Aliases: CDA1, CINAP, CTCL, DENTT, HRIHFB2216, NP79, SE204, TSPX
Chromosome No: X
Chromosome Band: Xp11.22
Genetic Category: Functional-Multigenic CNV/Functional-Rare single gene variant
ASD Reports: 7
Recent Reports: 0
Annotated variants: 12
Associated CNVs: 9
Evidence score: 2
| Associated Disorders: |
|
Relevance to Autism
A hemizygous missense variant in the TSPYL2 gene was identified in two ASD-affected brothers from a Qatari ASD cohort (Al-Sarraj et al., 2024). De novo missense variants and a de novo in-frame deletion variant in this gene have previously been identified in male ASD probands from the SPARK cohort (Zhou et al., 2022). Tspyl2 loss-of-function mice have been shown to exhibit downregulation of N-methyl-D-aspartate receptor subunits 2A and 2B (GluN2A and GluN2B) in the hippocampus, impaired long-term potentiation at hippocampal Schaffer collateral-CA1 synapses, deficits in fear learning and memory, marginal increases in activity, significantly impaired prepulse inhibition, significantly increased sensitivity to the dopamine agonist amphetamine, and significantly smaller lateral ventricles (Tsang et al., 2014; Li et al., 2016). Tsang et al., 2014 also demonstrated by luciferase reporter assays and chromatin immunoprecipitation studies that TSPYL2 regulated the expression of Grin2a and Grin2b, the genes encoding GluN2A and GluN2B, and that TSPYL2 interacted with CREBBP, indicating that TSPYL2 may activate gene expression through this interaction. Moey et al., 2016 reported that Xp11.22 microduplications including IQSEC2, TSPYL2 and KDM5C were identified in four males presenting with intellectual disability, deficits in speech development, and behavior disturbances, including one individual with autism spectrum disorder; lymphoblastic cell lines from patients showed markedly elevated levels of TSPYL2 and KDM5C.
Molecular Function
This gene encodes a member of the testis-specific protein Y-encoded, TSPY-like/SET/nucleosome assembly protein-1 superfamily. The encoded protein is localized to the nucleolus where it functions in chromatin remodeling and as an inhibitor of cell-cycle progression. This protein is part of the CASK/TBR1/TSPYL2 transcriptional complex which modulates gene expression in response to neuronal synaptic activity, probably by facilitating nucleosome assembly (Wang et al., 2004).
External Links
