PLK4

polo like kinase 4

Basic information

Region (hg38): 4:127880892-127899224

Previous symbols: [ "STK18" ]

Links

ENSG00000142731 ∙ NCBI:10733 ∙ OMIM:605031 ∙ HGNC:11397 ∙ Uniprot:O00444 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• microcephaly and chorioretinopathy 2 (Definitive), mode of inheritance: AR
• microcephaly and chorioretinopathy 2 (Strong), mode of inheritance: AR
• Seckel syndrome (Supportive), mode of inheritance: AR
• microcephaly and chorioretinopathy 1 (Supportive), mode of inheritance: AR
• microcephaly and chorioretinopathy 2 (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Microcephaly and chorioretinopathy, autosomal recessive 2	AR	General	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	Musculoskeletal; Neurologic; Ophthalmologic	25320347; 25344692

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PLK4 gene.

• not provided (516 variants)
• Inborn genetic diseases (43 variants)
• Microcephaly and chorioretinopathy 2 (11 variants)
• not specified (11 variants)
• PLK4-related microcephaly and growth failure with or without ocular features (2 variants)
• PLK4-related condition (1 variants)
• See cases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PLK4 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			4	89	8	101
missense			274	8	5	287
nonsense	4	1				5
start loss						0
frameshift	11	1	1			13
inframe indel			5			5
splice donor/acceptor (+/-2bp)		5		1	1	7
splice region			16	11	2	29
non coding			4	58	16	78
Total	15	7	288	156	30

Highest pathogenic variant AF is 0.0000132

Variants in PLK4

This is a list of pathogenic ClinVar variants found in the PLK4 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
4-127881139-C-T			Uncertain significance (Nov 22, 2022)
4-127881142-C-T			Uncertain significance (Jul 05, 2022)
4-127881143-C-G			Likely benign (Aug 04, 2023)
4-127881143-C-T		PLK4-related disorder	Likely benign (Mar 01, 2024)
4-127881144-T-A			Uncertain significance (Nov 28, 2022)
4-127881145-G-A			Uncertain significance (Nov 06, 2023)
4-127881145-G-C			Uncertain significance (Mar 10, 2022)
4-127881147-A-G		Inborn genetic diseases	Uncertain significance (Sep 13, 2023)
4-127881151-G-A		not specified • Inborn genetic diseases	Conflicting classifications of pathogenicity (Jan 19, 2024)
4-127881169-A-G			Uncertain significance (Aug 04, 2023)
4-127881173-A-G			Likely benign (Jan 25, 2024)
4-127881180-A-C			Likely benign (Oct 24, 2023)
4-127881183-C-G			Likely benign (Sep 17, 2022)
4-127881821-A-G			Likely benign (Sep 27, 2022)
4-127881823-C-T			Likely benign (Aug 17, 2023)
4-127881824-T-G			Uncertain significance (May 11, 2021)
4-127881835-T-A		Inborn genetic diseases	Uncertain significance (Aug 23, 2022)
4-127881837-A-T			Pathogenic (Jul 19, 2023)
4-127881852-C-A			Uncertain significance (Aug 02, 2022)
4-127881852-C-T			Uncertain significance (Nov 20, 2021)
4-127881857-TA-T			Pathogenic (Dec 22, 2023)
4-127881859-A-G			Uncertain significance (May 30, 2022)
4-127881860-AG-A			Pathogenic (Jul 12, 2022)
4-127881862-G-T			Uncertain significance (Oct 07, 2021)
4-127881866-A-G			Likely benign (Mar 10, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PLK4	protein_coding	protein_coding	ENST00000270861	16	18335

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00000708	1.00	125691	0	56	125747	0.000223

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.800	447	497	0.899	0.0000236	6395
Missense in Polyphen		130	198.85	0.65376		2555
Synonymous	-1.31	187	166	1.13	0.00000770	1805
Loss of Function	3.85	17	44.8	0.379	0.00000235	585

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000819	0.000712
Ashkenazi Jewish	0.000472	0.000298
East Asian	0.000180	0.000163
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.000208	0.000202
Middle Eastern	0.000180	0.000163
South Asian	0.000312	0.000294
Other	0.000326	0.000326

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Serine/threonine-protein kinase that plays a central role in centriole duplication. Able to trigger procentriole formation on the surface of the parental centriole cylinder, leading to the recruitment of centriole biogenesis proteins such as SASS6, CENPJ/CPAP, CCP110, CEP135 and gamma-tubulin. When overexpressed, it is able to induce centrosome amplification through the simultaneous generation of multiple procentrioles adjoining each parental centriole during S phase. Phosphorylates 'Ser-151' of FBXW5 during the G1/S transition, leading to inhibit FBXW5 ability to ubiquitinate SASS6. Its central role in centriole replication suggests a possible role in tumorigenesis, centrosome aberrations being frequently observed in tumors. Also involved in deuterosome-mediated centriole amplification in multiciliated that can generate more than 100 centrioles. Also involved in trophoblast differentiation by phosphorylating HAND1, leading to disrupt the interaction between HAND1 and MDFIC and activate HAND1. Phosphorylates CDC25C and CHEK2. Required for the recruitment of STIL to the centriole and for STIL-mediated centriole amplification (PubMed:22020124). {ECO:0000269|PubMed:16244668, ECO:0000269|PubMed:16326102, ECO:0000269|PubMed:17681131, ECO:0000269|PubMed:18239451, ECO:0000269|PubMed:19164942, ECO:0000269|PubMed:21725316, ECO:0000269|PubMed:22020124, ECO:0000269|PubMed:27796307}.
• Disease: DISEASE: Microcephaly and chorioretinopathy, autosomal recessive, 2 (MCCRP2) [MIM:616171]: A severe disorder characterized by microcephaly, delayed psychomotor development, growth retardation with dwarfism, and ocular abnormalities. {ECO:0000269|PubMed:25344692}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: FoxO signaling pathway - Homo sapiens (human);Retinoblastoma (RB) in Cancer;Regulation of PLK1 Activity at G2/M Transition;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;AURKA Activation by TPX2;G2/M Transition;Mitotic G2-G2/M phases;Recruitment of NuMA to mitotic centrosomes;Mitotic Prometaphase;M Phase;Cell Cycle;Cell Cycle, Mitotic;Anchoring of the basal body to the plasma membrane;Cilium Assembly;Organelle biogenesis and maintenance (Consensus)

Recessive Scores

• pRec: 0.246

Intolerance Scores

• loftool: 0.831
• rvis_EVS: -0.31
• rvis_percentile_EVS: 32.23

Haploinsufficiency Scores

• pHI: 0.542
• hipred: Y
• hipred_score: 0.704
• ghis: 0.667

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.970

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Plk4
• Phenotype: cellular phenotype; homeostasis/metabolism phenotype; endocrine/exocrine gland 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); reproductive system phenotype; growth/size/body region phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); embryo phenotype

Zebrafish Information Network

• Gene name: plk4
• Affected structure: photoreceptor cell
• Phenotype tag: abnormal
• Phenotype quality: absent

Gene ontology

• Biological process: G2/M transition of mitotic cell cycle;protein phosphorylation;centriole replication;regulation of G2/M transition of mitotic cell cycle;positive regulation of centriole replication;trophoblast giant cell differentiation;ciliary basal body-plasma membrane docking;de novo centriole assembly involved in multi-ciliated epithelial cell differentiation
• Cellular component: XY body;nucleolus;centrosome;centriole;cytosol;cleavage furrow;deuterosome
• Molecular function: protein serine/threonine kinase activity;protein binding;ATP binding;identical protein binding