Congenital disorders of glycosylation
Gene: GORAB
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
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
Variants in this GENE are reported as part of current diagnostic practice
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 OngarCreated: 19 Dec 2016, 4:01 p.m.
Comment on phenotypes: phenotype may be relevant to this panel, see Expert reviewer's commentsCreated: 19 Dec 2016, 3:58 p.m.
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 patientsCreated: 14 Dec 2016, 1:01 p.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Publications
Tag Q2_21_phenotype was removed from gene: GORAB. Tag Q2_22_rating was removed from gene: GORAB. Tag Q2_22_expert_review was removed from gene: GORAB.
Source Expert Review Green was added to GORAB. Source NHS GMS was added to GORAB. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Tag Q2_22_rating tag was added to gene: GORAB. Tag Q2_22_expert_review tag was added to gene: GORAB.
Publications for gene: GORAB were set to 26000619; 18348262; 28807865; 30631079
Gene: gorab has been classified as Amber List (Moderate Evidence).
Tag Q2_21_phenotype tag was added to gene: GORAB.
Phenotypes for gene: GORAB were changed from Geroderma osteodysplasticum 231070 to Geroderma osteodysplasticum OMIM:231070; geroderma osteodysplastica MONDO:0009271
Publications for gene: GORAB were set to 26000619
Promoted to V1 19th December 2016
This gene has been classified as Red List (Low Evidence).
Phenotypes for GORAB were set to Geroderma osteodysplasticum 231070
This gene has been classified as Red List (Low Evidence).
GORAB was added to Congenital disorders of glycosylationpanel. Sources: Emory Genetics Laboratory,Illumina TruGenome Clinical Sequencing Services,Radboud University Medical Center, Nijmegen,UKGTN
GORAB was created by ungardani
GORAB was added to Congenital disorders of glycosylationpanel. Sources: Research