INCENP

Summary

INCENP (inner centromere protein, HGNC:6058) is a protein-coding gene on chromosome 11q12.3, encoding Inner centromere protein (Q9NQS7). Component of the chromosomal passenger complex (CPC), a complex that acts as a key regulator of mitosis. It is a common-essential gene (DepMap: required in 98.9% of cancer cell lines).

In mammalian cells, 2 broad groups of centromere-interacting proteins have been described: constitutively binding centromere proteins and ‘passenger,’ or transiently interacting, proteins (reviewed by Choo, 1997). The constitutive proteins include CENPA (centromere protein A; MIM 117139), CENPB (MIM 117140), CENPC1 (MIM 117141), and CENPD (MIM 117142). The term ‘passenger proteins’ encompasses a broad collection of proteins that localize to the centromere during specific stages of the cell cycle (Earnshaw and Mackay, 1994 [PubMed 8088460]). These include CENPE (MIM 117143); MCAK (MIM 604538); KID (MIM 603213); cytoplasmic dynein (e.g., MIM 600112); CliPs (e.g., MIM 179838); and CENPF/mitosin (MIM 600236). The inner centromere proteins (INCENPs) (Earnshaw and Cooke, 1991 [PubMed 1860899]), the initial members of the passenger protein group, display a broad localization along chromosomes in the early stages of mitosis but gradually become concentrated at centromeres as the cell cycle progresses into mid-metaphase. During telophase, the proteins are located within the midbody in the intercellular bridge, where they are discarded after cytokinesis (Cutts et al., 1999 [PubMed 10369859]).

Source: NCBI Gene 3619 — RefSeq curated summary.

At a glance

• GWAS associations: 15
• Clinical variants (ClinVar): 294 total — 1 likely-pathogenic
• Phenotypes (HPO): 1
• Druggable target: yes — 7 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 98.9% of screened cell lines (common-essential)
• MANE Select transcript: NM_001040694

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6058
Approved symbol	INCENP
Name	inner centromere protein
Location	11q12.3
Locus type	gene with protein product
Status	Approved
Aliases	FLJ31633
Ensembl gene	ENSG00000149503
Ensembl biotype	protein_coding
OMIM	604411
Entrez	3619

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 7 protein_coding, 2 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000278849, ENST00000394818, ENST00000528037, ENST00000528375, ENST00000531099, ENST00000533896, ENST00000887854, ENST00000887855, ENST00000887856, ENST00000922527

RefSeq mRNA: 2 — MANE Select: NM_001040694 NM_001040694, NM_020238

CCDS: CCDS31582, CCDS44624

Canonical transcript exons

ENST00000394818 — 19 exons

Exon	Start	End
ENSE00000990922	62144982	62145091
ENSE00000990923	62145169	62145289
ENSE00000990924	62148739	62148846
ENSE00001195763	62150057	62150207
ENSE00001195774	62148476	62148554
ENSE00001195780	62146658	62146902
ENSE00001195786	62145629	62145751
ENSE00001195845	62151762	62153169
ENSE00002192312	62124011	62124163
ENSE00002466882	62141500	62141511
ENSE00003469945	62128151	62128301
ENSE00003511580	62138713	62138770
ENSE00003549147	62140704	62140821
ENSE00003591340	62138888	62139005
ENSE00003607636	62129782	62130590
ENSE00003615499	62128770	62128883
ENSE00003616320	62140913	62141044
ENSE00003619725	62140234	62140285
ENSE00003660627	62137832	62137883

Expression profiles

Bgee: expression breadth ubiquitous, 186 present calls, max score 92.94.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 25.6119 / max 179.7239, expressed in 1788 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
114666	25.1610	1787
114671	0.2993	168
114667	0.1273	23
114668	0.0243	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ventricular zone	UBERON:0003053	92.94	gold quality
ganglionic eminence	UBERON:0004023	88.92	gold quality
embryo	UBERON:0000922	88.91	gold quality
sural nerve	UBERON:0015488	86.67	gold quality
bone marrow cell	CL:0002092	85.83	gold quality
esophagus mucosa	UBERON:0002469	84.87	gold quality
cerebellar hemisphere	UBERON:0002245	83.92	gold quality
cerebellar cortex	UBERON:0002129	83.68	gold quality
right hemisphere of cerebellum	UBERON:0014890	82.97	gold quality
stromal cell of endometrium	CL:0002255	82.03	gold quality
cortical plate	UBERON:0005343	81.84	gold quality
lower esophagus mucosa	UBERON:0035834	81.73	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	81.72	gold quality
cerebellum	UBERON:0002037	81.50	gold quality
prefrontal cortex	UBERON:0000451	80.39	gold quality
secondary oocyte	CL:0000655	80.15	gold quality
lymph node	UBERON:0000029	79.09	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	78.98	gold quality
esophagus	UBERON:0001043	78.74	gold quality
rectum	UBERON:0001052	78.70	gold quality
ectocervix	UBERON:0012249	77.79	gold quality
leukocyte	CL:0000738	77.75	gold quality
mucosa of transverse colon	UBERON:0004991	77.71	gold quality
endothelial cell	CL:0000115	77.58	silver quality
minor salivary gland	UBERON:0001830	77.54	gold quality
monocyte	CL:0000576	77.52	gold quality
right lobe of thyroid gland	UBERON:0001119	77.39	gold quality
smooth muscle tissue	UBERON:0001135	77.28	gold quality
skin of leg	UBERON:0001511	76.92	gold quality
islet of Langerhans	UBERON:0000006	76.89	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	3.30

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

20 targeting INCENP, 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-4731-5P	99.89	67.23	2537
HSA-MIR-5582-3P	99.86	72.48	4221
HSA-MIR-3133	99.81	70.92	3506
HSA-MIR-4645-3P	99.76	69.33	993
HSA-MIR-4255	99.72	67.70	1541
HSA-MIR-10394-5P	99.65	66.83	1852
HSA-MIR-1205	99.65	66.76	1826
HSA-MIR-1251-3P	99.64	67.21	1408
HSA-MIR-182-3P	99.57	67.57	825
HSA-MIR-1324	99.46	66.57	1302
HSA-MIR-4326	98.97	67.63	962
HSA-MIR-6501-3P	98.71	67.45	1480
HSA-MIR-4290	98.51	65.17	907
HSA-MIR-6511B-5P	97.98	65.64	823
HSA-MIR-12116	97.94	68.91	595
HSA-MIR-3652	97.71	65.43	1890
HSA-MIR-1972	97.67	67.38	1172
HSA-MIR-1226-3P	97.51	66.32	1063
HSA-MIR-4430	97.47	65.61	1813
HSA-MIR-2355-3P	96.84	68.54	909

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 98.9% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 26)

• Aurora B kinase activity is stimulated by INCENP and C-terminal region of INCENP is sufficient for activation (PMID:12925766)
• association with inner centromere protein (INCENP) activates the novel chromosomal passenger protein, Aurora-C (PMID:15316025)
• Recruitment of MKLP1 to the midzone/midbody by INCENP is a crucial step for the midbody formation and completion of cytokinesis in mammalian cells. (PMID:15796717)
• Aurora-C is a chromosomal passenger protein that disrupts the association of INCENP with Aurora-B and may serve as a key regulator in cell division (PMID:15917996)
• Data show that INCENP has an important role in stabilizing the chromosomal passenger complex, and that Borealin acts to promote binding of Survivin to INCENP. (PMID:16239925)
• INCENP phosphorylation by Cdk1 is necessary for the recruitment of Plk1 to the kinetochore. (PMID:16378098)
• A functional module within the chromosomal passenger complex involving the inner centromere protein INCENP, Survivin, and Borealin. (PMID:16571674)
• protein truncation and in vitro mutagenesis,have identified the nucleolar localization sequences on INCENP (PMID:17623812)
• Borealin and INCENP associate with the helical domain of Survivin to form a tight three-helical bundle. (PMID:17956729)
• High INCENP expression is associated with high grade non-Hodgkin B-cell lymphomas. (PMID:18752045)
• Data show that binding to INCENP is alone critical to the distinct function of Aurora B, and although G198 of Aurora A is required for TPX2 binding, N142G Aurora B retains INCENP binding and Aurora B function. (PMID:19494039)
• Results indicate that INCENP-Aurora B localized at centromeres/inner kinetochores is sufficient to mediate SAC activity upon spindle disruption. (PMID:20372054)
• Dephosphorylation of INCENP at anaphase and the concomitant relocation of the chromosomal passenger protein complex prevents kinetochore recruitment of mitotic checkpoint proteins. (PMID:20619651)
• HP1alpha binding by INCENP or Shugoshin 1 (Sgo1) is dispensable for centromeric cohesion protection during mitosis of human cells, but might regulate yet unknown interphase functions of the chromosome passenger complex (CPC) or Sgo1 at the centromeres. (PMID:21346195)
• v-Src induces the failure of cytokinesis and the delocalization of Mklp1, Aurora B, and INCENP from the spindle midzone. (PMID:23562843)
• Our results provide the structural basis and energetics of the human Aurora-A(G198N) - INCENP complex (PMID:23848594)
• The data suggest that INCENP in the chromosomal passenger complex pathway contributes to estrogen receptor-negative breast cancer susceptibility in the European population. (PMID:25586992)
• Data unveils a novel mechanism of PRMT1-mediated CPC regulation through methylation of INCENP. (PMID:26460953)
• Aurora-C interactions with members of the Chromosome Passenger Complex (CPC), Survivin and Inner Centromere Protein (INCENP) in reference to known Aurora-B interactions to understand the functional significance of Aurora-C overexpression in human cancer cells, is reported. (PMID:27332895)
• Switching of INCENP paralogs controls transitions in mitotic chromosomal passenger complex functions. (PMID:31306061)
• Dysregulation of INCENP contributes to neuroblastoma tumorigenesis (PMID:31416840)
• lncRNA MIAT promotes esophageal squamous cell carcinoma progression by regulating miR-1301-3p/INCENP axis and interacting with SOX2. (PMID:31943174)
• In this study, we designed and synthesized 7-19 residues of inner centromere protein (INCENP)-derived small peptides (INC peptides) as novel survivin-targeting agents. (PMID:31991041)
• An ATM-Chk2-INCENP pathway activates the abscission checkpoint. (PMID:33355621)
• Computational study of the potential impact of AURKC missense SNPs on AURKC-INCENP interaction and their correlation to macrozoospermia. (PMID:36326488)
• High Inner Centromere Protein Expression Correlates with Aggressive Features and Predicts Poor Prognosis in Patients with Invasive Breast Cancer. (PMID:37031675)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio		ENSDARG00000099194
mus_musculus	Incenp	ENSMUSG00000024660
rattus_norvegicus	Incenp	ENSRNOG00000032929

Protein

Protein identifiers

Inner centromere protein — Q9NQS7 (reviewed: Q9NQS7)

All UniProt accessions (2): Q9NQS7, E9PM67

UniProt curated annotations — full annotation on UniProt →

Function. Component of the chromosomal passenger complex (CPC), a complex that acts as a key regulator of mitosis. The CPC complex has essential functions at the centromere in ensuring correct chromosome alignment and segregation and is required for chromatin-induced microtubule stabilization and spindle assembly. Acts as a scaffold regulating CPC localization and activity. The C-terminus associates with AURKB or AURKC, the N-terminus associated with BIRC5/survivin and CDCA8/borealin tethers the CPC to the inner centromere, and the microtubule binding activity within the central SAH domain directs AURKB/C toward substrates near microtubules. The flexibility of the SAH domain is proposed to allow AURKB/C to follow substrates on dynamic microtubules while ensuring CPC docking to static chromatin. Activates AURKB and AURKC. Required for localization of CBX5 to mitotic centromeres. Controls the kinetochore localization of BUB1.

Subunit / interactions. Component of the chromosomal passenger complex (CPC) composed of at least BIRC5/survivin, CDCA8/borealin, INCENP, AURKB or AURKC; in the complex binds directly to AURKB or AURKC via the IN box, and forms a triple-helix bundle-based subcomplex with BIRC5 and CDCA8 via its N-terminus. The reported homodimerization is questioned as the SAH domain is shown to be monomeric. Interacts with H2AZ1. Interacts with CBX1 and CBX3. Interacts with tubulin beta chain. Interacts with EVI5. Interacts with CBX5; POGZ and INCENP compete for interaction with CBX5; regulates INCENP (and probably CPC) localization to centromeres in interphase and not required for proper mitotic progression or sister chromatid cohesion. Interacts with POGZ. Interacts with JTB.

Subcellular location. Nucleus. Chromosome. Centromere. Cytoplasm. Cytoskeleton. Spindle. Midbody. Kinetochore.

Post-translational modifications. Phosphorylation by AURKB or AURKC at its C-terminal part is important for AURKB or AURKC activation by INCENP.

Domain organisation. The IN box mediates interaction with AURKB and AURKC. The SAH (single alpha-helix) region is characterized by a high content of charged residues which are predicted to stabilize the alpha-helical structure by ionic bonds. It can refold after extension suggesting an in vivo force-dependent function. The isolated SAH domain is monomeric.

Similarity. Belongs to the INCENP family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9NQS7-1	1	yes
Q9NQS7-2	2

RefSeq proteins (2): NP_001035784, NP_064623 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR005635	Inner_centromere_prot_ARK-bd	Domain
IPR022006	INCENP_N	Domain

Pfam: PF03941, PF12178

UniProt features (94 total): modified residue 37, region of interest 13, mutagenesis site 11, compositionally biased region 10, helix 9, sequence conflict 6, sequence variant 5, chain 1, short sequence motif 1, splice variant 1

Structure

Experimental structures (PDB)

16 structures.

PDB	Method	Resolution (Å)
2QFA	X-RAY DIFFRACTION	1.4
5IEH	X-RAY DIFFRACTION	1.5
6GR8	X-RAY DIFFRACTION	1.75
5IEK	X-RAY DIFFRACTION	1.8
6YIF	X-RAY DIFFRACTION	1.81
6GR9	X-RAY DIFFRACTION	2.25
8RUP	ELECTRON MICROSCOPY	2.42
6YIH	X-RAY DIFFRACTION	2.55
4AF3	X-RAY DIFFRACTION	2.75
9ESA	X-RAY DIFFRACTION	2.8
9SI3	ELECTRON MICROSCOPY	2.83
9SJ5	ELECTRON MICROSCOPY	2.85
9SI9	ELECTRON MICROSCOPY	2.86
9N9F	ELECTRON MICROSCOPY	2.91
6YIE	X-RAY DIFFRACTION	3.49
9SLJ	ELECTRON MICROSCOPY	3.8

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NQS7-F1	60.66	0.11

Functional residue map

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

Post-translational modifications (37): 72, 119, 143, 148, 150, 195, 197, 199, 213, 214, 219, 239, 263, 269, 275, 292, 296, 306, 312, 314 …

Mutagenesis-validated functional residues (11):

Position	Phenotype
22	loss of binding to cdca8 and birc5; when associated with r-34.
34	loss of binding to cdca8 and birc5; when associated with r-22.
35	loss of localization to the central spindle and midbody in anaphase or cytokinesis; when associated with r-36; r-39 and
36	loss of localization to the central spindle and midbody in anaphase or cytokinesis; when associated with r-35; r-39 and
39	loss of localization to the central spindle and midbody in anaphase or cytokinesis; when associated with r-35; r-36 and
40	loss of localization to the central spindle and midbody in anaphase or cytokinesis; when associated with r-35; r-36 and
167	decreases interaction with cbx5, abolishes localization to centromeres in interphase; when associated with a-169 and a-1
169	decreases interaction with cbx5, abolishes localization to centromeres in interphase; when associated with a-167 and a-1
169	abolishes interaction with cbx5.
171	decreases interaction with cbx5, abolishes localization to centromeres in interphase; when associated with a-167 and a-1
171	abolishes interaction with cbx5 and aurkb.

Function

Pathways and Gene Ontology

Reactome pathways

23 pathways

ID	Pathway
R-HSA-141444	Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal
R-HSA-2467813	Separation of Sister Chromatids
R-HSA-2500257	Resolution of Sister Chromatid Cohesion
R-HSA-4615885	SUMOylation of DNA replication proteins
R-HSA-5663220	RHO GTPases Activate Formins
R-HSA-68877	Mitotic Prometaphase
R-HSA-9648025	EML4 and NUDC in mitotic spindle formation
R-HSA-141424	Amplification of signal from the kinetochores
R-HSA-162582	Signal Transduction
R-HSA-1640170	Cell Cycle
R-HSA-194315	Signaling by Rho GTPases
R-HSA-195258	RHO GTPase Effectors
R-HSA-2555396	Mitotic Metaphase and Anaphase
R-HSA-2990846	SUMOylation
R-HSA-3108232	SUMO E3 ligases SUMOylate target proteins
R-HSA-392499	Metabolism of proteins
R-HSA-597592	Post-translational protein modification
R-HSA-68882	Mitotic Anaphase
R-HSA-68886	M Phase
R-HSA-69278	Cell Cycle, Mitotic
R-HSA-69618	Mitotic Spindle Checkpoint
R-HSA-69620	Cell Cycle Checkpoints
R-HSA-9716542	Signaling by Rho GTPases, Miro GTPases and RHOBTB3

MSigDB gene sets: 291 (showing top): GOBP_MITOTIC_CYTOKINESIS, GOBP_CHROMOSOME_ORGANIZATION, GOBP_ATTACHMENT_OF_SPINDLE_MICROTUBULES_TO_KINETOCHORE, GOBP_REGULATION_OF_CELL_CYCLE_CHECKPOINT, GOBP_REGULATION_OF_NUCLEAR_DIVISION, PAL_PRMT5_TARGETS_UP, OHASHI_AURKB_TARGETS, STARK_PREFRONTAL_CORTEX_22Q11_DELETION_DN, GOBP_CHROMOSOME_LOCALIZATION, GOBP_CELL_CYCLE_PHASE_TRANSITION, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GOBP_CHROMOSOME_SEPARATION, KONG_E2F3_TARGETS, GOLDRATH_ANTIGEN_RESPONSE, GOBP_NEGATIVE_REGULATION_OF_CELLULAR_COMPONENT_ORGANIZATION

GO Biological Process (12): mitotic cell cycle (GO:0000278), mitotic cytokinesis (GO:0000281), chromosome segregation (GO:0007059), mitotic spindle midzone assembly (GO:0051256), meiotic spindle midzone assembly (GO:0051257), metaphase chromosome alignment (GO:0051310), positive regulation of mitotic cell cycle spindle assembly checkpoint (GO:0090267), mitotic spindle assembly (GO:0090307), positive regulation of mitotic sister chromatid separation (GO:1901970), positive regulation of attachment of mitotic spindle microtubules to kinetochore (GO:1902425), positive regulation of mitotic cytokinesis (GO:1903490), cell division (GO:0051301)

GO Molecular Function (2): molecular function activator activity (GO:0140677), protein binding (GO:0005515)

GO Cellular Component (21): chromosome, centromeric region (GO:0000775), kinetochore (GO:0000776), lateral element (GO:0000800), central element (GO:0000801), nucleus (GO:0005634), nucleoplasm (GO:0005654), pericentric heterochromatin (GO:0005721), spindle (GO:0005819), cytosol (GO:0005829), microtubule (GO:0005874), chromocenter (GO:0010369), microtubule cytoskeleton (GO:0015630), nuclear body (GO:0016604), midbody (GO:0030496), chromosome passenger complex (GO:0032133), protein-containing complex (GO:0032991), meiotic spindle midzone (GO:1990385), synaptonemal complex (GO:0000795), chromosome (GO:0005694), cytoplasm (GO:0005737), cytoskeleton (GO:0005856)

Reactome top-level categories

Rollup of top-15 pathways:

Category	Pathways
Mitotic Prometaphase	2
M Phase	2
Amplification of signal from the kinetochores	1
Mitotic Anaphase	1
SUMO E3 ligases SUMOylate target proteins	1
RHO GTPase Effectors	1
Mitotic Spindle Checkpoint	1
Signaling by Rho GTPases, Miro GTPases and RHOBTB3	1
Signaling by Rho GTPases	1
Post-translational protein modification	1
SUMOylation	1
Metabolism of proteins	1
Mitotic Metaphase and Anaphase	1
Cell Cycle, Mitotic	1
Cell Cycle	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	6
intracellular membraneless organelle	5
mitotic nuclear division	3
mitotic cell cycle process	2
spindle midzone assembly	2
synaptonemal complex	2
microtubule cytoskeleton	2
cell cycle	1
mitotic cell cycle	1
cytoskeleton-dependent cytokinesis	1
cell cycle process	1
mitotic spindle elongation	1
mitotic spindle assembly	1
meiotic nuclear division	1
meiotic cell cycle process	1
chromosome localization	1
nuclear chromosome segregation	1
mitotic spindle assembly checkpoint signaling	1
positive regulation of cell cycle process	1
positive regulation of spindle checkpoint	1
regulation of mitotic cell cycle spindle assembly checkpoint	1
mitotic sister chromatid segregation	1
mitotic spindle organization	1
spindle assembly	1
regulation of mitotic sister chromatid separation	1
mitotic sister chromatid separation	1
positive regulation of chromosome separation	1
attachment of mitotic spindle microtubules to kinetochore	1
positive regulation of attachment of spindle microtubules to kinetochore	1
regulation of attachment of mitotic spindle microtubules to kinetochore	1
mitotic cytokinesis	1
positive regulation of cytokinesis	1
regulation of mitotic cytokinesis	1
cellular process	1
molecular function regulator activity	1
binding	1
chromosomal region	1
condensed chromosome, centromeric region	1
supramolecular complex	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

2126 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
INCENP	AURKB	Q96GD4	999
INCENP	CDCA8	Q53HL2	999
INCENP	BIRC5	O15392	995
INCENP	KCNJ6	P48051	990
INCENP	KIF20A	O95235	986
INCENP	AURKC	Q9UQB9	978
INCENP	TMEM63C	Q9P1W3	955
INCENP	RCC2	Q9P258	943
INCENP	ZW10	O43264	909
INCENP	NBL1	P41271	903
INCENP	AURKA	O14965	856
INCENP	ESPL1	Q14674	853
INCENP	CDK1	P06493	846
INCENP	ZWINT	O95229	841
INCENP	CDC14A	Q9UNH5	836

IntAct

108 interactions, top by confidence:

A	B	Type	Score
AURKB	INCENP	psi-mi:“MI:0914”(association)	0.960
INCENP	AURKB	psi-mi:“MI:0915”(physical association)	0.960
CDCA8	BIRC5	psi-mi:“MI:0914”(association)	0.960
BIRC5	CDCA8	psi-mi:“MI:0407”(direct interaction)	0.960
BIRC5	CDCA8	psi-mi:“MI:0915”(physical association)	0.960
AURKB	INCENP	psi-mi:“MI:0915”(physical association)	0.960
AURKB	INCENP	psi-mi:“MI:0407”(direct interaction)	0.960
BIRC5	CDCA8	psi-mi:“MI:2364”(proximity)	0.960
AURKB	INCENP	psi-mi:“MI:2364”(proximity)	0.960
AURKB	BIRC5	psi-mi:“MI:0914”(association)	0.950
PRKAA1	PRKAB2	psi-mi:“MI:0914”(association)	0.950
AURKB	BIRC5	psi-mi:“MI:2364”(proximity)	0.950
INCENP	BIRC5	psi-mi:“MI:0914”(association)	0.920
INCENP	BIRC5	psi-mi:“MI:0915”(physical association)	0.920
BIRC5	INCENP	psi-mi:“MI:0915”(physical association)	0.920
INCENP	BIRC5	psi-mi:“MI:2364”(proximity)	0.920
CDCA8	AURKB	psi-mi:“MI:0914”(association)	0.870
AURKB	CDCA8	psi-mi:“MI:2364”(proximity)	0.870
AURKB	CDC37	psi-mi:“MI:0914”(association)	0.830
AURKC	INCENP	psi-mi:“MI:0403”(colocalization)	0.810
AURKC	INCENP	psi-mi:“MI:0915”(physical association)	0.810

BioGRID (174): INCENP (Affinity Capture-Western), INCENP (Affinity Capture-MS), INCENP (Affinity Capture-MS), INCENP (Proximity Label-MS), INCENP (Proximity Label-MS), INCENP (Proximity Label-MS), INCENP (Affinity Capture-MS), INCENP (Affinity Capture-MS), INCENP (Affinity Capture-MS), INCENP (Affinity Capture-MS), INCENP (Affinity Capture-MS), INCENP (Affinity Capture-MS), INCENP (Affinity Capture-MS), INCENP (Affinity Capture-MS), INCENP (Affinity Capture-RNA)

ESM2 similar proteins: A0A8I5ZM56, A2AG50, A2AI08, A2AJI0, A5D7K1, D4A4L4, E1C2Q8, F1LR10, O00515, O14529, O75128, O88573, O88735, P51825, P57016, Q14244, Q32LQ1, Q3KQU3, Q3U2K0, Q5JTD0, Q5NBX1, Q5PR69, Q5R7F9, Q5XHX2, Q5ZIA2, Q5ZJJ1, Q68DK7, Q6IPM2, Q6NV74, Q6NZF1, Q6PDH0, Q6PDM1, Q6PG95, Q6ZU35, Q86UU1, Q8CCJ4, Q8K124, Q8N7J2, Q8TD55, Q96PV7

Diamond homologs: O13024, P53352, Q0IHP2, Q32N93, Q9NQS7, Q9WU62

SIGNOR signaling

10 interactions.

A	Effect	B	Mechanism
AURKB	up-regulates	INCENP	phosphorylation
CDK1	up-regulates	INCENP	phosphorylation
INCENP	“form complex”	CPC	binding
CHEK2	“up-regulates activity”	INCENP	phosphorylation
CIT	“up-regulates activity”	INCENP	phosphorylation
INCENP	up-regulates	AURKB	binding
AURKA	“up-regulates activity”	INCENP	phosphorylation
INCENP	“up-regulates activity”	AURKA	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 59 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
ChAHP complex assembly	6	29.9×	8e-06
SUMO E3 ligases SUMOylate target proteins	6	28.9×	8e-06
SUMOylation	6	26.5×	8e-06
Condensation of Prophase Chromosomes	6	25.4×	8e-06
Deposition of new CENPA-containing nucleosomes at the centromere	5	21.4×	1e-04
ERCC6 (CSB) and EHMT2 (G9a) positively regulate rRNA expression	5	20.6×	1e-04
Regulation of TP53 Activity	5	17.9×	2e-04
Regulation of endogenous retroelements by KRAB-ZFP proteins	6	17.3×	5e-05

GO biological processes:

GO term	Partners	Fold	FDR
mitotic spindle organization	5	27.2×	9e-05
mitotic cytokinesis	5	25.9×	9e-05
mitotic cell cycle	8	21.4×	1e-06

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	190
Likely benign	15
Benign	68

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
548641	NM_001040694.2(INCENP):c.2415G>C (p.Gln805His)	Likely pathogenic

SpliceAI

3571 predictions. Top by Δscore:

Variant	Effect	Δscore
11:62124159:GTCGA:G	donor_gain	1.0000
11:62124164:G:GG	donor_gain	1.0000
11:62128139:T:TA	acceptor_gain	1.0000
11:62128146:A:AG	acceptor_gain	1.0000
11:62128147:C:G	acceptor_gain	1.0000
11:62128147:CCAGA:C	acceptor_loss	1.0000
11:62128148:CA:C	acceptor_loss	1.0000
11:62128149:A:AG	acceptor_gain	1.0000
11:62128150:G:GA	acceptor_gain	1.0000
11:62128150:GAC:G	acceptor_gain	1.0000
11:62128150:GACA:G	acceptor_gain	1.0000
11:62128298:CCAG:C	donor_loss	1.0000
11:62128299:CAGG:C	donor_loss	1.0000
11:62128303:T:G	donor_loss	1.0000
11:62128766:ACAGA:A	acceptor_loss	1.0000
11:62128768:A:AG	acceptor_gain	1.0000
11:62128769:G:GA	acceptor_gain	1.0000
11:62128769:G:GT	acceptor_loss	1.0000
11:62128769:GA:G	acceptor_gain	1.0000
11:62128769:GAGA:G	acceptor_gain	1.0000
11:62128769:GAGAA:G	acceptor_gain	1.0000
11:62128855:G:GT	donor_gain	1.0000
11:62128880:GAAG:G	donor_gain	1.0000
11:62128883:GGT:G	donor_loss	1.0000
11:62128884:GTAGG:G	donor_loss	1.0000
11:62128885:T:A	donor_loss	1.0000
11:62137879:GTTGG:G	donor_gain	1.0000
11:62138710:CA:C	acceptor_loss	1.0000
11:62138711:A:AG	acceptor_gain	1.0000
11:62138711:A:AT	acceptor_loss	1.0000

AlphaMissense

5974 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:62151908:T:A	W897R	1.000
11:62151908:T:C	W897R	1.000
11:62128282:G:C	A41P	0.999
11:62150198:T:A	W845R	0.999
11:62150198:T:C	W845R	0.999
11:62150200:G:C	W845C	0.999
11:62150200:G:T	W845C	0.999
11:62151890:C:A	R891S	0.999
11:62151896:A:C	S893R	0.999
11:62151898:C:A	S893R	0.999
11:62151898:C:G	S893R	0.999
11:62151910:G:C	W897C	0.999
11:62151910:G:T	W897C	0.999
11:62128258:T:A	W33R	0.998
11:62128258:T:C	W33R	0.998
11:62150147:A:C	S828R	0.998
11:62150149:C:A	S828R	0.998
11:62150149:C:G	S828R	0.998
11:62150162:G:C	D833H	0.997
11:62151903:C:A	A895D	0.997
11:62151909:G:C	W897S	0.997
11:62145203:G:C	A584P	0.996
11:62145207:G:C	R585P	0.996
11:62151860:T:C	F881L	0.996
11:62151862:C:A	F881L	0.996
11:62151862:C:G	F881L	0.996
11:62128260:G:C	W33C	0.995
11:62128260:G:T	W33C	0.995
11:62145173:C:A	R574S	0.995
11:62145174:G:C	R574P	0.995

dbSNP variants (sampled 300 via entrez): RS1000293898 (11:62123129 G>A), RS1000372946 (11:62128726 G>A), RS1000425424 (11:62129049 G>A), RS1000566074 (11:62122368 G>A), RS1000597080 (11:62134346 G>A), RS1000812056 (11:62122631 G>A,C), RS1000938752 (11:62151320 C>T), RS1001047678 (11:62149882 A>G), RS1001051099 (11:62134612 T>C), RS1001053173 (11:62139899 C>T), RS1001101447 (11:62149659 C>T), RS1001163768 (11:62139536 T>G), RS1001176796 (11:62122840 G>C), RS1001178216 (11:62127849 G>A), RS1001372249 (11:62149314 T>C)

Disease associations

OMIM: gene MIM:604411 | disease phenotypes: MIM:256100

GenCC curated gene-disease

Mondo (1): nephronophthisis (MONDO:0019005)

Orphanet (1): Nephronophthisis (Orphanet:655)

HPO phenotypes

1 total (1 of 1 shown, HPO-id order):

HPO	Term
HP:0000090	Nephronophthisis

GWAS associations

15 associations (top):

Study	Trait	p-value
GCST001179_13	Plasma omega-3 polyunsaturated fatty acid levels (docosapentaenoic acid)	6.000000e-07
GCST002446_1	Plasma omega-6 polyunsaturated fatty acid levels (linoleic acid)	4.000000e-274
GCST002446_7	Plasma omega-6 polyunsaturated fatty acid levels (linoleic acid)	3.000000e-21
GCST002449_6	Plasma omega-6 polyunsaturated fatty acid levels (arachidonic acid)	0.000000e+00
GCST002449_8	Plasma omega-6 polyunsaturated fatty acid levels (arachidonic acid)	7.000000e-147
GCST005956_12	Waist-to-hip ratio adjusted for BMI	2.000000e-06
GCST005956_2	Waist-to-hip ratio adjusted for BMI	1.000000e-08
GCST005962_37	Waist-to-hip ratio adjusted for BMI x sex x age interaction (4df test)	5.000000e-07
GCST005962_51	Waist-to-hip ratio adjusted for BMI x sex x age interaction (4df test)	1.000000e-07
GCST006085_48	Prostate cancer	3.000000e-10
GCST010797_13	Breast cancer, ovarian cancer or prostate cancer (pleiotropy)	2.000000e-09
GCST012298_15	Schizophrenia, bipolar disorder or major depressive disorder x sex interaction	7.000000e-06
GCST012299_3	Schizophrenia, bipolar disorder or major depressive disorder x sex interaction (3df)	3.000000e-06
GCST012301_5	Schizophrenia, bipolar disorder or major depressive disorder x sex interaction	5.000000e-06
GCST012305_1	Major depressive disorder x sex interaction	2.000000e-06

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0006809	docosapentaenoic acid measurement
EFO:0005680	omega-6 polyunsaturated fatty acid measurement
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0008007	age at assessment
EFO:0008343	sex interaction measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (3): CHEMBL3430907 (PROTEIN COMPLEX), CHEMBL4106141 (PROTEIN COMPLEX), CHEMBL5177 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

7 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 13,175 (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
CHEMBL12856	INAMRINONE	4	9,690
CHEMBL483158	ALISERTIB	3	2,305
CHEMBL3408947	OCIFISERTIB	2	150
CHEMBL4871106	RUPITASERTIB	2	282
CHEMBL1090479	GSK-1070916	1	177
CHEMBL3544932	TAK-901	1	557
CHEMBL3600873	MK-5108	1	14

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

Binding affinities (BindingDB)

12 measured of 13 human assays (13 total across all organisms); most potent 12 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
(9S)-9-[3-(1H-benzimidazol-2-yloxy)phenyl]-3-ethyl-2,4,5,6,7,9-hexahydropyrrolo[3,4-b]quinolin-8-one	IC50	1 nM	US-9073917: Anti-cancer compound and pharmaceutical composition containing the same
9-[3-(1H-benzimidazol-2-yloxy)phenyl]-3-ethyl-6,6-dimethyl-4,5,7,9-tetrahydro-2H-pyrrolo[3,4-b]quinolin-8-one	IC50	3 nM	US-9073917: Anti-cancer compound and pharmaceutical composition containing the same
ethyl (9R)-9-[5-(1H-benzimidazol-2-ylsulfanyl)furan-2-yl]-8-oxo-2,4,5,6,7,9-hexahydropyrrolo[3,4-b]quinoline-3-carboxylate	IC50	4 nM	US-9073917: Anti-cancer compound and pharmaceutical composition containing the same
9-[3-(1H-benzimidazol-2-yloxy)phenyl]-3-ethyl-2,4,5,6,7,9-hexahydropyrrolo[3,4-b]quinolin-8-one	IC50	6 nM	US-9073917: Anti-cancer compound and pharmaceutical composition containing the same
ethyl 9-[5-[(4-methoxy-1H-benzimidazol-2-yl)sulfanyl]furan-2-yl]-8-oxo-2,4,5,6,7,9-hexahydropyrrolo[3,4-b]quinoline-3-carboxylate	IC50	11 nM	US-9073917: Anti-cancer compound and pharmaceutical composition containing the same
9-[3-(1H-benzimidazol-2-ylsulfanyl)phenyl]-3-ethyl-2,4,5,6,7,9-hexahydropyrrolo[3,4-b][1,7]naphthyridin-8-one	IC50	15 nM	US-9073917: Anti-cancer compound and pharmaceutical composition containing the same
4-[3-(1H-benzimidazol-2-yloxy)phenyl]-7,7-dimethyl-2,3,3a,4,6,8,9,9a-octahydro-1H-pyrazolo[3,4-b]quinolin-5-one	IC50	22 nM	US-9073917: Anti-cancer compound and pharmaceutical composition containing the same
4-[3-(1H-benzimidazol-2-yloxy)phenyl]-1,2,3,3a,4,6,7,8,9,9a-decahydropyrazolo[3,4-b]quinolin-5-one	IC50	23 nM	US-9073917: Anti-cancer compound and pharmaceutical composition containing the same
9-[3-(1H-benzimidazol-2-ylsulfanyl)phenyl]-3-ethyl-2,4,5,6,7,9-hexahydropyrrolo[3,4-b]quinolin-8-one	IC50	72 nM	US-9073917: Anti-cancer compound and pharmaceutical composition containing the same
9-[3-(1H-benzimidazol-2-ylsulfanyl)phenyl]-3-ethyl-6,6-dimethyl-4,5,7,9-tetrahydro-2H-pyrrolo[3,4-b]quinolin-8-one	IC50	102 nM	US-9073917: Anti-cancer compound and pharmaceutical composition containing the same
4-[3-(1H-benzimidazol-2-yloxy)phenyl]-1,2,3,3a,4,6,7,8,9,9a-decahydropyrazolo[3,4-b][1,7]naphthyridin-5-one	IC50	109 nM	US-9073917: Anti-cancer compound and pharmaceutical composition containing the same
(9R)-9-[3-(1H-benzimidazol-2-yloxy)phenyl]-3-ethyl-2,4,5,6,7,9-hexahydropyrrolo[3,4-b]quinolin-8-one	IC50	900 nM	US-9073917: Anti-cancer compound and pharmaceutical composition containing the same

ChEMBL bioactivities

152 potent at pChembl≥5 of 179 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.70	Ki	0.02	nM	TAK-901
9.42	Ki	0.38	nM	GSK-1070916
9.41	Ki	0.39	nM	GSK-1070916
9.30	IC50	0.5012	nM	CHEMBL587029
9.29	IC50	0.51	nM	CHEMBL587029
9.21	IC50	0.61	nM	CHEMBL1090832
9.20	IC50	0.631	nM	CHEMBL1090832
8.96	IC50	1.1	nM	ALISERTIB
8.84	Ki	1.45	nM	GSK-1070916
8.83	IC50	1.49	nM	MK-5108
8.82	Ki	1.5	nM	GSK-1070916
8.70	IC50	1.995	nM	CHEMBL1089116
8.52	IC50	3	nM	CHEMBL3663741
8.50	IC50	3.162	nM	GSK-1070916
8.49	IC50	3.2	nM	GSK-1070916
8.46	IC50	3.5	nM	GSK-1070916
8.40	IC50	4	nM	CHEMBL3663737
8.40	IC50	4	nM	CHEMBL3663733
8.40	IC50	4	nM	CHEMBL3685329
8.24	IC50	5.7	nM	CHEMBL1090670
8.23	IC50	5.9	nM	CHEMBL1090508
8.22	IC50	6	nM	CHEMBL3663734
8.22	IC50	6	nM	CHEMBL3663735
8.22	IC50	6	nM	CHEMBL4854144
8.20	IC50	6.31	nM	CHEMBL1090670
8.20	IC50	6.31	nM	CHEMBL1090508
8.19	IC50	6.5	nM	GSK-1070916
8.10	IC50	8	nM	CHEMBL3663739
8.05	IC50	9	nM	CHEMBL3663740
8.05	IC50	9	nM	CHEMBL3675415
8.00	IC50	10	nM	CHEMBL3663742
7.89	IC50	13	nM	CHEMBL3663736
7.82	IC50	15	nM	TAK-901
7.72	IC50	19	nM	CHEMBL4063500
7.68	IC50	21	nM	CHEMBL3663738
7.66	IC50	22	nM	CHEMBL4063500
7.60	IC50	25	nM	CHEMBL3951333
7.60	IC50	25.12	nM	CHEMBL1090156
7.58	IC50	26	nM	CHEMBL1090156
7.50	IC50	32	nM	CHEMBL3923139
7.43	IC50	37	nM	CHEMBL3915221
7.42	IC50	38	nM	CHEMBL3422063
7.41	IC50	39	nM	CHEMBL3904174
7.39	IC50	41	nM	CHEMBL4875416
7.35	IC50	45	nM	CHEMBL4851020
7.35	IC50	45	nM	CHEMBL4857965
7.33	IC50	47	nM	CHEMBL4855657
7.30	IC50	50	nM	CHEMBL5632112
7.29	IC50	51	nM	CHEMBL4869229
7.28	IC50	53	nM	CHEMBL3958845

PubChem BioAssay actives

107 with measured affinity, of 220 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
5-(3-ethylsulfonylphenyl)-3,8-dimethyl-N-(1-methylpiperidin-4-yl)-9H-pyrido[2,3-b]indole-7-carboxamide	1419647: Inhibition of Aurora B/INCENP (unknown origin) assessed as affinity constant pre-incubated for 1 hr followed by FL-PKAtide substrate and ATP addition	ki	<0.0001	uM
3-[4-[4-[2-[3-[(dimethylamino)methyl]phenyl]-1H-pyrrolo[2,3-b]pyridin-4-yl]-1-ethylpyrazol-3-yl]phenyl]-1,1-dimethylurea	1419701: Inhibition of human Aurora B/INCENP pre-incubated for 30 mins before 5-FAM-PKAtide substrate addition and measured after 120 mins	ki	0.0004	uM
1-[3-[5-chloro-4-(1-methylpyrazol-4-yl)-1H-pyrrolo[2,3-b]pyridin-2-yl]phenyl]-N,N-dimethylmethanamine	473665: Inhibition of human recombinant aurora B/INCENP complex after 120 mins by IMAP fluorescence polarization assay	ic50	0.0005	uM
1-[4-[5-chloro-4-(1-methylpyrazol-4-yl)-1H-pyrrolo[2,3-b]pyridin-2-yl]phenyl]-N,N-dimethylmethanamine	473665: Inhibition of human recombinant aurora B/INCENP complex after 120 mins by IMAP fluorescence polarization assay	ic50	0.0006	uM
4-[[9-chloro-7-(2-fluoro-6-methoxyphenyl)-5H-pyrimido[5,4-d][2]benzazepin-2-yl]amino]-2-methoxybenzoic acid	1323329: Inhibition of Aurora-B/INCENP (unknown origin) using biotinylated STK2 substrate incubated for 30 mins by HTRF assay	ic50	0.0011	uM
4-(3-chloro-2-fluorophenoxy)-1-[[6-(1,3-thiazol-2-ylamino)-2-pyridinyl]methyl]cyclohexane-1-carboxylic acid	1323329: Inhibition of Aurora-B/INCENP (unknown origin) using biotinylated STK2 substrate incubated for 30 mins by HTRF assay	ic50	0.0015	uM
1-[4-[1-ethyl-4-(1H-pyrrolo[2,3-b]pyridin-4-yl)pyrazol-3-yl]phenyl]-3-phenylurea	473665: Inhibition of human recombinant aurora B/INCENP complex after 120 mins by IMAP fluorescence polarization assay	ic50	0.0020	uM
4-[[(1S)-1-(3-fluorophenyl)-2-(methylamino)ethyl]amino]quinazoline-8-carboxamide	1771965: Inhibition of recombinant full length GST-tagged human Aurora B (1 to 344 residues) co-expressed with N-terminal His-tagged human recombinant INCENP (803 to 918 residues) in baculovirus infected Sf21 cells incubated for 90 mins by mobility shift assay	ic50	0.0040	uM
N,N-dimethyl-1-[3-[4-(1-methylpyrazol-4-yl)-1H-pyrrolo[2,3-b]pyridin-2-yl]phenyl]methanamine	473665: Inhibition of human recombinant aurora B/INCENP complex after 120 mins by IMAP fluorescence polarization assay	ic50	0.0057	uM
N,N-dimethyl-1-[4-[4-(1-methylpyrazol-4-yl)-1H-pyrrolo[2,3-b]pyridin-2-yl]phenyl]methanamine	473665: Inhibition of human recombinant aurora B/INCENP complex after 120 mins by IMAP fluorescence polarization assay	ic50	0.0059	uM
4-[[(1S)-1-(3-fluorophenyl)-2-(methylamino)ethyl]amino]-2-methylquinazoline-8-carboxamide	1771965: Inhibition of recombinant full length GST-tagged human Aurora B (1 to 344 residues) co-expressed with N-terminal His-tagged human recombinant INCENP (803 to 918 residues) in baculovirus infected Sf21 cells incubated for 90 mins by mobility shift assay	ic50	0.0060	uM
4-[[1-(3-fluorophenyl)-2-(methylamino)ethyl]amino]quinazoline-8-carboxamide	1771965: Inhibition of recombinant full length GST-tagged human Aurora B (1 to 344 residues) co-expressed with N-terminal His-tagged human recombinant INCENP (803 to 918 residues) in baculovirus infected Sf21 cells incubated for 90 mins by mobility shift assay	ic50	0.0090	uM
N-[4-[[7-cyclopentyl-6-(dimethylcarbamoyl)pyrrolo[2,3-d]pyrimidin-2-yl]amino]phenyl]-N’-hydroxyoctanediamide	1469278: Inhibition of recombinant human full length C-terminal His6-tagged Aurora B//N-terminal GST-tagged INCENP (821-end residues) expressed in baculovirus infected sf21 cells using AKRRRLSSLRA substrate in presence of [gamma33P]ATP after 10 mins by scintillation counting method	ic50	0.0190	uM
3-[4-[1-ethyl-4-(1H-pyrrolo[2,3-b]pyridin-4-yl)pyrazol-3-yl]phenyl]-1,1-dimethylurea	473665: Inhibition of human recombinant aurora B/INCENP complex after 120 mins by IMAP fluorescence polarization assay	ic50	0.0251	uM
N-[(1R)-1-(2-chlorophenyl)propyl]-3-[4-(1-methylpiperidin-4-yl)oxyphenyl]-1H-indazole-5-carboxamide	1203279: Inhibition of AURKB/INCENP (unknown origin) preincubated for 15 mins prior to ATP addition by FRET-based homogenous assay	ic50	0.0380	uM
4-[[(1S)-2-(azetidin-1-yl)-1-(4-fluorophenyl)ethyl]amino]quinazoline-8-carboxamide	1771965: Inhibition of recombinant full length GST-tagged human Aurora B (1 to 344 residues) co-expressed with N-terminal His-tagged human recombinant INCENP (803 to 918 residues) in baculovirus infected Sf21 cells incubated for 90 mins by mobility shift assay	ic50	0.0410	uM
4-[[(1S)-1-(3-fluorophenyl)-2-pyrrolidin-1-ylethyl]amino]quinazoline-8-carboxamide	1771965: Inhibition of recombinant full length GST-tagged human Aurora B (1 to 344 residues) co-expressed with N-terminal His-tagged human recombinant INCENP (803 to 918 residues) in baculovirus infected Sf21 cells incubated for 90 mins by mobility shift assay	ic50	0.0450	uM
4-[[(1S)-2-(azetidin-1-yl)-1-(3-fluorophenyl)ethyl]amino]quinazoline-8-carboxamide	1771965: Inhibition of recombinant full length GST-tagged human Aurora B (1 to 344 residues) co-expressed with N-terminal His-tagged human recombinant INCENP (803 to 918 residues) in baculovirus infected Sf21 cells incubated for 90 mins by mobility shift assay	ic50	0.0450	uM
4-[[(1S)-2-(azetidin-1-yl)-1-(3-chlorophenyl)ethyl]amino]quinazoline-8-carboxamide	1771965: Inhibition of recombinant full length GST-tagged human Aurora B (1 to 344 residues) co-expressed with N-terminal His-tagged human recombinant INCENP (803 to 918 residues) in baculovirus infected Sf21 cells incubated for 90 mins by mobility shift assay	ic50	0.0470	uM
N-phenyl-4-(7H-pyrrolo[2,3-d]pyrimidin-4-ylamino)benzamide	2139468: Inhibition of AURKB/INCENP (unknown origin) preincubated for 60 mins in the presence of ATP at Km concentration	ic50	0.0500	uM
2-ethyl-4-[[(1S)-1-(3-fluorophenyl)-2-(methylamino)ethyl]amino]quinazoline-8-carboxamide	1771965: Inhibition of recombinant full length GST-tagged human Aurora B (1 to 344 residues) co-expressed with N-terminal His-tagged human recombinant INCENP (803 to 918 residues) in baculovirus infected Sf21 cells incubated for 90 mins by mobility shift assay	ic50	0.0510	uM
4-[[(1S)-2-(azetidin-1-yl)-1-(3,4-difluorophenyl)ethyl]amino]quinazoline-8-carboxamide	1771965: Inhibition of recombinant full length GST-tagged human Aurora B (1 to 344 residues) co-expressed with N-terminal His-tagged human recombinant INCENP (803 to 918 residues) in baculovirus infected Sf21 cells incubated for 90 mins by mobility shift assay	ic50	0.0560	uM
N-[cyclopropyl(phenyl)methyl]-3-[4-(1-methylpiperidin-4-yl)oxyphenyl]-1H-indazole-5-carboxamide	1203279: Inhibition of AURKB/INCENP (unknown origin) preincubated for 15 mins prior to ATP addition by FRET-based homogenous assay	ic50	0.0570	uM
2-cyclopentyl-N-[3-[4-(1-methylpiperidin-4-yl)oxyphenyl]-1H-indazol-5-yl]-2-pyridin-2-ylacetamide	1203279: Inhibition of AURKB/INCENP (unknown origin) preincubated for 15 mins prior to ATP addition by FRET-based homogenous assay	ic50	0.0710	uM
4-[[(1S)-2-(azetidin-1-yl)-1-(4-chloro-3-fluorophenyl)ethyl]amino]quinazoline-8-carboxamide	1771965: Inhibition of recombinant full length GST-tagged human Aurora B (1 to 344 residues) co-expressed with N-terminal His-tagged human recombinant INCENP (803 to 918 residues) in baculovirus infected Sf21 cells incubated for 90 mins by mobility shift assay	ic50	0.0750	uM
N-[cyclopropyl(phenyl)methyl]-3-[4-[[(1S,5R)-8-methyl-8-azabicyclo[3.2.1]octan-3-yl]oxy]phenyl]-1H-indazole-5-carboxamide	1203279: Inhibition of AURKB/INCENP (unknown origin) preincubated for 15 mins prior to ATP addition by FRET-based homogenous assay	ic50	0.0930	uM
N-[cyclopropyl(pyridin-2-yl)methyl]-3-[4-(1-formylpiperidin-4-yl)oxyphenyl]-1H-indazole-5-carboxamide	1203279: Inhibition of AURKB/INCENP (unknown origin) preincubated for 15 mins prior to ATP addition by FRET-based homogenous assay	ic50	0.0950	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	1198699: Inhibition of AURKB/INCENP (unknown origin) by FRET analysis	ic50	0.0980	uM
6-[[4-[(Z)-[2-(4-ethylphenyl)imino-3-methyl-4-oxo-1,3-thiazolidin-5-ylidene]methyl]-2-pyridinyl]amino]pyridine-3-carboxylic acid	1323329: Inhibition of Aurora-B/INCENP (unknown origin) using biotinylated STK2 substrate incubated for 30 mins by HTRF assay	ic50	0.1500	uM
4-[[(1S)-2-(azetidin-1-yl)-1-[4-chloro-3-(trifluoromethyl)phenyl]ethyl]amino]quinazoline-8-carboxamide	1771965: Inhibition of recombinant full length GST-tagged human Aurora B (1 to 344 residues) co-expressed with N-terminal His-tagged human recombinant INCENP (803 to 918 residues) in baculovirus infected Sf21 cells incubated for 90 mins by mobility shift assay	ic50	0.1700	uM
4-[[(1S)-2-(azetidin-1-yl)-1-[3-(trifluoromethyl)phenyl]ethyl]amino]quinazoline-8-carboxamide	1771965: Inhibition of recombinant full length GST-tagged human Aurora B (1 to 344 residues) co-expressed with N-terminal His-tagged human recombinant INCENP (803 to 918 residues) in baculovirus infected Sf21 cells incubated for 90 mins by mobility shift assay	ic50	0.1800	uM
N-[cyclopentyl(pyridin-2-yl)methyl]-3-[4-(1-methylpiperidin-4-yl)oxyphenyl]-1H-indazole-5-carboxamide	1203279: Inhibition of AURKB/INCENP (unknown origin) preincubated for 15 mins prior to ATP addition by FRET-based homogenous assay	ic50	0.1800	uM
N-[cyclopropyl(phenyl)methyl]-3-(4-morpholin-4-ylphenyl)-1H-indazole-5-carboxamide	1203279: Inhibition of AURKB/INCENP (unknown origin) preincubated for 15 mins prior to ATP addition by FRET-based homogenous assay	ic50	0.1900	uM
7-[6-methyl-3-[(4-methyl-2-pyridinyl)methoxy]-2-pyridinyl]-2,3,4,5-tetrahydro-1H-3-benzazepine	1422062: Inhibition of recombinant human FLAG/His6-tagged Aurora-B (2 to 344 residues)/GST-tagged INCENP preincubated for 30 mins followed by 5FAM-PKA-tide substrate addition after 120 mins by fluorescence polarization assay	ic50	0.1995	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148590: Binding affinity to human INCENP incubated for 45 mins by Kinobead based pull down assay	kd	0.2045	uM
3-[4-[(1R,5R)-7-hydroxy-3-oxa-9-azabicyclo[3.3.1]nonan-9-yl]phenyl]-N-[(1S)-3-methyl-1-pyridin-2-ylbutyl]-1H-indazole-5-carboxamide	1203279: Inhibition of AURKB/INCENP (unknown origin) preincubated for 15 mins prior to ATP addition by FRET-based homogenous assay	ic50	0.2300	uM
4-[[(1S)-2-(azetidin-1-yl)-1-[4-fluoro-3-(trifluoromethyl)phenyl]ethyl]amino]quinazoline-8-carboxamide	1771965: Inhibition of recombinant full length GST-tagged human Aurora B (1 to 344 residues) co-expressed with N-terminal His-tagged human recombinant INCENP (803 to 918 residues) in baculovirus infected Sf21 cells incubated for 90 mins by mobility shift assay	ic50	0.2330	uM
4-[[(1S)-2-(azetidin-1-yl)-1-[4-(trifluoromethyl)phenyl]ethyl]amino]quinazoline-8-carboxamide	1771965: Inhibition of recombinant full length GST-tagged human Aurora B (1 to 344 residues) co-expressed with N-terminal His-tagged human recombinant INCENP (803 to 918 residues) in baculovirus infected Sf21 cells incubated for 90 mins by mobility shift assay	ic50	0.2600	uM
3-[4-[[(1S,5R)-8-formyl-8-azabicyclo[3.2.1]octan-3-yl]oxy]phenyl]-N-(3-methyl-1-pyridin-2-ylbutyl)-1H-indazole-5-carboxamide	1203279: Inhibition of AURKB/INCENP (unknown origin) preincubated for 15 mins prior to ATP addition by FRET-based homogenous assay	ic50	0.3000	uM
N-[(S)-cyclopropyl(pyridin-2-yl)methyl]-3-[4-(3-oxa-8-azabicyclo[3.2.1]octan-8-yl)phenyl]-1H-indazole-5-carboxamide	1203279: Inhibition of AURKB/INCENP (unknown origin) preincubated for 15 mins prior to ATP addition by FRET-based homogenous assay	ic50	0.3600	uM
3-[4-(4-methylpiperazin-1-yl)phenyl]-N-[(1-morpholin-4-ylcyclohexyl)methyl]-1H-indazole-5-carboxamide	1203279: Inhibition of AURKB/INCENP (unknown origin) preincubated for 15 mins prior to ATP addition by FRET-based homogenous assay	ic50	0.4400	uM
N-[(S)-cyclopropyl-(2-fluorophenyl)methyl]-3-[4-(3-oxa-8-azabicyclo[3.2.1]octan-8-yl)phenyl]-1H-indazole-5-carboxamide	1203279: Inhibition of AURKB/INCENP (unknown origin) preincubated for 15 mins prior to ATP addition by FRET-based homogenous assay	ic50	0.4700	uM
N-[(S)-cyclopropyl(pyridin-2-yl)methyl]-3-[4-[(1S,5S)-3-hydroxy-8-azabicyclo[3.2.1]octan-8-yl]phenyl]-1H-indazole-5-carboxamide	1203279: Inhibition of AURKB/INCENP (unknown origin) preincubated for 15 mins prior to ATP addition by FRET-based homogenous assay	ic50	0.5300	uM
N-[(S)-cyclopentyl(pyrimidin-2-yl)methyl]-3-[4-[(1S,5S)-3-hydroxy-8-azabicyclo[3.2.1]octan-8-yl]phenyl]-1H-indazole-5-carboxamide	1203279: Inhibition of AURKB/INCENP (unknown origin) preincubated for 15 mins prior to ATP addition by FRET-based homogenous assay	ic50	0.6200	uM
N-[(R)-cyclopentyl(pyridin-2-yl)methyl]-3-[4-[(1R,5R)-7-hydroxy-3-oxa-9-azabicyclo[3.3.1]nonan-9-yl]phenyl]-1H-indazole-5-carboxamide	1203279: Inhibition of AURKB/INCENP (unknown origin) preincubated for 15 mins prior to ATP addition by FRET-based homogenous assay	ic50	0.7400	uM
N-[(1-morpholin-4-ylcyclohexyl)methyl]-3-(4-morpholin-4-ylphenyl)-1H-indazole-5-carboxamide	1203279: Inhibition of AURKB/INCENP (unknown origin) preincubated for 15 mins prior to ATP addition by FRET-based homogenous assay	ic50	0.7500	uM
4-(1H-pyrazol-4-yl)-1H-pyrrolo[2,3-b]pyridine	473665: Inhibition of human recombinant aurora B/INCENP complex after 120 mins by IMAP fluorescence polarization assay	ic50	0.7820	uM
4-(1-methylpyrazol-4-yl)-1H-pyrrolo[2,3-b]pyridine	473665: Inhibition of human recombinant aurora B/INCENP complex after 120 mins by IMAP fluorescence polarization assay	ic50	0.7943	uM
N-[(1-morpholin-4-ylcyclohexyl)methyl]-3-[4-(3-oxa-8-azabicyclo[3.2.1]octan-8-yl)phenyl]-1H-indazole-5-carboxamide	1203279: Inhibition of AURKB/INCENP (unknown origin) preincubated for 15 mins prior to ATP addition by FRET-based homogenous assay	ic50	0.8000	uM
(5Z)-2-(4-ethylphenyl)imino-3-methyl-5-[[2-[4-(2H-tetrazol-5-yl)anilino]-4-pyridinyl]methylidene]-1,3-thiazolidin-4-one	1323329: Inhibition of Aurora-B/INCENP (unknown origin) using biotinylated STK2 substrate incubated for 30 mins by HTRF assay	ic50	0.8300	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression, decreases methylation	3
sodium arsenite	increases expression	2
Hydrogen Peroxide	affects expression, affects localization	2
Aflatoxin B1	increases methylation, increases expression	2
FR900359	affects phosphorylation	1
TAK-243	increases sumoylation	1
dicrotophos	increases expression	1
triphenyl phosphate	affects expression	1
potassium perchlorate	increases expression	1
kojic acid	increases expression	1
trichostatin A	decreases expression	1
arsenite	affects binding, decreases reaction	1
methylparaben	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
perfluorooctanoic acid	decreases expression	1
zinc chromate	decreases expression, increases abundance	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, increases expression	1
coumarin	affects phosphorylation	1
2-amino-3,8-dimethylimidazo(4,5-f)quinoxaline	increases expression	1
butylparaben	increases expression	1
diallyl trisulfide	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
chromium hexavalent ion	decreases expression, increases abundance	1
perfluoro-n-nonanoic acid	decreases expression	1
2-palmitoylglycerol	increases expression	1
belinostat	decreases expression	1
ICG 001	decreases expression	1
palbociclib	decreases expression	1
jinfukang	increases expression	1
NSC668394	decreases expression	1

ChEMBL screening assays

49 unique, capped per target: 49 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1110577	Binding	Inhibition of human recombinant aurora B/INCENP complex after 120 mins by IMAP fluorescence polarization assay	Discovery of a new series of Aurora inhibitors through truncation of GSK1070916. — Bioorg Med Chem Lett

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT01022957	Not specified	COMPLETED	Nephronophthisis : Clinical and Genetic Study
NCT01401998	Not specified	RECRUITING	ARPKD Database Study
NCT04874909	Not specified	COMPLETED	Classification, Functional Stratification and Biomarkers in Ciliopathy (CILLICORIRCM)
NCT05286632	Not specified	COMPLETED	KidneYou - Innovative Digital Therapy
NCT06065852	Not specified	RECRUITING	National Registry of Rare Kidney Diseases
NCT06648044	Not specified	RECRUITING	Research of Therapeutic Targets in the Frame of Nephronophthisis and Renal Associated Ciliopathies