PLK5

Summary

PLK5 (polo like kinase 5 (inactive), HGNC:27001) is a protein-coding gene on chromosome 19p13.3, encoding Inactive serine/threonine-protein kinase PLK5 (Q496M5). Inactive serine/threonine-protein kinase that plays a role in cell cycle progression and neuronal differentiation.

Predicted to enable ATP binding activity and protein kinase activity. Involved in several processes, including defense response to tumor cell; positive regulation of neuron projection development; and regulation of G1/S transition of mitotic cell cycle. Located in cytoplasm.

Source: NCBI Gene 126520 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 12 total
• MANE Select transcript: NM_001243079

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:27001
Approved symbol	PLK5
Name	polo like kinase 5 (inactive)
Location	19p13.3
Locus type	gene with protein product
Status	Approved
Aliases	SgK384ps
Ensembl gene	ENSG00000185988
Ensembl biotype	protein_coding
OMIM	621048
Entrez	126520

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 8 protein_coding, 2 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000334770, ENST00000454744, ENST00000588292, ENST00000588430, ENST00000642079, ENST00000673648, ENST00000673674, ENST00000673796, ENST00000673829, ENST00000673896, ENST00000957735

RefSeq mRNA: 1 — MANE Select: NM_001243079 NM_001243079

CCDS: CCDS59328

Canonical transcript exons

ENST00000454744 — 14 exons

Exon	Start	End
ENSE00001337873	1533931	1534041
ENSE00001337876	1531738	1531883
ENSE00001337877	1529747	1529824
ENSE00001337878	1529406	1529490
ENSE00001337882	1528302	1528428
ENSE00001337887	1527936	1528134
ENSE00001417366	1526704	1526791
ENSE00001427880	1525595	1525711
ENSE00001430056	1526486	1526615
ENSE00001433227	1526903	1526998
ENSE00001620858	1535065	1536046
ENSE00001693446	1525305	1525418
ENSE00002958435	1528898	1528974
ENSE00003811731	1524077	1524246

Expression profiles

Bgee: expression breadth ubiquitous, 141 present calls, max score 93.69.

FANTOM5 (CAGE): breadth broad, TPM avg 2.1938 / max 782.2929, expressed in 292 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
172991	1.7158	152
172990	0.4780	194

Top tissues by expression

242 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
right hemisphere of cerebellum	UBERON:0014890	93.69	gold quality
cerebellar hemisphere	UBERON:0002245	93.39	gold quality
cerebellar cortex	UBERON:0002129	93.12	gold quality
cerebellum	UBERON:0002037	90.68	gold quality
endocervix	UBERON:0000458	80.67	gold quality
left testis	UBERON:0004533	78.83	gold quality
right testis	UBERON:0004534	77.14	gold quality
right frontal lobe	UBERON:0002810	76.58	gold quality
ectocervix	UBERON:0012249	76.39	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	75.44	silver quality
amygdala	UBERON:0001876	75.41	gold quality
testis	UBERON:0000473	75.13	gold quality
caudate nucleus	UBERON:0001873	74.90	gold quality
putamen	UBERON:0001874	74.62	gold quality
Brodmann (1909) area 9	UBERON:0013540	74.20	gold quality
stromal cell of endometrium	CL:0002255	72.64	gold quality
anterior cingulate cortex	UBERON:0009835	72.57	gold quality
uterine cervix	UBERON:0000002	71.87	gold quality
nucleus accumbens	UBERON:0001882	70.58	gold quality
body of uterus	UBERON:0009853	70.30	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	69.25	gold quality
hypothalamus	UBERON:0001898	67.66	gold quality
brain	UBERON:0000955	67.13	gold quality
prefrontal cortex	UBERON:0000451	66.95	gold quality
cortical plate	UBERON:0005343	66.93	gold quality
vagina	UBERON:0000996	66.87	gold quality
neocortex	UBERON:0001950	66.27	gold quality
frontal cortex	UBERON:0001870	65.38	gold quality
forebrain	UBERON:0001890	64.95	gold quality
left uterine tube	UBERON:0001303	64.75	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	2.62

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

6 targeting PLK5, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-511-5P	98.97	70.94	2268
HSA-MIR-7977	98.65	66.18	2590
HSA-MIR-31-5P	98.58	68.35	1239
HSA-MIR-6827-5P	98.46	64.88	1256

Literature-anchored findings (GeneRIF, showing 2)

• The human polo-like kinase 5 gene is significantly silenced in astrocytoma and glioblastoma multiforme by promoter hypermethylation, suggesting a tumor suppressor function for this gene. (PMID:21245385)
• we report a three-nucleotide deletion near the C-region of Plk5 that is specifically associated with the lymphatic metastasis in patients with clear cell renal cell carcinoma (PMID:26908440)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Plk5	ENSMUSG00000035486
rattus_norvegicus	Plk5	ENSRNOG00000034102

Paralogs (4): PLK4 (ENSG00000142731), PLK2 (ENSG00000145632), PLK1 (ENSG00000166851), PLK3 (ENSG00000173846)

Protein

Protein identifiers

Inactive serine/threonine-protein kinase PLK5 — Q496M5 (reviewed: Q496M5)

Alternative names: Polo-like kinase 5

All UniProt accessions (3): A0A286YFL1, A0A669KBC1, Q496M5

UniProt curated annotations — full annotation on UniProt →

Function. Inactive serine/threonine-protein kinase that plays a role in cell cycle progression and neuronal differentiation.

Subcellular location. Nucleus. Nucleolus. Cytoplasm.

Tissue specificity. Expressed in the brain, neurons and glial cells. Also expressed in highly differentiated cells, such as the serous acini in the parotid gland, distal and proximal tubules of the kidney, tubules of the seminal gland, Kupffer cells and some hepatocytes in the liver, and some cells in the germinal center of lymph nodes (at protein level).

Domain organisation. The truncated protein kinase domain is predicted to be catalytically inactive; has lost the main activatory autophosphorylation site and the conserved key residues involved in phospho-substrate. The C-terminal region (containing the POLO box domain) is sufficient for inducing cell cycle arrest.

Induction. Down-regulated in primary brain tumors.

Similarity. Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. CDC5/Polo subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
Q496M5-1	1	yes
Q496M5-2	2

RefSeq proteins (1): NP_001230008* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000719	Prot_kinase_dom	Domain
IPR000959	POLO_box_dom	Domain
IPR011009	Kinase-like_dom_sf	Homologous_superfamily
IPR033701	POLO_box_1	Domain
IPR036947	POLO_box_dom_sf	Homologous_superfamily

UniProt features (9 total): sequence conflict 3, domain 2, region of interest 2, chain 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q496M5-F1	68.93	0.24

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 82 (showing top): GOBP_CELL_CYCLE_PHASE_TRANSITION, GOBP_NEUROGENESIS, GOCC_MICROTUBULE_ORGANIZING_CENTER, GOBP_REGULATION_OF_CELL_PROJECTION_ORGANIZATION, GOBP_REGULATION_OF_CELL_CYCLE, GOBP_REGULATION_OF_CELL_CYCLE_G1_S_PHASE_TRANSITION, GOCC_CENTROSOME, GOBP_CELL_CYCLE_G1_S_PHASE_TRANSITION, GOBP_DNA_DAMAGE_RESPONSE, GOBP_MITOTIC_CELL_CYCLE, GOBP_REGULATION_OF_NEURON_PROJECTION_DEVELOPMENT, GOBP_RESPONSE_TO_GROWTH_FACTOR, GOBP_CELL_PROJECTION_ORGANIZATION, GOBP_REGULATION_OF_CELL_CYCLE_PHASE_TRANSITION, GOBP_REGULATION_OF_CELL_CYCLE_PROCESS

GO Biological Process (11): defense response to tumor cell (GO:0002357), DNA damage response (GO:0006974), mitotic spindle organization (GO:0007052), positive regulation of neuron projection development (GO:0010976), cell differentiation (GO:0030154), regulation of apoptotic process (GO:0042981), cell division (GO:0051301), cellular response to growth factor stimulus (GO:0071363), regulation of G1/S transition of mitotic cell cycle (GO:2000045), protein phosphorylation (GO:0006468), regulation of cell cycle process (GO:0010564)

GO Molecular Function (3): protein kinase activity (GO:0004672), ATP binding (GO:0005524), protein binding (GO:0005515)

GO Cellular Component (6): kinetochore (GO:0000776), spindle pole (GO:0000922), nucleus (GO:0005634), nucleolus (GO:0005730), cytoplasm (GO:0005737), centrosome (GO:0005813)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
intracellular membraneless organelle	2
cellular anatomical structure	2
response to tumor cell	1
defense response	1
cellular response to stress	1
mitotic cell cycle	1
spindle organization	1
microtubule cytoskeleton organization involved in mitosis	1
regulation of neuron projection development	1
neuron projection development	1
positive regulation of cell projection organization	1
cellular developmental process	1
apoptotic process	1
regulation of programmed cell death	1
cellular process	1
response to growth factor	1
cellular response to endogenous stimulus	1
G1/S transition of mitotic cell cycle	1
regulation of mitotic cell cycle phase transition	1
regulation of cell cycle G1/S phase transition	1
phosphorylation	1
protein modification process	1
cell cycle process	1
regulation of cell cycle	1
kinase activity	1
phosphotransferase activity, alcohol group as acceptor	1
catalytic activity, acting on a protein	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
binding	1
condensed chromosome, centromeric region	1
supramolecular complex	1
spindle	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
intracellular anatomical structure	1
centriole	1
microtubule organizing center	1

Protein interactions and networks

STRING

2610 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PLK5	PLK4	O00444	739
PLK5	CDC5L	Q99459	568
PLK5	HIGD2B	Q4VC39	455
PLK5	DRICH1	Q6PGQ1	423
PLK5	C16orf89	Q6UX73	406
PLK5	EPHB1	P54762	389
PLK5	GLRA3	O75311	364
PLK5	TOPORS	Q9NS56	363
PLK5	CDC25C	P30307	360
PLK5	STATH	P02808	349
PLK5	HTN3	P15516	349
PLK5	AURKB	Q96GD4	338
PLK5	C19orf25	Q9UFG5	336
PLK5	CENPU	Q71F23	331
PLK5	ESPL1	Q14674	316

IntAct

1 interactions, top by confidence:

A	B	Type	Score
PLK5	USP7	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (1): PLK5 (Protein-peptide)

ESM2 similar proteins: A2APT9, A5PJC7, A5PKB7, D7PDD4, O08672, O94761, O94989, P33076, P51617, P79621, Q16671, Q2LGB3, Q3T0Y9, Q496M5, Q49LS3, Q53GL7, Q5FVN6, Q5FWH6, Q5R866, Q5R8H1, Q5RA67, Q5VTJ3, Q60837, Q6P9H5, Q6UX68, Q75NR7, Q7Z6P3, Q86UT6, Q8BTN6, Q8BWA8, Q8BWF2, Q8CIE4, Q8IUD6, Q8IW93, Q8IYJ3, Q8K349, Q8K3L6, Q8K558, Q8NAG6, Q8R2S1

Diamond homologs: O65554, P52497, P53350, P62205, P70032, P92958, Q07832, Q10LQ2, Q2QY53, Q2RAX3, Q2TA25, Q496M5, Q4FZD7, Q5JLD8, Q60806, Q60EY8, Q62673, Q6ERS4, Q6X4A2, Q6Z9F4, Q6ZLP5, Q7X996, Q7ZVS3, Q8C0N0, Q8LIG4, Q8S9D1, Q8SWM6, Q93VD3, Q9H4B4, Q9LWM4, Q9MAM1, Q9N2L7, Q9R011, A0A8I3S724, A2VDZ4, A3B529, A5GFW1, A7SNN5, B0WAU8, B1WAS2

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

12 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	1
Likely benign	1
Benign	5

Top pathogenic / likely-pathogenic (0)

SpliceAI

4412 predictions. Top by Δscore:

