SLC4A10 encodes a plasma membrane-bound transporter that mediates sodium-dependent bicarbonate import. This gene is highly expressed in the brain and regulates pH in neuronal cells. SLC4A10 was first reported with autosomal recessive complex neurodevelopmental disorder in 2023 (Fasham et al., PMID: 37459438). Most reported individuals have microcephaly, developmental delay/intellectual disability, and abnormal findings on brain MRI. A few have seizures. This curation includes one multi-exon deletion, one splicing, 2 nonsense, and seven missense variants (two composing a haplotype) reported in nine probands and eight affected siblings across two publications (PMIDs: 37459438 and 38054405). For the missense variants, the location of the altered protein within the cell and acid extrusion function were tested with the majority performing similarly to a null variant (PMID: 38054405). The mechanism of pathogenicity appears to be loss of function. An animal model also supports this gene-disease relationship (PMIDs: 18165320 and 37459438). In summary, there is strong evidence to support the relationship between SLC4A10 and autosomal recessive complex neurodevelopmental disorder.
This classification was approved by the ClinGen Epilepsy Gene Curation Expert Panel on December 17, 2024 (SOP version 11).
The GenCC data are available free of restriction under a CC0 1.0 Universal (CC0 1.0) Public Domain Dedication. The GenCC requests that you give attribution to GenCC and the contributing sources whenever possible and appropriate. The accepted Flagship manuscript is now available from Genetics in Medicine (https://www.gimjournal.org/article/S1098-3600(22)00746-8/fulltext).
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