GTPBP4

Chr 10

GTP binding protein 4

Also known as: CRFG, NGB, NOG1

This protein functions as a GTPase involved in 60S ribosomal subunit biogenesis and acts as a TP53 repressor to prevent cell cycle arrest. Mutations cause autosomal recessive intellectual disability with microcephaly and growth retardation. The gene is highly constrained against loss-of-function variants (pLI ~1.0, LOEUF 0.08), indicating intolerance to haploinsufficiency in the general population.

Summary from RefSeq, UniProt
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1
Active trials
10
Pubs (1 yr)
0
P/LP submissions
P/LP missense
0.08
LOEUF· LoF intol.
LOF
Mechanism· predicted
Clinical SummaryGTPBP4
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
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Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.08LOEUF
pLI 1.000
Z-score 5.66
OE 0.00 (0.000.08)
Highly constrained

Among the most LoF-intolerant genes (~top 3%)

Missense Constraint
0.08Z-score
OE missense 0.99 (0.911.08)
359 obs / 363.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.00 (0.000.08)
00.351.4
Missense OE0.99 (0.911.08)
00.61.4
Synonymous OE0.99
01.21.6
LoF obs/exp: 0 / 37.4Missense obs/exp: 359 / 363.2Syn Z: 0.13
DN
0.4586th %ile
GOF
0.3094th %ile
LOF
0.74top 10%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.08

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

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

GTPBP4 · protein map & ClinVar variants

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

Clinical Literature
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