The reference OMIM entry for this protein is 614828

Protein o-mannose beta-1,4-n-acetylglucosaminyltransferase 2; pomgnt2
Glycosyltransferase-like domain-containing protein 2; gtdc2
Chromosome 3 open reading frame 39; c3orf39
Ago61

CLONING

Using whole-exome sequencing to identify genes mutated in Walker-Warburg syndrome (see 236670), Manzini et al. (2012) identified GTDC2. The deduced 580-amino acid protein has an N-terminal signal peptide, a central putative glycosyltransferase domain, and a C-terminal fibronectin (135600) type III domain. Quantitative PCR detected variable GTDC2 expression in all adult and fetal tissues examined, with highest expression in pancreas, followed by adult and fetal brain, testis, skeletal muscle, heart, kidney, ovary, and prostate. Within specific brain regions, highest expression was detected in cerebellum and cortex. In situ hybridization showed high expression during brain and eye development in mouse. Expression in embryonic mouse cortex peaked during the last week of gestation in both neuronal progenitors in the ventricular zone and migrating and differentiating neurons. Expression declined around birth. A similar expression pattern was detected in developing zebrafish.

GENE FUNCTION

Yoshida-Moriguchi et al. (2013) found that GTDC2 is a protein O-linked mannose beta-1,4-N-acetylglucosaminyltransferase whose product could be extended by beta-1,3-N-acetylgalactosaminyltransferase-2 (B3GALNT2; 610194) to form the O-mannosyl trisaccharide. Furthermore, Yoshida-Moriguchi et al. (2013) identified SGK196 (615247) as an atypical kinase that phosphorylates the 6-position of O-mannose, specifically after the mannose has been modified by both GTDC2 and B3GALNT2. Yoshida-Moriguchi et al. (2013) concluded that these findings suggested how mutations in GTDC2, B3GALNT2, and SGK196 disrupt dystroglycan receptor function and lead to congenital muscular dystrophy.

GENE STRUCTURE

Manzini et al. (2012) determined that GTDC2 is a single-exon gene.

MAPPING

By genomic sequence analysis, Manzini et al. (2012) mapped the GTDC2 gene to chromosome 3p22.1.

MOLECULAR GENETICS

In affected members of 3 unrelated consanguineous families with congenital muscular dystrophy-dystroglycanopathy with brain and eye anomalies type A8 (MDDGA8; 614830), Manzini et al. (2012) identified 3 different homozygous mutations in the GTDC2 gene (614828.0001-614828.0003). The first 2 mutations, which were identified by homozygosity mapping combined with whole-exome sequencing, were confirmed by Sanger sequencing. All patients had classic features of Walker-Warburg syndrome, including cobblestone lissencephaly, enlarged ventricles, cerebellar hypoplasia, and eye abnormalities, resulting in early death.

ANIMAL MODEL

Manzini et al. (2012) found that knockdown of gtdc2 expression in zebrafish replicated many features of Walker-Warburg syndrome, including hydrocephalus, ocular defects, and muscular dystrophy. Gtdc2 knockdown severely decreased survival, but those embryos that survived were shorter than controls and often had a bent tail, impaired motility, smaller eyes in which the retina failed to fuse ventrally, and a domed appearance of the top of the head. Other features included hydrocephalus, a reduction in brain volume, disorganization of the retinal epithelium, and impaired muscle development with a loss of both dystrophin and glycosylated dystroglycan from the myosepta. ... More on the omim web site

Subscribe to this protein entry history

June 30, 2020: Protein entry updated
Automatic update: OMIM entry 614828 was added.

Oct. 19, 2018: Additional information
Initial protein addition to the database. This entry was referenced in Bryk and co-workers. (2017).