BUB3

Summary

BUB3 (BUB3 mitotic checkpoint protein, HGNC:1151) is a protein-coding gene on chromosome 10q26.13, encoding Mitotic checkpoint protein BUB3 (O43684). Has a dual function in spindle-assembly checkpoint signaling and in promoting the establishment of correct kinetochore-microtubule (K-MT) attachments. It is a common-essential gene (DepMap: required in 99.8% of cancer cell lines).

This gene encodes a protein involved in spindle checkpoint function. The encoded protein contains four WD repeat domains and has sequence similarity with the yeast BUB3 protein. Alternate transcriptional splice variants, encoding different isoforms, have been characterized.

Source: NCBI Gene 9184 — RefSeq curated summary.

At a glance

• Gene–disease (curated): mosaic variegated aneuploidy syndrome (Supportive, GenCC)
• GWAS associations: 7
• Clinical variants (ClinVar): 460 total
• Phenotypes (HPO): 64
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 99.8% of screened cell lines (common-essential)
• MANE Select transcript: NM_004725

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1151
Approved symbol	BUB3
Name	BUB3 mitotic checkpoint protein
Location	10q26.13
Locus type	gene with protein product
Status	Approved
Aliases	BUB3L
Ensembl gene	ENSG00000154473
Ensembl biotype	protein_coding
OMIM	603719
Entrez	9184

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 6 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000368858, ENST00000368859, ENST00000368865, ENST00000407911, ENST00000481952, ENST00000940618, ENST00000940619

RefSeq mRNA: 2 — MANE Select: NM_004725 NM_001007793, NM_004725

CCDS: CCDS31306, CCDS7635

Canonical transcript exons

ENST00000368865 — 8 exons

Exon	Start	End
ENSE00001016118	123157729	123157880
ENSE00001016125	123162236	123162413
ENSE00001016126	123160407	123160565
ENSE00001205502	123162612	123162828
ENSE00001448130	123154402	123154485
ENSE00001448135	123163820	123170467
ENSE00003392782	123154918	123155112
ENSE00003664327	123155658	123155727

Expression profiles

Bgee: expression breadth ubiquitous, 295 present calls, max score 98.96.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 83.1038 / max 898.3676, expressed in 1826 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
107488	70.9968	1825
107489	8.9187	1649
107490	2.3553	1000
107491	0.6497	323
107492	0.1832	75

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
gingival epithelium	UBERON:0001949	98.96	gold quality
sperm	CL:0000019	98.69	gold quality
epithelium of nasopharynx	UBERON:0001951	98.66	gold quality
gingiva	UBERON:0001828	98.39	gold quality
male germ cell	CL:0000015	98.35	gold quality
germinal epithelium of ovary	UBERON:0001304	98.31	gold quality
choroid plexus epithelium	UBERON:0003911	98.23	gold quality
ventricular zone	UBERON:0003053	98.12	gold quality
squamous epithelium	UBERON:0006914	97.92	gold quality
lymph node	UBERON:0000029	97.90	gold quality
embryo	UBERON:0000922	97.90	gold quality
esophagus squamous epithelium	UBERON:0006920	97.86	gold quality
ganglionic eminence	UBERON:0004023	97.71	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	97.67	gold quality
tibia	UBERON:0000979	97.58	gold quality
tongue squamous epithelium	UBERON:0006919	97.50	gold quality
epithelium of esophagus	UBERON:0001976	97.36	gold quality
hair follicle	UBERON:0002073	97.31	gold quality
buccal mucosa cell	CL:0002336	97.19	gold quality
amniotic fluid	UBERON:0000173	97.06	gold quality
parietal pleura	UBERON:0002400	97.01	gold quality
caecum	UBERON:0001153	97.00	gold quality
vermiform appendix	UBERON:0001154	97.00	gold quality
pleura	UBERON:0000977	96.95	gold quality
visceral pleura	UBERON:0002401	96.92	gold quality
mammalian vulva	UBERON:0000997	96.79	gold quality
superficial temporal artery	UBERON:0001614	96.79	gold quality
penis	UBERON:0000989	96.75	gold quality
trabecular bone tissue	UBERON:0002483	96.75	gold quality
oviduct epithelium	UBERON:0004804	96.71	gold quality

Single-cell (SCXA)

Detected in 15 experiment(s), a significant marker in 8.

Experiment	Marker?	Max mean expression
E-CURD-112	yes	40.32
E-HCAD-10	yes	37.32
E-HCAD-1	yes	18.38
E-GEOD-125970	yes	17.02
E-MTAB-10042	yes	10.03
E-MTAB-10553	yes	7.22
E-CURD-88	yes	5.37
E-MTAB-6819	no	1761.52
E-GEOD-70580	no	1141.78
E-CURD-10	no	1119.85
E-MTAB-6911	no	987.23
E-MTAB-7008	no	544.87
E-MTAB-5061	no	3.57
E-GEOD-83139	no	2.72
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): E2F4

miRNA regulators (miRDB)

19 targeting BUB3, 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-4262	100.00	73.26	3931
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-3120-3P	99.54	70.28	2669
HSA-MIR-578	99.46	68.36	1787
HSA-MIR-6828-5P	99.31	69.21	1433
HSA-MIR-3973	99.20	69.19	1990
HSA-MIR-8065	99.19	70.38	1289
HSA-MIR-3179	98.22	65.90	1445
HSA-MIR-6072	98.00	66.47	804
HSA-MIR-188-5P	97.89	67.01	756
HSA-MIR-3670	97.88	64.39	763
HSA-MIR-1255B-2-3P	97.80	67.04	880
HSA-MIR-6783-5P	97.67	67.21	1528
HSA-MIR-376C-3P	97.63	68.88	1263
HSA-MIR-618	97.62	67.46	861
HSA-MIR-585-5P	97.54	69.02	955
HSA-MIR-6866-3P	97.38	66.94	748
HSA-MIR-27A-5P	97.01	65.63	528
HSA-MIR-6891-3P	95.80	65.76	683

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 99.8% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 27)

• These results indicate that Bub3 and Cdc20 play additional roles in the integration of cell cycle arrest as transcriptional repressors. (PMID:15388328)
• Allelic loss at 10q26 in osteosarcoma is reported in the region of BUB3. (PMID:15796961)
• subpopulation of dynein, containing the DYNLT3 light chain, may be important for chromosome congression, in addition to having a role in the transport of checkpoint proteins from the kinetochore to the spindle pole (PMID:17289665)
• Using RNA interference and high-resolution microscopy, we analyzed kinetochore-microtubule attachments in Bub3-depleted cells and compared them to those in Bub1- or BubR1-depleted cells. (PMID:18199686)
• Results suggest a novel molecular mechanism leading to aneuploidy involving interference of TAp73alpha with Bub1 and Bub3 resulting in an altered mitotic checkpoint. (PMID:19182530)
• Mutations in BUB1 and BUB3 cause mosaic variegated aneuploidy and increase the risk of colorectal cancer at a young age. (PMID:23747338)
• Mutations targeting the Bub3 interface prevent kinetochore recruitment of the SAC kinase Bub1. Crucially, they also cause a checkpoint defect, showing that recognition of phosphorylated targets by Bub3 is required for checkpoint signaling (PMID:24066227)
• Results showed that neither variants in BUB3 nor variants in MAD2L1 caused any significant effect on the risk of breast cancer (PMID:24711138)
• Results suggest that these USP7-dependent effects are mediated by decreased levels of spindle assembly checkpoint (SAC) component Bub3. (PMID:25003721)
• Data indicate that cell cycle protein Bub3-mediated kinetochore recruitment of BubR1 kinase enhances mitotic checkpoint signaling. (PMID:25246557)
• Data show sequential multisite regulation of the microtubule-associated protein KNL1-kinase-adaptor complex BUB1/BUB3 interaction. (PMID:25661489)
• the mechanisms of BUB3 in mitotic checkpoint signaling (PMID:25814666)
• We show that kinetochore recruitment of BUBR1 and BUB3 by BUB1 is dispensable for SAC activation (PMID:26148513)
• a mutual antagonism exists between Bub3 and dynein to ensure optimal KT-MT attachments (PMID:26526612)
• The integrity of the mitotic checkpoint complex depends on the specific recognition between BubR1 and Bub3, for which the BubR1 Gle2 binding sequence motif is essential. (PMID:27030009)
• Small sequence differences in Bub1 and BubR1 direct Bub3 to different phosphorylated targets in the spindle assembly checkpoint signaling cascade. (PMID:28943088)
• The roles for the BUB3-BUB1 complex in S phase. (PMID:29727616)
• Findings reveal a regulatory role of Bub3 in DMAP1-mediated DNA methylation upon mitotic stress. (PMID:30553276)
• During mitosis, CRL4 dissociates from RepID and replaces it with RB Binding Protein 7 (RBBP7), which ubiquitinates the SAC mediator BUB3 to enable mitotic exit. (PMID:31911655)
• [Expression and clinical significance of Spindly and Bub3 in oral squamous cell carcinoma]. (PMID:33543222)
• Expression and prognosis analyses of BUB1, BUB1B and BUB3 in human sarcoma. (PMID:33872216)
• Research progress of Bub3 gene in malignant tumors. (PMID:34882895)
• The genes for sensory perception of sound should be considered in gene diagnosis of congenital sensorineural hearing loss and microtia. (PMID:35000142)
• Dual-functional significance of ATM-mediated phosphorylation of spindle assembly checkpoint component Bub3 in mitosis and the DNA damage response. (PMID:35085551)
• miR-664b-3p inhibits colon cell carcinoma via negatively regulating Budding uninhibited by benzimidazole 3. (PMID:35156516)
• BUBs Are New Biomarkers of Promoting Tumorigenesis and Affecting Prognosis in Breast Cancer. (PMID:35493295)
• SETD1A function in leukemia is mediated through interaction with mitotic regulators BuGZ/BUB3. (PMID:37535603)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	bub3	ENSDARG00000075883
mus_musculus	Bub3	ENSMUSG00000066979
rattus_norvegicus	Bub3	ENSRNOG00000020643
drosophila_melanogaster	Bub3	FBGN0025457
caenorhabditis_elegans		WBGENE00013209

Paralogs (2): RAE1 (ENSG00000101146), DNAAF10 (ENSG00000243667)

Protein

Protein identifiers

Mitotic checkpoint protein BUB3 — O43684 (reviewed: O43684)

All UniProt accessions (4): O43684, A0A140VJF3, J3QSX4, J3QT28

UniProt curated annotations — full annotation on UniProt →

Function. Has a dual function in spindle-assembly checkpoint signaling and in promoting the establishment of correct kinetochore-microtubule (K-MT) attachments. Promotes the formation of stable end-on bipolar attachments. Necessary for kinetochore localization of BUB1. Regulates chromosome segregation during oocyte meiosis. The BUB1/BUB3 complex plays a role in the inhibition of anaphase-promoting complex or cyclosome (APC/C) when spindle-assembly checkpoint is activated and inhibits the ubiquitin ligase activity of APC/C by phosphorylating its activator CDC20. This complex can also phosphorylate MAD1L1.

Subunit / interactions. Interacts with BUB1 and BUBR1. The BUB1/BUB3 complex interacts with MAD1L1. Interacts with ZNF207/BuGZ; leading to promote stability and kinetochore loading of BUB3.

Subcellular location. Nucleus. Chromosome. Centromere. Kinetochore.

Post-translational modifications. Poly-ADP-ribosylated by PARP1. Ubiquitinated by UBR5, promoting disassembly of the mitotic checkpoint complex from the APC/C complex.

Similarity. Belongs to the WD repeat BUB3 family.

