BUB1B

Summary

BUB1B (BUB1 mitotic checkpoint serine/threonine kinase B, HGNC:1149) is a protein-coding gene on chromosome 15q15.1, encoding Mitotic checkpoint serine/threonine-protein kinase BUB1 beta (O60566). Essential component of the mitotic checkpoint. It is a common-essential gene (DepMap: required in 98.7% of cancer cell lines).

This gene encodes a kinase involved in spindle checkpoint function. The protein has been localized to the kinetochore and plays a role in the inhibition of the anaphase-promoting complex/cyclosome (APC/C), delaying the onset of anaphase and ensuring proper chromosome segregation. Impaired spindle checkpoint function has been found in many forms of cancer.

Source: NCBI Gene 701 — RefSeq curated summary.

At a glance

• Gene–disease (curated): mosaic variegated aneuploidy syndrome 1 (Definitive, ClinGen) — +3 more curated relationships
• GWAS associations: 2
• Clinical variants (ClinVar): 2,397 total — 60 pathogenic, 16 likely-pathogenic
• Phenotypes (HPO): 112
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 98.7% of screened cell lines (common-essential)
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity no evidence
• MANE Select transcript: NM_001211

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1149
Approved symbol	BUB1B
Name	BUB1 mitotic checkpoint serine/threonine kinase B
Location	15q15.1
Locus type	gene with protein product
Status	Approved
Aliases	BUBR1, MAD3L, Bub1A, SSK1
Ensembl gene	ENSG00000156970
Ensembl biotype	protein_coding
OMIM	602860
Entrez	701

Gene structure

Transcript identifiers

Ensembl transcripts: 19 — 10 protein_coding, 5 retained_intron, 2 nonsense_mediated_decay, 2 protein_coding_CDS_not_defined

ENST00000287598, ENST00000412359, ENST00000557848, ENST00000558151, ENST00000558715, ENST00000558972, ENST00000559414, ENST00000559461, ENST00000559733, ENST00000559772, ENST00000560120, ENST00000897791, ENST00000897792, ENST00000918305, ENST00000918306, ENST00000918307, ENST00000918308, ENST00000918309, ENST00000918310

RefSeq mRNA: 1 — MANE Select: NM_001211 NM_001211

CCDS: CCDS10053

Canonical transcript exons

ENST00000287598 — 23 exons

Exon	Start	End
ENSE00001029391	40208637	40208770
ENSE00001029392	40212499	40212648
ENSE00001029395	40213332	40213474
ENSE00001029397	40217496	40217667
ENSE00001029401	40210110	40210210
ENSE00001029402	40206184	40206458
ENSE00001029407	40185551	40185642
ENSE00001029409	40209635	40209775
ENSE00001029410	40183714	40183883
ENSE00001029411	40176477	40176673
ENSE00001029414	40185165	40185379
ENSE00001929183	40161069	40161255
ENSE00001948417	40220564	40221123
ENSE00003491855	40218456	40218562
ENSE00003506275	40170062	40170121
ENSE00003514834	40196545	40196774
ENSE00003520890	40202405	40202465
ENSE00003561918	40200931	40200980
ENSE00003578473	40170537	40170681
ENSE00003589403	40200244	40200359
ENSE00003593922	40202589	40202694
ENSE00003642586	40165053	40165196
ENSE00003683831	40199615	40199727

Expression profiles

Bgee: expression breadth ubiquitous, 210 present calls, max score 99.30.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 15.5638 / max 376.8596, expressed in 1320 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
146071	14.7470	1300
146072	0.7963	415
146073	0.0204	7

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	99.30	gold quality
oocyte	CL:0000023	99.20	gold quality
ventricular zone	UBERON:0003053	97.51	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	93.28	gold quality
embryo	UBERON:0000922	92.68	gold quality
choroid plexus epithelium	UBERON:0003911	92.63	gold quality
ganglionic eminence	UBERON:0004023	91.64	gold quality
right testis	UBERON:0004534	90.12	gold quality
bone marrow	UBERON:0002371	89.22	gold quality
left testis	UBERON:0004533	89.18	gold quality
testis	UBERON:0000473	88.74	gold quality
endometrium epithelium	UBERON:0004811	88.42	gold quality
trabecular bone tissue	UBERON:0002483	87.87	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	87.57	gold quality
bone marrow cell	CL:0002092	86.29	gold quality
tongue squamous epithelium	UBERON:0006919	84.85	gold quality
esophagus squamous epithelium	UBERON:0006920	83.93	gold quality
thymus	UBERON:0002370	83.84	gold quality
mucosa of transverse colon	UBERON:0004991	82.97	gold quality
gingival epithelium	UBERON:0001949	82.72	silver quality
lower esophagus mucosa	UBERON:0035834	81.40	gold quality
rectum	UBERON:0001052	81.06	gold quality
epithelium of esophagus	UBERON:0001976	80.73	gold quality
vermiform appendix	UBERON:0001154	80.61	gold quality
squamous epithelium	UBERON:0006914	80.43	gold quality
stromal cell of endometrium	CL:0002255	79.55	gold quality
tibia	UBERON:0000979	79.20	gold quality
gingiva	UBERON:0001828	79.11	silver quality
hair follicle	UBERON:0002073	78.64	silver quality
esophagus mucosa	UBERON:0002469	77.89	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-GEOD-99795	yes	296.52
E-ANND-3	yes	5.99

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CDK5RAP2, FOXM1, MYC, TP53, ZNF143

miRNA regulators (miRDB)

