Aliases: P130, Rb2
Chromosome No: 16
Chromosome Band: 16q12.2
Genetic Category: Syndromic-Rare single gene variant
ASD Reports: 5
Recent Reports: 0
Annotated variants: 9
Associated CNVs: 2
Evidence score: 3
Associated Disorders: |
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Relevance to Autism
RBL2 was identified as an ASD candidate gene in Wilfert et al., 2021 based on the discovery of private likely gene-disruptive (LGD) variants in this highly constrained (pLI 0.99) gene that were exclusively transmitted to four ASD probands in three independent families. Exome sequencing in two siblings with severe intellectual disability, stereotypies and dysmorphic features in Brunet et al., 2020 had previously identified biallelic loss-of-function variants in RBL2, establishing this gene as a candidate gene for an autosomal recessive neurodevelopmental disorder; Samra et al., 2021 subsequently identified three patients carrying biallelic RBL2-truncating variants, all of whom presented with infantile hypotonia, severe developmental delay and microcephaly.
Molecular Function
Key regulator of entry into cell division. Directly involved in heterochromatin formation by maintaining overall chromatin structure and, in particular, that of constitutive heterochromatin by stabilizing histone methylation. Recruits and targets histone methyltransferases KMT5B and KMT5C, leading to epigenetic transcriptional repression. Controls histone H4 'Lys-20' trimethylation. Probably acts as a transcription repressor by recruiting chromatin-modifying enzymes to promoters. Potent inhibitor of E2F-mediated trans-activation, associates preferentially with E2F5. Binds to cyclins A and E. Binds to and may be involved in the transforming capacity of the adenovirus E1A protein. May act as a tumor suppressor.