Relevance to Autism

One de novo loss-of-function and two potentially damaging missense variants in the CPSF7 gene have been identified in ASD probands from the Autism Sequencing Consortium, the SPARK cohort, and the MSSNG cohort (Yuen et al., 2017; Satterstrom et al., 2020; Zhou et al., 2022). Transmission and de novo association (TADA) analysis of whole-exome and whole-genome sequencing data from the Autism Sequencing Consortium, the Simons Simplex Collection, the MSSNG cohort, and the SPARK cohort in Trost et al., 2022 identified CPSF7 as an ASD-associated gene with a false discovery rate (FDR) < 0.1. Furthermore, analysis of de novo mutations in the coding regions of 843 stress granule-associated genes from 40,853 NDD probands, including 9228 individuals primarily diagnosed with ASD and 31,625 individuals primarily diagnosed with intellectual disability or developmental delay from 26 published studies, in Jia et al., 2022 identified CPSF7 as an NDD candidate gene with a false discovery rate (FDR) less than 0.05.

Molecular Function

Cleavage factor Im (CFIm) is one of six factors necessary for correct cleavage and polyadenylation of pre-mRNAs. CFIm is composed of three different subunits of 25, 59, and 68 kDa, and it functions as a heterotetramer, with a dimer of the 25 kDa subunit binding to two of the 59 or 68 kDa subunits. The protein encoded by this gene represents the 59 kDa subunit, which can interact with the splicing factor U2 snRNP Auxiliary Factor (U2AF) 65 to link the splicing and polyadenylation complexes.

External Links

References