- Tools
- Downloads
- Links
- Community
- About
- Help
FB2026_01
,
released March 12, 2026
This report describes neurodevelopmental disorder with microcephaly, RBBP5-related. The human gene implicated is RBBP5, which encodes RB binding protein 5, histone lysine methyltransferase complex subunit. There is one high-scoring fly ortholog, Dmel\Rbbp5, for which multiple genetic reagents, including a loss of function allele, RNAi-targeting constructs, and alleles caused by insertional mutagenesis have been generated.
Multiple constructs of human Hsap\RBBP5 have been introduced into flies, including the wild-type gene, and constructs carrying variants implicated in human disease. See the 'Disease-Implicated Variants' table below.
Overexpression of wild-type or mutant Hsap\RBBP5 with a strong ubiquitous GAL4 driver is lethal at larval stages; pan-neuronal, pan-glia, or eye-specific expression does not affect viability. Ubiquitously driven Hsap\RBBP5 also results in a microcephaly phenotype, which is more severe for wild-type than mutant constructs. Loss of function mutation of Dmel\Rbbp5 also results in a microcephaly phenotype; this phenotype is not rescued but instead enhanced by heterologous expression of wild-type but not mutant Hsap\RBBP5.
[updated Jan. 2025 by FlyBase; FBrf0222196]
Five unrelated individuals with de novo heterozygous variants in the gene RBBP5 were identified. The individuals were identified in probands with neurodevelopmental symptoms, including global developmental delay, intellectual disability, microcephaly, and short stature (Huang, et al., 2024; pubmed:39036895; FBrf0260942).
Heterozygous de novo variants, including three nonsense/frameshift and two missense variants, are associated with this newly described neurodevelopmental disorder (Huang, et al., 2024; pubmed:39036895; FBrf0260942).
RBBP5 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. [provided by RefSeq, Jul 2010]
One to one (1 human to 1 Drosophila); RBBP5 has one high-scoring Drosophila ortholog, Rbbp5.
High-scoring ortholog of human RBBP5 (1 Drosophila to 1 human).