GTPBP2

Chr 6AR

GTP binding protein 2

Also known as: JABELS

NCBI Gene: 54676ENSG00000172432UniProt: Q9BX10

GTP-binding proteins, or G proteins, constitute a superfamily capable of binding GTP or GDP. G proteins are activated by binding GTP and are inactivated by hydrolyzing GTP to GDP. This general mechanism enables G proteins to perform a wide range of biologic activities.[supplied by OMIM, Jan 2003]

Primary Disease Associations & Inheritance

Jaberi-Elahi syndromeMIM #617988
AR
203
ClinVar variants
21
Pathogenic / LP
0.32
pLI score
0
Active trials
Clinical Summary— GTPBP2
🧬
Gene-Disease Validity (ClinGen)
Jaberi-Elahi syndrome · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.23) despite low pLI — interpret in context.
📋
ClinVar Variants
21 Pathogenic / Likely Pathogenic· 75 VUS of 203 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Missense constrained — critical functional residues
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.43LOEUF
pLI 0.317
Z-score 3.93
OE 0.23 (0.13–0.43)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
3.43Z-score
OE missense 0.50 (0.44–0.56)
182 obs / 366.8 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.23 (0.13–0.43)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.50 (0.44–0.56)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.01
0≤1.21.6
LoF obs/exp: 7 / 30.4Missense obs/exp: 182 / 366.8Syn Z: -0.10

ClinVar Variant Classifications

203 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic18
Likely Pathogenic3
VUS75
Likely Benign89
Benign17
Conflicting1
18
Pathogenic
3
Likely Pathogenic
75
VUS
89
Likely Benign
17
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
3
0
15
0
18
Likely Pathogenic
3
0
0
0
3
VUS
0
65
7
3
75
Likely Benign
0
2
29
58
89
Benign
0
2
9
6
17
Conflicting
—1
Total6696067203

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

GTPBP2 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

GTPBP2-related Jaberi-Elahi syndrome

definitive
ARLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Jaberi-Elahi syndrome

MIM #617988

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Clinical delineation of GTPBP2-associated neuro-ectodermal syndrome: Report of two new families and review of the literature.
Carter MT et al.·Clin Genet
2019Review
Bi-allelic genetic variants in the translational GTPases GTPBP1 and GTPBP2 cause a distinct identical neurodevelopmental syndrome.
Salpietro V et al.·Am J Hum Genet
2024
Jaberi-Elahi syndrome: Exploring a novel GTPBP2 mutation and a literature review.
Manoochehri J et al.·Eur J Med Genet
2024Review
GTPBP2 in-frame deletion in canine model with non-syndromic progressive retinal atrophy.
Murgiano L et al.·Sci Rep
2025Functional
Metabolic alterations in fibroblasts of patients presenting with the MPAN subtype of neurodegeneration with brain iron accumulation (NBIA).
Wydrych A et al.·Biochim Biophys Acta Mol Basis Dis
2025Cohort
Biallelic inactivating variants in the GTPBP2 gene cause a neurodevelopmental disorder with severe intellectual disability.
Bertoli-Avella AM et al.·Eur J Hum Genet
2018Case report
High-resolution genomic analysis does not qualify atypical plexus papilloma as a separate entity among choroid plexus tumors.
Japp AS et al.·J Neuropathol Exp Neurol
2015
New molecular insights into modulation of platelet reactivity in aspirin-treated patients using a network-based approach.
Zufferey A et al.·Hum Genet
2016Cohort
Lifetime risk of autosomal recessive neurodegeneration with brain iron accumulation (NBIA) disorders calculated from genetic databases.
Kolarova H et al.·EBioMedicine
2022
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools