TP53RK

Chr 20AR

TP53 regulating kinase

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

NCBI Gene: 112858ENSG00000172315UniProt: Q96S44

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]

Primary Disease Associations & Inheritance

Galloway-Mowat syndrome 4MIM #617730
AR
127
ClinVar variants
18
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— TP53RK
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
18 Pathogenic / Likely Pathogenic· 66 VUS of 127 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
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?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.20Z-score
OE missense 0.95 (0.82–1.11)
119 obs / 125.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.83 (0.43–1.65)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.95 (0.82–1.11)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.98
0≤1.21.6
LoF obs/exp: 5 / 6.0Missense obs/exp: 119 / 125.2Syn Z: 0.14

ClinVar Variant Classifications

127 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic12
Likely Pathogenic6
VUS66
Likely Benign29
Benign8
Conflicting6
12
Pathogenic
6
Likely Pathogenic
66
VUS
29
Likely Benign
8
Benign
6
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
2
2
8
0
12
Likely Pathogenic
2
1
3
0
6
VUS
3
56
5
2
66
Likely Benign
0
4
4
21
29
Benign
0
4
3
1
8
Conflicting
—6
Total7672324127

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

View in ClinVar →

Protein Context — Lollipop Plot

TP53RK · protein map & ClinVar variants

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

Gene2Phenotype Curations

TP53RK-related Galloway-Mowat syndrome

strong
ARLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Galloway-Mowat syndrome 4

MIM #617730

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Mutations in KEOPS-complex genes cause nephrotic syndrome with primary microcephaly.
Braun DA et al.·Nat Genet
2017
TP53RK Drives the Progression of Chronic Kidney Disease by Phosphorylating Birc5.
Wu M et al.·Adv Sci (Weinh)
2023
Genetics and phenotypic heterogeneity of Galloway-Mowat syndrome.
Huang L et al.·Cell Commun Signal
2025Review
Functional characterization of a novel TP53RK mutation identified in a family with Galloway-Mowat syndrome.
Treimer E et al.·Hum Mutat
2022Case report
Systematic screening for potential therapeutic targets in osteosarcoma through a kinome-wide CRISPR-Cas9 library.
Wu Y et al.·Cancer Biol Med
2020
A chemosensitization screen identifies TP53RK, a kinase that restrains apoptosis after mitotic stress.
Peterson D et al.·Cancer Res
2010
Rare heterozygous variants in paediatric steroid resistant nephrotic syndrome - a population-based analysis of their significance.
Platt CJ et al.·Sci Rep
2024
Novel homozygous OSGEP gene pathogenic variants in two unrelated patients with Galloway-Mowat syndrome: case report and review of the literature.
Domingo-Gallego A et al.·BMC Nephrol
2019Review
Proteome profile of the MCF7 cancer cell line: a mass spectrometric evaluation.
Sarvaiya HA et al.·Rapid Commun Mass Spectrom
2006
Diagnosis delay a family of Galloway-Mowat Syndrome caused by a classical splicing mutation of Lage3.
Chen Y et al.·BMC Nephrol
2023Case report
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools