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FB2026_03
,
released September 17, 2026
This report describes a newly characterized disease, neurodevelopmental disorder with developmental delay, hypotonia, and impaired language; this disease exhibits autosomal dominant inheritance. The human gene implicated in this disease is FBXW7; FBXW7 encodes one of the four subunits of SCF ubiquitin protein ligase complexes, which mediate the ubiquitination and subsequent proteasomal degradation of target proteins. There is a single orthologous gene in Drosophila, ago, for which multiple genetic reagents, including loss-of-function mutations, RNAi targeting constructs, overexpression constructs, and alleles caused by insertional mutagenesis, have been generated.
The human FBXW7 gene has not been introduced into flies.
Animals homozygous for loss-of-function mutations of Dmel\ago typically die in the first instant larval stage; tracheal defects are observed. Pan-neuronal knockdown of Dmel\ago, mediated by RNAi, allows survival to adulthood; adults exhibit impaired learning and compromised neuronal function.
[updated Oct. 2022 by FlyBase; FBrf0222196]
[DEVELOPMENTAL DELAY, HYPOTONIA, AND IMPAIRED LANGUAGE; DEDHIL](https://omim.org/entry/620012)
[F-BOX AND WD40 DOMAIN PROTEIN 7; FBXW7](https://omim.org/entry/606278)
The FBXW7 neurodevelopmental syndrome is distinguished by global developmental delay, borderline to severe intellectual disability, hypotonia, and gastrointestinal issues (Stephenson et al., 2022; pubmed:35395208, FBrf0253102).
Germline monoallelic FBXW7 variants were identified in 35 individuals from 32 families; 28 distinct variants in FBXW7 were identified. The variants arose de novo in 30 individuals; there were 2 cases of familial transmission from an affected parent (Stephenson et al., 2022; pubmed:35395208, FBrf0253102).
Developmental delay, hypotonia, and impaired language (DEDHIL) is caused by heterozygous mutation in the FBXW7 gene. [from MIM:620012; 2022.10.12]
Brain imaging detailed variable underlying structural abnormalities affecting the cerebellum, corpus collosum, and white matter (Stephenson et al., 2022; pubmed:35395208, FBrf0253102).
FBXW7 has been identified as a tumor suppressor and one of the commonly mutated genes in human cancer (FBrf0253102 and references cited therein).
FBXW7 encodes a member of the F-box protein family which is characterized by an approximately 40 amino acid motif, the F-box. The F-box proteins constitute one of the four subunits of ubiquitin protein ligase complexes called SCFs (SKP1-cullin-F-box), which mediate the ubiquitination and subsequent proteasomal degradation of target proteins. [Gene Cards, FBXW7; 2022.04.19]
One to one: 1 human gene to 1 Drosophila gene.
Moderate-scoring ortholog of human FBXW7 (1 Drosophila to 1 human).