Autism

Gene: SLC9A9

Red List (low evidence)

DISPUTED by ClinGen:

SLC9A9 was first reported in relation to autism spectrum disorder in 2008 (Morrow et al., 2008 PMID: 18621663). A homozygous deletion upstream of SLC9A9 (also known as NHE9) as well as several heterozygous variants (one nonsense and several missense) were reported in this gene; the sequence variants were later found to have high population frequencies in gnomAD.

According to gnomAD (v.2.1.1), SLC9A9 is not constrained for loss of function variants (pLI=0) or missense variants (z-score=-0.25).

Previously, a pericentric inversion of chromosome 3 disrupting SLC9A9 was reported in an extended pedigree with intellectual disability and behavioral problems (PMID: 14569117). The other inversion breakpoint affected DOCK3, a brain-expressed gene involved in neurodevelopmental disorders, and the inversion did not always segregate with the phenotype, therefore this family was not scored. An inherited exonic deletion of SLC9A9 is reported in an individual with autism spectrum disorder and epilepsy (PMID: 27123481). Two nonsense variants in individuals with autism spectrum disorder, including one reported several times in gnomAD are reported in PMID: 26185613.

Overall, variants are inherited and/or at high pop frequency, not consistent with Mendelian disease.

Created: 19 Feb 2020, 10:04 a.m. | Last Modified: 20 Mar 2022, 2 a.m.

Panel Version: 0.174

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
{?Autism susceptibility 16}, MIM# 613410

Publications

• 18621663
• 31134136
• 27123481
• 26755066