Incidental Mutation 'A5278:Pbk'
ID 66
Institutional Source Beutler Lab
Gene Symbol Pbk
Ensembl Gene ENSMUSG00000022033
Gene Name PDZ binding kinase
Synonyms D14Ertd732e, 2810434B10Rik, TOPK
Accession Numbers
Essential gene? Possibly essential (E-score: 0.694) question?
Stock # A5278 of strain 453
Quality Score
Status Validated
Chromosome 14
Chromosomal Location 66043337-66055271 bp(+) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) T to A at 66051388 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Isoleucine to Asparagine at position 142 (I142N)
Ref Sequence ENSEMBL: ENSMUSP00000022612 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000022612] [ENSMUST00000139644]
AlphaFold Q9JJ78
Predicted Effect probably damaging
Transcript: ENSMUST00000022612
AA Change: I142N

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)
SMART Domains Protein: ENSMUSP00000022612
Gene: ENSMUSG00000022033
AA Change: I142N

DomainStartEndE-ValueType
Pfam:Pkinase 32 317 1.7e-40 PFAM
Pfam:Pkinase_Tyr 32 317 2.4e-34 PFAM
Predicted Effect probably benign
Transcript: ENSMUST00000139644
SMART Domains Protein: ENSMUSP00000114484
Gene: ENSMUSG00000022033

DomainStartEndE-ValueType
Pfam:Pkinase_Tyr 32 119 3.5e-5 PFAM
Pfam:Pkinase 32 120 7.2e-9 PFAM
Predicted Effect noncoding transcript
Transcript: ENSMUST00000152130
Meta Mutation Damage Score 0.9173 question?
Coding Region Coverage
  • 1x: 88.2%
  • 3x: 73.8%
Validation Efficiency 87% (116/134)
MGI Phenotype FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] 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]
PHENOTYPE: Mice homozygous for a knock-out allele exhibit increased UV-induced loss of the horny layer, epidermis thickening, skin fibrosis, and deposition of extracellular matrix in the skin. [provided by MGI curators]
Allele List at MGI

All alleles(14) : Gene trapped(14)

Other mutations in this stock
Total: 7 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
Kat14 C A 2: 144,235,227 (GRCm39) S18* probably null Het
Kif17 T C 4: 138,015,261 (GRCm39) V278A probably benign Homo
Myo3a A G 2: 22,328,464 (GRCm39) T353A probably benign Het
Rab32 A G 10: 10,433,717 (GRCm39) I39T possibly damaging Het
Rhou G T 8: 124,387,730 (GRCm39) C154F probably damaging Het
Slc4a1 A G 11: 102,244,641 (GRCm39) probably benign Het
Tdrd7 C T 4: 46,007,622 (GRCm39) T558M probably benign Homo
Other mutations in Pbk
AlleleSourceChrCoordTypePredicted EffectPPH Score
IGL00227:Pbk APN 14 66,051,340 (GRCm39) missense probably damaging 1.00
IGL00858:Pbk APN 14 66,049,373 (GRCm39) splice site probably benign
IGL01472:Pbk APN 14 66,054,159 (GRCm39) missense probably benign 0.06
IGL03239:Pbk APN 14 66,054,667 (GRCm39) missense probably benign 0.22
R0067:Pbk UTSW 14 66,052,675 (GRCm39) missense possibly damaging 0.90
R0645:Pbk UTSW 14 66,051,245 (GRCm39) splice site probably benign
R4696:Pbk UTSW 14 66,049,386 (GRCm39) missense probably benign 0.00
R4834:Pbk UTSW 14 66,052,733 (GRCm39) nonsense probably null
R4856:Pbk UTSW 14 66,052,650 (GRCm39) missense probably damaging 1.00
R4886:Pbk UTSW 14 66,052,650 (GRCm39) missense probably damaging 1.00
R6006:Pbk UTSW 14 66,054,094 (GRCm39) missense probably damaging 0.97
R6086:Pbk UTSW 14 66,052,702 (GRCm39) nonsense probably null
R7272:Pbk UTSW 14 66,052,621 (GRCm39) missense probably damaging 1.00
R7960:Pbk UTSW 14 66,046,650 (GRCm39) splice site probably null
R8296:Pbk UTSW 14 66,054,185 (GRCm39) nonsense probably null
R8333:Pbk UTSW 14 66,054,680 (GRCm39) missense probably benign 0.23
R9061:Pbk UTSW 14 66,049,439 (GRCm39) missense probably benign 0.37
R9290:Pbk UTSW 14 66,054,713 (GRCm39) missense probably benign 0.02
Z1088:Pbk UTSW 14 66,051,397 (GRCm39) missense probably damaging 1.00
Nature of Mutation
DNA sequencing using the SOLiD technique identified a T to A transversion at position 669 of the Pbk transcript in exon 5 of 8 total exons. The mutated nucleotide causes an isoleucine to asparagine substitution at amino acid 142 of the encoded protein. The mutation has been confirmed by DNA sequencing using the Sanger method (Figure 1).
Protein Function and Prediction
The Pbk gene encodes a 330 amino acid protein kinase with similarity to mitogen activated protein kinase kinase (MAPKK). The PBK protein phosphorylates MAP kinase p38, and may play a role in the activation of lymphoid cells. It appears to be active only during mitosis. When phosphorylated, the PBK protein forms a complex with p53, leading to p53 destabilization. The kinase domain occurs at amino acids 31-330 with the nucleotide-binding site at residues 37-45. The proton acceptor site occurs at amino acid 166 (Uniprot Q9JJ78).
 
The I142N change occurs in the kinase domain, and is predicted to be probably damaging by the PolyPhen program.
Posted On 2009-12-03