2.A.36.1.14
Sodium/hydrogen exchanger 6 (Na⁺/H⁺ exchanger 6) (NHE-6) (Solute carrier family 9 member 6; SLC9A6).  This Na⁺/H⁺ exchanger is encoded by an X-linked gene that is widely expressed and especially abundant in brain, heart and skeletal muscle where it is implicated in endosomal pH homeostasis and trafficking as well as maintenance of cell polarity. Several mutations in the coding region of NHE6 are linked with severe intellectual disability, autistic behavior, ataxia and other abnormalities (Ilie et al. 2014).  A Christianson syndrome-linked mutation disrupts endosomal function and elicits neurodegeneration and cell death (Ilie et al. 2016; Hussain et al. 2023.  Heterozygous female mice suffer from visuospatial memory and motor coordination deficits similar to but less severe than those observed in X-chromosome hemizygous mutant males (Sikora et al. 2016). A novel peptide (SLC9A6-126 aas), encoded by circ-SLC9A6 , promotes lipid dyshomeostasis through the regulation of H4K16ac-mediated CD36 transcription in Non-alcoholic fatty acid disease (NAFLD) (Wang et al. 2024).  The SLC13A3 gene encodes a plasma membrane-localized Na+/dicarboxylate cotransporter 3 (NaDC3) primarily expressed in the kidney, astrocytes, and the choroid plexus. In addition to three Na⁺ ions, it brings four to six carbon dicarboxylates into the cytosol. Patients with acute reversible leukoencephalopathy and α-ketoglutarate accumulation (ARLIAK) carry pathogenic mutations in the SLC13A3 gene, and the X-linked neurodevelopmental condition Christianson Syndrome is caused by mutations in the SLC9A6 gene, which encodes the recycling endosomal alkali cation/proton exchanger NHE6, (sodium-hydrogen exchanger-6) (Hussain et al. 2023).