Relevance to Autism

Rare de novo variants in the ALDH1L1 gene have been identified in ASD probands, including a de novo missense variant (p.Asn900His) 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 a paternally-inherited loss-of-function variant in this gene was identified in an ASD proband from a multiplex family from the iHART cohort (Ruzzo et al. 2019). Functional assessment of the ASD-associated p.Asn900His missense variant in Drosophila using a rescue-based strategy in Macrogliese et al., 2022 demonstrated that humanized flies carrying the ALDH1L1-p.Asn900His mutation displayed a significant reduction in courtship and an increase in grooming behavior compared to the humanized reference fly or the TG4 mutant alone, potentially indicating that this variant acts as some sort of gain-of-function allele.

Molecular Function

The protein encoded by this gene catalyzes the conversion of 10-formyltetrahydrofolate, nicotinamide adenine dinucleotide phosphate (NADP+), and water to tetrahydrofolate, NADPH, and carbon dioxide. The encoded protein belongs to the aldehyde dehydrogenase family. Loss of function or expression of this gene is associated with decreased apoptosis, increased cell motility, and cancer progression.

External Links

References