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

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.

not_provided (28 variants)
not_specified (23 variants)
Galloway-Mowat_syndrome_5 (7 variants)
TPRKB-related_disorder (5 variants)
Nephrotic_syndrome (1 variants)

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. These statistics are base on transcript: NM_000016058.5. Only rare variants are included in the table.

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.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous				7 clinvar		7
missense	1 clinvar	2 clinvar	33 clinvar	2 clinvar	1 clinvar	39
nonsense						0
start loss						0
frameshift			5 clinvar			5
splice donor/acceptor (+/-2bp)						0
Total	1	2	38	9	1

Highest pathogenic variant AF is 0.0000032004343

Loading clinvar variants...

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
Phenotype

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