FRRS1Lferric chelate reductase 1 like

Relevance to Autism

Identification of rare variants shared by two or more siblings with ASD following integration of whole genome sequencing data of 866 multiplex families from the iHART and MSSNG cohorts in Lee et al., 2025 identified shared rare variants in the FRRS1L gene in two families; CRISPR/Cas9 experiments demonstrated downregulation of FRRS1L expression by the chr9:111924882C>T family variant. Furthermore, behavioral tests of Frrs1l heterozygous knockout mice (Frrs1l+/-) in Lee et al., 2025 showed specific impairment of social novetly recognition without altering other behavioral phenotypes. A maternally-inherited loss-of-function variant in FRRS1L had previously been identified in one of two ASD-affected siblings from a multiplex family from the AGRE cohort in Cirnigliaro et al., 2023.

Molecular Function

This gene encodes a component of the outer-core of an alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor protein in the brain. The encoded protein is thought to interact with inner-core components of the receptor, and play a role in the modulation of glutamate signaling. Homozygous variants in this gene are responsible for an autosomal recessive form of early infantile epileptic encephalopathy (DEE37; OMIM 616981).

External Links

Gene CardOpen Targets PlatformgnomAD browserPubMed

Human

Entrez GeneOMIMUniProtHumanBaseVariCarta

Mouse

Entrez GeneMouse Genome InformaticsAllen Brain Atlas

SFARI Genomic Platforms

GPF browser SFARI genome browser