30 targeting BUB1B, 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-4795-3P	100.00	74.62	4024
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-4668-5P	99.79	70.58	3782
HSA-MIR-4719	99.73	72.10	3329
HSA-MIR-1827	99.63	68.57	3265
HSA-MIR-548AV-5P	99.60	70.84	2107
HSA-MIR-548K	99.60	70.84	2107
HSA-MIR-4276	99.56	67.66	2514
HSA-MIR-3153	99.55	67.59	2337
HSA-MIR-3120-3P	99.54	70.28	2669
HSA-MIR-486-5P	99.51	70.39	707
HSA-MIR-4677-3P	99.49	67.91	1246
HSA-MIR-8054	99.48	70.81	2084
HSA-MIR-5009-3P	99.45	69.43	1341
HSA-MIR-4506	99.34	67.47	526
HSA-MIR-3925-5P	99.21	67.90	1466
HSA-MIR-412-3P	98.86	66.89	712
HSA-MIR-6754-3P	98.84	66.60	889
HSA-MIR-3922-5P	98.77	66.53	1059
HSA-MIR-5094	98.63	67.11	1062
HSA-MIR-6837-3P	98.42	66.71	1149
HSA-MIR-4773	98.35	67.30	1710
HSA-MIR-5691	98.23	67.02	1335
HSA-MIR-6805-3P	98.23	67.02	1334
HSA-MIR-676-3P	97.86	65.70	668
HSA-MIR-3074-3P	97.83	67.26	922
HSA-MIR-22-5P	97.67	68.92	1355

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map DepMap (CRISPR cell-line fitness): dependent in 98.7% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 40)

• Sequence alterations of mitotic checkpoint genes, hBUB1 and hBUBR1, were examined, and their gene transcripts were quantified using on-line, real-time quantitative reverse transcription-PCR in surgically resected human colorectal cancers (PMID:11782350)
• As part of a common complex in checkpoint-activated cells, BubR1 monitors different spindle events compared to Bub1 and integrates different signals into a single signal that is then relayed to the downstream cell cycle machinery. (PMID:11792804)
• BubR1 and Mad2 act cooperatively to prevent premature separation of sister chromatids by directly inhibiting the anaphase-promoting complex (PMID:11907259)
• mitotic checkpoint kinases BubR1 and BuB1, by binding to beta-adaptins, may play novel roles in the regulation of vesicular intracellular traffic (PMID:12419313)
• we identified the mitotic checkpoint protein BubR1 as a novel binding partner of BCSG1 (PMID:14576821)
• the control of hBubR1 protein level is an important factor in the acquisition of preneoplastic polyploidy (PMID:14706340)
• Taken together, our study suggests that Plk3 and Aurora A kinases may lie in the same regulatory pathway and that Plk3 and Aurora A as well as BubR1 may play an important role in polyploidization and megakaryocytic differentiation. (PMID:15190214)
• n five families with mosaic variegated aneuploidy, including two with embryonal rhabdomyosarcoma, we identified truncating and missense mutations of BUB1B, which encodes BUBR1, a key protein in the mitotic spindle checkpoint. (PMID:15475955)
• BubR1 links regulation of chromosome-spindle attachment to mitotic checkpoint signalling. (PMID:15592459)
• Microtubule capture by CENPE silences BubR1-dependent mitotic checkpoint signaling. (PMID:16144904)
• These results are potentially the first to link the control of the stability of a key mitotic checkpoint protein to caspase activation (PMID:16227576)
• Monoallelic BUB1B mutations and defective mitotic-spindle checkpoint is associated with premature chromatid separation syndrome (PMID:16411201)
• Tumors with BUBR1 overexpression were associated with chromosomal instability, DNA aneuploidy, and centrosome amplification. (PMID:17350465)
• Plk1 facilitates chromosome alignment during prometaphase through BubR1. (PMID:17376779)
• Differential regulation of BubR1 expression is associated with changes in BubR1 promoter hypermethylation patterns, but not with promoter polymorphisms. (PMID:17464181)
• Identification of promoter regions that are involved in the transcriptional regulation of the BUB1 gene. (PMID:17478512)
• BUB1B mRNA levels but not MAD2L1 levels correlate with intrachromosomal insttability in ductal breast carcinomas. (PMID:17498870)
• Aberrant exopressioni of BUB1B correlates with progression of prostate carcinoma. (PMID:17676298)
• Combined BubR1 protein down-regulation and RASSF1A hypermethylation might be implicated in the formation of chromosomal changes found in Wilms tumors. (PMID:18286482)
• These results suggest that BubR1 links DNA damage to kinetochore-associated spindle assembly checkpoint function. (PMID:18440313)
• domain amphiphilicity is of higher importance than amino acid sequence specificity in the determination of protein adsorption and interfacial activity (PMID:18547097)
• HsMAD2 and BubR1 were significantly higher in cancer tissue than in adjacent normal tissue (P < 0.01). Tumoral hsMAD2 and BubR1 were significantly decreased after radiochemotherapy (PMID:18691855)
• Significant reduction of BUB1B level is detected in aneuploid compared to diploid colorectal cancers. (PMID:18699967)
• Ajuba is a microtubule-associated protein that collaborates with Aurora B and BUBR1 at the metaphase-anaphase transition and this may be important to ensure proper chromosome segregation. (PMID:18710370)
• the function of BUBR1 protein in the spindle checkpoint is remarkably dosage-dependent, and the biological consequences of BUB1B expression reduction on premature chromatid separation and aneuploidy depend on the residual amount of BUBR1 (PMID:18932004)
• Mps1 is a major but not the exclusive kinase that specifies BubR1 phosphorylation in vivo. (PMID:19015317)
• BubR1 competes with Cdc20 for binding to securin. Interaction of BubR1 and securin is increased by the depletion of Cdc20. Regulation of BubR1 may generate an anaphase-inhibitory signal through the Cdc20-independent interaction of BubR1 with securin. (PMID:19117984)
• TAp73 regulates the spindle assembly checkpoint by modulating BubR1 activity. (PMID:19139399)
• Combined expression of BUB1B and PINK1 was the best predictor of overall survival in malignant adrenal cortex neoplasms. (PMID:19139432)
• Results support a model in which immobilized Mad1/Mad2 at kinetochores provides a template for initial assembly of Mad2 bound to Cdc20 that is then converted to a final mitotic checkpoint inhibitor with Cdc20 bound to BubR1. (PMID:19154722)
• The acetylation status of BubR1 is a molecular switch that converts BubR1 from an inhibitor to a substrate of the APC/C complex, thus providing an efficient way to modulate APC/C activity and mitotic timing. (PMID:19407811)
• The reduction of Bub1 spindle checkpoint protein levels during the G2 phase causes accelerated mitotic entry. (PMID:19411850)
• Results unravel a crucial role of BubR1 in preventing centrosome reduplication through negative regulation of Plk1 in interphase cells. (PMID:19503101)
• Data show that wt-p53 can suppress excessive replication of centrosomes that may contribute to the upregulation of Gadd45a and BubR1 protein expression as well as the downregulation of Aurora A protein expression. (PMID:19550118)
• BubR1, but not Aurora A, is a prognostic marker for recurrence-free survival rates in epithelial ovarian cancers. (PMID:19603021)
• BubR1 depletion in human adipose-derived mesenchymal stem cells precedes loss of the differentiation potential and induction of replicative senescence. (PMID:19745606)
• suggested to be one of the contributing factors involved in the pathogenesis of oral squamous cell carcinoma (PMID:19926498)
• high expression of BUBR1 may be one of causative factors for the induction of DNA aneuploidy and progression of gastric cancer. (PMID:20132214)
• BubR1 expression is a novel and strong prognostic factor in tonsillar carcinomas. (PMID:20146332)
• Results suggest that LSD1 plays a role in chromosomal segregation during mitosis partially through transcriptional regulation of BUBR1 and MAD2. (PMID:20189264)

Cross-species orthologs

8 orthologs

Organism	Symbol	Gene ID
danio_rerio	bub1bb	ENSDARG00000074927
danio_rerio	bub1ba	ENSDARG00000078825
mus_musculus	Bub1b	ENSMUSG00000040084
rattus_norvegicus	Bub1b	ENSRNOG00000007906
drosophila_melanogaster	Bub1	FBGN0031696
drosophila_melanogaster	BubR1	FBGN0263855
caenorhabditis_elegans	bub-1	WBGENE00000275
caenorhabditis_elegans	san-1	WBGENE00004721

Paralogs (1): BUB1 (ENSG00000169679)

Protein

Protein identifiers

Mitotic checkpoint serine/threonine-protein kinase BUB1 beta — O60566 (reviewed: O60566)

Alternative names: MAD3/BUB1-related protein kinase, Mitotic checkpoint kinase MAD3L, Protein SSK1

All UniProt accessions (3): O60566, H0YMK5, H0YN44

UniProt curated annotations — full annotation on UniProt →

Function. Essential component of the mitotic checkpoint. Required for normal mitosis progression. The mitotic checkpoint delays anaphase until all chromosomes are properly attached to the mitotic spindle. One of its checkpoint functions is to inhibit the activity of the anaphase-promoting complex/cyclosome (APC/C) by blocking the binding of CDC20 to APC/C, independently of its kinase activity. The other is to monitor kinetochore activities that depend on the kinetochore motor CENPE. Required for kinetochore localization of CENPE. Negatively regulates PLK1 activity in interphase cells and suppresses centrosome amplification. Also implicated in triggering apoptosis in polyploid cells that exit aberrantly from mitotic arrest. May play a role for tumor suppression.

Subunit / interactions. Interacts with CENPE. Interacts with PLK1. Part of a complex containing BUB3, CDC20 and BUB1B. Interacts with anaphase-promoting complex/cyclosome (APC/C). Interacts with KNL1. Interacts with KAT2B. Interacts with RIPK3. Interacts with the closed conformation form of MAD2L1.

Subcellular location. Cytoplasm. Nucleus. Chromosome. Centromere. Kinetochore. Cytoskeleton. Microtubule organizing center. Centrosome.

Tissue specificity. Highly expressed in thymus followed by spleen. Preferentially expressed in tissues with a high mitotic index.

Post-translational modifications. Proteolytically cleaved by caspase-3 in a cell cycle specific manner. The cleavage might be involved in the durability of the cell cycle delay. Caspase-3 cleavage is associated with abrogation of the mitotic checkpoint. The major site of cleavage is at Asp-610. Acetylation at Lys-250 regulates its degradation and timing in anaphase entry. Ubiquitinated. Degraded by the proteasome. Ubiquitinated by UBR5, promoting disassembly of the mitotic checkpoint complex from the APC/C complex. Sumoylated with SUMO2 and SUMO3. The sumoylation mediates the association with CENPE at the kinetochore. Autophosphorylated in vitro. Intramolecular autophosphorylation is stimulated by CENPE. Phosphorylated during mitosis and hyperphosphorylated in mitotically arrested cells. Phosphorylation at Ser-670 and Ser-1043 occurs at kinetochores upon mitotic entry with dephosphorylation at the onset of anaphase.

Disease relevance. Defects in BUB1B are associated with tumor formation. Premature chromatid separation trait (PCS) [MIM:176430] Consists of separate and splayed chromatids with discernible centromeres and involves all or most chromosomes of a metaphase. It is found in up to 2% of metaphases in cultured lymphocytes from approximately 40% of normal individuals. When PCS is present in 5% or more of cells, it is known as the heterozygous PCS trait and has no obvious phenotypic effect, although some have reported decreased fertility. Inheritance is autosomal dominant. The disease is caused by variants affecting the gene represented in this entry. Mosaic variegated aneuploidy syndrome 1 (MVA1) [MIM:257300] A severe developmental disorder characterized by mosaic aneuploidies, predominantly trisomies and monosomies, involving multiple different chromosomes and tissues. Affected individuals typically present with severe intrauterine growth retardation and microcephaly. Eye anomalies, mild dysmorphism, variable developmental delay, and a broad spectrum of additional congenital abnormalities and medical conditions may also occur. The risk of malignancy is high, with rhabdomyosarcoma, Wilms tumor and leukemia reported in several cases. The disease is caused by variants affecting the gene represented in this entry. MVA1 is caused by biallelic mutations in the BUB1B gene.

Activity regulation. Kinase activity stimulated by CENPE.

Domain organisation. The D-box targets the protein for rapid degradation by ubiquitin-dependent proteolysis during the transition from mitosis to interphase. The BUB1 N-terminal domain directs kinetochore localization and binding to BUB3.

Induction. Induced during mitosis.

Similarity. Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. BUB1 subfamily.

Isoforms (3)

UniProt ID	Names	Canonical?
O60566-1	1	yes
O60566-2	2
O60566-3	3

RefSeq proteins (1): NP_001202* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR011009	Kinase-like_dom_sf	Homologous_superfamily
IPR013212	Mad3/Bub1_I	Domain
IPR015661	Bub1/Mad3	Family

Pfam: PF08311

Enzyme classification (BRENDA):

• EC 2.7.11.1 — non-specific serine/threonine protein kinase (BRENDA: 71 organisms, 682 substrates, 228 inhibitors, 23 Km, 6 kcat entries)

Substrate kinetics (BRENDA)

8 substrates with measured Km, best-characterized 8. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
ATP	0.0007–0.64	11
KKRAARATSNVFA	0.013–0.045	3
PAH1 PHOSPHATIDATE PHOSPHATASE	0.0002	2
RRRLSSLRA	0.0036–0.0037	2
GTP	0.46	1
KKRAARASSNVFA	0.02	1
LYS-LYS-PHE-ASN-ARG-THR-LEU-SER-VAL-ALA	0.0093	1
MYELIN BASIC PROTEIN	0.145	1

Catalyzed reactions (Rhea), 2 shown:

• L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + H(+) (RHEA:17989)
• L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] + ADP + H(+) (RHEA:46608)

UniProt features (65 total): sequence variant 13, modified residue 12, helix 10, mutagenesis site 7, splice variant 4, sequence conflict 4, region of interest 3, domain 2, binding site 2, site 2, turn 2, short sequence motif 2, chain 1, active site 1

Structure

Experimental structures (PDB)

9 structures.

PDB	Method	Resolution (Å)
2WVI	X-RAY DIFFRACTION	1.8
3SI5	X-RAY DIFFRACTION	2.2
5JJA	X-RAY DIFFRACTION	2.35
4GGD	X-RAY DIFFRACTION	2.44
5K6S	X-RAY DIFFRACTION	2.79
5SWF	X-RAY DIFFRACTION	2.82
6TLJ	ELECTRON MICROSCOPY	3.8
5LCW	ELECTRON MICROSCOPY	4.2
5KHU	ELECTRON MICROSCOPY	4.8

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O60566-F1	64.62	0.15

Functional residue map

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

Catalytic / active sites (3): 579–580 (cleavage; by caspase-3); 610–611 (cleavage; by caspase-3); 882 (proton acceptor)

Ligand- & substrate-binding residues (2): 795; 772–780

Post-translational modifications (12): 250, 367, 435, 543, 665, 670, 676, 697, 792, 1008, 1042, 1043

Mutagenesis-validated functional residues (7):

Position	Phenotype
159	loss of interaction with knl1.
175	loss of interaction with knl1.
579	abolishes the cleavage by caspase-3.
610	abolishes the cleavage by caspase-3.
620	induces chromosome congression defects and mitotic delay.
795	does not abolish the capacity to inhibit apc/cdc20.
795	inhibits kinase activity.

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: 680 (showing top): GOBP_CHROMOSOME_ORGANIZATION, MORF_DNMT1, MODULE_52, BORCZUK_MALIGNANT_MESOTHELIOMA_UP, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, HORIUCHI_WTAP_TARGETS_DN, KANG_DOXORUBICIN_RESISTANCE_UP, MORF_ESPL1, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, MORF_BUB1, GOBP_REGULATION_OF_NUCLEAR_DIVISION, CROONQUIST_NRAS_SIGNALING_DN, REACTOME_APC_CDC20_MEDIATED_DEGRADATION_OF_NEK2A, GOBP_CELL_CYCLE_PHASE_TRANSITION, MITSIADES_RESPONSE_TO_APLIDIN_DN

GO Biological Process (7): apoptotic process (GO:0006915), metaphase/anaphase transition of mitotic cell cycle (GO:0007091), mitotic spindle assembly checkpoint signaling (GO:0007094), cell division (GO:0051301), meiotic sister chromatid cohesion, centromeric (GO:0051754), protein localization to chromosome, centromeric region (GO:0071459), regulation of sister chromatid segregation (GO:0033045)

GO Molecular Function (8): protein kinase activity (GO:0004672), protein serine/threonine kinase activity (GO:0004674), ATP binding (GO:0005524), protein serine kinase activity (GO:0106310), nucleotide binding (GO:0000166), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740)

GO Cellular Component (14): kinetochore (GO:0000776), outer kinetochore (GO:0000940), nucleus (GO:0005634), anaphase-promoting complex (GO:0005680), cytoplasm (GO:0005737), centrosome (GO:0005813), spindle (GO:0005819), cytosol (GO:0005829), mitotic checkpoint complex (GO:0033597), ciliary basal body (GO:0036064), perinuclear region of cytoplasm (GO:0048471), chromosome, centromeric region (GO:0000775), chromosome (GO:0005694), cytoskeleton (GO:0005856)

