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Nodes are publications, genes, proteins, variants, diseases, biological processes, drugs, evidence records and hypotheses of a research case. Solid lines are documented connections; dashed lines are hypotheses still under review. No connection is inferred from word co-occurrence.
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Cynthia J. Sieben, Karthik B. Jeganathan, Grace G. Nelson et al. · Journal of Clinical Investigation · 2019
pmcid PMC6934189 pmid 31738183 doi 10.1172/jci126863
Evidence-guided drug repurposing. Explore how two germline BUB1B variants raise separate RNA and protein questions in mosaic variegated aneuploidy, and which evidence could inform …
concerns Mosaic variegated aneuploidy syndrome 1 · concerns BUB1B · concerns L737* · concerns N1002K · includes Rescue of nonsense mutations by amlexanox in hum… · includes FDA historical Aphthasol label · and 30 more
BUB1 mitotic checkpoint serine/threonine kinase B (HGNC approved name). Located at 15q15.1.
concerns ← MVA · BUB1B · associated with Mosaic variegated aneuploidy syndrome 1 · encodes BUBR1 · investigates ← Rapamycin in human fibroblasts: BUB1B locus RNA … · affects ← L737* · affects ← N1002K
Mitotic checkpoint serine/threonine-protein kinase BUB1 beta (UniProt recommended name), 1050 amino acids.
encodes ← BUB1B · participates in Spindle assembly checkpoint · investigates ← BUBR1 functional controls: arrest duration
Premature stop codon at residue 737 of BUBR1 (p.Leu737Ter): an RNA availability and translation question.
concerns ← MVA · BUB1B · investigates ← L737* NMD-first: test truncated-protein function · investigates ← L737* readthrough: exact versus nearby contexts · affects BUB1B
Missense change in the kinase region of BUBR1 (p.Asn1002Lys): a protein stability and function question.
concerns ← MVA · BUB1B · investigates ← Arimoclomol: target engagement and exposure gap · investigates ← N1002K stabilization: equal-expression gate · affects BUB1B
Rare disorder of chromosome segregation; MONDO term "mosaic variegated aneuploidy syndrome 1".
concerns ← MVA · BUB1B · associated with ← BUB1B
mRNA surveillance pathway that degrades transcripts carrying premature stop codons. In this case: whether the L737* transcript is degraded.
investigates ← Amlexanox: context-dependent readthrough evidenc… · investigates ← L737* NMD-first: test truncated-protein function · investigates ← 704-drug NMD screen: reporter specificity
Suppression of a premature stop codon so translation continues; its efficiency depends on the exact sequence context.
investigates ← Amlexanox: context-dependent readthrough evidenc… · investigates ← L737* readthrough: exact versus nearby contexts · investigates ← Readthrough combinations: endogenous-protein tra…
Mitotic surveillance mechanism that delays anaphase until chromosomes attach to the spindle; BUBR1 is one of its components.
participates in ← BUBR1 · investigates ← BUBR1 functional controls: arrest duration
Audit topic: published immunotherapy results concern tumor control, which is not BUB1B disease rescue.
investigates ← Immunotherapy: disease rescue versus tumor contr…
Whether the N1002K protein is stable and functional; abundance alone does not answer it.
investigates ← N1002K stabilization: equal-expression gate
Readthrough combination reported in other-gene reporters; experimental branch, no exact-genotype rescue established.
investigates ← L737* readthrough: exact versus nearby contexts · investigates ← Readthrough combinations: endogenous-protein tra…
Readthrough / NMD-inhibition candidate with context-dependent published evidence; conditional in this case.
investigates ← Amlexanox: context-dependent readthrough evidenc…
HSF1 co-inducer audited for target engagement and exposure in relation to N1002K; gap documented.
investigates ← Arimoclomol: target engagement and exposure gap
Named in the 704-drug NMD screen reanalysis; response reporter-dependent, no functional BUBR1 rescue established.
investigates ← 704-drug NMD screen: reporter specificity
Reanalysed in public human fibroblast RNA data at the BUB1B locus; descriptive signal, not functional rescue.
investigates ← Rapamycin in human fibroblasts: BUB1B locus RNA …
Functional CFTR evidence supports investigating amlexanox, but negative NEFL rescue with neurite toxicity and context-dependent NMD responses prevent promotion to an established le…
includes ← MVA · BUB1B · cites Rescue of nonsense mutations by amlexanox in hum… · cites FDA historical Aphthasol label · cites Amlexanox: Readthrough Induction and Nonsense-Me… · cites Neurofilament Light Regulates Axon Caliber, Syna… · cites Molecular profiling of individual FDA-approved c… · and 4 more
No exact L737* measurement or exact six-flanking-base match in the 5,837-PTC table. Twelve nearest contexts have a median paired gentamicin increment of 0.0165 percentage points.
includes ← MVA · BUB1B · cites NanoLuc reporters identify COL4A5 nonsense mutat… · cites Genome-scale quantification and prediction of pa… · informs Research candidates stay conditional · informs Preserving RNA leaves the stop codon · investigates Gentamicin + mefloquine · and 2 more
No direct BUBR1 or N1002K rescue evidence was located in the audit. Heat-shock responses are context-dependent; arimoclomol is not promoted to lead candidate.
