SF3B1 ⊥ BAP1
SF3B1 and BAP1 mutual exclusivity in melanoma (MSK-IMPACT 2017)
DataMSK-IMPACT (2017) · Melanoma
Inconclusive. The current version of the test cannot measure this (the patient group is too small or no longer analysed, or the genes are too rarely altered there), so its earlier numbers are shown for reference only.
A well-studied pair (628 papers): on the map it is known biology, a positive control rather than an overlooked discovery.
Signal (x) is the corrected significance on the map's scale, discounted from 10% to 5% because the cohort-composition confound is not yet controlled. Efficacy (y) is credibility times actionability.
These genes are rarely altered in the same tumour: mutual exclusivity, often a sign they hit one shared pathway so a tumour needs only one broken.
Skin (melanoma)
This finding's tumour type arises in the highlighted organ.
No structure profile is curated for this gene.
A human gene in this finding. Not in the curated driver set, so no structured profile is shown.
SF3B1 mutations in melanoma →SF3B1 co-mutations by tumour type →Other findings with SF3B1 →No structure profile is curated for this gene.
A human gene in this finding. Not in the curated driver set, so no structured profile is shown.
BAP1 mutations in melanoma →BAP1 co-mutations by tumour type →Other findings with BAP1 →Anatomical figure from the EBI Expression Atlas anatomogram, and predicted structures from the AlphaFold Protein Structure Database (both CC-BY-4.0). A model shows the protein's healthy fold; a highlighted residue marks a recurrent cancer position, not a prediction of a specific mutation's effect.
Weak evidence. Below the α=0.05 reject threshold (e≥20). Unlike a single-look p, this stays valid under the engine's continuous re-testing.
Molecular-subtype certification is unresolved. Control scope was not recorded. Molecular-subtype control is unverified. The association remains visible, but does not qualify as a subtype-controlled discovery.
The two axes are variables: signal (x) and efficacy (y = credibility × actionability). A point high on both lands in the frontier (top-right). A strong signal with low credibility sits low and to the right: statistically strong, not worth pursuing.
Earlier model annotation (set aside)
A model wrote this for an earlier measurement of this record. The engine does not stand behind the current result (not measurable by the current pipeline), so the annotation is not part of the record; it is kept here for reference only.
A language model wrote this from the evidence listed below. It is annotation: the engine's verdict above comes only from the measured statistics, never from this text.
I hypothesize that the SF3B1–BAP1 mutual exclusivity in melanoma is driven primarily by differing molecular-subtype or lineage composition, rather than by established within-tumour functional redundancy or negative selection.
- 1The population-level signal is substantial: no tumour carried both alterations versus 8.1 expected, with log2 odds ratio -3.0; the heterogeneity-aware test also reduces concern that generic alteration burden explains the pattern. The result survives multiple-testing correction (q=2.5e-2).E1E13
- 2Despite the large effect size, the evidence does not adjust for melanoma molecular subtype, lineage, or other composition variables. Therefore, subtype enrichment remains a plausible explanation for the cross-patient pattern and should be prioritized over an inferred within-tumour interaction.E1
- 3This lead CONVERGES with the Cybergenic corpus finding for PBRM1–BAP1 in clear-cell renal cell carcinoma, which similarly judged differing molecular-subtype composition to be the leading explanation, although that prior result was inconclusive and does not directly validate the melanoma pair.E12
- 4The provided literature does not establish a specific SF3B1–BAP1 mechanism: the co-mention record reports extensive literature, but the highlighted abstracts concern uveal-melanoma biomarkers or meningeal melanocytic neoplasms and do not appear to test this gene pair or its functional interaction.E6E7E8
- 5SF3B1 and BAP1 are independently catalogued as drivers across multiple cancer types, which supports biological relevance of each gene but does not distinguish subtype composition from redundancy or negative selection in melanoma.E10E11
Perform a lineage-matched, isogenic clonal melanoma experiment in which SF3B1 and BAP1 are separately and jointly disrupted across representative melanoma subtype backgrounds, followed by competitive-growth and viability measurements. A reproducible selective loss of the double-perturbed clones would support negative selection/redundancy; persistence of double mutants with exclusivity disappearing after subtype matching would support composition as the leading explanation.
The strongest competing explanation is genuine negative selection or functional redundancy, which cannot be inferred from a patient-level exclusivity statistic without a paper directly studying this pair. Sparse counts (0 observed versus 8.1 expected), unmeasured subtype composition, sequencing or calling artefacts, and possible cohort-specific lineage imbalance could also inflate the effect. The literature evidence increases the plausibility that the relationship is under-explored, but does not provide mechanistic confirmation.
