CDCA8

Summary

CDCA8 (cell division cycle associated 8, HGNC:14629) is a protein-coding gene on chromosome 1p34.3, encoding Borealin (Q53HL2). Component of the chromosomal passenger complex (CPC), a complex that acts as a key regulator of mitosis. It is a common-essential gene (DepMap: required in 99.7% of cancer cell lines).

This gene encodes a component of the chromosomal passenger complex. This complex is an essential regulator of mitosis and cell division. This protein is cell-cycle regulated and is required for chromatin-induced microtubule stabilization and spindle formation. Alternate splicing results in multiple transcript variants. Pseudgenes of this gene are found on chromosomes 7, 8 and 16.

Source: NCBI Gene 55143 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 51 total
• Cancer dependency (DepMap): dependent in 99.7% of screened cell lines (common-essential)
• MANE Select transcript: NM_001256875

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:14629
Approved symbol	CDCA8
Name	cell division cycle associated 8
Location	1p34.3
Locus type	gene with protein product
Status	Approved
Aliases	FLJ12042, MESRGP, BOR, DasraB
Ensembl gene	ENSG00000134690
Ensembl biotype	protein_coding
OMIM	609977
Entrez	55143

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 6 protein_coding

ENST00000327331, ENST00000373055, ENST00000934262, ENST00000934263, ENST00000934264, ENST00000934265

RefSeq mRNA: 2 — MANE Select: NM_001256875 NM_001256875, NM_018101

CCDS: CCDS424

Canonical transcript exons

ENST00000373055 — 10 exons

Exon	Start	End
ENSE00000916824	37692905	37693033
ENSE00000916825	37698905	37698977
ENSE00000916826	37700436	37700521
ENSE00000916827	37701754	37701818
ENSE00000916828	37703252	37703347
ENSE00000916830	37706978	37707064
ENSE00001038181	37695910	37695950
ENSE00001199740	37705441	37705567
ENSE00001459421	37708322	37709719
ENSE00001459426	37692516	37692784

Expression profiles

Bgee: expression breadth ubiquitous, 182 present calls, max score 97.06.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 33.0136 / max 354.5567, expressed in 1577 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
2216	23.5620	1402
2215	9.4516	1368

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
oocyte	CL:0000023	97.06	gold quality
secondary oocyte	CL:0000655	95.06	gold quality
ventricular zone	UBERON:0003053	92.49	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	90.13	gold quality
embryo	UBERON:0000922	87.45	gold quality
ganglionic eminence	UBERON:0004023	87.21	gold quality
right testis	UBERON:0004534	86.75	gold quality
left testis	UBERON:0004533	86.30	gold quality
mucosa of transverse colon	UBERON:0004991	86.24	gold quality
testis	UBERON:0000473	84.70	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	83.44	gold quality
rectum	UBERON:0001052	81.49	gold quality
bone marrow	UBERON:0002371	80.74	gold quality
lower esophagus mucosa	UBERON:0035834	80.44	gold quality
stromal cell of endometrium	CL:0002255	79.00	gold quality
esophagus mucosa	UBERON:0002469	78.37	gold quality
trabecular bone tissue	UBERON:0002483	77.96	gold quality
vermiform appendix	UBERON:0001154	77.49	gold quality
esophagus squamous epithelium	UBERON:0006920	77.42	silver quality
bone marrow cell	CL:0002092	77.15	gold quality
thymus	UBERON:0002370	76.52	gold quality
epithelium of esophagus	UBERON:0001976	75.74	silver quality
mucosa of sigmoid colon	UBERON:0004993	75.64	gold quality
colonic mucosa	UBERON:0000317	75.41	gold quality
lymph node	UBERON:0000029	75.17	gold quality
squamous epithelium	UBERON:0006914	74.02	silver quality
caecum	UBERON:0001153	73.70	gold quality
transverse colon	UBERON:0001157	73.36	gold quality
duodenum	UBERON:0002114	73.32	gold quality
sperm	CL:0000019	72.59	gold quality

