Gallbladder neoplasm

Summary

Gallbladder neoplasm (MONDO:0021253) is a cancer (an umbrella term covering 6 Mondo subtypes) with 3 cohort genes (16 GWAS associations across 6 studies; 2 CIViC-evidence somatic drivers) and 11 clinical trials. Top therapeutic interventions include desflurane, epirubicin, and pertuzumab.

At a glance

• Classification: Cancer
• Umbrella term: 6 Mondo subtypes
• Cohort genes: 3
• GWAS associations: 16
• Clinical trials: 11

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	gallbladder neoplasm
Mondo ID	MONDO:0021253
EFO	EFO:0004606
MeSH	D005706
NCIT	C3048
UMLS	C0016978
MedGen	42134
Anatomy (UBERON)	UBERON:0002110
Is cancer (heuristic)	yes

Also known as: gall bladder neoplasm · gall bladder neoplasm (disease) · gall bladder tumor · gall bladder tumour · gallbladder tumor · gallbladder tumour · neoplasm of gall bladder · neoplasm of gallbladder · neoplasm of the gallbladder · tumor of gall bladder · tumor of gallbladder · tumor of the gallbladder · tumour of gall bladder · tumour of gallbladder · tumour of the gallbladder

Data availability: 16 GWAS associations (6 studies).

Disease family

An umbrella term covering 6 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › digestive system disorder › hepatobiliary disorder › hepatobiliary neoplasm › gallbladder neoplasm

Related subtypes (1): liver and intrahepatic bile duct neoplasm

Subtypes (6): gallbladder papillary neoplasm, gallbladder cancer, gallbladder adenoma, gallbladder biliary intraepithelial neoplasia, benign neoplasm of gallbladder, gallbladder neuroendocrine neoplasm

Genetics & variants

GWAS landscape

16 GWAS associations across 6 studies. Top hits map to 8 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs1558375	2e-10	ABCB4	A	1.47
rs17209837	2e-09	ABCB4 - ABCB1	A	1.61
rs139351050	4e-09	LINC02872 - DAPK1	?	5.47
rs115602890	2e-08	EPHB1 - SDHBP1	?	5.44
rs17824967	3e-08	PPP2R5E	T	0.59
rs77671828	3e-08	NPFFR2	?	4.5
rs185457923	4e-08	LINC00929 - LINC02248	T	1.24
rs73161370	4e-08	B3GLCT - RXFP2	?	5.21
rs77648787	4e-08	NWD1	?	5.47
rs7504990	7e-08	DCC	A	6.95
rs144104793	1e-07	PDE4D	G	1.27
rs79847613	3e-07	NEUROD1 - SAP18P2	A	0.75
rs975334	9e-07	CNTN4	C	8.3
rs13294589	2e-06	LINC03106 - CAAP1	G	12.78
rs6869388	7e-06	KIAA0825	C	72.7
rs10953615	9e-06	BUB3P1 - EIF3IP1	C	7.51

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST90432145	Jiang Y	2023	116,382	213,325	A cross-disorder study to identify causal relationships, shared genetic variants, and genes across 21 digestive disorders.
GCST004201	Mhatre S	2017	1,042	1,709	Common genetic variation and risk of gallbladder cancer in India: a case-control genome-wide association study.
GCST001404	Cha PC	2012	41	0	A genome-wide association study identifies SNP in DCC is associated with gallbladder cancer in the Japanese population.
GCST005857	Alberts R	2017	30	2,977	Genetic association analysis identifies variants associated with disease progression in primary sclerosing cholangitis.
GCST90255405	Nam K	2022	12	72,286	Genome-wide study on 72,298 individuals in Korean biobank data for 76 traits.
GCST90104144	Choe EK	2022	0	0	Leveraging deep phenotyping from health check-up cohort with 10,000 Korean individuals for phenome-wide association study of 136 traits.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

Tier	Variants
Tier 1: coding	0
Tier 2: splice/UTR	0
Tier 3: regulatory	0
Tier 4: intronic/intergenic	16

MAF distribution

Bucket	Variants
common (>=0.05)	9
low_freq (0.01-0.05)	3
rare (<0.01)	0
unknown	4

Functional consequences

Consequence	Count
intron_variant	9
intergenic_variant	7

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs1558375	7	87449753	T>C,G	0.26	intron_variant	ABCB4	2e-10	Tier 4: intronic/intergenic
rs17209837	7	87495506	T>C	0.15	intergenic_variant	ABCB4 - ABCB1	2e-09	Tier 4: intronic/intergenic
rs139351050	9	87468116	C>A,T		intergenic_variant	LINC02872 - DAPK1	4e-09	Tier 4: intronic/intergenic
rs115602890	3	135268180	G>A		intron_variant	EPHB1 - SDHBP1	2e-08	Tier 4: intronic/intergenic
rs17824967	14	63416073	G>A,C,T	0.152	intron_variant	PPP2R5E	3e-08	Tier 4: intronic/intergenic
rs77671828	4	72144732	C>T	0.05	intron_variant	NPFFR2	3e-08	Tier 4: intronic/intergenic
rs185457923	15	26299394	G>T	0.016	intergenic_variant	LINC00929 - LINC02248	4e-08	Tier 4: intronic/intergenic
rs73161370	13	31723413	C>A,T		intergenic_variant	B3GLCT - RXFP2	4e-08	Tier 4: intronic/intergenic
rs77648787	19	16733869	C>G,T		intron_variant	NWD1	4e-08	Tier 4: intronic/intergenic
rs7504990	18	52991406	T>A,C,G	0.21	intron_variant	DCC	7e-08	Tier 4: intronic/intergenic
rs144104793	5	59024942	A>G	0.014	intron_variant	PDE4D	1e-07	Tier 4: intronic/intergenic
rs79847613	2	181682342	G>A	0.061	intergenic_variant	NEUROD1 - SAP18P2	3e-07	Tier 4: intronic/intergenic
rs975334	3	2804632	G>A,C,T	0.16	intron_variant	CNTN4	9e-07	Tier 4: intronic/intergenic
rs13294589	9	26694890	A>C,G	0.11	intergenic_variant	LINC03106 - CAAP1	2e-06	Tier 4: intronic/intergenic
rs6869388	5	94474503	T>C	0.04	intron_variant	KIAA0825	7e-06	Tier 4: intronic/intergenic
rs10953615	7	109512654	A>G	0.11	intergenic_variant	BUB3P1 - EIF3IP1	9e-06	Tier 4: intronic/intergenic

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 6 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Somatic driver evidence (intOGen + CIViC, cohort fanout)

Gene	intOGen role	Cancer types	CIViC
DCC	LoF	COADREAD,ESCA,HCC,PAAD,PRAD	CIViC #1396
ABCB1			CIViC #4244

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
DCC	Orphanet:238722	Familial congenital mirror movements
DCC	Orphanet:2744	Horizontal gaze palsy with progressive scoliosis
DCC	Orphanet:478	Kallmann syndrome
ABCB4	Orphanet:69663	Low phospholipid-associated cholelithiasis
ABCB4	Orphanet:69665	Intrahepatic cholestasis of pregnancy
ABCB4	Orphanet:79305	Progressive familial intrahepatic cholestasis type 3

Cohort genes → proteins

3 cohort genes, 3 distinct canonical proteins.

Evidence partition

Subset	Genes
gwas_only	3

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
DCC	HGNC:2701	ENSG00000187323	P43146	Netrin receptor DCC	gwas
ABCB1	HGNC:40	ENSG00000085563	P08183	ATP-dependent translocase ABCB1	gwas
ABCB4	HGNC:45	ENSG00000005471	P21439	Phosphatidylcholine translocator ABCB4	gwas

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
DCC	Netrin receptor DCC	Receptor for netrin required for axon guidance.
ABCB1	ATP-dependent translocase ABCB1	Translocates drugs and phospholipids across the membrane.
ABCB4	Phosphatidylcholine translocator ABCB4	Energy-dependent phospholipid efflux translocator that acts as a positive regulator of biliary lipid secretion.

Protein-family classification

Druggable: 3 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

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
Transporter	2	51.9×	1e-03
Antibody/Immunoglobulin	1	9.7×	0.099

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
DCC	Antibody/Immunoglobulin	yes		Ig_sub2, Ig_sub, FN3_dom
ABCB1	Transporter	yes	7.6.2.2	ABC_transporter-like_ATP-bd, AAA+_ATPase, ABC1_TM_dom
ABCB4	Transporter	yes		ABC_transporter-like_ATP-bd, AAA+_ATPase, ABC1_TM_dom

Expression context

Cohort genes with no expression data: 0.

3 cohort genes 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)	3
unknown	0

Top tissues across cohort

Tissue	Cohort genes
cortical plate	1
left testis	1
right testis	1
left adrenal gland cortex	1
right adrenal gland	1
right adrenal gland cortex	1
oocyte	1
right lobe of liver	1
secondary oocyte	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
DCC	154	broad	marker	cortical plate, right testis, left testis
ABCB1	232	broad	marker	right adrenal gland, right adrenal gland cortex, left adrenal gland cortex
ABCB4	188	broad	marker	right lobe of liver, secondary oocyte, oocyte

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ABCB1	4,426
ABCB4	2,333
DCC	1,333

Intra-cohort edges

A	B	Sources
ABCB1	ABCB4	biogrid_interaction, string_interaction

Structural data

PDB: 3 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
ABCB1	P08183	24
DCC	P43146	9
ABCB4	P21439	4

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 22. Enrichment computed across 3 evidence-associated genes (3 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 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Defective ABCB4 causes PFIC3, ICP3 and GBD1	1	3806.7×	0.003	ABCB4
ABC-family protein mediated transport	2	81.0×	0.003	ABCB1, ABCB4
Abacavir transmembrane transport	1	761.3×	0.006	ABCB1
DSCAM interactions	1	761.3×	0.006	DCC
Abacavir ADME	1	475.8×	0.006	ABCB1
Atorvastatin ADME	1	475.8×	0.006	ABCB1
Netrin mediated repulsion signals	1	423.0×	0.006	DCC
Prednisone ADME	1	423.0×	0.006	ABCB1
Caspase activation via Dependence Receptors in the absence of ligand	1	380.7×	0.006	DCC
Role of second messengers in netrin-1 signaling	1	346.1×	0.006	DCC
Regulation of commissural axon pathfinding by SLIT and ROBO	1	317.2×	0.006	DCC
DCC mediated attractive signaling	1	237.9×	0.008	DCC
Transport of small molecules	2	16.8×	0.008	ABCB1, ABCB4
Netrin-1 signaling	1	146.4×	0.010	DCC
ABC transporter disorders	1	146.4×	0.010	ABCB4
Drug ADME	1	76.1×	0.018	ABCB1
Regulation of lipid metabolism by PPARalpha	1	47.0×	0.026	ABCB4
Disorders of transmembrane transporters	1	46.4×	0.026	ABCB4
PPARA activates gene expression	1	31.5×	0.036	ABCB4
Metabolism of lipids	1	10.5×	0.101	ABCB4
Disease	1	4.4×	0.222	ABCB4
Metabolism	1	3.9×	0.237	ABCB4

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
phospholipid translocation	2	416.1×	6e-04	ABCB1, ABCB4
daunorubicin transport	1	5617.3×	0.001	ABCB1
terpenoid transport	1	5617.3×	0.001	ABCB1
cellular response to nonylphenol	1	5617.3×	0.001	ABCB1
positive regulation of establishment of Sertoli cell barrier	1	5617.3×	0.001	ABCB1
cellular response to borneol	1	5617.3×	0.001	ABCB1
response to codeine	1	5617.3×	0.001	ABCB1
positive regulation of response to drug	1	5617.3×	0.001	ABCB1
hormone transport	1	2808.7×	0.001	ABCB1
cellular response to mycotoxin	1	2808.7×	0.001	ABCB1
cellular response to external biotic stimulus	1	2808.7×	0.001	ABCB1
response to antineoplastic agent	1	2808.7×	0.001	ABCB1
ceramide translocation	1	2808.7×	0.001	ABCB1
response to fenofibrate	1	2808.7×	0.001	ABCB4
regulation of intestinal absorption	1	2808.7×	0.001	ABCB1
response to quercetin	1	2808.7×	0.001	ABCB1
response to cyclosporin A	1	2808.7×	0.001	ABCB1
transmembrane transport	2	112.3×	0.001	ABCB1, ABCB4
spinal cord ventral commissure morphogenesis	1	1872.4×	0.002	DCC
response to thyroxine	1	1872.4×	0.002	ABCB1
dorsal/ventral axon guidance	1	1404.3×	0.002	DCC
positive regulation of phospholipid translocation	1	1404.3×	0.002	ABCB4
cellular response to bile acid	1	1404.3×	0.002	ABCB4
negative regulation of sensory perception of pain	1	1404.3×	0.002	ABCB1
regulation of chloride transport	1	1404.3×	0.002	ABCB1
bile acid secretion	1	1123.5×	0.002	ABCB4
cellular response to alkaloid	1	1123.5×	0.002	ABCB1
anterior/posterior axon guidance	1	936.2×	0.002	DCC
cellular hyperosmotic salinity response	1	936.2×	0.002	ABCB1
protein localization to bicellular tight junction	1	936.2×	0.002	ABCB1

Therapeutics

Drugs indicated for this disease

0 approved, 6 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Capecitabine	Phase 3 (in late-stage trials)
Cisplatin	Phase 3 (in late-stage trials)
Gemcitabine	Phase 3 (in late-stage trials)
Oxaliplatin	Phase 3 (in late-stage trials)
Porfimer Sodium	Phase 3 (in late-stage trials)
Somatostatin	Phase 3 (in late-stage trials)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Becatecarin, Bevacizumab, Bintrafusp Alfa, Carboplatin, Cetuximab, Copanlisib, Crizotinib, Durvalumab, Envafolimab, Everolimus, Filgrastim, Fluorouracil, Gefitinib, Incomplete Freund’S Adjuvant, Irinotecan, Ixabepilone, Lapatinib, Paclitaxel, Panitumumab, Pembrolizumab, Ramucirumab, Sargramostim, Selumetinib, Sintilimab, Sorafenib, Trastuzumab, Triapine.

Drug target analysis

Approved (phase 4): 1 · Phase ≥3: 1 · Phased (≥1): 2 · Undrugged: 1

Druggability breadth: 2 of 3 evidence-associated genes (67%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
ABCB1	PROGESTERONE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
ABCB1	119	4
ABCB4	1	2
DCC	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
PROGESTERONE	4	ABCB1
CLOTRIMAZOLE	4	ABCB1
SIMVASTATIN	4	ABCB1
ARIPIPRAZOLE	4	ABCB1
SAQUINAVIR	4	ABCB1
ATAZANAVIR	4	ABCB1
DESLORATADINE	4	ABCB1
SERTINDOLE	4	ABCB1
CLOFAZIMINE	4	ABCB1
QUINIDINE	4	ABCB1
DARUNAVIR	4	ABCB1
SPIRONOLACTONE	4	ABCB1
PIMOZIDE	4	ABCB1
FELODIPINE	4	ABCB1
NICARDIPINE	4	ABCB1
AMLODIPINE	4	ABCB1
PANTOPRAZOLE	4	ABCB1
OMEPRAZOLE	4	ABCB1
KETOCONAZOLE	4	ABCB1
VINBLASTINE	4	ABCB1
CYCLOSPORINE	4	ABCB1
RITONAVIR	4	ABCB1
QUININE	4	ABCB1
TERFENADINE	4	ABCB1
NISOLDIPINE	4	ABCB1
CLARITHROMYCIN	4	ABCB1
DAUNORUBICIN	4	ABCB1
TRAMETINIB	4	ABCB1
DILTIAZEM	4	ABCB1
CERITINIB	4	ABCB1

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
ABCB1	3,063	Binding:2135, Functional:746, ADMET:182
ABCB4	4	ADMET:3, Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
ABCB1	7.6.2.2, 7.6.2.3	ABC-type xenobiotic transporter, ABC-type glutathione-S-conjugate transporter

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

Symbol	ChEMBL assays
ABCB1	3,063

Pharmacogenomics

Cohort genes with a PharmGKB record: 3; with CPIC/DPWG dosing guidelines: 0.

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

Drug repurposing candidates

30 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.

Compound	Max phase	Cohort target (bioactivity)
PROGESTERONE	4	ABCB1
CLOTRIMAZOLE	4	ABCB1
SIMVASTATIN	4	ABCB1
ARIPIPRAZOLE	4	ABCB1
SAQUINAVIR	4	ABCB1
ATAZANAVIR	4	ABCB1
DESLORATADINE	4	ABCB1
SERTINDOLE	4	ABCB1
CLOFAZIMINE	4	ABCB1
QUINIDINE	4	ABCB1
DARUNAVIR	4	ABCB1
SPIRONOLACTONE	4	ABCB1
PIMOZIDE	4	ABCB1
FELODIPINE	4	ABCB1
NICARDIPINE	4	ABCB1
AMLODIPINE	4	ABCB1
PANTOPRAZOLE	4	ABCB1
OMEPRAZOLE	4	ABCB1
KETOCONAZOLE	4	ABCB1
VINBLASTINE	4	ABCB1
CYCLOSPORINE	4	ABCB1
RITONAVIR	4	ABCB1
QUININE	4	ABCB1
TERFENADINE	4	ABCB1
NISOLDIPINE	4	ABCB1
CLARITHROMYCIN	4	ABCB1
DAUNORUBICIN	4	ABCB1
TRAMETINIB	4	ABCB1
DILTIAZEM	4	ABCB1
CERITINIB	4	ABCB1

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	ABCB1
B	Phased (≥1) drug, not yet approved	1	ABCB4
C	Druggable family + PDB, no drug	1	DCC
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

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)
DCC	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 11.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	5
PHASE2	2
PHASE4	1
PHASE3	1
PHASE2/PHASE3	1
PHASE1	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT02174575	PHASE4	WITHDRAWN	Anesthetic Agents and Acute Kidney Injury After Liver Resection Surgery
NCT05786716	PHASE2/PHASE3	RECRUITING	DETERMINE Trial Treatment Arm 04: Trastuzumab in Combination With Pertuzumab in Adult, Paediatric and Teenage/Young Adult Patients With Cancers With HER2 Amplification or Activating Mutations
NCT01053390	PHASE3	COMPLETED	New Chemotherapy Regimen in the Treatment of Advanced Gallbladder Carcinoma
NCT06638931	PHASE2	RECRUITING	Agnostic Therapy in Rare Solid Tumors
NCT05007106	PHASE2	COMPLETED	MK-7684A With or Without Other Anticancer Therapies in Participants With Selected Solid Tumors (MK-7684A-005) (KEYVIBE-005)
NCT01242605	PHASE1	COMPLETED	ABC-04 a Study of Cisplatin, Gemcitabine and Selumetinib in Patients With Advanced Biliary Tract Cancer
NCT06276153	Not specified	NOT_YET_RECRUITING	Construction of Multicenter Retrospective Registry Cohort Database for Gallbladder Cancer
NCT02430662	Not specified	COMPLETED	Irreversible Electroporation(IRE) For Unresectable Gallbladder Neoplasms
NCT03510923	Not specified	COMPLETED	Selective Rather Than Routine Histopathological Examination Following Appendectomy and Cholecystectomy
NCT04140552	Not specified	UNKNOWN	Chinese Research Group of Gallbladder Cancer
NCT06178848	Not specified	COMPLETED	EEG Parameters Between Remimazolam- and Propofol-based Anesthesia

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
DESFLURANE	4	1
EPIRUBICIN	4	1
PERTUZUMAB	4	1
SELUMETINIB	4	1
SEVOFLURANE	4	1
SOMATOSTATIN	3	1
ZENIDOLOL	2	1
CHEMBL4463209	0	1
SCEPTRIN	0	1