Appendix cancer

Summary

Appendix cancer (MONDO:0001235) is a cancer with 1 cohort gene (1 CIViC-evidence somatic driver) and 20 clinical trials. Molecularly, GNAS R201H confers sensitivity to Trametinib in Appendix Cancer (CIViC Level C). Top therapeutic interventions include leucovorin, nintedanib, and certepetide.

At a glance

• Classification: Cancer
• Cohort genes: 1
• Clinical trials: 20
• Precision-medicine evidence (CIViC): 1 subtype–drug association

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	appendix cancer
Mondo ID	MONDO:0001235
DOID	DOID:11239
ICD-10-CM	C18.1
ICD-11	1892026854
NCIT	C9333
SNOMED CT	363411007
UMLS	C0496779
MedGen	141676
GARD	0027339
Anatomy (UBERON)	UBERON:0001154
Is cancer (heuristic)	yes

Also known as: cancer of vermiform appendix · malignant appendix neoplasm · malignant appendix tumor · malignant appendix tumour · malignant neoplasm of appendix · malignant neoplasm of appendix vermiformis · malignant neoplasm of the appendix · malignant neoplasm of vermiform appendix · malignant tumor of appendix · malignant tumor of the appendix · malignant tumour of appendix · malignant tumour of the appendix · malignant vermiform appendix neoplasm · vermiform appendix cancer

Disease family

An umbrella term covering 2 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › digestive system disorder › intestinal disorder › large intestine disorder › colonic disorder › cecal disorder › cecal neoplasm › appendiceal neoplasm › appendix cancer

Related subtypes (3): epithelial tumor of the appendix, benign neoplasm of appendix, appendix neuroendocrine neoplasm

Subtypes (2): appendix lymphoma, appendix carcinoma

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

No tiered GWAS variants or ClinVar records for this disease.

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 10 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Somatic driver evidence (intOGen + CIViC, cohort fanout)

Gene	intOGen role	Cancer types	CIViC
GNAS	Act	BRCA,COADREAD,ESCA,HCC,LUAD,MBL,PAAD,PANCREAS	CIViC #2319

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
GNAS	Orphanet:189427	Cushing syndrome due to bilateral macronodular adrenocortical disease
GNAS	Orphanet:2762	Progressive osseous heteroplasia
GNAS	Orphanet:562	McCune-Albright syndrome
GNAS	Orphanet:57782	Mazabraud syndrome
GNAS	Orphanet:79443	Pseudohypoparathyroidism type 1A
GNAS	Orphanet:79444	Pseudohypoparathyroidism type 1C
GNAS	Orphanet:79445	Pseudopseudohypoparathyroidism
GNAS	Orphanet:93276	Polyostotic fibrous dysplasia
GNAS	Orphanet:93277	Monostotic fibrous dysplasia
GNAS	Orphanet:94089	Pseudohypoparathyroidism type 1B

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
civic_only	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
GNAS	HGNC:4392	ENSG00000087460	O95467	Neuroendocrine secretory protein 55	civic_evidence

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Other/Unknown	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
GNAS	Other/Unknown	no		NESP55, Gprotein_alpha_S, Gprotein_alpha_su

Expression context

Cohort genes with no expression data: 0.

1 cohort gene are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
Brodmann (1909) area 46	1
postcentral gyrus	1
type B pancreatic cell	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
GNAS	312	ubiquitous	marker	type B pancreatic cell, postcentral gyrus, Brodmann (1909) area 46

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
GNAS	410

Structural data

PDB: 1 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
GNAS	O95467	490

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 13. Enrichment computed across 1 evidence-associated genes (1 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
PKA activation in glucagon signalling	1	671.8×	0.006	GNAS
Prostacyclin signalling through prostacyclin receptor	1	601.0×	0.006	GNAS
Glucagon signaling in metabolic regulation	1	346.1×	0.006	GNAS
Glucagon-type ligand receptors	1	346.1×	0.006	GNAS
Glucagon-like Peptide-1 (GLP1) regulates insulin secretion	1	265.6×	0.006	GNAS
Vasopressin regulates renal water homeostasis via Aquaporins	1	265.6×	0.006	GNAS
ADORA2B mediated anti-inflammatory cytokines production	1	253.8×	0.006	GNAS
GPER1 signaling	1	248.3×	0.006	GNAS
G alpha (z) signalling events	1	233.1×	0.006	GNAS
Hedgehog ‘off’ state	1	178.4×	0.007	GNAS
High laminar flow shear stress activates signaling by PIEZO1 and PECAM1:CDH5:KDR in endothelial cells	1	160.8×	0.007	GNAS
G alpha (s) signalling events	1	73.2×	0.015	GNAS
G alpha (i) signalling events	1	39.0×	0.026	GNAS

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
adenylate cyclase-activating G protein-coupled bile acid receptor signaling pathway	1	5617.3×	0.002	GNAS
response to parathyroid hormone	1	4213.0×	0.002	GNAS
adenylate cyclase-activating serotonin receptor signaling pathway	1	3370.4×	0.002	GNAS
hair follicle placode formation	1	3370.4×	0.002	GNAS
regulation of skeletal muscle contraction	1	2808.7×	0.002	GNAS
cellular response to catecholamine stimulus	1	2407.4×	0.002	GNAS
adenylate cyclase-activating dopamine receptor signaling pathway	1	1532.0×	0.002	GNAS
intracellular transport	1	1532.0×	0.002	GNAS
response to prostaglandin E	1	1404.3×	0.002	GNAS
adenylate cyclase-activating adrenergic receptor signaling pathway	1	1203.7×	0.002	GNAS
activation of adenylate cyclase activity	1	1123.5×	0.002	GNAS
sensory perception of chemical stimulus	1	1123.5×	0.002	GNAS
negative regulation of multicellular organism growth	1	1123.5×	0.002	GNAS
cellular response to glucagon stimulus	1	842.6×	0.003	GNAS
cellular response to prostaglandin E stimulus	1	842.6×	0.003	GNAS
developmental growth	1	732.7×	0.003	GNAS
cellular response to acidic pH	1	732.7×	0.003	GNAS
vascular endothelial cell response to laminar fluid shear stress	1	732.7×	0.003	GNAS
negative regulation of inflammatory response to antigenic stimulus	1	601.9×	0.003	GNAS
intracellular glucose homeostasis	1	581.1×	0.003	GNAS
renal water homeostasis	1	510.7×	0.003	GNAS
positive regulation of insulin secretion involved in cellular response to glucose stimulus	1	374.5×	0.004	GNAS
platelet aggregation	1	337.0×	0.004	GNAS
cognition	1	285.6×	0.005	GNAS
bone development	1	276.3×	0.005	GNAS
regulation of signal transduction	1	267.5×	0.005	GNAS
protein secretion	1	263.3×	0.005	GNAS
positive regulation of insulin secretion	1	255.3×	0.005	GNAS
female pregnancy	1	210.7×	0.005	GNAS
positive regulation of cold-induced thermogenesis	1	163.6×	0.007	GNAS

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 1

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
GNAS	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Drug repurposing candidates

0 approved/phased drugs hit cohort targets but don’t yet appear in disease-level clinical trials. Target-inhibition rationale is strongest for cancer driver genes; a bioactivity hit is a screening signal, not a treatment claim.

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	GNAS

Undrugged target profiles

1 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
GNAS	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 20.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	14
PHASE1	3
PHASE2	2
PHASE1/PHASE2	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT01815359	PHASE2	ACTIVE_NOT_RECRUITING	ICARuS Post-operative Intraperitoneal Chemotherapy (EPIC) and Hyperthermic Intraperitoneal Chemotherapy (HIPEC) After Optimal Cytoreductive Surgery (CRS) for Neoplasms of the Appendix, Colon or Rectum With Isolated Peritoneal Metastasis
NCT03287947	PHASE2	TERMINATED	LCI-GI-APX-NIN-001: Nintedanib in Metastatic Appendiceal Carcinoma
NCT04902872	PHASE1/PHASE2	COMPLETED	Study of CBX-12 in Subjects With Advanced or Metastatic Refractory Solid Tumors
NCT05277766	PHASE1	RECRUITING	Intraperitoneal Aerosolized Nanoliposomal Irinotecan (Nal-IRI) in Peritoneal Carcinomatosis From Gastrointestinal Cancer
NCT02833753	PHASE1	COMPLETED	Trial of Intraperitoneal (IP) Oxaliplatin in Combination With Intravenous FOLFIRI
NCT06216561	PHASE1	WITHDRAWN	Intraperitoneal LSTA1 in CRS-HIPEC
NCT04157322	Not specified	ACTIVE_NOT_RECRUITING	Plasma 5hmC Signatures as a Marker of Colorectal / Appendiceal Peritoneal Metastasis
NCT04634448	Not specified	NOT_YET_RECRUITING	The Prevalence of Appendiceal Tumours in Periappendicular Abscess
NCT04907643	Not specified	RECRUITING	Virtual Reality for GI Cancer Pain to Improve Patient Reported Outcomes
NCT05623787	Not specified	ACTIVE_NOT_RECRUITING	Diagnostic Value of Diffusion-weighted Magnetic Resonance in High-risk Colorectal and Appendiceal Neoplasms
NCT05734430	Not specified	RECRUITING	Genetics of Appendix Cancer Study
NCT05780684	Not specified	RECRUITING	Individualized Dose Escalation of 5-FU for Gastrointestinal Cancer
NCT05919758	Not specified	RECRUITING	Value of Right-sided Hemicolectomy for Chldren With High-risk Neuroendocrine Tumors of the Appendix
NCT06263088	Not specified	RECRUITING	EQUITY GI: A Prospective Study to Enhance Quality, Inclusivity, and Trial Participation in Black Patients With Gastrointestinal Cancer.
NCT06715839	Not specified	RECRUITING	Target-specific immunoPET Imaging of Digestive System Carcinoma
NCT02489422	Not specified	COMPLETED	Programs To Support You During Chemotherapy
NCT03210298	Not specified	UNKNOWN	International Registry of Patients Treated With Pressurized IntraPeritoneal Aerosol Chemotherapy (PIPAC)
NCT04028479	Not specified	COMPLETED	The Registry of Oncology Outcomes Associated With Testing and Treatment
NCT04526886	Not specified	COMPLETED	Clinical Trial of a Novel Dose Adjustment Algorithm for Preventing Cytopenia-Related Delays During FOLFOX Chemotherapy
NCT05305820	Not specified	UNKNOWN	Perioperative Exercise and Nutritional Optimisation Prehabilitation Before Surgery for Patients With Peritoneal Malignancy

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
LEUCOVORIN	4	1
NINTEDANIB	4	1
CERTEPETIDE	2	1

Precision-medicine subtype map (CIViC)

Drug × molecular subtype: 1 predictive associations from 1 curated evidence items.

Molecular subtype	Therapy	Effect	Level	CIViC
GNAS R201H	Trametinib	Sensitivity/Response	CIViC C	EID8676