Weakest link: E1 establishes only an adjusted cohort-level mutual-exclusivity signal, while none of the evidence tests subtype or lineage confounding or distinguishes it from within-tumour functional negative selection.
- E1In Melanoma, SF3B1 and BAP1 are mutually exclusive: DISCOVER heterogeneity-aware p = 1.8e-4 (a test that accounts for each tumor's overall alteration burden, so co-occurrence is not inflated by unstable tumors carrying more of everything), Benjamini-Hochberg FDR q = 2.5e-2, log2 odds ratio -3.0, 0 tumors carry both vs 8.1 expected.cBioPortal / MSK-IMPACT (2017)
- E2SF3B1 expression is lower in tumor than matched GTEx+adjacent normal tissue: log2 fold change -0.37 (137.9 vs 178.0 TPM, n=10519 tumor / 8167 normal).UCSC Xena (tumor vs GTEx normal)
- E3SF3B1 strongest disease associations (overall score 0–1): B-cell chronic lymphocytic leukemia 0.73; myelodysplastic syndrome 0.64; lymphoid leukemia 0.56; myeloproliferative disorder 0.54.Open Targets
- E4No approved drug directly targets SF3B1 (a tractability gap).Open Targets
- E5Tractability for SF3B1: Structure with Ligand, UniProt Ubiquitination, Database Ubiquitination, Half-life Data.Open Targets
- E6628 paper(s) co-mention this, well studied. Against each gene's own cancer literature, ~7 co-mentions would be expected by chance, so this pair is already studied more than its parts predict. Most relevant: "Functional validation of driver mutation-specific uveal melanoma biomarkers: role of COL9…" (2026).Europe PMC
- E7"Functional validation of driver mutation-specific uveal melanoma biomarkers: role of COL9A3 in cancer cell plasticity." (2026): Uveal melanoma (UM) is a deadly ocular malignancy with well-described genetic alterations that predict disease outcome. However, our current understanding of the biological underpinnings of high-risk uveal melanoma progression remains relatively limited. Using RNA expression profiles from 250 patients with UM, we identified 12 novel biomarkers associated wi…Europe PMC (paper)
- E8"Circumscribed Meningeal Melanocytic Neoplasms: CNS WHO Grade, Molecular Profile, and Clinical Outcomes." (2026): Circumscribed meningeal melanocytic neoplasms (CMMNs) represent a spectrum of rare central nervous system (CNS) tumors. Knowledge of their clinical behavior and molecular correlates remains limited. In this single-institution retrospective study, we analyzed 31 patients (14 male, 17 female; median age, 59 years) diagnosed with CMMN between 2004 and 2025. In…Europe PMC (paper)
- E90 clinical trial(s) match SF3B1/BAP1 in Melanoma, 0 currently open.ClinicalTrials.gov
- E10SF3B1: oncogene, driver in 14 cancer types (intOGen 2024.09.20)intOGen (driver catalogue)
- E11BAP1: tumor suppressor, driver in 14 cancer types (intOGen 2024.09.20)intOGen (driver catalogue)
- E12Prior finding, PBRM1 ⊥ BAP1 in Clear cell renal cell carcinoma: verdict inconclusive, confidence 47%. “The PBRM1–BAP1 mutual exclusivity in ccRCC is most likely driven primarily by differing molecular-subtype or …”Cybergenic corpus
- E13Significance is FDR-corrected: Benjamini-Hochberg q = 2.5e-2 across the cohort's whole pair family, so this pair SURVIVES multiple-testing correction (q ≤ 0.1). The q, not the nominal p, is the honest signal strength.Cybergenic method
Model-written annotation, not a finding. The statistics it cites are real and are shown above; the argument connecting them is a hypothesis that needs wet-lab or clinical validation before it means anything.
- Permalink
- https://cybergenic.im/findings/2da927f5-362a-4e9d-9151-37cc50b5dae4
- First seen
- 14 Aug 2026
- Prediction registry
- Locked 14 Aug 2026, row hash
09c5add96f52d829806aabf251f1da67(not testable out of sample). How the registry works
@misc{cybergenic_2da927f5,
author = {{Cybergenic}},
title = {{SF3B1 and BAP1 mutual exclusivity in melanoma (MSK-IMPACT 2017)}},
year = {2026},
howpublished = {\url{https://cybergenic.im/findings/2da927f5-362a-4e9d-9151-37cc50b5dae4}},
note = {Research engine finding, first seen 2026-08-14; prediction locked 2026-08-14, registry row hash 09c5add96f52d829806aabf251f1da67},
month = aug
}