Relevance to Autism

Trio-based whole-exome sequencing of 168 patients with low-functioning ASD at Sun Yat-sen Memorial Hospital in Wu et al., 2025 identified a de novo in-frame insertion variant in the SPTAN1 gene that was classified as likely pathogenic in ClinVar in a patient clinically diagnosed with ASD based on DSM-5 criteria and presenting with global developmental delay/intellectual disability. A de novo loss-of-function variant and multiple de novo missense variants, many of which are predicted to be deleterious by one or more in silico tools, have been identified in SPTAN1 in ASD probands from the Simons Simplex Collection, the SPARK cohort, the Autism Sequencing Consortium, the MSSNG cohort, the iHART cohort, and a cohort of 22 Bulgarian ASD probands (Iossifov et al., 2014; Ruzzo et al., 2019; Feliciano et al., 2019; Satterstrom et al., 2020; Zhou et al., 2022; Fu et al., 2022; Tan et al., 2025; Belenska-Todorova et al., 2025). Autism spectrum disorder has also been reported in a subset of individuals presenting with SPTAN1-associated disorders, including DEE5 and DEVEP (Syrbe et al., 2017; Marco Hernandez et al., 2022; Luongo-Zink et al., 2022).

Molecular Function

Spectrins are a family of filamentous cytoskeletal proteins that function as essential scaffold proteins that stabilize the plasma membrane and organize intracellular organelles. Spectrins are composed of alpha and beta dimers that associate to form tetramers linked in a head-to-head arrangement. This gene encodes an alpha spectrin that is specifically expressed in nonerythrocytic cells. The encoded protein has been implicated in other cellular functions including DNA repair and cell cycle regulation. Mutations in this gene are the cause of early infantile epileptic encephalopathy-5 (DEE5; OMIM 613477) and developmental delay with or without epilepsy (DEVEP; OMIM 620540).

External Links

References