Cytohesin-4 (CYTH4)

Cytohesin-4 (CYTH4) is a member of the cytohesin family of guanine nucleotide exchange factors, characterized by an N-terminal coiled-coil motif, central Sec7 domain (GEF activity), and C-terminal pleckstrin homology (PH) domain[1][2][4][5]. CYTH4 activates ADP-ribosylation factor (ARF) small GTPases, specifically ARF1 and ARF5, to regulate protein sorting, membrane trafficking, actin dynamics, and cell adhesion[1][2][3][4]. Its tissue distribution is distinct: notably high in leukocytes, especially monocytes, NK/T cells, and B cells[4]. While not currently a clinical drug target, it is implicated in disease mechanisms, including cancer, reproductive disorders, and neuropsychiatric diseases[1][3]. CYTH4’s evolutionary adaptations and regulation by promoter STRs have functional significance. Variants and expression levels have value as biomarkers in certain pathologies, but no drugs currently act on CYTH4 directly.

Other names

Cytohesin-4CYTH4CYT4PSCD4DJ63G5.1PH, SEC7 and coiled-coil domain-containing protein 4

Not established for therapeutic drugs, but as a guanine nucleotide exchange factor, inhibitors could potentially act by blocking GEF activity (blocking GDP-GTP exchange on ARF1/ARF5). Mechanisms discussed in research focus on its GEF activity that activates ARF1/ARF5 and membrane trafficking, but no drugs specifically exploit this yet.