CA4
protein-codingcarbonic anhydrase 4, the group of Carbonic anhydrases
Gene summary
Carbonic anhydrases (CAs) are a large family of zinc metalloenzymes that catalyze the reversible hydration of carbon dioxide. They participate in a variety of biological processes, including respiration, calcification, acid-base balance, bone resorption, and the formation of aqueous humor, cerebrospinal fluid, saliva, and gastric acid. They show extensive diversity in tissue distribution and in their subcellular localization. This gene encodes a glycosylphosphatidyl-inositol-anchored membrane isozyme expressed on the luminal surfaces of pulmonary (and certain other) capillaries and proximal renal tubules. Its exact function is not known; however, it may have a role in inherited renal abnormalities of bicarbonate transport. [provided by RefSeq, Jul 2008]
- RP17
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~21.0 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AD
Disease ID:MONDO:0010945
Submitter: Labcorp Genetics (formerly Invitae)
Inheritance Pattern: AD
Disease ID:MONDO:0019200
Submitter: G2P
Inheritance Pattern: AD
Disease ID:MONDO:0019200
Submitter: Orphanet
Clinical Genomic Database (CGD)
Manifestation: Ophthalmologic
Intervention: General
Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to CA4 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_000717.5. 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 | 4 | 75 | 2 | 81 | ||
| missense | 3 | 163 | 21 | 1 | 188 | |
| nonsense | 4 | 1 | 2 | 7 | ||
| start loss | 1 | 1 | ||||
| frameshift | 1 | 2 | 3 | |||
| splice donor/acceptor (+/-2bp) | 6 | 3 | 9 | |||
| Total | 4 | 11 | 175 | 96 | 3 | 289 |
Highest pathogenic variant AF is 0.00016694116
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_000708.1 | 8 | MANE Select | |
| Ensembl | ENSP00000300900.3 | 8 | MANE Select | |
| Ensembl | ENSP00000467465.1 | 4 | Standard | |
| Ensembl | ENSP00000464757.1 | 2 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Proximal tubule bicarbonate reclamation - Homo sapiens (human)
- Nitrogen metabolism - Homo sapiens (human)
- Metabolism
- O2/CO2 exchange in erythrocytes
- Transport of small molecules
Biological Process
- bicarbonate transport
Molecular Function
- carbonate dehydratase activity
- protein binding
- zinc ion binding
Cellular Component
- rough endoplasmic reticulum
- endoplasmic reticulum-Golgi intermediate compartment
- Golgi apparatus
- trans-Golgi network
- plasma membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000300900
- Coding exons
- 8
- Length
- 20964
- Individuals with no LoFs
- 125732
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 15
- Defined
- 125747
- p
- 0.0000596
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.122 | 179 | 174 | 1.03 | 0.0000101 | 2002 |
| Missense (PolyPhen) | 62 | 62.007 | 0.99989 | 748 | ||
| Synonymous | -1.50 | 98 | 80.9 | 1.21 | 0.00000544 | 616 |
| Loss of Function | 1.15 | 10 | 14.8 | 0.678 | 6.51e-7 | 176 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00012 | 0.00012 | rare |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0.000099 | 0.000099 | rare |
| East Asian | 0.000054 | 0.000054 | rare |
| Finnish | 0.000046 | 0.000046 | rare |
| European (Non-Finnish) | 0.000054 | 0.000053 | rare |
| South Asian | 0.000065 | 0.000065 | rare |
| Other | 0.00034 | 0.00033 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Reversible hydration of carbon dioxide. May stimulate the sodium/bicarbonate transporter activity of SLC4A4 that acts in pH homeostasis. It is essential for acid overload removal from the retina and retina epithelium, and acid release in the choriocapillaris in the choroid. {ECO:0000269|PubMed:15563508}.;
Recessive Scores
- pRec
- 0.216
Intolerance Scores
- LoFtool
- 0.529
- RVIS EVS
- 0.22
- RVIS percentile EVS
- 68.27
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.656
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |