Cybergenic
All findings

RNF43 + GNAS

RNF43 and GNAS co-occurrence in pancreatic cancer (MSK-CHORD)

Strengthened: held up under a stratified controlCo-occurrence · Evidence: pattern across patients, not yet tested within subtypes

DataMSK-CHORD (2024) · Pancreatic cancer · 3,065 tumours · both altered in 10 (2.5 expected if independent)

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.

Engine's conclusion

Strengthened. Significant, with a real effect in a consistent direction, and it still holds when tumours are compared only within the same tumour type (and within the same molecular subtype, wherever this cancer's subtypes are known in the data). No artifact check failed.

A well-studied pair (385 papers): on the map it is known biology, a positive control rather than an overlooked discovery.

Not called novel: a PubTator3 search finds 46 papers naming both RNF43 and GNAS in pancreatic cancer in the title or abstract. See the PubTator3 search.

Statistical support48%Significance (FDR q)0.0078Signal (x)8%Efficacy (y)1%

Signal (x) is the corrected significance on the map's scale, discounted from 19% to 8% because the cohort-composition confound is not yet controlled. Efficacy (y) is credibility times actionability.

Structure & site3D structure: AlphaFold

These genes are altered together more often than chance would predict.

Primary site

Pancreas

This finding's tumour type arises in the highlighted organ.

No structure profile is curated for this gene.

RNF43Gene

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.

GNASGene

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.

Statistical evidence
Test p (raw)
3.6 × 10-5
Effect (log₂ odds ratio)
2.3
Papers
385
Abstracts naming both
46
Trials
1
Contingency table: the source of the q3,065 tumours

The raw 2×2 the FDR q and log₂ odds ratio above were computed from. It is the immutable evidence the score re-derives from: every number on this page traces back to these four counts.

Gene stateRNF43 alteredRNF43 wild-type
GNAS altered1052
GNAS wild-type1122,891

both 10 (expected 2.5 if independent) · GNAS-only 52 · RNF43-only 112 · neither 2,891

Sources
cBioPortal / MSK-CHORD (2024)Genome NexusOmniPath / Reactome / STRINGUCSC XenaOpen TargetsPubTator3NIH iCiteEurope PMCClinicalTrials.gov
Anytime-valid evidence (e-value)e = 5.7

Substantial 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.

Why it sits here on the map

Molecular-subtype certification is unresolved. Recorded lineage only. Within-lineage molecular subtype remains unresolved. The association remains visible, but does not qualify as a subtype-controlled discovery.

Opacity: novelty (display only)22%

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.

RNF43GNAS
Same question in other cohorts
HypothesisModel-generated hypothesis (not evidence)
Written by gpt-6-luna

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.

The RNF43–GNAS co-occurrence in pancreatic cancer is most likely driven by unresolved molecular-subtype or lineage composition: subtypes enriched for both alterations may create a population-level association without the alterations cooperating within the same tumour. This explanation is testable by asking whether the association attenuates after subtype adjustment.

Argument strength (model self-report)17%
After adversarial review17%
The argument
  1. 1The association is a credible population-level signal: it remains significant after burden adjustment and multiple-testing correction, with a within-stratum log2 odds ratio of 2.3 (95% CI 1.3–3.3) across 10 double-altered tumours. These statistics support co-occurrence, not a within-tumour interaction.E1E18
  2. 2Subtype composition is the leading explanation because only lineage is recorded and molecular subtype remains unresolved; the measured heterogeneity test does not rule out subtype confounding. The same-pair Cybergenic finding explicitly favored molecular-subtype composition, so this lead CONVERGES with it.E2E15
  3. 3The supplied IPMN review abstracts provide context on pancreatic precancerous lesions but do not study or establish a specific RNF43–GNAS relationship. Thus they do not support a within-tumour mechanism; broad pair co-mentions in the literature are not mechanistic evidence.E8E9E10
  4. 4The result has not replicated across independent patient sources, so a cohort-specific effect or winner's-curse/data artifact is the strongest competing explanation. The other cited corpus findings do not directly contradict the same-pair result or resolve its cause.E3E14E16E17
What would confirm or refute it

Test an independent pancreatic cancer cohort with molecular-subtype annotations using a subtype-adjusted logistic model and subtype-stratified co-occurrence estimates; attenuation of the RNF43–GNAS association after adjustment would support subtype composition. To earn a within-tumour cooperation claim, first use single-cell or clonal genotyping to establish co-occurrence in the same tumour cells, then test functional co-dependency in an appropriate model.

Strongest competing explanation (model)

This is a conservative ranking, not a demonstrated cause: (1) unresolved molecular-subtype/lineage composition is most likely; (2) cohort-specific biology or a scanning-related artifact/winner's curse is a substantial alternative given the lack of cross-source replication; (3) a shared upstream driver is possible but is not identified by the evidence; (4) deterministic co-amplification is unsupported here because no shared amplicon or copy-number evidence is supplied; and (5) genuine within-tumour cooperation is least justified without a paper studying this pair and direct clonal or functional evidence. The supplied paper abstracts do not study the pair, which leaves the proposed within-tumour mechanism under-explored rather than supporting it (E3, E8–E10).

Adversarial review (second model pass)

Weakest link: The evidence establishes a cohort-specific co-occurrence but provides no subtype measurements or adjusted analysis showing that subtype composition explains it; the lineage-adjusted association remains substantial.

Cross-cohort agreement (intra-snapshot)single source

Significant (after FDR correction) in one independent source of this tumour type so far. The engine records where a pattern is significant, not every source that could test it, so this calls for caution: a pattern selected from many tests tends to overstate its effect. It does not count against the pattern.

Evidence the argument cites

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.

Cite this finding
Permalink
https://cybergenic.im/findings/4aa0fac6-f91e-47d3-830b-1069b586f217
First seen
29 Sep 2026
Prediction registry
Locked 29 Sep 2026, row hash 55b7179fcfb172bead1797e47cdba527 (not testable out of sample). How the registry works
BibTeX
@misc{cybergenic_4aa0fac6,
  author       = {{Cybergenic}},
  title        = {{RNF43 and GNAS co-occurrence in pancreatic cancer (MSK-CHORD)}},
  year         = {2026},
  howpublished = {\url{https://cybergenic.im/findings/4aa0fac6-f91e-47d3-830b-1069b586f217}},
  note         = {Research engine finding, first seen 2026-09-29; prediction locked 2026-09-29, registry row hash 55b7179fcfb172bead1797e47cdba527},
  month        = sep
}
See it on the live map Mutations in pancreatic cancerGNAS and RNF43 in every cohort

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