Relevance to Autism

This gene was identified in Iossifov et al. 2015 as a strong candidate to be an ASD risk gene based on a combination of de novo mutational evidence and the absence or very low frequency of mutations in controls (PMID 26401017). This gene was subsequently identified by TADA (transmission and de novo association) analysis of a combined dataset from the Simons Simplex Collection (SSC) and the Autism Sequencing Consortium (ASC) as a gene strongly enriched for variants likely to affect ASD risk with a false discovery rate (FDR) of < 0.1 (Sanders et al., 2015); among the variants identified in this gene was one de novo loss-of-function (LoF) variant. Marcogliese et al., 2018 reported seven individuals with damaging heterozygous variants in the IRF2BPL gene; the most commonly observed phenotypes in these individuals included developmental regression, hypotonia, and seizures, and one individual was also diagnosed with ASD. Mau-Them et al., 2018 identified 11 unrelated individuals with developmental epileptic encephalopathy and de novo truncating variants in the IRF2BPL gene; one of the individuals reported in this study (patient 9) also presented with autism. A de novo likely gene-disruptive variant in IRF2BPL was identified in an ASD proband from the SPARK cohort in Feliciano et al, 2019; a meta-analysis of de novo variants in 4773 published ASD trios and 465 SPARK trios using TADA in this report identified IRF2BPL as an ASD candidate gene with a false discovery rate between 0.01 and 0.05 (0.01 < FDR 0.05). A two-stage analysis of rare de novo and inherited coding variants in 42,607 ASD cases, including 35,130 new cases from the SPARK cohort, in Zhou et al., 2022 identified IRF2BPL as a gene reaching study-wide significance based on 5,754 constraint genes (P < 8.69E-06).

Molecular Function

This gene encodes a transcription factor that may play a role in regulating female reproductive function. It may play a role in gene transcription by transactivating the GNRH1 promoter and repressing the PENK promoter.

External Links

References