Relevance to Autism

De novo loss-of-function variants in the BSN gene have been identified in an ASD proband from the SPARK cohort (Trost et al., 2022) and in a Japanese ASD proband who also presented with developmental delay, intellectual disability, and epilepsy (Furukawa et al., 2025), while additional de novo missense and synonymous variants in this gene have been reported in ASD probands from the Autism Sequencing Consortium, the SPARK cohort, and the MSSNG cohort (De Rubeis et al., 2014; Yuen et al., 2017; Feliciano et al., 2019; Satterstrom et al., 2020; Zhou et al., 2022; Fu et al., 2022; Trost et al., 2022). Heterozygous and compound heterozygous variants in BSN have also been reported in individuals with epilepsy (Ye et al., 2023), and a genome-wide association study of febrile seizures in 7635 cases and 83,966 controls in Skotte et al., 2022 identified BSN as a novel loci with a P-value < 5.0E-10. Altrock et al., 2003 had previously demonstrated that mutant mice expressing a form of Bsn lacking the central exons critical for anchoring Bsn to the cytomatrix at the presynaptic active zone displayed a reduction in normal synaptic transmission that was attributable to inactivation of a significant fraction of glutamatergic synapses, an inability of vesicles at these synapses to fuse, and spontaneous epileptic seizures. More recently, Guzman et al., 2025 described 14 individuals with potentially disruptive de novo variants in the BSN gene and identified 15 additional individuals with protein-truncating variants (PTVs) from large biobanks; clinical features were standardized using the Human Phenotype Ontology (HPO) across all 29 individuals, which revealed common clinical characteristics including epilepsy (13/29, 45%), behavioral phenotypes (14/29, 48%) including ADHD (7/29, 25%) and autistic behavior (5/29, 17%), developmental delay (11/29, 38%), obesity (10/29, 34%), and delayed speech (8/29, 28%).

Molecular Function

Neurotransmitters are released from a specific site in the axon terminal called the active zone, which is composed of synaptic vesicles and a meshwork of cytoskeleton underlying the plasma membrane. The protein encoded by this gene is thought to be a scaffolding protein involved in organizing the presynaptic cytoskeleton. The gene is expressed primarily in neurons in the brain. A similar gene product in rodents is concentrated in the active zone of axon terminals and tightly associated with cytoskeletal structures, and is essential for regulating neurotransmitter release from a subset of synapses.

External Links

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