GTPBP1

Chr 22AR

GTP binding protein 1

Also known as: GP-1, GP1, HSPC018, NEDFET1

NCBI Gene: 9567 ENSG00000100226 UniProt: O00178 OMIM: 602245

GTPBP1 encodes a GTPase that delivers aminoacyl-tRNAs to ribosomes during protein synthesis and promotes degradation of faulty mRNAs through RNA quality control mechanisms. Autosomal recessive mutations cause neurodevelopmental disorder with characteristic facial and ectodermal features and tetraparesis. The gene is highly constrained against loss-of-function variants, indicating that functional GTPBP1 protein is essential for normal cellular processes.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene is upregulated by interferon-gamma and encodes a protein that is a member of the AGP11/GTPBP1 family of GTP-binding proteins. A structurally similar protein has been found in mouse, where disruption of the gene for that protein had no observable phenotype. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

LOFmechanismARLOEUF 0.351 OMIM phenotype

Clinical Summary— GTPBP1

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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.

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ClinVar Variants

4 unique Pathogenic / Likely Pathogenic· 247 VUS of 418 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Dual constrained — LoF & missense intolerant

LoF Constraint?

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?

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?

LoF OE?0.15 (0.07–0.35)

0≤0.351.4

Missense OE?0.52 (0.47–0.59)

0≤0.61.4

Synonymous OE?0.86

0≤1.21.6

LoF obs/exp: 4 / 26.1Missense obs/exp: 205 / 392.1Syn Z: 1.34

ClinVar Variant Classifications

418 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic4

VUS247

Likely Benign117

Benign18

Conflicting2

Pathogenic

247

VUS

117

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	3	1	0	0	4
Likely Pathogenic	0	0	0	0	0
VUS	7	231	8	1	247
Likely Benign	0	11	34	72	117
Benign	0	7	3	8	18
Conflicting	—				2
Total	10	250	45	81	388

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

View in ClinVar →

20 pathogenic / likely-pathogenic (of 25) ClinVar copy-number / structural variants overlap GTPBP1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →