ZDHHC9

ZDHHC9 is a protein-coding gene in humans. It encodes a member of the ZDHHC family of palmitoyltransferases, enzymes that catalyze S-palmitoylation, the reversible addition of palmitate to cysteine residues on substrate proteins. This lipid modification influences protein trafficking, stability, and interactions, and is particularly important in brain development and synaptic function.

ZDHHC9 proteins are integral membrane proteins characterized by a DHHC catalytic motif within the cytosolic region and multiple transmembrane domains; they are typically localized to intracellular membranes such as the Golgi apparatus and endoplasmic reticulum, where they palmitoylate substrate proteins.

Genetic variants in ZDHHC9 on the X chromosome have been associated with X-linked intellectual disability and neurodevelopmental disorders in several studies. Reported variants include loss-of-function and missense mutations, which can result in reduced enzymatic activity and altered neuronal signaling. Phenotypes described in affected males often include intellectual disability, language impairment, and sometimes seizures; carrier females may be mildly affected.

Research continues to define the substrate repertoire of ZDHHC9 and its precise role in neuronal development and function, as well as to determine the full spectrum of associated clinical features.