PLK1
polo like kinase 1
Basic information
Region (hg38): 16:23677655-23690367
Previous symbols: [ "PLK" ]
Links
Phenotypes
GenCC
Source:
No genCC data.
ClinVar
This is a list of variants' phenotypes submitted to
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the PLK1 gene is commonly pathogenic or not.
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.
| Variant type | Pathogenic | Likely pathogenic | VUS | Likely benign | Benign | Sum |
|---|---|---|---|---|---|---|
| synonymous | 1 | |||||
| missense | 20 | 20 | ||||
| nonsense | 1 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| inframe indel | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| splice region | 0 | |||||
| non coding | 0 | |||||
| Total | 0 | 0 | 21 | 0 | 1 |
Variants in PLK1
This is a list of pathogenic ClinVar variants found in the PLK1 region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 16-23678942-G-T | not specified | Uncertain significance (Jul 27, 2022) | ||
| 16-23678994-G-T | not specified | Uncertain significance (Dec 19, 2022) | ||
| 16-23679039-C-T | not specified | Uncertain significance (May 30, 2023) | ||
| 16-23679060-T-C | Recurrent spontaneous abortion | Uncertain significance (Jan 27, 2020) | ||
| 16-23679207-C-G | not specified | Uncertain significance (Jun 17, 2024) | ||
| 16-23680095-G-A | Benign (Dec 31, 2019) | |||
| 16-23680949-G-T | not specified | Uncertain significance (Oct 12, 2022) | ||
| 16-23683878-C-A | not specified | Uncertain significance (Dec 14, 2023) | ||
| 16-23683888-G-A | not specified | Uncertain significance (Dec 01, 2022) | ||
| 16-23683939-A-G | not specified | Uncertain significance (Feb 23, 2023) | ||
| 16-23683990-C-A | not specified | Uncertain significance (May 30, 2023) | ||
| 16-23684033-T-C | not specified | Uncertain significance (Oct 18, 2021) | ||
| 16-23684045-G-A | not specified | Uncertain significance (Jun 23, 2021) | ||
| 16-23687523-G-A | not specified | Uncertain significance (Feb 14, 2023) | ||
| 16-23689283-C-G | Trichothiodystrophy | Uncertain significance (-) | ||
| 16-23689334-G-A | not specified | Uncertain significance (Jan 03, 2024) | ||
| 16-23689516-G-A | not specified | Uncertain significance (Apr 12, 2024) | ||
| 16-23689564-C-T | not specified | Uncertain significance (Sep 01, 2021) | ||
| 16-23689656-G-A | not specified | Uncertain significance (Dec 08, 2023) | ||
| 16-23689939-G-A | not specified | Uncertain significance (May 17, 2023) | ||
| 16-23689998-G-A | not specified | Uncertain significance (Nov 20, 2023) | ||
| 16-23690001-C-T | not specified | Uncertain significance (Jul 27, 2021) | ||
| 16-23690031-C-T | not specified | Uncertain significance (Oct 27, 2023) | ||
| 16-23690032-G-A | not specified | Uncertain significance (Jul 08, 2022) | ||
| 16-23690053-A-C | not specified | Uncertain significance (Aug 28, 2023) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| PLK1 | protein_coding | protein_coding | ENST00000300093 | 10 | 12712 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.979 | 0.0215 | 125739 | 0 | 8 | 125747 | 0.0000318 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 2.52 | 241 | 379 | 0.635 | 0.0000235 | 3929 |
| Missense in Polyphen | 45 | 128.65 | 0.3498 | 1407 | ||
| Synonymous | 0.128 | 151 | 153 | 0.987 | 0.00000940 | 1238 |
| Loss of Function | 4.08 | 3 | 25.0 | 0.120 | 0.00000129 | 291 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.0000289 | 0.0000289 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.0000544 | 0.0000544 |
| Finnish | 0.0000466 | 0.0000462 |
| European (Non-Finnish) | 0.0000353 | 0.0000352 |
| Middle Eastern | 0.0000544 | 0.0000544 |
