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10 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
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GTPBP2
GTP binding protein 2
Chromosome 6 Β· 6p21.1
NCBI Gene: 54676Ensembl: ENSG00000172432.20HGNC: HGNC:4670UniProt: A8K2K2
39PubMed Papers
21Diseases
0Drugs
12Pathogenic Variants
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
translation elongation factor activityprotein bindingGTP bindingidentical protein bindingJaberi-Elahi syndromeIntellectual disabilityGlobal developmental delaySeizure
✦AI Summary

GTPBP2 (GTP binding protein 2) is a translational GTPase involved in ribosome rescue mechanisms during protein synthesis. The protein functions to resolve ribosome stalling caused by non-functional tRNAs, though it exhibits very low GTP-binding activity 1. GTPBP2 acts as a ribosome rescue factor, with inactivation leading to exacerbated peripheral neuropathy in disease models 2. The gene is highly conserved across species (>99% identity between human and mouse), suggesting fundamental biological importance 3. Bi-allelic loss-of-function variants in GTPBP2 cause Jaberi-Elahi syndrome, a rare neurodevelopmental disorder characterized by microcephaly, profound developmental delays, distinctive craniofacial features, ectodermal defects, progressive spasticity, refractory epilepsy, and brain atrophy 4. The syndrome also includes visual/hearing impairments, choreoathetoid movements, and brain iron accumulation that may appear after childhood 5. Clinical presentation shows age-related progression, with ectodermal findings and peripheral neuropathy most prominent in older individuals 5. Disease-associated variants demonstrate loss-of-function impacts in cellular studies, and reduced expression of the Drosophila ortholog causes locomotor impairment, highlighting conserved roles in CNS development 4.

Sources cited
1
GTPBP2 has very low GTP-binding activity
PMID: 30108131
2
GTPBP2 functions as a ribosome rescue factor and its inactivation exacerbates peripheral neuropathy
PMID: 34516840
3
GTPBP2 is highly conserved between human and mouse (>99% identity)
PMID: 10833435
4
Bi-allelic GTPBP2 variants cause neurodevelopmental syndrome with microcephaly, developmental delays, and distinctive features
PMID: 38118446
5
GTPBP2-associated syndrome includes brain iron accumulation appearing after childhood and age-related clinical progression
PMID: 30790272
Disease Associationsβ“˜21
Jaberi-Elahi syndromeOpen Targets
0.78Strong
Intellectual disabilityOpen Targets
0.49Moderate
Global developmental delayOpen Targets
0.46Moderate
SeizureOpen Targets
0.46Moderate
neurodegenerative diseaseOpen Targets
0.23Weak
Alzheimer diseaseOpen Targets
0.23Weak
lysosomal storage diseaseOpen Targets
0.23Weak
multiple sclerosisOpen Targets
0.23Weak
Parkinson diseaseOpen Targets
0.23Weak
genetic disorderOpen Targets
0.19Weak
xeroderma pigmentosumOpen Targets
0.12Weak
colorectal carcinomaOpen Targets
0.07Suggestive
non-small cell lung carcinomaOpen Targets
0.06Suggestive
neoplasmOpen Targets
0.06Suggestive
Abnormality of the skeletal systemOpen Targets
0.05Suggestive
