RNF43 + GNAS
RNF43 and GNAS co-occurrence in pancreatic cancer (MSK-MET)
DataMSK-MET (2021) · Pancreatic cancer
This cohort pools pancreatic adenocarcinoma with pancreatic neuroendocrine tumours, so a pattern here can reflect the mix of tumour types rather than biology within one of them.
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 (385 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 3% to 1% because the cohort-composition confound is not yet controlled. Efficacy (y) is credibility times actionability.
These genes are altered together more often than chance would predict.
Pancreas
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.
RNF43 mutations in pancreatic cancer →RNF43 co-mutations by tumour type →Other findings with RNF43 →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.
GNAS mutations in pancreatic cancer →GNAS co-mutations by tumour type →Other findings with GNAS →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.
RNF43 and GNAS most likely co-occur across pancreatic tumours because the cohort is enriched for a shared pancreatic molecular or lineage subgroup, potentially including IPMN-associated disease, in which both alterations are selected through related upstream biology; this is more plausible than deterministic co-amplification or demonstrated within-tumour cooperation.
- 1The co-occurrence is a reproducible population-level signal rather than a simple consequence of globally unstable tumours: the burden-adjusted DISCOVER test gives p = 1.3e-2, log2 odds ratio = 2.2, with 10 observed versus 4.3 expected double-altered tumours, and the association survives multiple testing at q = 6.6e-2.E1E16
- 2The leading explanation is molecular-subtype or lineage composition, ranked slightly above a shared upstream driver: a subgroup enriched for both alterations can generate population-level co-occurrence without implying that the genes cooperate within each tumour. The shared-upstream-driver explanation is a close second because both genes are catalogued as cancer drivers, although those catalogues do not establish a pancreatic relationship between them.E1E10E11
- 3Deterministic co-amplification of neighbouring genes is lower-ranked because the supplied evidence reports alteration co-occurrence but gives no genomic-location or copy-number evidence that RNF43 and GNAS reside on, or are driven by, the same amplicon.E1
- 4A generic data artifact is also lower-ranked, but remains possible through cohort composition, subtype imbalance, or assay-specific alteration calling; the heterogeneity-aware burden adjustment reduces, but does not eliminate, that concern.E1
- 5Genuine within-tumour cooperation ranks last on the current evidence. The provided paper records discuss IPMN as a pancreatic precursor or clinically relevant entity but do not establish that RNF43 and GNAS interact, cooperate, or are co-selected in the same tumour; the broader co-mention record therefore supports an under-explored lead rather than a mechanistic conclusion.E6E7E8
- 6This lead CONVERGES with the Cybergenic corpus at the level of interpretation: prior APC–RNF43, KRAS–RNF43, TP53–GNAS, and EGFR–GNAS analyses likewise frame alteration patterns as population-level selection or molecular partitioning rather than automatic within-tumour interaction. It is not direct replication because those findings concern different gene pairs and cancer contexts.E12E13E14E15
- 7The RNF43 tumour-expression increase is consistent with biologically relevant disease involvement, but it does not distinguish shared lineage composition from a shared upstream driver or prove that the DNA alterations cooperate.E2E3E10
In an independent pancreatic cancer cohort, annotate IPMN-associated versus conventional ductal tumours and relevant molecular subtypes, then test RNF43–GNAS co-occurrence with multivariable logistic regression adjusted for subtype, lineage, tumour purity, copy-number burden, and sequencing platform. In parallel, perform single-cell or clonal DNA sequencing on double-positive tumours to determine whether both alterations occur in the same clone; a functional co-dependency screen with individual and combined perturbation would be required before claiming within-tumour cooperation.
The strongest deflating explanation is unmeasured subtype or lineage composition, which could create the association without a direct shared driver; a shared upstream process remains nearly tied for first place. Co-amplification and technical calling bias cannot be excluded without locus-level copy-number and orthogonal validation. Because no cited paper actually studies the RNF43–GNAS relationship, a within-tumour cooperation mechanism is unearned, and the FDR-adjusted signal is only moderate despite the sizeable odds ratio.
Weakest link: The central IPMN/lineage explanation is unsupported by the numbered evidence, while the association rests on only 10 co-altered tumours with modest multiple-testing evidence and could reflect cohort composition or other artifacts.
- E1In Pancreatic cancer, RNF43 and GNAS are co-occurring: DISCOVER heterogeneity-aware p = 1.3e-2 (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 = 6.6e-2, log2 odds ratio 2.2, 10 tumors carry both vs 4.3 expected.cBioPortal / MSK-MET (2021)
- E2RNF43 expression is higher in tumor than matched GTEx+adjacent normal tissue: log2 fold change 2.04 (4.9 vs 1.2 TPM, n=10519 tumor / 8167 normal). A >2x shift is a real expression-level signal on top of the DNA alteration.UCSC Xena (tumor vs GTEx normal)
- E3RNF43 strongest disease associations (overall score 0–1): sessile serrated polyposis cancer syndrome 0.71; pancreatic adenocarcinoma 0.52; hyperplastic polyposis syndrome 0.52; prostate carcinoma 0.50.Open Targets
- E4No approved drug directly targets RNF43 (a tractability gap).Open Targets
- E5Tractability for RNF43: GO CC high conf, UniProt loc med conf, UniProt SigP or TMHMM, UniProt Ubiquitination.Open Targets
- E6385 paper(s) co-mention this, well studied. Against each gene's own cancer literature, ~3 co-mentions would be expected by chance, so this pair is already studied more than its parts predict. Most relevant: "DIAGNOSIS AND MANAGEMENT OF INTRADUCTAL PAPILLARY MUCINOUS NEOPLASMS: A NARRATIVE REVIEW …" (2026).Europe PMC
- E7"Intraductal Papillary Mucinous Neoplasm (IPMN) of the Pancreas: History, Myths, and Realities Between Past and Future." (2026): Intraductal papillary mucinous neoplasm (IPMN) of the pancreas is among the most clinically relevant and conceptually intricate precancerous lesions encountered in modern gastroenterology. First identified in the early 1980s as a "mucin-producing tumor," IPMN has since undergone a profound redefinition: from an obscure and poorly classified entity to a well…Europe PMC (paper)
- E8"DIAGNOSIS AND MANAGEMENT OF INTRADUCTAL PAPILLARY MUCINOUS NEOPLASMS: A NARRATIVE REVIEW BASED ON INTERNATIONAL GUIDELI…" (2026): Background: Intraductal papillary mucinous neoplasms (IPMNs) are the leading cause of incidentally detected pancreatic cysts and exhibit a wide biological spectrum with variable malignant potential. Recent advances in imaging, endoscopic assessment, molecular testing, and artificial intelligence have improved risk stratification and influenced contem…Europe PMC (paper)
- E91 clinical trial(s) match RNF43/GNAS in Pancreatic cancer, but ZERO are currently open (a clinical-translation WHITESPACE).ClinicalTrials.gov
- E10RNF43: tumor suppressor, driver in 12 cancer types (intOGen 2024.09.20)intOGen (driver catalogue)
- E11GNAS: oncogene, driver in 8 cancer types (intOGen 2024.09.20)intOGen (driver catalogue)
- E12Prior finding, APC ⊥ RNF43 in Colorectal cancer: verdict strengthened, confidence 63%. “APC–RNF43 mutual exclusivity in colorectal cancer most likely reflects population-level selection for tumors …”Cybergenic corpus
- E13Prior finding, KRAS ⊥ RNF43 in Colorectal cancer: verdict strengthened, confidence 55%. “KRAS–RNF43 mutual exclusivity in colorectal cancer most likely reflects population-level selection for altern…”Cybergenic corpus
- E14Prior finding, TP53 ⊥ GNAS in Colorectal cancer: verdict strengthened, confidence 52%. “TP53–GNAS mutual exclusivity in colorectal cancer most likely reflects population-level selection for alterna…”Cybergenic corpus
- E15Prior finding, EGFR ⊥ GNAS in Non-small cell lung cancer: verdict artifact-risk, confidence 50%. “EGFR–GNAS mutual exclusivity in NSCLC is most likely driven by population-level partitioning among molecular …”Cybergenic corpus
- E16Significance is FDR-corrected: Benjamini-Hochberg q = 6.6e-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/9b22e8f9-2f7e-497f-a1b5-1aa356011158
- First seen
- 13 Aug 2026
- Prediction registry
- Locked 13 Aug 2026, row hash
26dfb1b7cbe0f0e16e93bde3cc7813be(not testable out of sample). How the registry works
@misc{cybergenic_9b22e8f9,
author = {{Cybergenic}},
title = {{RNF43 and GNAS co-occurrence in pancreatic cancer (MSK-MET)}},
year = {2026},
howpublished = {\url{https://cybergenic.im/findings/9b22e8f9-2f7e-497f-a1b5-1aa356011158}},
note = {Research engine finding, first seen 2026-08-13; prediction locked 2026-08-13, registry row hash 26dfb1b7cbe0f0e16e93bde3cc7813be},
month = aug
}