| South Asian | 0.0000327 | 0.0000327 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Serine/threonine-protein kinase that performs several important functions throughout M phase of the cell cycle, including the regulation of centrosome maturation and spindle assembly, the removal of cohesins from chromosome arms, the inactivation of anaphase-promoting complex/cyclosome (APC/C) inhibitors, and the regulation of mitotic exit and cytokinesis. Polo-like kinase proteins acts by binding and phosphorylating proteins are that already phosphorylated on a specific motif recognized by the POLO box domains. Phosphorylates BORA, BUB1B/BUBR1, CCNB1, CDC25C, CEP55, ECT2, ERCC6L, FBXO5/EMI1, FOXM1, KIF20A/MKLP2, CENPU, NEDD1, NINL, NPM1, NUDC, PKMYT1/MYT1, KIZ, PPP1R12A/MYPT1, PRC1, RACGAP1/CYK4, SGO1, STAG2/SA2, TEX14, TOPORS, p73/TP73, TPT1, WEE1 and HNRNPU. Plays a key role in centrosome functions and the assembly of bipolar spindles by phosphorylating KIZ, NEDD1 and NINL. NEDD1 phosphorylation promotes subsequent targeting of the gamma-tubulin ring complex (gTuRC) to the centrosome, an important step for spindle formation. Phosphorylation of NINL component of the centrosome leads to NINL dissociation from other centrosomal proteins. Involved in mitosis exit and cytokinesis by phosphorylating CEP55, ECT2, KIF20A/MKLP2, CENPU, PRC1 and RACGAP1. Recruited at the central spindle by phosphorylating and docking PRC1 and KIF20A/MKLP2; creates its own docking sites on PRC1 and KIF20A/MKLP2 by mediating phosphorylation of sites subsequently recognized by the POLO box domains. Phosphorylates RACGAP1, thereby creating a docking site for the Rho GTP exchange factor ECT2 that is essential for the cleavage furrow formation. Promotes the central spindle recruitment of ECT2. Plays a central role in G2/M transition of mitotic cell cycle by phosphorylating CCNB1, CDC25C, FOXM1, CENPU, PKMYT1/MYT1, PPP1R12A/MYPT1 and WEE1. Part of a regulatory circuit that promotes the activation of CDK1 by phosphorylating the positive regulator CDC25C and inhibiting the negative regulators WEE1 and PKMYT1/MYT1. Also acts by mediating phosphorylation of cyclin-B1 (CCNB1) on centrosomes in prophase. Phosphorylates FOXM1, a key mitotic transcription regulator, leading to enhance FOXM1 transcriptional activity. Involved in kinetochore functions and sister chromatid cohesion by phosphorylating BUB1B/BUBR1, FBXO5/EMI1 and STAG2/SA2. PLK1 is high on non-attached kinetochores suggesting a role of PLK1 in kinetochore attachment or in spindle assembly checkpoint (SAC) regulation. Required for kinetochore localization of BUB1B. Regulates the dissociation of cohesin from chromosomes by phosphorylating cohesin subunits such as STAG2/SA2. Phosphorylates SGO1: required for spindle pole localization of isoform 3 of SGO1 and plays a role in regulating its centriole cohesion function. Mediates phosphorylation of FBXO5/EMI1, a negative regulator of the APC/C complex during prophase, leading to FBXO5/EMI1 ubiquitination and degradation by the proteasome. Acts as a negative regulator of p53 family members: phosphorylates TOPORS, leading to inhibit the sumoylation of p53/TP53 and simultaneously enhance the ubiquitination and subsequent degradation of p53/TP53. Phosphorylates the transactivation domain of the transcription factor p73/TP73, leading to inhibit p73/TP73-mediated transcriptional activation and pro-apoptotic functions. Phosphorylates BORA, and thereby promotes the degradation of BORA. Contributes to the regulation of AURKA function. Also required for recovery after DNA damage checkpoint and entry into mitosis. Phosphorylates MISP, leading to stabilization of cortical and astral microtubule attachments required for proper spindle positioning (PubMed:8991084, PubMed:11202906, PubMed:12207013, PubMed:12447691, PubMed:12524548, PubMed:12738781, PubMed:12852856, PubMed:12939256, PubMed:14532005, PubMed:14734534, PubMed:15070733, PubMed:15148369, PubMed:15469984, PubMed:16198290, PubMed:16247472, PubMed:16980960, PubMed:17081991, PubMed:17351640, PubMed:17376779, PubMed:17617734, PubMed:18174154, PubMed:18331714, PubMed:18418051, PubMed:18477460, PubMed:18521620, PubMed:18615013, PubMed:19160488, PubMed:19351716, PubMed:19468300, PubMed:19468302, PubMed:19473992, PubMed:19509060, PubMed:19597481, PubMed:23455478, PubMed:23509069). Together