TADA analysis of >15,000 Latin American individuals from the GALA Consortium (including 4,717 participants with an ASD diagnosis) in Natividad Avila et al., 2026 identified GSE1 as one of 35 genes reaching genome-wide significance (FDR < 0.05); among the Admixed American (AMR) individuals wtih ASD described in this report were three SPARK probands with de novo loss-of-function variants (one of whom was previously reported in Fu et al., 2022) and a Simons Simplex Collection proband with a de novo synonymous variant originally described in Iossifov et al., 2014. Additional de novo missense variants in this gene were reported in non-AMR ASD probands from the Simons Simplex Collection, the SPARK cohort, and the Sanger_UK10K cohort, as well as in an ASD proband from the MSSNG cohort (De Rubeis et al., 2014; Iossifov et al., 2014; Yuen et al., 2017; Zhou et al., 2022). Inherited loss-of-function and damaging missense (Mis3) variants in GSE1 have also been reported in ASD probands from the Autism Sequencing Consortium and the mAGRE cohort (De Rubeis et al., 2014; Cirnigliaro et al., 2023).
Molecular Function
This gene encodes a proline-rich protein with coiled coil domains that may be a subunit of a BRAF35-HDAC (BHC) histone deacetylase complex. This gene may function as an oncogene in breast cancer and enhanced expression of the encoded protein has been observed in breast cancer patients. GSE1 has been shown to link the HDAC1/CoREST co-repressor complex to DNA damage (Vcelkova et al., 2023).
External Links
References
Type
Title
Type of Disorder
Associated Disorders
Author, Year
Primary
Deleterious coding variation associated with autism is shared across ancestries.
