GeneBe

PLK3

protein-coding

polo like kinase 3

Gene summary

The protein encoded by this gene is a member of the highly conserved polo-like kinase family of serine/threonine kinases. Members of this family are characterized by an amino-terminal kinase domain and a carboxy-terminal bipartite polo box domain that functions as a substrate-binding motif and a cellular localization signal. Polo-like kinases are important regulators of cell cycle progression. This gene has also been implicated in stress responses and double-strand break repair. In human cell lines, this protein is reported to associate with centrosomes in a microtubule-dependent manner, and during mitosis, the protein becomes localized to the mitotic apparatus. Expression of a kinase-defective mutant results in abnormal cell morphology caused by changes in microtubule dynamics and mitotic arrest followed by apoptosis. [provided by RefSeq, Sep 2015]

Previous symbols:
  • CNK

MANE transcript

NM_004073.4

Inheritance

—

ClinVar variants

U:103B:10

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.46

Max pathogenic AF

—

Genomic locus

chr1:44,800,377-44,805,995

External References & Databases

Ensembl (ENSG00000173846)NCBI Gene (1263)OMIM (602913)HGNC:2154GenCCUniProt (Q9H4B4)AlphaFoldClinVar (PLK3)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~5.6 kb
Loading mutation effect viewer...

GenCC 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 PLK3 variants in ClinVar

2 Conditions Cataloged
not specifiedTotal: 95
not providedTotal: 7

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_004073.4. 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.

EffectPLPVUSLBBSum
synonymous
4
clinvar
1
clinvar
6
clinvar
 11
missense
94
clinvar
3
clinvar
 97
nonsense
1
clinvar
 1
start loss
0
frameshift
0
splice donor/acceptor (+/-2bp)
4
clinvar
 4
Total0010346113
Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 16 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_004073.4RefSeqNP_004064.215MANE Select
ENST00000372201.5EnsemblENSP00000361275.415MANE Select
ENST00000850614.1EnsemblENSP00000520901.115Standard
ENST00000850614.2EnsemblENSP00000520901.115Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

  • FoxO signaling pathway - Homo sapiens (human)
  • C-type lectin receptor signaling pathway - Homo sapiens (human)
  • Tuberculosis - Homo sapiens (human)
  • Integrated Breast Cancer Pathway
  • TP53 Regulates Transcription of Cell Cycle Genes

Biological Process

  • G1/S transition of mitotic cell cycle
  • G2/M transition of mitotic cell cycle
  • negative regulation of transcription by RNA polymerase II
  • response to reactive oxygen species
  • protein phosphorylation

Molecular Function

  • p53 binding
  • protein serine/threonine kinase activity
  • protein binding
  • ATP binding

Cellular Component

  • nucleus
  • nucleoplasm
  • nucleolus
  • cytoplasm
  • Golgi stack

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000372201
Coding exons
15
Length
5766
Individuals with no LoFs
125706
Homozygous LoFs
0
Heterozygous LoFs
42
Defined
125748
p
0.000167
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense1.243183860.8230.00002414135
Missense (PolyPhen)125144.710.863821684
Synonymous-0.1161581561.010.000009341378
Loss of Function2.831532.40.4630.00000177354

Population LoF Frequency

PopulationCAFp-valueStatus
African0.000310.00031rare
Latino/Admixed American0.000200.00020rare
Ashkenazi Jewish00.0absent
East Asian0.000270.00027rare
Finnish00.0absent
European (Non-Finnish)0.000160.00016rare
South Asian0.000160.00016rare
Other0.000330.00033rare

dbNSFP Gene Annotations

Source: dbNSFP

Function
FUNCTION: Serine/threonine-protein kinase involved in cell cycle regulation, response to stress and Golgi disassembly. Polo-like kinases act by binding and phosphorylating proteins are that already phosphorylated on a specific motif recognized by the POLO box domains. Phosphorylates ATF2, BCL2L1, CDC25A, CDC25C, CHEK2, HIF1A, JUN, p53/TP53, p73/TP73, PTEN, TOP2A and VRK1. Involved in cell cycle regulation: required for entry into S phase and cytokinesis. Phosphorylates BCL2L1, leading to regulate the G2 checkpoint and progression to cytokinesis during mitosis. Plays a key role in response to stress: rapidly activated upon stress stimulation, such as ionizing radiation, reactive oxygen species (ROS), hyperosmotic stress, UV irradiation and hypoxia. Involved in DNA damage response and G1/S transition checkpoint by phosphorylating CDC25A, p53/TP53 and p73/TP73. Phosphorylates p53/TP53 in response to reactive oxygen species (ROS), thereby promoting p53/TP53-mediated apoptosis. Phosphorylates CHEK2 in response to DNA damage, promoting the G2/M transition checkpoint. Phosphorylates the transcription factor p73/TP73 in response to DNA damage, leading to inhibit p73/TP73-mediated transcriptional activation and pro-apoptotic functions. Phosphorylates HIF1A and JUN is response to hypoxia. Phosphorylates ATF2 following hyperosmotic stress in corneal epithelium. Also involved in Golgi disassembly during the cell cycle: part of a MEK1/MAP2K1-dependent pathway that induces Golgi fragmentation during mitosis by mediating phosphorylation of VRK1. May participate in endomitotic cell cycle, a form of mitosis in which both karyokinesis and cytokinesis are interrupted and is a hallmark of megakaryocyte differentiation, via its interaction with CIB1. {ECO:0000269|PubMed:10557092, ECO:0000269|PubMed:11156373, ECO:0000269|PubMed:11447225, ECO:0000269|PubMed:11551930, ECO:0000269|PubMed:11971976, ECO:0000269|PubMed:12242661, ECO:0000269|PubMed:14968113, ECO:0000269|PubMed:14980500, ECO:0000269|PubMed:15021912, ECO:0000269|PubMed:16478733, ECO:0000269|PubMed:16481012, ECO:0000269|PubMed:17264206, ECO:0000269|PubMed:17804415, ECO:0000269|PubMed:18062778, ECO:0000269|PubMed:18650425, ECO:0000269|PubMed:19103756, ECO:0000269|PubMed:19490146, ECO:0000269|PubMed:20889502, ECO:0000269|PubMed:20940307, ECO:0000269|PubMed:20951827, ECO:0000269|PubMed:21098032, ECO:0000269|PubMed:21264284, ECO:0000269|PubMed:21376736, ECO:0000269|PubMed:21840391, ECO:0000269|PubMed:9353331}.;

Recessive Scores

pRec
0.185

Intolerance Scores

LoFtool
0.834
RVIS EVS
-1.11
RVIS percentile EVS
6.78

Essentials

Essential (CRISPR)
N
Essential (CRISPR2)
N
Essential (gene trap)
N
Indispensability pred.
E
Indispensability score
0.990

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
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