GTPBP2

Chr 6AR

GTP binding protein 2

Also known as: JABELS

NCBI Gene: 54676 ENSG00000172432 UniProt: Q9BX10 OMIM: 607434

GTPBP2 encodes a GTP-binding protein that binds GTP/GDP and is activated by GTP binding and inactivated by hydrolyzing GTP to GDP. Autosomal recessive mutations cause Jaberi-Elahi syndrome. The mechanism of pathogenicity is not established from the available data.

OMIM ResearchSummary from RefSeq, OMIM

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]

OMIM ResearchGenerating clinical summary…

LOFmechanismARLOEUF 0.431 OMIM phenotype

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

12 unique Pathogenic / Likely Pathogenic· 72 VUS of 208 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Missense constrained — critical functional residues

LoF Constraint?

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?

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?

LoF OE?0.23 (0.13–0.43)

0≤0.351.4

Missense OE?0.50 (0.44–0.56)

0≤0.61.4

Synonymous OE?1.01

0≤1.21.6

LoF obs/exp: 7 / 30.4Missense obs/exp: 182 / 366.8Syn Z: -0.10

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

definitiveGTPBP2-related Jaberi-Elahi syndromeLOFAR

This gene — mechanism propensity

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

0.6453th %ile

GOF

0.6052th %ile

LOF

0.4233th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

208 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic9

Likely Pathogenic3

VUS72

Likely Benign89

Benign17

Conflicting1

Pathogenic

Likely Pathogenic

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	9	0	0	0	9
Likely Pathogenic	3	0	0	0	3
VUS	1	66	2	3	72
Likely Benign	0	2	29	58	89
Benign	0	2	9	6	17
Conflicting	—				1
Total	13	70	40	67	191

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

View in ClinVar →

9 pathogenic / likely-pathogenic (of 13) ClinVar copy-number / structural variants overlap GTPBP2 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →