TP53RK

TP53 regulating kinase, the group of KEOPS complex

Basic information

Region (hg38): 20:46684364-46689444

Previous symbols: [ "C20orf64" ]

Links

ENSG00000172315 ∙ NCBI:112858 ∙ OMIM:608679 ∙ HGNC:16197 ∙ Uniprot:Q96S44 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Galloway-Mowat syndrome 4 (Strong), mode of inheritance: AR
• Galloway-Mowat syndrome 4 (Strong), mode of inheritance: AR
• Galloway-Mowat syndrome (Supportive), mode of inheritance: AR
• Galloway-Mowat syndrome 4 (Limited), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Galloway-Mowat syndrome 4	AR	General	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	Craniofacial; Musculoskeletal; Neurologic	28805828

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TP53RK gene.

• not provided (44 variants)
• Galloway-Mowat syndrome 4 (10 variants)
• Inborn genetic diseases (2 variants)
• TP53RK-related condition (1 variants)
• Global developmental delay;Seizure (1 variants)
• Microcephaly (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TP53RK gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				10	1	11
missense		1	26	2	4	33
nonsense			1			1
start loss						0
frameshift			2			2
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region				1		1
non coding				1	3	4
Total	0	1	29	13	8

Variants in TP53RK

This is a list of pathogenic ClinVar variants found in the TP53RK region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
20-46686707-C-T			Benign (May 16, 2021)
20-46686756-C-T			Likely benign (Aug 11, 2018)
20-46686757-C-A			Uncertain significance (Aug 21, 2022)
20-46686760-A-G			Uncertain significance (Aug 05, 2022)
20-46686787-C-A		Galloway-Mowat syndrome 4	Pathogenic (Oct 27, 2017)
20-46686787-C-T		not specified	Uncertain significance (Jul 22, 2022)
20-46686788-G-A		Global developmental delay;Seizure • Galloway-Mowat syndrome 4	Conflicting classifications of pathogenicity (Feb 22, 2023)
20-46686826-T-G			Uncertain significance (Nov 01, 2023)
20-46686875-T-G			Uncertain significance (Oct 13, 2023)
20-46686886-G-A			Uncertain significance (Aug 13, 2022)
20-46686897-G-C			Likely benign (Dec 14, 2018)
20-46686899-C-G		Galloway-Mowat syndrome 4	Uncertain significance (Aug 28, 2019)
20-46686912-A-G			Likely benign (Nov 16, 2023)
20-46686917-G-C		Galloway-Mowat syndrome 4	Uncertain significance (Jan 11, 2022)
20-46686932-C-T		not specified	Uncertain significance (Aug 10, 2021)
20-46686936-T-C			Likely benign (Sep 26, 2022)
20-46686957-C-G		TP53RK-related disorder	Likely benign (Mar 22, 2019)
20-46686971-T-C		Galloway-Mowat syndrome 4	Uncertain significance (Dec 23, 2018)
20-46686996-G-C		Galloway-Mowat syndrome 4 • TP53RK-related disorder	Likely benign (Jan 13, 2024)
20-46687036-T-C			Uncertain significance (Mar 01, 2022)
20-46687053-G-A			Likely benign (Jun 14, 2018)
20-46687053-GT-AG			Uncertain significance (Apr 07, 2022)
20-46687061-G-A			Uncertain significance (Mar 27, 2022)
20-46687082-T-C		Galloway-Mowat syndrome 4 • TP53RK-related disorder	Benign/Likely benign (Dec 13, 2023)
20-46687084-T-TTGGCTAAGTTGGAGAGACCC			Uncertain significance (Mar 01, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TP53RK	protein_coding	protein_coding	ENST00000372114	2	5415

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.000775	0.552	125686	0	62	125748	0.000247

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.198	119	125	0.950	0.00000592	1592
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000406	0.000406
Ashkenazi Jewish	0.00	0.00
East Asian	0.000272	0.000272
Finnish	0.0000924	0.0000924
European (Non-Finnish)	0.000202	0.000202
Middle Eastern	0.000272	0.000272
South Asian	0.000555	0.000555
Other	0.000165	0.000163

dbNSFP

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.
• Pathway: tRNA modification in the nucleus and cytosol;tRNA processing;Gene expression (Transcription);Generic Transcription Pathway;RNA Polymerase II Transcription;Metabolism of RNA;Regulation of TP53 Activity through Phosphorylation;Regulation of TP53 Activity;Transcriptional Regulation by TP53 (Consensus)

Haploinsufficiency Scores

• pHI: 0.185
• hipred: Y
• hipred_score: 0.642
• ghis: 0.423

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.991

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Trp53rka

Gene ontology

• Biological process: protein phosphorylation;tRNA processing;tRNA threonylcarbamoyladenosine metabolic process;regulation of signal transduction by p53 class mediator
• Cellular component: EKC/KEOPS complex;nucleus;nucleoplasm;cytoplasm;cytosol
• Molecular function: p53 binding;protein serine/threonine kinase activity;protein binding;ATP binding;hydrolase activity