Variant	Effect	Δscore
19:1508441:A:AC	donor_gain	1.0000
19:1508442:C:CC	donor_gain	1.0000
19:1508442:CAAGG:C	donor_gain	1.0000
19:1508468:C:CA	donor_gain	1.0000
19:1510144:ACT:A	donor_loss	1.0000
19:1510145:CTC:C	donor_loss	1.0000
19:1510146:TCACC:T	donor_loss	1.0000
19:1510147:C:CG	donor_loss	1.0000
19:1510148:A:T	donor_loss	1.0000
19:1510148:AC:A	donor_gain	1.0000
19:1510148:ACC:A	donor_gain	1.0000
19:1510148:ACCC:A	donor_gain	1.0000
19:1510148:ACCCC:A	donor_gain	1.0000
19:1510149:C:CT	donor_loss	1.0000
19:1510149:CC:C	donor_gain	1.0000
19:1510149:CCC:C	donor_gain	1.0000
19:1510149:CCCC:C	donor_gain	1.0000
19:1510149:CCCCC:C	donor_gain	1.0000
19:1510168:A:AC	donor_gain	1.0000
19:1510169:C:CC	donor_gain	1.0000
19:1510366:A:AC	donor_gain	1.0000
19:1510367:C:CC	donor_gain	1.0000
19:1510729:CCCTA:C	acceptor_gain	1.0000
19:1510730:CCTAC:C	acceptor_gain	1.0000
19:1510731:CTA:C	acceptor_gain	1.0000
19:1512958:CTTA:C	donor_loss	1.0000
19:1512960:TA:T	donor_loss	1.0000
19:1512962:CCGG:C	donor_gain	1.0000
19:1525300:CACA:C	acceptor_loss	1.0000
19:1525303:A:AG	acceptor_gain	1.0000

AlphaMissense

2149 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:1527964:T:C	F11L	0.976
19:1527966:C:A	F11L	0.976
19:1527966:C:G	F11L	0.976
19:1528123:T:C	F64L	0.966
19:1528125:C:A	F64L	0.966
19:1528125:C:G	F64L	0.966
19:1528305:T:C	F69L	0.962
19:1528307:C:A	F69L	0.962
19:1528307:C:G	F69L	0.962
19:1527937:T:G	Y2D	0.942
19:1527938:A:C	Y2S	0.929
19:1531815:T:C	F216L	0.917
19:1531817:T:A	F216L	0.917
19:1531817:T:G	F216L	0.917
19:1528001:T:C	I23T	0.913
19:1528126:T:C	F65L	0.905
19:1528128:C:A	F65L	0.905
19:1528128:C:G	F65L	0.905
19:1528127:T:C	F65S	0.901
19:1533988:T:C	F258L	0.897
19:1533990:C:A	F258L	0.897
19:1533990:C:G	F258L	0.897
19:1528058:T:A	I42N	0.896
19:1527937:T:C	Y2H	0.895
19:1528124:T:C	F64S	0.890
19:1527965:T:C	F11S	0.886
19:1528015:T:G	Y28D	0.886
19:1527938:A:G	Y2C	0.884
19:1527965:T:G	F11C	0.869
19:1527953:G:T	G7V	0.865

dbSNP variants (sampled 300 via entrez): RS1000179276 (19:1531020 G>A,C), RS1000182542 (19:1528844 C>A,G,T), RS1000276567 (19:1535055 C>A,T), RS1000366546 (19:1533280 G>A), RS1000383397 (19:1534664 A>G), RS1000440052 (19:1533384 C>A,T), RS1001242589 (19:1529814 A>C), RS1001313289 (19:1533584 G>A,C,T), RS1001460206 (19:1522209 C>T), RS1001528404 (19:1523462 A>G), RS1001550948 (19:1525216 C>A,T), RS1001581970 (19:1525386 G>A,C), RS1001589114 (19:1529947 C>T), RS1001646072 (19:1526066 T>C), RS1002161705 (19:1529189 A>G)

Disease associations

OMIM: gene MIM:621048 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

8 total (human), top 8 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases methylation	1
sodium arsenite	increases expression	1
licochalcone B	increases expression	1
Arsenic	decreases expression	1
Benzo(a)pyrene	increases methylation	1
Dichlorodiphenyl Dichloroethylene	decreases expression	1
Valproic Acid	increases methylation	1
Cadmium Chloride	decreases expression	1

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.