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…

Primary Disease Associations & Inheritance

Jaberi-Elahi syndromeMIM #617988

Clinical highlights

Gene–disease validity (ClinGen)

Definitive · Jaberi-Elahi syndrome · AR · ClinGen 2024

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.43

LOEUF

LOF

Mechanism· G2P

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

Background carrier burden — how many people carry a rare variant somewhere in GTPBP2?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 150

661 rare PASS variants

Rare truncating (LoF)

1 in 1,500

94 rare PASS variants

Rare synonymous (reference)

1 in 150

386 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for GTPBP2. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 170	1 in 2,300
South Asian	~43k	1 in 130	1 in 2,000
Remaining (unassigned)	~30k	1 in 150	1 in 1,100
European (Finnish)	~27k	1 in 1,100	1 in 5,300
Admixed American	~22k	1 in 140	1 in 530
African / African American	~21k	1 in 140	1 in 620
East Asian	~20k	1 in 130	1 in 630
Ashkenazi Jewish	~13k	1 in 680	≈ 1 in 13,000
Middle Eastern	~2,884	1 in 120	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 12 coding exons well covered in gnomAD exomes and genomes.? see exons ↓