Relevance to Autism

A de novo nonsense variant and two de novo missense variants in the SPTBN1 gene have been identified in ASD probands from the Simons Simplex Collection (Iossifov et al., 2014) and the Autism Sequencing Consortium (Satterstrom et al., 2010), while rare inherited missense variants in this gene were identified in two Chinese ASD probands in Li et al., 2017. Rosenfeld et al., 2021 reported seven unrelated individuals with heterozygous SPTBN1 variants, all of whom presented with developmental delay and/or intellectual disability; three of these individuals were diagnosed with autism spectrum disorder, while autistic features were observed in a fourth. Additional de novo loss-of-function and missense variants in the SPTBN1 gene were observed in ASD probands from the MSSNG cohort and the SPARK cohort in Zhou et al., 2022. A two-stage analysis of rare de novo and inherited coding variants in 42,607 ASD cases, including 35,130 new cases from the SPARK cohort, in Zhou et al., 2022 identified SPTBN1 as a gene reaching exome-wide significance (P < 2.5E-06); association of SPTBN1 with ASD risk in this analysis was found to be driven predominantly by rare inherited loss-of-function variants transmitted from unaffected parents to affected offspring.

Molecular Function

Spectrin is an actin crosslinking and molecular scaffold protein that links the plasma membrane to the actin cytoskeleton, and functions in the determination of cell shape, arrangement of transmembrane proteins, and organization of organelles. It is composed of two antiparallel dimers of alpha- and beta- subunits. This gene is one member of a family of beta-spectrin genes. The encoded protein contains an N-terminal actin-binding domain, and 17 spectrin repeats which are involved in dimer formation.

External Links

References