CHM Gene: Rab Escort Protein 1 in Choroideremia - NCBI, UniProt, OMIM

The CHM gene (Xq21.2) encodes Rab escort protein 1 (REP1), a component of the Rab geranylgeranyltransferase complex. REP1 binds newly synthesized Rab proteins and presents them to the catalytic RabGGTase subunit for prenylation, a lipid modification essential for Rab membrane targeting and vesicular trafficking. Loss-of-function mutations in CHM cause choroideremia, an X-linked progressive degeneration of the choroid, retinal pigment epithelium, and retina, leading to blindness. REP1 deficiency disrupts Rab27a prenylation and vesicle transport in retinal cells.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• Rab geranylgeranylation (Reactome R-HSA-8873719)

• Vesicle-mediated transport (Reactome R-HSA-5653656)

• Membrane trafficking (Reactome R-HSA-199991)

Rab escort protein 1 (REP1) is a 653-amino acid protein (UniProt P24386) that forms a complex with RabGGTase to catalyze the geranylgeranylation of Rab GTPases. REP1 binds newly synthesized Rab proteins, presents them to the catalytic subunit, and then delivers the prenylated Rab to the target membrane. REP1 is ubiquitously expressed but particularly critical in retinal pigment epithelium and choroid, where Rab27a-mediated melanosome transport is essential for photoreceptor survival. Loss of REP1 leads to accumulation of unprenylated Rab proteins and disrupted vesicular trafficking, causing choroideremia.