Congenital disorders of glycosylation

Gene: GORAB

Green List (high evidence)

The rating of this gene has been updated to Green following NHS Genomic Medicine Service approval.

Created: 1 Feb 2023, 9:14 a.m. | Last Modified: 1 Feb 2023, 9:14 a.m.

Panel Version: 3.4

Green List (high evidence)

Many individuals reported in consanguineous families with Geroderma osteodysplasticum. Patients often have normal isoelectric focusing of serum transferrin. Recent publication demonstrated that loss of GORAB causes impairment of COPI-mediated retrieval of trans-Golgi
enzymes, resulting in a deficit in glycosylation of secretory cargo proteins, thus supporting the view that defective protein glycosylation is a major disease mechanism in geroderma osteodysplastica (PMID: 30631079).

Created: 22 Jul 2020, 7:36 a.m. | Last Modified: 22 Jul 2020, 7:36 a.m.

Panel Version: 2.14

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Geroderma osteodysplasticum MIM#231070

Publications

• 18348262
• 28807865
• 30631079

Variants in this GENE are reported as part of current diagnostic practice

Green List (high evidence)

PMID 30631079 demonstrates that disrupting variants in GORAB result in "impairment of COPI-mediated retrieval of trans-Golgi enzymes, resulting in a deficit in glycosylation of secretory cargo proteins. Our results therefore identify GORAB as a COPI scaffolding factor". The authors conclude that this finding supports the view that "defective protein glycosylation is a major disease mechanism in gerodermia osteodysplastica".
Therefore variants in GORAB are relevant to this panel based on this mechanism.

Created: 8 Feb 2021, 2:12 p.m. | Last Modified: 8 Feb 2021, 2:12 p.m.

Panel Version: 2.47

Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.

Created: 8 Feb 2021, 1:59 p.m. | Last Modified: 8 Feb 2021, 1:59 p.m.

Panel Version: 2.46

Comment when marking as ready: Associated with phenotype in OMIM and as a confirmed Developmental Disorder Gene / G2P. At least 6 variants reported in at least 10 unrelated families. Phenotype suggested to be relevant to this panel by expert reviewer Dani Ongar

Created: 19 Dec 2016, 4:01 p.m.

Comment on phenotypes: phenotype may be relevant to this panel, see Expert reviewer's comments

Created: 19 Dec 2016, 3:58 p.m.

Red List (low evidence)

Gerodermia osteodysplastica
No glycosylation defects reported in patients but model organisms and studies with patient derived cells imply that glycosylation defects are a likely phenotype of the patients

Created: 14 Dec 2016, 1:01 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Publications

• 26000619