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FB2026_01
,
released March 12, 2026
This report describes DeSanto-Shinawi syndrome (DESSH), which is inherited as an autosomal dominant. The gene implicated in this disease is WAC, a signaling protein that regulates transcription-coupled histone H2B ubiquitination and appears to be involved in regulation of autophagy. There is a single Drosophila ortholog, wcy, for which loss-of-function alleles and RNAi-targeting constructs have been generated.
A UAS construct carrying a wild-type human Hsap\WAC gene has been introduced into flies; heterologous rescue (functional complementation) has been demonstrated.
Animals homozygous for a loss-of-function mutation of Dmel\wcy typically die during the larval stage. Many phenotypes have been assessed using somatic clones in the adult stage. When expressed in neural tissues, RNAi targeted to wcy allows survival to adulthood; the adults exhibit learning defects. Genetic and physical interactions of Dmel\wcy have been described; see below and in the wcy gene report.
[updated Sep. 2017 by FlyBase; FBrf0222196]
[DESANTO-SHINAWI SYNDROME; DESSH](https://omim.org/entry/616708)
[WW DOMAIN-CONTAINING ADAPTOR WITH COILED-COIL REGION; WAC](https://omim.org/entry/615049)
DeSanto-Shinawi syndrome is a rare neurodevelopmental disorder characterized by global developmental delay apparent in infancy or early childhood and associated with characteristic dysmorphic facial features and neurocognitive phenotypes (DeSanto et al., 2015; pubmed:26264232). [from MIM:616708; 2017.09.08]
DeSanto-Shinawi syndrome (DESSH) is caused by heterozygous mutation in the WAC gene. Some patients with an overlapping phenotype have a deletion at chromosome 10p12-p11 encompassing several genes and consistent with a contiguous gene deletion syndrome. [from MIM:616708; 2017.09.08]
In mammalian cells, WAC has been found to be a positive regulator of autophagy; this has been confirmed for the Drosophila ortholog wcy (FBrf0230747).
The protein encoded by WAC contains a WW domain, which is a protein module found in a wide range of signaling proteins. WAC impacts multiple processes via regulation of transcription-coupled histone H2B ubiquitination. [Gene Cards, WAC; 2017.09.08]
One to one: 1 human to 1 Drosophila.
Moderate-to-high-scoring ortholog of human WAC (1 Drosophila to 1 human); Dmel\wcy shares 25% identity and 41% similarity with the human gene.