Relevance to Autism

Rare de novo variants in the ABL2 gene have been identified in ASD probands, including a de novo missense variant (p.Ala1099Thr) in a proband from the Simons Simplex Collection (Iossifov et al., 2014; Yuen et al., 2017; Turner et al., 2017; Satterstrom et al., 2020), while an maternally-inherited loss-of-function variant in this gene was observed in all four ASD-affected siblings from a multiplex family from the iHART cohort (Ruzzo et al., 2019). Functional assessment of the ASD-associated p.Ala1099Thr missense variant in Drosophila using a rescue-based strategy in Macrogliese et al., 2022 demonstrated that humanized flies carrying the ABL2-p.Ala1099Thr mutation had significantly decreased lifespan compared with reference animals, indicating a reduced ability to rescue TG4 lethality that was consistent with a loss-of-function effect. Previous studies have shown that genetic knock-out of this gene in mice resulted in synapse, dendritic spine, and dendrite arbor loss accompanied by behavioral deficits (Moresco et al., 2005; Sfakianos et al., 2007).

Molecular Function

This gene encodes a member of the Abelson family of nonreceptor tyrosine protein kinases. The protein is highly similar to the c-abl oncogene 1 protein, including the tyrosine kinase, SH2 and SH3 domains, and it plays a role in cytoskeletal rearrangements through its C-terminal F-actin- and microtubule-binding sequences. This gene is expressed in both normal and tumor cells, and is involved in translocation with the ets variant 6 gene in leukemia.

External Links

References