CHRNA7 (exons 5-10) and FAM7A (exons A-E) fusion protein (CHRFAM7A)

CHRFAM7A is a uniquely human fusion protein resulting from the partial duplication of the CHRNA7 gene (exons 5–10, encoding the neuronal acetylcholine receptor alpha-7 subunit) and fusion with the FAM7A gene (exons A–E). The encoded protein can be incorporated into the α7 nicotinic acetylcholine receptor pentamer, producing a hypomorphic receptor complex with reduced channel open probability and lowered calcium permeability. CHRFAM7A acts as a negative modulator of α7 nAChR function, affecting synaptic transmission and cholinergic signaling. Its genotype is associated with altered risk and drug response in several neuropsychiatric and neurodegenerative diseases, particularly Alzheimer’s disease, where it can mitigate β-amyloid uptake and neuronal toxicity. Unlike CHRNA7, CHRFAM7A is only found in humans and displays population-specific allelic variation; these features are thought to underlie differences between animal and human clinical responses to cholinergic ligands targeting α7 nAChR.

Other names

CHRFAM7ACHRNA7-FAM7A fusion proteinD-10CHRNA7-DR1NACHRA7alpha 7 neuronal nicotinic acetylcholine receptor-FAM7A hybridalpha-7 nicotinic cholinergic receptor subunitNeuronal acetylcholine receptor subunit alpha-7 (fusion)

Dominant negative modulation of α7 nAChR by incorporation into heteropentamers, resulting in reduced channel open probability and lower calcium influx; Interference with Aβ1–42 uptake at the α7 nAChR