with MEIKIN, acts as a regulator of kinetochore function during meiosis I: required both for mono-orientation of kinetochores on sister chromosomes and protection of centromeric cohesin from separase-mediated cleavage (By similarity). Phosphorylates CEP68 and is required for its degradation (PubMed:25503564). Regulates nuclear envelope breakdown during prophase by phosphorylating DCTN1 resulting in its localization in the nuclear envelope (PubMed:20679239). Phosphorylates the heat shock transcription factor HSF1, promoting HSF1 nuclear translocation upon heat shock (PubMed:15661742). Phosphorylates HSF1 also in the early mitotic period; this phosphorylation regulates HSF1 localization to the spindle pole, the recruitment of the SCF(BTRC) ubiquitin ligase complex induicing HSF1 degradation, and hence mitotic progression (PubMed:18794143). Regulates mitotic progression by phosphorylating RIOK2 (PubMed:21880710). {ECO:0000250|UniProtKB:Q5F2C3, ECO:0000269|PubMed:11202906, ECO:0000269|PubMed:12207013, ECO:0000269|PubMed:12447691, ECO:0000269|PubMed:12524548, ECO:0000269|PubMed:12738781, ECO:0000269|PubMed:12852856, ECO:0000269|PubMed:12939256, ECO:0000269|PubMed:14532005, ECO:0000269|PubMed:14734534, ECO:0000269|PubMed:15070733, ECO:0000269|PubMed:15148369, ECO:0000269|PubMed:15469984, ECO:0000269|PubMed:15661742, ECO:0000269|PubMed:16198290, ECO:0000269|PubMed:16247472, ECO:0000269|PubMed:16980960, ECO:0000269|PubMed:17081991, ECO:0000269|PubMed:17351640, ECO:0000269|PubMed:17376779, ECO:0000269|PubMed:17617734, ECO:0000269|PubMed:18174154, ECO:0000269|PubMed:18331714, ECO:0000269|PubMed:18418051, ECO:0000269|PubMed:18477460, ECO:0000269|PubMed:18521620, ECO:0000269|PubMed:18615013, ECO:0000269|PubMed:18794143, ECO:0000269|PubMed:19160488, ECO:0000269|PubMed:19351716, ECO:0000269|PubMed:19468300, ECO:0000269|PubMed:19468302, ECO:0000269|PubMed:19473992, ECO:0000269|PubMed:19509060, ECO:0000269|PubMed:19597481, ECO:0000269|PubMed:20679239, ECO:0000269|PubMed:21880710, ECO:0000269|PubMed:23455478, ECO:0000269|PubMed:23509069, ECO:0000269|PubMed:25503564, ECO:0000269|PubMed:25986610, ECO:0000269|PubMed:8991084}.;
- Disease
- DISEASE: Note=Defects in PLK1 are associated with some cancers, such as gastric, thyroid or B-cell lymphomas. Expression is cancer increased in tumor tissues with a poor prognosis, suggesting a role in malignant transformations and carcinogenesis.;
- Pathway
- Cell cycle - Homo sapiens (human);Oocyte meiosis - Homo sapiens (human);FoxO signaling pathway - Homo sapiens (human);Progesterone-mediated oocyte maturation - Homo sapiens (human);Cell Cycle;Regulation of toll-like receptor signaling pathway;Integrated Cancer Pathway;miR-targeted genes in epithelium - TarBase;miR-targeted genes in lymphocytes - TarBase;miR-targeted genes in muscle cell - TarBase;Mitotic G2-G2-M phases;Androgen Receptor Network in Prostate Cancer;TNF alpha Signaling Pathway;Signal Transduction;Polo-like kinase mediated events;Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal;Amplification of signal from the kinetochores;Mitotic Spindle Checkpoint;Cell Cycle Checkpoints;p73 transcription factor network;RHO GTPases Activate Formins;Cyclin A/B1/B2 associated events during G2/M transition;IL-7 signaling;RHO GTPase Effectors;Signaling by Rho GTPases;Regulation of PLK1 Activity at G2/M Transition;Golgi Cisternae Pericentriolar Stack Reorganization;Recruitment of mitotic centrosome proteins and complexes;Loss of Nlp from mitotic centrosomes;Loss of proteins required for interphase microtubule organization from the centrosome;Centrosome maturation;The role of GTSE1 in G2/M progression after G2 checkpoint;Validated transcriptional targets of TAp63 isoforms;AURKA Activation by TPX2;G2/M Transition;Mitotic G2-G2/M phases;JAK STAT pathway and regulation;Condensation of Prophase Chromosomes;Activation of NIMA