TPX2

Summary

TPX2 (TPX2 microtubule nucleation factor, HGNC:1249) is a protein-coding gene on chromosome 20q11.21, encoding Targeting protein for Xklp2 (Q9ULW0). Spindle assembly factor required for normal assembly of mitotic spindles. It is a common-essential gene (DepMap: required in 99.3% of cancer cell lines).

Enables importin-alpha family protein binding activity; molecular adaptor activity; and protein kinase binding activity. Involved in activation of protein kinase activity; microtubule cytoskeleton organization; and negative regulation of microtubule depolymerization. Located in intercellular bridge; nucleoplasm; and spindle. Is active in spindle.

Source: NCBI Gene 22974 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Tourette syndrome (No Known Disease Relationship, GenCC)
• GWAS associations: 9
• Clinical variants (ClinVar): 119 total
• Druggable target: yes — 2 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 99.3% of screened cell lines (common-essential)
• MANE Select transcript: NM_012112

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1249
Approved symbol	TPX2
Name	TPX2 microtubule nucleation factor
Location	20q11.21
Locus type	gene with protein product
Status	Approved
Aliases	p100, DIL-2, HCA519, FLS353
Ensembl gene	ENSG00000088325
Ensembl biotype	protein_coding
OMIM	605917
Entrez	22974

Gene structure

Transcript identifiers

Ensembl transcripts: 33 — 33 protein_coding

ENST00000300403, ENST00000340513, ENST00000853939, ENST00000853940, ENST00000853941, ENST00000853942, ENST00000853943, ENST00000853944, ENST00000853945, ENST00000853946, ENST00000853947, ENST00000853948, ENST00000853949, ENST00000853950, ENST00000853951, ENST00000853952, ENST00000853953, ENST00000934050, ENST00000934051, ENST00000934052, ENST00000934053, ENST00000934054, ENST00000934055, ENST00000934056, ENST00000934057, ENST00000934058, ENST00000934059, ENST00000934060, ENST00000934061, ENST00000934062, ENST00000934063, ENST00000934064, ENST00000934065

RefSeq mRNA: 1 — MANE Select: NM_012112 NM_012112

CCDS: CCDS13190

Canonical transcript exons

ENST00000300403 — 18 exons

Exon	Start	End
ENSE00000560794	31760057	31760179
ENSE00000560800	31778813	31778984
ENSE00000560807	31798365	31798552
ENSE00000661090	31766556	31766682
ENSE00000661091	31770343	31770471
ENSE00000661092	31771560	31771682
ENSE00000661094	31775867	31775988
ENSE00000661095	31777487	31777638
ENSE00000661097	31782249	31782390
ENSE00000661098	31783705	31783921
ENSE00000661099	31792735	31792830
ENSE00000661100	31793848	31794024
ENSE00000661101	31794402	31794548
ENSE00000661102	31797404	31797515
ENSE00000859866	31757407	31757582
ENSE00001388212	31742541	31742647
ENSE00003848934	31739290	31739621
ENSE00003849573	31800970	31801800

Expression profiles

Bgee: expression breadth ubiquitous, 200 present calls, max score 98.79.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 47.3123 / max 509.6753, expressed in 1634 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
183981	45.4156	1623
183982	1.6602	772
209071	0.1799	80
183984	0.0492	19
183985	0.0073	4

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ventricular zone	UBERON:0003053	98.79	gold quality
ganglionic eminence	UBERON:0004023	96.63	gold quality
embryo	UBERON:0000922	96.29	gold quality
endometrium epithelium	UBERON:0004811	94.57	gold quality
oocyte	CL:0000023	94.13	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	93.46	gold quality
secondary oocyte	CL:0000655	92.76	gold quality
bone marrow	UBERON:0002371	88.91	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	88.45	gold quality
trabecular bone tissue	UBERON:0002483	87.59	gold quality
bone element	UBERON:0001474	86.89	gold quality
right testis	UBERON:0004534	86.72	gold quality
left testis	UBERON:0004533	86.46	gold quality
bone marrow cell	CL:0002092	86.44	gold quality
testis	UBERON:0000473	86.31	gold quality
mucosa of transverse colon	UBERON:0004991	86.16	gold quality
thymus	UBERON:0002370	85.75	gold quality
stromal cell of endometrium	CL:0002255	85.69	gold quality
rectum	UBERON:0001052	83.78	gold quality
vermiform appendix	UBERON:0001154	82.17	gold quality
ileal mucosa	UBERON:0000331	82.08	silver quality
sperm	CL:0000019	81.48	silver quality
esophagus mucosa	UBERON:0002469	81.19	gold quality
male germ cell	CL:0000015	80.85	silver quality
lower esophagus mucosa	UBERON:0035834	79.87	gold quality
adrenal tissue	UBERON:0018303	79.41	gold quality
caecum	UBERON:0001153	78.30	gold quality
cartilage tissue	UBERON:0002418	77.98	gold quality
lymph node	UBERON:0000029	77.62	gold quality
tongue squamous epithelium	UBERON:0006919	77.41	gold quality

Single-cell (SCXA)

Detected in 22 experiment(s), a significant marker in 18.

Experiment	Marker?	Max mean expression
E-MTAB-11121	yes	1430.50
E-MTAB-8559	yes	1100.01
E-MTAB-10485	yes	1044.63
E-ENAD-20	yes	867.92
E-GEOD-93593	yes	865.60
E-MTAB-8894	yes	784.79
E-MTAB-10290	yes	608.80
E-MTAB-7249	yes	525.43
E-MTAB-8271	yes	522.74
E-MTAB-7052	yes	396.33
E-MTAB-8530	yes	221.67
E-HCAD-10	yes	36.38
E-HCAD-13	yes	23.55
E-HCAD-6	yes	21.13
E-HCAD-5	yes	18.81

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): STAT3

miRNA regulators (miRDB)

28 targeting TPX2, 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-4282	99.99	75.36	6408
HSA-MIR-3617-3P	99.98	67.86	918
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-4778-3P	99.93	70.40	1818
HSA-MIR-3065-3P	99.87	70.25	1407
HSA-MIR-1296-3P	99.72	64.04	636
HSA-MIR-6762-3P	99.66	66.94	1188
HSA-MIR-516B-5P	99.56	66.33	1495
HSA-MIR-4688	99.48	64.68	828
HSA-MIR-6743-5P	99.48	63.60	721
HSA-MIR-3678-3P	99.31	67.10	1432
HSA-MIR-29A-5P	99.08	68.59	1813
HSA-MIR-670-3P	99.03	68.88	2404
HSA-MIR-4326	98.97	67.63	962
HSA-MIR-4464	98.95	67.73	820
HSA-MIR-4748	98.95	67.53	810
HSA-MIR-655-5P	98.74	65.93	888
HSA-MIR-4703-5P	98.53	70.13	1645
HSA-MIR-3942-5P	98.52	69.51	1517
HSA-MIR-4766-3P	98.48	67.94	1347
HSA-MIR-4294	97.86	65.72	1110
HSA-MIR-1289	97.46	65.37	655
HSA-MIR-7855-5P	97.39	67.18	925
HSA-MIR-3667-5P	97.16	64.87	591
HSA-MIR-216B-5P	97.16	66.76	1126
HSA-MIR-8069	97.05	66.79	718
HSA-MIR-759	96.16	66.77	873

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 99.3% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 40)

• TPX2 is required for targeting Aurora-A kinase to the spindle apparatus and Aurora-A might regulate the function of TPX2 during spindle assembly (PMID:12177045)
• spindle formation requires the function of TPX2 to generate a stable bipolar spindle with overlapping antiparallel microtubule arrays (PMID:12389033)
• observations reveal a structural role for hTPX2 in spindles and provide evidence for a balance between microtubule-based motor forces and structural spindle components (PMID:12477396)
• molecular cloning; overexpression provokes accumulation of cells in G(2)-M phase and subsequent polyploidization, suggesting that excess repp86 may interfere with correct nuclear division (PMID:12612055)
• APC/C(Cdh1) controls the stability of TPX2, thereby ensuring accurate regulation of the spindle assembly in the cell cycle (PMID:16287863)
• Aberrant expression of TPX2 may play important role(s) in both malignant transformation of respiratory epithelium and progression of squamous cell lung cancer and could serve as a prognostic predictor for the disease. (PMID:16489064)
• TPX2 binding decreases the size and accessibility of a hydrophobic pocket, adjacent to the ATP site, to inhibitors. (PMID:17705509)
• Data show that Siah2 is an important mediator of repp86 protein degradation. (PMID:17716627)
• Chromosome nucleation is involved in spindle pole separation and setting spindle length. A second Aurora A-independent function of TPX2 is required to bipolarize spindles. (PMID:18663142)
• human TPX2 mRNA is closely linked to increased or abnormal cell proliferation in malignant salivary gland tumors. (PMID:19148505)
• Data provide a molecular explanation for the assembly of the apoptotic microtubule network, and suggest important similarities with the process of RanGTP- and TPX2-mediated mitotic spindle formation. (PMID:19208764)
• Overexpression of TPX2 is associated with oral squamous cell carcinomas. (PMID:19424574)
• Data show that Aurora A(S155R) mutant reduced cellular activity and mislocalization are due to loss of interaction with TPX2. (PMID:19801554)
• TPX2 expression is associated with the progression of malignant astrocytoma. (PMID:20599806)
• association of Aurora-A and TPX2 gives rise to a novel functional unit with oncogenic properties.[review] (PMID:20708655)
• Decreased AurA-TPX2 complex formation in response to irradiation results from reduced cellular levels of TPX2, as a result of protein degradation and decreased translation of TPX2 mRNA. (PMID:21099343)
• TPX2 protects Aurora-A from degradation both in interphase and in mitosis. (PMID:21147853)
• Results demonstrate a role for PP6 as the T-loop phosphatase regulating Aurora A activity bound to its activator TPX2 during mitotic spindle formation. (PMID:21187329)
• two switches determining Aurora A activation (PMID:21347367)
• TPX2 promote 20q amplicon-driven progression of colorectal adenoma to carcinoma. (PMID:22207630)
• TPX2 shows potential to be used as a new marker for cervical cancer diagnosis and therapy. (PMID:22307108)
• The data support the role of TPX2 as a novel co-activator of Aurora kinase B. (PMID:22560880)
• AIM1, ERGIC1, and TPX2 were shown to be highly expressed especially in prostate cancer tissues, and high mRNA expression of ERGIC1 and TMED3 associated with AR and ERG oncogene expression (PMID:22761906)
• the regulation of gamma-H2AX signals by TPX2 is not associated with apoptosis or the mitotic functions of TPX2. (PMID:23045526)
• Data indicate that the sensitivity of cell-lines with amplification of AURKA depends upon the activity of the kinase, which correlates with the expression of the regulatory gene products TPX2 and HMMR/RHAMM. (PMID:23328114)
• GLIPR1 interacts with Hsc70, and GLIPR1 overexpression or Hsc70 knockdown leads to transcriptional suppression of AURKA and TPX2. (PMID:23333597)
• Data indicate that expression-based risk indices of three genes UBE2C, TPX2, and MELK were more strongly associated with poor 5-year survival in adenocarcinoma patients. (PMID:23357462)
• Data show that five genes CKAP5, KPNB1, RAN, TPX2 and KIF11 were shown to be essential for tumor cell survival in both head and neck squamous cell carcinoma (HNSCC)and non-small cell lung cancer (NSCLC), but most particularly in HNSCC. (PMID:23444224)
• The expression of TPX2 protein and mRNA were correlated with invasive depth and lymphatic metastasis of esophageal squamous cell carcinoma. (PMID:23725757)
• Data indicate that TPX2 (target protein for Xklp2) may play a role in the development and progression of bladder carcinoma, and suggest that inhibition of TPX2 level may be a novel strategy for therapy of the patients with bladder carcinoma. (PMID:23873098)
• TPX2 expression is associated with cell proliferation and poor prognosis among patients with resected esophageal squamous cell carcinoma (PMID:23963785)
• TPX2 plays an important role in promoting tumorigenesis and metastasis of human colon cancer, and may represent a novel prognostic biomarker and therapeutic target for the disease (PMID:24341487)
• TPX2 overexpression is associated with medullary thyroid carcinoma. (PMID:24488334)
• This review provides an historic overview of the discovery of TPX2 and summarizes its cytoskeletal and signaling roles with relevance to cancer therapies. [review] (PMID:24556998)
• RAN nucleo-cytoplasmic transport and mitotic spindle assembly partners XPO7 and TPX2 have roles in serous epithelial ovarian cancer (PMID:24625450)
• The results demonstrated that TPX2 is important in the regulation of tumor growth in cervical cancer and therefore may be a potential therapeutic target as a novel treatment strategy. (PMID:24718984)
• the molecular mechanisms of two distinct activation strategies (autophosphorylation and TPX2-mediated activation) in human Aurora A kinase, was elucidated. (PMID:24867643)
• Identify RHAMM as a critical regulator of TPX2 location/ Aurora kinase A signaling and suggest that RHAMM ensures bipolar spindle assembly and mitotic progression through the integration of biochemical and structural pathways. (PMID:24875404)
• TPX2 siRNA transfection significantly reduced tumor growth. (PMID:25239289)
• In vitro studies found that TPX2 knockdown significantly inhibited cell proliferation and viability in both Hep3B and HepG2 cells. (PMID:25302620)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	tpx2	ENSDARG00000078654
mus_musculus	Tpx2	ENSMUSG00000027469
rattus_norvegicus	Tpx2	ENSRNOG00000008165

Protein

Protein identifiers

Targeting protein for Xklp2 — Q9ULW0 (reviewed: Q9ULW0)

Alternative names: Differentially expressed in cancerous and non-cancerous lung cells 2, Hepatocellular carcinoma-associated antigen 519, Hepatocellular carcinoma-associated antigen 90, Protein fls353, Restricted expression proliferation-associated protein 100

All UniProt accessions (2): Q9ULW0, Q643R0

UniProt curated annotations — full annotation on UniProt →

Function. Spindle assembly factor required for normal assembly of mitotic spindles. Required for normal assembly of microtubules during apoptosis. Required for chromatin and/or kinetochore dependent microtubule nucleation. Mediates AURKA localization to spindle microtubules. Activates AURKA by promoting its autophosphorylation at ‘Thr-288’ and protects this residue against dephosphorylation. TPX2 is inactivated upon binding to importin-alpha. At the onset of mitosis, GOLGA2 interacts with importin-alpha, liberating TPX2 from importin-alpha, allowing TPX2 to activate AURKA kinase and stimulate local microtubule nucleation.

Subunit / interactions. Interacts with AURKA. Interacts with importin-alpha; leading to inactivate TPX2. Interacts with HNRNPU; this interaction recruits HNRNPU to spindle microtubules (MTs). Interacts with BCL2L10. Interacts with KIF11.

Subcellular location. Nucleus. Cytoplasm. Cytoskeleton. Spindle. Spindle pole.

Tissue specificity. Expressed in lung carcinoma cell lines but not in normal lung tissues.

Similarity. Belongs to the TPX2 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9ULW0-1	1	yes
Q9ULW0-2	2, HCA90

RefSeq proteins (1): NP_036244* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR009675	TPX2_fam	Family
IPR015128	Aurora-A-bd	Domain
IPR027329	TPX2_C	Domain
IPR027330	TPX2_central_dom	Domain

Pfam: PF06886, PF09041, PF12214

UniProt features (34 total): modified residue 18, cross-link 4, helix 3, region of interest 2, sequence conflict 2, chain 1, splice variant 1, sequence variant 1, compositionally biased region 1, turn 1

Structure

Experimental structures (PDB)

14 structures.

PDB	Method	Resolution (Å)
6VPM	X-RAY DIFFRACTION	1.58
6VPL	X-RAY DIFFRACTION	1.86
6VPI	X-RAY DIFFRACTION	2
5LXM	X-RAY DIFFRACTION	2.08
6VPJ	X-RAY DIFFRACTION	2.1
6VPH	X-RAY DIFFRACTION	2.14
9SUY	X-RAY DIFFRACTION	2.27
3E5A	X-RAY DIFFRACTION	2.3
3HA6	X-RAY DIFFRACTION	2.36
1OL5	X-RAY DIFFRACTION	2.5
6VPG	X-RAY DIFFRACTION	2.64
6XKA	X-RAY DIFFRACTION	2.65
4C3P	X-RAY DIFFRACTION	2.69
6BJC	ELECTRON MICROSCOPY	3.3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9ULW0-F1	64.23	0.05

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 (22): 257, 292, 293, 305, 310, 338, 359, 369, 375, 486, 499, 738, 477, 500, 641, 740, 59, 72, 121, 125 …

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-6804756	Regulation of TP53 Activity through Phosphorylation
R-HSA-8854518	AURKA Activation by TPX2

MSigDB gene sets: 433 (showing top): GNF2_CKS1B, GOBP_CHROMOSOME_ORGANIZATION, WU_APOPTOSIS_BY_CDKN1A_VIA_TP53, MODULE_52, BORCZUK_MALIGNANT_MESOTHELIOMA_UP, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, HORIUCHI_WTAP_TARGETS_DN, KANG_DOXORUBICIN_RESISTANCE_UP, GNF2_CENPF, GOBP_REGULATION_OF_MICROTUBULE_BASED_PROCESS, MORF_BUB1, GOBP_REGULATION_OF_PHOSPHORYLATION, BASSO_B_LYMPHOCYTE_NETWORK, CROONQUIST_NRAS_SIGNALING_DN, CHIANG_LIVER_CANCER_SUBCLASS_UNANNOTATED_DN

GO Biological Process (8): mitotic cell cycle (GO:0000278), apoptotic process (GO:0006915), microtubule nucleation (GO:0007020), negative regulation of microtubule depolymerization (GO:0007026), activation of protein kinase activity (GO:0032147), cell division (GO:0051301), regulation of mitotic spindle organization (GO:0060236), mitotic spindle assembly (GO:0090307)

GO Molecular Function (5): protein kinase binding (GO:0019901), protein serine/threonine kinase activator activity (GO:0043539), molecular adaptor activity (GO:0060090), importin-alpha family protein binding (GO:0061676), protein binding (GO:0005515)

GO Cellular Component (12): spindle pole (GO:0000922), nucleus (GO:0005634), nucleoplasm (GO:0005654), spindle (GO:0005819), cytosol (GO:0005829), microtubule (GO:0005874), microtubule cytoskeleton (GO:0015630), axon hillock (GO:0043203), intercellular bridge (GO:0045171), mitotic spindle (GO:0072686), cytoplasm (GO:0005737), cytoskeleton (GO:0005856)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Regulation of TP53 Activity	1
G2/M Transition	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	6
mitotic nuclear division	2
mitotic spindle organization	2
binding	2
spindle	2
microtubule cytoskeleton	2
intracellular membraneless organelle	2
cell cycle	1
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
microtubule cytoskeleton organization	1
microtubule polymerization	1
microtubule depolymerization	1
negative regulation of microtubule polymerization or depolymerization	1
regulation of microtubule depolymerization	1
negative regulation of protein depolymerization	1
negative regulation of supramolecular fiber organization	1
positive regulation of protein kinase activity	1
cellular process	1
regulation of spindle organization	1
mitotic sister chromatid segregation	1
spindle assembly	1
kinase binding	1
protein serine/threonine kinase activity	1
protein kinase activator activity	1
molecular_function	1
protein binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
cytoplasm	1
polymeric cytoskeletal fiber	1
cytoskeleton	1
axon	1
neuronal cell body	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

2676 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TPX2	AURKA	O14965	995
TPX2	HMMR	O75330	857
TPX2	DLGAP5	Q15398	831
TPX2	SPON2	Q9BUD6	817
TPX2	KIF11	P52732	790
TPX2	NUSAP1	Q9BXS6	768
TPX2	KIF4A	O95239	765
TPX2	UBE2C	O00762	751
TPX2	AURKB	Q96GD4	751
TPX2	KIF15	Q9NS87	750
TPX2	CENPF	P49454	746
TPX2	MELK	Q14680	740
TPX2	BUB1	O43683	740
TPX2	CDK1	P06493	736
TPX2	CDC20	Q12834	736

IntAct

156 interactions, top by confidence:

A	B	Type	Score
TPX2	AURKA	psi-mi:“MI:0407”(direct interaction)	0.890
AURKA	TPX2	psi-mi:“MI:0915”(physical association)	0.890
TPX2	AURKA	psi-mi:“MI:0914”(association)	0.890
GOLGA2	TPX2	psi-mi:“MI:0915”(physical association)	0.720
TPX2	GOLGA2	psi-mi:“MI:0915”(physical association)	0.720
Mad2l1	BUB1B	psi-mi:“MI:0915”(physical association)	0.560
CALR	TPX2	psi-mi:“MI:0915”(physical association)	0.560
TPX2	CDH1	psi-mi:“MI:0915”(physical association)	0.560
DLST	TPX2	psi-mi:“MI:0915”(physical association)	0.560
CDK5R1	TPX2	psi-mi:“MI:0915”(physical association)	0.560
TPX2	NEK7	psi-mi:“MI:0915”(physical association)	0.560
GSTM3	ECT2L	psi-mi:“MI:0914”(association)	0.530
EPHA2	GOLIM4	psi-mi:“MI:0914”(association)	0.530
BAG2	HGS	psi-mi:“MI:0914”(association)	0.530

BioGRID (387): TPX2 (Two-hybrid), TPX2 (Affinity Capture-MS), TPX2 (Affinity Capture-MS), TPX2 (Affinity Capture-MS), TPX2 (Affinity Capture-MS), TPX2 (Proximity Label-MS), AFAP1 (Affinity Capture-MS), SAP130 (Affinity Capture-MS), TPX2 (Affinity Capture-MS), TPX2 (Affinity Capture-MS), TPX2 (Affinity Capture-MS), TPX2 (Affinity Capture-MS), TPX2 (Affinity Capture-MS), TPX2 (Affinity Capture-MS), TPX2 (Affinity Capture-MS)

ESM2 similar proteins: A1A5R9, A2AVQ5, A2RRW4, A2RSX4, A5WUY6, A9JS51, B0BM24, B0S4Q5, B1H283, D4A039, F1MMV1, Q08BC4, Q0VB26, Q2T9Q3, Q2TA11, Q2TBS4, Q3KQ80, Q3SX64, Q3TZ65, Q3ZCV2, Q4KKZ1, Q4KLY8, Q4R5Y0, Q5PQN4, Q5RAF2, Q5XI56, Q6ZN84, Q810P2, Q8BUG5, Q8C008, Q8C8J0, Q8IXM7, Q8N412, Q8N6G2, Q8N7U6, Q8N801, Q8TCI5, Q8WW14, Q9D067, Q9D131

Diamond homologs: A2APB8, A4IH24, A6H6Z7, E2RYF8, Q5RAF2, Q6DDV8, Q6NUF4, Q9ULW0, F4I2H7

SIGNOR signaling

7 interactions.

A	Effect	B	Mechanism
AURKA	“up-regulates activity”	TPX2	phosphorylation
TPX2	“up-regulates activity”	CLASP1	binding
CDK5	“up-regulates quantity by stabilization”	TPX2	phosphorylation
CDK1	“down-regulates activity”	TPX2	phosphorylation
TPX2	“down-regulates activity”	KIF11	binding
CDK2	“down-regulates activity”	TPX2	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 143 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
RHOU GTPase cycle	5	13.0×	2e-03
TP53 Regulates Transcription of DNA Repair Genes	6	10.2×	1e-03
mRNA 3’-end processing	5	9.2×	6e-03
G2/M DNA damage checkpoint	8	9.0×	4e-04
Regulation of TP53 Activity	7	8.7×	1e-03
Transport of Mature mRNA derived from an Intron-Containing Transcript	6	8.5×	3e-03
MITF-M-dependent gene expression	5	8.5×	7e-03
mRNA Splicing	8	8.2×	5e-04

GO biological processes:

GO term	Partners	Fold	FDR
positive regulation of miRNA transcription	7	15.8×	1e-04
cellular response to UV	6	13.8×	1e-03
mRNA transport	6	12.2×	1e-03
cellular senescence	5	11.5×	6e-03
heterochromatin formation	5	9.9×	1e-02
protein import into nucleus	7	7.8×	4e-03
mRNA splicing, via spliceosome	11	7.8×	1e-04
mRNA processing	10	6.1×	1e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	86
Likely benign	7
Benign	3

Top pathogenic / likely-pathogenic (0)

SpliceAI

2415 predictions. Top by Δscore:

Variant	Effect	Δscore
20:31757401:CCTCA:C	acceptor_loss	1.0000
20:31757402:CTCA:C	acceptor_loss	1.0000
20:31757403:TCAGA:T	acceptor_loss	1.0000
20:31757405:A:AG	acceptor_gain	1.0000
20:31757405:A:G	acceptor_loss	1.0000
20:31757405:AGAAG:A	acceptor_gain	1.0000
20:31757406:G:GA	acceptor_gain	1.0000
20:31757406:G:T	acceptor_loss	1.0000
20:31757406:GA:G	acceptor_gain	1.0000
20:31757406:GAA:G	acceptor_gain	1.0000
20:31757406:GAAGG:G	acceptor_gain	1.0000
20:31757578:GTTTG:G	donor_gain	1.0000
20:31757583:G:A	donor_loss	1.0000
20:31757583:G:GG	donor_gain	1.0000
20:31757584:T:G	donor_loss	1.0000
20:31760024:T:A	acceptor_gain	1.0000
20:31760054:C:G	acceptor_gain	1.0000
20:31760055:A:AG	acceptor_gain	1.0000
20:31760055:AGAG:A	acceptor_gain	1.0000
20:31760056:G:GT	acceptor_gain	1.0000
20:31760056:GA:G	acceptor_gain	1.0000
20:31760056:GAGG:G	acceptor_gain	1.0000
20:31760056:GAGGA:G	acceptor_gain	1.0000
20:31760177:CAGG:C	donor_loss	1.0000
20:31760178:AGG:A	donor_loss	1.0000
20:31760179:GGTAA:G	donor_loss	1.0000
20:31760180:G:A	donor_loss	1.0000
20:31760181:T:A	donor_loss	1.0000
20:31766551:CGCA:C	acceptor_loss	1.0000
20:31766553:CA:C	acceptor_loss	1.0000

AlphaMissense

4908 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
20:31783877:T:C	F457L	0.996
20:31783879:T:A	F457L	0.996
20:31783879:T:G	F457L	0.996
20:31798431:G:C	R671P	0.992
20:31798421:G:C	A668P	0.991
20:31783892:T:C	C462R	0.990
20:31793950:T:C	F538L	0.990
20:31793952:C:A	F538L	0.990
20:31793952:C:G	F538L	0.990
20:31797443:T:C	F625L	0.990
20:31797445:C:A	F625L	0.990
20:31797445:C:G	F625L	0.990
20:31792739:T:A	V473D	0.989
20:31793978:G:C	R547P	0.989
20:31794411:T:C	F566L	0.989
20:31794413:C:A	F566L	0.989
20:31794413:C:G	F566L	0.989
20:31778849:T:C	F307L	0.988
20:31778851:C:A	F307L	0.988
20:31778851:C:G	F307L	0.988
20:31778930:T:C	F334L	0.988
20:31778932:C:A	F334L	0.988
20:31778932:C:G	F334L	0.988
20:31783878:T:C	F457S	0.988
20:31797482:T:C	F638L	0.987
20:31797484:T:A	F638L	0.987
20:31797484:T:G	F638L	0.987
20:31801058:T:C	F741S	0.987
20:31782323:C:A	R377S	0.986
20:31775944:G:C	R229P	0.985

dbSNP variants (sampled 300 via entrez): RS1000019961 (20:31738867 C>T), RS1000046520 (20:31781670 A>C), RS1000109871 (20:31787459 G>C), RS1000154924 (20:31743069 C>T), RS1000200617 (20:31775043 T>A), RS1000223043 (20:31760714 T>C), RS1000225388 (20:31741641 G>A), RS1000282591 (20:31780648 T>A), RS1000390062 (20:31773589 C>G), RS1000408358 (20:31768935 C>T), RS1000459144 (20:31762285 A>G), RS1000497424 (20:31739118 G>A,C,T), RS1000558720 (20:31761957 G>A,C), RS1000682911 (20:31769753 G>A), RS1000695730 (20:31774912 G>A)

Disease associations

OMIM: gene MIM:605917 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
Tourette syndrome	No Known Disease Relationship	Unknown

Mondo (1): Tourette syndrome (MONDO:0007661)

Orphanet (0):

HPO phenotypes

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

GWAS associations

9 associations (top):

Study	Trait	p-value
GCST003030_10	Oppositional defiant disorder dimensions in attention-deficit hyperactivity disorder	3.000000e-06
GCST003030_9	Oppositional defiant disorder dimensions in attention-deficit hyperactivity disorder	4.000000e-06
GCST004639_6	Prudent dietary pattern	2.000000e-06
GCST009067_1	Mosaic loss of chromosome Y (Y chromosome dosage)	2.000000e-17
GCST009375_7	Mosaic loss of chromosome Y (Y chromosome dosage)	2.000000e-17
GCST010703_295	Brain morphology (MOSTest)	1.000000e-14
GCST90002387_162	Immature fraction of reticulocytes	2.000000e-12
GCST90002394_571	Monocyte percentage of white cells	5.000000e-12
GCST90002396_52	Mean reticulocyte volume	9.000000e-37

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0007679	oppositional defiant disorder measurement
EFO:0008111	diet measurement
EFO:0007783	mosaic loss of chromosome Y measurement
EFO:0004346	neuroimaging measurement
EFO:0007989	monocyte percentage of leukocytes
EFO:0010701	mean reticulocyte volume

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D005879	Tourette Syndrome	C10.228.140.079.898; C10.228.662.825.800; C10.574.500.850; C16.320.400.820; F03.625.992.850

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL3883304 (PROTEIN COMPLEX), CHEMBL5389 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

2 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 734 (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
CHEMBL1090479	GSK-1070916	1	177
CHEMBL3544932	TAK-901	1	557

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

Binding affinities (BindingDB)

5 measured of 5 human assays (5 total across all organisms); most potent 5 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
2-[(1E,3E)-5-[(2E)-3-(3-{[(5R)-5-carbamoyl-5-{[4- (3-chloro-2-fluorophenoxy)-1-{[6-(1,3-thiazol-2- ylamino)pyridin-2- yl]methyl}cyclohexyl]formamido}pentyl]carbamoyl}propyl)-1- ethyl-3-methyl-5-sulfoindol-2-ylidene]penta-1,3- dien-1-yl]-1-ethyl-3,3-dimethylindol-1-ium-5- sulfonate (Compound III)	KD	0.2 nM
2-[(1E,3E)-5-[(2E)-3-(3-{[(5R)-5-carbamoyl-5-[(4- {[13-chloro-10-(2-fluoro-6-methoxyphenyl)-3,5,9- triazatricyclo[9.4.0.0,⁷]pentadeca- 1(11),2(7),3,5,9,12,14-heptaen-4-yl]amino}-2- methoxyphenyl)formamido]pentyl]carbamoyl}propyl)-1- ethyl-3-methyl-5-sulfoindol-2-ylidene]penta-1,3- dien-1-yl]-1-ethyl-3,3-dimethylindol-1-ium-5- sulfonate (Compound I)	KD	0.273 nM
VX-689	IC50	0.6 nM
4-(9-chloro-7-(2-fluoro-6-methoxyphenyl)-5H-benzo[c]pyrimido[4,5-e]azepin-2-ylamino)-2-methoxybenzoic acid	IC50	0.6 nM	US-9346787: Piperidine compound or salt thereof
Compound II: Ac-D-Arg6-D-Lys(PromoFluor 647)-D-Lys(MLN8237*)-NH2	KD	5.2 nM

ChEMBL bioactivities

40 potent at pChembl≥5 of 43 total, top 38 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.21	IC50	6.2	nM	CHEMBL587029
8.10	IC50	7.9	nM	CHEMBL1090832
7.80	IC50	16	nM	CHEMBL1243200
7.75	Kd	18	nM	CHEMBL5598235
7.72	Kd	19	nM	CHEMBL5597404
7.68	IC50	21	nM	TAK-901
7.39	IC50	41	nM	CHEMBL1243326
7.21	IC50	62	nM	CHEMBL1243137
7.20	Kd	63	nM	CHEMBL5596916
7.12	IC50	76	nM	CHEMBL1090508
7.10	Kd	79	nM	CHEMBL5596260
7.00	Kd	100	nM	CHEMBL5598288
6.89	IC50	128	nM	CHEMBL1090670
6.83	IC50	149	nM	CHEMBL1243294
6.80	Kd	158	nM	CHEMBL5598166
6.70	Kd	200	nM	CHEMBL5597168
6.31	Ki	490	nM	GSK-1070916
6.31	Ki	492	nM	GSK-1070916
6.23	IC50	584	nM	CHEMBL1089985
6.23	IC50	586	nM	CHEMBL1242977
6.02	Kd	955	nM	CHEMBL5596300
6.02	IC50	964	nM	CHEMBL1243073
6.01	IC50	982	nM	CHEMBL1089986
5.96	IC50	1100	nM	GSK-1070916
5.90	Kd	1260	nM	CHEMBL5597558
5.89	EC50	1300	nM	CHEMBL5596916
5.81	IC50	1546	nM	CHEMBL1243008
5.81	IC50	1544	nM	CHEMBL1243042
5.66	EC50	2200	nM	CHEMBL5598288
5.63	IC50	2342	nM	CHEMBL1243009
5.46	EC50	3500	nM	CHEMBL5596260
5.41	EC50	3900	nM	CHEMBL5597404
5.35	EC50	4500	nM	CHEMBL5596916
5.26	EC50	5500	nM	CHEMBL5597168
5.23	EC50	5900	nM	CHEMBL5596260
5.21	EC50	6100	nM	CHEMBL5597404
5.19	EC50	6400	nM	CHEMBL5597168
5.16	EC50	6900	nM	CHEMBL5598288

PubChem BioAssay actives

45 with measured affinity, of 72 total; 31 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
2-[(1E,3E,5E)-5-[3-[4-[[(5R)-6-amino-5-[[4-[[9-chloro-7-(2-fluoro-6-methoxyphenyl)-5H-pyrimido[5,4-d][2]benzazepin-2-yl]amino]-2-methoxybenzoyl]amino]-6-oxohexyl]amino]-4-oxobutyl]-1-ethyl-3-methyl-5-sulfoindol-2-ylidene]penta-1,3-dienyl]-1-ethyl-3,3-dimethylindol-1-ium-5-sulfonate	1800235: Dissociation Kinetics Assay from Article 10.1002/cbic.201300613: “Long residence times revealed by Aurora A kinase-targeting fluorescent probes derived from inhibitors MLN8237 and VX-689.”	kd	0.0005	uM
2-[(1E,3E,5E)-5-[3-[4-[[(5R)-6-amino-5-[[4-(3-chloro-2-fluorophenoxy)-1-[[6-(1,3-thiazol-2-ylamino)-2-pyridinyl]methyl]cyclohexanecarbonyl]amino]-6-oxohexyl]amino]-4-oxobutyl]-1-ethyl-3-methyl-5-sulfoindol-2-ylidene]penta-1,3-dienyl]-1-ethyl-3,3-dimethylindol-1-ium-5-sulfonate	1800235: Dissociation Kinetics Assay from Article 10.1002/cbic.201300613: “Long residence times revealed by Aurora A kinase-targeting fluorescent probes derived from inhibitors MLN8237 and VX-689.”	kd	0.0005	uM
4-[[9-chloro-7-(2-fluoro-6-methoxyphenyl)-5H-pyrimido[5,4-d][2]benzazepin-2-yl]amino]-2-methoxybenzoic acid	1800233: Inhibition Assay Protocol A from Article 10.1002/cbic.201300613: “Long residence times revealed by Aurora A kinase-targeting fluorescent probes derived from inhibitors MLN8237 and VX-689.”	ki	0.0019	uM
4-(3-chloro-2-fluorophenoxy)-1-[[6-(1,3-thiazol-2-ylamino)-2-pyridinyl]methyl]cyclohexane-1-carboxylic acid	1800233: Inhibition Assay Protocol A from Article 10.1002/cbic.201300613: “Long residence times revealed by Aurora A kinase-targeting fluorescent probes derived from inhibitors MLN8237 and VX-689.”	ki	0.0022	uM
(2E)-3-[4-[[5-[[2-[[2-[[2-[[2-[[2-[[2-acetamido-5-[[amino(azaniumylidene)methyl]amino]pentanoyl]amino]-5-[[amino(azaniumylidene)methyl]amino]pentanoyl]amino]-5-[[amino(azaniumylidene)methyl]amino]pentanoyl]amino]-5-[[amino(azaniumylidene)methyl]amino]pentanoyl]amino]-5-[[amino(azaniumylidene)methyl]amino]pentanoyl]amino]-5-(diaminomethylideneazaniumyl)pentanoyl]amino]-6-[[1-amino-6-[[4-[[9-chloro-7-(2-fluoro-6-methoxyphenyl)-5H-pyrimido[5,4-d][2]benzazepin-2-yl]amino]-2-methoxybenzoyl]amino]-1-oxohexan-2-yl]amino]-6-oxohexyl]amino]-4-oxobutyl]-1-ethyl-2-[(2E,4E)-5-(1-ethyl-3,3-dimethyl-5-sulfonatoindol-1-ium-2-yl)penta-2,4-dienylidene]-3-methylindole-5-sulfonate	1800235: Dissociation Kinetics Assay from Article 10.1002/cbic.201300613: “Long residence times revealed by Aurora A kinase-targeting fluorescent probes derived from inhibitors MLN8237 and VX-689.”	kd	0.0043	uM
1-[3-[5-chloro-4-(1-methylpyrazol-4-yl)-1H-pyrrolo[2,3-b]pyridin-2-yl]phenyl]-N,N-dimethylmethanamine	473664: Inhibition of human recombinant aurora A/TPX2 complex after 120 mins by IMAP fluorescence polarization assay	ic50	0.0062	uM
1-[4-[5-chloro-4-(1-methylpyrazol-4-yl)-1H-pyrrolo[2,3-b]pyridin-2-yl]phenyl]-N,N-dimethylmethanamine	473664: Inhibition of human recombinant aurora A/TPX2 complex after 120 mins by IMAP fluorescence polarization assay	ic50	0.0079	uM
2-anilino-N-[4-[[3-[2-(methylamino)pyrimidin-4-yl]-2-pyridinyl]oxy]phenyl]benzamide	511478: Inhibition of Aurora A/TPX2 (1-43) by HTRF assay	ic50	0.0160	uM
4-(4-chloro-3-pyridin-2-yloxyphenyl)-N-cyclopropylsulfonyl-7-methyl-1H-indole-6-carboxamide	2123180: Inhibition of 6-His-tagged human Aurora A (126 to 390 residues) expressed in Escherichia coli BL21 (DE3) cells/N-terminal his-tagged/GB-1 fused human TPX2 (7 to 43 residues) expressed in Escherichia coli protein-protein interaction assessed as dissociation constant of compound binding to aurora A in presence of ATP by competitive fluorescence polarization assay	kd	0.0180	uM
4-(4-chloro-3-pyridin-2-yloxyphenyl)-N-(dimethylsulfamoyl)-7-methyl-1H-indole-6-carboxamide	2123180: Inhibition of 6-His-tagged human Aurora A (126 to 390 residues) expressed in Escherichia coli BL21 (DE3) cells/N-terminal his-tagged/GB-1 fused human TPX2 (7 to 43 residues) expressed in Escherichia coli protein-protein interaction assessed as dissociation constant of compound binding to aurora A in presence of ATP by competitive fluorescence polarization assay	kd	0.0190	uM
5-(3-ethylsulfonylphenyl)-3,8-dimethyl-N-(1-methylpiperidin-4-yl)-9H-pyrido[2,3-b]indole-7-carboxamide	1419650: Inhibition of Aurora A/TPX2 (unknown origin) pre-incubated for 1 hr followed by FL-Kemptide substrate and ATP addition	ic50	0.0210	uM
4-(4-fluorophenyl)-N-[4-[[3-[2-(methylamino)pyrimidin-4-yl]-2-pyridinyl]oxy]phenyl]phthalazin-1-amine	511478: Inhibition of Aurora A/TPX2 (1-43) by HTRF assay	ic50	0.0410	uM
2-anilino-N-[3-methyl-4-[[3-[2-(methylamino)pyrimidin-4-yl]-2-pyridinyl]oxy]phenyl]benzamide	511478: Inhibition of Aurora A/TPX2 (1-43) by HTRF assay	ic50	0.0620	uM
4-(4-chloro-3-pyrazin-2-yloxyphenyl)-N-(dimethylsulfamoyl)-7-methyl-1H-indole-6-carboxamide	2123180: Inhibition of 6-His-tagged human Aurora A (126 to 390 residues) expressed in Escherichia coli BL21 (DE3) cells/N-terminal his-tagged/GB-1 fused human TPX2 (7 to 43 residues) expressed in Escherichia coli protein-protein interaction assessed as dissociation constant of compound binding to aurora A in presence of ATP by competitive fluorescence polarization assay	kd	0.0630	uM
N,N-dimethyl-1-[4-[4-(1-methylpyrazol-4-yl)-1H-pyrrolo[2,3-b]pyridin-2-yl]phenyl]methanamine	473664: Inhibition of human recombinant aurora A/TPX2 complex after 120 mins by IMAP fluorescence polarization assay	ic50	0.0760	uM
4-(4-chlorophenyl)-N-cyclopropylsulfonyl-7-methyl-1H-indole-6-carboxamide	2123180: Inhibition of 6-His-tagged human Aurora A (126 to 390 residues) expressed in Escherichia coli BL21 (DE3) cells/N-terminal his-tagged/GB-1 fused human TPX2 (7 to 43 residues) expressed in Escherichia coli protein-protein interaction assessed as dissociation constant of compound binding to aurora A in presence of ATP by competitive fluorescence polarization assay	kd	0.0790	uM
4-(4-chlorophenyl)-N-(dimethylsulfamoyl)-7-methyl-1H-indole-6-carboxamide	2123180: Inhibition of 6-His-tagged human Aurora A (126 to 390 residues) expressed in Escherichia coli BL21 (DE3) cells/N-terminal his-tagged/GB-1 fused human TPX2 (7 to 43 residues) expressed in Escherichia coli protein-protein interaction assessed as dissociation constant of compound binding to aurora A in presence of ATP by competitive fluorescence polarization assay	kd	0.1000	uM
N,N-dimethyl-1-[3-[4-(1-methylpyrazol-4-yl)-1H-pyrrolo[2,3-b]pyridin-2-yl]phenyl]methanamine	473664: Inhibition of human recombinant aurora A/TPX2 complex after 120 mins by IMAP fluorescence polarization assay	ic50	0.1280	uM
N-[4-[[3-[2-(methylamino)pyrimidin-4-yl]-2-pyridinyl]oxy]phenyl]-4-phenylphthalazin-1-amine	511478: Inhibition of Aurora A/TPX2 (1-43) by HTRF assay	ic50	0.1490	uM
4-(4-chlorophenyl)-7-methyl-1H-indole-6-carboxylic acid	2123180: Inhibition of 6-His-tagged human Aurora A (126 to 390 residues) expressed in Escherichia coli BL21 (DE3) cells/N-terminal his-tagged/GB-1 fused human TPX2 (7 to 43 residues) expressed in Escherichia coli protein-protein interaction assessed as dissociation constant of compound binding to aurora A in presence of ATP by competitive fluorescence polarization assay	kd	0.1580	uM
4-(4-chloro-3-cyanophenyl)-7-methyl-1H-indole-6-carboxylic acid	2123180: Inhibition of 6-His-tagged human Aurora A (126 to 390 residues) expressed in Escherichia coli BL21 (DE3) cells/N-terminal his-tagged/GB-1 fused human TPX2 (7 to 43 residues) expressed in Escherichia coli protein-protein interaction assessed as dissociation constant of compound binding to aurora A in presence of ATP by competitive fluorescence polarization assay	kd	0.2000	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	1419700: Inhibition of human Aurora A/TPX2 (unknown origin) pre-incubated for 30 mins before Biotin-Ahx-RARRRLSFFFFAKKK-NH2 substrate addition and measured after 120 mins	ki	0.4900	uM
4-(1H-pyrazol-4-yl)-1H-pyrrolo[2,3-b]pyridine	473664: Inhibition of human recombinant aurora A/TPX2 complex after 120 mins by IMAP fluorescence polarization assay	ic50	0.5840	uM
N-[3-methyl-4-[[3-[2-(methylamino)pyrimidin-4-yl]-2-pyridinyl]oxy]phenyl]-3-(trifluoromethyl)benzamide	511478: Inhibition of Aurora A/TPX2 (1-43) by HTRF assay	ic50	0.5860	uM
4-(4-chloro-3-cyanophenyl)-1H-indole-6-carboxylic acid	2123180: Inhibition of 6-His-tagged human Aurora A (126 to 390 residues) expressed in Escherichia coli BL21 (DE3) cells/N-terminal his-tagged/GB-1 fused human TPX2 (7 to 43 residues) expressed in Escherichia coli protein-protein interaction assessed as dissociation constant of compound binding to aurora A in presence of ATP by competitive fluorescence polarization assay	kd	0.9550	uM
N-[3-methyl-4-[[3-[2-(methylamino)pyrimidin-4-yl]-2-pyridinyl]oxy]phenyl]-3-phenoxybenzamide	511478: Inhibition of Aurora A/TPX2 (1-43) by HTRF assay	ic50	0.9640	uM
4-(1-methylpyrazol-4-yl)-1H-pyrrolo[2,3-b]pyridine	473664: Inhibition of human recombinant aurora A/TPX2 complex after 120 mins by IMAP fluorescence polarization assay	ic50	0.9820	uM
4-(4-chlorophenyl)-1H-indole-6-carboxylic acid	2123180: Inhibition of 6-His-tagged human Aurora A (126 to 390 residues) expressed in Escherichia coli BL21 (DE3) cells/N-terminal his-tagged/GB-1 fused human TPX2 (7 to 43 residues) expressed in Escherichia coli protein-protein interaction assessed as dissociation constant of compound binding to aurora A in presence of ATP by competitive fluorescence polarization assay	kd	1.2600	uM
N-[3-methyl-4-[[3-[2-(methylamino)pyrimidin-4-yl]-2-pyridinyl]oxy]phenyl]-2-phenoxybenzamide	511478: Inhibition of Aurora A/TPX2 (1-43) by HTRF assay	ic50	1.5440	uM
3-chloro-N-[3-methyl-4-[[3-[2-(methylamino)pyrimidin-4-yl]-2-pyridinyl]oxy]phenyl]benzamide	511478: Inhibition of Aurora A/TPX2 (1-43) by HTRF assay	ic50	1.5460	uM
4-chloro-N-[3-methyl-4-[[3-[2-(methylamino)pyrimidin-4-yl]-2-pyridinyl]oxy]phenyl]benzamide	511478: Inhibition of Aurora A/TPX2 (1-43) by HTRF assay	ic50	2.3420	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects expression, affects localization, decreases expression, affects cotreatment	4
sodium arsenite	decreases expression, increases expression	3
Cyclosporine	decreases expression	3
cobaltous chloride	decreases expression	2
perfluorooctane sulfonic acid	decreases expression, increases expression	2
Acetaminophen	decreases expression	2
Cadmium	decreases expression, increases expression	2
Nickel	increases expression	2
Tobacco Smoke Pollution	decreases expression	2
Tretinoin	decreases expression	2
Valproic Acid	affects expression, decreases methylation	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	2
Aflatoxin B1	affects expression, affects cotreatment, increases expression	2
aristolochic acid I	decreases expression	1
SP2509	decreases expression	1
FR900359	affects phosphorylation	1
TAK-243	increases sumoylation	1
triphenyl phosphate	affects expression	1
deoxynivalenol	increases expression	1
geraniol	decreases expression	1
trichostatin A	decreases expression	1
arsenite	decreases reaction, affects binding	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
perfluorooctanoic acid	decreases expression	1
zinc chromate	decreases expression, increases abundance	1
ochratoxin A	decreases expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, increases expression	1
coumarin	decreases phosphorylation	1
cupric oxide	decreases expression	1
nivalenol	increases expression	1

ChEMBL screening assays

24 unique, capped per target: 24 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1105942	Binding	Inhibition of Aurora A/TPX2 at 5 uM	Structure-activity relationship study of EphB3 receptor tyrosine kinase inhibitors. — Bioorg Med Chem Lett

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00152750	PHASE4	UNKNOWN	Study of Clonidine on Sleep Architecture in Children With Tourette’s Syndrome (TS) and Comorbid ADHD
NCT00226824	PHASE4	TERMINATED	Safety Study of Galantamine in Tic Disorders
NCT00241176	PHASE4	COMPLETED	Open Label Trial of Aripiprazole in Children and Adolescents With Tourette’s Disorder
NCT00370838	PHASE4	COMPLETED	Comparison of Keppra and Clonidine in the Treatment of Tics
NCT01018056	PHASE4	COMPLETED	Developing New Treatments for Tourette Syndrome: Therapeutic Trials With Modulators of Glutamatergic Neurotransmission
NCT01547000	PHASE4	COMPLETED	Guanfacine in Children With Tic Disorders
NCT03239210	PHASE4	COMPLETED	Effects of Ondansetron in Obsessive-compulsive and Tic Disorders
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