Aliases: ZNF926
Chromosome No: X
Chromosome Band: Xp22.11
Genetic Category: Rare single gene variant-Syndromic/Functional
ASD Reports: 4
Recent Reports: 0
Annotated variants: 19
Associated CNVs: 10
Evidence score: 3
Associated Disorders: |
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Relevance to Autism
Shepherdson et al., 2024 described a cohort of 18 individuals with germline variants in the ZFX gene who presented with an X-linked neurodevelopmental disorder characterized by developmental delay/intellectual disability, behavioral abnormalities (including a diagnosis of autism spectrum disorder in six individuals), hypotonia, congenital anomalies, and recurrent facial features including thickening and medial broadening of the eyebrows, variations in facial shape, external eye abnormalities, long and/or smooth philtrum, and ear abnormalities. Additional functional assessment in Shepherdson et al., 2024 demonstrated that disease-associated ZFX missense variants resulted in altered target gene expression, while behavioral characterization of zfx knockout zebrafish demonstrated neurocognitive abnormalities. Additional coding variants in the ZFX gene have been previously identified in ASD probands (Chahrour et al., 2012; Ruzzo et al., 2019; Zhou et al., 2022).
Molecular Function
This gene on the X chromosome is structurally similar to a related gene on the Y chromosome. It encodes a member of the krueppel C2H2-type zinc-finger protein family. The full-length protein contains an acidic transcriptional activation domain (AD), a nuclear localization sequence (NLS) and a DNA binding domain (DBD) consisting of 13 C2H2-type zinc fingers. Studies in mouse embryonic and adult hematopoietic stem cells showed that this gene was required as a transcriptional regulator for self-renewal of both stem cell types, but it was dispensable for growth and differentiation of their progeny.