CENPE

Summary

CENPE (centromere protein E, HGNC:1856) is a protein-coding gene on chromosome 4q24, encoding Centromere-associated protein E (Q02224). Microtubule plus-end-directed kinetochore motor which plays an important role in chromosome congression, microtubule-kinetochore conjugation and spindle assembly checkpoint activation. It is a selective cancer dependency (DepMap: 77.7% of cell lines).

Centrosome-associated protein E (CENPE) is a kinesin-like motor protein that accumulates in the G2 phase of the cell cycle. Unlike other centrosome-associated proteins, it is not present during interphase and first appears at the centromere region of chromosomes during prometaphase. This protein is required for stable spindle microtubule capture at kinetochores which is a necessary step in chromosome alignment during prometaphase. This protein also couples chromosome position to microtubule depolymerizing activity. Alternative splicing results in multiple transcript variants encoding distinct protein isoforms.

Source: NCBI Gene 1062 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Seckel syndrome (Supportive, GenCC) — +2 more curated relationships
• GWAS associations: 9
• Clinical variants (ClinVar): 591 total — 1 pathogenic, 4 likely-pathogenic
• Phenotypes (HPO): 58
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 77.7% of screened cell lines
• MANE Select transcript: NM_001813

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1856
Approved symbol	CENPE
Name	centromere protein E
Location	4q24
Locus type	gene with protein product
Status	Approved
Aliases	KIF10, PPP1R61
Ensembl gene	ENSG00000138778
Ensembl biotype	protein_coding
OMIM	117143
Entrez	1062

Gene structure

Transcript identifiers

Ensembl transcripts: 13 — 11 protein_coding, 2 retained_intron

ENST00000265148, ENST00000380026, ENST00000509120, ENST00000509823, ENST00000514974, ENST00000515478, ENST00000933319, ENST00000933320, ENST00000933321, ENST00000933322, ENST00000933323, ENST00000933324, ENST00000960876

RefSeq mRNA: 2 — MANE Select: NM_001813 NM_001286734, NM_001813

CCDS: CCDS34042, CCDS68768

Canonical transcript exons

ENST00000265148 — 49 exons

Exon	Start	End
ENSE00000801486	103175960	103176048
ENSE00000970081	103196759	103196850
ENSE00000970082	103196163	103196252
ENSE00000970083	103195920	103196038
ENSE00000970084	103195114	103195233
ENSE00000970085	103194603	103194684
ENSE00000970086	103194374	103194441
ENSE00000970087	103194229	103194294
ENSE00000970088	103185810	103185861
ENSE00000970089	103183201	103183288
ENSE00000970090	103182762	103182891
ENSE00000970091	103181337	103181456
ENSE00000970092	103180311	103180469
ENSE00000970093	103176899	103177046
ENSE00000970094	103174736	103174903
ENSE00000970095	103163479	103163553
ENSE00000970096	103163137	103163256
ENSE00000970097	103161335	103161457
ENSE00000970098	103161086	103161251
ENSE00000970099	103160625	103160779
ENSE00000970100	103159010	103159324
ENSE00000970101	103158614	103158886
ENSE00000970102	103158300	103158458
ENSE00000970103	103153047	103153250
ENSE00000970104	103151219	103151377
ENSE00000970105	103149118	103149408
ENSE00000970106	103148844	103148999
ENSE00000970107	103147356	103147646
ENSE00000970108	103145829	103146107
ENSE00000970109	103145523	103145681
ENSE00000970110	103145050	103145334
ENSE00000970111	103144331	103144618
ENSE00000970112	103143248	103143406
ENSE00000970113	103141750	103141908
ENSE00000970114	103140814	103141104
ENSE00000970115	103140256	103140414
ENSE00000970116	103139789	103140079
ENSE00000970117	103138351	103138449
ENSE00000970118	103136141	103136359
ENSE00000970119	103133695	103133892
ENSE00000970120	103132693	103132896
ENSE00002045919	103198264	103198343
ENSE00002437408	103105811	103106316
ENSE00002445504	103114455	103114552
ENSE00002471541	103120148	103120333
ENSE00002473878	103116577	103116689
ENSE00002480633	103110828	103111011
ENSE00002501201	103108803	103109089
ENSE00002709088	103122871	103123089

Expression profiles

Bgee: expression breadth ubiquitous, 176 present calls, max score 95.42.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 5.0806 / max 199.4382, expressed in 1163 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
53446	2.8607	854
53447	2.2199	891

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
oocyte	CL:0000023	95.42	gold quality
ventricular zone	UBERON:0003053	92.91	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	91.47	gold quality
secondary oocyte	CL:0000655	91.01	gold quality
ganglionic eminence	UBERON:0004023	87.46	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	87.37	gold quality
trabecular bone tissue	UBERON:0002483	83.79	gold quality
embryo	UBERON:0000922	81.61	gold quality
bone marrow	UBERON:0002371	77.92	gold quality
stromal cell of endometrium	CL:0002255	76.55	gold quality
bone marrow cell	CL:0002092	76.46	gold quality
adrenal tissue	UBERON:0018303	73.83	gold quality
rectum	UBERON:0001052	67.94	gold quality
cortical plate	UBERON:0005343	67.49	gold quality
vermiform appendix	UBERON:0001154	67.47	gold quality
esophagus mucosa	UBERON:0002469	66.76	gold quality
calcaneal tendon	UBERON:0003701	66.73	gold quality
lower esophagus mucosa	UBERON:0035834	66.71	gold quality
lymph node	UBERON:0000029	66.51	gold quality
colonic epithelium	UBERON:0000397	66.51	gold quality
testis	UBERON:0000473	65.58	gold quality
oral cavity	UBERON:0000167	64.75	gold quality
duodenum	UBERON:0002114	63.94	gold quality
caecum	UBERON:0001153	63.74	gold quality
thymus	UBERON:0002370	63.67	silver quality
endometrium	UBERON:0001295	63.22	gold quality
mucosa of transverse colon	UBERON:0004991	63.04	gold quality
left testis	UBERON:0004533	62.61	gold quality
right testis	UBERON:0004534	61.57	gold quality
ileal mucosa	UBERON:0000331	61.45	silver quality

Single-cell (SCXA)

Detected in 8 experiment(s), a significant marker in 5.

Experiment	Marker?	Max mean expression
E-MTAB-7249	yes	1255.41
E-MTAB-11121	yes	600.36
E-MTAB-10018	yes	317.97
E-MTAB-7052	yes	211.03
E-ANND-3	yes	7.38
E-GEOD-109979	no	973.46
E-GEOD-99795	no	426.12
E-MTAB-9689	no	286.68

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CDR2, E2F4

miRNA regulators (miRDB)

26 targeting CENPE, 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-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-511-3P	99.99	68.85	1467
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-4307	99.82	70.45	3374
HSA-MIR-4639-5P	99.81	67.37	1028
HSA-MIR-556-3P	99.74	68.75	1203
HSA-MIR-4755-5P	99.71	70.34	2716
HSA-MIR-5006-3P	99.71	70.26	2728
HSA-MIR-4729	99.69	72.18	4233
HSA-MIR-7161-5P	99.68	68.92	1592
HSA-MIR-548U	99.65	67.78	1463
HSA-MIR-4499	99.62	67.29	1470
HSA-MIR-2053	99.57	69.15	1635
HSA-MIR-569	99.42	66.32	1009
HSA-MIR-297	99.40	69.58	1418
HSA-MIR-642A-3P	99.23	67.67	1258
HSA-MIR-642B-3P	99.23	67.67	1258
HSA-MIR-3688-5P	99.12	69.67	1091
HSA-MIR-4678	97.59	68.31	902
HSA-MIR-3935	96.33	66.79	797
HSA-MIR-6753-5P	94.70	64.08	470

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 77.7% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 40)

• MPS1 is required by cells to arrest in mitosis in response to spindle defects and kinetochore defects resulting from the loss of the kinesin-like protein. (PMID:12686615)
• x-ray crystallographic analysis of the motor domain of human kinetochore-associated protein CENP-E using an automated crystallization procedure (PMID:15159587)
• Depletion of CENP-E leads to chromosomes missegregation and cell death during mitotic delay. (PMID:15181147)
• crystal structure reveals that the CENP-E linker region is in a “docked” position identical to that in the human plus-end directed conventional kinesin (PMID:15236970)
• Microtubule capture by CENPE silences BubR1-dependent mitotic checkpoint signaling. (PMID:16144904)
• Results support a plus end motion for CENP-E, based on a cryoelectron microscopy density map of the complex to 17 A resolution, which is consistent with features of the crystallographic structure. (PMID:16926026)
• HsNUF2 and CENP-E are required for organization of stable microtubule-kinetochore attachment that is essential for faithful chromosome segregation in mitosis (PMID:17535814)
• Global inhibition of SUMOylation caused a prometaphase arrest due to defects in targeting the microtubule motor protein CENP-E to kinetochores. (PMID:18374647)
• SEPT7 forms a link between kinetochore distribution of CENP-E and the mitotic spindle checkpoint. (PMID:18460473)
• Chromosome congression in HSET + hNuf2 co-depleted cells required the plus-end directed motor CENP-E , which has been implicated in the gliding of mono-oriented kinetochores alongside adjacent K-fibres. (PMID:19525938)
• Data show that the kinetochore localization of PinX1 is dependent on Hec1 and CENP-E. (PMID:19553660)
• Studies strongly suggest that chromosome congression defects as the result of KIF18A depletion is at least in part mediated through destabilizing kinetochore CENP-E. (PMID:19625775)
• Study analyzed the distribution of PARP-1 and its interaction with CENP-B, -E, and -F during mitosis and apoptosis. (PMID:19723035)
• CENP-E integrates two critical functions that are important for accurate chromosome movement and spindle architecture: one relying directly on its motor activity, and the other involving the targeting of key microtubule regulators to kinetochores. (PMID:19733075)
• CENP-E expression was reduced in human hepatocellular carcinoma (PMID:20021663)
• Targeting of CENP-E and BubR1 to the kinetochores and the interaction between CENP-E and BubR1 are significantly reduced in EpoB-resistant A549 cell line, compared to A549 cells. (PMID:20237434)
• Aurora B allowed chromosome alignment in CENP-E-compromised cells; implied that by destabilizing pole proximal syntelic attachments, Aurora B cooperates with CENP-E to mediate congression of mono-oriented polar chromosomes (PMID:20354862)
• An Aurora/PP1 phosphorylation switch modulates CENP-E motor activity as a feature of chromosome congression from poles and localized PP1 delivery by CENP-E to the outer kinetochore is necessary for stable microtubule capture by those chromosomes. (PMID:20691903)
• SKAP cooperates with CENP-E to orchestrate dynamic kinetochore-microtubule interaction for faithful chromosome segregation. (PMID:22110139)
• Data show that CENP-E-mediated traction forces on misaligned chromosomes are responsible for the irreversible loss of spindle-pole integrity in CLASP1/2-depleted cells. (PMID:22307330)
• the unusually slow CENP-E microtubule association step favors CENP-E binding of stable microtubules over dynamic ones, a mechanism that would bias CENP-E binding to kinetochore fibers. (PMID:22637578)
• It was shown that the state of CENP-E-dependent BubR1 autophosphorylation in response to spindle microtubule capture by CENP-E is important for kinetochore function in achieving accurate chromosome segregation. (PMID:22801780)
• In this study we investigated the pathogenic effect of 132 nsSNPs reported in CENP-E using computational platform. (PMID:22974711)
• Evolutionarily conserved protein ERH controls CENP-E mRNA splicing and is required for the survival of KRAS mutant cancer cells. (PMID:23236152)
• The changes in ATP binding affinity and conformational deviations in human CENP-E motor domain, were studied. (PMID:23740391)
• A CENP-E mediated wall-tethering event and a MCAK-mediated wall-removing event show that human chromosome-microtubule attachment is achieved through a set of deterministic sequential events rather than stochastic direct capture of microtubule ends. (PMID:23891108)
• Kinetochore kinesin CENP-E is a processive bi-directional tracker of dynamic microtubule tips. (PMID:23955301)
• Mutations in CENPE define a novel kinetochore-centromeric mechanism for microcephalic primordial dwarfism. (PMID:24748105)
• An unexpected role of CENP-E elongated stalk in ensuring stability of kinetochore-microtubule attachments during chromosome congression and segregation. (PMID:24920822)
• CENP-E expression is highest in basal-like subtype among breast cancer patients. (PMID:24928852)
• dynein and CENP-E at kinetochores drive congression of peripheral polar chromosomes by preventing arm-ejection forces mediated by chromokinesins from working in the wrong direction. (PMID:25383660)
• CENP-Q - a subunit of the CENP-O complex (comprising CENP-O, CENP-P, CENP-Q and CENP-U) that targets polo-like kinase (Plk1) to kinetochores - is also required for the recruitment of CENP-E to kinetochores. (PMID:25395579)
• Chromokinesin Kid and kinetochore kinesin CENP-E differentially support chromosome congression without end-on attachment to microtubules. (PMID:25743205)
• CENP-E-driven chromosome congression is guided by microtubule detyrosination. (PMID:25908662)
• CTCF helps recruit CENP-E to the centromere during mitosis and that it may do so through a structure stabilized by the CTCF/CENP-E complex. (PMID:26321640)
• Data indicate that three genes, KIF14, NCAPG and CENPE that were upregulated in Pediatric high-grade gliomas (pHGGs) and were direct miR-137 or miR-6500-3p targets. (PMID:26933822)
• SUMOylated NKAP is essential for chromosome alignment by anchoring CENP-E to kinetochores (PMID:27694884)
• these results support a novel function of XAB2 in mitotic cell cycle regulation, which is partially mediated by transcription regulation on CENPE. (PMID:27735937)
• CENP-E motor activity appears to play important roles in the organization of midbody proteins to complete cytokinetic abscission. (PMID:27835888)
• CENPE was regulated by the co-binding of LSD1 and AR to its promoter, which was associated with loss of RB1 in CRPC. (PMID:28916652)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	cenpe	ENSDARG00000063385
mus_musculus	Cenpe	ENSMUSG00000045328
rattus_norvegicus	Cenpe	ENSRNOG00000009339
drosophila_melanogaster	cmet	FBGN0040232
drosophila_melanogaster	cana	FBGN0040233

Paralogs (41): KIF1B (ENSG00000054523), KIF26A (ENSG00000066735), KIF2A (ENSG00000068796), KIF22 (ENSG00000079616), KIF3C (ENSG00000084731), KIF9 (ENSG00000088727), KIF16B (ENSG00000089177), KIF4A (ENSG00000090889), KIF3B (ENSG00000101350), KIF20A (ENSG00000112984), KIF21B (ENSG00000116852), KIF17 (ENSG00000117245), KIF14 (ENSG00000118193), KIF18A (ENSG00000121621), KIF25 (ENSG00000125337), KIF1C (ENSG00000129250), KIF1A (ENSG00000130294), KIF3A (ENSG00000131437), KIF12 (ENSG00000136883), KIF13A (ENSG00000137177), KIF23 (ENSG00000137807), KIF11 (ENSG00000138160), KIF21A (ENSG00000139116), KIFC3 (ENSG00000140859), KIF2B (ENSG00000141200), KIF2C (ENSG00000142945), KIF5A (ENSG00000155980), KIF26B (ENSG00000162849), KIF15 (ENSG00000163808), KIF6 (ENSG00000164627), KIF27 (ENSG00000165115), KIF7 (ENSG00000166813), KIFC2 (ENSG00000167702), KIF5C (ENSG00000168280), KIF5B (ENSG00000170759), KIF18B (ENSG00000186185), KIF24 (ENSG00000186638), KIF19 (ENSG00000196169), KIF13B (ENSG00000197892), KIF4B (ENSG00000226650)

Protein

Protein identifiers

Centromere-associated protein E — Q02224 (reviewed: Q02224)

Alternative names: Centromere protein E, Kinesin-7, Kinesin-related protein CENPE

All UniProt accessions (3): Q02224, A0A5F9ZH24, D6RHK2

UniProt curated annotations — full annotation on UniProt →

Function. Microtubule plus-end-directed kinetochore motor which plays an important role in chromosome congression, microtubule-kinetochore conjugation and spindle assembly checkpoint activation. Drives chromosome congression (alignment of chromosomes at the spindle equator resulting in the formation of the metaphase plate) by mediating the lateral sliding of polar chromosomes along spindle microtubules towards the spindle equator and by aiding the establishment and maintenance of connections between kinetochores and spindle microtubules. The transport of pole-proximal chromosomes towards the spindle equator is favored by microtubule tracks that are detyrosinated. Acts as a processive bi-directional tracker of dynamic microtubule tips; after chromosomes have congressed, continues to play an active role at kinetochores, enhancing their links with dynamic microtubule ends. Suppresses chromosome congression in NDC80-depleted cells and contributes positively to congression only when microtubules are stabilized. Plays an important role in the formation of stable attachments between kinetochores and spindle microtubules The stabilization of kinetochore-microtubule attachment also requires CENPE-dependent localization of other proteins to the kinetochore including BUB1B, MAD1 and MAD2. Plays a role in spindle assembly checkpoint activation (SAC) via its interaction with BUB1B resulting in the activation of its kinase activity, which is important for activating SAC. Necessary for the mitotic checkpoint signal at individual kinetochores to prevent aneuploidy due to single chromosome loss.

Subunit / interactions. Monomer. Interacts with CENPF. Interacts with BUB1B. Interacts with SEPT7. Interacts with KIF18A. Interacts with PRC1. Interacts with NUF2; this interaction determines kinetochore localization. Interacts with SKAP; this interaction greatly favors SKAP binding to microtubules. Interacts with TRAPPC12. Interacts with CTCF.

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

Post-translational modifications. The C-terminal inhibitory domain is phosphorylated. Phosphorylation relieves autoinhibition of the kinetochore motor. Sumoylated with SUMO2 and SUMO3. The sumoylation mediates the association to the kinetochore.

Disease relevance. Microcephaly 13, primary, autosomal recessive (MCPH13) [MIM:616051] A form of microcephaly, a disease defined as a head circumference more than 3 standard deviations below the age-related mean. Brain weight is markedly reduced and the cerebral cortex is disproportionately small. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. The protein is composed of a N-terminal kinesin-motor domain involved in the chromosome movements, a long coil-coiled region involved in the homodimerization and an inhibitory C-tail involved in autoinhibition of the N-terminal catalytic part.

Similarity. Belongs to the TRAFAC class myosin-kinesin ATPase superfamily. Kinesin family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q02224-1	1	yes
Q02224-3	3

RefSeq proteins (2): NP_001273663, NP_001804* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001752	Kinesin_motor_dom	Domain
IPR019821	Kinesin_motor_CS	Conserved_site
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR027640	Kinesin-like_fam	Family
IPR036961	Kinesin_motor_dom_sf	Homologous_superfamily

Pfam: PF00225

UniProt features (78 total): helix 18, strand 16, sequence conflict 11, modified residue 7, sequence variant 7, region of interest 5, compositionally biased region 4, splice variant 2, turn 2, chain 1, propeptide 1, binding site 1, domain 1, lipid moiety-binding region 1, coiled-coil region 1

Structure

Experimental structures (PDB)

6 structures.

PDB	Method	Resolution (Å)
8HFH	X-RAY DIFFRACTION	1.8
6M4I	X-RAY DIFFRACTION	1.9
5JVP	X-RAY DIFFRACTION	2.1
8OWI	X-RAY DIFFRACTION	2.14
1T5C	X-RAY DIFFRACTION	2.5
8WHL	X-RAY DIFFRACTION	3.2

Predicted structure (AlphaFold)

No AlphaFold model available for Q02224 — AlphaFold DB does not currently provide models for proteins above ~3000 aa.

Functional residue map

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

Ligand- & substrate-binding residues (1): 86–93

Post-translational modifications (8): 611, 2083, 2389, 2639, 2647, 2651, 2698, 2698

Function

Pathways and Gene Ontology

Reactome pathways

29 pathways

ID	Pathway
R-HSA-141444	Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal
R-HSA-2132295	MHC class II antigen presentation
R-HSA-2467813	Separation of Sister Chromatids
R-HSA-2500257	Resolution of Sister Chromatid Cohesion
R-HSA-5663220	RHO GTPases Activate Formins
R-HSA-6811434	COPI-dependent Golgi-to-ER retrograde traffic
R-HSA-68877	Mitotic Prometaphase
R-HSA-9648025	EML4 and NUDC in mitotic spindle formation
R-HSA-983189	Kinesins
R-HSA-109582	Hemostasis
R-HSA-1280218	Adaptive Immune System
R-HSA-141424	Amplification of signal from the kinetochores
R-HSA-162582	Signal Transduction
R-HSA-1640170	Cell Cycle
R-HSA-168256	Immune System
R-HSA-194315	Signaling by Rho GTPases
R-HSA-195258	RHO GTPase Effectors
R-HSA-199991	Membrane Trafficking
R-HSA-2555396	Mitotic Metaphase and Anaphase
R-HSA-5653656	Vesicle-mediated transport
R-HSA-6811442	Intra-Golgi and retrograde Golgi-to-ER traffic
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-8856688	Golgi-to-ER retrograde transport
R-HSA-9716542	Signaling by Rho GTPases, Miro GTPases and RHOBTB3
R-HSA-983231	Factors involved in megakaryocyte development and platelet production

MSigDB gene sets: 568 (showing top): BROWNE_HCMV_INFECTION_30MIN_DN, GSE45365_NK_CELL_VS_CD8A_DC_MCMV_INFECTION_UP, GNF2_CKS1B, GOBP_CHROMOSOME_ORGANIZATION, GOBP_ATTACHMENT_OF_SPINDLE_MICROTUBULES_TO_KINETOCHORE, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, GNF2_CENPF, chr4q24, GOBP_REGULATION_OF_PHOSPHORYLATION, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, GOBP_CHROMOSOME_LOCALIZATION, GOBP_CELL_CYCLE_PHASE_TRANSITION, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_UP, GAUSSMANN_MLL_AF4_FUSION_TARGETS_A_UP

GO Biological Process (18): mitotic cell cycle (GO:0000278), microtubule-based movement (GO:0007018), mitotic spindle organization (GO:0007052), chromosome segregation (GO:0007059), mitotic chromosome movement towards spindle pole (GO:0007079), mitotic metaphase chromosome alignment (GO:0007080), regulation of mitotic metaphase/anaphase transition (GO:0030071), positive regulation of protein kinase activity (GO:0045860), cell division (GO:0051301), metaphase chromosome alignment (GO:0051310), attachment of mitotic spindle microtubules to kinetochore (GO:0051315), kinetochore assembly (GO:0051382), microtubule plus-end directed mitotic chromosome migration (GO:0099606), lateral attachment of mitotic spindle microtubules to kinetochore (GO:0099607), nuclear division (GO:0000280), spindle organization (GO:0007051), attachment of spindle microtubules to kinetochore (GO:0008608), membraneless organelle assembly (GO:0140694)

GO Molecular Function (7): microtubule motor activity (GO:0003777), ATP binding (GO:0005524), microtubule binding (GO:0008017), kinetochore binding (GO:0043515), nucleotide binding (GO:0000166), cytoskeletal motor activity (GO:0003774), protein binding (GO:0005515)

GO Cellular Component (18): chromosome, centromeric region (GO:0000775), kinetochore (GO:0000776), condensed chromosome, centromeric region (GO:0000779), nucleus (GO:0005634), chromosome (GO:0005694), kinetochore microtubule (GO:0005828), cytosol (GO:0005829), microtubule (GO:0005874), microtubule cytoskeleton (GO:0015630), membrane (GO:0016020), midbody (GO:0030496), intercellular bridge (GO:0045171), spindle midzone (GO:0051233), mitotic spindle (GO:0072686), mitotic spindle midzone (GO:1990023), cytoplasm (GO:0005737), spindle (GO:0005819), cytoskeleton (GO:0005856)

Reactome top-level categories

Rollup of top-13 pathways:

Category	Pathways
Mitotic Prometaphase	2
M Phase	2
Amplification of signal from the kinetochores	1
Adaptive Immune System	1
Mitotic Anaphase	1
RHO GTPase Effectors	1
Golgi-to-ER retrograde transport	1
Factors involved in megakaryocyte development and platelet production	1
Immune System	1
Mitotic Spindle Checkpoint	1
Signaling by Rho GTPases, Miro GTPases and RHOBTB3	1
Signaling by Rho GTPases	1
Vesicle-mediated transport	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	6
mitotic cell cycle process	4
intracellular membraneless organelle	4
mitotic cell cycle	3
cell cycle process	3
mitotic sister chromatid segregation	2
metaphase chromosome alignment	2
chromosome localization	2
mitotic metaphase chromosome alignment	2
binding	2
microtubule cytoskeleton	2
spindle	2
cell cycle	1
mitotic nuclear division	1
microtubule-based process	1
spindle organization	1
microtubule cytoskeleton organization involved in mitosis	1
chromosome movement towards spindle pole	1
metaphase/anaphase transition of mitotic cell cycle	1
regulation of mitotic cell cycle phase transition	1
regulation of metaphase/anaphase transition of cell cycle	1
positive regulation of protein phosphorylation	1
protein kinase activity	1
positive regulation of kinase activity	1
regulation of protein kinase activity	1
cellular process	1
nuclear chromosome segregation	1
attachment of spindle microtubules to kinetochore	1
kinetochore organization	1
protein-containing complex assembly	1
membraneless organelle assembly	1
microtubule-based movement	1
establishment of localization in cell	1
establishment of organelle localization	1
attachment of mitotic spindle microtubules to kinetochore	1
organelle fission	1
microtubule cytoskeleton organization	1
microtubule binding	1
organelle assembly	1
cytoskeletal motor activity	1

Protein interactions and networks

STRING

2190 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CENPE	BUB1B	O60566	998
CENPE	CENPF	P49454	987
CENPE	CENPA	P49450	968
CENPE	NUF2	Q9BZD4	958
CENPE	AURKB	Q96GD4	946
CENPE	BUB1	O43683	935
CENPE	CENPB	P07199	901
CENPE	CENPC	Q03188	877
CENPE	CDC20	Q12834	865
CENPE	CENPS	Q8N2Z9	865
CENPE	PRC1	O43663	859
CENPE	CENPH	Q9H3R5	856
CENPE	BUB3	O43684	855
CENPE	NDC80	O14777	835
CENPE	BIRC5	O15392	834

IntAct

55 interactions, top by confidence:

A	B	Type	Score
MED4	MED19	psi-mi:“MI:0914”(association)	0.900
LMO1	ZBTB43	psi-mi:“MI:0914”(association)	0.830
MED4	MED14	psi-mi:“MI:0914”(association)	0.740
NUF2	CENPE	psi-mi:“MI:0915”(physical association)	0.670
CENPE	NUF2	psi-mi:“MI:0915”(physical association)	0.670
NUF2	CENPE	psi-mi:“MI:0407”(direct interaction)	0.670
CENPE	NUF2	psi-mi:“MI:0403”(colocalization)	0.670
NUF2	CENPE	psi-mi:“MI:0403”(colocalization)	0.670
MAD1L1	CENPE	psi-mi:“MI:0407”(direct interaction)	0.590
MAD1L1	CENPE	psi-mi:“MI:0914”(association)	0.590
MAD1L1	CENPE	psi-mi:“MI:0915”(physical association)	0.590
BUB1B	CENPE	psi-mi:“MI:0915”(physical association)	0.580
CENPE	BUB1B	psi-mi:“MI:0915”(physical association)	0.580
CENPE	CLASP2	psi-mi:“MI:0914”(association)	0.530
SYCE3	RER1	psi-mi:“MI:0914”(association)	0.530
CENPE	PPP1CA	psi-mi:“MI:0407”(direct interaction)	0.440
CENPE	RPL21	psi-mi:“MI:0915”(physical association)	0.400
KTN1	CENPE	psi-mi:“MI:0915”(physical association)	0.400
Cenpe	CENPE	psi-mi:“MI:0915”(physical association)	0.400
DUX1	CENPE	psi-mi:“MI:0915”(physical association)	0.370
CENPE	CENPF	psi-mi:“MI:0915”(physical association)	0.370
CENPE	CENPE	psi-mi:“MI:0915”(physical association)	0.370
CENPF	CENPE	psi-mi:“MI:0915”(physical association)	0.370
Max	PABPN1	psi-mi:“MI:0914”(association)	0.350

BioGRID (121): CENPE (Co-fractionation), CENPE (Co-fractionation), TPM4 (Co-fractionation), TSN (Co-fractionation), CENPE (Biochemical Activity), CENPE (Proximity Label-MS), ADARB2 (Affinity Capture-MS), CENPE (Affinity Capture-MS), PCM1 (Affinity Capture-MS), SPTAN1 (Affinity Capture-MS), SVIL (Affinity Capture-MS), OFD1 (Affinity Capture-MS), SYNPO (Affinity Capture-MS), CEP131 (Affinity Capture-MS), CLASP2 (Affinity Capture-MS)

ESM2 similar proteins: A0A068FIK2, B9EUM5, B9F7C8, B9FAF3, B9FFA3, B9FL70, B9FS33, B9FTR1, B9FUF9, B9G2X9, B9G3M6, B9GE13, F4IAR2, F4IBQ9, F4IL57, F4J1U4, F4J2K4, F4J2M6, F4JDI6, F4JGP4, F4JUI9, O81635, P46864, Q02224, Q07970, Q0IMS9, Q0WVX5, Q12840, Q27IK6, Q27IK7, Q2R2P7, Q5W6L9, Q6H638, Q6K765, Q6P9L6, Q6RT24, Q75LL2, Q7TSP2, Q7X7H4, Q7XKR9

Diamond homologs: A0A068FIK2, A0JN40, A1ZAJ2, A8BB91, A8BKD1, B1AVY7, B2GU58, B7EJ91, B7ZNG0, B9F7C8, B9FAF3, B9FUF9, F1M4A4, F1QN54, F4IIS5, F4K0J3, O14782, O15066, O23826, O35066, O35071, O35787, O43093, O43896, O55165, O60333, O88658, O95239, P17120, P17210, P23678, P28025, P28741, P28742, P33173, P33174, P46863, P46867, P46869, P46871

SIGNOR signaling

14 interactions.

A	Effect	B	Mechanism
RPS6KA3	“up-regulates activity”	CENPE
SEPTIN7	“up-regulates activity”	CENPE	binding
SPAG5	“up-regulates activity”	CENPE
PRC1	“up-regulates activity”	CENPE	binding
KIFC1	“up-regulates activity”	CENPE	binding
TTK	“up-regulates activity”	CENPE	phosphorylation
AURKA	“down-regulates activity”	CENPE	phosphorylation
CENPE	“up-regulates activity”	BUB1B	binding
CENPE	“up-regulates activity”	MAD1L1
CENPE	“up-regulates activity”	MAD2L1
CENPE	up-regulates	Spindle_assembly
BUB1	“up-regulates activity”	CENPE	relocalization
CDR2	“up-regulates quantity by expression”	CENPE	“transcriptional regulation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 56 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
Amplification of signal from the kinetochores	7	36.3×	2e-08
Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal	10	30.7×	2e-10
Mitotic Spindle Checkpoint	7	29.2×	9e-08
EML4 and NUDC in mitotic spindle formation	10	24.4×	5e-10
Resolution of Sister Chromatid Cohesion	10	22.8×	8e-10
RHO GTPases Activate Formins	10	20.4×	2e-09
Mitotic Prometaphase	11	20.0×	5e-10
Cell Cycle Checkpoints	8	18.6×	2e-07

GO biological processes:

GO term	Partners	Fold	FDR
attachment of mitotic spindle microtubules to kinetochore	5	105.3×	2e-07
mitotic spindle assembly checkpoint signaling	5	56.2×	3e-06
mitotic spindle organization	5	27.2×	1e-04
chromosome segregation	5	17.4×	6e-04
cell division	14	12.9×	7e-10
protein transport	8	7.0×	7e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	4
Uncertain significance	305
Likely benign	149
Benign	80

Top pathogenic / likely-pathogenic (5)

Variant ID	HGVS	Classification
3899392	NM_001813.3(CENPE):c.2906C>T (p.Ala969Val)	Pathogenic
3065153	NM_001813.3(CENPE):c.1403_1404del (p.Glu468fs)	Likely pathogenic
3065382	NM_001813.3(CENPE):c.885del (p.Leu296fs)	Likely pathogenic
430262	NM_001813.3(CENPE):c.767G>A (p.Cys256Tyr)	Likely pathogenic
932106	NM_001813.3(CENPE):c.2132-1G>C	Likely pathogenic

SpliceAI

5595 predictions. Top by Δscore:

Variant	Effect	Δscore
4:103109095:A:AC	acceptor_gain	1.0000
4:103109095:A:C	acceptor_gain	1.0000
4:103109097:G:C	acceptor_gain	1.0000
4:103109097:G:GC	acceptor_gain	1.0000
4:103111009:TCA:T	acceptor_gain	1.0000
4:103111010:CAC:C	acceptor_gain	1.0000
4:103111012:C:CC	acceptor_gain	1.0000
4:103114553:C:CC	acceptor_gain	1.0000
4:103116572:CGTA:C	donor_gain	1.0000
4:103116573:GTAC:G	donor_loss	1.0000
4:103116574:TACT:T	donor_loss	1.0000
4:103116575:A:AC	donor_gain	1.0000
4:103116575:ACT:A	donor_gain	1.0000
4:103116575:ACTC:A	donor_gain	1.0000
4:103116575:ACTCC:A	donor_loss	1.0000
4:103116576:C:CA	donor_gain	1.0000
4:103116576:CT:C	donor_gain	1.0000
4:103116576:CTC:C	donor_gain	1.0000
4:103116576:CTCC:C	donor_gain	1.0000
4:103116576:CTCCT:C	donor_gain	1.0000
4:103116577:T:TA	donor_gain	1.0000
4:103116578:C:CA	donor_gain	1.0000
4:103116685:TTGTC:T	acceptor_gain	1.0000
4:103116686:TGTC:T	acceptor_gain	1.0000
4:103116695:T:TC	acceptor_gain	1.0000
4:103116696:T:C	acceptor_gain	1.0000
4:103116696:T:TC	acceptor_gain	1.0000
4:103116697:T:C	acceptor_gain	1.0000
4:103116698:T:C	acceptor_gain	1.0000
4:103116698:T:TC	acceptor_gain	1.0000

AlphaMissense

18162 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:103181356:A:G	L355P	1.000
4:103194237:A:G	S229P	0.999
4:103194671:A:T	V164D	0.999
4:103195208:C:G	R128P	0.999
4:103195214:A:G	L126P	0.999
4:103195216:A:C	F125L	0.999
4:103195216:A:T	F125L	0.999
4:103195217:A:G	F125S	0.999
4:103195218:A:G	F125L	0.999
4:103181443:G:T	A326D	0.998
4:103182850:A:G	L292P	0.998
4:103194662:A:G	L167P	0.998
4:103182856:C:G	R290P	0.997
4:103185854:A:T	V234D	0.997
4:103194283:G:C	S213R	0.997
4:103194283:G:T	S213R	0.997
4:103194285:T:G	S213R	0.997
4:103194375:A:C	M209R	0.997
4:103196032:A:T	I82K	0.997
4:103196038:C:T	G80D	0.997
4:103177029:T:A	R420S	0.996
4:103177029:T:G	R420S	0.996
4:103181454:A:C	F322L	0.996
4:103181454:A:T	F322L	0.996
4:103181456:A:G	F322L	0.996
4:103182867:G:C	S286R	0.996
4:103182867:G:T	S286R	0.996
4:103182869:T:G	S286R	0.996
4:103194230:A:G	L231S	0.996
4:103194236:G:A	S229F	0.996

dbSNP variants (sampled 300 via entrez): RS1000003955 (4:103111421 G>T), RS1000004362 (4:103176554 T>C), RS1000050850 (4:103158709 A>C), RS1000059328 (4:103111166 T>C), RS1000098885 (4:103177017 G>A), RS1000198729 (4:103157219 T>A,C), RS1000224997 (4:103105456 C>T), RS1000255360 (4:103150514 G>A,C,T), RS1000320133 (4:103172211 T>C), RS1000352586 (4:103198745 C>G), RS1000362112 (4:103124344 G>A), RS1000369918 (4:103192027 A>G), RS1000382704 (4:103183678 T>C), RS1000422542 (4:103124025 G>A), RS1000443371 (4:103191779 A>G)

Disease associations

OMIM: gene MIM:117143 | disease phenotypes: MIM:616051, MIM:209850

GenCC curated gene-disease

Disease	Classification	Inheritance
Seckel syndrome	Supportive	Autosomal recessive
microcephaly 13, primary, autosomal recessive	Limited	Autosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
autosomal recessive primary microcephaly	Limited	AR

Mondo (4): microcephaly 13, primary, autosomal recessive (MONDO:0014473), breast ductal adenocarcinoma (MONDO:0005590), autism (MONDO:0005260), Seckel syndrome (MONDO:0019342)

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

HPO phenotypes

58 total (30 of 58 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000076	Vesicoureteral reflux
HP:0000122	Unilateral renal agenesis
HP:0000219	Thin upper lip vermilion
HP:0000252	Microcephaly
HP:0000275	Narrow face
HP:0000311	Round face
HP:0000340	Sloping forehead
HP:0000347	Micrognathia
HP:0000363	Abnormal earlobe morphology
HP:0000387	Absent earlobe
HP:0000400	Macrotia
HP:0000444	Convex nasal ridge
HP:0000448	Prominent nose
HP:0000494	Downslanted palpebral fissures
HP:0000501	Glaucoma
HP:0000582	Upslanted palpebral fissure
HP:0000639	Nystagmus
HP:0000682	Abnormal dental enamel morphology
HP:0001249	Intellectual disability
HP:0001263	Global developmental delay
HP:0001274	Agenesis of corpus callosum
HP:0001302	Pachygyria
HP:0001321	Cerebellar hypoplasia
HP:0001338	Partial agenesis of the corpus callosum
HP:0001347	Hyperreflexia
HP:0001363	Craniosynostosis
HP:0001382	Joint hypermobility
HP:0001385	Hip dysplasia
HP:0001510	Growth delay

GWAS associations

9 associations (top):

Study	Trait	p-value
GCST002022_3	Testicular germ cell tumor	2.000000e-10
GCST002855_5	Testicular germ cell tumor	6.000000e-12
GCST004635_10	Testicular germ cell tumor	7.000000e-20
GCST004713_18	Testicular germ cell tumor	1.000000e-16
GCST004946_70	Schizophrenia	3.000000e-08
GCST006225_1	Anti-chlamydia trachomatis IgG seropositivity	9.000000e-07
GCST008181_18	Spontaneous preterm birth without premature rupture of membranes	6.000000e-06
GCST010241_380	Apolipoprotein A1 levels	5.000000e-10
GCST010242_145	HDL cholesterol levels	4.000000e-12

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0009330	Chlamydia trachomatis seropositivity
EFO:0006917	spontaneous preterm birth
EFO:0004614	apolipoprotein A 1 measurement
EFO:0004612	high density lipoprotein cholesterol measurement

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D001321	Autistic Disorder	F03.625.164.113.500
D018270	Carcinoma, Ductal, Breast	C04.557.470.200.025.232.500; C04.557.470.615.132.500; C04.588.180.390; C17.800.090.500.390

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5870 (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: 87 (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
CHEMBL4303470	GSK-923295A	1	87

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

ChEMBL bioactivities

91 potent at pChembl≥5 of 94 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.82	IC50	1.5	nM	CHEMBL4470356
8.80	IC50	1.6	nM	CHEMBL4579540
8.77	IC50	1.7	nM	CHEMBL4549646
8.66	IC50	2.2	nM	CHEMBL4468555
8.64	IC50	2.3	nM	GSK-923295A
8.57	IC50	2.7	nM	CHEMBL4515745
8.51	Ki	3.1	nM	GSK-923295A
8.49	Ki	3.2	nM	GSK-923295A
8.43	IC50	3.7	nM	CHEMBL5712053
8.38	Ki	4.2	nM	CHEMBL5712065
8.38	Ki	4.2	nM	CHEMBL5712053
8.33	Ki	4.7	nM	CHEMBL5712053
7.92	Ki	12	nM	GSK-923295A
7.92	IC50	12.02	nM	CHEMBL6146884
7.89	Ki	13	nM	GSK-923295A
7.85	IC50	14	nM	CHEMBL4579162
7.85	Ki	14	nM	GSK-923295A
7.82	IC50	15.14	nM	CHEMBL6172036
7.80	IC50	15.85	nM	CHEMBL6168492
7.76	IC50	17.2	nM	GSK-923295A
7.75	Ki	18	nM	GSK-923295A
7.72	IC50	19	nM	CHEMBL4466617
7.70	IC50	19.95	nM	CHEMBL6169882
7.62	IC50	24	nM	CHEMBL4483703
7.50	IC50	32	nM	CHEMBL2413142
7.47	IC50	33.88	nM	CHEMBL6141698
7.46	IC50	35	nM	CHEMBL2413143
7.41	EC50	39	nM	CHEMBL4468555
7.38	IC50	42	nM	GSK-923295A
7.30	IC50	50	nM	CHEMBL2413146
7.29	IC50	51.9	nM	GSK-923295A
7.29	IC50	51.29	nM	CHEMBL6171315
7.25	IC50	55.6	nM	GSK-923295A
7.21	Ki	61	nM	GSK-923295A
7.19	Ki	64	nM	GSK-923295A
7.14	IC50	72	nM	CHEMBL2413135
7.14	Ki	73	nM	CHEMBL5712065
7.10	EC50	79	nM	CHEMBL4515745
7.08	IC50	83.18	nM	CHEMBL6141698
7.03	IC50	93.33	nM	CHEMBL6171857
7.01	IC50	97.72	nM	CHEMBL6162348
7.00	IC50	100	nM	CHEMBL2413137
6.98	IC50	104.7	nM	CHEMBL6162348
6.96	IC50	109.7	nM	CHEMBL6143485
6.92	IC50	120.2	nM	CHEMBL6151734
6.91	IC50	123	nM	CHEMBL6147066
6.91	IC50	123	nM	CHEMBL6151734
6.89	IC50	128.8	nM	CHEMBL6172036
6.89	IC50	128.8	nM	CHEMBL6146397
6.87	IC50	134	nM	GSK-923295A

PubChem BioAssay actives

51 with measured affinity, of 175 total; 26 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
N-[2-(dimethylamino)ethyl]-N-[(3S)-7-fluoro-1,1-dioxo-6-(trifluoromethyl)-2,3-dihydro-1-benzothiophen-3-yl]-3-(4-fluoro-3-methylphenyl)-5-methoxyimidazo[1,2-a]pyridine-2-carboxamide	1627856: Inhibition of human CENP-E motor domain assessed as ADP levels preincubated with protein motor domain/microtubule for 60 mins followed by ATP addition measured after 20 mins by ADPglo assay	ic50	0.0015	uM
N-[(3S)-6,7-dichloro-1,1-dioxo-2,3-dihydro-1-benzothiophen-3-yl]-N-[2-(dimethylamino)ethyl]-3-(4-fluoro-3-methylphenyl)-5-methoxyimidazo[1,2-a]pyridine-2-carboxamide	1627856: Inhibition of human CENP-E motor domain assessed as ADP levels preincubated with protein motor domain/microtubule for 60 mins followed by ATP addition measured after 20 mins by ADPglo assay	ic50	0.0016	uM
N-[(3S)-7-chloro-1,1-dioxo-6-(trifluoromethyl)-2,3-dihydro-1-benzothiophen-3-yl]-N-[2-(dimethylamino)ethyl]-3-(4-fluoro-3-methylphenyl)-5-methoxyimidazo[1,2-a]pyridine-2-carboxamide	1627856: Inhibition of human CENP-E motor domain assessed as ADP levels preincubated with protein motor domain/microtubule for 60 mins followed by ATP addition measured after 20 mins by ADPglo assay	ic50	0.0017	uM
N-[(3S)-7-cyano-1,1-dioxo-6-(trifluoromethyl)-2,3-dihydro-1-benzothiophen-3-yl]-N-[2-(dimethylamino)ethyl]-3-(4-fluoro-3-methylphenyl)-5-methoxyimidazo[1,2-a]pyridine-2-carboxamide	1627856: Inhibition of human CENP-E motor domain assessed as ADP levels preincubated with protein motor domain/microtubule for 60 mins followed by ATP addition measured after 20 mins by ADPglo assay	ic50	0.0022	uM
3-chloro-N-[(2S)-1-[[2-(dimethylamino)acetyl]amino]-3-[4-[8-[(1S)-1-hydroxyethyl]imidazo[1,2-a]pyridin-2-yl]phenyl]propan-2-yl]-4-propan-2-yloxybenzamide	2185223: Inhibition of microtubule-stimulated ATPase activity of C-terminal 6-his-tagged CENP-E (2 to 340 residues)(unknown origin) expressed in Escherichia coli BL21(DE3) in presence of ATP	ic50	0.0023	uM
N-(6,7-dichloro-1,1-dioxo-2,3-dihydro-1-benzothiophen-3-yl)-N-[2-(dimethylamino)ethyl]-3-(4-fluoro-3-methylphenyl)-5-methoxyimidazo[1,2-a]pyridine-2-carboxamide	1627856: Inhibition of human CENP-E motor domain assessed as ADP levels preincubated with protein motor domain/microtubule for 60 mins followed by ATP addition measured after 20 mins by ADPglo assay	ic50	0.0027	uM
3-cyano-N-[(2S)-4-hydroxy-1-[4-(8-methylimidazo[1,2-a]pyridin-2-yl)phenyl]butan-2-yl]-4-propan-2-yloxybenzamide	2185223: Inhibition of microtubule-stimulated ATPase activity of C-terminal 6-his-tagged CENP-E (2 to 340 residues)(unknown origin) expressed in Escherichia coli BL21(DE3) in presence of ATP	ic50	0.0037	uM
N-[3-(4-benzoylphenyl)-1-(methylamino)-1-oxopropan-2-yl]-3-chloro-4-propan-2-yloxybenzamide	2185173: Binding affinity to wild-type human CENP-E assessed as inhibition constant	ki	0.0042	uM
N-(6,7-dichloro-2,3-dihydro-1-benzothiophen-3-yl)-N-[2-(dimethylamino)ethyl]-3-(4-fluoro-3-methylphenyl)-5-methoxyimidazo[1,2-a]pyridine-2-carboxamide	1627856: Inhibition of human CENP-E motor domain assessed as ADP levels preincubated with protein motor domain/microtubule for 60 mins followed by ATP addition measured after 20 mins by ADPglo assay	ic50	0.0140	uM
N-(4,5-dichloro-2,3-dihydro-1H-inden-1-yl)-N-[2-(dimethylamino)ethyl]-3-(4-fluoro-3-methylphenyl)-5-methoxyimidazo[1,2-a]pyridine-2-carboxamide	1627856: Inhibition of human CENP-E motor domain assessed as ADP levels preincubated with protein motor domain/microtubule for 60 mins followed by ATP addition measured after 20 mins by ADPglo assay	ic50	0.0190	uM
N-(6,7-dichloro-2,3-dihydro-1H-indol-3-yl)-N-[2-(dimethylamino)ethyl]-3-(4-fluoro-3-methylphenyl)-5-methoxyimidazo[1,2-a]pyridine-2-carboxamide	1627856: Inhibition of human CENP-E motor domain assessed as ADP levels preincubated with protein motor domain/microtubule for 60 mins followed by ATP addition measured after 20 mins by ADPglo assay	ic50	0.0240	uM
3-bromo-N-[(3,4-dichlorophenyl)methyl]-N-[2-(dimethylamino)ethyl]-4-(4-fluorophenyl)thieno[3,2-b]pyrrole-5-carboxamide	764126: Inhibition of human ATPase activity of CENP-E motor domain assessed as ADP production after 60 mins by ADP-Glo luminescence assay	ic50	0.0320	uM
3-chloro-N-[(3,4-dichlorophenyl)methyl]-N-[2-(dimethylamino)ethyl]-4-(4-fluorophenyl)thieno[3,2-b]pyrrole-5-carboxamide	764126: Inhibition of human ATPase activity of CENP-E motor domain assessed as ADP production after 60 mins by ADP-Glo luminescence assay	ic50	0.0350	uM
5-bromo-N-[(3,4-dichlorophenyl)methyl]-N-[2-(dimethylamino)ethyl]-3-(4-fluorophenyl)imidazo[1,2-a]pyridine-2-carboxamide	764126: Inhibition of human ATPase activity of CENP-E motor domain assessed as ADP production after 60 mins by ADP-Glo luminescence assay	ic50	0.0500	uM
N-[(3,4-dichlorophenyl)methyl]-5-[2-(dimethylamino)ethyl]-7-(4-fluorophenyl)-N-methyl-4-oxothieno[3,4-c]pyridine-6-carboxamide	764126: Inhibition of human ATPase activity of CENP-E motor domain assessed as ADP production after 60 mins by ADP-Glo luminescence assay	ic50	0.0720	uM
N-[(3,4-dichlorophenyl)methyl]-N-[2-(dimethylamino)ethyl]-7-(4-fluorophenyl)-5-methyl-4-oxothieno[3,4-c]pyridine-6-carboxamide	764126: Inhibition of human ATPase activity of CENP-E motor domain assessed as ADP production after 60 mins by ADP-Glo luminescence assay	ic50	0.1000	uM
N-[(3,4-dichlorophenyl)methyl]-N-[2-(dimethylamino)ethyl]-4-(4-fluorophenyl)-3-(trifluoromethyl)thieno[3,2-b]pyrrole-5-carboxamide	764126: Inhibition of human ATPase activity of CENP-E motor domain assessed as ADP production after 60 mins by ADP-Glo luminescence assay	ic50	0.1400	uM
N-[(3,4-dichlorophenyl)methyl]-5-[3-(dimethylamino)propyl]-7-(4-fluorophenyl)-N-methyl-4-oxothieno[3,4-c]pyridine-6-carboxamide	764126: Inhibition of human ATPase activity of CENP-E motor domain assessed as ADP production after 60 mins by ADP-Glo luminescence assay	ic50	0.3000	uM
N-[(3,4-dichlorophenyl)methyl]-N-[2-(dimethylamino)ethyl]-4-(4-fluorophenyl)-3-methylthieno[3,2-b]pyrrole-5-carboxamide	764126: Inhibition of human ATPase activity of CENP-E motor domain assessed as ADP production after 60 mins by ADP-Glo luminescence assay	ic50	0.3700	uM
3-cyano-N-[(3,4-dichlorophenyl)methyl]-N-[2-(dimethylamino)ethyl]-4-(4-fluorophenyl)thieno[3,2-b]pyrrole-5-carboxamide	764126: Inhibition of human ATPase activity of CENP-E motor domain assessed as ADP production after 60 mins by ADP-Glo luminescence assay	ic50	0.5400	uM
N-[(3,4-dichlorophenyl)methyl]-7-(4-fluorophenyl)-N,5-dimethyl-4-oxothieno[3,4-c]pyridine-6-carboxamide	764125: Inhibition of ATPase activity of CENP-E motor domain (unknown origin) by high throughput screening assay	ic50	1.5000	uM
N-[(3,4-dichlorophenyl)methyl]-7-(4-fluorophenyl)-5-(2-hydroxyethyl)-N-methyl-4-oxothieno[3,4-c]pyridine-6-carboxamide	764126: Inhibition of human ATPase activity of CENP-E motor domain assessed as ADP production after 60 mins by ADP-Glo luminescence assay	ic50	1.8000	uM
N-[(3,4-dichlorophenyl)methyl]-N-[2-(dimethylamino)ethyl]-4-(4-fluorophenyl)thieno[3,2-b]pyrrole-5-carboxamide	764126: Inhibition of human ATPase activity of CENP-E motor domain assessed as ADP production after 60 mins by ADP-Glo luminescence assay	ic50	2.0000	uM
N-[[3,5-bis(trifluoromethyl)phenyl]methyl]-7-(4-fluorophenyl)-N,5-dimethyl-4-oxothieno[3,4-c]pyridine-6-carboxamide	764125: Inhibition of ATPase activity of CENP-E motor domain (unknown origin) by high throughput screening assay	ic50	2.1000	uM
N-[(3,4-dichlorophenyl)methyl]-N-[2-(dimethylamino)ethyl]-1-(4-fluorophenyl)-3-methylindole-2-carboxamide	764126: Inhibition of human ATPase activity of CENP-E motor domain assessed as ADP production after 60 mins by ADP-Glo luminescence assay	ic50	2.1000	uM
N-[(3,4-dichlorophenyl)methyl]-N-[2-(dimethylamino)ethyl]-3-(4-fluorophenyl)-1-methylindole-2-carboxamide	764126: Inhibition of human ATPase activity of CENP-E motor domain assessed as ADP production after 60 mins by ADP-Glo luminescence assay	ic50	8.5000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects methylation, affects binding, increases reaction, decreases expression, increases expression	4
Cyclosporine	decreases expression	4
Resveratrol	decreases expression, affects cotreatment, increases expression	3
Valproic Acid	decreases expression	3
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	3
Aflatoxin B1	affects expression, decreases expression, decreases methylation	3
potassium chromate(VI)	affects cotreatment, decreases expression	2
Irinotecan	decreases expression	2
Air Pollutants	increases abundance, decreases expression	2
Formaldehyde	decreases expression, increases expression	2
Tobacco Smoke Pollution	decreases expression	2
Particulate Matter	decreases expression, increases abundance	2
FR900359	increases phosphorylation	1
dicrotophos	decreases expression	1
methylmercuric chloride	decreases expression	1
methyleugenol	decreases expression	1
triphenyl phosphate	affects expression	1
propionaldehyde	decreases expression	1
pirinixic acid	affects binding, decreases expression, increases activity	1
bisphenol A	decreases expression	1
geraniol	decreases expression	1
hydroxyhydroquinone	decreases expression	1
beta-lapachone	decreases expression	1
arsenite	affects binding, decreases reaction	1
mono-(2-ethylhexyl)phthalate	decreases expression	1
butyraldehyde	decreases expression	1
perfluorooctanoic acid	decreases expression	1
diallyl trisulfide	decreases expression	1
beta-methylcholine	affects expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1

ChEMBL screening assays

346 unique, capped per target: 241 functional, 105 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1020049	Binding	Inhibition of cloned human CENP-E	Kinesin spindle protein (KSP) inhibitors. 9. Discovery of (2S)-4-(2,5-difluorophenyl)-n-[(3R,4S)-3-fluoro-1-methylpiperidin-4-yl]-2-(hydroxymethyl)-N-methyl-2-phenyl-2,5-dihydro-1H-pyrrole-1-carboxamide (MK-0731) for the treatment of taxane-refractory cancer. — J Med Chem
CHEMBL5444563	Functional	Affinity Phenotypic Cellular interaction: (Growth inhibitory effect colon cancer cell line SW48) EUB0000734a CENPE	Affinity Phenotypic Cellular Literature for EUbOPEN Chemogenomic Library

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_SI70	HAP1 CENPE (-) 1	Cancer cell line	Male
CVCL_SI71	HAP1 CENPE (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00211796	PHASE4	COMPLETED	Divalproex Sodium ER in Adult Autism
NCT00391261	PHASE4	COMPLETED	An Open-label Trial of Metformin for Weight Control of Pediatric Patients on Antipsychotic Medications.
NCT00409747	PHASE4	COMPLETED	Minocycline to Treat Childhood Regressive Autism
NCT00576732	PHASE4	COMPLETED	A Study of the Effectiveness and Safety of Two Doses of Risperidone in the Treatment of Children and Adolescents With Autistic Disorder
NCT00844753	PHASE4	COMPLETED	Atomoxetine, Placebo and Parent Management Training in Autism
NCT01028820	PHASE4	COMPLETED	FMRI Brain Activation of Aripiprazole Treatment in Autism Spectrum Disorders
NCT01098383	PHASE4	UNKNOWN	Treatment With Acetyl-Choline Esterase Inhibitors in Children With Autism Spectrum Disorders
NCT01333865	PHASE4	COMPLETED	A Study of Memantine Hydrochloride (Namenda®) for Cognitive and Behavioral Impairment in Adults With Autism Spectrum Disorders
NCT01337700	PHASE4	COMPLETED	Milnacipran in Autism and the Functional Locus Coeruleus and Noradrenergic Model of Autism
NCT01695200	PHASE4	COMPLETED	Omega-3 Fatty Acids in Autism Spectrum Disorders
NCT02069977	PHASE4	UNKNOWN	Study to Evaluate the Efficacy and Safety of Aripiprazole
NCT02096952	PHASE4	COMPLETED	Methylphenidate ER Liquid Formulation in Adults With ASD and ADHD
NCT02199925	PHASE4	UNKNOWN	An Open-Label Study to Evaluate the Efficacy of High-Dose Gammaplex in Children on the Autism Spectrum
NCT02235467	PHASE4	COMPLETED	Multisite Study: Parental Training Using Video Modelling to Develop Social Skills in Children With Autism
NCT02255565	PHASE4	COMPLETED	Dose Response Effects of Quillivant XR in Children With ADHD and Autism: A Pilot Study
NCT02940574	PHASE4	COMPLETED	Neural and Behavioral Effects of Oxytocin in Autism Spectrum Disorders
NCT03333629	PHASE4	COMPLETED	Promoting Positive Outcomes for Individuals With ASD: Linking Early Detection, Treatment, and Long-term Outcomes
NCT03337646	PHASE4	COMPLETED	Evaluation of the Effect and Safety of Lisdexamfetamine in Children Aged 6-12 With ADHD and Autism
NCT03538431	PHASE4	COMPLETED	Improving Driving in Young People With Autism Spectrum Disorders
NCT03757585	PHASE4	COMPLETED	Natural Treatments for the Management of Emotional Dysregulation in Youth With Non-verbal Learning Disability (NVLD) and/or Autism Spectrum Disorders (ASD)
NCT04903353	PHASE4	COMPLETED	Pragmatic Trial Comparing Weight Gain in Children With Autism Taking Risperidone Versus Aripiprazole
NCT05063656	PHASE4	COMPLETED	Biomarker-Driven Pharmacological Treatment of Adolescents With Autism Spectrum Disorder With Gabapentin
NCT05146245	PHASE4	UNKNOWN	Safety and Pharmacokinetics of Antipsychotics in Children 2: Studying TDM in an RCT
NCT05916339	PHASE4	RECRUITING	AWARE: Management of ADHD in Autism Spectrum Disorder
NCT05954052	PHASE4	TERMINATED	A Study of Glutathione in Children With Autism Spectrum Disorder
NCT06853665	PHASE4	RECRUITING	The TEAM Study - Treatment Efficacy for Autism/Attention Using Mixed Amphetamine
NCT07054697	PHASE4	COMPLETED	Pilot-RCT With Individualized Homeopathic Treatment in the Children With Autism Spectrum Disorder
NCT07161804	PHASE4	COMPLETED	Pilot RCT Using Homeopathic Medicines in ASD
NCT07439042	PHASE4	NOT_YET_RECRUITING	Buspirone for Anxiety in Autistic Youth
NCT03414970	PHASE3	ACTIVE_NOT_RECRUITING	Hypofractionated Radiation Therapy After Mastectomy in Preventing Recurrence in Patients With Stage IIa-IIIa Breast Cancer
NCT00036231	PHASE3	TERMINATED	Synthetic Human Secretin in Children With Autism and Gastrointestinal Dysfunction
NCT00036244	PHASE3	COMPLETED	Synthetic Human Secretin in Children With Autism
NCT00065884	PHASE3	UNKNOWN	Valproate Response in Aggressive Autistic Adolescents
NCT00065962	PHASE3	COMPLETED	Secretin for the Treatment of Autism
NCT00252603	PHASE3	COMPLETED	Galantamine Versus Placebo in Childhood Autism
NCT00346736	PHASE3	COMPLETED	Use of Acupuncture In Children With Autistic Spectrum Disorder
NCT00352248	PHASE3	COMPLETED	Randomized Controlled Trial of Acupuncture Versus Sham Acupuncture in Autistic Spectrum Disorder
NCT00352352	PHASE3	COMPLETED	Use of Acupuncture In Children With Autistic Spectrum Disorder
NCT00355329	PHASE3	COMPLETED	Randomized Control Trial of Using Tongue Acupuncture in Autistic Spectrum Disorder Using PET Scan for Clinical Correlation
NCT00498173	PHASE3	COMPLETED	Effectiveness of Atomoxetine in Treating ADHD Symptoms in Children and Adolescents With Autism