OGT

Chr XXLR

O-linked N-acetylglucosamine (GlcNAc) transferase

Also known as: HINCUT-1, HRNT1, MRX106, O-GLCNAC, OGT1, XLID106

NCBI Gene: 8473 ENSG00000147162 UniProt: O15294 OMIM: 300255

This glycosyltransferase catalyzes the addition of N-acetylglucosamine to serine and threonine residues on cytoplasmic and nuclear proteins, regulating diverse cellular processes including chromatin structure, circadian rhythms, autophagy, and mTOR signaling. Mutations cause X-linked intellectual developmental disorder with inheritance following an X-linked recessive pattern. The gene is extremely intolerant to loss-of-function variation (pLI 1.0, LOEUF 0.08), indicating that complete loss of function is likely incompatible with survival in males.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene 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. [provided by RefSeq, Oct 2009]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Intellectual developmental disorder, X-linked 106MIM #300997

XLR

Clinical highlights

Gene-disease validity (ClinGen)

intellectual disability, X-linked 106 · XLModerateconsider for supplementary testing

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

313

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.08

LOEUF· LoF intol.

LOF

Mechanism· G2P