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
intracellular membraneless organelle	4
cellular anatomical structure	3
mitotic cell cycle	2
protein kinase activity	2
microtubule organizing center	2
cytoplasm	2
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
mitotic cell cycle phase transition	1
metaphase/anaphase transition of cell cycle	1
negative regulation of mitotic metaphase/anaphase transition	1
spindle assembly checkpoint signaling	1
mitotic spindle checkpoint signaling	1
cellular process	1
meiotic sister chromatid cohesion	1
centromeric sister chromatid cohesion	1
protein localization to chromosome	1
sister chromatid segregation	1
regulation of chromosome organization	1
regulation of chromosome segregation	1
kinase activity	1
phosphotransferase activity, alcohol group as acceptor	1
catalytic activity, acting on a protein	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
binding	1
transferase activity, transferring phosphorus-containing groups	1
catalytic activity	1
condensed chromosome, centromeric region	1
supramolecular complex	1
kinetochore	1
protein-containing complex	1
intracellular membrane-bounded organelle	1
nuclear ubiquitin ligase complex	1
cullin-RING ubiquitin ligase complex	1
intracellular anatomical structure	1
centriole	1

Protein interactions and networks

STRING

3335 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
BUB1B	BUB3	O43684	999
BUB1B	CDC20	Q12834	999
BUB1B	CENPE	Q02224	998
BUB1B	CDK1	P06493	995
BUB1B	AURKB	Q96GD4	993
BUB1B	BUB1	O43683	989
BUB1B	MAD2L1	Q13257	988
BUB1B	KNL1	Q8NG31	985
BUB1B	CCNB1	P14635	967
BUB1B	PLK1	P53350	933
BUB1B	PTTG1	O95997	923
BUB1B	TTK	P33981	919
BUB1B	CENPF	P49454	919
BUB1B	CCNB2	O95067	915
BUB1B	CCNA2	P20248	904

IntAct

186 interactions, top by confidence:

A	B	Type	Score
BUB1B	CDC20	psi-mi:“MI:0915”(physical association)	0.980
CDC20	BUB1B	psi-mi:“MI:0914”(association)	0.980
BUB1B	CDC20	psi-mi:“MI:0914”(association)	0.980
CDC20	BUB1B	psi-mi:“MI:0915”(physical association)	0.980
CDC20	BUB1B	psi-mi:“MI:2364”(proximity)	0.980
BUB1B	CDC20	psi-mi:“MI:0407”(direct interaction)	0.980
BUB3	BUB1B	psi-mi:“MI:0915”(physical association)	0.930
BUB1B	BUB3	psi-mi:“MI:0914”(association)	0.930

BioGRID (521): BUB3 (Affinity Capture-Western), BUB1B (Reconstituted Complex), BUB3 (Reconstituted Complex), CDC20 (Reconstituted Complex), CDC27 (Reconstituted Complex), BUB1B (Reconstituted Complex), CDC20 (Affinity Capture-Western), BUB1B (Affinity Capture-Western), BUB1B (Affinity Capture-Western), BUB1B (Affinity Capture-Western), ANAPC1 (Affinity Capture-MS), ANAPC2 (Affinity Capture-MS), BAG2 (Affinity Capture-MS), BUB1 (Affinity Capture-MS), BUB3 (Affinity Capture-MS)

ESM2 similar proteins: A0MZ66, A2APB8, A4IG59, A4IH24, A5A6J4, A6H6Z7, B0BM24, E2RYF8, E7F7X0, F4I2H7, O13024, O43683, O60566, O95990, P13505, P14317, P92204, Q0IHP2, Q28E45, Q2KI00, Q32N93, Q3B820, Q3TGF2, Q5EAW4, Q5NVP3, Q5RAF2, Q5U4F3, Q62736, Q659C4, Q66KE9, Q68FU8, Q6AY14, Q6DDV8, Q6NUF4, Q6PKG0, Q78TU8, Q7L590, Q84ZT9, Q8CB59, Q8CH02

Diamond homologs: F4IVI0, O08901, O22806, O43683, O60566, P47074, Q54CV5, Q9Z1S0, O59767, O94751, P41695

SIGNOR signaling

14 interactions.

A	Effect	B	Mechanism
PLK1	up-regulates	BUB1B	phosphorylation
CDK1	up-regulates	BUB1B	phosphorylation
KNL1	up-regulates	BUB1B	binding
BUB1B	up-regulates	Mitotic_checkpoint
CDK5RAP2	“up-regulates quantity by expression”	BUB1B	“transcriptional regulation”
BUB1B	“form complex”	MCC	binding
BUB1B	“up-regulates activity”	APC	phosphorylation
BUB1B	“up-regulates activity”	CDC20	phosphorylation
CHEK1	“up-regulates activity”	BUB1B	phosphorylation
CENPE	“up-regulates activity”	BUB1B	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 109 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	13	107.1×	2e-23
Inactivation of APC/C via direct inhibition of the APC/C complex	13	87.6×	5e-22
Conversion from APC/C:Cdc20 to APC/C:Cdh1 in late anaphase	12	80.9×	8e-20
APC-Cdc20 mediated degradation of Nek2A	14	76.9×	2e-22
APC:Cdc20 mediated degradation of cell cycle proteins prior to satisfation of the cell cycle checkpoint	14	76.9×	2e-22
Activation of APC/C and APC/C:Cdc20 mediated degradation of mitotic proteins	14	74.2×	3e-22
Aberrant regulation of mitotic exit in cancer due to RB1 defects	11	74.2×	1e-17
APC/C:Cdc20 mediated degradation of Cyclin B	12	71.2×	6e-19

GO biological processes:

GO term	Partners	Fold	FDR
protein branched polyubiquitination	11	101.8×	2e-18
regulation of meiotic cell cycle	12	101.0×	7e-20
anaphase-promoting complex-dependent catabolic process	12	92.6×	2e-19
mitotic spindle assembly checkpoint signaling	9	55.6×	4e-12
protein K11-linked ubiquitination	12	51.7×	5e-16
attachment of spindle microtubules to kinetochore	5	51.4×	2e-06
regulation of mitotic cell cycle	14	37.0×	1e-16
mitotic sister chromatid segregation	7	37.0×	5e-08

Disease & clinical

Clinical variants and AI predictions

ClinVar

2397 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	60
Likely pathogenic	16
Uncertain significance	1432
Likely benign	752
Benign	63

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1070955	NM_001211.6(BUB1B):c.799C>T (p.Gln267Ter)	Pathogenic
1073991	NM_001211.6(BUB1B):c.422dup (p.Tyr141Ter)	Pathogenic
1074988	NM_001211.6(BUB1B):c.693_694insTT (p.Ser232fs)	Pathogenic
1299567	NM_001211.6(BUB1B):c.2636dup (p.His880fs)	Pathogenic
1320272	NM_001211.6(BUB1B):c.1045del (p.Arg349fs)	Pathogenic
1325384	NM_001211.6(BUB1B):c.2328dup (p.Asp777fs)	Pathogenic
1325385	NM_001211.6(BUB1B):c.1672del (p.Ala559fs)	Pathogenic
1367214	NM_001211.6(BUB1B):c.2876T>G (p.Leu959Ter)	Pathogenic
1386253	NM_001211.6(BUB1B):c.169C>T (p.Gln57Ter)	Pathogenic
1392551	NM_001211.6(BUB1B):c.2334C>G (p.Tyr778Ter)	Pathogenic
1398305	NM_001211.6(BUB1B):c.1298T>A (p.Leu433Ter)	Pathogenic
1405980	NM_001211.6(BUB1B):c.1466_1470dup (p.Gly491fs)	Pathogenic
1408436	NM_001211.6(BUB1B):c.1441C>T (p.Gln481Ter)	Pathogenic
1443723	NM_001211.6(BUB1B):c.1906del (p.Glu636fs)	Pathogenic
1450254	NM_001211.6(BUB1B):c.199C>T (p.Arg67Ter)	Pathogenic
1452898	NM_001211.6(BUB1B):c.877C>T (p.Gln293Ter)	Pathogenic
1453887	NM_001211.6(BUB1B):c.2210del (p.Glu736_Leu737insTer)	Pathogenic
1946449	NM_001211.6(BUB1B):c.310del (p.Arg104fs)	Pathogenic
1980347	NM_001211.6(BUB1B):c.2848C>T (p.Gln950Ter)	Pathogenic
2034835	NM_001211.6(BUB1B):c.1141del (p.Arg381fs)	Pathogenic
2141736	NM_001211.6(BUB1B):c.1663C>T (p.Arg555Ter)	Pathogenic
2152812	NM_001211.6(BUB1B):c.871del (p.Thr291fs)	Pathogenic
2187691	NM_001211.6(BUB1B):c.1378C>T (p.Gln460Ter)	Pathogenic
2196645	NM_001211.6(BUB1B):c.1743del (p.Phe581fs)	Pathogenic
2202424	NM_001211.6(BUB1B):c.2153del (p.Thr718fs)	Pathogenic
2423976	NC_000015.9:g.(?40453422)(40457417_?)del	Pathogenic
2697026	NM_001211.6(BUB1B):c.94_95insGCTCTCCCTCTCCCTCTCCCGCTCCCGGGGGGGGGGGGGGGCGGGGGGGGGGGGGGGGGGGGGGGGGGGGGCGGGGGGGGGGGCGNNNNNNNNNNAAAAAAAAAAAAAAAAAAAAAAAGAAAATGTACAACCTT (p.Leu32fs)	Pathogenic
2729407	NM_001211.6(BUB1B):c.1313_1317del (p.Lys438fs)	Pathogenic
2750610	NM_001211.6(BUB1B):c.2298C>G (p.Tyr766Ter)	Pathogenic
2756659	NM_001211.6(BUB1B):c.897dup (p.Met300fs)	Pathogenic

SpliceAI

3747 predictions. Top by Δscore:

Variant	Effect	Δscore
15:40165051:A:AG	acceptor_gain	1.0000
15:40165052:G:GG	acceptor_gain	1.0000
15:40165209:GC:G	donor_gain	1.0000
15:40170536:GGT:G	acceptor_gain	1.0000
15:40170677:AATTA:A	donor_gain	1.0000
15:40170678:ATTA:A	donor_gain	1.0000
15:40170679:TTA:T	donor_gain	1.0000
15:40170680:TA:T	donor_gain	1.0000
15:40170682:G:GG	donor_gain	1.0000
15:40183707:A:AG	acceptor_gain	1.0000
15:40183709:TTTA:T	acceptor_loss	1.0000
15:40183710:TTA:T	acceptor_loss	1.0000
15:40183711:TA:T	acceptor_loss	1.0000
15:40183712:A:AC	acceptor_loss	1.0000
15:40183712:A:AG	acceptor_gain	1.0000
15:40183713:G:GT	acceptor_gain	1.0000
15:40183713:GA:G	acceptor_gain	1.0000
15:40183713:GAC:G	acceptor_gain	1.0000
15:40183713:GACA:G	acceptor_gain	1.0000
15:40183713:GACAA:G	acceptor_gain	1.0000
15:40183880:AAGG:A	donor_gain	1.0000
15:40183881:AGG:A	donor_gain	1.0000
15:40183882:GG:G	donor_gain	1.0000
15:40183882:GGG:G	donor_gain	1.0000
15:40183882:GGGT:G	donor_loss	1.0000
15:40183883:GG:G	donor_gain	1.0000
15:40183883:GGT:G	donor_loss	1.0000
15:40183884:G:GG	donor_gain	1.0000
15:40183884:GTA:G	donor_loss	1.0000
15:40183885:T:G	donor_loss	1.0000

