TPRKB

Chr 2AR

TP53RK binding protein

Also known as: CGI-121, CGI121, GAMOS5

TPRKB encodes a component of the EKC/KEOPS complex that modifies tRNAs by adding threonylcarbamoyl groups to specific adenosine residues, acting as an allosteric regulator of this tRNA modification process. Biallelic mutations cause Galloway-Mowat syndrome 5, an autosomal recessive disorder characterized by nephrotic syndrome and microcephaly with developmental delays. The gene shows tolerance to loss-of-function variants (LOEUF 1.3), indicating that complete loss of function may be required for disease manifestation.

OMIMResearchSummary from RefSeq, OMIM, UniProt
MultiplemechanismARLOEUF 1.311 OMIM phenotype
Clinical SummaryTPRKB
Population Constraint (gnomAD)
Low constraint (pLI 0.01) — loss-of-function variants are relatively tolerated in the population.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.31LOEUF
pLI 0.008
Z-score 1.03
OE 0.58 (0.281.31)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.10Z-score
OE missense 0.97 (0.811.17)
80 obs / 82.6 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.58 (0.281.31)
00.351.4
Missense OE0.97 (0.811.17)
00.61.4
Synonymous OE1.07
01.21.6
LoF obs/exp: 4 / 6.9Missense obs/exp: 80 / 82.6Syn Z: -0.30
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
limitedTPRKB-related Galloway-Mowat syndromeOTHERAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.6455th %ile
GOF
0.7125th %ile
LOF
0.3067th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

TPRKB · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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