PBK

Summary

PBK (PDZ binding kinase, HGNC:18282) is a protein-coding gene on chromosome 8p21.1, encoding Lymphokine-activated killer T-cell-originated protein kinase (Q96KB5). Phosphorylates MAP kinase p38. In precision oncology, PBK OVEREXPRESSION is associated with resistance to Gefitinib in Lung Non-small Cell Carcinoma (CIViC Level D).

This gene encodes a serine/threonine protein kinase related to the dual specific mitogen-activated protein kinase kinase (MAPKK) family. Evidence suggests that mitotic phosphorylation is required for its catalytic activity. The encoded protein may be involved in the activation of lymphoid cells and support testicular functions, with a suggested role in the process of spermatogenesis. Overexpression of this gene has been implicated in tumorigenesis. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 55872 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 25 total
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• Precision-oncology evidence (CIViC): 1 curated variant–drug association
• MANE Select transcript: NM_018492

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18282
Approved symbol	PBK
Name	PDZ binding kinase
Location	8p21.1
Locus type	gene with protein product
Status	Approved
Aliases	TOPK, FLJ14385, Nori-3, SPK, CT84
Ensembl gene	ENSG00000168078
Ensembl biotype	protein_coding
OMIM	611210
Entrez	55872

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 5 protein_coding, 1 nonsense_mediated_decay

ENST00000301905, ENST00000521226, ENST00000522944, ENST00000524266, ENST00000884617, ENST00000884618

RefSeq mRNA: 3 — MANE Select: NM_018492 NM_001278945, NM_001363040, NM_018492

CCDS: CCDS6063, CCDS64858

Canonical transcript exons

ENST00000301905 — 8 exons

Exon	Start	End
ENSE00001120145	27833056	27833133
ENSE00001120151	27809624	27810501
ENSE00001159563	27837652	27837817
ENSE00003532619	27820565	27820694
ENSE00003545989	27810958	27811134
ENSE00003648502	27822319	27822488
ENSE00003654412	27823063	27823205
ENSE00003662851	27828105	27828198

Expression profiles

Bgee: expression breadth ubiquitous, 189 present calls, max score 98.14.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 15.2858 / max 842.0722, expressed in 1343 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
92513	14.2643	1331
92514	0.9593	562
92515	0.0621	14

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ventricular zone	UBERON:0003053	98.14	gold quality
sperm	CL:0000019	97.71	gold quality
male germ cell	CL:0000015	96.16	gold quality
ganglionic eminence	UBERON:0004023	95.39	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	93.81	gold quality
adult organism	UBERON:0007023	93.58	gold quality
embryo	UBERON:0000922	92.88	gold quality
left testis	UBERON:0004533	92.31	gold quality
right testis	UBERON:0004534	92.16	gold quality
testis	UBERON:0000473	91.12	gold quality
secondary oocyte	CL:0000655	90.04	gold quality
oocyte	CL:0000023	86.46	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	86.11	gold quality
mucosa of transverse colon	UBERON:0004991	82.22	gold quality
rectum	UBERON:0001052	81.83	gold quality
stromal cell of endometrium	CL:0002255	81.19	gold quality
adrenal tissue	UBERON:0018303	81.12	gold quality
esophagus squamous epithelium	UBERON:0006920	79.64	gold quality
esophagus mucosa	UBERON:0002469	78.00	gold quality
epithelium of esophagus	UBERON:0001976	77.09	gold quality
vermiform appendix	UBERON:0001154	76.80	gold quality
cartilage tissue	UBERON:0002418	76.65	gold quality
lower esophagus mucosa	UBERON:0035834	76.27	gold quality
oral cavity	UBERON:0000167	76.05	gold quality
thymus	UBERON:0002370	75.46	gold quality
mucosa of sigmoid colon	UBERON:0004993	75.34	gold quality
duodenum	UBERON:0002114	75.27	gold quality
colonic mucosa	UBERON:0000317	75.24	gold quality
bone marrow	UBERON:0002371	74.88	gold quality
trabecular bone tissue	UBERON:0002483	74.62	gold quality

Single-cell (SCXA)

Detected in 15 experiment(s), a significant marker in 14.

Experiment	Marker?	Max mean expression
E-MTAB-8894	yes	555.97
E-ENAD-17	yes	501.56
E-GEOD-81383	yes	476.57
E-MTAB-9435	yes	386.61
E-GEOD-75140	yes	352.68
E-MTAB-5061	yes	320.75
E-GEOD-110499	yes	294.92
E-HCAD-10	yes	260.39
E-MTAB-7052	yes	208.83
E-CURD-114	yes	95.92
E-GEOD-134144	yes	29.62
E-HCAD-13	yes	21.38
E-HCAD-5	yes	19.75
E-ANND-3	yes	4.44
E-CURD-11	no	337.60

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ATM, CREB1

miRNA regulators (miRDB)

49 targeting PBK, 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-548N	99.98	71.94	4170
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-145-5P	99.92	71.13	1836
HSA-MIR-5195-3P	99.92	70.92	1877
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-302A-3P	99.89	71.23	1777
HSA-MIR-302B-3P	99.89	71.23	1777
HSA-MIR-302C-3P	99.89	71.20	1778
HSA-MIR-302D-3P	99.89	71.25	1777
HSA-MIR-5582-3P	99.86	72.48	4221
HSA-MIR-373-3P	99.84	70.68	1668
HSA-MIR-520E-3P	99.84	70.55	1698
HSA-MIR-372-3P	99.83	70.58	1691
HSA-MIR-520A-3P	99.83	70.59	1687
HSA-MIR-520B-3P	99.83	70.56	1699
HSA-MIR-520C-3P	99.83	70.56	1699
HSA-MIR-520D-3P	99.83	70.78	1676
HSA-MIR-520F-3P	99.82	71.32	1216
HSA-MIR-4495	99.82	72.08	3080
HSA-MIR-548AG	99.77	69.25	1492
HSA-MIR-6505-5P	99.73	69.25	1595
HSA-MIR-4255	99.72	67.70	1541
HSA-MIR-548AI	99.69	69.24	1494

Literature-anchored findings (GeneRIF, showing 40)

• PBK/TOPK is upregulated in Burkitt’s lymphoma and other highly proliferative malignant cells and during normal fetal development. (PMID:11783945)
• TOPK protein is up-regulated in a variety of hematologic malignancies and may be involved in leukemic cell growth; 4 of 5 clinical that strongly expressed TOPK also strongly expressed phosphorylated c-Myc (PMID:14757441)
• PBK/TOPK plays an important role in transiently amplifying neural progenitors in the adult subependymal zone of transgenically targeted mice. (PMID:16291951)
• PBK augments tumor cell growth following transient appearance in different types of progenitor cells in vivo as reported. (PMID:17482142)
• Findings showed that TOPK positively modulated UVB-induced JNK1 activity and played a pivotal role in JNK1-mediated cell transformation induced by H-Ras. (PMID:17545598)
• The positive feedback loop between TOPK and ERK2 increases tumorigenesis properties of HCT116 colorectal cancer cells, and TOPK-regulated signaling may serve as a potential therapeutic target in colorectal cancer (PMID:17631144)
• TOPK is indispensable for cancer cell cytokinesis throughout phosphorylation on p97. (PMID:19900192)
• PBK/TOPK protein could serve as a useful indicator for histopathologic differentiation between cholangiocarcinoma and hepatocellular carcinomas and the low expression of PBK/TOPK is predicative of poor survival in cholangiocarcinoma patients. (PMID:19954816)
• Upregulation of TOPK is associated with breast cancer. (PMID:20589935)
• increased levels of PBK/TOPK may contribute to tumor cell development and progression through suppression of p53 function and consequent reductions in the cell-cycle regulatory proteins such as p21. (PMID:20622899)
• Phosphorylation of Prx1 (Ser-32) by TOPK prevents UVB-induced apoptosis in RPMI7951 melanoma cells through regulation of Prx1 peroxidase activity and blockade of intracellular H(2)O(2) accumulation. (PMID:20647304)
• T-LAK cell-originated protein kinase (TOPK) phosphorylation of MKP1 protein prevents solar ultraviolet light-induced inflammation through inhibition of the p38 protein signaling pathway. (PMID:21715333)
• Our results indicate that overexpression of TOPK could predetermine the metastatic capability of tumors and could serve as a significant prognostic predictor of shortened overall survival and time to recurrence. (PMID:22192142)
• The 3D structure of TOPK protein has been constructed by using multiple templates. (PMID:22940854)
• that the serine-threonine kinase PBK/TOPK is frequently overexpressed in high-grade lymphomas and its expression is positively correlated to that of c-Myc and E2F1 (PMID:23237560)
• TOPK directly interacted with and phosphorylated IkappaBalpha at Ser-32, leading to p65 nuclear translocation and NF-kappaB activation. (PMID:23250755)
• These results suggest that the malignant transformation of plexiform neurofibroma is associated with distinct changes in the expression of BUB1B, PBK and NEK2 (PMID:23370767)
• Antibody screening revealed 3 candidate prognostic markers in breast cancer: the Anillin (ANLN); PDZ-Binding Kinase (PBK); and, PDZ-Domain Containing 1 (PDZK1). (PMID:23547718)
• CHFR ubiquitinates and regulates TOPK levels, which is essential for its checkpoint function. (PMID:24012691)
• PBK/TOPK expression is positively correlated with Ki67 and p53 expression, and can be used as an independent prognostic factor in non-small-cell lung cancer. (PMID:24025073)
• TOPK protein upregulates iNOS gene expression in T cell leukemia Jurkat cells or macrophage leukemic Raw 264.7 cells via NF-kappaB activation in response to LPS, and might act as a critical effector in LPS/TLR4-mediated signaling cascade. (PMID:24440499)
• Study findings suggest that the PBK/TOPK mRNA/protein expression is specific to human bladder cancer and might be used as a novel target for development of cancer immunotherapy and diagnostic biomarker. (PMID:24629784)
• PDZ-binding kinase/T-LAK cell-originated protein kinase correlates with mutant p53 and affects cell proliferation and viability as well as prognosis in lung adenocarcinoma (PMID:25466965)
• PBK/TOPK expression is closely associated with cervical cancer and cervical intraepithelial neoplasia, which may be served as a useful target for tumor diagnosis and immunotherapy. (PMID:25550851)
• Authors identified TOPK/PBK, in vitro and in vivo, as the master ZFP linker kinase. Furthermore, they show precise temporal correlation between TOPK activating phosphorylation by Cdk1 and linker phosphorylation in mitosis. (PMID:25575812)
• TOPK, overexpressed in colorectal cancer, enhances the resistance of colorectal cancer cells to anoikis. (PMID:25687885)
• TOPK was speculated to be one of a potential marker and therapeutic target in advanced prostate cancer (PMID:25881543)
• The in vitro data have been consistent with a role for PBK/TOPK in facilitating invasion in prostate cancer. PBK could be a prognostic biomarker for prostate cancer that would discriminate aggressive prostate cancer from indolent disease. (PMID:25909225)
• Overexpression of Nrf2 inhibited the PBK/TOPK KD-induced decrease in cdc2 and cyclin B expression and cell cycle arrest, and blocked ROS production and apoptosis. (PMID:26503118)
• TOPK silencing sensitizes EGFR-TKI-resistant lung cancer cells to gefitinib and increases gefitinib efficacy in preclinical lung adenocarcinoma xenograft models. (PMID:26745678)
• Upregulation of proteasome subunit beta type 8 PSMB8 and PDZ binding kinase PBK was confirmed by real-time reverse transcription-PCR analysis. (PMID:26894977)
• Study shows that BUB1beta and PDZ binding kinase are up-regulated in breast cancer tumors and their expression is associated with improved overall survival (OS) in basal-like tumors but worse OS in luminal and untreated patients. (PMID:26897635)
• Results indicate that src-family kinase (Src) is a upstream kinase of T-LAK cell-originated protein kinase (TOPK). (PMID:27016416)
• Determined the crystal structure of PBK, which has two phospho-mimicking mutations T9E and T198E. The structural data indicated that PBK may assemble into an inactive dimer in alkaline conditions. Analytical size-exclusion chromatography and analytical ultracentrifugation confirmed that PBK exists in a conformational transition between dimers and monomers at different pH conditions. (PMID:27262437)
• TOPK protein and transcriptional levels of FOXM1 were reduced by TOPK inhibitor treatment. (PMID:27334838)
• A high PBK expression level was correlated with long overall survival in oral squamous cell carcinoma. (PMID:27347940)
• High TOPK expression is associated with liver cancer. (PMID:27582549)
• PBK/TOPK plays a crucial role in tumour malignant potential through its overexpression and highlight its usefulness as a prognostic factor and potential therapeutic target in gastric cancer. (PMID:27898655)
• findings suggest that PBK/TOPK plays a crucial role in tumor malignant potential through its overexpression in ESCC (PMID:27919968)
• Data suggest that T-LAK cell-originated protein kinase (TOPK) might play a pivotal role in breast cancer invasion and metastasis. (PMID:28212583)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	pbk	ENSDARG00000007221
mus_musculus	Pbk	ENSMUSG00000022033
rattus_norvegicus	Pbk	ENSRNOG00000015308
drosophila_melanogaster	CG8173	FBGN0030864

Protein

Protein identifiers

Lymphokine-activated killer T-cell-originated protein kinase — Q96KB5 (reviewed: Q96KB5)

Alternative names: Cancer/testis antigen 84, MAPKK-like protein kinase, Nori-3, PDZ-binding kinase, Spermatogenesis-related protein kinase, T-LAK cell-originated protein kinase

All UniProt accessions (4): Q96KB5, E5RFX4, E5RIE1, V9HWH0

UniProt curated annotations — full annotation on UniProt →

Function. Phosphorylates MAP kinase p38. Seems to be active only in mitosis. May also play a role in the activation of lymphoid cells. When phosphorylated, forms a complex with TP53, leading to TP53 destabilization and attenuation of G2/M checkpoint during doxorubicin-induced DNA damage.

Subunit / interactions. Interacts with DLG1 and TP53.

Tissue specificity. Expressed in the testis and placenta. In the testis, restrictedly expressed in outer cell layer of seminiferous tubules.

Post-translational modifications. Phosphorylated; in a cell-cycle dependent manner at mitosis.

Activity regulation. Activated by phosphorylation.

Similarity. Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. MAP kinase kinase subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
Q96KB5-1	1	yes
Q96KB5-2	2

RefSeq proteins (3): NP_001265874, NP_001349969, NP_060962* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000719	Prot_kinase_dom	Domain
IPR008271	Ser/Thr_kinase_AS	Active_site
IPR011009	Kinase-like_dom_sf	Homologous_superfamily
IPR041989	PKc_TOPK	Domain

Pfam: PF00069

Catalyzed reactions (Rhea), 3 shown:

• L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+) (RHEA:10596)
• 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 (55 total): helix 17, strand 11, modified residue 5, mutagenesis site 4, turn 4, sequence variant 3, sequence conflict 3, binding site 2, chain 1, domain 1, cross-link 1, splice variant 1, region of interest 1, active site 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
5J0A	X-RAY DIFFRACTION	2.74

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96KB5-F1	84.66	0.59

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): 167 (proton acceptor)

Ligand- & substrate-binding residues (2): 38–46; 64

Post-translational modifications (6): 59, 169, 1, 9, 24, 32

Mutagenesis-validated functional residues (4):

Position	Phenotype
9	tp53-binding.
64–65	loss of activity.
320	decrease in the binding to dlg1.
322	decrease in the binding to dlg1.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 318 (showing top): WU_APOPTOSIS_BY_CDKN1A_VIA_TP53, HORIUCHI_WTAP_TARGETS_DN, GOBP_NEGATIVE_REGULATION_OF_PROTEOLYSIS, GOBP_REGULATION_OF_PROTEASOMAL_UBIQUITIN_DEPENDENT_PROTEIN_CATABOLIC_PROCESS, KANG_DOXORUBICIN_RESISTANCE_UP, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, GOBP_REGULATION_OF_STRESS_ACTIVATED_PROTEIN_KINASE_SIGNALING_CASCADE, GOBP_CELLULAR_RESPONSE_TO_UV, GOBP_INFLAMMATORY_RESPONSE, GOBP_CELLULAR_RESPONSE_TO_LIGHT_STIMULUS, CHIANG_LIVER_CANCER_SUBCLASS_UNANNOTATED_DN, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, IVANOVA_HEMATOPOIESIS_LATE_PROGENITOR

GO Biological Process (8): mitotic cell cycle (GO:0000278), negative regulation of proteasomal ubiquitin-dependent protein catabolic process (GO:0032435), negative regulation of stress-activated MAPK cascade (GO:0032873), cellular response to UV (GO:0034644), proteasome-mediated ubiquitin-dependent protein catabolic process (GO:0043161), negative regulation of inflammatory response (GO:0050728), stress-activated MAPK cascade (GO:0051403), protein phosphorylation (GO:0006468)

GO Molecular Function (10): protein serine/threonine kinase activity (GO:0004674), MAP kinase kinase activity (GO:0004708), protein tyrosine kinase activity (GO:0004713), ATP binding (GO:0005524), 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 (1): nucleus (GO:0005634)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein kinase activity	3
MAPK cascade	2
cell cycle	1
mitotic nuclear division	1
regulation of proteasomal ubiquitin-dependent protein catabolic process	1
proteasome-mediated ubiquitin-dependent protein catabolic process	1
negative regulation of proteasomal protein catabolic process	1
negative regulation of ubiquitin-dependent protein catabolic process	1
regulation of stress-activated MAPK cascade	1
negative regulation of MAPK cascade	1
stress-activated MAPK cascade	1
negative regulation of stress-activated protein kinase signaling cascade	1
response to UV	1
cellular response to light stimulus	1
ubiquitin-dependent protein catabolic process	1
proteasomal protein catabolic process	1
inflammatory response	1
negative regulation of defense response	1
negative regulation of response to external stimulus	1
regulation of inflammatory response	1
stress-activated protein kinase signaling cascade	1
phosphorylation	1
protein modification process	1
protein serine/threonine/tyrosine kinase activity	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate 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
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

2880 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PBK	CDK1	P06493	832
PBK	TOP2A	P11388	754
PBK	DLG1	Q12959	740
PBK	CEP55	Q53EZ4	740
PBK	DLGAP5	Q15398	732
PBK	CCNB1	P14635	730
PBK	KIF20A	O95235	725
PBK	CENPF	P49454	704
PBK	ASPM	Q8IZT6	703
PBK	TTK	P33981	700
PBK	RRM2	P31350	690
PBK	BIRC5	O15392	684
PBK	TPX2	Q9ULW0	683
PBK	CDC20	Q12834	661
PBK	FOXM1	Q08050	653

IntAct

362 interactions, top by confidence:

A	B	Type	Score
	RAB8A	psi-mi:“MI:0217”(phosphorylation reaction)	0.820
	RAB8A	psi-mi:“MI:0217”(phosphorylation reaction)	0.790
PBK	DLG1	psi-mi:“MI:0407”(direct interaction)	0.750
PBK	TP53	psi-mi:“MI:0915”(physical association)	0.710
TP53	PBK	psi-mi:“MI:0915”(physical association)	0.710
TGIF2LY	PGP	psi-mi:“MI:0914”(association)	0.640
ARRDC1	NEDD4	psi-mi:“MI:0914”(association)	0.640
ZNF414	AHCYL1	psi-mi:“MI:0914”(association)	0.640
SCRIB	PBK	psi-mi:“MI:0407”(direct interaction)	0.610
PBK	MAST2	psi-mi:“MI:0407”(direct interaction)	0.610
PBK	SCRIB	psi-mi:“MI:0407”(direct interaction)	0.610
SCRIB	PBK	psi-mi:“MI:0915”(physical association)	0.610
MAST2	PBK	psi-mi:“MI:0915”(physical association)	0.610
PBK	DDIT4L	psi-mi:“MI:0915”(physical association)	0.560
DDIT4L	PBK	psi-mi:“MI:0915”(physical association)	0.560
ZNF526	PBK	psi-mi:“MI:0915”(physical association)	0.560
MCRS1	PBK	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (190): PBK (Two-hybrid), ZBTB26 (Two-hybrid), PBK (Affinity Capture-RNA), PBK (Affinity Capture-MS), LGALS9B (Affinity Capture-MS), LGALS9 (Affinity Capture-MS), PBK (Affinity Capture-MS), PBK (Affinity Capture-MS), PBK (Two-hybrid), CHFR (Affinity Capture-Western), PBK (Affinity Capture-Western), PTEN (Affinity Capture-Western), PTEN (Biochemical Activity), PBK (Biochemical Activity), SRC (Affinity Capture-Western)

ESM2 similar proteins: O14757, O35280, O35942, O42099, O54785, O54992, P35295, P45983, P45984, P49185, P49186, P49187, P51955, P53350, P53670, P53671, P53779, P62205, P70032, P87347, Q07832, Q32L23, Q32PP3, Q5F361, Q5RER6, Q61831, Q63651, Q6DHU8, Q6NU47, Q6NU98, Q6ZN16, Q8AYC9, Q8BM85, Q8IW41, Q8N165, Q8QHF0, Q8QHK8, Q8QZR7, Q8TEA7, Q90327

Diamond homologs: A4K2Q5, A4K2S1, A4PES0, A4QNA8, A5D791, D2HHP1, E1BTE1, E2RSS3, F4I1N8, O02827, O13148, O13889, O18209, O22042, O57473, O80397, P07527, P0C1S8, P11799, P15442, P27636, P29294, P30291, P32581, P33279, P47810, P47817, P54350, P54737, Q15746, Q1LX51, Q28824, Q4R8E0, Q54E34, Q54F40, Q54JQ1, Q54RP7, Q54ZN3, Q558U1, Q55F45

SIGNOR signaling

23 interactions.

A	Effect	B	Mechanism
CDK1	unknown	PBK	phosphorylation
PBK	unknown	H3C1	phosphorylation
PBK	up-regulates	GPSM2	phosphorylation
PBK	up-regulates	PRDX1	phosphorylation
CyclinB/CDK1	unknown	PBK	phosphorylation
PBK	unknown	“Histone H3”	phosphorylation
CHFR	“down-regulates quantity by destabilization”	PBK	polyubiquitination
PBK	“down-regulates activity”	PTEN	phosphorylation
LNX1	“down-regulates quantity by destabilization”	PBK	ubiquitination
SRC	“up-regulates quantity by stabilization”	PBK	phosphorylation
PBK	“down-regulates activity”	ULK1	phosphorylation
PBK	“up-regulates activity”	JUN	phosphorylation
PBK	“up-regulates activity”	TP53RK	phosphorylation
PBK	“up-regulates activity”	MAPK1	phosphorylation
PBK	“up-regulates activity”	HDAC1	phosphorylation
PBK	“up-regulates activity”	HDAC2	phosphorylation
MAPK1	“up-regulates activity”	PBK	phosphorylation
PBK	“up-regulates activity”	MAPK8	phosphorylation
CyclinB/CDK1	“up-regulates activity”	PBK	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 161 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
Ras activation upon Ca2+ influx through NMDA receptor	5	26.7×	1e-04
Unblocking of NMDA receptors, glutamate binding and activation	5	25.4×	1e-04
Negative regulation of NMDA receptor-mediated neuronal transmission	5	25.4×	1e-04
Long-term potentiation	5	22.2×	2e-04
Assembly and cell surface presentation of NMDA receptors	9	21.4×	8e-08
Neurexins and neuroligins	10	18.4×	8e-08
Protein-protein interactions at synapses	5	12.4×	3e-03

GO biological processes:

GO term	Partners	Fold	FDR
establishment or maintenance of epithelial cell apical/basal polarity	10	39.8×	3e-11
receptor clustering	6	25.6×	3e-05
regulation of postsynaptic membrane neurotransmitter receptor levels	7	23.8×	5e-06
Rho protein signal transduction	6	10.2×	4e-03
protein-containing complex assembly	8	6.2×	5e-03
chemical synaptic transmission	10	5.3×	3e-03

Disease & clinical

Cancer significance

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	20
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1413 predictions. Top by Δscore:

Variant	Effect	Δscore
8:27810512:T:C	acceptor_gain	1.0000
8:27810512:T:TC	acceptor_gain	1.0000
8:27811135:C:CC	acceptor_gain	1.0000
8:27820558:AACTT:A	donor_loss	1.0000
8:27820559:ACTTA:A	donor_loss	1.0000
8:27820560:CTTAC:C	donor_loss	1.0000
8:27820561:TTACC:T	donor_loss	1.0000
8:27820562:TACCA:T	donor_loss	1.0000
8:27820563:A:AC	donor_gain	1.0000
8:27820563:AC:A	donor_gain	1.0000
8:27820564:C:CG	donor_gain	1.0000
8:27820564:CC:C	donor_gain	1.0000
8:27820564:CCA:C	donor_gain	1.0000
8:27820564:CCAG:C	donor_gain	1.0000
8:27820564:CCAGT:C	donor_gain	1.0000
8:27820690:AGATA:A	acceptor_gain	1.0000
8:27820691:GATA:G	acceptor_gain	1.0000
8:27820692:ATA:A	acceptor_gain	1.0000
8:27820693:TA:T	acceptor_gain	1.0000
8:27820694:ACTA:A	acceptor_loss	1.0000
8:27820695:C:CC	acceptor_gain	1.0000
8:27820695:C:CG	acceptor_loss	1.0000
8:27820696:T:C	acceptor_loss	1.0000
8:27822314:GTTA:G	donor_loss	1.0000
8:27822315:TTAC:T	donor_loss	1.0000
8:27822316:TACC:T	donor_loss	1.0000
8:27822318:C:A	donor_loss	1.0000
8:27822318:CCTT:C	donor_gain	1.0000
8:27822320:TTTA:T	donor_gain	1.0000
8:27822485:TAAC:T	acceptor_gain	1.0000

AlphaMissense

2143 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:27823166:T:A	K64N	1.000
8:27823166:T:G	K64N	1.000
8:27810352:G:T	R308S	0.999
8:27811096:A:G	W212R	0.999
8:27811096:A:T	W212R	0.999
8:27820602:A:C	D186E	0.999
8:27820602:A:T	D186E	0.999
8:27820603:T:A	D186V	0.999
8:27820603:T:G	D186A	0.999
8:27810376:A:G	C300R	0.998
8:27811029:C:T	G234D	0.998
8:27820655:T:C	K169E	0.998
8:27820659:G:C	D167E	0.998
8:27820659:G:T	D167E	0.998
8:27820660:T:A	D167V	0.998
8:27820663:C:T	G166E	0.998
8:27820688:G:C	H158D	0.998
8:27822327:C:A	G153W	0.998
8:27823167:T:A	K64I	0.998
8:27823177:A:G	W61R	0.998
8:27823177:A:T	W61R	0.998
8:27810352:G:C	R308G	0.997
8:27810374:G:C	C300W	0.997
8:27811011:A:C	M240R	0.997
8:27811037:A:C	F231L	0.997
8:27811037:A:T	F231L	0.997
8:27811039:A:G	F231L	0.997
8:27820603:T:C	D186G	0.997
8:27820604:C:G	D186H	0.997
8:27820605:A:C	C185W	0.997

dbSNP variants (sampled 300 via entrez): RS1000087509 (8:27817325 C>T), RS1000155854 (8:27828021 G>A), RS1000182774 (8:27832966 C>A,T), RS1000231528 (8:27830030 C>T), RS1000291889 (8:27836043 C>G,T), RS1000382349 (8:27821628 T>C), RS1000415411 (8:27817043 A>G), RS1000418833 (8:27816261 T>C), RS1000619029 (8:27812300 G>A,T), RS1000806072 (8:27817483 CTTT>C), RS1000808695 (8:27810673 A>C), RS1000815622 (8:27812406 T>C,G), RS1000929994 (8:27813046 A>G), RS1001222622 (8:27833292 C>T), RS1001265747 (8:27809637 G>C)

Disease associations

OMIM: gene MIM:611210 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4896 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 3,925 (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
CHEMBL223360	LINIFANIB	3	3,925

Clinical evidence (CIViC)

Drug × variant × indication: 1 predictive associations from 1 curated evidence items; also 1 prognostic.

Variant	Therapy	Indication	Effect	Level	CIViC
PBK OVEREXPRESSION	Gefitinib	Lung Non-small Cell Carcinoma	Resistance	CIViC D	EID835

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — TOPK family

Most potent curated ligand interactions (1 total), top 1:

Ligand	Action	Affinity	Parameter
OTS964	Inhibition	7.55	pIC50

Binding affinities (BindingDB)

223 measured of 223 human assays (223 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
9-[4-(aminomethyl)phenyl]-8-hydroxy-5,5a,6,7,8,9,9a,9b-octahydro-3aH-thieno[2,3-c]quinolin-4-one	IC50	0.38 nM	US-8962648: Tricyclic compounds and PBK inhibitors containing the same
9-[4-(2-aminopropan-2-yl)phenyl]-8-hydroxy-5,5a,6,7,8,9,9a,9b-octahydro-3aH-thieno[2,3-c]quinolin-4-one	IC50	0.43 nM	US-8962648: Tricyclic compounds and PBK inhibitors containing the same
9-[4-(2-aminoethyl)-3-fluorophenyl]-8-hydroxy-5,5a,6,7,8,9,9a,9b-octahydro-3aH-thieno[2,3-c]quinolin-4-one	IC50	0.5 nM	US-8962648: Tricyclic compounds and PBK inhibitors containing the same
9-[4-[(1R)-1-aminoethyl]phenyl]-8-hydroxy-5,5a,6,7,8,9,9a,9b-octahydro-3aH-thieno[2,3-c]quinolin-4-one	IC50	0.54 nM	US-8962648: Tricyclic compounds and PBK inhibitors containing the same
9-[4-[[4-(aminomethyl)piperidin-1-yl]methyl]-3-fluorophenyl]-8-hydroxy-5,5a,6,7,8,9,9a,9b-octahydro-3aH-thieno[2,3-c]quinolin-4-one	IC50	0.57 nM	US-8962648: Tricyclic compounds and PBK inhibitors containing the same
9-[4-[(2R)-1-aminopropan-2-yl]phenyl]-8-hydroxy-5,5a,6,7,8,9,9a,9b-octahydro-3aH-thieno[2,3-c]quinolin-4-one	IC50	0.64 nM	US-8962648: Tricyclic compounds and PBK inhibitors containing the same
9-[4-(1-amino-2-methylpropan-2-yl)phenyl]-8-hydroxy-5,5a,6,7,8,9,9a,9b-octahydro-3aH-thieno[2,3-c]quinolin-4-one	IC50	0.67 nM	US-8962648: Tricyclic compounds and PBK inhibitors containing the same
9-[4-(1-aminoethyl)phenyl]-8-hydroxy-5,5a,6,7,8,9,9a,9b-octahydro-3aH-thieno[2,3-c]quinolin-4-one	IC50	0.73 nM	US-8962648: Tricyclic compounds and PBK inhibitors containing the same
9-[4-(3-aminopropyl)phenyl]-8-hydroxy-5,5a,6,7,8,9,9a,9b-octahydro-3aH-thieno[2,3-c]quinolin-4-one	IC50	0.74 nM	US-8962648: Tricyclic compounds and PBK inhibitors containing the same
9-[4-(1-aminobutan-2-yl)phenyl]-8-hydroxy-5,5a,6,7,8,9,9a,9b-octahydro-3aH-thieno[2,3-c]quinolin-4-one	IC50	0.74 nM	US-8962648: Tricyclic compounds and PBK inhibitors containing the same
8-hydroxy-9-(1,2,3,6-tetrahydropyridin-4-yl)-3aH-thieno[2,3-c]quinolin-4-one	IC50	0.78 nM	US-8962648: Tricyclic compounds and PBK inhibitors containing the same
9-[5-(aminomethyl)thiophen-2-yl]-8-hydroxy-3aH-thieno[2,3-c]quinolin-4-one	IC50	0.78 nM	US-8962648: Tricyclic compounds and PBK inhibitors containing the same
9-[4-[(1S)-1-aminoethyl]phenyl]-8-hydroxy-5,5a,6,7,8,9,9a,9b-octahydro-3aH-thieno[2,3-c]quinolin-4-one	IC50	0.81 nM	US-8962648: Tricyclic compounds and PBK inhibitors containing the same
9-[4-(1-aminopropyl)phenyl]-8-hydroxy-5,5a,6,7,8,9,9a,9b-octahydro-3aH-thieno[2,3-c]quinolin-4-one	IC50	0.82 nM	US-8962648: Tricyclic compounds and PBK inhibitors containing the same
9-[4-[(1R)-1-(dimethylamino)ethyl]phenyl]-8-hydroxy-5,5a,6,7,8,9,9a,9b-octahydro-3aH-thieno[2,3-c]quinolin-4-one	IC50	0.88 nM	US-8962648: Tricyclic compounds and PBK inhibitors containing the same
9-[4-[(1S)-1-aminopropyl]phenyl]-8-hydroxy-5,5a,6,7,8,9,9a,9b-octahydro-3aH-thieno[2,3-c]quinolin-4-one	IC50	0.88 nM	US-8962648: Tricyclic compounds and PBK inhibitors containing the same
8-hydroxy-9-[4-(methylaminomethyl)phenyl]-5,5a,6,7,8,9,9a,9b-octahydro-3aH-thieno[2,3-c]quinolin-4-one	IC50	0.9 nM	US-8962648: Tricyclic compounds and PBK inhibitors containing the same
9-[4-(1-aminoethyl)-3-fluorophenyl]-8-hydroxy-5,5a,6,7,8,9,9a,9b-octahydro-3aH-thieno[2,3-c]quinolin-4-one	IC50	0.92 nM	US-8962648: Tricyclic compounds and PBK inhibitors containing the same
9-[3-fluoro-4-[(3-hydroxypyrrolidin-1-yl)methyl]phenyl]-8-hydroxy-5,5a,6,7,8,9,9a,9b-octahydro-3aH-thieno[2,3-c]quinolin-4-one	IC50	0.97 nM	US-8962648: Tricyclic compounds and PBK inhibitors containing the same
9-[4-(1-amino-2-methylpropan-2-yl)-3-fluorophenyl]-8-hydroxy-5,5a,6,7,8,9,9a,9b-octahydro-3aH-thieno[2,3-c]quinolin-4-one	IC50	1 nM	US-8962648: Tricyclic compounds and PBK inhibitors containing the same
9-[4-(2-aminoethyl)phenyl]-8-hydroxy-5,5a,6,7,8,9,9a,9b-octahydro-3aH-thieno[2,3-c]quinolin-4-one	IC50	1.1 nM	US-8962648: Tricyclic compounds and PBK inhibitors containing the same
8-hydroxy-9-[4-[(1S)-1-(methylamino)ethyl]phenyl]-5,5a,6,7,8,9,9a,9b-octahydro-3aH-thieno[2,3-c]quinolin-4-one	IC50	1.1 nM	US-8962648: Tricyclic compounds and PBK inhibitors containing the same
9-(2-amino-2,3-dihydro-1H-inden-5-yl)-8-hydroxy-5,5a,6,7,8,9,9a,9b-octahydro-3aH-thieno[2,3-c]quinolin-4-one	IC50	1.2 nM	US-8962648: Tricyclic compounds and PBK inhibitors containing the same
8-hydroxy-9-[4-[(1R)-1-(methylamino)ethyl]phenyl]-5,5a,6,7,8,9,9a,9b-octahydro-3aH-thieno[2,3-c]quinolin-4-one	IC50	1.3 nM	US-8962648: Tricyclic compounds and PBK inhibitors containing the same
9-[4-(2-aminopropyl)phenyl]-8-hydroxy-5,5a,6,7,8,9,9a,9b-octahydro-3aH-thieno[2,3-c]quinolin-4-one	IC50	1.3 nM	US-8962648: Tricyclic compounds and PBK inhibitors containing the same
9-[4-(1-aminopropan-2-yl)phenyl]-8-hydroxy-5,5a,6,7,8,9,9a,9b-octahydro-3aH-thieno[2,3-c]quinolin-4-one	IC50	1.3 nM	US-8962648: Tricyclic compounds and PBK inhibitors containing the same
9-[4-[(1R)-1-aminopropyl]phenyl]-8-hydroxy-5,5a,6,7,8,9,9a,9b-octahydro-3aH-thieno[2,3-c]quinolin-4-one	IC50	1.3 nM	US-8962648: Tricyclic compounds and PBK inhibitors containing the same
8-hydroxy-9-[4-[(1S)-1-(methylamino)propyl]phenyl]-5,5a,6,7,8,9,9a,9b-octahydro-3aH-thieno[2,3-c]quinolin-4-one	IC50	1.3 nM	US-8962648: Tricyclic compounds and PBK inhibitors containing the same
9-[4-[(2S)-1-aminopropan-2-yl]phenyl]-8-hydroxy-5,5a,6,7,8,9,9a,9b-octahydro-3aH-thieno[2,3-c]quinolin-4-one	IC50	1.3 nM	US-8962648: Tricyclic compounds and PBK inhibitors containing the same
8-hydroxy-9-[4-[(2R)-1-(methylamino)propan-2-yl]phenyl]-5,5a,6,7,8,9,9a,9b-octahydro-3aH-thieno[2,3-c]quinolin-4-one	IC50	1.3 nM	US-8962648: Tricyclic compounds and PBK inhibitors containing the same
9-[4-[(1R)-1-(ethylamino)propyl]phenyl]-8-hydroxy-5,5a,6,7,8,9,9a,9b-octahydro-3aH-thieno[2,3-c]quinolin-4-one	IC50	1.4 nM	US-8962648: Tricyclic compounds and PBK inhibitors containing the same
9-[4-(1-amino-3-methylbutan-2-yl)phenyl]-8-hydroxy-5,5a,6,7,8,9,9a,9b-octahydro-3aH-thieno[2,3-c]quinolin-4-one	IC50	1.4 nM	US-8962648: Tricyclic compounds and PBK inhibitors containing the same
9-[4-(1-aminopropan-2-yl)-3-fluorophenyl]-8-hydroxy-5,5a,6,7,8,9,9a,9b-octahydro-3aH-thieno[2,3-c]quinolin-4-one	IC50	1.5 nM	US-8962648: Tricyclic compounds and PBK inhibitors containing the same
9-[4-[1-(dimethylamino)ethyl]phenyl]-8-hydroxy-5,5a,6,7,8,9,9a,9b-octahydro-3aH-thieno[2,3-c]quinolin-4-one	IC50	1.6 nM	US-8962648: Tricyclic compounds and PBK inhibitors containing the same
9-[4-[1-(aminomethyl)cyclobutyl]phenyl]-8-hydroxy-5,5a,6,7,8,9,9a,9b-octahydro-3aH-thieno[2,3-c]quinolin-4-one	IC50	1.7 nM	US-8962648: Tricyclic compounds and PBK inhibitors containing the same
4-(8-hydroxy-4-oxo-5,5a,6,7,8,9,9a,9b-octahydro-3aH-thieno[2,3-c]quinolin-9-yl)benzenesulfonamide	IC50	1.8 nM	US-8962648: Tricyclic compounds and PBK inhibitors containing the same
9-[4-[3-(aminomethyl)pentan-3-yl]phenyl]-8-hydroxy-5,5a,6,7,8,9,9a,9b-octahydro-3aH-thieno[2,3-c]quinolin-4-one	IC50	1.8 nM	US-8962648: Tricyclic compounds and PBK inhibitors containing the same
9-[4-[2-(dimethylamino)ethyl]-3-fluorophenyl]-8-hydroxy-5,5a,6,7,8,9,9a,9b-octahydro-3aH-thieno[2,3-c]quinolin-4-one	IC50	1.9 nM	US-8962648: Tricyclic compounds and PBK inhibitors containing the same
9-[4-[1-(dimethylamino)propyl]phenyl]-8-hydroxy-5,5a,6,7,8,9,9a,9b-octahydro-3aH-thieno[2,3-c]quinolin-4-one	IC50	1.9 nM	US-8962648: Tricyclic compounds and PBK inhibitors containing the same
9-[4-[1-(aminomethyl)cyclopropyl]phenyl]-8-hydroxy-5,5a,6,7,8,9,9a,9b-octahydro-3aH-thieno[2,3-c]quinolin-4-one	IC50	1.9 nM	US-8962648: Tricyclic compounds and PBK inhibitors containing the same
9-[4-[1-(dimethylamino)ethyl]-3-fluorophenyl]-8-hydroxy-5,5a,6,7,8,9,9a,9b-octahydro-3aH-thieno[2,3-c]quinolin-4-one	IC50	1.9 nM	US-8962648: Tricyclic compounds and PBK inhibitors containing the same
N-[1-[4-(8-hydroxy-4-oxo-5,5a,6,7,8,9,9a,9b-octahydro-3aH-thieno[2,3-c]quinolin-9-yl)phenyl]ethyl]methanesulfonamide	IC50	2 nM	US-8962648: Tricyclic compounds and PBK inhibitors containing the same
9-[4-(ethylaminomethyl)phenyl]-8-hydroxy-5,5a,6,7,8,9,9a,9b-octahydro-3aH-thieno[2,3-c]quinolin-4-one	IC50	2 nM	US-8962648: Tricyclic compounds and PBK inhibitors containing the same
8-hydroxy-9-[4-(1-hydroxyethyl)phenyl]-5,5a,6,7,8,9,9a,9b-octahydro-3aH-thieno[2,3-c]quinolin-4-one	IC50	2 nM	US-8962648: Tricyclic compounds and PBK inhibitors containing the same
8-hydroxy-9-(1,2,3,4-tetrahydroisoquinolin-7-yl)-5,5a,6,7,8,9,9a,9b-octahydro-3aH-thieno[2,3-c]quinolin-4-one	IC50	2 nM	US-8962648: Tricyclic compounds and PBK inhibitors containing the same
9-[4-[(2R)-1-aminopropan-2-yl]phenyl]-8-methoxy-5,5a,6,7,8,9,9a,9b-octahydro-3aH-thieno[2,3-c]quinolin-4-one	IC50	2 nM	US-8962648: Tricyclic compounds and PBK inhibitors containing the same
9-[4-[(1S)-1-(dimethylamino)propyl]phenyl]-8-hydroxy-5,5a,6,7,8,9,9a,9b-octahydro-3aH-thieno[2,3-c]quinolin-4-one	IC50	2.2 nM	US-8962648: Tricyclic compounds and PBK inhibitors containing the same
9-(4-amino-3-hydroxyphenyl)-8-hydroxy-5,5a,6,7,8,9,9a,9b-octahydro-3aH-thieno[2,3-c]quinolin-4-one	IC50	2.3 nM	US-8962648: Tricyclic compounds and PBK inhibitors containing the same
9-[4-(aminomethyl)phenyl]-6-fluoro-8-hydroxy-5,5a,6,7,8,9,9a,9b-octahydro-3aH-thieno[2,3-c]quinolin-4-one	IC50	2.5 nM	US-8962648: Tricyclic compounds and PBK inhibitors containing the same
8-methoxy-9-[4-[(1S)-1-(methylamino)ethyl]phenyl]-5,5a,6,7,8,9,9a,9b-octahydro-3aH-thieno[2,3-c]quinolin-4-one	IC50	2.5 nM	US-8962648: Tricyclic compounds and PBK inhibitors containing the same

ChEMBL bioactivities

270 potent at pChembl≥5 of 285 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.30	IC50	0.5	nM	CHEMBL4445123
8.81	IC50	1.56	nM	CHEMBL4452726
8.59	IC50	2.6	nM	CHEMBL3672295
8.57	IC50	2.71	nM	CHEMBL4440222
8.53	IC50	2.94	nM	CHEMBL4527920
8.34	IC50	4.59	nM	CHEMBL4564624
8.28	IC50	5.2	nM	CHEMBL3715360
8.28	IC50	5.3	nM	CHEMBL3716544
8.26	IC50	5.44	nM	CHEMBL4536593
8.19	IC50	6.44	nM	CHEMBL4452595
8.00	Ki	10	nM	CHEMBL1974328
7.97	IC50	10.69	nM	CHEMBL4537262
7.72	IC50	19.06	nM	CHEMBL4469640
7.68	IC50	21	nM	CHEMBL4593398
7.68	IC50	20.88	nM	CHEMBL4455498
7.64	IC50	23	nM	CHEMBL3672271
7.62	IC50	24	nM	CHEMBL3715388
7.60	IC50	25.1	nM	CHEMBL4458265
7.58	IC50	26.13	nM	CHEMBL4438486
7.55	IC50	28	nM	CHEMBL3672369
7.48	IC50	33	nM	CHEMBL3716635
7.47	IC50	34	nM	CHEMBL3715121
7.47	IC50	34	nM	CHEMBL3718105
7.46	IC50	35	nM	CHEMBL3718439
7.44	IC50	36	nM	CHEMBL3715494
7.41	IC50	39	nM	CHEMBL3718039
7.35	IC50	44.89	nM	CHEMBL4451419
7.29	IC50	50.9	nM	STAUROSPORINE
7.26	IC50	55	nM	CHEMBL3718730
7.26	IC50	54.3	nM	STAUROSPORINE
7.23	IC50	59	nM	CHEMBL3717059
7.21	IC50	61.41	nM	CHEMBL4473141
7.20	IC50	63	nM	CHEMBL3717532
7.20	IC50	63	nM	CHEMBL3718268
7.20	IC50	63.83	nM	CHEMBL4444190
7.19	IC50	64.46	nM	CHEMBL4534841
7.19	IC50	65	nM	CHEMBL4534499
7.14	IC50	72	nM	CHEMBL3715032
7.13	IC50	74	nM	CHEMBL3715508
7.11	IC50	78	nM	CHEMBL3717297
7.08	IC50	83.9	nM	STAUROSPORINE
7.07	IC50	86	nM	CHEMBL3717841
7.01	IC50	98	nM	CHEMBL3718758
7.00	IC50	99	nM	CHEMBL3715825
6.96	IC50	110	nM	CHEMBL3719067
6.90	Ki	125.9	nM	CHEMBL1973098
6.85	IC50	140	nM	CHEMBL3717063
6.85	IC50	142.5	nM	CHEMBL4552688
6.84	IC50	143.9	nM	CHEMBL4455728
6.82	IC50	150	nM	CHEMBL3718368

PubChem BioAssay actives

48 with measured affinity, of 305 total; 44 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
1-[4-[(2R)-1-aminopropan-2-yl]phenyl]-2-hydroxy-4-methyl-5H-phenanthridin-6-one	1585718: Inhibition of human TOPK using MBP as substrate after 2 hrs in presence of [gamma-33P]-ATP by filter-binding method	ic50	0.0005	uM
1-[4-[(1R)-1-aminoethyl]phenyl]-2-hydroxy-4,9-dimethyl-5H-phenanthridin-6-one	1585718: Inhibition of human TOPK using MBP as substrate after 2 hrs in presence of [gamma-33P]-ATP by filter-binding method	ic50	0.0016	uM
9-[4-[(2R)-1-aminopropan-2-yl]phenyl]-8-hydroxy-6-methyl-5H-thieno[2,3-c]quinolin-4-one	1415292: Inhibition of full length N-terminal GST-fused human PBK expressed in baculovirus expression system using FITC-labeled histone H3 peptide as substrate after 1 hr by IMAP method	ic50	0.0026	uM
1-[4-[(1R)-1-aminoethyl]phenyl]-4-chloro-2-hydroxy-5H-phenanthridin-6-one	1585718: Inhibition of human TOPK using MBP as substrate after 2 hrs in presence of [gamma-33P]-ATP by filter-binding method	ic50	0.0027	uM
1-[4-[(1R)-1-aminoethyl]phenyl]-2-hydroxy-4-methyl-5H-phenanthridin-6-one	1585718: Inhibition of human TOPK using MBP as substrate after 2 hrs in presence of [gamma-33P]-ATP by filter-binding method	ic50	0.0029	uM
1-[4-[(2R)-1-aminopropan-2-yl]phenyl]-4-chloro-2-hydroxy-5H-phenanthridin-6-one	1585718: Inhibition of human TOPK using MBP as substrate after 2 hrs in presence of [gamma-33P]-ATP by filter-binding method	ic50	0.0046	uM
1-[4-[(2R)-1-aminopropan-2-yl]phenyl]-2-methoxy-4-methyl-5H-phenanthridin-6-one	1585718: Inhibition of human TOPK using MBP as substrate after 2 hrs in presence of [gamma-33P]-ATP by filter-binding method	ic50	0.0054	uM
1-[4-[(2R)-1-aminopropan-2-yl]phenyl]-2-hydroxy-4,9-dimethyl-5H-phenanthridin-6-one	1585718: Inhibition of human TOPK using MBP as substrate after 2 hrs in presence of [gamma-33P]-ATP by filter-binding method	ic50	0.0064	uM
9-[4-[(2R)-1-aminopropan-2-yl]phenyl]-8-hydroxy-6-methyl-5H-thieno[2,3-c]quinolin-4-one;hydrochloride	1585718: Inhibition of human TOPK using MBP as substrate after 2 hrs in presence of [gamma-33P]-ATP by filter-binding method	ic50	0.0107	uM
1-[4-[(2R)-1-(dimethylamino)propan-2-yl]phenyl]-2-hydroxy-4,9-dimethyl-5H-phenanthridin-6-one	1585718: Inhibition of human TOPK using MBP as substrate after 2 hrs in presence of [gamma-33P]-ATP by filter-binding method	ic50	0.0191	uM
1-[4-[(1R)-1-(dimethylamino)ethyl]phenyl]-2-hydroxy-4,9-dimethyl-5H-phenanthridin-6-one	1585718: Inhibition of human TOPK using MBP as substrate after 2 hrs in presence of [gamma-33P]-ATP by filter-binding method	ic50	0.0209	uM
7-[5-(trifluoromethyl)-1H-pyrazol-4-yl]-8,9,10,11-tetrahydro-3H-pyrazolo[4,5-a]phenanthridine	1562833: Inhibition of TOPK (unknown origin) using MBP as substrate after 3 hrs by ADP-Glo assay	ic50	0.0210	uM
9-[4-[(1R)-1-aminoethyl]phenyl]-8-hydroxy-6-methyl-5H-thieno[2,3-c]quinolin-4-one	1585718: Inhibition of human TOPK using MBP as substrate after 2 hrs in presence of [gamma-33P]-ATP by filter-binding method	ic50	0.0230	uM
1-[4-[1-(aminomethyl)cyclopropyl]phenyl]-2-hydroxy-4-methyl-5H-phenanthridin-6-one	1585718: Inhibition of human TOPK using MBP as substrate after 2 hrs in presence of [gamma-33P]-ATP by filter-binding method	ic50	0.0251	uM
4-chloro-1-[4-[(1R)-1-(dimethylamino)ethyl]phenyl]-2-hydroxy-5H-phenanthridin-6-one	1585718: Inhibition of human TOPK using MBP as substrate after 2 hrs in presence of [gamma-33P]-ATP by filter-binding method	ic50	0.0261	uM
9-[4-[(2R)-1-(dimethylamino)propan-2-yl]phenyl]-8-hydroxy-6-methyl-5H-thieno[2,3-c]quinolin-4-one	1415292: Inhibition of full length N-terminal GST-fused human PBK expressed in baculovirus expression system using FITC-labeled histone H3 peptide as substrate after 1 hr by IMAP method	ic50	0.0280	uM
1-[4-[(1R)-1-(dimethylamino)ethyl]phenyl]-2-hydroxy-4-methyl-5H-phenanthridin-6-one	1585718: Inhibition of human TOPK using MBP as substrate after 2 hrs in presence of [gamma-33P]-ATP by filter-binding method	ic50	0.0449	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	2198361: Inhibition of human PBK using myelin basic protein as substrate preincubated for 20 mins followed by [gamma-33P]-ATP addition and measured after 120 mins by radiometric Hot-SpotSM Kinase assay	ic50	0.0509	uM
1-[4-[(1R)-1-aminoethyl]phenyl]-7-fluoro-2-hydroxy-4-methyl-5H-phenanthridin-6-one	1585718: Inhibition of human TOPK using MBP as substrate after 2 hrs in presence of [gamma-33P]-ATP by filter-binding method	ic50	0.0614	uM
1-[4-[(2R)-1-(dimethylamino)propan-2-yl]phenyl]-2-hydroxy-4-methyl-5H-phenanthridin-6-one	1585718: Inhibition of human TOPK using MBP as substrate after 2 hrs in presence of [gamma-33P]-ATP by filter-binding method	ic50	0.0638	uM
1-[4-[(2R)-1-aminopropan-2-yl]phenyl]-7-fluoro-2-hydroxy-4-methyl-5H-phenanthridin-6-one	1585718: Inhibition of human TOPK using MBP as substrate after 2 hrs in presence of [gamma-33P]-ATP by filter-binding method	ic50	0.0645	uM
4-chloro-1-[4-[(2R)-1-(dimethylamino)propan-2-yl]phenyl]-2-hydroxy-5H-phenanthridin-6-one	1585718: Inhibition of human TOPK using MBP as substrate after 2 hrs in presence of [gamma-33P]-ATP by filter-binding method	ic50	0.0650	uM
1-[4-[(1R)-1-aminoethyl]phenyl]-2-methoxy-4-methyl-5H-phenanthridin-6-one	1585718: Inhibition of human TOPK using MBP as substrate after 2 hrs in presence of [gamma-33P]-ATP by filter-binding method	ic50	0.1425	uM
1-[4-[1-[(dimethylamino)methyl]cyclopropyl]phenyl]-2-hydroxy-4-methyl-5H-phenanthridin-6-one	1585718: Inhibition of human TOPK using MBP as substrate after 2 hrs in presence of [gamma-33P]-ATP by filter-binding method	ic50	0.1439	uM
1-[4-[(2R)-1-aminopropan-2-yl]phenyl]-2-hydroxy-4,8-dimethyl-5H-phenanthridin-6-one	1585718: Inhibition of human TOPK using MBP as substrate after 2 hrs in presence of [gamma-33P]-ATP by filter-binding method	ic50	0.2237	uM
6,9-dichloro-3H-[1]benzothiolo[3,2-d]pyrimidin-4-one	437693: Inhibition of PBK by HTRF assay	ki	0.3161	uM
1-[4-[(2R)-1-aminopropan-2-yl]phenyl]-4-chloro-2,7-dihydroxy-5H-phenanthridin-6-one	1585718: Inhibition of human TOPK using MBP as substrate after 2 hrs in presence of [gamma-33P]-ATP by filter-binding method	ic50	0.3213	uM
1-[4-[(2R)-1-aminopropan-2-yl]phenyl]-2,7-dihydroxy-4-methyl-5H-phenanthridin-6-one	1585718: Inhibition of human TOPK using MBP as substrate after 2 hrs in presence of [gamma-33P]-ATP by filter-binding method	ic50	0.3357	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148941: Binding affinity to human PBK incubated for 45 mins by Kinobead based pull down assay	kd	0.3630	uM
1-[4-[(2R)-1-aminopropan-2-yl]phenyl]-2-hydroxy-4,7-dimethyl-5H-phenanthridin-6-one	1585718: Inhibition of human TOPK using MBP as substrate after 2 hrs in presence of [gamma-33P]-ATP by filter-binding method	ic50	0.5861	uM
1-[4-[(1R)-1-aminoethyl]phenyl]-4-chloro-2,7-dihydroxy-5H-phenanthridin-6-one	1585718: Inhibition of human TOPK using MBP as substrate after 2 hrs in presence of [gamma-33P]-ATP by filter-binding method	ic50	0.6429	uM
1-[4-[(1R)-1-aminoethyl]phenyl]-2-hydroxy-4,7-dimethyl-5H-phenanthridin-6-one	1585718: Inhibition of human TOPK using MBP as substrate after 2 hrs in presence of [gamma-33P]-ATP by filter-binding method	ic50	0.7214	uM
1-[4-[(1R)-1-aminoethyl]phenyl]-2-hydroxy-4,8-dimethyl-5H-phenanthridin-6-one	1585718: Inhibition of human TOPK using MBP as substrate after 2 hrs in presence of [gamma-33P]-ATP by filter-binding method	ic50	0.8943	uM
1-[4-[(1R)-1-aminoethyl]phenyl]-2,7-dihydroxy-4-methyl-5H-phenanthridin-6-one	1585718: Inhibition of human TOPK using MBP as substrate after 2 hrs in presence of [gamma-33P]-ATP by filter-binding method	ic50	0.9775	uM
1-[4-[1-(aminomethyl)cyclopropyl]phenyl]-4-chloro-2,7-dihydroxy-5H-phenanthridin-6-one	1585718: Inhibition of human TOPK using MBP as substrate after 2 hrs in presence of [gamma-33P]-ATP by filter-binding method	ic50	1.2660	uM
1-[4-[1-(aminomethyl)cyclopropyl]phenyl]-2,7-dihydroxy-4-methyl-5H-phenanthridin-6-one	1585718: Inhibition of human TOPK using MBP as substrate after 2 hrs in presence of [gamma-33P]-ATP by filter-binding method	ic50	1.5050	uM
4-chloro-1-[4-[(1R)-1-(dimethylamino)ethyl]phenyl]-2,7-dihydroxy-5H-phenanthridin-6-one	1585718: Inhibition of human TOPK using MBP as substrate after 2 hrs in presence of [gamma-33P]-ATP by filter-binding method	ic50	2.4400	uM
4-chloro-1-[4-[(2R)-1-(dimethylamino)propan-2-yl]phenyl]-2,7-dihydroxy-5H-phenanthridin-6-one	1585718: Inhibition of human TOPK using MBP as substrate after 2 hrs in presence of [gamma-33P]-ATP by filter-binding method	ic50	2.6630	uM
1-[4-[(1R)-1-(dimethylamino)ethyl]phenyl]-2-hydroxy-4,7-dimethyl-5H-phenanthridin-6-one	1585718: Inhibition of human TOPK using MBP as substrate after 2 hrs in presence of [gamma-33P]-ATP by filter-binding method	ic50	3.0130	uM
1-[4-[(1R)-1-(dimethylamino)ethyl]phenyl]-2,7-dihydroxy-4-methyl-5H-phenanthridin-6-one	1585718: Inhibition of human TOPK using MBP as substrate after 2 hrs in presence of [gamma-33P]-ATP by filter-binding method	ic50	4.7900	uM
7-chloro-3-oxo-8-(1,3-thiazol-5-ylmethylamino)-11,16-dioxa-2,4,19,21-tetrazatricyclo[15.3.1.05,10]henicosa-1(20),5,7,9,17(21),18-hexaene-18-carbonitrile	310379: Inhibition of PBK	ki	5.1950	uM
4-chloro-1-[4-[1-[(dimethylamino)methyl]cyclopropyl]phenyl]-2,7-dihydroxy-5H-phenanthridin-6-one	1585718: Inhibition of human TOPK using MBP as substrate after 2 hrs in presence of [gamma-33P]-ATP by filter-binding method	ic50	5.2380	uM
1-[4-[(1R)-1-(dimethylamino)ethyl]phenyl]-2-hydroxy-4,8-dimethyl-5H-phenanthridin-6-one	1585718: Inhibition of human TOPK using MBP as substrate after 2 hrs in presence of [gamma-33P]-ATP by filter-binding method	ic50	6.4150	uM
1-[4-[(2R)-1-(dimethylamino)propan-2-yl]phenyl]-2-hydroxy-4,8-dimethyl-5H-phenanthridin-6-one	1585718: Inhibition of human TOPK using MBP as substrate after 2 hrs in presence of [gamma-33P]-ATP by filter-binding method	ic50	7.0550	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects binding, increases reaction, increases expression, affects cotreatment, decreases expression	5
bisphenol A	affects expression, decreases expression, increases expression	4
Benzo(a)pyrene	decreases expression, increases methylation	4
Estradiol	decreases expression, increases expression	4
Valproic Acid	increases expression, affects expression, affects cotreatment	4
Resveratrol	decreases expression, affects cotreatment, increases expression	3
Cyclosporine	decreases expression	3
Cadmium Chloride	increases palmitoylation, decreases expression, decreases reaction, increases abundance	3
(+)-JQ1 compound	decreases expression	2
Cadmium	increases abundance, increases palmitoylation, increases expression, decreases reaction	2
Cisplatin	increases expression, decreases expression, increases reaction	2
Lipopolysaccharides	affects expression, affects reaction, affects cotreatment, decreases expression	2
Nickel	increases expression	2
Progesterone	decreases expression, increases expression	2
Tretinoin	affects cotreatment, decreases expression	2
Aflatoxin B1	affects expression, decreases methylation	2
Genistein	increases expression, affects expression	2
aristolochic acid I	decreases expression	1
afuresertib	decreases expression	1
FR900359	decreases phosphorylation	1
dicrotophos	decreases expression	1
propionaldehyde	decreases expression	1
kojic acid	decreases expression	1
trichostatin A	increases expression	1
methylparaben	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
cobaltous chloride	decreases expression	1
2-bromopalmitate	increases abundance, increases palmitoylation, decreases reaction	1
perfluorooctanoic acid	decreases expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, increases expression	1

ChEMBL screening assays

90 unique, capped per target: 89 binding, 1 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1041173	Binding	Residual activity of PBK at 1 uM by microplate scintillation counting	Substituted 2-arylbenzothiazoles as kinase inhibitors: hit-to-lead optimization. — Bioorg Med Chem
CHEMBL1964100	Functional	PUBCHEM_BIOASSAY: Navigating the Kinome. (Class of assay: other) Panel member name: TOPK	PubChem BioAssay data set

Cellosaurus cell lines

9 cell lines: 8 cancer cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B3DH	Abcam HEK293T PBK KO	Transformed cell line	Female
CVCL_B8M5	Abcam HCT 116 PBK KO	Cancer cell line	Male
CVCL_B9PC	Abcam A-549 PBK KO	Cancer cell line	Male
CVCL_E1DU	Ubigene U2OS PBK KO	Cancer cell line	Female
CVCL_TC34	HAP1 PBK (-) 1	Cancer cell line	Male
CVCL_TC35	HAP1 PBK (-) 2	Cancer cell line	Male
CVCL_XR40	HAP1 PBK (-) 3	Cancer cell line	Male
CVCL_XR41	HAP1 PBK (-) 4	Cancer cell line	Male
CVCL_XR42	HAP1 PBK (-) 5	Cancer cell line	Male

Clinical trials (associated diseases)

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