Relevance to Autism

An intronic polymorphism in the FGFR1 gene (rs60527016) was the index SNP for a loci that reached genome-wide significance with ASD (odds ratio 0.84 (95% CI 0.790.90), P-value 4.70E-08) in a genome-wide association study on 6222 case-pseudocontrol pairs from the SPARK cohort (Matoba et al., 2020). Several rare de novo variants in the FGFR1 gene have been identified in ASD probands, including a splice-site variant (c.1971+5G>A) that was experimentally shown to result in retention of intron 14 of the FGFR1 gene and two de novo missense variants that were predicted to be damaging with REVEL scores > 0.5 (Satterstrom et al., 2020; Zhou et al., 2022; Li et al., 2023).

Molecular Function

The protein encoded by this gene is a member of the fibroblast growth factor receptor (FGFR) family, where amino acid sequence is highly conserved between members and throughout evolution. FGFR family members differ from one another in their ligand affinities and tissue distribution. A full-length representative protein consists of an extracellular region, composed of three immunoglobulin-like domains, a single hydrophobic membrane-spanning segment and a cytoplasmic tyrosine kinase domain. The extracellular portion of the protein interacts with fibroblast growth factors, setting in motion a cascade of downstream signals, ultimately influencing mitogenesis and differentiation. This particular family member binds both acidic and basic fibroblast growth factors and is involved in limb induction. Mutations in this gene have been associated with Pfeiffer syndrome, Jackson-Weiss syndrome, Antley-Bixler syndrome, osteoglophonic dysplasia, and autosomal dominant Kallmann syndrome 2.

External Links

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