Spectrin repeat containing nuclear envelope protein 4 (SYNE4)

Spectrin repeat containing nuclear envelope protein 4 (SYNE4), also called Nesprin-4, is a component of the linker of nucleoskeleton and cytoskeleton (LINC) complex, localized to the outer nuclear membrane[2][3][1]. It is distinguished by a C-terminal KASH (Klarsicht, ANC-1, Syne Homology) domain, spectrin repeats, coiled-coil and leucine zipper regions, and a kinesin-1 binding domain[2][1]. SYNE4/Nesprin-4 physically connects the nuclear envelope to the microtubule cytoskeleton by recruiting kinesin-1, thus regulating nuclear positioning, particularly in secretory epithelial cells and cochlear outer hair cells[2][3][1]. Loss-of-function mutations in SYNE4 cause mislocalization of hair cell nuclei, leading to progressive hearing loss (deafness, DFNB76), with no described phenotypes other than deafness observed in humans and mice[3][2]. The functional importance of Nesprin-4 is most evident in outer hair cells of the cochlea, where its interaction with kinesin-1 is essential for nuclear anchoring and cell survival; mutations in its key binding motif abolish function and recapitulate the hearing loss phenotype in vivo[3]. SYNE4 has not been described as a direct therapeutic target, nor are there drugs known to act upon it[2][3][1].

Other names

Nesprin-4C19orf46KASH4FLJ36445Nesp4KASH domain-containing protein 4Nuclear envelope spectrin repeat protein 4DFNB76deafness, autosomal recessive 76