Isoforms (2)

UniProt ID	Names	Canonical?
O43684-1	1	yes
O43684-2	2

RefSeq proteins (2): NP_001007794, NP_004716* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001680	WD40_rpt	Repeat
IPR015943	WD40/YVTN_repeat-like_dom_sf	Homologous_superfamily
IPR020472	WD40_PAC1	Repeat
IPR036322	WD40_repeat_dom_sf	Homologous_superfamily

Pfam: PF00400

UniProt features (12 total): repeat 7, modified residue 2, chain 1, cross-link 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O43684-F1	96.10	0.93

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 (3): 216, 179, 211

Function

Pathways and Gene Ontology

Reactome pathways

28 pathways

ID	Pathway
R-HSA-141430	Inactivation of APC/C via direct inhibition of the APC/C complex
R-HSA-141444	Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal
R-HSA-174184	Cdc20:Phospho-APC/C mediated degradation of Cyclin A
R-HSA-176409	APC/C:Cdc20 mediated degradation of mitotic proteins
R-HSA-179409	APC-Cdc20 mediated degradation of Nek2A
R-HSA-2467813	Separation of Sister Chromatids
R-HSA-2500257	Resolution of Sister Chromatid Cohesion
R-HSA-5663220	RHO GTPases Activate Formins
R-HSA-68877	Mitotic Prometaphase
R-HSA-9648025	EML4 and NUDC in mitotic spindle formation
R-HSA-141405	Inhibition of the proteolytic activity of APC/C required for the onset of anaphase by mitotic spindle checkpoint components
R-HSA-141424	Amplification of signal from the kinetochores
R-HSA-162582	Signal Transduction
R-HSA-1640170	Cell Cycle
R-HSA-174143	APC/C-mediated degradation of cell cycle proteins
R-HSA-176408	Regulation of APC/C activators between G1/S and early anaphase
R-HSA-176814	Activation of APC/C and APC/C:Cdc20 mediated degradation of mitotic proteins
R-HSA-179419	APC:Cdc20 mediated degradation of cell cycle proteins prior to satisfation of the cell cycle checkpoint
R-HSA-194315	Signaling by Rho GTPases
R-HSA-195258	RHO GTPase Effectors
R-HSA-2555396	Mitotic Metaphase and Anaphase
R-HSA-453276	Regulation of mitotic cell cycle
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: 502 (showing top): GOBP_CHROMOSOME_ORGANIZATION, MORF_DNMT1, GOBP_ATTACHMENT_OF_SPINDLE_MICROTUBULES_TO_KINETOCHORE, BORCZUK_MALIGNANT_MESOTHELIOMA_UP, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, HORIUCHI_WTAP_TARGETS_DN, MORF_ESPL1, HNF3ALPHA_Q6, MORF_SMC1L1, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, MORF_BUB1, GOBP_REGULATION_OF_NUCLEAR_DIVISION, REACTOME_APC_CDC20_MEDIATED_DEGRADATION_OF_NEK2A, GOBP_CHROMOSOME_LOCALIZATION, GOBP_CELL_CYCLE_PHASE_TRANSITION

GO Biological Process (7): mitotic spindle assembly checkpoint signaling (GO:0007094), attachment of spindle microtubules to kinetochore (GO:0008608), protein localization to kinetochore (GO:0034501), cell division (GO:0051301), meiotic cell cycle (GO:0051321), chromosome segregation (GO:0007059), regulation of chromosome segregation (GO:0051983)

GO Molecular Function (2): ubiquitin binding (GO:0043130), protein binding (GO:0005515)

GO Cellular Component (8): kinetochore (GO:0000776), nucleoplasm (GO:0005654), cytosol (GO:0005829), mitotic checkpoint complex (GO:0033597), bub1-bub3 complex (GO:1990298), chromosome, centromeric region (GO:0000775), nucleus (GO:0005634), chromosome (GO:0005694)

Reactome top-level categories

Rollup of top-15 pathways:

Category	Pathways
APC:Cdc20 mediated degradation of cell cycle proteins prior to satisfation of the cell cycle checkpoint	2
Mitotic Prometaphase	2
Mitotic Spindle Checkpoint	2
APC/C-mediated degradation of cell cycle proteins	2
Inhibition of the proteolytic activity of APC/C required for the onset of anaphase by mitotic spindle checkpoint components	1
Amplification of signal from the kinetochores	1
Activation of APC/C and APC/C:Cdc20 mediated degradation of mitotic proteins	1
Mitotic Anaphase	1
RHO GTPase Effectors	1
M Phase	1
Regulation of APC/C activators between G1/S and early anaphase	1
Regulation of mitotic cell cycle	1
APC/C:Cdc20 mediated degradation of mitotic proteins	1
Signaling by Rho GTPases, Miro GTPases and RHOBTB3	1
Signaling by Rho GTPases	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cell cycle process	2
intracellular membraneless organelle	2
cellular anatomical structure	2
mitotic cell cycle	1
negative regulation of mitotic metaphase/anaphase transition	1
spindle assembly checkpoint signaling	1
mitotic spindle checkpoint signaling	1
microtubule binding	1
metaphase chromosome alignment	1
protein localization to chromosome, centromeric region	1
protein localization to condensed chromosome	1
cellular process	1
cell cycle	1
sexual reproduction	1
reproductive process	1
meiotic nuclear division	1
chromosome segregation	1
regulation of cell cycle process	1
ubiquitin-like protein binding	1
binding	1
condensed chromosome, centromeric region	1
supramolecular complex	1
nuclear lumen	1
cytoplasm	1
nuclear protein-containing complex	1
bub1-bub3 complex	1
protein-containing complex	1
chromosomal region	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

3745 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
BUB3	BUB1B	O60566	999
BUB3	BUB1	O43683	999
BUB3	CDC20	Q12834	999
BUB3	KNL1	Q8NG31	991
BUB3	MAD2L1	Q13257	967
BUB3	ZNF207	O43670	962
BUB3	TTK	P33981	898
BUB3	PARP2	Q9UGN5	893
BUB3	DYNLT3	P51808	880
BUB3	ESPL1	Q14674	868
BUB3	AURKB	Q96GD4	859
BUB3	CENPE	Q02224	855
BUB3	FZR1	Q9UM11	855
BUB3	ZW10	O43264	852
BUB3	PTTG2	Q9NZH5	826

IntAct

150 interactions, top by confidence:

A	B	Type	Score
BUB3	BUB1B	psi-mi:“MI:0915”(physical association)	0.930
BUB1B	BUB3	psi-mi:“MI:0914”(association)	0.930
BUB1B	BUB3	psi-mi:“MI:0915”(physical association)	0.930
BUB3	BUB1	psi-mi:“MI:0915”(physical association)	0.800
BUB1	BUB3	psi-mi:“MI:0915”(physical association)	0.800
CCT2	TXNDC9	psi-mi:“MI:0914”(association)	0.730
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
BUB3	ZNF207	psi-mi:“MI:0915”(physical association)	0.690
ZNF207	BUB3	psi-mi:“MI:0403”(colocalization)	0.690
BUB3	ZNF207	psi-mi:“MI:0914”(association)	0.690
ZNF207	BUB3	psi-mi:“MI:0915”(physical association)	0.690
BUB3	ATXN1	psi-mi:“MI:0915”(physical association)	0.670
BUB1	NDC80	psi-mi:“MI:0914”(association)	0.670
NCBP2	KPNA3	psi-mi:“MI:0914”(association)	0.640
CCT3	TXNDC9	psi-mi:“MI:0914”(association)	0.640
PSTPIP1	BUB3	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (431): BUB3 (Affinity Capture-Western), BUB3 (Reconstituted Complex), BUB3 (Affinity Capture-MS), BUB3 (Two-hybrid), BUB3 (Two-hybrid), BUB3 (Affinity Capture-Western), BUB3 (Affinity Capture-Western), BUB3 (Affinity Capture-MS), CCT7 (Affinity Capture-MS), BUB1B (Affinity Capture-MS), CCT2 (Affinity Capture-MS), BUB1 (Affinity Capture-MS), BTBD10 (Affinity Capture-MS), KCTD20 (Affinity Capture-MS), ZNF207 (Affinity Capture-MS)

ESM2 similar proteins: A0A1L8EXB5, A4QNE6, A8WGF4, C1BK83, O35142, O43684, O55029, P35605, P35606, Q17QU5, Q1JP79, Q1JQB2, Q29RH4, Q29RZ9, Q3UGF1, Q4FZW5, Q4R4I8, Q561Y0, Q5I0B4, Q5M7F6, Q5MNZ6, Q5R664, Q5RB58, Q5U4Y8, Q5VQ78, Q6GNF1, Q6NWV3, Q6PA72, Q6TGU2, Q803V5, Q8AVT9, Q8BGF3, Q8IWZ6, Q8K2G4, Q8L828, Q8NEZ3, Q8VE80, Q92747, Q96J01, Q96MX6

Diamond homologs: A0A1W5T363, A5GFN6, A8IR43, G0SEA3, O42860, O43684, O60097, P40066, P41838, P78406, Q1JQB2, Q38942, Q3SWS8, Q4R6D2, Q54DM1, Q5E9A4, Q5FVA9, Q5RB58, Q5RF99, Q7ZWF0, Q8C570, Q8VYZ5, Q93454, Q9C1X1, Q9C701, Q9LJN8, Q9W2E7, Q9WVA3, Q9XWH0, Q9YGY3, S8ASK6, O43071, O93277, Q54MP8, Q5ZJW8, Q6GPU3, Q9FE91, F4I241, O60907, Q4R8H1

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
BUB3	“form complex”	MCC	binding
ATM	“up-regulates activity”	BUB3	phosphorylation
BUB1	“up-regulates activity”	BUB3	relocalization

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 142 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
Inhibition of the proteolytic activity of APC/C required for the onset of anaphase by mitotic spindle checkpoint components	9	51.4×	1e-11
Inactivation of APC/C via direct inhibition of the APC/C complex	9	42.1×	4e-11
APC:Cdc20 mediated degradation of cell cycle proteins prior to satisfation of the cell cycle checkpoint	10	38.1×	1e-11
Conversion from APC/C:Cdc20 to APC/C:Cdh1 in late anaphase	8	37.4×	9e-10
Activation of APC/C and APC/C:Cdc20 mediated degradation of mitotic proteins	10	36.7×	1e-11
APC-Cdc20 mediated degradation of Nek2A	9	34.3×	2e-10
Phosphorylation of the APC/C	7	34.3×	2e-08
APC/C:Cdc20 mediated degradation of Cyclin B	8	32.9×	2e-09

GO biological processes:

GO term	Partners	Fold	FDR
protein branched polyubiquitination	9	59.2×	1e-11
anaphase-promoting complex-dependent catabolic process	9	49.4×	4e-11
regulation of meiotic cell cycle	8	47.9×	9e-10
protein K11-linked ubiquitination	8	24.5×	3e-07
mitotic spindle assembly checkpoint signaling	5	21.9×	2e-04
regulation of mitotic cell cycle	9	16.9×	6e-07
mRNA transcription by RNA polymerase II	6	15.5×	2e-04
protein K48-linked ubiquitination	9	11.8×	1e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	271
Likely benign	177
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

949 predictions. Top by Δscore:

