TPRKB

TP53RK binding protein, the group of KEOPS complex

Basic information

Region (hg38): 2:73729104-73737400

Links

ENSG00000144034 ∙ NCBI:51002 ∙ OMIM:608680 ∙ HGNC:24259 ∙ Uniprot:Q9Y3C4 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Galloway-Mowat syndrome 5 (Limited), mode of inheritance: AR
• Galloway-Mowat syndrome (Supportive), mode of inheritance: AR
• Galloway-Mowat syndrome 5 (Limited), mode of inheritance: Unknown

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Galloway-Mowat syndrome 5	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; Neurologic; Renal	28805828

ClinVar

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

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TPRKB 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				6	1	7
missense		1	19	1		21
nonsense						0
start loss						0
frameshift			5			5
inframe indel			1			1
splice donor/acceptor (+/-2bp)						0
splice region					1	1
non coding				1	2	3
Total	0	1	25	8	3

Variants in TPRKB

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

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

Position	Type	Phenotype	Significance	ClinVar
2-73729754-T-C			Benign (May 15, 2021)
2-73729813-CT-C			Benign (May 15, 2021)
2-73729988-T-A			Uncertain significance (Feb 01, 2022)
2-73729997-A-G		Galloway-Mowat syndrome 5	Benign (Jan 31, 2024)
2-73730008-C-T			Uncertain significance (Jul 06, 2022)
2-73730014-AAG-A		not specified	Uncertain significance (Nov 07, 2017)
2-73730018-G-A		TPRKB-related disorder	Likely benign (Dec 19, 2022)
2-73730019-A-G		not specified	Uncertain significance (Sep 26, 2022)
2-73730022-T-TTA			Uncertain significance (Jan 12, 2023)
2-73730025-T-C		Galloway-Mowat syndrome 5	Pathogenic (Oct 27, 2017)
2-73730026-A-T		Galloway-Mowat syndrome 5	Likely pathogenic (Mar 26, 2024)
2-73730100-T-A			Benign (May 15, 2021)
2-73730577-TATTC-T		not specified	Uncertain significance (Jul 03, 2023)
2-73730594-A-G		Galloway-Mowat syndrome 5 • Nephrotic syndrome	Conflicting classifications of pathogenicity (Nov 10, 2017)
2-73730595-G-C		not specified	Uncertain significance (Jun 21, 2022)
2-73730596-A-G			Likely benign (Aug 07, 2022)
2-73730611-C-T		Galloway-Mowat syndrome 5	Benign/Likely benign (Oct 23, 2023)
2-73730628-G-C		not specified	Likely benign (Dec 04, 2023)
2-73730632-T-C			Uncertain significance (Sep 21, 2022)
2-73730651-ATTTG-A			Uncertain significance (Nov 27, 2023)
2-73730673-T-C		not specified	Uncertain significance (Jan 18, 2023)
2-73730674-G-A		TPRKB-related disorder	Likely benign (Mar 14, 2020)
2-73730679-C-G		not specified	Uncertain significance (Jan 11, 2023)
2-73730715-A-T			Uncertain significance (Dec 17, 2023)
2-73730724-A-G		TPRKB-related disorder	Likely benign (Dec 16, 2019)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TPRKB	protein_coding	protein_coding	ENST00000272424	4	8297

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00821	0.805	125700	0	43	125743	0.000171

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.101	80	82.6	0.969	0.00000371	1127
Missense in Polyphen		17	19.578	0.86831		285
Synonymous	-0.296	33	30.9	1.07	0.00000156	332
Loss of Function	1.03	4	6.93	0.577	2.89e-7	103

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000263	0.000250
Ashkenazi Jewish	0.000640	0.000595
East Asian	0.000763	0.000707
Finnish	0.00	0.00
European (Non-Finnish)	0.000137	0.000132
Middle Eastern	0.000763	0.000707
South Asian	0.000156	0.000131
Other	0.00	0.00

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:28805828). 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:28805828). TPRKB acts as an allosteric effector that regulates the t(6)A activity of the complex. TPRKB is not required for tRNA modification (PubMed:22912744, PubMed:28805828). {ECO:0000269|PubMed:28805828, ECO:0000305|PubMed:22912744}.
• Pathway: tRNA modification in the nucleus and cytosol;tRNA processing;Metabolism of RNA (Consensus)

Recessive Scores

• pRec: 0.105

Intolerance Scores

• loftool: 0.526
• rvis_EVS: -0.34
• rvis_percentile_EVS: 30.07

Haploinsufficiency Scores

• pHI: 0.230
• hipred: N
• hipred_score: 0.394
• ghis: 0.661

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: H
• gene_indispensability_pred: E
• gene_indispensability_score: 0.782

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Tprkb

Zebrafish Information Network

• Gene name: tprkb
• Affected structure: head
• Phenotype tag: abnormal
• Phenotype quality: decreased diameter

Gene ontology

• Biological process: tRNA threonylcarbamoyladenosine modification
• Cellular component: EKC/KEOPS complex;nucleus;cytoplasm;cytosol
• Molecular function: protein binding;protein kinase binding