includes ← MVA · BUB1B · cites FDA — MIPLYFFA prescribing information (2024) · cites Induction of heat shock proteins in differentiat… · cites Quantitative Comparison of HSF1 Activators · informs Abundance is a starting point · investigates Arimoclomol · and 1 more
Genetic senescent-cell ablation delayed selected phenotypes in BubR1-deficient mice; uPAR CAR T benefits came from other mouse models. HER2 CAR T and nivolumab/ipilimumab show limi…
includes ← MVA · BUB1B · cites Prophylactic and long-lasting efficacy of senoly… · cites Clearance of p16Ink4a-positive senescent cells d… · cites Autologous HER2-specific CAR T cells after lymph… · cites Nivolumab in children and young adults with rela… · cites A Phase I/II Trial of Nivolumab plus Ipilimumab … · and 1 more
No exact-N1002K functional experiment was located. I909T/L1012P checkpoint rescue at matched abundance makes an abundance-limited mechanism plausible, but equally expressed B56-bin…
includes ← MVA · BUB1B · cites BubR1 allelic effects drive phenotypic heterogen… · cites Molecular Causes for BUBR1 Dysfunction in the Hu… · cites BUBR1 recruits PP2A via the B56 family of target… · informs Abundance is a starting point · investigates Protein stability · and 1 more
Montelukast has a published permutation q of 0.021150, but the response is reporter-dependent and confounded by non-NMD isoform changes. No hit establishes functional BUBR1 rescue.
includes ← MVA · BUB1B · cites Molecular profiling of individual FDA-approved c… · informs Research candidates stay conditional · investigates Montelukast · investigates Nonsense-mediated decay
A related 731X construct motivates testing whether L737* retains useful function when NMD is bypassed. The exact L737* experiment has not been performed.
includes ← MVA · BUB1B · cites Molecular Causes for BUBR1 Dysfunction in the Hu… · informs Preserving RNA leaves the stop codon · investigates Nonsense-mediated decay · investigates L737*
G418/ELX-02 with or without mefloquine were studied beyond reporters, including endogenous PKD1 protein and withdrawal measurements. This does not establish gentamicin-combination …
includes ← MVA · BUB1B · cites Translational readthrough therapy for ADPKD indu… · informs Preserving RNA leaves the stop codon · investigates Gentamicin + mefloquine · investigates Translational readthrough
Figure 4B source-data medians are 650 minutes for WT and 60 minutes for D137R. A control for checkpoint competence, not a drug-rescue result.
includes ← MVA · BUB1B · cites BubR1 TPR domain supports the mitotic checkpoint… · investigates Spindle assembly checkpoint · investigates BUBR1
The primary BUB1B-spanning feature has a Rap/Pro mean ratio of 0.585706 (41.43% lower); reduced-serum/Pro is 0.186191. Three nearly full-span features give the same direction. This…
includes ← MVA · BUB1B · cites Rapamycin reduces fibroblast proliferation witho… · investigates Rapamycin · investigates BUB1B
The synthetic fixture flags fewer raw error-positive divisions without a lower error rate per completed division. It does not measure sirolimus activity.
includes ← MVA · BUB1B
Saskia J.E. Suijkerbuijk, Maria H.J. van Osch, Frank L. Bos et al. · Cancer Research · 2010
includes ← MVA · BUB1B · cites ← L737* NMD-first: test truncated-protein function · cites ← N1002K stabilization: equal-expression gate
Jingrong Zhao, Zhelin Li, Ruchira Puri et al. · Molecular Therapy Nucleic Acids · 2022
includes ← MVA · BUB1B · cites ← Amlexanox: context-dependent readthrough evidenc… · cites ← 704-drug NMD screen: reporter specificity
Kara L. Davis, Elizabeth Fox, Emasenyie Isikwei et al. · Clinical Cancer Research · 2022
includes ← MVA · BUB1B · cites ← Immunotherapy: disease rescue versus tumor contr…
Nesrine Benslimane, Federica Miressi, Camille Loret et al. · Pharmaceuticals · 2023
includes ← MVA · BUB1B · cites ← Amlexanox: context-dependent readthrough evidenc…
Meenakshi Hegde, Shoba Navai, Christopher DeRenzo et al. · Nature Cancer · 2024
includes ← MVA · BUB1B · cites ← Immunotherapy: disease rescue versus tumor contr…
Cynthia J. Sieben, Karthik B. Jeganathan, Grace G. Nelson et al. · Journal of Clinical Investigation · 2019
includes ← MVA · BUB1B · cites ← N1002K stabilization: equal-expression gate
Peng Xu, Elizabeth A. Raetz, Mayumi Kitagawa et al. · Biology Open · 2013
includes ← MVA · BUB1B · cites ← N1002K stabilization: equal-expression gate
Mingzhe Zhang, Tingting Lei, Ying Wang et al. · Communications Biology · 2026
includes ← MVA · BUB1B · cites ← BUBR1 functional controls: arrest duration
Darren J. Baker, Tobias Wijshake, Tamar Tchkonia et al. · Nature · 2011
includes ← MVA · BUB1B · cites ← Immunotherapy: disease rescue versus tumor contr…
www.accessdata.fda.gov
includes ← MVA · BUB1B · cites ← Arimoclomol: target engagement and exposure gap
www.accessdata.fda.gov
