CACNA1F

CACNA1F is a human gene that encodes the alpha-1F subunit of the Cav1.4 voltage-gated calcium channel, a member of the L-type (Cav1) family. The channel forms the pore that allows calcium influx in response to membrane depolarization and thereby drives neurotransmitter release at photoreceptor synapses in the retina. The CACNA1F gene is located on the X chromosome and is expressed predominantly in retinal tissue, with strong enrichment in photoreceptor terminals where cone pathways are prominent.

The protein features the typical architecture of voltage-gated calcium channel alpha1 subunits, consisting of four homologous domains (I–IV), each with six transmembrane segments. Cav1.4 assembles with auxiliary beta and alpha2delta subunits that influence trafficking and biophysical properties. In the retina, Cav1.4 mediates sustained calcium entry that supports continuous neurotransmitter release from cone (and to a lesser extent rod) photoreceptors toward downstream bipolar cells, a process essential for normal visual signaling and light adaptation.

Clinical significance associated with CACNA1F mutations principally includes X-linked congenital stationary night blindness type 2 (CSNB2). Affected individuals typically exhibit impaired photoreceptor signal transmission, nystagmus, reduced visual acuity, and characteristic electroretinography patterns, with disease usually non-progressive. Variants may also be associated with refractive errors or other retinal phenotypes in some cases. Diagnosis is aided by genetic testing; management is primarily supportive, addressing visual function and orientation, while research continues into potential gene-based therapies and targeted interventions.