PKN3

Summary

PKN3 (protein kinase N3, HGNC:17999) is a protein-coding gene on chromosome 9q34.11, encoding Serine/threonine-protein kinase N3 (Q6P5Z2). Contributes to invasiveness in malignant prostate cancer.

Predicted to enable protein serine/threonine kinase activity. Involved in epithelial cell migration. Predicted to be located in Golgi apparatus; cytosol; and nucleus.

Source: NCBI Gene 29941 — RefSeq curated summary.

At a glance

• GWAS associations: 16
• Clinical variants (ClinVar): 223 total
• Druggable target: yes — 3 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_013355

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17999
Approved symbol	PKN3
Name	protein kinase N3
Location	9q34.11
Locus type	gene with protein product
Status	Approved
Aliases	PKNbeta, UTDP4-1
Ensembl gene	ENSG00000160447
Ensembl biotype	protein_coding
OMIM	610714
Entrez	29941

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 9 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000291906, ENST00000483521, ENST00000485301, ENST00000855131, ENST00000855132, ENST00000855133, ENST00000935674, ENST00000935675, ENST00000935676, ENST00000935677, ENST00000935678

RefSeq mRNA: 2 — MANE Select: NM_013355 NM_001317926, NM_013355

CCDS: CCDS6908

Canonical transcript exons

ENST00000291906 — 22 exons

Exon	Start	End
ENSE00001052437	128714562	128714664
ENSE00001052439	128705303	128705543
ENSE00001052450	128706713	128706824
ENSE00001052451	128720203	128720283
ENSE00001052452	128707222	128707405
ENSE00001052454	128713052	128713198
ENSE00001052457	128719910	128720017
ENSE00001052460	128706896	128707023
ENSE00001052463	128715369	128715460
ENSE00001052466	128714197	128714365
ENSE00001110159	128705734	128705879
ENSE00001347826	128702503	128702939
ENSE00001367841	128720394	128720916
ENSE00003477017	128719686	128719828
ENSE00003506740	128715172	128715235
ENSE00003554293	128718325	128718387
ENSE00003587818	128713278	128713387
ENSE00003589647	128714798	128714865
ENSE00003610508	128713499	128713642
ENSE00003678687	128714046	128714121
ENSE00003682866	128718549	128718625
ENSE00003694121	128716747	128716923

Expression profiles

Bgee: expression breadth ubiquitous, 175 present calls, max score 89.79.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 2.8033 / max 45.8352, expressed in 1038 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
98831	1.8644	880
98833	0.5740	351
98832	0.3649	186

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
apex of heart	UBERON:0002098	89.79	gold quality
ventricular zone	UBERON:0003053	85.15	gold quality
right lung	UBERON:0002167	83.27	gold quality
omental fat pad	UBERON:0010414	82.78	gold quality
peritoneum	UBERON:0002358	82.71	gold quality
adipose tissue of abdominal region	UBERON:0007808	82.30	gold quality
upper lobe of left lung	UBERON:0008952	81.95	gold quality
subcutaneous adipose tissue	UBERON:0002190	81.90	gold quality
minor salivary gland	UBERON:0001830	81.60	gold quality
upper lobe of lung	UBERON:0008948	81.42	gold quality
heart left ventricle	UBERON:0002084	81.01	gold quality
right hemisphere of cerebellum	UBERON:0014890	80.85	gold quality
cerebellar hemisphere	UBERON:0002245	80.83	gold quality
cerebellar cortex	UBERON:0002129	80.59	gold quality
cardiac ventricle	UBERON:0002082	80.26	gold quality
saliva-secreting gland	UBERON:0001044	79.97	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	79.96	gold quality
adipose tissue	UBERON:0001013	79.52	gold quality
cerebellum	UBERON:0002037	79.26	gold quality
left uterine tube	UBERON:0001303	79.09	gold quality
body of uterus	UBERON:0009853	78.69	gold quality
ganglionic eminence	UBERON:0004023	78.63	gold quality
body of stomach	UBERON:0001161	78.13	gold quality
right lobe of thyroid gland	UBERON:0001119	77.81	gold quality
right atrium auricular region	UBERON:0006631	77.74	gold quality
mouth mucosa	UBERON:0003729	77.56	gold quality
metanephros cortex	UBERON:0010533	77.48	gold quality
mucosa of transverse colon	UBERON:0004991	77.35	gold quality
spleen	UBERON:0002106	77.24	gold quality
lower esophagus muscularis layer	UBERON:0035833	77.21	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.02

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

5 targeting PKN3, 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-4447	99.85	67.81	2900
HSA-MIR-4472	99.56	66.08	1478
HSA-MIR-6799-5P	99.14	65.72	2093
HSA-MIR-216B-3P	98.55	67.19	1223
HSA-MIR-5088-5P	97.97	64.28	487

Literature-anchored findings (GeneRIF, showing 7)

• PKN3 might represent a preferred target for therapeutic intervention in cancers that lack tumor suppressor PTEN function or depend on chronic activation of phosphoinositide 3-kinase (PMID:15282551)
• PKN isoforms are not simply redundant in supporting migration, but appear to be linked through isoform specific regulatory domain properties to selective upstream signals. It (PMID:21754995)
• PKN3 can be considered a novel protein implicated in remodeling the actin-adherens junction, possibly by linking ICAM-1-signaling with actin/AJ dynamics. (PMID:22609186)
• PKN3 is the major regulator of angiogenesis in humans and mice and tumor metastasis in mice. (PMID:26742562)
• Steady-state kinetic analysis revealed that PKN1-3 follows a sequential ordered Bi-Bi kinetic mechanism, where peptide substrate binding is preceded by ATP binding. This kinetic mechanism was confirmed by additional kinetic studies for product inhibition and affinity of small molecule inhibitors. (PMID:27919031)
• a novel interaction of p130Cas with Ser/Thr kinase PKN3, is reported. (PMID:30422386)
• A Screen for PKN3 Substrates Reveals an Activating Phosphorylation of ARHGAP18. (PMID:33092266)

Cross-species orthologs

11 orthologs

Organism	Symbol	Gene ID
danio_rerio	prkcg	ENSDARG00000004561
danio_rerio	pkn3	ENSDARG00000079585
mus_musculus	Pkn3	ENSMUSG00000026785
rattus_norvegicus	Pkn3	ENSRNOG00000025892
drosophila_melanogaster	Pkc53E	FBGN0003091
drosophila_melanogaster	inaC	FBGN0004784
drosophila_melanogaster	Pkn	FBGN0020621
drosophila_melanogaster	Pkcdelta	FBGN0287828
caenorhabditis_elegans		WBGENE00004033
caenorhabditis_elegans		WBGENE00006599
caenorhabditis_elegans		WBGENE00009793

Paralogs (9): PRKCH (ENSG00000027075), PKN2 (ENSG00000065243), PRKCZ (ENSG00000067606), PKN1 (ENSG00000123143), PRKCG (ENSG00000126583), PRKCA (ENSG00000154229), PRKCI (ENSG00000163558), PRKCB (ENSG00000166501), PRKCE (ENSG00000171132)

Protein

Protein identifiers

Serine/threonine-protein kinase N3 — Q6P5Z2 (reviewed: Q6P5Z2)

Alternative names: Protein kinase PKN-beta, Protein-kinase C-related kinase 3

All UniProt accessions (1): Q6P5Z2

UniProt curated annotations — full annotation on UniProt →

Function. Contributes to invasiveness in malignant prostate cancer.

Subcellular location. Nucleus. Cytoplasm. Perinuclear region.

Tissue specificity. Expressed in prostate tumors and various cancer cell lines. Not expressed in adult tissues.

Post-translational modifications. Autophosphorylated.

Activity regulation. Two specific sites, Thr-718 (activation loop of the kinase domain) and Thr-860 (turn motif), need to be phosphorylated for its full activation.

Domain organisation. The C1 domain does not bind the diacylglycerol (DAG).

Similarity. Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. PKC subfamily.

RefSeq proteins (2): NP_001304855, NP_037487* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000719	Prot_kinase_dom	Domain
IPR000961	AGC-kinase_C	Domain
IPR008271	Ser/Thr_kinase_AS	Active_site
IPR011009	Kinase-like_dom_sf	Homologous_superfamily
IPR011072	HR1_rho-bd	Domain
IPR017441	Protein_kinase_ATP_BS	Binding_site
IPR017892	Pkinase_C	Domain
IPR035892	C2_domain_sf	Homologous_superfamily
IPR036274	HR1_rpt_sf	Homologous_superfamily
IPR037313	PKN_HR1_1	Domain

Pfam: PF00069, PF00433, PF02185

Catalyzed reactions (Rhea), 2 shown:

• 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 (28 total): modified residue 6, domain 5, sequence conflict 5, mutagenesis site 3, binding site 2, sequence variant 2, compositionally biased region 2, chain 1, region of interest 1, active site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6P5Z2-F1	75.11	0.33

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): 684 (proton acceptor)

Ligand- & substrate-binding residues (2): 565–573; 588

Post-translational modifications (6): 171, 544, 548, 718, 722, 860

Mutagenesis-validated functional residues (3):

Position	Phenotype
588	abolishes autophosphorylation and catalytic activity.
588	abolishes catalytic activity.
718	abolishes phosphorylation.

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-5625740	RHO GTPases activate PKNs
R-HSA-8980692	RHOA GTPase cycle
R-HSA-9013026	RHOB GTPase cycle
R-HSA-9013106	RHOC GTPase cycle

MSigDB gene sets: 94 (showing top): GOMF_GTPASE_BINDING, GOBP_AMEBOIDAL_TYPE_CELL_MIGRATION, IRF7_01, GOBP_TISSUE_MIGRATION, BILD_E2F3_ONCOGENIC_SIGNATURE, BACH2_01, TGANTCA_AP1_C, NRF2_Q4, RYTTCCTG_ETS2_B, BARIS_THYROID_CANCER_DN, NFE2_01, AP1FJ_Q2, MARSON_BOUND_BY_FOXP3_UNSTIMULATED, SANSOM_APC_MYC_TARGETS, SCGGAAGY_ELK1_02

GO Biological Process (4): protein phosphorylation (GO:0006468), signal transduction (GO:0007165), epithelial cell migration (GO:0010631), intracellular signal transduction (GO:0035556)

GO Molecular Function (10): protein kinase activity (GO:0004672), protein serine/threonine kinase activity (GO:0004674), diacylglycerol-dependent serine/threonine kinase activity (GO:0004697), ATP binding (GO:0005524), small GTPase binding (GO:0031267), protein serine kinase activity (GO:0106310), nucleotide binding (GO:0000166), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740)

GO Cellular Component (5): nucleus (GO:0005634), Golgi apparatus (GO:0005794), cytosol (GO:0005829), perinuclear region of cytoplasm (GO:0048471), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
RHO GTPase cycle	3
RHO GTPase Effectors	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cytoplasm	3
cellular anatomical structure	3
intracellular anatomical structure	2
protein kinase activity	2
intracellular membrane-bounded organelle	2
phosphorylation	1
protein modification process	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
ameboidal-type cell migration	1
epithelium migration	1
signal transduction	1
kinase activity	1
phosphotransferase activity, alcohol group as acceptor	1
catalytic activity, acting on a protein	1
protein serine/threonine kinase activity	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
GTPase binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
binding	1
transferase activity, transferring phosphorus-containing groups	1
catalytic activity	1
endomembrane system	1

Protein interactions and networks

STRING

1242 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PKN3	ARHGAP10	A1A4S6	934
PKN3	ARHGAP26	Q9UNA1	895
PKN3	RHOC	P08134	750
PKN3	RHOA	P06749	699
PKN3	SRC	P12931	634
PKN3	RRM2	P31350	578
PKN3	PTK2	Q05397	512
PKN3	GTPBP4	Q9BZE4	497
PKN3	NCK2	O43639	493
PKN3	ARHGAP1	Q07960	487
PKN3	RAC1	P15154	466
PKN3	CCDC8	Q9H0W5	457
PKN3	CDC42	P21181	451
PKN3	NCK1	P16333	442
PKN3	FGD6	Q6ZV73	432

IntAct

176 interactions, top by confidence:

A	B	Type	Score
RHOA	ARHGEF11	psi-mi:“MI:0914”(association)	0.900
KRT31	HGS	psi-mi:“MI:0914”(association)	0.780
PKN3	ARHGAP26	psi-mi:“MI:0915”(physical association)	0.680
PKN3	ARHGAP10	psi-mi:“MI:0915”(physical association)	0.680
ARHGAP26	PKN3	psi-mi:“MI:0915”(physical association)	0.680
PKN3	ARHGAP10	psi-mi:“MI:0914”(association)	0.680
KRT31	PKN3	psi-mi:“MI:0915”(physical association)	0.670
EFNB3	DENND11	psi-mi:“MI:0914”(association)	0.640
MTUS2	PKN3	psi-mi:“MI:0915”(physical association)	0.560
PKN3	PNMA1	psi-mi:“MI:0915”(physical association)	0.560
PKN3	TFIP11	psi-mi:“MI:0915”(physical association)	0.560
PKN3	VPS52	psi-mi:“MI:0915”(physical association)	0.560
GOLGA2	PKN3	psi-mi:“MI:0915”(physical association)	0.560
PLD1	PKN3	psi-mi:“MI:0915”(physical association)	0.540
PLD1	PKN3	psi-mi:“MI:0407”(direct interaction)	0.540
rho-1	PKN3	psi-mi:“MI:0407”(direct interaction)	0.540
PKN3	rho-1	psi-mi:“MI:0915”(physical association)	0.540
HNRNPH2	PLOD2	psi-mi:“MI:0914”(association)	0.530
MANSC1	KLRG2	psi-mi:“MI:0914”(association)	0.530
MAS1	POTEF	psi-mi:“MI:0914”(association)	0.530
HAVCR2	TCAF2	psi-mi:“MI:0914”(association)	0.530
VSIG4	TCAF2	psi-mi:“MI:0914”(association)	0.530

BioGRID (228): PKN3 (Affinity Capture-MS), PKN3 (Affinity Capture-MS), PKN3 (Affinity Capture-MS), PKN3 (Affinity Capture-MS), PKN3 (Affinity Capture-MS), PKN3 (Affinity Capture-MS), PKN3 (Affinity Capture-MS), PKN3 (Affinity Capture-MS), PKN3 (Affinity Capture-MS), PKN3 (Affinity Capture-MS), PKN3 (Affinity Capture-MS), PKN3 (Affinity Capture-MS), PKN3 (Affinity Capture-MS), PKN3 (Affinity Capture-MS), PKN3 (Affinity Capture-MS)

ESM2 similar proteins: A1A4I4, A1A5B6, A4D2P6, B2DCZ9, B4F7F3, O00192, O08773, O08874, O08908, O35465, O43566, O62683, O75808, O95049, P70268, P97492, Q0QWG9, Q12851, Q14164, Q14318, Q16512, Q16513, Q3B7U9, Q3KR56, Q3MII6, Q3UFB7, Q5FVC2, Q60875, Q61161, Q63433, Q63788, Q6P5Z2, Q6PFQ7, Q6V7V2, Q6ZT62, Q7Z5H3, Q865S3, Q8BWW9, Q8IYK8, Q8K045

Diamond homologs: A0A509AKL0, A1A4I4, A5K0N4, A7MBL8, A8XJQ6, A8XNJ6, A8XW88, F4HYG2, G1X456, J9W0G9, O42632, O43930, O77676, P00516, P00517, P04409, P05131, P05132, P05383, P05696, P05986, P06244, P06245, P0C605, P10102, P10665, P10666, P11792, P12370, P12688, P16911, P16912, P17252, P17612, P18652, P18654, P18961, P20444, P21137, P22612

SIGNOR signaling

5 interactions.

A	Effect	B	Mechanism
BCAR1	“up-regulates activity”	PKN3	binding
PKN3	“up-regulates activity”	ARHGAP18	phosphorylation
PKN3	unknown	BCAR1	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 190 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
RHOJ GTPase cycle	6	11.7×	7e-04
RHOQ GTPase cycle	6	10.6×	1e-03
RHOB GTPase cycle	7	10.5×	4e-04
RHOD GTPase cycle	5	9.9×	4e-03
RHOC GTPase cycle	6	8.5×	2e-03
PKR-mediated signaling	6	8.2×	3e-03
EML4 and NUDC in mitotic spindle formation	9	8.1×	3e-04
Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal	7	7.9×	1e-03

GO biological processes:

GO term	Partners	Fold	FDR
endocytic recycling	7	11.9×	1e-03
mitotic cell cycle	9	7.7×	1e-03
protein transport	15	4.2×	1e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	189
Likely benign	8
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

3315 predictions. Top by Δscore:

Variant	Effect	Δscore
9:128705540:GCTG:G	donor_gain	1.0000
9:128706702:T:TA	acceptor_gain	1.0000
9:128706703:G:A	acceptor_gain	1.0000
9:128706710:T:G	acceptor_gain	1.0000
9:128706711:A:AG	acceptor_gain	1.0000
9:128706711:AGG:A	acceptor_loss	1.0000
9:128706712:G:A	acceptor_loss	1.0000
9:128706712:G:GG	acceptor_gain	1.0000
9:128706712:GGA:G	acceptor_gain	1.0000
9:128706712:GGAGA:G	acceptor_gain	1.0000
9:128706807:G:GG	donor_gain	1.0000
9:128706823:AG:A	donor_loss	1.0000
9:128706825:G:C	donor_loss	1.0000
9:128706826:T:A	donor_loss	1.0000
9:128706890:CCACA:C	acceptor_loss	1.0000
9:128706891:CACAG:C	acceptor_loss	1.0000
9:128706893:CA:C	acceptor_loss	1.0000
9:128706894:A:AG	acceptor_gain	1.0000
9:128706894:A:AT	acceptor_loss	1.0000
9:128706894:AG:A	acceptor_gain	1.0000
9:128706895:G:GG	acceptor_gain	1.0000
9:128706895:GG:G	acceptor_gain	1.0000
9:128707003:G:GT	donor_gain	1.0000
9:128707018:GC:G	donor_gain	1.0000
9:128707019:C:G	donor_gain	1.0000
9:128707020:TGAG:T	donor_loss	1.0000
9:128707021:GAGG:G	donor_loss	1.0000
9:128707023:GGTC:G	donor_loss	1.0000
9:128707024:G:A	donor_loss	1.0000
9:128707217:TGCA:T	acceptor_loss	1.0000

AlphaMissense

5701 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:128718551:A:C	D684A	0.999
9:128718551:A:T	D684V	0.998
9:128719733:T:C	F725L	0.997
9:128719735:C:A	F725L	0.997
9:128719735:C:G	F725L	0.997
9:128719787:T:A	W743R	0.997
9:128719787:T:C	W743R	0.997
9:128715416:A:C	K588N	0.996
9:128715416:A:T	K588N	0.996
9:128718354:T:C	L672P	0.996
9:128718551:A:G	D684G	0.996
9:128718618:C:G	C706W	0.996
9:128719784:T:A	W742R	0.996
9:128719784:T:C	W742R	0.996
9:128720227:C:A	R801S	0.996
9:128718387:G:T	R683M	0.995
9:128718552:C:A	D684E	0.995
9:128718552:C:G	D684E	0.995
9:128718605:A:T	D702V	0.995
9:128719715:T:C	F719L	0.995
9:128719717:C:A	F719L	0.995
9:128719717:C:G	F719L	0.995
9:128719789:G:C	W743C	0.995
9:128719789:G:T	W743C	0.995
9:128718387:G:C	R683T	0.994
9:128718558:G:C	K686N	0.994
9:128718558:G:T	K686N	0.994
9:128715415:A:T	K588I	0.993
9:128716758:A:T	E607V	0.993
9:128718554:T:C	L685P	0.993

dbSNP variants (sampled 300 via entrez): RS1000044013 (9:128701657 C>G,T), RS1000281213 (9:128712804 G>T), RS1000341417 (9:128712633 G>A), RS1000648025 (9:128704443 C>A), RS1000773464 (9:128710509 T>G), RS1000886318 (9:128713955 G>A), RS1001018590 (9:128704224 C>A,T), RS1001235314 (9:128717091 A>G), RS1001272842 (9:128713793 G>A,C), RS1001453760 (9:128705153 C>A,T), RS1001601733 (9:128712201 C>T), RS1001688137 (9:128718546 C>T), RS1001821792 (9:128709538 G>A,C), RS1001906061 (9:128710113 A>G), RS1001957290 (9:128704959 G>A)

Disease associations

OMIM: gene MIM:610714 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

16 associations (top):

Study	Trait	p-value
GCST001762_133	Obesity-related traits	6.000000e-06
GCST001959_7	Eating disorders (purging via substances)	5.000000e-06
GCST002115_14	Axial length	6.000000e-06
GCST004607_111	Plateletcrit	6.000000e-11
GCST005951_65	Body mass index	5.000000e-09
GCST006019_34	Gamma glutamyl transferase levels	8.000000e-10
GCST009720_47	Asthma	2.000000e-08
GCST010204_216	Low density lipoprotein cholesterol levels	3.000000e-14
GCST010243_137	Apolipoprotein B levels	5.000000e-09
GCST010245_124	LDL cholesterol levels	3.000000e-12
GCST011349_13	Gamma glutamyl transferase levels	6.000000e-09
GCST90002398_161	Neutrophil count	8.000000e-16
GCST90002400_389	Plateletcrit	1.000000e-27
GCST90002402_73	Platelet count	2.000000e-19
GCST90002407_76	White blood cell count	2.000000e-15
GCST90013407_31	Liver enzyme levels (gamma-glutamyl transferase)	5.000000e-59

EFO canonical traits (9, from GWAS)

EFO ID	Trait name
EFO:0004626	IGFBP-3 measurement
EFO:0005318	axial length measurement
EFO:0007985	platelet crit
EFO:0004340	body mass index
EFO:0004532	serum gamma-glutamyl transferase measurement
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0004615	apolipoprotein B measurement
EFO:0004833	neutrophil count
EFO:0004309	platelet count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3627581 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

3 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 12,330 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL38380	FASUDIL	3	11,953
CHEMBL603469	LESTAURTINIB	3
CHEMBL551064	AEW-541	1	377

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — Protein kinase N (PKN) family

ChEMBL bioactivities

13 potent at pChembl≥5 of 13 total, top 11 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.11	IC50	7.8	nM	STAUROSPORINE
7.94	IC50	11.6	nM	STAUROSPORINE
7.89	Kd	13	nM	CHEMBL3991933
7.88	IC50	13.2	nM	STAUROSPORINE
7.64	Kd	23	nM	AEW-541
7.00	Kd	99	nM	FASUDIL
5.86	Kd	1374	nM	LESTAURTINIB
5.85	IC50	1400	nM	CHEMBL5090394
5.76	Kd	1738	nM	CHEMBL5653589
5.76	ED50	1738	nM	CHEMBL5653589
5.17	IC50	6700	nM	CHEMBL5090394

PubChem BioAssay actives

10 with measured affinity, of 177 total; 7 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
(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	1715194: Inhibition of human PKN3 using KKLNRTLSVA as substrate by [gamma-33P]-ATP assay	ic50	0.0078	uM
3-(2-methyl-1,3-benzoxazol-5-yl)-1-propan-2-ylpyrazolo[3,4-d]pyrimidin-4-amine	1425119: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.0130	uM
7-[3-(azetidin-1-yl)cyclobutyl]-5-(3-phenylmethoxyphenyl)pyrrolo[2,3-d]pyrimidin-4-amine	1425119: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.0230	uM
5-(1,4-diazepan-1-ylsulfonyl)isoquinoline	1425119: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.0990	uM
(15S,16S,18R)-16-hydroxy-16-(hydroxymethyl)-15-methyl-28-oxa-4,14,19-triazaoctacyclo[12.11.2.115,18.02,6.07,27.08,13.019,26.020,25]octacosa-1,6,8,10,12,20,22,24,26-nonaen-3-one	1425119: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	1.3740	uM
8-[(5-amino-1,3-dioxan-2-yl)methyl]-6-[2-chloro-4-(3-fluoro-2-pyridinyl)phenyl]-2-(methylamino)pyrido[2,3-d]pyrimidin-7-one	1895124: Inhibition of human PKN3 by radiometric PanQinase activity assay	ic50	1.4000	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149020: Binding affinity to human PKN3 incubated for 45 mins by Kinobead based pull down assay	kd	1.7377	uM

CTD chemical–gene interactions

27 total (human), top 27 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, increases methylation	2
Cadmium Chloride	decreases expression, increases expression	2
GSK-J4	decreases expression	1
bufotalin	increases expression	1
cobaltous chloride	decreases expression	1
tobacco tar	decreases expression	1
bleomycetin	decreases expression	1
muconaldehyde	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
coniferaldehyde	increases phosphorylation, increases expression, affects localization, decreases reaction	1
monomethylarsonous acid	decreases expression	1
(+)-JQ1 compound	decreases expression	1
Temozolomide	increases expression	1
Sunitinib	decreases expression	1
Troglitazone	decreases expression	1
Leflunomide	decreases expression	1
Acetaminophen	decreases expression	1
Caffeine	decreases phosphorylation	1
Chelating Agents	decreases expression, affects binding	1
Cisplatin	decreases expression	1
Copper	affects binding, decreases expression	1
Rotenone	increases expression	1
Smoke	decreases expression	1
Thimerosal	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Valproic Acid	decreases expression, increases methylation	1
Cyclosporine	decreases expression	1

ChEMBL screening assays

28 unique, capped per target: 28 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3630944	Binding	Inhibition of PKN3 (unknown origin) at 10 uM after 120 mins P33 radiolabeled kinase activity assay	Crystal structures of human RIP2 kinase catalytic domain complexed with ATP-competitive inhibitors: Foundations for understanding inhibitor selectivity. — Bioorg Med Chem

Cellosaurus cell lines

6 cell lines: 5 cancer cell line, 1 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_D7XQ	Ubigene A-549 PKN3 KO	Cancer cell line	Male
CVCL_D8T6	Ubigene HCT 116 PKN3 KO	Cancer cell line	Male
CVCL_D9NQ	Ubigene HEK293 PKN3 KO	Transformed cell line	Female
CVCL_E0L2	Ubigene HeLa PKN3 KO	Cancer cell line	Female
CVCL_TE03	HAP1 PKN3 (-) 1	Cancer cell line	Male
CVCL_TE04	HAP1 PKN3 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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