includes ← MVA · BUB1B · cites ← Amlexanox: context-dependent readthrough evidenc…
Ignasi Toledano, Fran Supek, Ben Lehner · Nature Genetics · 2024
includes ← MVA · BUB1B · cites ← L737* readthrough: exact versus nearby contexts
Catherine A.S. Deane, Ian R. Brown · Cell Stress and Chaperones · 2016
includes ← MVA · BUB1B · cites ← Arimoclomol: target engagement and exposure gap
Kohei Omachi, Hirofumi Kai, Michel Roberge et al. · iScience · 2022
includes ← MVA · BUB1B · cites ← L737* readthrough: exact versus nearby contexts
Markus T. Sainio, Tiina Rasila, Svetlana M. Molchanova et al. · Frontiers in Cell and Developmental Biology · 2022
includes ← MVA · BUB1B · cites ← Amlexanox: context-dependent readthrough evidenc…
Kara L Davis, Elizabeth Fox, Melinda S Merchant et al. · The Lancet Oncology · 2020
includes ← MVA · BUB1B · cites ← Immunotherapy: disease rescue versus tumor contr…
Corina Amor, Inés Fernández-Maestre, Saria Chowdhury et al. · Nature Aging · 2024
includes ← MVA · BUB1B · cites ← Immunotherapy: disease rescue versus tumor contr…
Christoph Steurer, Sarah Kerschbaum, Christina Wegrostek et al. · Molecular Biotechnology · 2022
includes ← MVA · BUB1B · cites ← Arimoclomol: target engagement and exposure gap
Zoe E Gillespie, Kimberly MacKay, Michelle Sander et al. · Nucleus · 2015
includes ← MVA · BUB1B · cites ← Rapamycin in human fibroblasts: BUB1B locus RNA …
Sara Gonzalez-Hilarion, Terence Beghyn, Jieshuang Jia et al. · Orphanet Journal of Rare Diseases · 2012
includes ← MVA · BUB1B · cites ← Amlexanox: context-dependent readthrough evidenc…
Elena Torban, Lucie Canaff, Sima Babayeva et al. · Scientific Reports · 2025
includes ← MVA · BUB1B · cites ← Readthrough combinations: endogenous-protein tra…
NMD modulation alone cannot establish a useful protein product for L737*; readthrough needs exact-context and functional validation.
informs ← L737* NMD-first: test truncated-protein function · informs ← L737* readthrough: exact versus nearby contexts · informs ← Readthrough combinations: endogenous-protein tra…
Amlexanox and montelukast remain conditional; gentamicin plus mefloquine remains an experimental branch. No exact-genotype pharmacological rescue is established.
informs ← Amlexanox: context-dependent readthrough evidenc… · informs ← 704-drug NMD screen: reporter specificity · informs ← L737* readthrough: exact versus nearby contexts
For N1002K, matched protein abundance must be followed by independent functional measurements; stability and residual function remain unresolved.
informs ← Arimoclomol: target engagement and exposure gap · informs ← N1002K stabilization: equal-expression gate
BioLab is the biomedical research area of Stackfire Labs: research cases built around open evidence, reproducible reanalyses and an explicit record of what remains unresolved. It organizes evidence and proposes experiments; it does not run patient experiments or recommend treatments.
Where to look
Two germline BUB1B variants in mosaic variegated aneuploidy raise separate questions: L737* is an RNA and translation question, N1002K a protein stability and function question. The case records reanalyses and evidence audits, an October 24, 2026 robustness audit and a candidate decision matrix. No exact-genotype pharmacological rescue is established; wet-lab validation remains future work.
Where to look
A shared research library of publications kept as references, not copies. Every entry links to its original source and records which public bibliographic services supplied its metadata and when. Reading states and collections are bibliographic organization, never scientific validation.
Where to look
The graph connects a case to its variants, processes, evidence records, publications and hypotheses. Solid lines are documented connections; dashed lines are hypotheses under review. A connection says that a source or record links two items: it is not evidence of causation or efficacy. Every view also has a list alternative.
Where to look
A research trail is an ordered reading of the evidence, step by step. Hypotheses are statements under research with the evidence that informs or limits them; none is marked validated. Evidence gaps name what has not been measured or located. All of them link to existing records and publications instead of copying them.
Where to look
The auditable record of the MVA reanalyses with their execution records and downloads, and a Protein Structure Explorer of the predicted BUBR1 model. Tools marked Planned are not built yet. Reanalyses of public processed data and predicted structures are not biological experiments.
Where to look
No. BioLab is research context, not a clinical diagnostic report or a treatment recommendation. Drug candidates are research hypotheses with explicit gates, not proven treatments. Questions about a person’s care belong with their clinical team.