Kinases NEK9, NEK6, NEK7;EPO signaling;Nuclear Envelope Breakdown;Mitotic Prophase;Recruitment of NuMA to mitotic centrosomes;Mitotic Prometaphase;Mitotic Metaphase/Anaphase Transition;Separation of Sister Chromatids;Mitotic Anaphase;Mitotic Metaphase and Anaphase;Mitotic Telophase/Cytokinesis;M Phase;Phosphorylation of Emi1;Regulation of APC/C activators between G1/S and early anaphase;Phosphorylation of the APC/C;Activation of APC/C and APC/C:Cdc20 mediated degradation of mitotic proteins;APC/C:Cdh1 mediated degradation of Cdc20 and other APC/C:Cdh1 targeted proteins in late mitosis/early G1;APC/C-mediated degradation of cell cycle proteins;Regulation of mitotic cell cycle;Cell Cycle;Resolution of Sister Chromatid Cohesion;VEGF;Cell Cycle, Mitotic;Anchoring of the basal body to the plasma membrane;PLK1 signaling events;FOXM1 transcription factor network;FoxO family signaling;ATR signaling pathway;Optineurin and Myosin Phosphatase Negatively Regulate PLK1;Cilium Assembly;Organelle biogenesis and maintenance
(Consensus)
Recessive Scores
- pRec
- 0.635
Intolerance Scores
- loftool
- 0.215
- rvis_EVS
- -0.29
- rvis_percentile_EVS
- 33.34
Haploinsufficiency Scores
- pHI
- 0.997
- hipred
- Y
- hipred_score
- 0.825
- ghis
- 0.654
Essentials
- essential_gene_CRISPR
- E
- essential_gene_CRISPR2
- E
- essential_gene_gene_trap
- E
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.991
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Plk1
- Phenotype
- cellular phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); embryo phenotype; neoplasm;
Zebrafish Information Network
- Gene name
- plk1
- Affected structure
- neuron
- Phenotype tag
- abnormal
- Phenotype quality
- decreased amount
Gene ontology
- Biological process
- mitotic sister chromatid segregation;G2/M transition of mitotic cell cycle;negative regulation of transcription by RNA polymerase II;mitotic cell cycle;mitotic cytokinesis;microtubule bundle formation;protein phosphorylation;sister chromatid cohesion;mitotic nuclear envelope disassembly;mitotic spindle assembly checkpoint;centrosome cycle;regulation of mitotic cell cycle;cell population proliferation;regulation of G2/M transition of mitotic cell cycle;positive regulation of peptidyl-threonine phosphorylation;female meiosis chromosome segregation;protein ubiquitination;peptidyl-serine phosphorylation;regulation of mitotic metaphase/anaphase transition;anaphase-promoting complex-dependent catabolic process;protein destabilization;positive regulation of proteasomal ubiquitin-dependent protein catabolic process;regulation of cytokinesis;negative regulation of apoptotic process;regulation of protein binding;homologous chromosome segregation;establishment of protein localization;negative regulation of cyclin-dependent protein serine/threonine kinase activity;positive regulation of proteolysis;nuclear envelope disassembly;positive regulation of ubiquitin-protein transferase activity;regulation of cell cycle;synaptonemal complex disassembly;protein localization to chromatin;signal transduction involved in G2 DNA damage checkpoint;protein localization to nuclear envelope;ciliary basal body-plasma membrane docking;positive regulation of protein localization to nucleus;regulation of mitotic spindle assembly;regulation of mitotic cell cycle phase transition;regulation of cell cycle G2/M phase transition;positive regulation of ubiquitin protein ligase activity
- Cellular component
- kinetochore;chromatin;synaptonemal complex;spindle pole;condensed nuclear chromosome outer kinetochore;nucleus;nucleoplasm;centrosome;centriole;spindle;cytosol;spindle microtubule;microtubule cytoskeleton;midbody;centriolar satellite;spindle midzone
- Molecular function
- magnesium ion binding;protein kinase activity;protein serine/threonine kinase activity;protein binding;ATP binding;microtubule binding;anaphase-promoting complex binding;kinase activity;protein kinase binding;identical protein binding