Carbonic anhydrase 4 (CA4) (CA4)

Carbonic anhydrase 4 (CA4) is a glycosylphosphatidylinositol (GPI)-anchored enzyme primarily located on the luminal and basolateral membranes of the renal proximal tubule and the thick ascending limb (UniProt P22748). It is essential for systemic acid-base homeostasis, catalyzing the reversible hydration of carbon dioxide to bicarbonate and protons, which facilitates the reabsorption of approximately 80% of filtered bicarbonate in the kidney (PubMed: 10336015). Beyond the renal system, CA4 is expressed in the choriocapillaris of the eye and the endothelium of various capillaries (NCBI Gene ID: 762). Clinically, CA4 is a target for carbonic anhydrase inhibitors like acetazolamide, which are utilized to manage glaucoma, altitude sickness, and certain types of edema by promoting diuresis and reducing fluid secretion (StatPearls: Carbonic Anhydrase Inhibitors). Mutations in the CA4 gene have been specifically linked to Retinitis pigmentosa 17, an autosomal dominant form of retinal degeneration (OMIM: 600827). Therapeutic challenges include systemic side effects such as metabolic acidosis and electrolyte imbalances due to the widespread distribution of CA isoforms (PubMed: 24511862).

Other names

Carbonic anhydrase IVCA-IVCAIVCarbonate dehydratase IVGPI-anchored carbonic anhydrase

Inhibition of the enzyme's catalytic activity prevents the dehydration of luminal bicarbonate and the hydration of intracellular carbon dioxide, thereby reducing bicarbonate reabsorption and promoting diuresis.