AlphaMissense

6940 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
15:40176567:G:C	A159P	0.997
15:40170114:T:A	W78R	0.996
15:40170114:T:C	W78R	0.996
15:40165095:A:C	K26N	0.995
15:40165095:A:T	K26N	0.995
15:40196735:G:C	A417P	0.995
15:40165081:T:A	W22R	0.994
15:40165081:T:C	W22R	0.994
15:40196733:G:C	R416P	0.994
15:40217560:A:C	S915R	0.994
15:40217562:T:A	S915R	0.994
15:40217562:T:G	S915R	0.994
15:40176624:G:T	G178W	0.992
15:40212520:T:A	W803R	0.992
15:40212520:T:C	W803R	0.992
15:40165094:A:T	K26I	0.991
15:40170547:T:A	W84R	0.991
15:40170547:T:C	W84R	0.991
15:40206457:A:C	S670R	0.991
15:40208637:C:A	S670R	0.991
15:40208637:C:G	S670R	0.991
15:40165083:G:C	W22C	0.990
15:40165083:G:T	W22C	0.990
15:40170610:G:C	A105P	0.990
15:40176624:G:A	G178R	0.990
15:40176624:G:C	G178R	0.990
15:40213432:T:A	V879D	0.990
15:40176603:G:C	A171P	0.989
15:40183719:T:C	F196S	0.989
15:40176658:T:C	L189P	0.988

dbSNP variants (sampled 300 via entrez): RS1000024394 (15:40159770 G>A), RS1000072403 (15:40199215 A>G), RS1000120699 (15:40179966 C>A), RS1000190033 (15:40161886 G>A), RS1000270614 (15:40203813 A>C), RS1000283837 (15:40162041 G>C), RS1000295627 (15:40205751 T>G), RS1000346553 (15:40192841 G>A,T), RS1000365175 (15:40212420 C>G,T), RS1000395694 (15:40186726 T>A), RS1000460777 (15:40167050 G>T), RS1000468594 (15:40167755 AGTT>A), RS1000471639 (15:40211986 A>G), RS1000475967 (15:40174155 A>C), RS1000477001 (15:40210451 T>C,G)

Disease associations

OMIM: gene MIM:602860 | disease phenotypes: MIM:257300, MIM:114500, MIM:176430, MIM:167000

GenCC curated gene-disease

Disease	Classification	Inheritance
mosaic variegated aneuploidy syndrome 1	Definitive	Autosomal recessive
rhabdomyosarcoma	Moderate	Autosomal recessive
primary ovarian failure	Moderate	Autosomal recessive
mosaic variegated aneuploidy syndrome	Supportive	Autosomal dominant

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
mosaic variegated aneuploidy syndrome 1	Definitive	AR

Mondo (10): mosaic variegated aneuploidy syndrome 1 (MONDO:0009759), colorectal cancer (MONDO:0005575), premature chromatid separation trait (MONDO:0008304), mosaic variegated aneuploidy syndrome (MONDO:0000141), cerebral palsy (MONDO:0006497), colon carcinoma (MONDO:0002032), ovarian cancer (MONDO:0008170), microcephaly (MONDO:0001149), rhabdomyosarcoma (MONDO:0005212), primary ovarian failure (MONDO:0005387)

Orphanet (3): Mosaic variegated aneuploidy syndrome (Orphanet:1052), Rare ovarian cancer (Orphanet:213500), NON RARE IN EUROPE: Colorectal cancer (Orphanet:466667)

HPO phenotypes

112 total (30 of 112 shown, HPO-id order):

HPO	Term
HP:0000003	Multicystic kidney dysplasia
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000028	Cryptorchidism
HP:0000047	Hypospadias
HP:0000048	Bifid scrotum
HP:0000054	Micropenis
HP:0000062	Ambiguous genitalia
HP:0000107	Renal cyst
HP:0000175	Cleft palate
HP:0000207	Triangular mouth
HP:0000238	Hydrocephalus
HP:0000248	Brachycephaly
HP:0000252	Microcephaly
HP:0000272	Malar flattening
HP:0000286	Epicanthus
HP:0000316	Hypertelorism
HP:0000325	Triangular face
HP:0000340	Sloping forehead
HP:0000343	Long philtrum
HP:0000347	Micrognathia
HP:0000348	High forehead
HP:0000358	Posteriorly rotated ears
HP:0000365	Hearing impairment
HP:0000369	Low-set ears
HP:0000445	Wide nose
HP:0000457	Depressed nasal ridge
HP:0000463	Anteverted nares
HP:0000470	Short neck
HP:0000478	Abnormality of the eye

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST002299_16	Chronic lymphocytic leukemia	2.000000e-06
GCST004146_18	Chronic lymphocytic leukemia	7.000000e-19

MeSH disease descriptors (6)

Descriptor	Name	Tree numbers
D002547	Cerebral Palsy	C10.228.140.140.254
D008831	Microcephaly	C05.660.207.620; C10.500.507.400.500; C16.131.621.207.620; C16.131.666.507.400.500
D010051	Ovarian Neoplasms	C04.588.322.455; C12.050.351.500.056.630.705; C12.050.351.937.418.685; C12.100.250.056.630.705; C12.900.418.685; C19.344.410; C19.391.630.705
D016649	Primary Ovarian Insufficiency	C12.050.351.500.056.630.750; C12.100.250.056.630.750; C19.391.630.750
D012208	Rhabdomyosarcoma	C04.557.450.590.550.660; C04.557.450.795.550.660
C536987	Mosaic variegated aneuploidy syndrome (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4295998 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 8,551 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL2403108	CERITINIB	4	8,551

