CA4 Gene: Carbonic Anhydrase IV - Function, Disease Associations, and Expression
Comprehensive resource for the CA4 gene, covering its genomic context, protein function, tissue expression, associated diseases, and clinical significance.
Gene Information Card
| Symbol | CA4 |
|---|---|
| Full Name | carbonic anhydrase 4 |
| Gene Type | protein coding |
| Chromosomal Location | 17q23.1 |
| NCBI Gene ID | 762 ncbi.nlm.nih.gov/gene/762 |
| Ensembl ID | ENSG00000115286 |
| UniProt ID | P22748 |
| OMIM ID | 114760 |
| HGNC ID | 1375 |
| Aliases | CAIV, RP17 |
Description
The CA4 gene encodes carbonic anhydrase IV, a glycosylphosphatidylinositol (GPI)-anchored membrane enzyme. This protein catalyzes the reversible hydration of carbon dioxide to bicarbonate and a proton, a fundamental reaction for pH regulation, ion transport, and fluid secretion in various tissues. CA4 is particularly abundant in the kidney, lung, and eye, where it plays a critical role in acid-base balance and visual function. Mutations in this gene are associated with Retinitis Pigmentosa type 17 (RP17).
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Retinitis Pigmentosa 17 (RP17) | Mutations in CA4 cause a progressive degeneration of rod and cone photoreceptors. The mechanism is thought to involve impaired pH buffering in the retinal microenvironment, leading to cellular stress and apoptosis. Specific mutations may also cause protein misfolding and ER stress. | OMIM: 114760, ClinVar |
| Retinitis Pigmentosa | CA4 mutations are a rare cause of autosomal dominant retinitis pigmentosa. The disease is characterized by night blindness, constriction of visual fields, and eventual loss of central vision. | OMIM: 114760, PubMed |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Kidney | High | High |
| Lung | High | High |
| Eye (Retina) | High | High |
| Brain | Low | Low |
| Heart | Low | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | Low | Low expression in this cell line. |
| HeLa | Low | Low expression in this cell line. |
| A549 | Medium | Moderate expression in this lung carcinoma cell line. |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| R14W | Missense | Rare | Associated with Retinitis Pigmentosa 17. Likely causes protein misfolding and ER retention. |
| R67H | Missense | Rare | Associated with Retinitis Pigmentosa 17. May affect catalytic activity or protein stability. |
| K18E | Missense | Rare | Associated with Retinitis Pigmentosa 17. Likely affects protein folding and function. |
Mutation functional classification
Loss of Function (LOF)
Most CA4 mutations associated with RP17 are considered loss-of-function or dominant-negative. They lead to reduced enzymatic activity, protein misfolding, and/or impaired trafficking to the cell surface.
Gain of Function (GOF)
No evidence for a gain-of-function mechanism for CA4 mutations in disease.
Dominant Negative (DN)
The autosomal dominant inheritance pattern of RP17 suggests a dominant-negative effect. Mutant CA4 proteins may interfere with the function of the wild-type protein, possibly by forming inactive oligomers or by overwhelming the cellular quality control machinery.
View complete mutation data：
Gene Ontology (GO)
| • carbonate dehydratase activity | • zinc ion binding |
| • lyase activity | • membrane |
| • anchored component of membrane | • extracellular exosome |
| • one-carbon metabolic process | • bicarbonate transport |
Pathways
• Carbonate dehydratase (carbonic anhydrase) pathway
• Nitric oxide pathway (modulation)
Protein Summary
Carbonic anhydrase 4 (CA4) is a 312-amino acid protein with a molecular weight of approximately 35 kDa. It is attached to the extracellular surface of the plasma membrane via a glycosylphosphatidylinositol (GPI) anchor. The protein has a characteristic alpha-carbonic anhydrase domain that contains an active site with a zinc ion, essential for its catalytic function. CA4 is highly expressed in the kidney, lung, and eye, where it facilitates rapid CO2 hydration. In the retina, it is localized to the choriocapillaris endothelium and the retinal pigment epithelium, playing a crucial role in maintaining pH homeostasis. Defects in this protein lead to Retinitis Pigmentosa 17.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| ABCA4 Knockout HEK293 Cell Line | EDJ-KQ1043 | Human | 24 | Details Get a Quote |
| CDCA4 Knockout HEK293 Cell Line | EDJ-KQ3636 | Human | 55038 | Details Get a Quote |
| CA4 Knockout HEK293 Cell Line | EDJ-KQ4169 | Human | 762 | Details Get a Quote |
| SPACA4 Knockout HEK293 Cell Line | EDJ-KQ7441 | Human | 171169 | Details Get a Quote |
| CLCA4 Knockout HEK293 Cell Line | EDJ-KQ7677 | Human | 22802 | Details Get a Quote |
| SMARCA4 Knockout HEK293 Cell Line | EDJ-KQ15359 | Human | 6597 | Details Get a Quote |
| SMARCA4 Knockout HeLa Cell Line | EDJ-KQ18175 | Human | 6597 | Details Get a Quote |
| CDCA4 Knockout A-549 Cell Line | EDJ-KQ24209 | Human | 55038 | Details Get a Quote |
| SMARCA4 Knockout HCT 116 Cell Line | EDJ-KQ46095 | Human | 6597 | Details Get a Quote |
| SMARCA4 Knockout A-549 Cell Line | EDJ-KQ44863 | Human | 6597 | Details Get a Quote |
| ABCA4 Knockout HeLa Cell Line | EDJ-KQ18293 | Human | 24 | Details Get a Quote |
| CDCA4 Knockout HCT 116 Cell Line | EDJ-KQ25583 | Human | 55038 | Details Get a Quote |
| CDCA4 Knockout HeLa Cell Line | EDJ-KQ25584 | Human | 55038 | Details Get a Quote |
| Smarca4 Knockout 4T1 Cell Line | EDJ-KZ48 | Mouse | 20586 | Details Get a Quote |
| SMARCA4 Knockout Hep-G2 Cell Line | EDJ-KZ480 | Human | 6597 | Details Get a Quote |
Displaying Records 1 To 15 Of 27 Records
