This report describes intellectual disability, X-linked 106 (XLID106), which is one of the series of diseases classified as intellectual disability, X-linked, nonsyndromic. The human gene implicated in this disease is OGT, a glycosyltransferase that catalyzes the addition of a single N-acetylglucosamine in O-glycosidic linkage to serine or threonine residues. There is a single orthologous gene in Drosophila, Dmel\sxc, for which classical loss-of-function alleles, RNAi-targeting constructs, and alleles caused by insertional mutagenesis have been generated.
UAS constructs of the human Hsap\OGT gene have been introduced into flies. Heterologous rescue (functional complementation) of amorphic phenotypes of Dmel\sxc has been demonstrated (FBrf0208697).
Variant(s) implicated in human disease tested (as analogous mutation in fly gene): L283F, R313P, and A348T in the Dmel\sxc gene (corresponds to L254F, R284P, and A319T in the human OGT gene). See the 'Disease-Implicated Variants' table below.
Amorphic and loss-of-function mutations of Dmel\sxc are lethal when homozygous; some alleles survive to pharate adult stages, allowing phenotypic assessment. Neuroanatomy-defective and neurophysiology-defective phenotypes are observed. Physical interactions of the Dmel\sxc protein product have been described; see below and in the FlyBase gene report for sxc.
[updated Apr. 2024 by FlyBase; FBrf0222196]
Intellectual disability is characterized by impairments in intellectual functioning and adaptive behavior; symptoms must be present before a child becomes 18 years old (http://medical-dictionary.thefreedictionary.com/mental+retardation; 2016.01.19).
Intellectual disability can be subdivided into syndromic forms, characterized by cognitive impairment accompanied by dysmorphic features, malformations or neurological abnormalities, and nonsyndromic forms, characterized by cognitive impairment without additional features (Basel-Vanagaite, 2008; DOI: 10.1002/9780470015902.a0021454).
[INTELLECTUAL DEVELOPMENTAL DISORDER, X-LINKED 106; XLID106](https://omim.org/entry/300997)
[O-LINKED N-ACETYLGLUCOSAMINE TRANSFERASE; OGT](https://omim.org/entry/300255)
Affected patients show decreased intellectual ability. In addition, all patients show mental and physical developmental delay, including intrauterine growth retardation, low birth weight, short stature, drooling, and delayed and/or very restricted language skills (Pravata et al., 2020; pubmed:32080367).
X-linked intellectual developmental disorder-106 is caused by hemizygous mutation in the OGT gene on chromosome Xq13. [from MIM:300997; 2022.06.10]
OGT encodes a glycosyltransferase that catalyzes the addition of a single N-acetylglucosamine in O-glycosidic linkage to serine or threonine residues. Since both phosphorylation and glycosylation compete for similar serine or threonine residues, the two processes may compete for sites, or they may alter the substrate specificity of nearby sites by steric or electrostatic effects. The protein contains multiple tetratricopeptide repeats that are required for optimal recognition of substrates. Alternatively spliced transcript variants encoding distinct isoforms have been found for this gene. [Gene Cards, OGT; 2022.06.10]
OGT catalyzes the addition of a single N-acetylglucosamine in O-glycosidic linkage to serine or threonine residues. [from MIM:300255; 2022.06.10]
One to one: human gene to Drosophila gene.
High-scoring ortholog of human OGT; (1 Drosophila to 1 human).
