PBK
protein-codingPDZ binding kinase
Gene summary
This gene encodes a serine/threonine protein kinase related to the dual specific mitogen-activated protein kinase kinase (MAPKK) family. Evidence suggests that mitotic phosphorylation is required for its catalytic activity. The encoded protein may be involved in the activation of lymphoid cells and support testicular functions, with a suggested role in the process of spermatogenesis. Overexpression of this gene has been implicated in tumorigenesis. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2013]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~28.5 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to PBK variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_018492.4. 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 | 1 | 1 | 2 | |||
| missense | 34 | 1 | 1 | 36 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 35 | 1 | 2 | 38 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_060962.2 | 7 | MANE Select | |
| Ensembl | ENSP00000301905.4 | 7 | MANE Select | |
| RefSeq | NP_001265874.1 | 7 | Standard | |
| RefSeq | NP_001349969.1 | 7 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- 4-hydroxytamoxifen, Dexamethasone, and Retinoic Acids Regulation of p27 Expression
- VEGFA-VEGFR2 Signaling Pathway
Biological Process
- mitotic cell cycle
- protein phosphorylation
- negative regulation of proteasomal ubiquitin-dependent protein catabolic process
- negative regulation of stress-activated MAPK cascade
- cellular response to UV
Molecular Function
- protein serine/threonine kinase activity
- protein binding
- ATP binding
Cellular Component
- nucleus
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000301905
- Coding exons
- 7
- Length
- 28476
- Individuals with no LoFs
- 125672
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 75
- Defined
- 125747
- p
- 0.000298
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.663 | 143 | 167 | 0.856 | 0.00000791 | 2128 |
| Missense (PolyPhen) | 52 | 57.874 | 0.89851 | 752 | ||
| Synonymous | -0.402 | 59 | 55.2 | 1.07 | 0.00000262 | 581 |
| Loss of Function | 0.958 | 11 | 15.0 | 0.733 | 7.90e-7 | 199 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00025 | 0.00025 | rare |
| Latino/Admixed American | 0.00044 | 0.00043 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00022 | 0.00022 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.00035 | 0.00033 | rare |
| South Asian | 0.00046 | 0.00042 | rare |
| Other | 0.00016 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Phosphorylates MAP kinase p38. Seems to be active only in mitosis. May also play a role in the activation of lymphoid cells. When phosphorylated, forms a complex with TP53, leading to TP53 destabilization and attenuation of G2/M checkpoint during doxorubicin-induced DNA damage. {ECO:0000269|PubMed:10781613, ECO:0000269|PubMed:17482142}.;
Recessive Scores
- pRec
- 0.334
Intolerance Scores
- LoFtool
- 0.625
- RVIS EVS
- 0.31
- RVIS percentile EVS
- 72.23
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.978
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |