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Intellectual disability

Gene: GTPBP2

Green List (high evidence)

GTPBP2 (GTP binding protein 2)
EnsemblGeneIds (GRCh38): ENSG00000172432
EnsemblGeneIds (GRCh37): ENSG00000172432
OMIM: 607434, Gene2Phenotype
GTPBP2 is in 5 panels

2 reviews

Louise Daugherty (Genomics England Curator)

Comment on list classification: New gene suggested by external reviewer and reviewed by curation team. More than three unrelated individuals reported in the literature, ID is part of the phenotype. Publications support gene-disease association and rating of this gene to Green. At least 4 variants homozygous variants identified in 4 unrelated cases, common features included developmental delay and severe intellectual disability.
Created: 31 Oct 2018, 3:44 p.m.
Comment on phenotypes: added phenotype from OMIM and MIMid
Created: 31 Oct 2018, 3:39 p.m.

Konstantinos Varvagiannis (Other)

Green List (high evidence)

PMID: 26675814 describes the phenotype of 3 sibs born to consanguineous parents. All presented with delayed early milestones and moderate intellectual disability (IQ 40-50). Cerebellar vermian atrophy was a feature noted in all. Movement anomalies, skeletal problems, abnormal vision and abnormalities of the skin and the hair were part of the phenotype. SWI MRI images were suggestive of brain iron accumulation. All 3 affected sibs shared a single homozygous region not found in homozygosity in their 2 unaffected sibs. Exome sequencing revealed a homozygous GTPBP2 splice variant within this region, leading to skipping of exon 9. The latter was confirmed by RT-PCR experiments. Presence of a truncated protein was confirmed following transfection of HEK293 cells. Mice homozygous for a splice variant were previously (PMID: 25061210) reported to present with similar features although it is not clear whether homozygosity for the GTPBP2 splice variant itself or presence of a concomitant mutation in a tRNA gene was responsible for all the features. //

PMID: 29449720 reports on 3 individuals born to consanguineous parents, all homozygous for GTPBP2 nonsense variants. These 3 individuals belonged to unrelated families. Common features included developmental delay and severe intellectual disability, seizures, visual impairment and skeletal anomalies. Brain MRI was suggestive of hypogenesis/agenesis of corpus callosum, brain atrophy with variable cerebellar hypoplasia. Hair, teeth or skin anomalies may be part of the phenotype. Compared to the previous article, MRI images were did not demonstrate hypointensities compatible with brain iron accumulation. //

DD/ID appears to be a universal feature while seizures have been reported in 4/6 individuals. As a result the gene can be considered for inclusion in the ID panel as green (or amber).
Created: 6 Sep 2018, 1:10 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Global developmental delay; Intellectual disability; Seizures



Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
  • Expert Review Green
  • Jaberi-Elahi syndrome, 617988
  • Global developmental delay
  • Intellectual disability
  • Seizures
Clinvar variants
Variants in GTPBP2
Panels with this gene

History Filter Activity

31 Oct 2018, Gel status: 3

Entity classified by Genomics England curator

Louise Daugherty (Genomics England Curator)

Gene: gtpbp2 has been classified as Green List (High Evidence).

31 Oct 2018, Gel status: 0

Set Phenotypes

Louise Daugherty (Genomics England Curator)

Phenotypes for gene: GTPBP2 were changed from Global developmental delay; Intellectual disability; Seizures to Jaberi-Elahi syndrome, 617988; Global developmental delay; Intellectual disability; Seizures

6 Sep 2018, Gel status: 0

Added New Source

Konstantinos Varvagiannis (Other)

GTPBP2 was added to Intellectual disability panel. Sources: Literature

6 Sep 2018, Gel status: 0


Konstantinos Varvagiannis (Other)

GTPBP2 was created by Konstantinos Varvagiannis