A de novo missense variant with a CADD score > 25 was identified in the ZNF536 gene in a Korean ASD proband in Kim et al., 2024; this gene was subsequently classified as an ASD candidate gene in males following a combined TADA analysis consisting of the Korean ASD cohort described in Kim et al., 2024 in addition to the Simons Simplex Collection and the SPARK cohort. De novo loss-of-function variants in ZNF536 had previously been identified in an ASD proband from the Simons Simplex Collection and in an ASD proband from a Brazilian cohort (Krumm et al., 2015; Costa et al., 2023). ZNF536 has also been shown to significantly associate with schizophrenia (Schizophrenia Working Group of the Psychiatric Genomics Consortium 2014). Studies of znf536 in zebrafish have demonstrated a role for this gene in the development of forebrain neurons implicated in social behavior and stress (Thyme et al., 2019), while adult znf536 knockout (KO) zebrafish were subsequently found to display significant reductions in anxiety-like behavior and social interaction, as well as decreased cerebellar volume (Kim et al., 2024).
Molecular Function
The protein encoded by this gene is a highly conserved zinc finger protein. The encoded protein is most abundant in brain, where it negatively regulates neuronal differentiation by repressing retinoic acid-induced gene transcription (Qin et al., 2009).
External Links
References
Type
Title
Type of Disorder
Associated Disorders
Author, Year
Primary
Whole genome sequencing analysis identifies sex differences of familial pattern contributing to phenotypic diversity in autism
ZNF536, a novel zinc finger protein specifically expressed in the brain, negatively regulates neuron differentiation by repressing retinoic acid-induced gene transcription