attention deficit hyperactivity disorderOpen Targets
0.04Suggestive
hereditary attention deficit-hyperactivity disorderOpen Targets
0.04Suggestive
Potocki-Lupski syndromeOpen Targets
0.03Suggestive
schizophrenia 15Open Targets
0.03Suggestive
cancerOpen Targets
0.02Suggestive
Jaberi-Elahi syndromeUniProt
Pathogenic Variants12
NM_019096.5(GTPBP2):c.1236+1G>APathogenic
Jaberi-Elahi syndrome
β˜…β˜…β˜†β˜†2024
NM_019096.5(GTPBP2):c.8C>A (p.Ser3Ter)Pathogenic
Jaberi-Elahi syndrome
β˜…β˜†β˜†β˜†2022β†’ Residue 3
NM_019096.5(GTPBP2):c.589dup (p.Leu197fs)Pathogenic
not provided
β˜…β˜†β˜†β˜†2022β†’ Residue 197
NM_019096.5(GTPBP2):c.1053_1054del (p.Glu352fs)Pathogenic
Jaberi-Elahi syndrome
β˜…β˜†β˜†β˜†2022β†’ Residue 352
NM_019096.5(GTPBP2):c.1187_1188insT (p.Asn397fs)Likely pathogenic
Jaberi-Elahi syndrome
β˜…β˜†β˜†β˜†2021β†’ Residue 397
NM_019096.5(GTPBP2):c.1527_1528del (p.Glu509fs)Likely pathogenic
Jaberi-Elahi syndrome
β˜…β˜†β˜†β˜†β†’ Residue 509
NM_019096.5(GTPBP2):c.1408C>T (p.Arg470Ter)Pathogenic
Jaberi-Elahi syndrome
β˜†β˜†β˜†β˜†2022β†’ Residue 470
NM_019096.5(GTPBP2):c.1558C>T (p.Arg520Ter)Pathogenic
Jaberi-Elahi syndrome
β˜†β˜†β˜†β˜†2022β†’ Residue 520
NM_019096.5(GTPBP2):c.655C>T (p.Arg219Ter)Pathogenic
Jaberi-Elahi syndrome
β˜†β˜†β˜†β˜†2022β†’ Residue 219
NM_019096.5(GTPBP2):c.1237-1G>TPathogenic
Jaberi-Elahi syndrome
β˜†β˜†β˜†β˜†2018
NM_019096.5(GTPBP2):c.1219C>T (p.Gln407Ter)Pathogenic
Jaberi-Elahi syndrome
β˜†β˜†β˜†β˜†2018β†’ Residue 407
NM_019096.5(GTPBP2):c.430C>T (p.Arg144Ter)Pathogenic
Jaberi-Elahi syndrome
β˜†β˜†β˜†β˜†2018β†’ Residue 144
View on ClinVar β†—
Related Genes
EEF1B2Shared pathway100%EIF5AL1Shared pathway100%PCDH7Protein interaction83%MRRFProtein interaction76%DCAF17Protein interaction71%EEF1DShared pathway50%
Tissue Expression6 tissues
Lung
100%
Bone Marrow
70%
Ovary
59%
Liver
48%
Heart
43%
Brain
32%
Gene Interaction Network
Click a node to explore
GTPBP2EEF1B2EIF5AL1PCDH7MRRFDCAF17EEF1D
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted Β· UniProt Q9BX10
View on AlphaFold β†—
Constraintβ“˜
LOEUFβ“˜
0.69LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF0.51 [0.39–0.69]
RankingsWhere GTPBP2 stands among ~20K protein-coding genes
  • #10,331of 20,598
    Most Researched39
  • #2,702of 5,498
    Most Pathogenic Variants12
  • #5,232of 17,882
    Most Constrained (LOEUF)0.69
Genes detectedGTPBP2
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
tRNA overexpression rescues peripheral neuropathy caused by mutations in tRNA synthetase.
PMID: 34516840
Science Β· 2021
1.00
2
Mouse and human GTPBP2, newly identified members of the GP-1 family of GTPase.
PMID: 10833435
Biochem Biophys Res Commun Β· 2000
0.90
3
Bi-allelic genetic variants in the translational GTPases GTPBP1 and GTPBP2 cause a distinct identical neurodevelopmental syndrome.
PMID: 38118446
Am J Hum Genet Β· 2024
0.80
4
Clinical delineation of GTPBP2-associated neuro-ectodermal syndrome: Report of two new families and review of the literature.
PMID: 30790272
Clin Genet Β· 2019
0.70
5
Jaberi-Elahi syndrome: Exploring a novel GTPBP2 mutation and a literature review.
PMID: 38852771
Eur J Med Genet Β· 2024
0.60