Relevance to Autism

De novo variants in the EPHA1 gene have been identified in ASD probands, including a de novo missense variant (p.Val567Ile) in a proband from the Simons Simplex Collection and two additional de novo missense variants in probands from the SPARK cohort and the Autism Sequencing Consortium (Iossifov et al., 2014; Sanders et al., 2015; Feliciano et al. 2019; Satterstrom et al., 2020), while inherited loss-of-function variants in this gene were observed in multiple ASD-affected siblings in two unrelated multiplex families from the iHART cohort (Ruzzo et al., 2019). Functional assessment of the ASD-associated p.Val567Ile missense variant in Drosophila using an overexpression-based strategy in Macrogliese et al., 2022 demonstrated that flies overexpressing EPHA1-p.Val567Ile presented with a phenotype of serrated wings of normal size, compared to the reduced wing-size and wing-margin serration phenotypes caused by the reference EPHA1 allele, indicating a partial loss-of-function effect.

Molecular Function

This gene belongs to the ephrin receptor subfamily of the protein-tyrosine kinase family. EPH and EPH-related receptors have been implicated in mediating developmental events, particularly in the nervous system. Receptors in the EPH subfamily typically have a single kinase domain and an extracellular region containing a Cys-rich domain and 2 fibronectin type III repeats. The ephrin receptors are divided into 2 groups based on the similarity of their extracellular domain sequences and their affinities for binding ephrin-A and ephrin-B ligands. This gene is expressed in some human cancer cell lines and has been implicated in carcinogenesis.

External Links

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