TP53RK

protein-coding

TP53 regulating kinase, the group of KEOPS complex

Gene summary

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]

Previous symbols:

C20orf64

MANE transcript

NM_033550.4

Inheritance

ClinVar variants

P:14U:66B:30

Top phenotype

Galloway-Mowat syndrome 4

gnomAD constraint

pLI —, LoF o/e 0.83

Max pathogenic AF

—

Genomic locus

chr20:46,684,365-46,689,444

External References & Databases

Ensembl (ENSG00000172315)

Transcript & Mutation Effects

hg38 • Region Span ~5.1 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

Galloway-Mowat syndromeSUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0009627

Submitter: Orphanet

Galloway-Mowat syndrome 4STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0033008

Submitter: PanelApp Australia

Galloway-Mowat syndrome 4STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0033008

Submitter: G2P

Galloway-Mowat syndrome 4STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0033008

Submitter: Labcorp Genetics (formerly Invitae)

Galloway-Mowat syndrome 4LIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0033008

Submitter: Ambry Genetics

Clinical Genomic Database (CGD)

Galloway-Mowat syndrome 4AR

Manifestation: Craniofacial; Musculoskeletal; Neurologic

Intervention: General

Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing

Refs: 28805828

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to TP53RK variants in ClinVar

7 Conditions Cataloged

Galloway-Mowat syndrome 4Total: 59

not providedTotal: 57

not specifiedTotal: 11

TP53RK-related disorderTotal: 11

SeizureTotal: 2

Global developmental delayTotal: 2

MicrocephalyTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_033550.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			2 clinvar	22 clinvar		24
missense	2 clinvar	3 clinvar	57 clinvar	6 clinvar	2 clinvar	70
nonsense		2 clinvar	3 clinvar			5
start loss						0
frameshift	2 clinvar	5 clinvar	3 clinvar			10
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	4	10	66	28	2	110

Highest pathogenic variant AF is 0.000045231263

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 5 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_033550.4	RefSeq	NP_291028.3	2	MANE Select
ENST00000372114.4	Ensembl	ENSP00000361186.3	2	MANE Select
ENST00000372102.3	Ensembl	ENSP00000361174.3	2	Standard
ENST00000372102.4	Ensembl	ENSP00000361174.3	2	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

tRNA modification in the nucleus and cytosol
tRNA processing
Gene expression (Transcription)
Generic Transcription Pathway
RNA Polymerase II Transcription

Biological Process

protein phosphorylation
tRNA processing
tRNA threonylcarbamoyladenosine metabolic process
regulation of signal transduction by p53 class mediator

Molecular Function

p53 binding
protein serine/threonine kinase activity
protein binding
ATP binding
hydrolase activity

Cellular Component

EKC/KEOPS complex
nucleus
nucleoplasm
cytoplasm
cytosol

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000372114
Coding exons: 2
Length: 5415
Individuals with no LoFs: 125686
Homozygous LoFs: 0
Heterozygous LoFs: 62
Defined: 125748
p: 0.000247

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.198	119	125	0.950	0.00000592	1592
Missense (PolyPhen)		28	48.724	0.57466		623
Synonymous	0.137	51	52.3	0.976	0.00000248	546
Loss of Function	0.389	5	6.03	0.829	3.88e-7	80

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.00041	0.00040	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00027	0.00027	rare
Finnish	0.000092	0.000092	rare
European (Non-Finnish)	0.00020	0.00020	rare
South Asian	0.00056	0.00056	rare
Other	0.00017	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Component of the EKC/KEOPS complex that is required for the formation of a threonylcarbamoyl group on adenosine at position 37 (t(6)A37) in tRNAs that read codons beginning with adenine (PubMed:22912744, PubMed:27903914). The complex is probably involved in the transfer of the threonylcarbamoyl moiety of threonylcarbamoyl-AMP (TC-AMP) to the N6 group of A37 (PubMed:22912744, PubMed:27903914). TP53RK has ATPase activity in the context of the EKC/KEOPS complex and likely plays a supporting role to the catalytic subunit OSGEP (By similarity). Atypical protein kinase that phosphorylates 'Ser-15' of p53/TP53 protein and may therefore participate in its activation (PubMed:11546806). {ECO:0000250|UniProtKB:P53323, ECO:0000250|UniProtKB:Q9UYB9, ECO:0000269|PubMed:11546806, ECO:0000305|PubMed:22912744, ECO:0000305|PubMed:27903914}.;
Disease: DISEASE: Galloway-Mowat syndrome 4 (GAMOS4) [MIM:617730]: A form of Galloway-Mowat syndrome, a severe renal-neurological disease characterized by early-onset nephrotic syndrome associated with microcephaly, central nervous system abnormalities, developmental delays, and a propensity for seizures. Brain anomalies include gyration defects ranging from lissencephaly to pachygyria and polymicrogyria, and cerebellar hypoplasia. Most patients show facial dysmorphism characterized by a small, narrow forehead, large/floppy ears, deep-set eyes, hypertelorism and micrognathia. Additional variable features are visual impairment and arachnodactyly. Most patients die in early childhood. {ECO:0000269|PubMed:28805828}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Essentials

Essential (CRISPR): E
Essential (CRISPR2): E
Essential (gene trap): E
Indispensability pred.: E
Indispensability score: 0.991

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium