TACC3

Summary

TACC3 (transforming acidic coiled-coil containing protein 3, HGNC:11524) is a protein-coding gene on chromosome 4p16.3, encoding Transforming acidic coiled-coil-containing protein 3 (Q9Y6A5). Plays a role in the microtubule-dependent coupling of the nucleus and the centrosome. It is a selective cancer dependency (DepMap: 54.3% of cell lines).

This gene encodes a member of the transforming acidic colied-coil protein family. The encoded protein is a motor spindle protein that may play a role in stabilization of the mitotic spindle. This protein may also play a role in growth a differentiation of certain cancer cells.

Source: NCBI Gene 10460 — RefSeq curated summary.

At a glance

• GWAS associations: 12
• Clinical variants (ClinVar): 224 total
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 54.3% of screened cell lines
• MANE Select transcript: NM_006342

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11524
Approved symbol	TACC3
Name	transforming acidic coiled-coil containing protein 3
Location	4p16.3
Locus type	gene with protein product
Status	Approved
Aliases	ERIC1, ERIC-1, maskin, Tacc4
Ensembl gene	ENSG00000013810
Ensembl biotype	protein_coding
OMIM	605303
Entrez	10460

Gene structure

Transcript identifiers

Ensembl transcripts: 34 — 24 protein_coding, 6 retained_intron, 2 nonsense_mediated_decay, 2 protein_coding_CDS_not_defined

ENST00000313288, ENST00000404054, ENST00000458173, ENST00000466077, ENST00000467746, ENST00000470136, ENST00000470808, ENST00000484264, ENST00000484651, ENST00000493975, ENST00000612220, ENST00000650779, ENST00000651251, ENST00000651472, ENST00000651817, ENST00000652002, ENST00000652770, ENST00000874198, ENST00000874199, ENST00000874200, ENST00000874201, ENST00000918507, ENST00000918508, ENST00000918509, ENST00000918510, ENST00000918511, ENST00000918512, ENST00000918513, ENST00000918514, ENST00000918515, ENST00000918516, ENST00000954273, ENST00000954274, ENST00000954275

RefSeq mRNA: 2 — MANE Select: NM_006342 NM_001410699, NM_006342

CCDS: CCDS3352, CCDS93465

Canonical transcript exons

ENST00000313288 — 16 exons

Exon	Start	End
ENSE00001610942	1740826	1740986
ENSE00001655127	1739702	1739778
ENSE00001672388	1737598	1737702
ENSE00001727535	1744518	1744624
ENSE00001793214	1744948	1745171
ENSE00001799683	1744712	1744832
ENSE00001935865	1721521	1721643
ENSE00003486953	1727708	1728787
ENSE00003488815	1731172	1731301
ENSE00003544791	1735731	1735834
ENSE00003564248	1730887	1730962
ENSE00003574124	1737241	1737328
ENSE00003597099	1723421	1723583
ENSE00003611123	1723728	1723870
ENSE00003623404	1739959	1740002
ENSE00003655542	1735273	1735325

Expression profiles

Bgee: expression breadth ubiquitous, 197 present calls, max score 98.62.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 34.9179 / max 292.0966, expressed in 1721 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
46565	29.6591	1517
46568	3.3665	319
46564	1.0732	593
46566	0.6223	431
46569	0.1825	51
46567	0.0142	4

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
oocyte	CL:0000023	98.62	gold quality
ventricular zone	UBERON:0003053	97.46	gold quality
secondary oocyte	CL:0000655	96.68	gold quality
right testis	UBERON:0004534	96.37	gold quality
left testis	UBERON:0004533	96.30	gold quality
granulocyte	CL:0000094	95.92	gold quality
monocyte	CL:0000576	95.05	gold quality
mononuclear cell	CL:0000842	94.62	gold quality
leukocyte	CL:0000738	94.52	gold quality
blood	UBERON:0000178	94.28	gold quality
testis	UBERON:0000473	94.07	gold quality
ganglionic eminence	UBERON:0004023	93.47	gold quality
embryo	UBERON:0000922	92.49	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	92.15	gold quality
vermiform appendix	UBERON:0001154	91.74	gold quality
spleen	UBERON:0002106	91.50	gold quality
mucosa of transverse colon	UBERON:0004991	91.37	gold quality
lymph node	UBERON:0000029	91.30	gold quality
bone marrow cell	CL:0002092	90.77	gold quality
bone marrow	UBERON:0002371	90.46	gold quality
lower esophagus mucosa	UBERON:0035834	90.34	gold quality
trabecular bone tissue	UBERON:0002483	89.69	gold quality
bone element	UBERON:0001474	89.09	gold quality
thymus	UBERON:0002370	87.41	silver quality
caecum	UBERON:0001153	87.23	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	87.12	gold quality
esophagus mucosa	UBERON:0002469	87.00	gold quality
stromal cell of endometrium	CL:0002255	86.00	gold quality
small intestine Peyer’s patch	UBERON:0003454	85.84	gold quality
apex of heart	UBERON:0002098	85.79	gold quality

Single-cell (SCXA)

Detected in 7 experiment(s), a significant marker in 5.

Experiment	Marker?	Max mean expression
E-GEOD-99795	yes	269.09
E-MTAB-10662	yes	204.84
E-MTAB-10596	yes	103.80
E-MTAB-6678	yes	10.36
E-ANND-3	yes	6.06
E-CURD-53	no	1404.34
E-MTAB-6142	no	362.30

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ZFPM1

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 54.3% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 40)

• REVIEW: genetics, expression, gene expression regulation, and function studies (PMID:12389629)
• TACC3 has an essential role in spindle assembly and cellular survival (PMID:17675670)
• Aurora-A and TACC3 interaction is important to control the mitotic spindle organization required for proper chromosome segregation. (PMID:17914111)
• overexpression of TACC3 may be associated with the mechanisms of chemoresistance, tumor progression, cell proliferation and metastasis (PMID:19148534)
• these findings suggest that Cdh1 controls TACC3 protein stability during mitotic exit. (PMID:19823035)
• These findings link TACC3 to novel structural and cell division functions of TSC2. (PMID:20237422)
• the association between aurora A phosphorylation and spindle apparatus; regulation from aurora A is mediated by CHC in recruiting phospho-TACC3 and subsequently ch-TOG to mitotic spindles. (PMID:20566684)
• TACC3 controls paclitaxel sensitivity by modulating a premature senescence program. (PMID:20729911)
• Data show that ILK performs its centrosome clustering activity in a centrosome-dependent, manner through the microtubule regulating proteins TACC3 and ch-TOG. (PMID:20838383)
• recruitment to spindle poles by clathrin ensures proper spindle assembly and chromosome alignment in mitotic cells through a RanGTP-dependent pathway (PMID:20923838)
• multifaceted genomic evaluation of glioblastoma establishes ERRFI1 as a potential candidate tumor suppressor gene and TACC3 as a potential oncogene, and provides insight on targets for oncogenic pathway-based therapy (PMID:21113414)
• TACC3 recruits ch-TOG and clathrin to the mitotic spindle. Together the complex forms inter-microtubule bridges in kinetochore fibres. (PMID:21297582)
• we have identified a novel submicroscopic duplication involving dosage sensitive genes TACC3, FGFR3, and LETM1. (PMID:21815251)
• study reports that a small subset of glioblastoma multiforme tumors harbors oncogenic chromosomal translocations that fuse in-frame the tyrosine kinase coding domains of fibroblast growth factor receptor genes(FGFR1 or FGFR3) to the transforming acidic coiled-coil coding domains of TACC1 or TACC3; the FGFR-TACC fusion protein displays oncogenic activity (PMID:22837387)
• Identification of a novel oncogenic FGFR3-TACC3 fusion protein in bladder cancer. (PMID:23175443)
• discovered FGFR3-TACC3 fusions in 4 of 48 glioblastoma samples, but not in any of 43 low-grade glioma samples tested. The fusion, caused by tandem duplication on 4p16.3, led to the loss of the 3’-UTR of FGFR3, blocking gene regulation of miR-99a. (PMID:23298836)
• Identify TACC3 as a driver of tumorigenesis as well as an inducer of oncogenic epithelial-mesenchymal transition. (PMID:23348690)
• [review] TACC3 protein complexes are crucial for proper mitotic spindle assembly and dynamics to prevent faulty cell division and aneuploidy. (PMID:23787465)
• TACC3 phosphorylation by Aurora A kinase is required for central spindle assembly. (PMID:23887685)
• a novel function for TACC3 in EGF-mediated epithelial-mesenchymal transition in cervical cancer (PMID:23936413)
• Self-assembly and sorting of acentrosomal microtubules by TACC3 facilitate kinetochore capture during the mitotic spindle assembly. (PMID:24003142)
• TACC3 contributes to spindle formation in proliferating cancer cells. (PMID:24077290)
• Aurora-A kinase does not regulate TACC3-chTOG complex formation, indicating that Aurora-A solely functions as a recruitment factor for the TACC3-chTOG complex to centrosomes and proximal mitotic spindles. (PMID:24273164)
• findings provide critical information regarding the mechanisms by which TACC3 contributes to genomic instability (PMID:24769898)
• TACC3 is involved in the regulation of microtubule nucleation at the centrosome and functions in the stabilization of the gamma-tubulin ring complex assembly (PMID:25246530)
• FGFR3-TACC3 rearrangements occur in a subset of patients with lung adenocarcinoma. Such patients should be considered for clinical trials featuring FGFR inhibitors. (PMID:25294908)
• our data demonstrated the oncogenic role of FGFR3-TACC3 in vitro, indicating that FGFR3-TACC3 may be useful as a diagnostic marker and therapeutic target in cancers. (PMID:25535896)
• TACC3 depletion induces G1 arrest and cell death by activating p38-p53-p21 signaling and triggering a centrosome-mediated cellular stress response. (PMID:25613365)
• findings suggest that TACC3 could be recruited as a bridge to cooperatively mediate between the HIF-2alpha PAS-B.ARNT PAS-B complex, thereby participating more directly in HIF-dependent gene transcription than previously anticipated (PMID:25627682)
• TACC3 is expressed in esophageal squamous cell carcinoma and correlates with poor prognosis (PMID:25760075)
• The measurement of TACC3 protein expression may be beneficial for predicting clinical outcomes for gastric cancer patients (PMID:26133271)
• TACC3 depletion in human cell lines causes shorter mitotic spindles. co-immunoprecipitation experiments showed reduced binding between TACC3-F543A and Aurora-A. (PMID:26134678)
• TACC3 is enriched in hepatocellular carcinoma and down-regulation inhibits the proliferation, clonogenicity, and cancer stem cell-like phenotype of HCC cells (PMID:26219398)
• TACC3 overexpression was associated with clinicopathological features of aggressiveness, increased EMT-related protein expression, and poor survival, suggesting a potential role for TACC3 as a prognostic biomarker and therapeutic target in HCC (PMID:26219896)
• Results showed that high level of TACC3 expression was correlated with advanced clinicopathological classifications, and poor prognosis in non-small cell lung cancer patients indicating that TACC3 is a potential prognostic marker. (PMID:26531241)
• Study provides evidence of the significant oncogenic potential of the FGFR3-TACC3 fusion protein. The presence of the TACC coiled-coil domain leads to increased and altered levels of FGFR3 activation, fusion protein phosphorylation, downstream signaling, cellular transformation, proliferation, and viability. (PMID:26869289)
• Data indicate that transforming acidic coiled-coil protein-3 (TACC3) promotes CRC progression and could be an independent prognostic factor and a potential therapeutic target for colorectal cancer (CRC). (PMID:27248823)
• this study suggests that TACC3 might be an important molecular marker for diagnosis and prognosis of breast cancer (PMID:27258563)
• The results showed that the expression of TACC3 was downregulated in preeclamptic placentas. (PMID:27572091)
• TACC3 was highly expressed in CCA tissues and predicted a poor prognosis in CCA patients. TACC3 knockdown induced G2/M cycle arrest and suppressed the invasion, metastasis, and proliferation of CCA cells, both in vitro and in vivo. (PMID:27705912)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	tacc3	ENSDARG00000005454
mus_musculus	Tacc3	ENSMUSG00000037313
rattus_norvegicus	Tacc3	ENSRNOG00000017259
drosophila_melanogaster	tacc	FBGN0026620

Paralogs (2): TACC2 (ENSG00000138162), TACC1 (ENSG00000147526)

Protein

Protein identifiers

Transforming acidic coiled-coil-containing protein 3 — Q9Y6A5 (reviewed: Q9Y6A5)

Alternative names: ERIC-1

All UniProt accessions (8): Q9Y6A5, A0A087WUE2, A0A494BZT8, A0A494C117, C9JA91, E7EMT0, F8WC55, H0Y8F2

UniProt curated annotations — full annotation on UniProt →

Function. Plays a role in the microtubule-dependent coupling of the nucleus and the centrosome. Involved in the processes that regulate centrosome-mediated interkinetic nuclear migration (INM) of neural progenitors. Acts as a component of the TACC3/ch-TOG/clathrin complex proposed to contribute to stabilization of kinetochore fibers of the mitotic spindle by acting as inter-microtubule bridge. The TACC3/ch-TOG/clathrin complex is required for the maintenance of kinetochore fiber tension. May be involved in the control of cell growth and differentiation. May contribute to cancer.

Subunit / interactions. Interacts with microtubules. Interacts with CKAP5 independently of clathrin. Interacts with CKAP5 and clathrin forming the TACC3/ch-TOG/clathrin complex located at spindle inter-microtubules bridges; TACC3 (phosphorylated at Ser-558 by AURKA) and CLTC are proposed to form a composite microtubule interaction surface. Interacts with CCDC100/CEP120. The coiled coil C-terminal region interacts with AH receptor nuclear translocator protein (ARNT) and ARNT2. Interacts with GCN5L2 and PCAF.