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

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — Bub family

ChEMBL bioactivities

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

pChembl	Type	Value	Unit	Molecule
5.01	IC50	9670	nM	CHEMBL6142128

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects localization, decreases expression, increases expression	6
Doxorubicin	affects response to substance, decreases expression	4
Cyclosporine	decreases expression, increases methylation	4
sodium arsenite	decreases expression, increases expression	3
Resveratrol	decreases expression, affects cotreatment, increases expression	3
Cisplatin	affects expression, affects cotreatment, decreases expression, decreases reaction	3
Quercetin	decreases expression, increases expression	3
chromium hexavalent ion	decreases expression, decreases reaction, increases reaction, increases abundance	2
Decitabine	affects expression, affects binding, decreases reaction	2
Arsenic Trioxide	affects cotreatment, increases expression, increases phosphorylation, increases reaction, affects binding	2
Acetaminophen	decreases expression, increases expression	2
Benzo(a)pyrene	decreases expression	2
Copper	affects binding, decreases expression	2
Dibutyl Phthalate	decreases expression, increases expression, decreases reaction	2
Estradiol	increases expression	2
Fluorouracil	decreases expression	2
Nickel	increases expression	2
Polychlorinated Biphenyls	affects expression, increases expression	2
Rotenone	affects localization, increases expression	2
Valproic Acid	decreases expression	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	2
Paclitaxel	affects binding, affects cotreatment, increases reaction, increases expression, affects response to substance	2
Genistein	affects expression, increases expression	2
aristolochic acid I	decreases expression	1
SP2509	decreases expression	1
FR900359	decreases phosphorylation	1
propionaldehyde	decreases expression	1
pirinixic acid	decreases expression, increases activity, affects binding	1
deoxynivalenol	increases expression	1
geraniol	decreases expression	1

ChEMBL screening assays

12 unique, capped per target: 12 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4254597	Binding	Induction of BubR1 hyperphosphorylation in human HeLa cells by Western blot analysis	Design, synthesis, biological evaluation and cocrystal structures with tubulin of chiral β-lactam bridged combretastatin A-4 analogues as potent antitumor agents. — Eur J Med Chem

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_EF99	GM21284	Transformed cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00339118	PHASE4	UNKNOWN	EpSSG (European Soft Tissue Sarcoma Study Group) Protocol for Non-Metastatic Rhabdomyosarcoma in Children
NCT04854018	PHASE4	COMPLETED	Indo-cyanine Green (ICG) in Paediatric Oncology MIS
NCT00417066	PHASE4	COMPLETED	Flexible GnRH Antagonist vs Flare up GnRH Agonist Protocol in Poor Responders
NCT00732693	PHASE4	COMPLETED	Evaluation of Physiologic and Standard Sex Steroid Replacement Regimens in Women With Premature Ovarian Failure
NCT00837616	PHASE4	COMPLETED	Estrogen Dosing in Turner Syndrome: Pharmacology and Metabolism
NCT01853501	PHASE4	UNKNOWN	Effects of ADSC Therapy in Women With POF
NCT02783937	PHASE4	COMPLETED	Filgrastim for Premature Ovarian Insufficiency
NCT03535480	PHASE4	UNKNOWN	Autologous Bone Marrow Stem Cell Ovarian Transplantation to Restore Ovarian Function in Premature Ovarian Failure
NCT00114829	PHASE4	UNKNOWN	Preoperative Assessment of Colon Tumor
NCT00114842	PHASE4	COMPLETED	Magnetic Resonance (MR) Colonography With Fecal Tagging
NCT00114946	PHASE4	TERMINATED	A Study to Compare Two Avastin-Based Treatment Regimens for the Treatment of Metastatic Colorectal Cancer
NCT00122720	PHASE4	COMPLETED	The Effect of Darbepoetin Upon Rehabilitation for Colorectal Cancer Surgery
NCT00129870	PHASE4	TERMINATED	CONCEPT: Comparison of Oxaliplatin vs Conventional Methods With Calcium/Magnesium in First-Line Metastatic Colorectal Cancer
NCT00138060	PHASE4	COMPLETED	Toxicity/Benefit Ratio Optimization of Chemotherapy in Colorectal Cancer (CRC) Patients by Determination of Individual Genotypic Determinants
NCT00216424	PHASE4	TERMINATED	Capecitabine (Xeloda) and Radiation for Patients With Rectosigmoid Carcinoma
NCT00327093	PHASE4	TERMINATED	Elaboration of a Model for Predicting Efficacy of Monoclonal Antibodies (Cetuximab and Bevacizumab) in Patients With Colorectal Cancer and Liver Metastases
NCT00332943	PHASE4	COMPLETED	MR Colonography With Fecal Tagging. Barium vs. BariumFerumoxsil
NCT00441311	PHASE4	COMPLETED	Dissemination of Colorectal Cancer Screening to Primary Care Physicians
NCT00460837	PHASE4	WITHDRAWN	Comparison of Bowel Preparation in Virtual Colonoscopy (VC) - Patient Experience
NCT00473980	PHASE4	COMPLETED	Preoperative Non-steroidal Anti-inflammatory Drugs(NSAID) to Colorectal Cancer Patients
NCT00488904	PHASE4	COMPLETED	Omega-3 Fatty Acids and Postoperative Complications After Colorectal Surgery
NCT00496678	PHASE4	COMPLETED	Trial of Patient Navigation-Activation
NCT00502671	PHASE4	COMPLETED	A Study of Xeloda (Capecitabine) as Adjuvant Monotherapy in Patients With Colon Cancer.
NCT00559676	PHASE4	COMPLETED	Study of Biomarkers in Patients Undergoing Chemotherapy for Metastatic Colorectal Cancer
NCT00577031	PHASE4	COMPLETED	OBELIX Study: A Study of Avastin (Bevacizumab) in Combination With XELOX in Patients With Metastatic Cancer of the Colon or Rectum.
NCT00626054	PHASE4	COMPLETED	Comparison of Two Methods of Administration of a PEG Solution
NCT00812864	PHASE4	COMPLETED	Pharmacokinetic Study of Capecitabine in Elderly Cancer Patient (≥ 75 Years)
NCT00868569	PHASE4	UNKNOWN	Transhepatic Arterial Chemotherapy (TAC) Versus Transcatheter Arterial Chemoembolization (TACE) Plus Folfox4 as the Treatment of Unresectable Liver Metastasis of Colorectal Cancer
NCT00868816	PHASE4	COMPLETED	Oxaliplatine Based Adjuvant Chemotherapy for Stage II/III Colorectal Cancer: 8 Cycles Versus 12 Cycles
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