Single-cell (SCXA)

Detected in 6 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-MTAB-6911	yes	531.01
E-ENAD-17	yes	323.50
E-GEOD-110499	yes	205.65
E-ANND-3	yes	5.01
E-MTAB-6142	no	958.59
E-GEOD-99795	no	335.55

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): OLIG2, TP53

miRNA regulators (miRDB)

60 targeting CDCA8, 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-5692A	100.00	74.40	6850
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-338-5P	99.92	72.34	2951
HSA-MIR-589-3P	99.91	69.62	2088
HSA-MIR-4648	99.91	67.00	710
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-1321	99.84	65.30	1811
HSA-MIR-4756-5P	99.84	64.98	1809
HSA-MIR-4739	99.84	65.25	1832
HSA-MIR-765	99.84	68.24	2442
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-3133	99.81	70.92	3506
HSA-MIR-5002-5P	99.76	70.84	1763
HSA-MIR-4428	99.73	66.41	1733
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-4755-5P	99.71	70.34	2716
HSA-MIR-5006-3P	99.71	70.26	2728
HSA-MIR-6883-5P	99.69	68.05	3785
HSA-MIR-545-5P	99.66	70.18	2308
HSA-MIR-4804-3P	99.65	67.78	866
HSA-MIR-6715B-5P	99.64	69.63	1420
HSA-MIR-4269	99.55	69.89	1373
HSA-MIR-7106-5P	99.53	67.47	3574
HSA-MIR-1207-5P	99.49	69.11	2983
HSA-MIR-4441	99.49	66.56	3216
HSA-MIR-4696	99.48	67.48	1040
HSA-MIR-3612	99.45	66.02	1333

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 99.7% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 36)

• Data show that INCENP has an important role in stabilizing the chromosomal passenger complex, and that Borealin acts to promote binding of Survivin to INCENP. (PMID:16239925)
• Cell cycle-regulated chromosomal passenger protein whose aberrant expression and nuclear accumulation are linked to poor prognosis for gastric cancer. (PMID:16427043)
• A functional module within the chromosomal passenger complex involving the inner centromere protein INCENP, Survivin, and Borealin. (PMID:16571674)
• Borealin is phosphorylated during mitosis. Neither residue S165, T106 nor phosphorylation of borealin by Aurora B Kinase is required to generate the mitotic, shifted form of Borealin. (PMID:17241471)
• Suppression of CDCA8 expression with small interfering RNA against CDCA8 significantly suppressed the growth of lung cancer cells. (PMID:17483322)
• It is recorded that borealin is a cell cycle regulator, down-regulated in response to p53/Rb-signaling, and up-regulated in many types of cancerous tissues. (PMID:17716930)
• mitotic regulator Survivin binds as a monomer to its functional interactor Borealin (PMID:17881355)
• Borealin and INCENP associate with the helical domain of Survivin to form a tight three-helical bundle. (PMID:17956729)
• Borealin plays a crucial role in the early mouse embryonic development (PMID:18311593)
• Data describe a mitotic SUMO2/3 conjugation-deconjugation cycle of Borealin and further assign a regulatory function of RanBP2 and SENP3 in the mitotic SUMO pathway. (PMID:18946085)
• found that substitutions at Borealin T230, recently identified as an Mps1 phosphorylation site, can modulate the dimerization state of Borealin (PMID:19530738)
• important role for phosphorylation of Borealin at S219 in the proper progression through mitosis (PMID:20803554)
• Borealin interacts directly with the Snf7 components of ESCRT-III in human cells.the Borealin central region encompassing residues 110-207 was both necessary & sufficient to bind to CHMP4C. (PMID:22724069)
• MLL5 functionally interacts with Borealin, facilitates the expression of chromosomal passenger complex, and hence contributes to mitotic fidelity and genomic integrity. (PMID:22797924)
• These findings reveal a previously unrecognized but direct link between HP1 and CPC localization in the centromere and illustrate the critical role of borealin-HP1 interaction in orchestrating an accurate cell division. (PMID:24917673)
• In colorectal cancer patients, Borealin expression was positively correlated with age, lymph node metastasis and neoplasm staging. (PMID:25260804)
• Borealin dimerization mediates chromosomal passenger complex checkpoint function by enhancing localization to centromeres and kinetochores. (PMID:25854549)
• enhanced CDCA8 promoter activities by NF-Y overexpression and reduced CDCA8 transcription by NF-Y knockdown further verified that NF-Y is a positive regulator of CDCA8 transcription. (PMID:26170459)
• These results were well correlated with the same gene expression pattern analysed in the thyroid tissue of the patient with BOREALIN-p.R114W. These studies open new avenues in the genetics of TD in humans. (PMID:28025328)
• Results show that CDCA8 is overexpressed in bladder cancer (BC) and its high levels are correlated with poor clinicopathological features of BC patients. Therefore, CDCA8 may act as a novel prognostic marker in the diagnosis of patients with BC. (PMID:30142792)
• CDCA8 was overexpressed in cutaneous melanoma tissues and cells lines compared with normal tissues. (PMID:30431060)
• Results indicate that higher CDCA8 expression in breast cancer cells is positively associated with poor prognosis and suggest that CDCA8 is a key mediator of estrogen-stimulated breast cancer cell growth and survival. (PMID:30953709)
• Borealin is a master regulator determining the chromosome association and function of the chromosome association of the chromosomal passenger complex (PMID:31570499)
• KIF18B promotes the proliferation of pancreatic ductal adenocarcinoma via activating the expression of CDCA8. (PMID:31875977)
• These results indicate that CDCA8 is associated with bipolar spindle formation, chromosome segregation, PBE during human oocyte meiosis, and that it may affect the incidence of aneuploidy embryos in older women (PMID:32088244)
• Development and validation of hub genes for lymph node metastasis in patients with prostate cancer. (PMID:32130760)
• The Correct Localization of Borealin in Midbody during Cytokinesis Depends on IQGAP1. (PMID:32685508)
• Identification of CDCA8, DSN1 and BIRC5 in Regulating Cell Cycle and Apoptosis in Osteosarcoma Using Bioinformatics and Cell Biology. (PMID:33153400)
• Double-targeting CDCA8 and E2F1 inhibits the growth and migration of malignant glioma. (PMID:33542211)
• MiR-133a-3p inhibits the malignant progression of oesophageal cancer by targeting CDCA8. (PMID:34117764)
• Methylation-dependent and -independent roles of EZH2 synergize in CDCA8 activation in prostate cancer. (PMID:35094010)
• Regulators CDCA8 as potential targets and biomarkers for the prognosis of human skin cutaneous melanoma. (PMID:35575979)
• Cell division cycle-associated 8 is a prognostic biomarker related to immune invasion in hepatocellular carcinoma. (PMID:36855818)
• A 1-kb human CDCA8 promoter directs the spermatogonia-specific luciferase expression in adult testis. (PMID:36898512)
• CDCA8 Facilitates Tumor Proliferation and Predicts a Poor Prognosis in Hepatocellular Carcinoma. (PMID:37428386)
• CDCA8 promotes bladder cancer survival by stabilizing HIF1alpha expression under hypoxia. (PMID:37813876)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	cdca8	ENSDARG00000043137
mus_musculus	Cdca8	ENSMUSG00000028873
rattus_norvegicus	Cdca8	ENSRNOG00000031431

Protein

Protein identifiers

Borealin — Q53HL2 (reviewed: Q53HL2)

Alternative names: Cell division cycle-associated protein 8, Dasra-B, Pluripotent embryonic stem cell-related gene 3 protein

All UniProt accessions (1): Q53HL2

UniProt curated annotations — full annotation on UniProt →

Function. Component of the chromosomal passenger complex (CPC), a complex that acts as a key regulator of mitosis. The CPC complex has essential functions at the centromere in ensuring correct chromosome alignment and segregation and is required for chromatin-induced microtubule stabilization and spindle assembly. Major effector of the TTK kinase in the control of attachment-error-correction and chromosome alignment.

Subunit / interactions. May form homooligomers and homodimers. Component of the chromosomal passenger complex (CPC) composed of at least BIRC5/survivin, CDCA8/borealin, INCENP, AURKB or AURKC; in the complex forms a triple-helix bundle-based subcomplex with INCENP and BIRC5. Interacts with SENP3, UBE2I and RANBP2. Interacts (phosphorylated) with SGO1 and SGO2; the association is dependent on CDK1.

Subcellular location. Nucleus. Nucleolus. Cytoplasm. Cytoskeleton. Spindle. Chromosome. Centromere.

Post-translational modifications. Phosphorylated by TTK, essentially at Thr-88, Thr94, Thr-169 and Thr-230. Phosphorylation (probably by CDK1) promotes targeting of the CPC to centromeric DNA. Sumoylated by UBE2I and RANBP2. Desumoylated by SENP3 through the removal of SUMO2 and SUMO3.

Domain organisation. The C-terminal region (aa 207-280) represents the dimerization motif.

Miscellaneous. Cells lacking CDCA8 display a slight decrease in histone H3 ‘Ser-10’ phosphorylation, suggesting that the CPC complex mediates phosphorylation of ‘Ser-10’ of histone H3.

Similarity. Belongs to the borealin family.

RefSeq proteins (2): NP_001243804, NP_060571 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR018851	Borealin_N	Domain
IPR018867	Cell_div_borealin	Family
IPR046466	Borealin_C	Domain

Pfam: PF10444, PF10512

UniProt features (55 total): mutagenesis site 23, modified residue 13, region of interest 6, helix 5, sequence conflict 2, chain 1, cross-link 1, sequence variant 1, strand 1, turn 1, compositionally biased region 1

Structure

Experimental structures (PDB)

15 structures.

PDB	Method	Resolution (Å)
2QFA	X-RAY DIFFRACTION	1.4
6YIF	X-RAY DIFFRACTION	1.81
9D41	X-RAY DIFFRACTION	1.84
8RUQ	ELECTRON MICROSCOPY	2.29
2RAW	X-RAY DIFFRACTION	2.4
8RUP	ELECTRON MICROSCOPY	2.42
6YIH	X-RAY DIFFRACTION	2.55
7U5V	X-RAY DIFFRACTION	2.59
9SI3	ELECTRON MICROSCOPY	2.83
9SJ5	ELECTRON MICROSCOPY	2.85
9SI9	ELECTRON MICROSCOPY	2.86
2RAX	X-RAY DIFFRACTION	3.3
6YIE	X-RAY DIFFRACTION	3.49
9SLJ	ELECTRON MICROSCOPY	3.8
2KDD	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q53HL2-F1	68.28	0.21

Antibody-complex structures (SAbDab): 1 — 9D41

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 (14): 106, 110, 165, 169, 189, 204, 219, 224, 230, 238, 244, 135, 88, 94

Mutagenesis-validated functional residues (23):

Position	Phenotype
17	loss of localization to the central spindle and midbody in anaphase or cytokinesis; when associated with e-19 and e-20.
19	loss of localization to the central spindle and midbody in anaphase or cytokinesis; when associated with e-17 and e-20.
20	loss of localization to the central spindle and midbody in anaphase or cytokinesis; when associated with e-17 and e-19.
26	fails to exhibit normal localization to the nucleolus in interphase depleted cells.
35	loss of binding to incenp; when associated with y-46.
46	loss of binding to incenp; when associated with e-35.
70	loss of binding to birc5; when associated with e-74.
74	loss of binding to birc5; when associated with e-70.
88	decrease in aurkb activity and almost no phosphorylation by ttk; when associated with a-94; a-169 and a-230.
94	decrease in aurkb activity and almost no phosphorylation by ttk; when associated with a-88; a-169 and a-230.
106	decreases interaction with sog1 and sog2, abolishes localization to centromeres in prometaphase; when associated with a-
165	results in reduction but not abolition of phosphorylation.
169	decrease in aurkb activity and almost no phosphorylation by ttk; when associated with a-88; a-94 and a-230.
171	decreases interaction with sog1 and sog2, abolishes localization to centromeres in prometaphase; when associated with a-
185	decreases interaction with sog1 and sog2, abolishes localization to centromeres in prometaphase; when associated with a-
189	decreases interaction with sog1 and sog2, abolishes localization to centromeres in prometaphase; when associated with a-
199	decreases interaction with sog1 and sog2, abolishes localization to centromeres in prometaphase; when associated with a-
204	decreases interaction with sog1 and sog2, abolishes localization to centromeres in prometaphase; when associated with a-
219	decreases interaction with sog1 and sog2, abolishes localization to centromeres in prometaphase; when associated with a-
219	no effect on the structure.
230	decrease in aurkb activity and dimer disruption. decrease in aurkb activity and almost no phosphorylation by ttk; when a
230	substantial loss of structure.
230	decrease in aurkb activity and no effect on the structure.

Function

Pathways and Gene Ontology

Reactome pathways

23 pathways

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

MSigDB gene sets: 344 (showing top): GNF2_CKS1B, GOBP_MITOTIC_CYTOKINESIS, GOBP_CHROMOSOME_ORGANIZATION, GOBP_ATTACHMENT_OF_SPINDLE_MICROTUBULES_TO_KINETOCHORE, GOBP_REGULATION_OF_CELL_CYCLE_CHECKPOINT, HORIUCHI_WTAP_TARGETS_DN, KANG_DOXORUBICIN_RESISTANCE_UP, GNF2_CENPF, GOBP_REGULATION_OF_NUCLEAR_DIVISION, GOBP_CHROMOSOME_LOCALIZATION, GOBP_CELL_CYCLE_PHASE_TRANSITION, GNF2_H2AFX, MITSIADES_RESPONSE_TO_APLIDIN_DN, GOBP_CHROMOSOME_SEPARATION, GNF2_MCM5

GO Biological Process (12): mitotic sister chromatid segregation (GO:0000070), mitotic cell cycle (GO:0000278), mitotic cytokinesis (GO:0000281), mitotic metaphase chromosome alignment (GO:0007080), mitotic spindle midzone assembly (GO:0051256), chromosome organization (GO:0051276), positive regulation of mitotic cell cycle spindle assembly checkpoint (GO:0090267), mitotic spindle assembly (GO:0090307), positive regulation of mitotic sister chromatid separation (GO:1901970), positive regulation of attachment of mitotic spindle microtubules to kinetochore (GO:1902425), positive regulation of mitotic cytokinesis (GO:1903490), cell division (GO:0051301)

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

GO Cellular Component (16): chromosome, centromeric region (GO:0000775), nucleoplasm (GO:0005654), nucleolus (GO:0005730), cytosol (GO:0005829), chromocenter (GO:0010369), microtubule cytoskeleton (GO:0015630), midbody (GO:0030496), chromosome passenger complex (GO:0032133), protein-containing complex (GO:0032991), intercellular bridge (GO:0045171), spindle midzone (GO:0051233), nucleus (GO:0005634), chromosome (GO:0005694), cytoplasm (GO:0005737), spindle (GO:0005819), cytoskeleton (GO:0005856)

Reactome top-level categories

Rollup of top-15 pathways:

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

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	6
intracellular membraneless organelle	5
mitotic nuclear division	4
mitotic cell cycle process	4
mitotic cell cycle	2
mitotic sister chromatid segregation	2
nuclear lumen	2
sister chromatid segregation	1
cell cycle	1
cytoskeleton-dependent cytokinesis	1
metaphase chromosome alignment	1
mitotic spindle elongation	1
spindle midzone assembly	1
mitotic spindle assembly	1
organelle organization	1
mitotic spindle assembly checkpoint signaling	1
positive regulation of cell cycle process	1
positive regulation of spindle checkpoint	1
regulation of mitotic cell cycle spindle assembly checkpoint	1
mitotic spindle organization	1
spindle assembly	1
regulation of mitotic sister chromatid separation	1
mitotic sister chromatid separation	1
positive regulation of chromosome separation	1
attachment of mitotic spindle microtubules to kinetochore	1
positive regulation of attachment of spindle microtubules to kinetochore	1
regulation of attachment of mitotic spindle microtubules to kinetochore	1
mitotic cytokinesis	1
positive regulation of cytokinesis	1
regulation of mitotic cytokinesis	1
cellular process	1
binding	1
chromosomal region	1
cytoplasm	1
cytoskeleton	1
microtubule associated complex	1
cellular_component	1
spindle	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

4537 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CDCA8	INCENP	Q9NQS7	999
CDCA8	AURKB	Q96GD4	998
CDCA8	BIRC5	O15392	997
CDCA8	SGO1	Q5FBB7	966
CDCA8	KCNJ6	P48051	927
CDCA8	SGO2	Q562F6	922
CDCA8	CDK1	P06493	901
CDCA8	RCC2	Q9P258	901
CDCA8	CCNB1	P14635	879
CDCA8	AURKC	Q9UQB9	871
CDCA8	PLK1	P53350	867
CDCA8	BUB1B	O60566	862
CDCA8	CCNB2	O95067	838
CDCA8	BUB1	O43683	818
CDCA8	CHMP4A	Q9BY43	816

IntAct

115 interactions, top by confidence:

A	B	Type	Score
BIRC5	CDCA8	psi-mi:“MI:0407”(direct interaction)	0.960
CDCA8	BIRC5	psi-mi:“MI:0914”(association)	0.960
CDCA8	BIRC5	psi-mi:“MI:0915”(physical association)	0.960
CDCA8	BIRC5	psi-mi:“MI:0407”(direct interaction)	0.960
BIRC5	CDCA8	psi-mi:“MI:0915”(physical association)	0.960
BIRC5	CDCA8	psi-mi:“MI:0403”(colocalization)	0.960
BIRC5	CDCA8	psi-mi:“MI:2364”(proximity)	0.960
INCENP	BIRC5	psi-mi:“MI:0914”(association)	0.920
CDCA8	AURKB	psi-mi:“MI:0914”(association)	0.870
AURKB	CDCA8	psi-mi:“MI:0915”(physical association)	0.870
AURKB	CDCA8	psi-mi:“MI:2364”(proximity)	0.870
AURKB	CDC37	psi-mi:“MI:0914”(association)	0.830
CDCA8	INCENP	psi-mi:“MI:0915”(physical association)	0.610
AURKB	SEC16A	psi-mi:“MI:2364”(proximity)	0.570
FBXO17	CDCA8	psi-mi:“MI:0915”(physical association)	0.560
HMBOX1	CDCA8	psi-mi:“MI:0915”(physical association)	0.560
EMILIN1	CDCA8	psi-mi:“MI:0915”(physical association)	0.560
ZNF277	CDCA8	psi-mi:“MI:0915”(physical association)	0.560
GYS1	CDCA8	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (238): CDCA8 (Affinity Capture-MS), CDCA8 (Biochemical Activity), PIAS2 (Two-hybrid), SENP3 (Two-hybrid), AURKB (Affinity Capture-Western), RANBP2 (Affinity Capture-Western), CDCA8 (Biochemical Activity), INCENP (Affinity Capture-Western), BIRC5 (Affinity Capture-Western), SENP3 (Affinity Capture-Western), CDCA8 (Biochemical Activity), ATP4A (Affinity Capture-MS), GPM6B (Affinity Capture-MS), MYH3 (Affinity Capture-MS), MYH7 (Affinity Capture-MS)

ESM2 similar proteins: A0JMT0, A0JMZ1, A1L2F3, A1L3I5, A5D7U0, A8PUI7, A9C3N6, O13024, O14216, O60293, O75167, P53352, P86345, P86346, P86347, Q0IHP2, Q0P5H2, Q0V9F7, Q15398, Q1W1G1, Q24595, Q2YDJ0, Q32N93, Q3KPK4, Q3KQW7, Q4KLP8, Q4V7H8, Q53HL2, Q563C3, Q5BKG8, Q5RBS5, Q5XG21, Q5XLR4, Q5ZJU5, Q6CK38, Q6CNI5, Q6FME9, Q6GLC7, Q76FK4, Q7K3L1

Diamond homologs: P86346, Q3KPK4, Q53HL2, Q5RBS5, Q5XLR4, Q6AXW0, Q6GLC7, Q8BHX3, P86345, P86347, Q0V9F7, Q4V7H8

SIGNOR signaling

7 interactions.

A	Effect	B	Mechanism
TTK	up-regulates	CDCA8	phosphorylation
CDCA8	“form complex”	CPC	binding
AURKB	“up-regulates activity”	CDCA8	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 76 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	6	26.2×	8e-06
Mitotic Spindle Checkpoint	6	21.1×	2e-05
SUMO E3 ligases SUMOylate target proteins	5	19.8×	2e-04
SUMOylation	5	18.1×	2e-04
Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal	6	15.5×	1e-04
M Phase	9	13.2×	3e-06
Mitotic Metaphase and Anaphase	6	12.9×	2e-04
Mitotic Anaphase	6	12.9×	2e-04

GO biological processes:

GO term	Partners	Fold	FDR
mitotic spindle organization	5	19.7×	5e-04
mitotic cell cycle	7	13.6×	2e-04
chromosome segregation	5	12.6×	2e-03
nucleosome assembly	5	10.2×	5e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	26
Likely benign	5
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1201 predictions. Top by Δscore:

Variant	Effect	Δscore
1:37692784:GGTAA:G	donor_loss	1.0000
1:37692785:G:GC	donor_loss	1.0000
1:37692786:T:A	donor_loss	1.0000
1:37692903:A:AG	acceptor_gain	1.0000
1:37692903:AGT:A	acceptor_gain	1.0000
1:37692903:AGTG:A	acceptor_gain	1.0000
1:37692904:G:GT	acceptor_gain	1.0000
1:37692904:GT:G	acceptor_gain	1.0000
1:37692904:GTG:G	acceptor_gain	1.0000
1:37692904:GTGG:G	acceptor_gain	1.0000
1:37692904:GTGGA:G	acceptor_gain	1.0000
1:37693032:CGGTA:C	donor_loss	1.0000
1:37693034:G:GG	donor_gain	1.0000
1:37693035:T:A	donor_loss	1.0000
1:37698978:G:GG	donor_gain	1.0000
1:37700520:GA:G	donor_gain	1.0000
1:37700522:G:GG	donor_gain	1.0000
1:37705570:G:GT	donor_gain	1.0000
1:37705585:G:GT	donor_gain	1.0000
1:37705585:G:T	donor_gain	1.0000
1:37706974:TCA:T	acceptor_loss	1.0000
1:37706975:CA:C	acceptor_loss	1.0000
1:37706976:A:AG	acceptor_gain	1.0000
1:37706976:A:AT	acceptor_loss	1.0000
1:37706977:G:GG	acceptor_gain	1.0000
1:37706977:GA:G	acceptor_gain	1.0000
1:37706977:GAGC:G	acceptor_gain	1.0000
1:37707060:TCTCC:T	donor_gain	1.0000
1:37707061:CTCC:C	donor_gain	1.0000
1:37707061:CTCCG:C	donor_loss	1.0000

AlphaMissense

1818 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:37705511:A:C	S219R	0.996
1:37705513:C:A	S219R	0.996
1:37705513:C:G	S219R	0.996
1:37692992:T:C	L61P	0.989
1:37692914:G:C	R35P	0.987
1:37705463:C:A	R203S	0.986
1:37708329:T:C	L269P	0.985
1:37705548:T:A	V231E	0.984
1:37708329:T:A	L269H	0.984
1:37707060:T:C	L265P	0.983
1:37692947:T:C	L46P	0.979
1:37692764:T:C	L25P	0.978
1:37693018:T:A	W70R	0.978
1:37693018:T:C	W70R	0.978
1:37692772:T:C	F28L	0.977
1:37692774:C:A	F28L	0.977
1:37692774:C:G	F28L	0.977
1:37706988:T:C	L241S	0.977
1:37695942:G:C	A86P	0.976
1:37703337:T:C	F192L	0.976
1:37703339:T:A	F192L	0.976
1:37703339:T:G	F192L	0.976
1:37692779:G:C	R30P	0.975
1:37692989:G:C	R60P	0.975
1:37692773:T:C	F28S	0.973
1:37705509:G:A	G218D	0.971
1:37705512:G:A	S219N	0.971
1:37695945:G:C	A87P	0.970
1:37692986:T:C	L59P	0.969
1:37698927:T:C	I96T	0.967

dbSNP variants (sampled 300 via entrez): RS1000307898 (1:37698214 T>C), RS1000468782 (1:37691486 C>T), RS1000775158 (1:37704579 G>A,C), RS1000810575 (1:37698695 A>T), RS1000823175 (1:37691036 G>C), RS1000915742 (1:37705806 G>A,T), RS1001104245 (1:37692150 A>C), RS1001206307 (1:37690624 C>T), RS1001604077 (1:37704232 G>A,C), RS1001656449 (1:37704483 T>C), RS1001714252 (1:37697078 G>A), RS1001818842 (1:37697788 A>G,T), RS1001945945 (1:37692632 C>A), RS1002095153 (1:37698505 TAAG>T), RS1002159646 (1:37691930 C>A,G,T)

Disease associations

OMIM: gene MIM:609977 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST002115_4	Axial length	4.000000e-13
GCST003476_2	Eyebrow thickness	7.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0005318	axial length measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases expression	5
bisphenol A	affects expression, decreases expression, increases expression	4
(+)-JQ1 compound	decreases expression	3
cobaltous chloride	decreases expression	2
Air Pollutants	increases abundance, decreases expression	2
Tretinoin	decreases expression	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	2
Cyclosporine	decreases expression	2
Aflatoxin B1	decreases expression, increases methylation	2
Particulate Matter	increases abundance, decreases expression	2
afuresertib	decreases expression	1
FR900359	affects phosphorylation	1
TAK-243	increases sumoylation	1
triphenyl phosphate	affects expression	1
propionaldehyde	decreases expression	1
arsenite	affects binding, increases reaction	1
o,p’-DDT	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
perfluorooctanoic acid	decreases expression	1
zinc chromate	decreases expression, increases abundance	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, increases expression	1
diallyl trisulfide	decreases expression	1
chromium hexavalent ion	decreases expression, increases abundance	1
perfluorooctane sulfonic acid	decreases expression	1
2-palmitoylglycerol	increases expression	1
K 7174	decreases expression	1
erucylphospho-N,N,N-trimethylpropylammonium	decreases expression	1
abrine	increases expression	1
palbociclib	decreases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1

Clinical trials (associated diseases)

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