TPRKB
protein-codingTP53RK binding protein, the group of KEOPS complex
Gene summary
Enables protein kinase binding activity. Involved in tRNA threonylcarbamoyladenosine modification. Located in cytosol and nucleus. Part of EKC/KEOPS complex. Implicated in Galloway-Mowat syndrome 5. [provided by Alliance of Genome Resources, Jul 2025]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~8.3 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0033009
Submitter: Ambry Genetics
Inheritance Pattern: AR
Disease ID:MONDO:0033009
Submitter: Ambry Genetics
Inheritance Pattern: AR
Disease ID:MONDO:0033009
Submitter: G2P
Inheritance Pattern: AR
Disease ID:MONDO:0009627
Submitter: Orphanet
Inheritance Pattern: AR
Disease ID:MONDO:0033009
Submitter: PanelApp Australia
Inheritance Pattern: Unknown
Disease ID:MONDO:0033009
Submitter: Labcorp Genetics (formerly Invitae)
Clinical Genomic Database (CGD)
Manifestation: Craniofacial; Neurologic; Renal
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
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to TPRKB variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_016058.5. 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 | 7 | 7 | ||||
| missense | 1 | 2 | 38 | 2 | 1 | 44 |
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 5 | 5 | ||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 1 | 2 | 43 | 9 | 1 | 56 |
Highest pathogenic variant AF is 0.0000032004343
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_057142.1 | 4 | MANE Select | |
| Ensembl | ENSP00000272424.5 | 4 | MANE Select | |
| RefSeq | NP_001317315.1 | 5 | Standard | |
| RefSeq | NP_001317316.1 | 5 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| tprkb | Danio rerio | Structure: head Quality: decreased diameter abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- tRNA modification in the nucleus and cytosol
- tRNA processing
- Metabolism of RNA
Biological Process
- tRNA threonylcarbamoyladenosine modification
Molecular Function
- protein binding
- protein kinase binding
Cellular Component
- EKC/KEOPS complex
- nucleus
- cytoplasm
- cytosol
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000272424
- Coding exons
- 4
- Length
- 8297
- Individuals with no LoFs
- 125700
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 43
- Defined
- 125743
- p
- 0.000171
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.101 | 80 | 82.6 | 0.969 | 0.00000371 | 1127 |
| Missense (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 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00020 | 0.00018 | rare |
| Latino/Admixed American | 0.000065 | 0.000058 | rare |
| Ashkenazi Jewish | 0.00064 | 0.00060 | rare |
| East Asian | 0.00076 | 0.00071 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.00014 | 0.00013 | rare |
| South Asian | 0.00016 | 0.00013 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- 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}.;
Recessive Scores
- pRec
- 0.105
Intolerance Scores
- LoFtool
- 0.526
- RVIS EVS
- -0.34
- RVIS percentile EVS
- 30.07
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- H
- Indispensability pred.
- E
- Indispensability score
- 0.782
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |