TP53RK

Chr 20

TP53 regulating kinase

Also known as: BUD32, C20orf64, GAMOS4, Nori-2, Nori-2p, PRPK, TPRKB, dJ101A2

NCBI Gene: 112858 ENSG00000172315 UniProt: Q96S44

TP53RK is a component of the EKC/KEOPS complex required for threonylcarbamoyl modification of tRNAs and functions as an atypical protein kinase that phosphorylates p53 at serine-15. Mutations cause Galloway-Mowat syndrome 4, a disorder characterized by early-onset nephrotic syndrome and microcephaly with developmental delay. This condition follows autosomal recessive inheritance.

ResearchSummary from RefSeq, OMIM, UniProt

Enables p53 binding activity and protein serine/threonine kinase activity. Involved in protein phosphorylation. Located in cytoplasm and nucleus. Part of EKC/KEOPS complex. Implicated in Galloway-Mowat syndrome 4. [provided by Alliance of Genome Resources, Jul 2025]

ResearchGenerating clinical summary…

LOFmechanismLOEUF 1.65

Clinical Summary— TP53RK

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

9 unique Pathogenic / Likely Pathogenic· 65 VUS of 119 total submissions

Explore recent and relevant literature in Research Assistant →

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.65LOEUF

pLI 0.001

Z-score 0.39

OE 0.83 (0.43–1.65)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.20Z-score

OE missense 0.95 (0.82–1.11)

119 obs / 125.2 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.83 (0.43–1.65)

0≤0.351.4

Missense OE?0.95 (0.82–1.11)

0≤0.61.4

Synonymous OE?0.98

0≤1.21.6

LoF obs/exp: 5 / 6.0Missense obs/exp: 119 / 125.2Syn Z: 0.14

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

strongTP53RK-related Galloway-Mowat syndromeLOFAR

This gene — mechanism propensity

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

0.7033th %ile

GOF

0.5072th %ile

LOF

0.3452th %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

119 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic4

Likely Pathogenic5

VUS65

Likely Benign29

Benign8

Conflicting7

Pathogenic

Likely Pathogenic

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	2	2	0	0	4
Likely Pathogenic	4	1	0	0	5
VUS	5	56	2	2	65
Likely Benign	0	4	4	21	29
Benign	0	4	3	1	8
Conflicting	—				7
Total	11	67	9	24	118

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

View in ClinVar →

9 pathogenic / likely-pathogenic (of 9) ClinVar copy-number / structural variants overlap TP53RK — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →