101 | 11 | 4 | 116 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001276.3 | 14 | MANE Select | |
| Ensembl | ENSP00000378200.1 | 14 | MANE Select | |
| Ensembl | ENSP00000234701.3 | 14 | Standard | |
| Ensembl | ENSP00000234701.3 | 14 | 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
- Alpha6Beta4Integrin
Biological Process
- proteolysis
- calcium ion transport
- ion transmembrane transport
- cellular response to hypoxia
- chloride transmembrane transport
Molecular Function
- metalloendopeptidase activity
- intracellular calcium activated chloride channel activity
- chloride channel activity
- metal ion binding
Cellular Component
- extracellular space
- plasma membrane
- integral component of plasma membrane
- microvillus
- zymogen granule membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000234701
- Coding exons
- 14
- Length
- 31922
- Individuals with no LoFs
- 125641
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 107
- Defined
- 125748
- p
- 0.000426
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.705 | 449 | 493 | 0.911 | 0.0000253 | 5973 |
| Missense (PolyPhen) | 154 | 187.4 | 0.82176 | 2316 | ||
| Synonymous | -0.554 | 194 | 184 | 1.05 | 0.0000101 | 1813 |
| Loss of Function | 2.99 | 21 | 41.9 | 0.501 | 0.00000233 | 471 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00043 | 0.00043 | rare |
| Latino/Admixed American | 0.00073 | 0.00072 | rare |
| Ashkenazi Jewish | 0.00050 | 0.00050 | rare |
| East Asian | 0.00022 | 0.00022 | rare |
| Finnish | 0.00014 | 0.00014 | rare |
| European (Non-Finnish) | 0.00039 | 0.00039 | rare |
| South Asian | 0.00053 | 0.00052 | rare |
| Other | 0.00049 | 0.00049 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: May be involved in mediating calcium-activated chloride conductance. May play critical roles in goblet cell metaplasia, mucus hypersecretion, cystic fibrosis and AHR. May be involved in the regulation of mucus production and/or secretion by goblet cells. Involved in the regulation of tissue inflammation in the innate immune response. May play a role as a tumor suppressor. Induces MUC5AC. {ECO:0000269|PubMed:11445004, ECO:0000269|PubMed:11842292, ECO:0000269|PubMed:11956057, ECO:0000269|PubMed:23112050, ECO:0000269|PubMed:9828122}.;
Recessive Scores
- pRec
- 0.143
Intolerance Scores
- LoFtool
- 0.827
- RVIS EVS
- 0.25
- RVIS percentile EVS
- 69.66
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.542
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |