GTPBP1

Chr 22AR

GTP binding protein 1

NCBI Gene: 9567ENSG00000100226UniProt: O00178

GTPase that plays a role in the elongation phase of protein synthesis by forming ternary complexes with GTP and aminoacyl-transfer RNAs (aa-tRNAs), and delivering aa-tRNAs to the ribosomal A site in a GTP-dependent manner (PubMed:30108131). Is also able to deliver deacylated tRNA to the A site (PubMed:30108131). Additionally, it is involved in RNA quality control; after GTP hydrolysis, which is not immediately followed by rapid peptide bond formation, GTPBP1 likely retains aa-tRNA in the A site and promotes exosomal degradation of faulty mRNAs engaged in 80S elongation complexes (PubMed:30108131). Plays a role in the regulation of circadian mRNA stability (By similarity)

Primary Disease Associations & Inheritance

Neurodevelopmental disorder with characteristic facial and ectodermal features and tetraparesis 1MIM #620888
AR
439
ClinVar variants
23
Pathogenic / LP
0.93
pLI score· haploinsufficient
0
Active trials
Clinical Summary— GTPBP1
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.93). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
23 Pathogenic / Likely Pathogenic· 249 VUS of 439 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Dual constrained — LoF & missense intolerant
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.
0.35LOEUF
pLI 0.930
Z-score 4.01
OE 0.15 (0.07–0.35)
Highly 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.
3.36Z-score
OE missense 0.52 (0.47–0.59)
205 obs / 392.1 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.0.15 (0.07–0.35)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.52 (0.47–0.59)
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.0.86
0≤1.21.6
LoF obs/exp: 4 / 26.1Missense obs/exp: 205 / 392.1Syn Z: 1.34

ClinVar Variant Classifications

439 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic21
Likely Pathogenic2
VUS249
Likely Benign116
Benign18
Conflicting3
21
Pathogenic
2
Likely Pathogenic
249
VUS
116
Likely Benign
18
Benign
3
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
1
20
0
21
Likely Pathogenic
0
0
2
0
2
VUS
3
227
18
1
249
Likely Benign
0
11
34
71
116
Benign
0
7
3
8
18
Conflicting
—3
Total32467780409

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

View in ClinVar →

Protein Context — Lollipop Plot

GTPBP1 · protein map & ClinVar variants

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

Gene2Phenotype Curations

GTPBP1-related neurodevelopmental disorder with severe-profound intellectual disability, spasticity and ectodermal features

moderate
ARLoss Of FunctionAbsent Gene Product, Altered Gene Product Structure
Dev. Disorders
G2P ↗
missense variantstop gained NMD triggeringframeshift variant NMD triggering

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Neurodevelopmental disorder with characteristic facial and ectodermal features and tetraparesis 1

MIM #620888

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
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