Variant	Effect	Δscore
10:123155110:TAC:T	donor_gain	1.0000
10:123155111:AC:A	donor_gain	1.0000
10:123155111:ACG:A	donor_loss	1.0000
10:123155112:CGTA:C	donor_loss	1.0000
10:123155113:G:GG	donor_gain	1.0000
10:123155113:GTAG:G	donor_loss	1.0000
10:123155114:T:G	donor_loss	1.0000
10:123155652:TTATA:T	acceptor_loss	1.0000
10:123155653:TATAG:T	acceptor_loss	1.0000
10:123155654:ATAGG:A	acceptor_loss	1.0000
10:123155655:TA:T	acceptor_loss	1.0000
10:123155656:A:AG	acceptor_gain	1.0000
10:123155656:AG:A	acceptor_gain	1.0000
10:123155656:AGGAT:A	acceptor_loss	1.0000
10:123155657:G:GG	acceptor_gain	1.0000
10:123155657:G:GT	acceptor_loss	1.0000
10:123155657:GG:G	acceptor_gain	1.0000
10:123155724:CAAG:C	donor_loss	1.0000
10:123155725:AAGGT:A	donor_loss	1.0000
10:123155726:AGGTA:A	donor_loss	1.0000
10:123155729:T:A	donor_loss	1.0000
10:123157725:A:AG	acceptor_gain	1.0000
10:123157726:T:G	acceptor_gain	1.0000
10:123157726:TA:T	acceptor_loss	1.0000
10:123157727:A:AG	acceptor_gain	1.0000
10:123157728:G:GT	acceptor_gain	1.0000
10:123157728:GA:G	acceptor_gain	1.0000
10:123157728:GAA:G	acceptor_gain	1.0000
10:123157728:GAAA:G	acceptor_gain	1.0000
10:123157728:GAAAA:G	acceptor_gain	1.0000

AlphaMissense

2163 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:123155020:T:A	W35R	1.000
10:123155020:T:C	W35R	1.000
10:123155022:G:C	W35C	1.000
10:123155022:G:T	W35C	1.000
10:123155036:G:C	R40P	1.000
10:123157803:G:A	G114R	1.000
10:123157803:G:C	G114R	1.000
10:123157804:G:A	G114E	1.000
10:123157809:T:A	W116R	1.000
10:123157809:T:C	W116R	1.000
10:123157822:T:A	V120D	1.000
10:123157830:T:A	W123R	1.000
10:123157830:T:C	W123R	1.000
10:123160446:G:A	G153R	1.000
10:123160446:G:C	G153R	1.000
10:123160447:G:A	G153E	1.000
10:123160473:T:A	W162R	1.000
10:123160473:T:C	W162R	1.000
10:123160522:T:C	L178P	1.000
10:123162248:A:C	S197R	1.000
10:123162250:C:A	S197R	1.000
10:123162250:C:G	S197R	1.000
10:123162251:T:C	S198P	1.000
10:123162252:C:A	S198Y	1.000
10:123162252:C:T	S198F	1.000
10:123162257:G:A	E200K	1.000
10:123162258:A:T	E200V	1.000
10:123162260:G:A	G201S	1.000
10:123162260:G:C	G201R	1.000
10:123162260:G:T	G201C	1.000

dbSNP variants (sampled 300 via entrez): RS1000021848 (10:123170944 A>T), RS1000200858 (10:123164880 G>A), RS1000290886 (10:123165169 T>C), RS1000324840 (10:123154470 C>T), RS1000457644 (10:123156421 T>A,C), RS1000575695 (10:123154674 G>A), RS1000596367 (10:123156140 G>T), RS1000612064 (10:123163967 G>A,T), RS1000731474 (10:123159866 C>G), RS1000782344 (10:123169774 G>A,T), RS1000855564 (10:123168293 A>C,G), RS1000929395 (10:123159507 CAGG>C), RS1001193586 (10:123153645 G>A), RS1001415352 (10:123165853 A>C), RS1001728176 (10:123153221 T>C)

Disease associations

OMIM: gene MIM:603719 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
mosaic variegated aneuploidy syndrome	Supportive	Autosomal dominant

Mondo (1): mosaic variegated aneuploidy syndrome (MONDO:0000141)

Orphanet (0):

HPO phenotypes

64 total (30 of 64 shown, HPO-id order):

HPO	Term
HP:0000003	Multicystic kidney dysplasia
HP:0000062	Ambiguous genitalia
HP:0000175	Cleft palate
HP:0000252	Microcephaly
HP:0000286	Epicanthus
HP:0000325	Triangular face
HP:0000340	Sloping forehead
HP:0000347	Micrognathia
HP:0000348	High forehead
HP:0000358	Posteriorly rotated ears
HP:0000365	Hearing impairment
HP:0000445	Wide nose
HP:0000457	Depressed nasal ridge
HP:0000478	Abnormality of the eye
HP:0000494	Downslanted palpebral fissures
HP:0000501	Glaucoma
HP:0000504	Abnormality of vision
HP:0000518	Cataract
HP:0000568	Microphthalmia
HP:0000821	Hypothyroidism
HP:0000924	Abnormality of the skeletal system
HP:0000929	Abnormal skull morphology
HP:0001000	Abnormality of skin pigmentation
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001252	Hypotonia
HP:0001263	Global developmental delay
HP:0001305	Dandy-Walker malformation
HP:0001360	Holoprosencephaly
HP:0001510	Growth delay

GWAS associations

7 associations (top):

Study	Trait	p-value
GCST002192_1	Menopause (age at onset)	1.000000e-07
GCST004904_164	Body mass index	2.000000e-12
GCST004904_233	Body mass index	3.000000e-08
GCST006224_1	Right lateral prefrontal cortical growth	4.000000e-06
GCST012244_6	Childhood asthma exacerbations in long-acting beta2-agonist treatment	5.000000e-06
GCST90013421_41	Left-handedness	5.000000e-08
GCST90016668_6	Lung volume	4.000000e-09

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004704	age at menopause
EFO:0004340	body mass index
EFO:0007614	asthma exacerbation measurement
EFO:0009902	handedness

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C536987	Mosaic variegated aneuploidy syndrome (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5724769 (SINGLE PROTEIN)

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

ChEMBL bioactivities

4 potent at pChembl≥5 of 4 total, top 4 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.28	Kd	5.278	nM	CHEMBL3752910
8.28	ED50	5.278	nM	CHEMBL3752910
7.17	Kd	67.91	nM	CHEMBL5653589
7.17	ED50	67.91	nM	CHEMBL5653589

PubChem BioAssay actives

2 with measured affinity, of 10 total; 2 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
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2147964: Binding affinity to human BUB3 incubated for 45 mins by Kinobead based pull down assay	kd	0.0053	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2147964: Binding affinity to human BUB3 incubated for 45 mins by Kinobead based pull down assay	kd	0.0679	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression, decreases methylation, affects cotreatment	4
Benzo(a)pyrene	affects methylation, increases expression	3
Fluorouracil	affects response to substance, decreases expression	3
deoxynivalenol	increases expression	2
Doxorubicin	decreases response to substance, affects cotreatment, affects expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Quercetin	decreases expression	2
aristolochic acid I	increases expression	1
FR900359	increases phosphorylation	1
TAK-243	increases sumoylation	1
triphenyl phosphate	affects expression	1
sodium arsenate	decreases expression	1
arsenite	increases reaction, affects binding	1
sodium arsenite	decreases expression	1
hydroquinone	decreases expression	1
beta-methylcholine	affects expression	1
16-hydroxycleroda-3,13(14)-dien-15,16-olide	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
ICG 001	increases expression	1
bisphenol B	increases expression	1
2-methyl-2H-pyrazole-3-carboxylic acid (2-methyl-4-o-tolylazophenyl)amide	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
bisphenol AF	increases expression	1
Resveratrol	increases expression	1
Acetaminophen	increases expression	1
Air Pollutants	increases abundance, affects expression	1
Chelating Agents	increases expression, affects binding	1
Cisplatin	increases expression	1
Copper	affects binding, increases expression	1
Cyclophosphamide	affects expression, affects cotreatment	1

ChEMBL screening assays

7 unique, capped per target: 7 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5651006	Binding	Binding affinity to human BUB3 incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Clinical trials (associated diseases)

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