TPRKB

Chr 2AR

TP53RK binding protein

Also known as: CGI-121, CGI121, GAMOS5

NCBI Gene: 51002 ENSG00000144034 UniProt: Q9Y3C4 OMIM: 608680

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.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

Enables protein kinase binding activity. Involved in tRNA threonylcarbamoyladenosine modification. Located in cytosol and nucleus. Part of EKC/KEOPS complex. Implicated in Galloway-Mowat syndrome 5. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

MultiplemechanismARLOEUF 1.311 OMIM phenotype

Clinical Summary— TPRKB

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Population Constraint (gnomAD)

Low constraint (pLI 0.01) — loss-of-function variants are relatively tolerated in the population.

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.31LOEUF

pLI 0.008

Z-score 1.03

OE 0.58 (0.28–1.31)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.10Z-score

OE missense 0.97 (0.81–1.17)

80 obs / 82.6 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.58 (0.28–1.31)

0≤0.351.4

Missense OE?0.97 (0.81–1.17)

0≤0.61.4

Synonymous OE?1.07

0≤1.21.6

LoF obs/exp: 4 / 6.9Missense obs/exp: 80 / 82.6Syn Z: -0.30

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

limitedTPRKB-related Galloway-Mowat syndromeOTHERAR

This gene — mechanism propensity

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

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.