De novo missense variants in the PLXNA1 gene have been identified in probands diagnosed with ASD (De Rubeis et al., 2014; Satterstrom et al., 2020), epilepsy (Epi4K Consortium 2013), and schizophrenia (Fromer et al., 2014). Park et al., 2017 reported a male patient with a de novo missense variant in the PLXNA1 gene presenting with infantile-onset epilepsy, intellectual disability, autism spectrum disorder, and other syndromic features. Dworschak et al., 2021 assembled ten patients from seven families with biallelic or de novo PLXNA1 variants; global developmental delay (9/10), brain anomalies (6/10), and eye anomalies (7/10) were frequently observed in this cohort, and autism spectrum disorder was reported in 3/7 individuals with biallelic PLXNA1 variants. PLXNA1 was also identified as an ASD candidate gene in Wilfert et al., 2021 based on the discovery of private likely gene-disruptive (LGD) variants in this highly constrained (pLI 0.99) gene that were exclusively transmitted to ASD probands in four independent families.
Molecular Function
Coreceptor for SEMA3A, SEMA3C, SEMA3F and SEMA6D. Necessary for signaling by class 3 semaphorins and subsequent remodeling of the cytoskeleton. Plays a role in axon guidance, invasive growth and cell migration. Class 3 semaphorins bind to a complex composed of a neuropilin and a plexin. The plexin modulates the affinity of the complex for specific semaphorins, and its cytoplasmic domain is required for the activation of down-stream signaling events in the cytoplasm.
External Links
References
Type
Title
Type of Disorder
Associated Disorders
Author, Year
Primary
Synaptic, transcriptional and chromatin genes disrupted in autism.