Subcellular location. Cytoplasm. Cytoskeleton. Microtubule organizing center. Centrosome. Spindle. Spindle pole.

Induction. Up-regulated in various cancer cell lines.

Similarity. Belongs to the TACC family.

RefSeq proteins (2): NP_001397628, NP_006333* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR007707	TACC_C	Domain
IPR039915	TACC	Family
IPR057663	TACC3_Aurora-A_bind	Binding_site

Pfam: PF05010, PF25777

UniProt features (36 total): modified residue 11, compositionally biased region 5, region of interest 5, sequence variant 4, helix 3, mutagenesis site 2, sequence conflict 2, initiator methionine 1, chain 1, turn 1, coiled-coil region 1

Structure

Experimental structures (PDB)

6 structures.

PDB	Method	Resolution (Å)
5ODT	X-RAY DIFFRACTION	2.02
5LXN	X-RAY DIFFRACTION	2.08
5LXO	X-RAY DIFFRACTION	2.18
9YDY	X-RAY DIFFRACTION	2.3
5ODS	X-RAY DIFFRACTION	3.09
9OPF

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9Y6A5-F1	57.96	0.24

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 (11): 2, 25, 39, 71, 175, 177, 250, 317, 402, 434, 558

Mutagenesis-validated functional residues (2):

Position	Phenotype
558	disrupts localization to mitotic spindle and impairs recruitment of clathrin to mitotic spindle.
566–567	impairs localization to mitotic spindle.

Function

Pathways and Gene Ontology

Reactome pathways

6 pathways

ID	Pathway
R-HSA-9013507	NOTCH3 Activation and Transmission of Signal to the Nucleus
R-HSA-9604323	Negative regulation of NOTCH4 signaling
R-HSA-157118	Signaling by NOTCH
R-HSA-162582	Signal Transduction
R-HSA-9012852	Signaling by NOTCH3
R-HSA-9013694	Signaling by NOTCH4

MSigDB gene sets: 303 (showing top): GOBP_CHROMOSOME_ORGANIZATION, REACTOME_SIGNALING_BY_NOTCH, GOBP_CYTOPLASMIC_MICROTUBULE_ORGANIZATION, GOBP_REGULATION_OF_MICROTUBULE_BASED_PROCESS, PAL_PRMT5_TARGETS_UP, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_DN, GOBP_CELL_CYCLE_PHASE_TRANSITION, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_UP, KENNY_CTNNB1_TARGETS_UP, MITSIADES_RESPONSE_TO_APLIDIN_DN, MODULE_308, KONG_E2F3_TARGETS, GOCC_MICROTUBULE_ORGANIZING_CENTER, GOBP_FOREBRAIN_DEVELOPMENT

GO Biological Process (8): microtubule cytoskeleton organization (GO:0000226), mitotic spindle organization (GO:0007052), metaphase/anaphase transition of mitotic cell cycle (GO:0007091), nuclear migration (GO:0007097), cerebral cortex development (GO:0021987), cell division (GO:0051301), regulation of mitotic spindle organization (GO:0060236), microtubule cytoskeleton organization involved in mitosis (GO:1902850)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (10): spindle pole (GO:0000922), cytoplasm (GO:0005737), Golgi apparatus (GO:0005794), cytosol (GO:0005829), centriolar satellite (GO:0034451), ciliary basal body (GO:0036064), mitotic spindle (GO:0072686), centrosome (GO:0005813), spindle (GO:0005819), cytoskeleton (GO:0005856)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
Signaling by NOTCH	2
Signaling by NOTCH3	1
Signaling by NOTCH4	1
Signal Transduction	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
mitotic cell cycle	3
spindle	2
cytoplasm	2
microtubule organizing center	2
intracellular membraneless organelle	2
cytoskeleton organization	1
microtubule-based process	1
spindle organization	1
microtubule cytoskeleton organization involved in mitosis	1
mitotic cell cycle phase transition	1
metaphase/anaphase transition of cell cycle	1
intracellular transport	1
nucleus localization	1
establishment of organelle localization	1
pallium development	1
anatomical structure development	1
cellular process	1
mitotic spindle organization	1
regulation of spindle organization	1
microtubule cytoskeleton organization	1
mitotic cell cycle process	1
binding	1
intracellular anatomical structure	1
endomembrane system	1
intracellular membrane-bounded organelle	1
centrosome	1
cilium	1
centriole	1
microtubule cytoskeleton	1

Protein interactions and networks

STRING

2760 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TACC3	CKAP5	Q14008	999
TACC3	AURKA	O14965	939
TACC3	FGFR3	P22607	938
TACC3	CPEB1	Q9BZB8	867
TACC3	EIF4E	P06730	843
TACC3	CEP120	Q8N960	842
TACC3	SPICE1	Q8N0Z3	746
TACC3	FGFR1	P11362	728
TACC3	TSC2	P49815	725
TACC3	CLTC	Q00610	716
TACC3	DLGAP5	Q15398	680
TACC3	TMEM129	A0AVI4	677
TACC3	KAT2A	Q92830	664
TACC3	KIF2C	Q99661	664
TACC3	PARN	O95453	662

IntAct

154 interactions, top by confidence:

A	B	Type	Score
TACC3	CKAP5	psi-mi:“MI:0915”(physical association)	0.860
CKAP5	TACC3	psi-mi:“MI:0403”(colocalization)	0.860
CKAP5	TACC3	psi-mi:“MI:0915”(physical association)	0.860
TACC3	CKAP5	psi-mi:“MI:0403”(colocalization)	0.860
CKAP5	TACC1	psi-mi:“MI:0914”(association)	0.800
TBC1D22B	TACC3	psi-mi:“MI:0915”(physical association)	0.780
TACC3	TBC1D22B	psi-mi:“MI:0915”(physical association)	0.780
HSPA8	GAK	psi-mi:“MI:0914”(association)	0.760
KIZ	TACC3	psi-mi:“MI:0915”(physical association)	0.720
CIB3	TACC3	psi-mi:“MI:0915”(physical association)	0.720
TACC3	CIB3	psi-mi:“MI:0915”(physical association)	0.720
TACC3	CEP55	psi-mi:“MI:0915”(physical association)	0.710
KLHL38	TACC3	psi-mi:“MI:0915”(physical association)	0.600
MPDZ	SMCHD1	psi-mi:“MI:0914”(association)	0.590
CLP1	PCF11	psi-mi:“MI:0914”(association)	0.590
VPS37C	TACC3	psi-mi:“MI:0915”(physical association)	0.560
TACC3	SNX20	psi-mi:“MI:0915”(physical association)	0.560
ASPSCR1	TACC3	psi-mi:“MI:0915”(physical association)	0.560
TACC3	VPS37C	psi-mi:“MI:0915”(physical association)	0.560
SNX20	TACC3	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (219): VPS37C (Two-hybrid), TBC1D22B (Two-hybrid), KIZ (Two-hybrid), ASPSCR1 (Two-hybrid), CIB3 (Two-hybrid), SNX20 (Two-hybrid), FZR1 (Two-hybrid), FZR1 (Reconstituted Complex), FZR1 (Affinity Capture-Western), TACC3 (Affinity Capture-Western), TACC3 (Affinity Capture-MS), TACC3 (Affinity Capture-MS), TACC3 (Affinity Capture-MS), TACC3 (Affinity Capture-MS), MRE11A (Co-fractionation)

ESM2 similar proteins: A2A870, A2AUM9, B9EKI3, D3YV10, E1U8D0, E7F5E1, O54931, O75420, P39880, P53564, P55937, P60853, Q08378, Q0KK56, Q15025, Q2TAC2, Q32PN7, Q499E4, Q4KLH6, Q5T1M5, Q5U2Y9, Q5XIA0, Q5ZIB2, Q5ZLT3, Q62036, Q6AW69, Q6IPM2, Q6P2H3, Q6P9Q6, Q6PCQ0, Q6PHN1, Q6ZQ06, Q7T019, Q80ST9, Q86VQ0, Q86YF9, Q8BMD2, Q8BMK0, Q8CB62, Q8CFC9

Diamond homologs: O75410, O95359, Q6Y685, Q9JJ11, Q9JJG0, Q9PTG8, Q9Y6A5

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
AURKA	“up-regulates activity”	TACC3	phosphorylation
AURKA	unknown	TACC3	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 105 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
Recycling pathway of L1	6	21.7×	2e-05
Kinesins	7	20.1×	2e-05
Aggrephagy	5	20.0×	1e-04
HSP90 chaperone cycle for steroid hormone receptors (SHR) in the presence of ligand	5	15.6×	2e-04
Golgi-to-ER retrograde transport	7	15.0×	2e-05
Translocation of SLC2A4 (GLUT4) to the plasma membrane	6	14.9×	9e-05
Intra-Golgi and retrograde Golgi-to-ER traffic	8	13.5×	2e-05
COPI-dependent Golgi-to-ER retrograde traffic	7	12.5×	5e-05

GO biological processes:

GO term	Partners	Fold	FDR
mitotic spindle organization	7	20.2×	2e-05
mitotic cell cycle	8	11.4×	1e-04
cell division	10	4.9×	4e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	167
Likely benign	9
Benign	9

Top pathogenic / likely-pathogenic (0)

SpliceAI

3886 predictions. Top by Δscore:

Variant	Effect	Δscore
4:1717429:CTG:C	acceptor_loss	1.0000
4:1718146:TCTTA:T	donor_loss	1.0000
4:1718147:CTTA:C	donor_loss	1.0000
4:1718148:TTAC:T	donor_loss	1.0000
4:1718149:TAC:T	donor_loss	1.0000
4:1718150:A:AC	donor_gain	1.0000
4:1718150:A:AT	donor_loss	1.0000
4:1718151:C:CC	donor_gain	1.0000
4:1718625:GCCTG:G	acceptor_loss	1.0000
4:1718626:CCT:C	acceptor_loss	1.0000
4:1718627:C:CC	acceptor_gain	1.0000
4:1723416:TCCA:T	acceptor_loss	1.0000
4:1723418:CAG:C	acceptor_loss	1.0000
4:1723419:A:AG	acceptor_gain	1.0000
4:1723419:A:AT	acceptor_loss	1.0000
4:1723419:AGAAT:A	acceptor_gain	1.0000
4:1723420:G:GA	acceptor_gain	1.0000
4:1723420:GA:G	acceptor_gain	1.0000
4:1723420:GAA:G	acceptor_gain	1.0000
4:1723420:GAAT:G	acceptor_gain	1.0000
4:1723420:GAATG:G	acceptor_gain	1.0000
4:1723580:GAAG:G	donor_gain	1.0000
4:1723581:AAG:A	donor_gain	1.0000
4:1723582:AG:A	donor_gain	1.0000
4:1723583:GG:G	donor_gain	1.0000
4:1723584:G:GA	donor_loss	1.0000
4:1723584:G:GG	donor_gain	1.0000
4:1723868:GAA:G	donor_gain	1.0000
4:1723871:G:GG	donor_gain	1.0000
4:1728788:G:GG	donor_gain	1.0000

AlphaMissense

5480 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:1744988:T:C	L831P	0.999
4:1744605:G:C	A771P	0.998
4:1744967:T:C	L824P	0.998
4:1735773:T:C	F563L	0.997
4:1735775:C:A	F563L	0.997
4:1735775:C:G	F563L	0.997
4:1744531:T:C	L746P	0.997
4:1744598:G:C	K768N	0.996
4:1744598:G:T	K768N	0.996
4:1740907:T:C	L715P	0.995
4:1740937:T:C	L725P	0.995
4:1740946:G:C	R728P	0.995
4:1744976:T:C	I827T	0.995
4:1744618:T:C	L775P	0.994
4:1744976:T:G	I827S	0.994
4:1735311:T:C	F544L	0.992
4:1735313:T:A	F544L	0.992
4:1735313:T:G	F544L	0.992
4:1744594:T:C	L767P	0.992
4:1744713:G:C	A778P	0.992
4:1723734:T:C	F57L	0.991
4:1723736:T:A	F57L	0.991
4:1723736:T:G	F57L	0.991
4:1735754:G:C	K556N	0.990
4:1735754:G:T	K556N	0.990
4:1744988:T:A	L831H	0.990
4:1744810:T:C	L810P	0.989
4:1744991:T:A	I832N	0.989
4:1735777:A:G	D564G	0.988
4:1744584:T:G	Y764D	0.988

dbSNP variants (sampled 300 via entrez): RS1000033570 (4:1734266 C>G,T), RS1000120885 (4:1725223 C>G,T), RS1000156188 (4:1729719 A>G), RS1000616773 (4:1721296 C>G,T), RS1000790565 (4:1722759 C>T), RS1000807937 (4:1721623 C>T), RS1000818014 (4:1738000 T>G), RS1001007510 (4:1730420 C>A,T), RS1001144666 (4:1741415 A>G), RS1001179704 (4:1724346 G>A), RS1001284562 (4:1739169 G>A), RS1001414623 (4:1737034 G>A), RS1001564497 (4:1730651 G>A), RS10015712 (4:1741425 G>T), RS1001656549 (4:1732919 G>A)

Disease associations

OMIM: gene MIM:605303 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): hereditary breast ovarian cancer syndrome (MONDO:0003582)

Orphanet (1): Hereditary breast and/or ovarian cancer syndrome (Orphanet:145)

HPO phenotypes

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

GWAS associations

12 associations (top):

