Relevance to Autism

Whole genome and/or whole exome sequencing of 435 individuals in 116 ASD families in Viggiano et al., 2024 identified a de novo missense variant with an MPC score greater than or equal to 2 in the SLC9A1 gene in a male ASD proband who also presented with language consisting of single words and borderline IQ. Li and Fliegel, 2015 had previously demonstrated that a de novo missense variant in this gene that was originally identiified in a patient with ASD, intellectual disability, and seizures in Zhu et al., 2015 resulted in abolition of Na+/H+ exchanger activity. Additional de novo missense variants in SLC9A1 have also been identified in ASD probands from multiple cohorts (Yuen et al., 2017; Trost et al., 2022; Yuan et al., 2023; Wang et al., 2023).

Molecular Function

This gene encodes a Na+/H+ antiporter that is a member of the solute carrier family 9. The encoded protein is a plasma membrane transporter that is expressed in the kidney and intestine. This protein plays a central role in regulating pH homeostasis, cell migration and cell volume. This protein may also be involved in tumor growth. Homozygous mutations in this gene are responsible for Lichtenstein-Knorr syndrome (OMIM 616291), an autosomal recessive neurologic disorder characterized by postnatal onset of severe progressive sensorineural hearing loss and progressive cerebellar ataxia.

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