TMEM38B

Trimeric intracellular cation-selective channel B is a monovalent cation channel in the ER membrane encoded by the transmembrane protein 38B gene. It is one of two known Trimeric [intracellular cation-selective channel|TRIC proteins], the other being TRIC-A.

Function

TRIC-B is permeable to both Na⁺ and K⁺ but not divalent cations like Ca²⁺. The channel exhibits marked voltage-dependence, becoming more open when the cytosol is more positively charged than the ER lumen. There at least four major sub-conductance states. TMEM38B-knockout mice exhibit reduced IP₃-receptor-mediated Ca²⁺ release. As such, K⁺ flux into the ER through TRIC-B is thought to support IP₃-induced efflux of Ca²⁺ ions through IP₃-gated Ca²⁺ channels in the ER membrane.

Clinical significance

Null mutations in TMEM38B reduce the levels of functional TRIC-B in heterozygotes and abolish expression of functional TRIC-B in homozygotes. Such mutations are an uncommon but relatively severe cause of autosomal recessive osteogenesis imperfecta or "brittle bone disease".