Relevance to Autism

RBBP5 was identified as an ASD candidate gene based on having a p-value < 0.001 following DeNovoWEST analysis of de novo variants in 16,877 ASD trios from the Simons Simplex Collection, the Autism Sequencing Consortium, the MSSNG cohort, and the SPARK cohort in Zhou et al., 2022; among the de novo variants observed in ASD cases in this analysis were three damaging de novo missense variants (defined as having a REVEL score > 0.5). Lee et al., 2007 had previously shown that RBBP5 was a component of mammalian SETD1A/SETD1B histone H3-Lys4 methyltransferase complexes, while Li et al., 2016 demonstrated that a minimized human RBBP5-ASH2L heterodimer was the structural unit that interacted with and activated all MLL family histone methyltransferases, including those encoded for by the ASD candidate genes KMT2A, KMT2C, SETD1A, and SETD1B.

Molecular Function

This gene encodes a ubiquitously expressed nuclear protein which belongs to a highly conserved subfamily of WD-repeat proteins. The encoded protein binds directly to retinoblastoma protein, which regulates cell proliferation. It interacts preferentially with the underphosphorylated retinoblastoma protein via the E1A-binding pocket B.

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