Relevance to Autism

TADA analysis of an integrated cohort of over 40,000 ASD cases across unpublished and published global cohort in Tan et al., 2026 identified SLC4A8 as an ASD risk gene with a false discovery rare of <0.05; among the ASD-associated variants used in this analysis were a de novo loss-of-function variant identified in a SPARK proband and four de novo missense variants (three from the SPARK cohort, one from a Chinese ASD cohort originally reported in Wang et al., 2023; three of the four missense variants had MPC scores greater than 2). Two additional ASD-associated de novo missense variants in the SLC4A8 gene that were not included in the Tan et al., 2026 analysis were reported in a SPARK proband and a GALA proband in Natividad Avila et al., 2026.

Molecular Function

The protein encoded by this gene is a membrane protein that functions to transport sodium and bicarbonate ions across the cell membrane. The encoded protein is important for pH regulation in neurons. The activity of this protein can be inhibited by 4,4'-Di-isothiocyanatostilbene-2,2'-disulfonic acid (DIDS). Sinning et al., 2011 demonstrated that steady-state pH and acid extrusion were diminished in cultured hippocampal neurons of mice with a targeted disruption of Slc4a8.

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