Study	Trait	p-value
GCST000639_2	Urinary bladder cancer	1.000000e-11
GCST000842_6	Bladder cancer	4.000000e-13
GCST002240_3	Bladder cancer	7.000000e-25
GCST010699_17	Brain morphology (min-P)	5.000000e-10
GCST010701_28	Cortical surface area (MOSTest)	3.000000e-32
GCST010702_46	Subcortical volume (MOSTest)	5.000000e-10
GCST010703_270	Brain morphology (MOSTest)	5.000000e-13
GCST012227_1016	Hip circumference adjusted for BMI	2.000000e-08
GCST012227_1017	Hip circumference adjusted for BMI	1.000000e-15
GCST90000025_254	Appendicular lean mass	2.000000e-20
GCST90002397_99	Mean spheric corpuscular volume	2.000000e-13
GCST90020028_1704	Hip circumference adjusted for BMI	8.000000e-11

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004346	neuroimaging measurement
EFO:0008039	BMI-adjusted hip circumference
EFO:0004980	appendicular lean mass

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D061325	Hereditary Breast and Ovarian Cancer Syndrome	C04.588.180.483; C04.588.322.455.431; C04.700.517; C12.050.351.500.056.630.705.431; C12.050.351.937.418.685.431; C12.100.250.056.630.705.431; C12.900.418.685.431; C16.320.700.517; C17.800.090.500.483; C19.344.410.431; C19.391.630.705.431

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL5291560 (SINGLE PROTEIN), CHEMBL6193807 (PROTEIN-PROTEIN INTERACTION)

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects binding, decreases expression, decreases methylation, increases expression, affects expression	6
sodium arsenite	decreases expression, increases expression	4
Estradiol	affects cotreatment, increases expression	4
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	3
Cyclosporine	decreases expression	3
methylmercuric chloride	increases expression, affects cotreatment	2
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression, increases expression	2
Air Pollutants	affects cotreatment, increases abundance, increases oxidation, decreases expression	2
Rotenone	decreases expression, increases expression	2
Tunicamycin	decreases expression	2
aristolochic acid I	increases expression	1
abemaciclib	decreases expression	1
FR900359	affects phosphorylation	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
beta-lapachone	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
zinc chromate	decreases expression, increases abundance	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	increases expression, affects cotreatment	1
coumarin	decreases phosphorylation	1
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	1
diallyl trisulfide	decreases expression	1
diethyl malate	increases expression	1
di-n-butylphosphoric acid	affects expression	1
chromium hexavalent ion	increases abundance, decreases expression	1
perfluorooctane sulfonic acid	decreases expression	1
azoxystrobin	increases expression	1
AM 251	decreases expression	1
deguelin	increases expression	1
corosolic acid	decreases expression	1

ChEMBL screening assays

3 unique, capped per target: 3 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5250719	Binding	Inhibition of TACC3 in human U87 cells assessed as stabilization of protein by measuring shift in thermal melting curve at 10 uM incubated for 6 hrs by cellular thermal shift assay	Discovery of novel analogs of KHS101 as transforming acidic coiled coil containing protein 3 (TACC3) inhibitors for the treatment of glioblastoma. — Eur J Med Chem

Cellosaurus cell lines

18 cell lines: 17 cancer cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_0036	RT-4	Cancer cell line	Male
CVCL_1670	RT-112	Cancer cell line	Female
CVCL_2714	RT112/84	Cancer cell line	Female
CVCL_2715	RT4/31	Cancer cell line	Male
CVCL_6215	RT112/D21	Cancer cell line	Female
CVCL_B3IY	Abcam HEK293T TACC3 KO	Transformed cell line	Female
CVCL_B7BP	RT112-CP	Cancer cell line	Female
CVCL_C7JU	RT112 CP1.5	Cancer cell line	Female
CVCL_C7JV	RT112 CP2	Cancer cell line	Female
CVCL_C7JW	RT112 CP2.5	Cancer cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT02562170	PHASE4	COMPLETED	Protexa® Versus TiLoopBra® in Immediate Breast Reconstruction- A Pilot Study
NCT00673335	PHASE3	COMPLETED	Letrozole in Preventing Breast Cancer in Postmenopausal Women With a BRCA1 or BRCA2 Mutation
NCT00685256	PHASE3	COMPLETED	Standard Genetic Counseling With or Without a Decision Guide in Improving Communication Between Mothers Undergoing BRCA1/2 Testing and Their Minor-Age Children
NCT03162276	PHASE3	UNKNOWN	Trial of Inquiry Based Stress Reduction (IBSR) Program for BRCA1/2 Mutation Carriers
NCT00253539	PHASE2	COMPLETED	Arzoxifene or Tamoxifen in Preventing Breast Cancer in Premenopausal Women at High Risk for Breast Cancer
NCT00305695	PHASE2	COMPLETED	Zoledronate or Observation in Maintaining Bone Mineral Density in Patients Who Are Undergoing Surgery to Remove Both Ovaries
NCT00321633	PHASE2	COMPLETED	Carboplatin or Docetaxel in Treating Women With Metastatic Genetic Breast Cancer
NCT01333748	PHASE2	COMPLETED	Search Allelic Imbalance of Expression of BRCA Genes in Hereditary Risk of Breast and/or Ovarian Cancer
NCT01367639	PHASE2	COMPLETED	Trial of Inquiry Based Stress Reduction (IBSR) Program for BRCA1/2 Mutation Carriers
NCT00535119	PHASE1	COMPLETED	Veliparib, Carboplatin, and Paclitaxel in Treating Patients With Advanced Solid Cancer
NCT00892736	PHASE1	COMPLETED	Veliparib in Treating Patients With Malignant Solid Tumors That Do Not Respond to Previous Therapy
NCT03832985	EARLY_PHASE1	COMPLETED	Pediatric Reporting of Adult-Onset Genomic Results
NCT00005095	Not specified	RECRUITING	Specimen and Data Study for Ovarian Cancer Early Detection and Prevention
NCT00609505	Not specified	COMPLETED	Telemedicine vs. Face-to-Face Cancer Genetic Counseling
NCT01273909	Not specified	UNKNOWN	Outcomes After Perforator Flap Reconstruction for Breast Reconstruction and/or Lymphedema Treatment
NCT01445275	Not specified	WITHDRAWN	Cost of Cancer Risk Management in Women at Elevated Genetic Risk for Ovarian Cancer Who Participated on GOG-0199
NCT01608074	Not specified	ACTIVE_NOT_RECRUITING	Radical Fimbriectomy for Young BRCA Mutation Carriers
NCT02087592	Not specified	COMPLETED	Feasibility of Lifestyle Intervention in BRCA1/2 Mutation Carriers
NCT02302742	Not specified	RECRUITING	Triple Negative Breast Cancer and Germline Hereditary Breast and Ovarian Cancer Mutation Carrier Registry
NCT02324062	Not specified	COMPLETED	Cancer Genetics Hereditary Cancer Panel Testing
NCT02516540	Not specified	UNKNOWN	Efficacy of Lifestyle Intervention in BRCA1/2 Mutation Carriers
NCT02653105	Not specified	ACTIVE_NOT_RECRUITING	Women at Risk of Breast Cancer and OLFM4
NCT02705924	Not specified	TERMINATED	Impact of a Psychoeducational Intervention on Expectations and Coping in Young Women Exposed to a High HBOC Risk
NCT02760849	Not specified	ACTIVE_NOT_RECRUITING	Surgery in Preventing Ovarian Cancer in Patients With Genetic Mutations
NCT02786147	Not specified	COMPLETED	Identification and Referral of Women at Risk for Hereditary Breast/Ovarian Cancer
NCT02956681	Not specified	COMPLETED	Statewide Communication to Reach Diverse Low Income Women
NCT03015376	Not specified	UNKNOWN	Inherited Susceptible Genes Among Epithelial Ovarian Cancer
NCT03050268	Not specified	RECRUITING	Familial Investigations of Childhood Cancer Predisposition
NCT03075540	Not specified	COMPLETED	Enhancing At-risk Latina Women’s Use of Genetic Counseling for Hereditary Breast and Ovarian Cancer
NCT03124212	Not specified	RECRUITING	Cascade Genetic Testing for Hereditary Breast/Ovarian Cancer and Lynch Syndrome in Switzerland
NCT03246841	Not specified	ACTIVE_NOT_RECRUITING	Investigation of Tumour Spectrum of Germline Mutations in Breast and Ovarian Cancer Genes.
NCT03294343	Not specified	UNKNOWN	Risk-Reducing Surgeries for Hereditary Ovarian Cancer
NCT03421327	Not specified	COMPLETED	Genetic Risk: Whether, When, and How to Tell Adolescents
NCT03510689	Not specified	COMPLETED	Genetics and Heart Health After Cancer Therapy
NCT03511690	Not specified	COMPLETED	Testing an Intelligent Tutoring System to Enhance Genetic Risk Assessment
NCT03784859	Not specified	COMPLETED	Tissue Expansion in Breast Reconstruction Without Drains
NCT03979612	Not specified	UNKNOWN	Evaluation of the Adhesion to the GENEPY Network
NCT04197856	Not specified	ACTIVE_NOT_RECRUITING	Direct Information to At-risk Relatives
NCT04407611	Not specified	COMPLETED	Scalable Communication Modalities for Returning Genetic Research Results
NCT04508764	Not specified	TERMINATED	Implementation of the Families Accelerating Cascade Testing Toolkit (FACTT) for Hereditary Breast and Ovarian Cancer and Lynch Syndrome