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FB2026_01
,
released March 12, 2026
This report describes CHARGE syndrome, CHD7-related; CHARGE syndrome exhibits autosomal dominant inheritance. The human gene implicated in this disease is CHD7, chromodomain helicase DNA binding protein 7, which encodes a protein that contains several helicase family domains and may act as a component of epigenetic remodelling complexes to regulate transcription. There is one high-scoring fly ortholog, kis, for which classical loss-of-function mutations, RNAi targeting constructs, and alleles caused by insertional mutagenesis have been generated. Dmel\kis is also orthologous to human CHD6, CHD8, and CHD9. The human CHD7 gene is also associated with the disease hypogonadotropic hypogonadism 5 with or without anosmia, (HH5; MIM:612370), also known as Kallmann syndrome (DOID:3614); this disorder is less severe, with overlapping phenotype.
A UAS construct of Hsap\CHD7 has been introduced into flies. Partial functional complementation (heterologous rescue) of Dmel\kis mutant phenotypes has been demonstrated.
Homozygous loss-of-function alleles of Dmel\kis are lethal in the embryonic or larval stages; homozygous larvae are observed to have locomotor, neurophysiology, and neuroanatomy defects. Adult flies with reduced kis expression effected via RNAi exhibit defects in neuroanatomy, memory, and motor function. In addition to expression in neurons, kis expression is required in muscle cells. Physical and genetic interactions of Dmel\kis have been characterized; see below and in the kis gene report.
CHD7 has been identified as a strong candidate in a large-scale screen designed to validate orthologous candidate genes implicated in congenital heart disease in human (see FBhh0000921).
[updated Nov. 2024 by FlyBase; FBrf0222196]
[CHARGE SYNDROME](https://omim.org/entry/214800)
[CHROMODOMAIN HELICASE DNA-BINDING PROTEIN 7; CHD7](https://omim.org/entry/608892)
CHARGE syndrome is characterized by a pattern of congenital anomalies including choanal atresia and malformations of the heart, inner ear, and retina (summary by Kallen et al., 1999, pubmed:10590394). Choanal atresia (see MIM:608911) is a feature of the CHARGE association: coloboma of the eye; heart anomaly; atresia, choanal; retardation of mental and somatic development; microphallus; ear abnormalities and/or deafness (Pagon et al., 1981, pubmed:6166737). Facial palsy, cleft palate, and dysphagia are commonly associated. The first descriptions of this syndrome were provided by Hall (1979, pubmed:469662) and Hittner et al. (1979, pubmed:458518). [From MIM:214800, 2016.01.12]
CHARGE syndrome is caused by heterozygous mutation in the CHD7 gene. There is also evidence that the phenotype may be caused by mutation in the semaphorin-3E gene (SEMA3E) (Lalani, et al., 2004, pubmed:15235037). Kallmann syndrome (hypogonadotropic hypogonadism 5 with or without anosmia, HH5; MIM:612370, DOID:3614) is a CHD7-associated allelic disorder with a less severe but overlapping phenotype.[From MIM:214800, 2016.01.12]
Members of the chromodomain helicase DNA-binding (CHD) family of enzymes belong to the SNF2 superfamily of ATP-dependent chromatin remodelers. The CHD proteins are distinguished by the presence of two N-terminal chromodomains that function as interaction surfaces for a variety of chromatin components. Genetic, biochemical, and structural studies demonstrate that CHD proteins are important regulators of transcription and play critical roles during developmental processes (Marfella and Imbalzano, 2007; pubmed:17350655).
Many to one: 4 human to 1 Drosophila; the human genes are CHD6, CHD7, CHD8, and CHD9.
Moderate- to high-scoring ortholog of human CHD6, CHD7, CHD8, and CHD9 (1 Drosophila to 4 human). Dmel\kis is most closely related to CHD7; it shares 28% identity and 38% similarity with the human CHD7 gene.