CLCA4
protein-codingchloride channel accessory 4, the group of Chloride channel accessory
Gene summary
The protein encoded by this gene belongs to the calcium sensitive chloride conductance protein family. To date, all members of this gene family map to the same site on chromosome 1p31-p22 and share high degrees of homology in size, sequence and predicted structure, but differ significantly in their tissue distributions. Alternative splicing results in multiple transcript variants, only one of which is thought to be protein coding. [provided by RefSeq, Dec 2008]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~33.7 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0009061
Submitter: Orphanet
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to CLCA4 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_012128.4. 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 | 3 | 1 | 4 | |||
| missense | 118 | 12 | 2 | 132 | ||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 1 | 1 | 2 | |||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 120 | 16 | 3 | 139 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_036260.2 | 14 | MANE Select | |
| Ensembl | ENSP00000359594.3 | 14 | MANE Select | |
| Ensembl | ENSP00000532198.1 | 14 | Standard | |
| Ensembl | ENSP00000532199.1 | 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
- Transport of small molecules
Biological Process
- proteolysis
- ion transmembrane transport
- chloride transmembrane transport
Molecular Function
- metalloendopeptidase activity
- intracellular calcium activated chloride channel activity
- chloride channel activity
- metal ion binding
Cellular Component
- extracellular region
- plasma membrane
- integral component of plasma membrane
- apical plasma membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000370563
- Coding exons
- 14
- Length
- 33677
- Individuals with no LoFs
- 124941
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 367
- Defined
- 125308
- p
- 0.00147
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.231 | 468 | 482 | 0.970 | 0.0000235 | 6072 |
| Missense (PolyPhen) | 120 | 142.49 | 0.84215 | 1890 | ||
| Synonymous | 0.121 | 168 | 170 | 0.988 | 0.00000874 | 1765 |
| Loss of Function | 1.41 | 27 | 36.1 | 0.747 | 0.00000175 | 453 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.0067 | 0.0066 | notable |
| Latino/Admixed American | 0.00068 | 0.00064 | rare |
| Ashkenazi Jewish | 0.00010 | 0.000099 | rare |
| East Asian | 0.00028 | 0.00027 | rare |
| Finnish | 0.000046 | 0.000046 | rare |
| European (Non-Finnish) | 0.0017 | 0.0017 | notable |
| South Asian | 0.0013 | 0.0013 | notable |
| Other | 0.0012 | 0.0011 | notable |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: May be involved in mediating calcium-activated chloride conductance.;
Recessive Scores
- pRec
- 0.122
Intolerance Scores
- LoFtool
- 0.946
- RVIS EVS
- -0.75
- RVIS percentile EVS
- 13.71
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.160
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |