PLK4

Summary

PLK4 (polo like kinase 4, HGNC:11397) is a protein-coding gene on chromosome 4q28.1, encoding Serine/threonine-protein kinase PLK4 (O00444). Serine/threonine-protein kinase that plays a central role in centriole duplication. It is a common-essential gene (DepMap: required in 95.4% of cancer cell lines).

This gene encodes a member of the polo family of serine/threonine protein kinases. The protein localizes to centrioles, complex microtubule-based structures found in centrosomes, and regulates centriole duplication during the cell cycle. Three alternatively spliced transcript variants that encode different protein isoforms have been found for this gene.

Source: NCBI Gene 10733 — RefSeq curated summary.

At a glance

• Gene–disease (curated): microcephaly and chorioretinopathy 2 (Definitive, GenCC) — +2 more curated relationships
• Clinical variants (ClinVar): 722 total — 21 pathogenic, 13 likely-pathogenic (top 4% of genes corpus-wide)
• GTEx eGene: eQTL in 5 tissues, sQTL in 0 (q < 0.05)
• Phenotypes (HPO): 66
• Drug target: yes — 3 curated mechanism-of-action drugs; 65 molecules with ChEMBL bioactivity (top 1% of genes corpus-wide)
• Cancer dependency (DepMap): dependent in 95.4% of screened cell lines (common-essential)
• Constraint (gnomAD): pLI 0.18 (intermediate), LOEUF 0.62 (unconstrained)
• MANE Select transcript: NM_014264
• Interaction hub: 2,169 STRING partners (top 6% of genes corpus-wide)

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11397
Approved symbol	PLK4
Name	polo like kinase 4
Location	4q28.1
Locus type	gene with protein product
Status	Approved
Aliases	Sak
Ensembl gene	ENSG00000142731
Ensembl biotype	protein_coding
OMIM	605031
Entrez	10733

Gene structure

Transcript identifiers

Ensembl transcripts: 17 — 10 protein_coding, 4 retained_intron, 2 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

MANE Select: ENST00000270861

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 1, TSL 2: 5, TSL 3: 2, TSL 4: 1, TSL 5: 2

ENST00000270861, ENST00000503914, ENST00000507249, ENST00000507454, ENST00000508113, ENST00000510192, ENST00000510605, ENST00000511942, ENST00000513090, ENST00000514379, ENST00000515069, ENST00000852980, ENST00001083692, ENST00001083693, ENST00001115916, ENST00001129379, ENST00001134494

RefSeq mRNA: 14 — MANE Select: NM_014264 NM_001190799, NM_001190801, NM_001441357, NM_001441358, NM_001441359, NM_001441360, NM_001441361, NM_001441362, NM_001441366, NM_001441367, NM_001441368, NM_001441369, NM_001441371, NM_014264

CCDS: CCDS3735, CCDS54803, CCDS54804

Canonical transcript exons

ENST00000270861 — 16 exons

Exon	Start	End
ENSE00000956077	127883262	127883357
ENSE00000956078	127883439	127883553
ENSE00000956079	127885708	127886728
ENSE00000956080	127887396	127887496
ENSE00000956082	127891092	127891196
ENSE00000956084	127892365	127892514
ENSE00000956085	127893285	127893418
ENSE00001280184	127898439	127899224
ENSE00002068636	127880893	127881164
ENSE00003483918	127893734	127893881
ENSE00003518610	127893513	127893604
ENSE00003599372	127891579	127891681
ENSE00003608012	127896801	127896907
ENSE00003630062	127894953	127895093
ENSE00003656252	127881831	127881926
ENSE00003668667	127889866	127890236

Expression profiles

Bgee: expression breadth ubiquitous, 201 present calls, max score 96.71.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 6.7695 / max 133.3829, expressed in 1309 samples.

Highest expression (Bgee): ventricular zone, ganglionic eminence, primordial germ cell in gonad, sperm, male germ line stem cell (sensu Vertebrata) in testis.

Genetic regulation across tissues (GTEx eQTL / sQTL)

PLK4 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 5 tissues and its splicing (sQTL) in 0 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

5 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Skin Sun Exposed Lower leg	eqtl	2.1e-02	+0.30	4:128212726:A:G
Cells Cultured fibroblasts	eqtl	3.2e-02	-0.24	4:128319446:T:C
Adipose Subcutaneous	eqtl	3.3e-02	-0.45	4:127346417:G:A
Stomach	eqtl	3.7e-02	-0.68	4:127020984:G:A
Esophagus Mucosa	eqtl	3.9e-02	+0.17	4:127153054:A:C

FANTOM5 promoters

2 alternative TSS:

Promoter ID	TPM avg	Samples expressed
49607	6.6563	1304
49608	0.1131	52

Top tissues by expression

showing 100 of 288 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
ventricular zone	UBERON:0003053	96.71	gold quality
ganglionic eminence	UBERON:0004023	91.66	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	89.42	gold quality
sperm	CL:0000019	89.32	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	88.79	gold quality
embryo	UBERON:0000922	87.51	gold quality
male germ cell	CL:0000015	87.05	gold quality
left testis	UBERON:0004533	86.99	gold quality
testis	UBERON:0000473	86.83	gold quality
right testis	UBERON:0004534	86.45	gold quality
bone marrow	UBERON:0002371	84.39	gold quality
bone marrow cell	CL:0002092	82.73	gold quality
rectum	UBERON:0001052	82.34	gold quality
endometrium epithelium	UBERON:0004811	80.11	gold quality
vermiform appendix	UBERON:0001154	78.29	gold quality
mucosa of transverse colon	UBERON:0004991	78.14	gold quality
stromal cell of endometrium	CL:0002255	77.98	gold quality
lower esophagus mucosa	UBERON:0035834	77.35	gold quality
esophagus mucosa	UBERON:0002469	77.17	gold quality
adrenal tissue	UBERON:0018303	76.76	gold quality
cortical plate	UBERON:0005343	75.89	gold quality
trabecular bone tissue	UBERON:0002483	75.79	gold quality
secondary oocyte	CL:0000655	75.59	gold quality
lymph node	UBERON:0000029	75.44	gold quality
skin of abdomen	UBERON:0001416	72.91	gold quality
endometrium	UBERON:0001295	72.65	gold quality
pancreatic ductal cell	CL:0002079	72.08	silver quality
skin of leg	UBERON:0001511	72.01	gold quality
caecum	UBERON:0001153	71.75	gold quality
diaphragm	UBERON:0001103	71.45	gold quality
smooth muscle tissue	UBERON:0001135	70.85	gold quality
transverse colon	UBERON:0001157	70.58	gold quality
zone of skin	UBERON:0000014	70.29	gold quality
cartilage tissue	UBERON:0002418	70.29	gold quality
epithelium of esophagus	UBERON:0001976	69.98	silver quality
esophagus squamous epithelium	UBERON:0006920	69.91	silver quality
vagina	UBERON:0000996	69.54	gold quality
small intestine Peyer’s patch	UBERON:0003454	69.47	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	69.23	gold quality
esophagus	UBERON:0001043	68.83	gold quality
monocyte	CL:0000576	68.60	gold quality
small intestine	UBERON:0002108	68.57	gold quality
amniotic fluid	UBERON:0000173	68.50	gold quality
leukocyte	CL:0000738	68.47	gold quality
thymus	UBERON:0002370	68.42	gold quality
mononuclear cell	CL:0000842	68.29	gold quality
colonic epithelium	UBERON:0000397	68.26	silver quality
spleen	UBERON:0002106	68.06	gold quality
adult organism	UBERON:0007023	68.05	gold quality
oral cavity	UBERON:0000167	67.94	silver quality
granulocyte	CL:0000094	67.71	gold quality
duodenum	UBERON:0002114	67.64	gold quality
intestine	UBERON:0000160	67.61	gold quality
right adrenal gland	UBERON:0001233	67.51	gold quality
right adrenal gland cortex	UBERON:0035827	67.34	gold quality
gall bladder	UBERON:0002110	67.16	gold quality
large intestine	UBERON:0000059	66.83	gold quality
colonic mucosa	UBERON:0000317	66.65	gold quality
colon	UBERON:0001155	66.65	gold quality
mucosa of sigmoid colon	UBERON:0004993	66.63	gold quality
epithelium of nasopharynx	UBERON:0001951	66.48	silver quality
tonsil	UBERON:0002372	66.46	gold quality
calcaneal tendon	UBERON:0003701	66.37	gold quality
islet of Langerhans	UBERON:0000006	66.25	gold quality
oviduct epithelium	UBERON:0004804	66.01	silver quality
placenta	UBERON:0001987	65.94	gold quality
female reproductive system	UBERON:0000474	65.84	gold quality
bronchial epithelial cell	CL:0002328	65.74	gold quality
ovary	UBERON:0000992	65.66	gold quality
left adrenal gland	UBERON:0001234	65.50	gold quality
prefrontal cortex	UBERON:0000451	65.39	gold quality
left adrenal gland cortex	UBERON:0035825	65.39	gold quality
metanephros cortex	UBERON:0010533	65.36	gold quality
ileal mucosa	UBERON:0000331	65.25	silver quality
minor salivary gland	UBERON:0001830	65.08	gold quality
uterus	UBERON:0000995	64.90	gold quality
adrenal gland	UBERON:0002369	64.90	gold quality
squamous epithelium	UBERON:0006914	64.64	silver quality
upper leg skin	UBERON:0004262	64.52	gold quality
body of stomach	UBERON:0001161	64.41	gold quality
buccal mucosa cell	CL:0002336	64.40	silver quality
stomach	UBERON:0000945	64.20	gold quality
upper lobe of left lung	UBERON:0008952	64.14	gold quality
mouth mucosa	UBERON:0003729	64.12	gold quality
adrenal cortex	UBERON:0001235	64.02	gold quality
left ovary	UBERON:0002119	64.01	gold quality
right ovary	UBERON:0002118	63.99	gold quality
upper lobe of lung	UBERON:0008948	63.82	gold quality
jejunal mucosa	UBERON:0000399	63.53	silver quality
subcutaneous adipose tissue	UBERON:0002190	63.51	gold quality
fallopian tube	UBERON:0003889	63.50	gold quality
descending thoracic aorta	UBERON:0002345	63.49	gold quality
epithelium of bronchus	UBERON:0002031	63.39	silver quality
body of uterus	UBERON:0009853	63.27	gold quality
ectocervix	UBERON:0012249	62.96	gold quality
tibial nerve	UBERON:0001323	62.95	gold quality
bronchus	UBERON:0002185	62.57	silver quality
omental fat pad	UBERON:0010414	62.56	gold quality
peritoneum	UBERON:0002358	62.50	gold quality
pancreas	UBERON:0001264	62.31	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.19

HPA expression

RNA tissue specificity: Group enriched

showing 60 of 77 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Bone marrow	tissue	21.3	medium
Testis	tissue	21.2	high
Thymus	tissue	13.4
Lymph node	tissue	6.9	medium
Tonsil	tissue	6.9	medium
Appendix	tissue	4.6	medium
Rectum	tissue	4.0	medium
Colon	tissue	3.3	medium
Placenta	tissue	3.3	medium
Frontal cortex	tissue	3.1
Caudate putamen	tissue	3.1
Esophagus	tissue	2.8	low
Small intestine	tissue	2.7	medium
Duodenum	tissue	2.7	medium
Cerebral cortex	tissue	2.5	low
Putamen	tissue	2.5
Occipital cortex	tissue	2.5
Somatosensory cortex	tissue	2.4
Basal ganglia	tissue	2.3	not detected
Amygdala	tissue	2.3
Skin 1	tissue	2.2	low
Motor cortex	tissue	2.2
Hippocampal formation	tissue	2.2
Ventral forebrain	tissue	2.2
Retrosplenial and cingulate cortex	tissue	2.2
Retrosplenial cortex	tissue	2.2
Temporal cortex	tissue	2.2
Insular cortex	tissue	2.2
Prefrontal cortex	tissue	2.1
Entorhinal cortex	tissue	2.1
Septum	tissue	2.1
Hypothalamus	tissue	2.0
Olfactory bulb	tissue	2.0
Breast	tissue	1.9	not detected
Stomach 1	tissue	1.9	medium
Retina	tissue	1.9
Periaqueductal gray	tissue	1.9
Midbrain	tissue	1.8
Thalamus	tissue	1.8
Cerebellum	tissue	1.8	not detected
Pons	tissue	1.7
Smooth muscle	tissue	1.7	not detected
Corpus callosum	tissue	1.7
Superior colliculi	tissue	1.5
Substantia nigra	tissue	1.5
Spleen	tissue	1.5	medium
Ovary	tissue	1.4	medium
Endometrium 1	tissue	1.4	medium
Vagina	tissue	1.3	medium
Urinary bladder	tissue	1.3	not detected
Nucleus accumbens	tissue	1.3
Medulla oblongata	tissue	1.3
Spinal cord	tissue	1.3
Fallopian tube	tissue	1.3	medium
Postcentral gyrus	tissue	1.1
Gallbladder	tissue	1.0	medium
Locus coeruleus	tissue	1.0
Adrenal gland	tissue	1.0	not detected
Adipose tissue	tissue	0.9	not detected
Lung	tissue	0.9	medium

Brain sub-regions (HPA Brain Atlas): detected in 191; highest nTPM — Dorsal hippocampus (2.2), Subiculum (2.1), Ventral hippocampus (1.8), White matter (1.7), Anterior thalamic nucleus, ventral (1.5).

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CREB1, E2F1, E2F2, E2F3, E2F4, KCNIP3, NFKB, SP1, TP53

miRNA regulators (miRDB)

Targeting PLK4 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 53 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-6835-3P	99.93	70.49	2904
HSA-MIR-450B-5P	99.92	71.48	3175
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-6885-3P	99.75	70.36	3187
HSA-MIR-4699-3P	99.71	70.15	3142
HSA-MIR-518A-5P	99.70	69.01	2209
HSA-MIR-527	99.70	69.01	2209
HSA-MIR-5580-3P	99.70	69.41	2052
HSA-MIR-4530	99.69	66.47	1509
HSA-MIR-4729	99.69	72.18	4233
HSA-MIR-466	99.67	70.85	2863
HSA-MIR-7156-5P	99.64	68.81	1369
HSA-MIR-5700	99.64	69.88	2280
HSA-MIR-3942-3P	99.57	69.03	2854

Functional genomics

gnomAD constraint: pLI 0.18, LOEUF 0.619, missense Z 1.09 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000270861 splits into 4 regions with different missense tolerance; 0 are missense-constrained. Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. gnomAD

Region (GRCh38)	Missense obs / exp	o/e	Constrained
4:127,881,135–127,886,037	199 / 270.1	0.74	no
4:127,886,038–127,893,526	680 / 660.3	1.03	no
4:127,893,527–127,898,489	167 / 200.7	0.83	no
4:127,898,490–127,898,538	8 / 19.9	0.40	no
DepMap (CRISPR cell-line fitness): dependent in 95.4% of screened cell lines, common-essential.

Most-dependent cell lines (DepMap gene-effect, lower = stronger; ≤ −0.5 shown): HT-29 (-2.626), TC-71 (-2.439), SK-N-FI (-2.342), MHH-ES-1 (-2.32), SU-DHL-10 (-2.123), NCI-N87 (-1.928), KARPAS-299 (-1.911), TALL-1 (-1.827), RERF-LC-Sq1 (-1.82), OPM-2 (-1.815), OCI-LY-19 (-1.814), LP-1 (-1.795), MCF-7 (-1.787), NIH:OVCAR-3 (-1.76), HCC38 (-1.68).

Literature-anchored findings (GeneRIF, showing 40)

• SAK repression by p53 is likely mediated through the recruitment of HDAC repressors, and SAK repression contributes to p53-induced apoptosis (PMID:15967108)
• we identify Plk4 as a key regulator of centriole duplication.These findings provide an attractive explanation for the crucial function of Plk4 in cell proliferation and have implications for the role of Polo kinases in tumorigenesis. (PMID:16244668)
• SAK/PLK4 is required for centriole duplication and flagella development in Drosophila and human cells. (PMID:16326102)
• Overexpression of Polo-like kinase 4 (Plk4) in human cells induces centrosome amplification through the simultaneous generation of multiple procentrioles adjoining each parental centriole. (PMID:17681131)
• Human Plk4 phosphorylates Cdc25C. (PMID:18239451)
• Plk2 mediated centriole duplication is dependent on Plk4 function (PMID:19001868)
• HCT116 cells fail to organize the ninefold symmetry of centrioles due to insufficient Plk4. (PMID:19454482)
• CUL1 may function as a tumor suppressor by regulating PLK4 protein levels and thereby restraining excessive daughter centriole formation at maternal centrioles. (PMID:19679553)
• Data suggest that polo-like kinase 4 activity is restricted to the centrosome to prevent aberrant centriole assembly and sustained kinase activity is required for centriole duplication. (PMID:20032307)
• Plk4 is required for cytokinesis and maintenance of chromosomal stability (PMID:20348415)
• Data suggest that active Plk4 promotes its own degradation by catalyzing betaTrCP binding through trans-autophosphorylation (phosphorylation by the other kinase in the dimer) within homodimers. (PMID:20516151)
• Results suggest that Cep152 recruits Plk4 and CPAP to the centrosome to ensure a faithful centrosome duplication process. (PMID:21059844)
• Data show that Cep152 can be phosphorylated by Plk4 in vitro, suggesting that Cep152 acts with Plk4 to initiate centriole formation. (PMID:21059850)
• CDK11(p58), which accumulates only in the vicinity of mitotic centrosomes, directly interacts with the centriole-associated protein kinase Plk4 that regulates centriole number in cells. (PMID:21297952)
• These results highlight the critical role of PLK4 transcriptional deregulation in centriole multiplication in HPV-16 E7-expressing cells. (PMID:21609466)
• The activity of SCF-FBXW5 is negatively regulated by Polo-like kinase 4 (PLK4), which phosphorylates FBXW5 at Ser 151 to suppress its ability to ubiquitylate HsSAS-6. (PMID:21725316)
• STIL cooperates with SAS-6 and PLK4 in the control of centriole number and represents a key centriole duplication factor in human cells. (PMID:22349698)
• Plk4 is a centriole-localized kinase that does not directly regulate cytokinesis. (PMID:22456511)
• Study demonstrated that PLK4 was remarkably downregulated in HCC and could be served as a potential prognostic marker for patients with this deadly disease. (PMID:22829937)
• CAND1 promotes PLK4-mediated centriole overduplication and is frequently disrupted in prostate cancer. (PMID:23019411)
• Preventing Plk4 autoregulation causes centrosome amplification, stabilization of p53, and loss of cell proliferation (PMID:23249732)
• cooperation between Cep192 and Cep152 is crucial for centriole recruitment of Plk4 and centriole duplication during the cell cycle. (PMID:23641073)
• If both p53 and the SAPKK MKK4 are simultaneously inactivated, persistent polo-like kinase 4 activity combined with the lack of SAPK-mediated inhibition of centrosome duplication conspire to induce supernumerary centrosomes under stress. (PMID:23653187)
• Studies indicate that autophosphorylation of Nek7 and Plk4 occurred through an intermolecular mechanism, the kinases Aurora-A and Chk2 followed an intramolecular mechanism. (PMID:23821772)
• PLK4 is a new NFkappaB target gene, providing a direct link between NFkappaB activity and centrosome duplication, with implications for the role of these transcription factors in tumorigenesis. (PMID:23974100)
• Plk4 dynamically localizes to distinct subcentrosomal regions by interacting with two hierarchically regulated scaffolds, Cep192 and Cep152. (PMID:24277814)
• it appears that Nek2 and Plk4 might synergize to promote breast tumorigenesis and may also be involved in tamoxifen and trastuzumab resistance (PMID:24389189)
• p53-Dependent and cell specific epigenetic regulation of the polo-like kinases under oxidative stress. (PMID:24498222)
• HPVs16 and 18 commonly are present in normal oral mucosa and emphasize the importance of distinguishing clinical (PMID:24588599)
• Results demonstrated that Plk4 is under the direct control of the E2F activators in breast cancer cells. (PMID:24797070)
• Studies indicate that overexpression of polo-like kinase 4 (PLK4) is found in several cancer and suggest the PLK4 inhibitors as anticancer therapeutics. (PMID:24867403)
• PLK4 overexpression induces centrosome amplification and chromosome instability and causes the suppression of primary cilia formation. (PMID:24981932)
• Plk4 is intricately regulated in time and space through ordered interactions with two distinct scaffolds, Cep192 and Cep152, and a failure in this process may lead to human cancer. (PMID:24997597)
• Breast cancer cell viability is dependent on PLK4 expression. (PMID:25043604)
• An unexpected activity of Plk4 that promotes cell migration and may underlie an association between increased Plk4 expression, cancer progression and death from metastasis in solid tumor patients. (PMID:25174401)
• Mutation in PLK4, encoding a master regulator of centriole formation, defines a novel locus for primordial dwarfism. (PMID:25320347)
• Negative feedback by centriolar STIL regulates bimodal centriolar distribution of Plk4 and seemingly restricts occurrence of procentriole formation to one site on each parental centriole. (PMID:25342035)
• different levels of impaired PLK4 activity result in growth and cilia phenotypes, providing a mechanism by which microcephaly disorders can occur with or without ciliopathic features (PMID:25344692)
• Decreased PLK4 protein expression due to promoter hypermethylation was negatively correlated with JAK2 overexpression, a common occurrence in hematological malignancies. (PMID:25347426)
• PLK4 functions downstream of ROCK2 to drive centrosome amplification in arrested cells. (PMID:25590559)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	plk4	ENSDARG00000004576
mus_musculus	Plk4	ENSMUSG00000025758
rattus_norvegicus	Plk4	ENSRNOG00000011654
drosophila_melanogaster	SAK	FBGN0026371

Paralogs (4): PLK2 (ENSG00000145632), PLK1 (ENSG00000166851), PLK3 (ENSG00000173846), PLK5 (ENSG00000185988)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:101783) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 12 distinct phenotype terms.

Mouse phenotype (MP)	Records
small testis	1
abnormal apoptosis	1
decreased embryo size	1
embryonic growth arrest	1
increased circulating follicle stimulating hormone level	1
abnormal neural tube morphology	1
abnormal mitosis	1
decreased testis weight	1
decreased male germ cell number	1
absent somites	1
embryonic lethality, complete penetrance	1
embryonic lethality between implantation and somite formation, complete penetrance	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Drosophila persimilis	B4HBU3	99.9%	Diamond
Drosophila pseudoobscura pseudoobscura	Q2LYK3	99.9%	Diamond
Pongo abelii	Q5R4L1	99.9%	Diamond
Saccharomyces cerevisiae YJM789	A6ZQG7	99.2%	Diamond
Saccharomyces cerevisiae S288C	P38970	99.2%	Diamond
Drosophila sechellia	B4IAQ8	99.0%	Diamond
Drosophila simulans	B4QK53	99.0%	Diamond
Xenopus tropicalis	P62205	96.5%	Diamond
Xenopus laevis	P70032	96.5%	Diamond
Drosophila erecta	B3NE99	96.1%	Diamond
Drosophila yakuba	B4PDM5	96.1%	Diamond
Bos taurus	Q2TA25	95.7%	Diamond
Sus scrofa	Q9N0X0	94.8%	Diamond
Arabidopsis thaliana	Q683C9	93.9%	Diamond
Canis lupus familiaris	A0A8I3S724	89.4%	Diamond
Drosophila virilis	B4LDJ6	85.6%	Diamond
Drosophila mojavensis	B4KYX8	85.4%	Diamond
Drosophila grimshawi	B4J3F1	83.3%	Diamond
Drosophila ananassae	B3M6I4	82.9%	Diamond
Gallus gallus	Q5ZJH6	78.4%	Diamond
Patiria pectinifera	D7UQM5	76.4%	Diamond
Culex quinquefasciatus	B0WAU8	74.0%	Diamond
Aedes aegypti	Q16W24	74.0%	Diamond
Caenorhabditis elegans	P34331	72.1%	Diamond
Oryza sativa Japonica Group	Q60DG4	71.6%	Diamond
Drosophila willistoni	B4MXR8	69.6%	Diamond
Kluyveromyces lactis NRRL Y-1140	Q6CWQ4	68.2%	Diamond
Eremothecium gossypii ATCC 10895	Q755C4	62.6%	Diamond
Schizosaccharomyces pombe 972h-	O59790	62.3%	Diamond
Nakaseomyces glabratus CBS 138	Q6FV07	62.1%	Diamond
Dictyostelium discoideum	Q54WX4	60.7%	Diamond
Debaryomyces hansenii CBS767	Q6BVA0	60.6%	Diamond
Yarrowia lipolytica CLIB122	Q6C3J2	60.2%	Diamond
Candida albicans SC5314	Q59S66	59.0%	Diamond
Caenorhabditis briggsae	Q621J7	57.5%	Diamond
Encephalitozoon cuniculi GB-M1	Q8SRL5	51.4%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
PGRMC2	protein-coding	10424
MFSD8	protein-coding	256471
LARP1B	protein-coding	55132
ABHD18	protein-coding	80167
HSPA4L	protein-coding	22824
INTU	protein-coding	27152
SLC25A31	protein-coding	83447
LINC02615	ncRNA	100507487

Protein

Protein identifiers

Serine/threonine-protein kinase PLK4 — O00444 (reviewed: O00444)

Alternative names: Polo-like kinase 4, Serine/threonine-protein kinase 18, Serine/threonine-protein kinase Sak

All UniProt accessions (4): O00444, H0YAL6, J3KR82, J3KR84

UniProt curated annotations — full annotation on UniProt →

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, 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. Phosphorylates CEP131 at ‘Ser-78’ and PCM1 at ‘Ser-372’ which is essential for proper organization and integrity of centriolar satellites.

Subunit / interactions. Homodimer. Interacts with CEP152 (via N-terminus). Interacts with CEP78; this interaction may be important for proper PLK4 localization to the centriole and PLK4-induced overduplication of centrioles. Interacts with CEP131. Interacts simultaneously with TENT5C and CEP192. Interacts with TENT5C; this interaction leads to the TENT5C recruitment in the centrosome. Interacts with CEP85; this interaction may be important in cell migration and centriole assembly.

Subcellular location. Cytoplasm. Cytoskeleton. Microtubule organizing center. Centrosome. Centriole. Nucleus. Nucleolus. Cleavage furrow.

Post-translational modifications. Acetylation by KAT2A and KAT2B impairs kinase activity by shifting the kinase to an inactive conformation. Ubiquitinated; leading to its degradation by the proteasome. Deubiquitinated by USP54; leading to PLK4 stabilization. Tyrosine-phosphorylated by TEC.

Disease relevance. 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. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. Cryptic POLO box 1 (CPB1) and Cryptic POLO box 2 (CPB2) domains can simultaneously bind to both TENT5C and CEP192.

Induction. Down-regulated in HCT 116 colorectal cancer cells, leading to aberrant centrioles composed of disorganized cylindrical microtubules and displaced appendages. Down-regulated by p53/TP53.

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

Isoforms (3)

UniProt ID	Names	Canonical?
O00444-1	1	yes
O00444-2	2
O00444-3	3

RefSeq proteins (14): NP_001177728, NP_001177730, NP_001428286, NP_001428287, NP_001428288, NP_001428289, NP_001428290, NP_001428291, NP_001428295, NP_001428296, NP_001428297, NP_001428298, NP_001428300, NP_055079* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000719	Prot_kinase_dom	Domain
IPR000959	POLO_box_dom	Domain
IPR008266	Tyr_kinase_AS	Active_site
IPR011009	Kinase-like_dom_sf	Homologous_superfamily
IPR017441	Protein_kinase_ATP_BS	Binding_site
IPR033696	POLO_box_Plk4_C	Domain
IPR033698	POLO_box_Plk4_2	Domain
IPR033699	POLO_box_Plk4_1	Domain
IPR046437	Ser_Thr-PK_POLO_box_1_sf	Homologous_superfamily
IPR047108	Plk4-like_POLO_box_2_sf	Homologous_superfamily

Pfam: PF00069, PF18190, PF18409

Enzyme classification (BRENDA)

• EC 2.7.11.21 — polo kinase (BRENDA: 16 organisms, 193 substrates, 436 inhibitors, 20 Km, 14 kcat entries)

Substrate kinetics (BRENDA)

3 substrates with measured Km, best-characterized 3. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
ATP	0.0002–0.0076	13
CDC25C	0.0006–0.0008	6
CASEIN	0.0014	1

Catalyzed reactions (Rhea)

• L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + H(+) (RHEA:17989)
• L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] + ADP + H(+) (RHEA:46608)

UniProt features (105 total): strand 27, helix 25, mutagenesis site 9, sequence variant 8, sequence conflict 8, compositionally biased region 5, turn 5, modified residue 5, domain 4, region of interest 3, binding site 2, splice variant 2, chain 1, active site 1

Structure

Experimental structures (PDB)

19 structures by resolution:

PDB	Title	Method	Resolution (Å)
9Y9N	PLK4 in complex with Compound 25 …	X-RAY DIFFRACTION	1.81
3COK	Crystal structure of PLK4 kinase	X-RAY DIFFRACTION	2.25
9O63	Crystal structure of PLK4 and RP1664 complex	X-RAY DIFFRACTION	2.26
4JXF	Crystal Structure of PLK4 Kinase with an inhibitor: 400631 …	X-RAY DIFFRACTION	2.4
5LHZ	PB3 Domain of Human PLK4 in Complex with Coiled-Coil Domain of STIL	X-RAY DIFFRACTION	2.51
4YYP	Crystal structure of human PLK4-PB3 in complex with STIL-CC	X-RAY DIFFRACTION	2.6
4N9J	Crystal structure of the cryptic polo box domain of human Plk4	X-RAY DIFFRACTION	2.6
6N45	Crystal structure of the cryptic polo box domain of human activated Plk4 variant 1	X-RAY DIFFRACTION	2.64
4YUR	Crystal Structure of Plk4 Kinase Domain Bound to Centrinone	X-RAY DIFFRACTION	2.65
8XPG	The Crystal Structure of polo box domain of Plk4 from Biortus.	X-RAY DIFFRACTION	2.7
9Y9B	PLK4 in complex with Compound 6 …	X-RAY DIFFRACTION	2.7
4N7V	Crystal structure of human Plk4 cryptic polo box (CPB) in complex with a Cep152 …	X-RAY DIFFRACTION	2.76
4N7Z	Crystal structure of human Plk4 cryptic polo box (CPB) in complex with a Cep192 …	X-RAY DIFFRACTION	2.85
5LHY	PB3 Domain of Human PLK4 (apo)	X-RAY DIFFRACTION	3.31
6N46	Crystal structure of the cryptic polo box domain of a human activated Plk4	X-RAY DIFFRACTION	3.71
6W3I	Crystal structure of a FAM46C mutant in complex with Plk4	X-RAY DIFFRACTION	3.8
6W3J	Crystal structure of the FAM46C/Plk4/Cep192 complex	X-RAY DIFFRACTION	4.38
6W38	Crystal structure of the FAM46C/Plk4 complex	X-RAY DIFFRACTION	4.48
2N19	STIL binding to the Polo-box domain 3 of PLK4 regulates centriole duplication	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O00444-F1	66.31	0.37

Human Protein Atlas

Protein class: Enzymes, ENZYME proteins, Transferases, Kinases, Predicted intracellular proteins, Disease related genes, Potential drug targets, Human disease related genes, Congenital malformations, Other congenital malformations, Essential proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): centrosome; cytosol

Antibody reliability (HPA): IH approved · IF supported

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (1)

Position	Role
136	proton acceptor

Ligand- & substrate-binding residues (2)

Position	Role
18–26	ATP
41	ATP

Post-translational modifications (5)

Type	Positions
N6-acetyllysine	45, 46
Phosphoserine	401, 665, 817

Mutagenesis-validated functional residues (9)

Position	Phenotype
13	does not affect interaction with ubp54.
41	abolishes ability to phosphorylate cdc25c and chek2.
151	does not affect interaction with ubp54.
154	catalytically inactive mutant that causes some centrosome amplification above background levels when overexpressed.
162	abolishes interaction with ubp54.
167	does not affect interaction with ubp54.
170	activating mutant.
669	does not affect the interaction with tent5c.
670	decreases substantially the interaction with tent5c. does not affect localization to the centrosome. loss of tent5c recruitment to the …

Function

Pathways and Gene Ontology

Reactome pathways

7 curated (TAS) of 16; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

16 pathways:

ID	Pathway	Evidence
R-HSA-8854518	AURKA Activation by TPX2	curated
R-HSA-5620912	Anchoring of the basal body to the plasma membrane	curated
R-HSA-380259	Loss of Nlp from mitotic centrosomes	curated
R-HSA-380284	Loss of proteins required for interphase microtubule organization from the centrosome	curated
R-HSA-380320	Recruitment of NuMA to mitotic centrosomes	curated
R-HSA-380270	Recruitment of mitotic centrosome proteins and complexes	curated
R-HSA-2565942	Regulation of PLK1 Activity at G2/M Transition	curated
R-HSA-1640170	Cell Cycle	—
R-HSA-69278	Cell Cycle, Mitotic	—
R-HSA-380287	Centrosome maturation	—
R-HSA-5617833	Cilium Assembly	—
R-HSA-69275	G2/M Transition	—
R-HSA-68886	M Phase	—
R-HSA-453274	Mitotic G2-G2/M phases	—
R-HSA-68877	Mitotic Prometaphase	—
R-HSA-1852241	Organelle biogenesis and maintenance	—

MSigDB gene sets: 492 (showing top): E2F_Q4_01, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOBP_EPITHELIUM_DEVELOPMENT, WANG_CLIM2_TARGETS_UP, KANG_DOXORUBICIN_RESISTANCE_UP, GNF2_CENPF, GOBP_REGULATION_OF_MICROTUBULE_BASED_PROCESS, SEMBA_FHIT_TARGETS_DN, CCAWYNNGAAR_UNKNOWN, CROONQUIST_NRAS_SIGNALING_DN, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, KENNY_CTNNB1_TARGETS_UP, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, GENTILE_RESPONSE_CLUSTER_D3

GO Biological Process (7): protein phosphorylation (GO:0006468), centriole replication (GO:0007099), positive regulation of centriole replication (GO:0046601), cilium assembly (GO:0060271), trophoblast giant cell differentiation (GO:0060707), de novo centriole assembly involved in multi-ciliated epithelial cell differentiation (GO:0098535), regulation of cell cycle process (GO:0010564)

GO Molecular Function (9): protein serine/threonine kinase activity (GO:0004674), ATP binding (GO:0005524), identical protein binding (GO:0042802), protein serine kinase activity (GO:0106310), nucleotide binding (GO:0000166), protein kinase activity (GO:0004672), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740)

GO Cellular Component (9): XY body (GO:0001741), nucleus (GO:0005634), nucleolus (GO:0005730), centrosome (GO:0005813), centriole (GO:0005814), cytosol (GO:0005829), cleavage furrow (GO:0032154), deuterosome (GO:0098536), procentriole (GO:0120098)

Reactome top-level categories

10 top-level categories:

Category	Pathways
G2/M Transition	3
Centrosome maturation	2
Cell Cycle, Mitotic	2
Loss of proteins required for interphase microtubule organization from the centrosome	1
Mitotic Prometaphase	1
Assembly of the 9+0 primary cilium	1
Organelle biogenesis and maintenance	1
M Phase	1
Mitotic G2-G2/M phases	1
Cell Cycle	1

GO top-level categories

46 GO namespaces:

Category	Terms
intracellular membraneless organelle	3
cell cycle process	2
protein kinase activity	2
microtubule organizing center	2
cytoplasm	2
cellular anatomical structure	2
phosphorylation	1
protein modification process	1
centrosome duplication	1
centriole assembly	1
centriole replication	1
regulation of centriole replication	1
positive regulation of cytoskeleton organization	1
positive regulation of cell cycle process	1
positive regulation of organelle assembly	1
axoneme assembly	1
intraciliary transport involved in cilium assembly	1
cilium organization	1
protein localization to cilium	1
organelle assembly	1
trans-Golgi to periciliary membrane compartment transport	1
plasma membrane bounded cell projection assembly	1
ciliary transition zone assembly	1
cell differentiation involved in embryonic placenta development	1
de novo centriole assembly	1
multi-ciliated epithelial cell differentiation	1
regulation of cell cycle	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
anion binding	1
protein binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
kinase activity	1
phosphotransferase activity, alcohol group as acceptor	1
catalytic activity, acting on a protein	1
binding	1
transferase activity, transferring phosphorus-containing groups	1
catalytic activity	1
sex chromosome	1
condensed chromatin of inactivated sex chromosome	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
centriole	1
cell division site	1
plasma membrane region	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 9 of 25 annotations. The rest are phylogenetic / computational / electronic (IEA).

9 experimentally-supported GO terms:

GO term	NS	Evidence
centriole replication	BP	direct assay
cilium assembly	BP	mutant phenotype
positive regulation of centriole replication	BP	direct assay
protein phosphorylation	BP	direct assay
centriole	CC	direct assay
centrosome	CC	direct assay
procentriole	CC	direct assay
identical protein binding	MF	physical interaction
protein serine/threonine kinase activity	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 2,169 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PLK4	SASS6	Q6UVJ0	984
PLK4	CPAP	Q9HC77	966
PLK4	CEP135	Q66GS9	964
PLK4	CCP110	O43303	952
PLK4	CEP152	O94986	938
PLK4	TUBG1	P23258	840
PLK4	CNTLN	Q9NXG0	835
PLK4	STIL	Q15468	834
PLK4	CETN2	P41208	815
PLK4	CEP63	Q96MT8	813
PLK4	CEP192	Q8TEP8	808
PLK4	PCNT	O95613	790
PLK4	PLK5	Q496M5	741
PLK4	BUB1B	O60566	705
PLK4	CEP295	Q9C0D2	696

IntAct

Human interaction partners of PLK4 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

showing 30 of 38 partners by confidence:

Partner	Interaction type	MIscore	Records
CEP152	physical association	0.850	20
ELOA	physical association	0.720	6
CEP192	direct interaction	0.700	13
BTRC	physical association	0.680	4
STIL	colocalization	0.660	9
SFN	physical association	0.650	3
ECT2	physical association	0.600	3
AIRIM	physical association	0.560	3
ARR3	physical association	0.560	3
DNAJB13	physical association	0.560	3
DUN1	physical association	0.560	3
GAS8	physical association	0.560	3
OSBPL3	physical association	0.560	3
P4HB	physical association	0.560	3
RSM26	physical association	0.560	3
SKI8	physical association	0.560	3
SPAG5	physical association	0.560	3
TENT5B	physical association	0.560	3
TFIP11	physical association	0.560	3
TRIM54	physical association	0.560	3
YPK2	physical association	0.560	3
ZBTB39	physical association	0.560	3
YWHAE	physical association	0.560	2
YWHAH	physical association	0.560	1
CPAP	phosphorylation reaction	0.440	1
CCDC85C	physical association	0.400	2
DUSP23	physical association	0.400	1
CEP76	physical association	0.370	1
CHD3	physical association	0.370	1
MAD1L1	physical association	0.370	1

BioGRID (188 interactions; top human partners by supporting records): ACTR2 (Affinity Capture-MS; 4 records), CEP152 (Proximity Label-MS; 4 records), BTRC (Two-hybrid; 3 records), ALMS1 (Proximity Label-MS; 2 records), CEP192 (Proximity Label-MS; 2 records), CEP350 (Proximity Label-MS; 2 records), CEP63 (Proximity Label-MS; 2 records), CEP85 (Proximity Label-MS; 2 records), CYLD (Affinity Capture-Western; 2 records), FBXW5 (Affinity Capture-Western; 2 records), MIB1 (Affinity Capture-Western; 2 records), NEDD1 (Proximity Label-MS; 2 records), NEK7 (Affinity Capture-Western; 2 records), PLOD1 (Affinity Capture-MS; 2 records), SASS6 (Proximity Label-MS; 2 records)

SIGNOR signaling

showing 8 of 17 signaling interactions:

A	Effect	B	Mechanism
PLK4	up-regulates	PLK4	phosphorylation
PLK4	up-regulates	CENPJ	phosphorylation
PLK4	“up-regulates activity”	PCM1	phosphorylation
PLK4	“up-regulates quantity”	CDC25C	phosphorylation
PLK4	“up-regulates activity”	CEP131	phosphorylation
PLK4	“up-regulates activity”	TUBGCP6	phosphorylation
PLK4	“up-regulates activity”	NEDD1	phosphorylation
PLK4	“down-regulates activity”	FBXW5	phosphorylation

Protein complexes (CORUM) (2)

Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).

2 complexes by size:

Complex	Subunits	Members
PLK4-TENT5C complex	2	PLK4, TENT5C
PLK4-STIL complex	2	PLK4, STIL

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 38 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Loss of Nlp from mitotic centrosomes	6	47.6×	9e-08
Loss of proteins required for interphase microtubule organization from the centrosome	6	47.6×	9e-08
AURKA Activation by TPX2	6	45.7×	9e-08
Regulation of PLK1 Activity at G2/M Transition	7	44.4×	2e-08
Recruitment of mitotic centrosome proteins and complexes	6	40.8×	2e-07
Recruitment of NuMA to mitotic centrosomes	6	35.0×	3e-07
Anchoring of the basal body to the plasma membrane	6	33.9×	3e-07
Mitotic Prometaphase	5	17.3×	9e-05

Disease & clinical

Genetic variants

Variant evidence for PLK4: 722 ClinVar records (34 pathogenic / likely pathogenic). Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	21
Likely pathogenic	13
Uncertain significance	355
Likely benign	254
Benign	22

Top pathogenic / likely-pathogenic (15)

Showing the 15 best-reviewed of 34 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
1495735	NM_014264.5(PLK4):c.1358+1G>C	Likely pathogenic	criteria provided, multiple submitters, no conflicts	2
960158	NM_014264.5(PLK4):c.37A>T (p.Lys13Ter)	Pathogenic	criteria provided, single submitter	1
1021501	NM_014264.5(PLK4):c.1679del (p.Cys560fs)	Pathogenic	criteria provided, single submitter	1
1075626	NM_014264.5(PLK4):c.60del (p.Gly21fs)	Pathogenic	criteria provided, single submitter	1
1452199	NM_014264.5(PLK4):c.1201del (p.Ser401fs)	Pathogenic	criteria provided, single submitter	1
1455498	NM_014264.5(PLK4):c.319_331del (p.Pro107fs)	Pathogenic	criteria provided, single submitter	1
1457246	NM_014264.5(PLK4):c.168_169del (p.Arg56fs)	Pathogenic	criteria provided, single submitter	1
1458419	NM_014264.5(PLK4):c.62del (p.Gly21fs)	Pathogenic	criteria provided, single submitter	1
1952871	NM_014264.5(PLK4):c.799C>T (p.Arg267Ter)	Pathogenic	criteria provided, single submitter	1
1976021	NM_014264.5(PLK4):c.1567_1568insTTGT (p.Lys523fs)	Pathogenic	criteria provided, single submitter	1
2028466	NM_014264.5(PLK4):c.419_420del (p.Leu139_Ser140insTer)	Pathogenic	criteria provided, single submitter	1
2095296	NM_014264.5(PLK4):c.644_645del (p.Thr215fs)	Pathogenic	criteria provided, single submitter	1
2098334	NM_014264.5(PLK4):c.2701C>T (p.Gln901Ter)	Pathogenic	criteria provided, single submitter	1
2106876	NM_014264.5(PLK4):c.1796T>G (p.Leu599Ter)	Pathogenic	criteria provided, single submitter	1
2788633	NM_014264.5(PLK4):c.1261_1264del (p.Ser421fs)	Pathogenic	criteria provided, single submitter	1

Per-variant reference — Sugi Variant

Explore PLK4’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 31 predictions of 1,245):

Position(s)	Effect	Δscore	Sites
4:127881927–127881928	donor_loss	1.0000	5
4:127883554–127883555	donor_loss	1.0000	5
4:127885696	acceptor_gain	1.0000
4:127887497–127887498	donor_loss	1.0000	5
4:127891091	acceptor_gain	1.0000
4:127891197–127891198	donor_loss	1.0000	6
4:127892448	acceptor_gain	1.0000
4:127894948	acceptor_gain	1.0000
4:127881165–127881166	donor_loss	0.9900	5
4:127881829	acceptor_gain	0.9900

AlphaMissense

1,923 missense substitutions predicted likely pathogenic (of 6,425 scored), across 444 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
M48	9	0.930	0.996
M42	9	0.912	0.984
M53	9	0.900	0.990
D154	8	1.000	1.000
D136	8	0.998	1.000
D193	8	0.997	0.999
F155	8	0.992	0.999
F211	8	0.991	0.999
H134	8	0.990	0.998
F23	8	0.989	1.000
N141	8	0.985	0.998
F79	8	0.983	0.999
D81	8	0.977	0.998
H128	8	0.967	0.993
D44	8	0.958	0.994
F692	8	0.956	0.996
F12	8	0.955	1.000
F911	8	0.949	0.998
F264	8	0.941	0.996
H69	8	0.938	0.994

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

6 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Chromophobe (TCGA)	unfavorable	1.32e-05
Liver Hepatocellular Carcinoma (TCGA)	unfavorable	4.39e-05
Lung Adenocarcinoma (TCGA)	unfavorable	9.07e-05
Liver Hepatocellular Carcinoma (validation)	unfavorable	0.00011
Lung Adenocarcinoma (validation)	unfavorable	0.000377
Pancreatic Adenocarcinoma (validation)	unfavorable	0.000631

Disease associations

OMIM: gene MIM:605031 | disease phenotypes: MIM:616171

GenCC curated gene-disease

3 curated gene-disease records:

Disease	Classification	Inheritance	Records
microcephaly and chorioretinopathy 2	Definitive	Autosomal recessive	4
microcephaly and chorioretinopathy 1	Supportive	Autosomal recessive
Seckel syndrome	Supportive	Autosomal recessive

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (11 panels, 9 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

11 panels:

Panel	Rating
DDG2P	green
Fetal anomalies	green
Hypotonic infant	green
Intellectual disability	green
Leukodystrophy, childhood onset	green
Monogenic short stature	green
Paediatric disorders	green
Retinal disorders	green
Severe microcephaly	green
Anophthalmia or microphthalmia	amber
Structural eye disease	amber

Mondo (3): microcephaly and chorioretinopathy 2 (MONDO:0014516), microcephaly and chorioretinopathy 1 (MONDO:0009624), Seckel syndrome (MONDO:0019342)

Orphanet (1): Seckel syndrome (Orphanet:808)

HPO phenotypes

showing 60 of 66 phenotypes (HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000252	Microcephaly
HP:0000275	Narrow face
HP:0000307	Pointed chin
HP:0000340	Sloping forehead
HP:0000347	Micrognathia
HP:0000363	Abnormal earlobe morphology
HP:0000387	Absent earlobe
HP:0000411	Protruding ear
HP:0000431	Wide nasal bridge
HP:0000444	Convex nasal ridge
HP:0000448	Prominent nose
HP:0000463	Anteverted nares
HP:0000482	Microcornea
HP:0000486	Strabismus
HP:0000488	Retinopathy
HP:0000494	Downslanted palpebral fissures
HP:0000499	Abnormal eyelash morphology
HP:0000501	Glaucoma
HP:0000505	Visual impairment
HP:0000518	Cataract
HP:0000520	Proptosis
HP:0000543	Optic disc pallor
HP:0000568	Microphthalmia
HP:0000639	Nystagmus
HP:0000648	Optic atrophy
HP:0000682	Abnormal dental enamel morphology
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001263	Global developmental delay
HP:0001272	Cerebellar atrophy
HP:0001276	Hypertonia
HP:0001321	Cerebellar hypoplasia
HP:0001338	Partial agenesis of the corpus callosum
HP:0001344	Absent speech
HP:0001363	Craniosynostosis
HP:0001382	Joint hypermobility
HP:0001385	Hip dysplasia
HP:0001511	Intrauterine growth retardation
HP:0001762	Talipes equinovarus
HP:0001852	Sandal gap
HP:0002059	Cerebral atrophy
HP:0002120	Cerebral cortical atrophy
HP:0002209	Sparse scalp hair
HP:0002269	Abnormality of neuronal migration
HP:0002650	Scoliosis
HP:0002750	Delayed skeletal maturation
HP:0002943	Thoracic scoliosis
HP:0003577	Congenital onset
HP:0004209	Clinodactyly of the 5th finger
HP:0004322	Short stature
HP:0004326	Cachexia
HP:0004422	Biparietal narrowing
HP:0004626	Lumbar scoliosis
HP:0007165	Periventricular heterotopia
HP:0007360	Aplasia/Hypoplasia of the cerebellum
HP:0007401	Macular atrophy
HP:0007495	Prematurely aged appearance
HP:0007703	Abnormal retinal pigmentation
HP:0009804	Tooth agenesis

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL3788 (SINGLE PROTEIN), CHEMBL5465203 (PROTEIN-PROTEIN INTERACTION)

Drugs by curated mechanism of action (ChEMBL)

Drugs whose curated ChEMBL mechanism of action targets the PLK4 protein itself — single-protein targets only (drugs acting on a protein family or complex that merely includes it are excluded). Includes antibodies and oligonucleotides that bioactivity screening does not capture.

3 curated-mechanism drugs:

Drug	Modality	Max phase
CFI-400945	Small molecule	2
OCIFISERTIB	Small molecule	2
RG-1530	Small molecule	1

Molecules with ChEMBL bioactivity

Phase ≥1, by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 553,520 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

showing 60 of 65 molecules by phase:

Molecule	Name	Phase	Patents
CHEMBL1289926	AXITINIB	4	16,510
CHEMBL2403108	CERITINIB	4	9,002
CHEMBL601719	CRIZOTINIB	4	15,133
CHEMBL2028663	DABRAFENIB	4	13,060
CHEMBL5416410	DASATINIB	4	674
CHEMBL1983268	ENTRECTINIB	4	3,737
CHEMBL553	ERLOTINIB	4	109,860
CHEMBL1287853	FEDRATINIB	4	3,770
CHEMBL2103830	FOSTAMATINIB	4	4,026
CHEMBL3301622	GILTERITINIB	4	2,542
CHEMBL941	IMATINIB	4	113,105
CHEMBL608533	MIDOSTAURIN	4	7,641
CHEMBL1078178	MOMELOTINIB	4	3,649
CHEMBL502835	NINTEDANIB	4	8,978
CHEMBL477772	PAZOPANIB	4	16,241
CHEMBL1789941	RUXOLITINIB	4	12,161
CHEMBL1336	SORAFENIB	4	87,476
CHEMBL535	SUNITINIB	4	80,232
CHEMBL24828	VANDETANIB	4	43,290
CHEMBL483158	ALISERTIB	3	2,433
CHEMBL428690	ALVOCIDIB	3
CHEMBL491473	CEDIRANIB	3
CHEMBL522892	DOVITINIB	3
CHEMBL603469	LESTAURTINIB	3
CHEMBL223360	LINIFANIB	3
CHEMBL3426621	RIPASUDIL	3
CHEMBL91829	RUBOXISTAURIN	3
CHEMBL3408947	OCIFISERTIB	2
CHEMBL495727	AT-9283	2
CHEMBL1231124	AZD-1480	2
CHEMBL575448	BMS-754807	2
CHEMBL460702	BMS-777607	2
CHEMBL1967878	CENISERTIB	2
CHEMBL402548	DANUSERTIB	2
CHEMBL3039513	DECERNOTINIB	2
CHEMBL215152	DEFOSBARASERTIB	2
CHEMBL6246	ELLAGIC ACID	2
CHEMBL482968	ENMD-2076	2
CHEMBL1230609	FORETINIB	2
CHEMBL3989914	GLESATINIB	2
CHEMBL1980297	ILORASERTIB	2
CHEMBL3545307	MERESTINIB	2
CHEMBL253969	OSI-632	2
CHEMBL521851	PICTILISIB	2
CHEMBL475251	R-406	2
CHEMBL1738757	REBASTINIB	2
CHEMBL1721885	SU-014813	2
CHEMBL124660	TANDUTINIB	2
CHEMBL572878	TOZASERTIB	2
CHEMBL1980391	RG-1530	1
CHEMBL3545360	ASP-3026	1
CHEMBL2041933	AZD-7762	1
CHEMBL482967	CYC-116	1
CHEMBL260933	GS 6201	1
CHEMBL1090479	GSK-1070916	1
CHEMBL1908397	KW-2449	1
CHEMBL3600873	MK-5108	1
CHEMBL259084	MLN-8054	1
CHEMBL1084546	PF-00562271	1
CHEMBL3128043	PF-03758309	1

PharmGKB: 1 entry (CPIC guideline: no)

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — Polo-like kinase (PLK) family

Most potent curated ligand interactions (7 total), top 7:

Ligand	Action	Affinity	Parameter
centrinone B	Inhibition	9.23	pKi
CZS-241	Inhibition	8.59	pIC50
ocifisertib	Inhibition	8.55	pIC50
RP-1664	Inhibition	8.52	pIC50
RG-1530	Inhibition	7.96	pKd
axitinib	Inhibition	7.34	pIC50
XMD8-92	Inhibition	6.22	pKd

Binding affinities (BindingDB)

649 measured of 983 human assays (986 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
1-[2-(4-methylphenyl)-5-tert-butyl-pyrazol-3-yl]-3-[4-(2-morpholin-4-ylethoxy)naphthalen-1-yl]urea	KD	0.37 nM
(2’S,3R)-2’-[3-[[(3S)-3-hydroxy-2,3-dihydro-1-benzofuran-7-yl]amino]-2,3,3a,4,5,6,7,7a-octahydro-1H-indazol-6-yl]-5-methoxyspiro[1H-indole-3,1’-cyclopropane]-2-one	IC50	0.375 nM	US-20230365537: POLO LIKE KINASE 4 INHIBITORS
CHEMBL3408954	IC50	0.64 nM
CHEMBL5407522	KI	0.65 nM
CHEMBL5183346	IC50	0.7 nM
CHEMBL3353351	IC50	0.71 nM
CHEMBL5194020	IC50	1.1 nM
CHEMBL3353350	IC50	1.2 nM
CHEMBL5408998	IC50	1.5 nM
Staurosporine	KD	1.7 nM
CHEMBL5191641	IC50	1.8 nM
CHEMBL5430165	IC50	1.9 nM
(2’S,3R)-2’-[3-[(3-hydroxy-2,3-dihydro-1-benzofuran-7-yl)amino]-2,3,3a,4,5,6,7,7a-octahydro-1H-indazol-6-yl]-5-methoxyspiro[1H-indole-3,1’-cyclopropane]-2-one	IC50	2.08 nM	US-20230365537: POLO LIKE KINASE 4 INHIBITORS
(2’S,3R)-2’-[3-[(5-ethoxypyrimidin-4-yl)amino]-2,3,3a,4,5,6,7,7a-octahydro-1H-indazol-6-yl]-5-methoxyspiro[1H-indole-3,1’-cyclopropane]-2-one	IC50	2.18 nM	US-20230365537: POLO LIKE KINASE 4 INHIBITORS
(2’S,3R)-5-methoxy-2’-[3-[(2-methoxy-3-pyridinyl)amino]-2,3,3a,4,5,6,7,7a-octahydro-1H-indazol-6-yl]spiro[1H-indole-3,1’-cyclopropane]-2-one	IC50	2.25 nM	US-20230365537: POLO LIKE KINASE 4 INHIBITORS
CHEMBL5407696	IC50	2.6 nM
CHEMBL5422518	IC50	3.1 nM
CEP-701	KD	3.4 nM
CHEMBL5440306	IC50	3.6 nM
CHEMBL5190548	IC50	3.7 nM
CHEMBL5207473	IC50	3.8 nM
(2’S,3R)-2’-[3-(1-benzofuran-7-ylamino)-2,3,3a,4,5,6,7,7a-octahydro-1H-indazol-6-yl]-5-methoxyspiro[1H-indole-3,1’-cyclopropane]-2-one	IC50	3.85 nM	US-20230365537: POLO LIKE KINASE 4 INHIBITORS
CHEMBL5201909	IC50	4 nM
(2’S,3R)-5-methoxy-2’-[3-[(5-methoxy-6-piperidin-1-ylpyrimidin-4-yl)amino]-2,3,3a,4,5,6,7,7a-octahydro-1H-indazol-6-yl]spiro[1H-indole-3,1’-cyclopropane]-2-one	IC50	4.96 nM	US-20230365537: POLO LIKE KINASE 4 INHIBITORS
CHEMBL6188303	IC50	5 nM
CHEMBL3408952	IC50	5.2 nM
Biochemistry 469551 Compound 12	IC50	5.4 nM
CHEMBL5396625	IC50	5.5 nM
CHEMBL5433109	IC50	5.5 nM
3-methoxy-2-methyl-4-(methylamino)-29-oxa-1,7,17-triazaoctacyclo[12.12.2.12,6.07,28.08,13.015,19.020,27.021,26]nonacosa-8,10,12,14,19,21,23,25,27-nonaen-16-one	IC50	5.6 nM	US-8822500: Tyrosine kinase inhibitors
CHEMBL5405221	IC50	5.6 nM
CHEMBL3969370	EC50	5.8 nM
CHEMBL5175418	IC50	5.9 nM
(2’S,3R)-2’-[3-[[(3R)-3-hydroxy-2,3-dihydro-1-benzofuran-7-yl]amino]-2,3,3a,4,5,6,7,7a-octahydro-1H-indazol-6-yl]-5-methoxyspiro[1H-indole-3,1’-cyclopropane]-2-one	IC50	5.97 nM	US-20230365537: POLO LIKE KINASE 4 INHIBITORS
CHEMBL6193379	IC50	6 nM
Staurosporine, 8	IC50	6.5 nM
CHEMBL5198607	IC50	6.5 nM
CHEMBL5200125	IC50	7 nM
CHEMBL5430526	IC50	7 nM
CHEMBL5185001	IC50	7.3 nM
CHEMBL5180759	IC50	7.9 nM
CHEMBL4465866	KD	8 nM
CHEMBL4576489	KD	8 nM
CHEMBL5434630	IC50	8.1 nM
CHEMBL5410922	IC50	8.4 nM
CHEMBL5433434	IC50	8.6 nM
CHEMBL5422161	IC50	9.1 nM
CHEMBL5430793	IC50	9.4 nM
CHEMBL5397330	IC50	10 nM
CHEMBL6189091	IC50	10 nM

ChEMBL bioactivities

911 potent at pChembl≥5 of 926 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.00	Ki	0.1	nM	CHEMBL3408945
10.00	IC50	0.1	nM	CHEMBL5209160
9.80	Ki	0.16	nM	CHEMBL5185225
9.70	IC50	0.2	nM	CHEMBL5185001
9.59	Ki	0.26	nM	OCIFISERTIB
9.52	IC50	0.3	nM	CHEMBL5171469
9.52	IC50	0.3	nM	CHEMBL5428085
9.52	IC50	0.3	nM	CHEMBL5404983
9.49	IC50	0.32	nM	CHEMBL2407898
9.43	IC50	0.37	nM	CHEMBL3353348
9.41	IC50	0.39	nM	CHEMBL3408955
9.40	IC50	0.4	nM	CHEMBL5439790
9.35	IC50	0.45	nM	CHEMBL2407894
9.35	IC50	0.45	nM	CHEMBL4553351
9.32	IC50	0.48	nM	CHEMBL2407748
9.23	IC50	0.59	nM	CHEMBL3353347
9.22	IC50	0.6	nM	CHEMBL3408944
9.22	Ki	0.6	nM	CHEMBL5556344
9.21	IC50	0.61	nM	CHEMBL2407900
9.19	IC50	0.64	nM	CHEMBL3408954
9.16	IC50	0.69	nM	CHEMBL4516793
9.15	IC50	0.71	nM	CHEMBL3353351
9.15	IC50	0.7	nM	CHEMBL5171233
9.15	IC50	0.7	nM	CHEMBL5188129
9.15	IC50	0.7	nM	CHEMBL5183346
9.14	Ki	0.73	nM	CHEMBL3408946
9.12	IC50	0.75	nM	CHEMBL3353341
9.12	Kd	0.75	nM	STAUROSPORINE
9.11	Kd	0.77	nM	STAUROSPORINE
9.10	IC50	0.79	nM	CHEMBL3353352
9.10	IC50	0.8	nM	CHEMBL5200865
9.09	IC50	0.82	nM	CHEMBL2407744
9.05	IC50	0.9	nM	CHEMBL2407895
9.05	IC50	0.9	nM	CHEMBL3408941
9.05	IC50	0.9	nM	CHEMBL3353361
9.05	IC50	0.9	nM	CHEMBL3353362
9.05	IC50	0.9	nM	CHEMBL3353355
9.05	IC50	0.9	nM	CHEMBL5402864
9.03	IC50	0.94	nM	CHEMBL4448596
9.03	Kd	0.93	nM	TAE-684
9.00	IC50	1	nM	CHEMBL4516793
9.00	IC50	1	nM	CHEMBL5185324
9.00	IC50	1	nM	CHEMBL5420150
8.96	IC50	1.1	nM	CHEMBL3353348
8.96	IC50	1.1	nM	CHEMBL3353347
8.96	IC50	1.1	nM	CHEMBL3408956
8.96	IC50	1.1	nM	CHEMBL5194020
8.92	IC50	1.2	nM	CHEMBL3353350
8.92	IC50	1.2	nM	CHEMBL4440053
8.92	IC50	1.2	nM	CHEMBL4470693

PubChem BioAssay actives

588 with measured affinity, of 2161 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
6-N-[(2,4-difluorophenyl)methyl]-4-N-(5-methyl-1H-pyrazol-3-yl)-1H-pyrazolo[5,4-d]pyrimidine-4,6-diamine	1860388: Inhibition of recombinant human PLK4 incubated for 60 mins by Lanthascreen Eu kinase binding assay	ic50	0.0001	uM
(1R,2S)-5’-methoxy-1’-methyl-2-[3-[(E)-2-[4-(morpholin-4-ylmethyl)phenyl]ethenyl]-1H-indazol-6-yl]spiro[cyclopropane-1,3’-indole]-2’-one	1198709: Competitive binding to PLK4 (unknown origin) by double reciprocal plot analysis in presence of ATP	ki	0.0001	uM
6-N-[(2,4-difluorophenyl)methyl]-4-N-(5-methyl-1H-pyrazol-3-yl)-1-(oxan-4-yl)pyrazolo[3,4-d]pyrimidine-4,6-diamine	1860388: Inhibition of recombinant human PLK4 incubated for 60 mins by Lanthascreen Eu kinase binding assay	ic50	0.0002	uM
2-[2-fluoro-4-[(2-fluoro-3-nitrophenyl)methylsulfonyl]phenyl]sulfanyl-5-methoxy-N-(5-methyl-1H-pyrazol-3-yl)-6-morpholin-4-ylpyrimidin-4-amine	2073833: Binding affinity to PLK4 (unknown origin) assessed as inhibition constant	ki	0.0002	uM
3-[(E)-[3-[(E)-2-[4-[(dimethylamino)methyl]phenyl]ethenyl]indazol-6-ylidene]methyl]-5-methoxy-1H-indol-2-ol	762246: Inhibition of N-terminal GST-tagged human PLK4 (1 to 391 amino acids) expressed in Escherichia coli using TMB as substrate after 30 mins by indirect ELISA assay	ic50	0.0003	uM
6-N-[(4-chlorophenyl)methyl]-4-N-(5-methyl-1H-pyrazol-3-yl)-1H-pyrazolo[5,4-d]pyrimidine-4,6-diamine	1860388: Inhibition of recombinant human PLK4 incubated for 60 mins by Lanthascreen Eu kinase binding assay	ic50	0.0003	uM
2-chloro-N-(2,5-difluorophenyl)-5-[[[4-[(5-methyl-1H-pyrazol-3-yl)amino]-1H-pyrazolo[5,4-d]pyrimidin-6-yl]amino]methyl]benzamide	2027756: Inhibition of PLK4 (unknown origin) incubated for 1 hr by FRET assay	ic50	0.0003	uM
5-[[[1-(1-acetylpiperidin-4-yl)-4-[(5-methyl-1H-pyrazol-3-yl)amino]pyrazolo[3,4-d]pyrimidin-6-yl]amino]methyl]-2-chloro-N-(2,5-difluorophenyl)benzamide	2027756: Inhibition of PLK4 (unknown origin) incubated for 1 hr by FRET assay	ic50	0.0003	uM
(2’S,3R)-2’-[3-[(E)-2-[4-[[(2S,6R)-2,6-dimethylmorpholin-4-yl]methyl]phenyl]ethenyl]-1H-indazol-6-yl]-5-methoxyspiro[1H-indole-3,1’-cyclopropane]-2-one	1198709: Competitive binding to PLK4 (unknown origin) by double reciprocal plot analysis in presence of ATP	ki	0.0003	uM
5-methoxy-3-[(E)-[3-[(E)-2-pyridin-4-ylethenyl]indazol-6-ylidene]methyl]-1H-indol-2-ol	762246: Inhibition of N-terminal GST-tagged human PLK4 (1 to 391 amino acids) expressed in Escherichia coli using TMB as substrate after 30 mins by indirect ELISA assay	ic50	0.0004	uM
2-chloro-N-(2,5-difluorophenyl)-5-[[[1-(1,1-dioxothian-4-yl)-4-[(5-methyl-1H-pyrazol-3-yl)amino]pyrazolo[3,4-d]pyrimidin-6-yl]amino]methyl]benzamide	2027756: Inhibition of PLK4 (unknown origin) incubated for 1 hr by FRET assay	ic50	0.0004	uM
(2’S,3R)-5-methoxy-2’-[3-[(E)-2-[4-[[(2S,6R)-2,4,6-trimethylpiperazin-1-yl]methyl]phenyl]ethenyl]-1H-indazol-6-yl]spiro[1H-indole-3,1’-cyclopropane]-2-one	1198659: Inhibition of PLK4 (unknown origin) by ELISA	ic50	0.0004	uM
(2’S,3R)-2’-[3-[(E)-2-[4-[(dimethylamino)methyl]phenyl]ethenyl]-1H-indazol-6-yl]-5-methoxyspiro[1H-indole-3,1’-cyclopropane]-2-one	1198659: Inhibition of PLK4 (unknown origin) by ELISA	ic50	0.0004	uM
(2’S,3R)-5-methoxy-2’-[3-(4-piperazin-1-ylphenyl)-1H-indazol-6-yl]spiro[1H-indole-3,1’-cyclopropane]-2-one	1630306: Inhibition of PLK4 (unknown origin)	ic50	0.0004	uM
5-methoxy-3-[(E)-[3-[(E)-2-pyridin-3-ylethenyl]indazol-6-ylidene]methyl]-1H-indol-2-ol	762246: Inhibition of N-terminal GST-tagged human PLK4 (1 to 391 amino acids) expressed in Escherichia coli using TMB as substrate after 30 mins by indirect ELISA assay	ic50	0.0005	uM
2-[2-fluoro-4-[(2-fluoro-3-nitrophenyl)methylsulfonyl]phenyl]sulfanyl-5-methoxy-N-(5-methyl-1H-pyrazol-3-yl)-6-piperidin-1-ylpyrimidin-4-amine	2073833: Binding affinity to PLK4 (unknown origin) assessed as inhibition constant	ki	0.0006	uM
5-methoxy-3-[(E)-[3-[(E)-2-[6-(4-methylpiperazin-1-yl)-3-pyridinyl]ethenyl]indazol-6-ylidene]methyl]-1H-indol-2-ol	762246: Inhibition of N-terminal GST-tagged human PLK4 (1 to 391 amino acids) expressed in Escherichia coli using TMB as substrate after 30 mins by indirect ELISA assay	ic50	0.0006	uM
(2’S,3R)-2’-[3-[(E)-2-[4-[[(3S,5R)-3,4,5-trimethylpiperazin-1-yl]methyl]phenyl]ethenyl]-1H-indazol-6-yl]spiro[1H-indole-3,1’-cyclopropane]-2-one	1198659: Inhibition of PLK4 (unknown origin) by ELISA	ic50	0.0006	uM
(2’S,3R)-2’-[3-[(E)-2-[4-[(dimethylamino)methyl]phenyl]ethenyl]-1H-indazol-6-yl]spiro[1H-indole-3,1’-cyclopropane]-2-one	1198659: Inhibition of PLK4 (unknown origin) by ELISA	ic50	0.0006	uM
(2’S,3R)-5-methoxy-2’-[3-[(E)-2-[4-(piperidin-1-ylmethyl)phenyl]ethenyl]-1H-indazol-6-yl]spiro[1H-indole-3,1’-cyclopropane]-2-one	1198659: Inhibition of PLK4 (unknown origin) by ELISA	ic50	0.0006	uM
6-N-[(2-chlorophenyl)methyl]-4-N-(5-methyl-1H-pyrazol-3-yl)-1H-pyrazolo[5,4-d]pyrimidine-4,6-diamine	1860388: Inhibition of recombinant human PLK4 incubated for 60 mins by Lanthascreen Eu kinase binding assay	ic50	0.0007	uM
6-N-[(2,4-difluorophenyl)methyl]-4-N-(5-ethyl-1H-pyrazol-3-yl)-1-(oxan-4-yl)pyrazolo[3,4-d]pyrimidine-4,6-diamine	1860388: Inhibition of recombinant human PLK4 incubated for 60 mins by Lanthascreen Eu kinase binding assay	ic50	0.0007	uM
6-N-[(2,4-difluorophenyl)methyl]-4-N-(5-methyl-1H-pyrazol-3-yl)-1-piperidin-4-ylpyrazolo[3,4-d]pyrimidine-4,6-diamine	1860388: Inhibition of recombinant human PLK4 incubated for 60 mins by Lanthascreen Eu kinase binding assay	ic50	0.0007	uM
(2’S,3R)-2’-[3-[(E)-2-[4-[[(2S,6R)-2,6-dimethylmorpholin-4-yl]methyl]phenyl]ethenyl]-1H-indazol-6-yl]spiro[1H-indole-3,1’-cyclopropane]-2-one	1198709: Competitive binding to PLK4 (unknown origin) by double reciprocal plot analysis in presence of ATP	ki	0.0007	uM
(2’S,3R)-2’-[3-[(E)-2-[4-[(dimethylamino)methyl]phenyl]ethenyl]-1H-indazol-6-yl]-5-methylspiro[1H-indole-3,1’-cyclopropane]-2-one	1178617: Inhibition of human N-terminal GST-tagged PLK4 (1 to 391 residues) expressed in Escherichia coli incubated for 30 mins by ELISA method	ic50	0.0007	uM
(2’S,3R)-5-methoxy-2’-[3-[6-(4-methylpiperazin-1-yl)-3-pyridinyl]-1H-indazol-6-yl]spiro[1H-indole-3,1’-cyclopropane]-2-one	1630306: Inhibition of PLK4 (unknown origin)	ic50	0.0007	uM
4-[(E)-2-[(6E)-6-[(2-hydroxy-1H-indol-3-yl)methylidene]indazol-3-yl]ethenyl]benzoic acid	762246: Inhibition of N-terminal GST-tagged human PLK4 (1 to 391 amino acids) expressed in Escherichia coli using TMB as substrate after 30 mins by indirect ELISA assay	ic50	0.0008	uM
6-N-[(4-fluorophenyl)methyl]-4-N-(5-methyl-1H-pyrazol-3-yl)-1H-pyrazolo[5,4-d]pyrimidine-4,6-diamine	1860388: Inhibition of recombinant human PLK4 incubated for 60 mins by Lanthascreen Eu kinase binding assay	ic50	0.0008	uM
(2S,3R,4R,6R)-3-methoxy-2-methyl-4-(methylamino)-29-oxa-1,7,17-triazaoctacyclo[12.12.2.12,6.07,28.08,13.015,19.020,27.021,26]nonacosa-8,10,12,14,19,21,23,25,27-nonaen-16-one	256607: Average Binding Constant for STK18; NA=Not Active at 10 uM	kd	0.0008	uM
(2’S,3R)-5-methoxy-2’-[3-[(E)-2-[6-(4-methylpiperazin-1-yl)-3-pyridinyl]ethenyl]-1H-indazol-6-yl]spiro[1H-indole-3,1’-cyclopropane]-2-one	1198659: Inhibition of PLK4 (unknown origin) by ELISA	ic50	0.0008	uM
(2’S,3R)-2’-[3-[(E)-2-[4-[(dimethylamino)methyl]phenyl]ethenyl]-1H-indazol-6-yl]-5-fluorospiro[1H-indole-3,1’-cyclopropane]-2-one	1178617: Inhibition of human N-terminal GST-tagged PLK4 (1 to 391 residues) expressed in Escherichia coli incubated for 30 mins by ELISA method	ic50	0.0008	uM
3-[(E)-[3-[(E)-2-pyridin-4-ylethenyl]indazol-6-ylidene]methyl]-1H-indole-2,5-diol	762246: Inhibition of N-terminal GST-tagged human PLK4 (1 to 391 amino acids) expressed in Escherichia coli using TMB as substrate after 30 mins by indirect ELISA assay	ic50	0.0009	uM
5-chloro-2-N-[2-methoxy-4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]phenyl]-4-N-(2-propan-2-ylsulfonylphenyl)pyrimidine-2,4-diamine	625076: Binding constant for PLK4 kinase domain	kd	0.0009	uM
2-chloro-N-(2,5-difluorophenyl)-5-[[[4-[(5-methyl-1H-pyrazol-3-yl)amino]-1-(oxan-4-yl)pyrazolo[3,4-d]pyrimidin-6-yl]amino]methyl]benzamide	2027756: Inhibition of PLK4 (unknown origin) incubated for 1 hr by FRET assay	ic50	0.0009	uM
(2’S,3R)-5-methoxy-2’-[3-[(E)-2-[4-(morpholin-4-ylmethyl)phenyl]ethenyl]-1H-indazol-6-yl]spiro[1H-indole-3,1’-cyclopropane]-2-one	1198659: Inhibition of PLK4 (unknown origin) by ELISA	ic50	0.0009	uM
(2’S,3R)-2’-[3-[(E)-2-(4-piperazin-1-ylphenyl)ethenyl]-1H-indazol-6-yl]spiro[1H-indole-3,1’-cyclopropane]-2-one	1198659: Inhibition of PLK4 (unknown origin) by ELISA	ic50	0.0009	uM
(2’S,3R)-2’-[3-[(E)-2-[4-(piperidin-1-ylmethyl)phenyl]ethenyl]-1H-indazol-6-yl]spiro[1H-indole-3,1’-cyclopropane]-2-one	1198659: Inhibition of PLK4 (unknown origin) by ELISA	ic50	0.0009	uM
(2’S,3R)-5-methoxy-2’-[3-[4-(4-methylpiperazin-1-yl)phenyl]-1H-indazol-6-yl]spiro[1H-indole-3,1’-cyclopropane]-2-one	1630306: Inhibition of PLK4 (unknown origin)	ic50	0.0009	uM
(2’S,3R)-2’-[3-[(E)-2-[4-(pyrrolidin-1-ylmethyl)phenyl]ethenyl]-1H-indazol-6-yl]spiro[1H-indole-3,1’-cyclopropane]-2-one	1198659: Inhibition of PLK4 (unknown origin) by ELISA	ic50	0.0009	uM
6-N-[(2-fluorophenyl)methyl]-4-N-(5-methyl-1H-pyrazol-3-yl)-1H-pyrazolo[5,4-d]pyrimidine-4,6-diamine	1860388: Inhibition of recombinant human PLK4 incubated for 60 mins by Lanthascreen Eu kinase binding assay	ic50	0.0010	uM
2-chloro-N-(2,5-difluorophenyl)-5-[[[4-[(5-methyl-1H-pyrazol-3-yl)amino]-1-(1-methylsulfonylpiperidin-4-yl)pyrazolo[3,4-d]pyrimidin-6-yl]amino]methyl]benzamide	2027756: Inhibition of PLK4 (unknown origin) incubated for 1 hr by FRET assay	ic50	0.0010	uM
6-N-[(2,4-difluorophenyl)methyl]-4-N-(5-methyl-1H-pyrazol-3-yl)-1-propan-2-ylpyrazolo[3,4-d]pyrimidine-4,6-diamine	1860388: Inhibition of recombinant human PLK4 incubated for 60 mins by Lanthascreen Eu kinase binding assay	ic50	0.0011	uM
(2’S,3R)-2’-[3-[(E)-2-[4-(1-methylpiperidin-4-yl)oxyphenyl]ethenyl]-1H-indazol-6-yl]spiro[1H-indole-3,1’-cyclopropane]-2-one	1198659: Inhibition of PLK4 (unknown origin) by ELISA	ic50	0.0011	uM
2-chloro-N-(2,5-difluorophenyl)-5-[[[1-methyl-4-[(5-methyl-1H-pyrazol-3-yl)amino]pyrazolo[3,4-d]pyrimidin-6-yl]amino]methyl]benzamide	2027756: Inhibition of PLK4 (unknown origin) incubated for 1 hr by FRET assay	ic50	0.0012	uM
(2’S,3R)-2’-[3-[4-[(3R,5S)-3,5-dimethylpiperazin-1-yl]phenyl]-1H-indazol-6-yl]-5-methoxyspiro[1H-indole-3,1’-cyclopropane]-2-one	1630306: Inhibition of PLK4 (unknown origin)	ic50	0.0012	uM
(2’S,3R)-2’-[3-[4-[4-(2-hydroxyethyl)piperazin-1-yl]phenyl]-1H-indazol-6-yl]-5-methoxyspiro[1H-indole-3,1’-cyclopropane]-2-one	1630306: Inhibition of PLK4 (unknown origin)	ic50	0.0012	uM
(2’S,3R)-5-chloro-2’-[3-[(E)-2-[4-[(dimethylamino)methyl]phenyl]ethenyl]-1H-indazol-6-yl]spiro[1H-indole-3,1’-cyclopropane]-2-one	1178617: Inhibition of human N-terminal GST-tagged PLK4 (1 to 391 residues) expressed in Escherichia coli incubated for 30 mins by ELISA method	ic50	0.0012	uM
(1R,2S)-1’-methyl-2-[3-[(E)-2-[6-(4-methylpiperazin-1-yl)-3-pyridinyl]ethenyl]-1H-indazol-6-yl]spiro[cyclopropane-1,3’-indole]-2’-one	1198659: Inhibition of PLK4 (unknown origin) by ELISA	ic50	0.0013	uM
5-methyl-3-[(E)-[3-[(E)-2-pyridin-4-ylethenyl]indazol-6-ylidene]methyl]-1H-indol-2-ol	762246: Inhibition of N-terminal GST-tagged human PLK4 (1 to 391 amino acids) expressed in Escherichia coli using TMB as substrate after 30 mins by indirect ELISA assay	ic50	0.0014	uM
3-[(E)-[3-[(E)-2-[6-(4-methylpiperazin-1-yl)-3-pyridinyl]ethenyl]indazol-6-ylidene]methyl]-1H-indol-2-ol	762246: Inhibition of N-terminal GST-tagged human PLK4 (1 to 391 amino acids) expressed in Escherichia coli using TMB as substrate after 30 mins by indirect ELISA assay	ic50	0.0014	uM

CTD chemical–gene interactions

76 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects expression, decreases expression, affects cotreatment, increases abundance	3
Valproic Acid	decreases expression, affects expression	3
Cyclosporine	decreases expression	3
bisphenol A	decreases expression, increases expression	2
Resveratrol	affects cotreatment, increases expression	2
Acetaminophen	increases expression, decreases expression	2
Estradiol	increases expression	2
Tretinoin	decreases expression	2
Cadmium Chloride	affects binding, increases reaction, increases localization, decreases expression, increases expression	2
aristolochic acid I	decreases expression	1
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
afuresertib	decreases expression	1
echimidine	decreases expression, increases metabolic processing	1
dicrotophos	decreases expression	1
diminazene aceturate	decreases expression	1
lasiocarpine	decreases expression, increases metabolic processing	1
triphenyl phosphate	affects expression	1
propionaldehyde	decreases expression	1
trichostatin A	affects expression	1
riddelliine	decreases expression, increases metabolic processing	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
perfluorooctanoic acid	decreases expression	1
manganese chloride	affects cotreatment, decreases expression, increases abundance	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, increases expression	1
caffeic acid	increases expression, increases reaction	1
beta-methylcholine	affects expression	1
phenethyl isothiocyanate	decreases expression	1
tamibarotene	decreases expression	1
4-methoxycinnamate methyl ester	increases expression, increases reaction	1
2-palmitoylglycerol	increases expression	1

ChEMBL screening assays

303 unique, capped per target: 293 binding, 10 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1004495	Binding	Binding affinity to human recombinant PLK4 expressed in Escherichia coli assessed as thermal shift by differential scanning fluorimetry	Discovery of a potent and selective inhibitor for human carbonyl reductase 1 from propionate scanning applied to the macrolide zearalenone. — *Bioorg Med Chem*
CHEMBL1963705	Functional	PUBCHEM_BIOASSAY: Navigating the Kinome. (Class of assay: other) Panel member name: PLK4	PubChem BioAssay data set

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

54 trials:

NCT	Phase	Status	Title
NCT04224207	Phase 3	COMPLETED	Management of Retinitis Pigmentosa by Mesenchymal Stem Cells by Wharton’s Jelly Derived Mesenchymal Stem Cells
NCT07082855	Phase 3	NOT_YET_RECRUITING	A Multicenter, Randomized, Double-Blind, Controlled Clinical Study of Minocycline for the Treatment of Retinitis Pigmentosa
NCT03763227	Phase 2	COMPLETED	Intravitreal Ranibizumab (Lucentis®) in the Treatment of Non-leaking Macular Cysts in Retinal Dystrophy
NCT04068207	Phase 2	COMPLETED	Minocycline Treatment in Retinitis Pigmentosa
NCT04945772	Phase 2	COMPLETED	Efficacy and Safety of MCO-010 Optogenetic Therapy in Adults With Retinitis Pigmentosa [RESTORE]
NCT05902962	Phase 1	COMPLETED	SAD of IVT VP-001 in PRPF31 Mutation-Associated Retinal Dystrophy Subjects
NCT06319872	Phase 1	RECRUITING	The Effects of Disulfiram (Antabuse®) on Visual Acuity in Patients With Retinal Degeneration
NCT06455826	Phase 1	COMPLETED	MAD of IVT VP-001 in PRPF31 Mutation-Associated Retinal Dystrophy Subjects (Wallaby)
NCT04737460	Phase 1	ACTIVE_NOT_RECRUITING	Study for the Treatment for CLN7 Disease
NCT01064505	Phase 1	COMPLETED	Safety Study of a Single IVT Injection of QPI-1007 in Chronic Optic Nerve Atrophy and Recent Onset NAION Patients
NCT05147701	Phase 1	RECRUITING	Safety of Cultured Allogeneic Adult Umbilical Cord Derived Mesenchymal Stem Cells for NAION
NCT03139903	Not specified	COMPLETED	The Primordial Dwarfisms: Diagnosis, Identification of the Molecular Basis of Seckel Syndrome and Microcephalic Osteodysplastic Primordial Dwarfism Type II
NCT04855045	Phase 2/3	UNKNOWN	An Open-label, Dose Escalation and Double-masked, Randomized, Controlled Trial Evaluating Safety and Tolerability of Sepofarsen in Children (<8 Years of Age) With LCA10 Caused by Mutations in the CEP290 Gene.
NCT03872479	Phase 1/2	UNKNOWN	Single Ascending Dose Study in Participants With LCA10
NCT04123626	Phase 1/2	ACTIVE_NOT_RECRUITING	A Study to Evaluate the Safety and Tolerability of QR-1123 in Subjects With Autosomal Dominant Retinitis Pigmentosa Due to the P23H Mutation in the RHO Gene
NCT04545736	Phase 1/2	ACTIVE_NOT_RECRUITING	Oral Metformin for Treatment of ABCA4 Retinopathy
NCT06212297	Phase 1/2	ACTIVE_NOT_RECRUITING	Fellow-eye Study (FE) of LX101 in Subjects With Inherited Retinal Dystrophy
NCT06852963	Phase 1/2	ACTIVE_NOT_RECRUITING	A Repeat-Dose, Open-Label, Two Arm Safety and Efficacy Study of Two Doses of VP-001 Administered Intravitreally in Participants With Confirmed PRPF31 Mutation-Associated Retinal Dystrophy, Including Participants Previously Treated With VP001
NCT07177196	Phase 1/2	ACTIVE_NOT_RECRUITING	Personalized Antisense Oligonucleotide Therapy for a Single Participant With PRPH2 Mutation Associated With Retinal Dystrophy
NCT07063030	Early Phase 1	RECRUITING	A Study of LX107 Gene Therapy in AIPL1-IRD Patients
NCT07656753	Early Phase 1	RECRUITING	Safety and Efficacy Study of PUMCH-E111 Injection in Subjects With RLBP1 Related Inherited Retinal Dystrophy
NCT01546181	Not specified	COMPLETED	Retinal Imaging by Adaptive Optics in Healthy Eyes and During Retinal and General Diseases
NCT01876147	Not specified	COMPLETED	Visual and Functional Assessment in Low Vision Patients
NCT01920867	Not specified	UNKNOWN	Stem Cell Ophthalmology Treatment Study
NCT02014389	Not specified	RECRUITING	Evaluation of Objective Perimetry Using Chromatic Multifocal Pupillometer
NCT02983305	Not specified	COMPLETED	Optical Head-Mounted Display Technology for Low Vision Rehabilitation
NCT03592017	Not specified	COMPLETED	Performance of Long-wavelength Autofluorescence Imaging
NCT03662386	Not specified	TERMINATED	Prospective Analysis of Genotype-phenotype Correlations Observed in a Large Cohort of Patients With Hereditary Retinal Dystrophies - GEPHIRD
NCT03691168	Not specified	UNKNOWN	Multi-center Observation of the Natural Course of Inherited Retinal Dystrophies
NCT03843840	Not specified	COMPLETED	Dual Wavelength OCT
NCT03853252	Not specified	COMPLETED	iPS Cells of Patients for Models of Retinal Dystrophies
NCT05130385	Not specified	UNKNOWN	High Resolution Optical Coherence Tomography
NCT05294978	Not specified	RECRUITING	EyeConic: Qualification for Cone-Optogenetics
NCT05573984	Not specified	ACTIVE_NOT_RECRUITING	Natural History of PRPF31 Mutation-Associated Retinal Dystrophy
NCT05793515	Not specified	COMPLETED	Mechanisms of Inherited Retinal Dystrophies Using Whole Genome Sequencing and in Vitro and in Vivo Models
NCT05820100	Not specified	COMPLETED	Observational Study to Assess the Reliability and Validity of the MLYMT and MLSDT
NCT05976139	Not specified	RECRUITING	Micropulsed Laser in Patients With Macular Oedema in Retinal Dystrophies
NCT06162585	Not specified	ACTIVE_NOT_RECRUITING	Non-Interventional Long Term Follow-up Study of Participants Previously Enrolled in the RESTORE Study
NCT06177977	Not specified	RECRUITING	SS-HH-OCT as a Novel Diagnostic Modality for Early-Onset Retinal Dystrophies (EORDs)
NCT06375239	Not specified	RECRUITING	Observational Study to Assess Endpoint Operational Feasibility & Measurement Properties in Patients with Retinal Degeneration
NCT06908161	Not specified	NOT_YET_RECRUITING	Functional Assessments in Vision Impairment
NCT07085533	Not specified	RECRUITING	Natural History Study of Inherited Retinal Diseases
NCT07502664	Not specified	RECRUITING	Development and Evaluation of Functional Visual Field and Navigation Endpoints in Moderate to Profound Inherited Retinal Disease (DEFINE-IRD)
NCT07529041	Not specified	ENROLLING_BY_INVITATION	Real-time Acoustic Biofeedback for Enhancing Fixation Stability: A Proof-of-concept Study to Improve Ophthalmic Imaging Diagnostic Quality
NCT04613089	Not specified	RECRUITING	Natural History and Longitudinal Clinical Assessments in NCL / Batten Disease, the International DEM-CHILD Database
NCT02882477	Phase 2/3	UNKNOWN	Treatment of Wolfram Syndrome Type 2 With the Chelator Deferiprone and Incretin Based Therapy
NCT01834079	Phase 1/2	UNKNOWN	Study the Safety and Efficacy of Bone Marrow Derived Autologous Cells for the Treatment of Optic Nerve Disease
NCT04680143	Phase 1/2	COMPLETED	Systemic Erythropoietin Injection in Patients Having Optic Atrophy
NCT03011541	Not specified	RECRUITING	Stem Cell Ophthalmology Treatment Study II
NCT04580979	Not specified	COMPLETED	Natural History Study of FDXR Mutation-related Mitochondriopathy
NCT04594590	Not specified	COMPLETED	Natural History Study of SLC25A46 Mutation-related Mitochondriopathy
NCT04723160	Not specified	COMPLETED	Computer Aided Diagnosis of Multiple Eye Fundus Diseases From Color Fundus Photograph
NCT06390579	Not specified	COMPLETED	Building Research With Artificial Intelligence in Neuro-Ophthalmology
NCT06566066	Not specified	RECRUITING	Register for Patients With Thyroid Hormone Resistance.

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for PLK4 across ~30M SureChEMBL compounds — explore on Sugi Predict.