Evidence Graph
Every connection carries its source.
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.
- Nodes
- 51
- Connections
- 93
- Under review
- 11
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- Research case
- Gene
- Protein
- Variant
- Disease
- Biological process
- Drug / compound
- Evidence record
- Publication
- Hypothesis
- Documented connection
- Under review
Research case 1
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MVA · BUB1B 36
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
Gene 1
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BUB1B 6
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
Protein 1
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BUBR1 3
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
Variant 2
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L737* 4
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
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N1002K 4
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
Disease 1
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Rare disorder of chromosome segregation; MONDO term "mosaic variegated aneuploidy syndrome 1".
concerns ← MVA · BUB1B · associated with ← BUB1B
Biological process 5
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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
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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…
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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
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Audit topic: published immunotherapy results concern tumor control, which is not BUB1B disease rescue.
investigates ← Immunotherapy: disease rescue versus tumor contr…
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Whether the N1002K protein is stable and functional; abundance alone does not answer it.
investigates ← N1002K stabilization: equal-expression gate
Drug / compound 5
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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…
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Readthrough / NMD-inhibition candidate with context-dependent published evidence; conditional in this case.
investigates ← Amlexanox: context-dependent readthrough evidenc…
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HSF1 co-inducer audited for target engagement and exposure in relation to N1002K; gap documented.
investigates ← Arimoclomol: target engagement and exposure gap
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Named in the 704-drug NMD screen reanalysis; response reporter-dependent, no functional BUBR1 rescue established.
investigates ← 704-drug NMD screen: reporter specificity
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Reanalysed in public human fibroblast RNA data at the BUB1B locus; descriptive signal, not functional rescue.
investigates ← Rapamycin in human fibroblasts: BUB1B locus RNA …
Evidence record 11
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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
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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
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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
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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
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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
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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
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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*
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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
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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
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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
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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
Publication 21
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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
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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
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Kara L. Davis, Elizabeth Fox, Emasenyie Isikwei et al. · Clinical Cancer Research · 2022
includes ← MVA · BUB1B · cites ← Immunotherapy: disease rescue versus tumor contr…
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Nesrine Benslimane, Federica Miressi, Camille Loret et al. · Pharmaceuticals · 2023
includes ← MVA · BUB1B · cites ← Amlexanox: context-dependent readthrough evidenc…
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Meenakshi Hegde, Shoba Navai, Christopher DeRenzo et al. · Nature Cancer · 2024
includes ← MVA · BUB1B · cites ← Immunotherapy: disease rescue versus tumor contr…
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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
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Peng Xu, Elizabeth A. Raetz, Mayumi Kitagawa et al. · Biology Open · 2013
includes ← MVA · BUB1B · cites ← N1002K stabilization: equal-expression gate
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Mingzhe Zhang, Tingting Lei, Ying Wang et al. · Communications Biology · 2026
includes ← MVA · BUB1B · cites ← BUBR1 functional controls: arrest duration
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Darren J. Baker, Tobias Wijshake, Tamar Tchkonia et al. · Nature · 2011
includes ← MVA · BUB1B · cites ← Immunotherapy: disease rescue versus tumor contr…
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www.accessdata.fda.gov
includes ← MVA · BUB1B · cites ← Arimoclomol: target engagement and exposure gap
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www.accessdata.fda.gov
includes ← MVA · BUB1B · cites ← Amlexanox: context-dependent readthrough evidenc…
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Genome-scale quantification and prediction of pathogenic stop codon readthrough by small molecules 2
Ignasi Toledano, Fran Supek, Ben Lehner · Nature Genetics · 2024
includes ← MVA · BUB1B · cites ← L737* readthrough: exact versus nearby contexts
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Catherine A.S. Deane, Ian R. Brown · Cell Stress and Chaperones · 2016
includes ← MVA · BUB1B · cites ← Arimoclomol: target engagement and exposure gap
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Kohei Omachi, Hirofumi Kai, Michel Roberge et al. · iScience · 2022
includes ← MVA · BUB1B · cites ← L737* readthrough: exact versus nearby contexts
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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…
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Kara L Davis, Elizabeth Fox, Melinda S Merchant et al. · The Lancet Oncology · 2020
includes ← MVA · BUB1B · cites ← Immunotherapy: disease rescue versus tumor contr…
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Corina Amor, Inés Fernández-Maestre, Saria Chowdhury et al. · Nature Aging · 2024
includes ← MVA · BUB1B · cites ← Immunotherapy: disease rescue versus tumor contr…
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Christoph Steurer, Sarah Kerschbaum, Christina Wegrostek et al. · Molecular Biotechnology · 2022
includes ← MVA · BUB1B · cites ← Arimoclomol: target engagement and exposure gap
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Zoe E Gillespie, Kimberly MacKay, Michelle Sander et al. · Nucleus · 2015
includes ← MVA · BUB1B · cites ← Rapamycin in human fibroblasts: BUB1B locus RNA …
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Sara Gonzalez-Hilarion, Terence Beghyn, Jieshuang Jia et al. · Orphanet Journal of Rare Diseases · 2012
includes ← MVA · BUB1B · cites ← Amlexanox: context-dependent readthrough evidenc…
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Elena Torban, Lucie Canaff, Sima Babayeva et al. · Scientific Reports · 2025
includes ← MVA · BUB1B · cites ← Readthrough combinations: endogenous-protein tra…
Hypothesis 3
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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…
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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
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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