Extrahepatic bile duct carcinoma

Summary

Extrahepatic bile duct carcinoma (MONDO:0003090) is a cancer (an umbrella term covering 6 Mondo subtypes) with 2 cohort genes (2 GWAS associations across 1 studies; 1 CIViC-evidence somatic driver) and 69 clinical trials. Top therapeutic interventions include lapatinib, cisplatin, and gemcitabine.

At a glance

• Classification: Cancer
• Umbrella term: 6 Mondo subtypes
• Cohort genes: 2
• GWAS associations: 2
• Clinical trials: 69

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	extrahepatic bile duct carcinoma
Mondo ID	MONDO:0003090
DOID	DOID:4682
NCIT	C3860
SNOMED CT	372101000
UMLS	C0238019
MedGen	116036
GARD	0023363
Anatomy (UBERON)	UBERON:0003703
Is cancer (heuristic)	yes

Also known as: carcinoma of extrahepatic bile duct · carcinoma of the extrahepatic bile duct · extrahepatic bile duct cancer · extrahepatic bile duct carcinoma

Data availability: 2 GWAS associations (1 study).

Disease family

An umbrella term covering 6 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › digestive system disorder › digestive system cancer › liver cancer › biliary tract cancer › bile duct cancer › bile duct carcinoma › extrahepatic bile duct carcinoma

Related subtypes (3): bile duct carcinoma in situ, bile duct adenocarcinoma, squamous cell bile duct carcinoma

Subtypes (6): extrahepatic bile duct adenocarcinoma, extrahepatic bile duct leiomyosarcoma, distal biliary tract carcinoma, extrahepatic bile duct squamous cell carcinoma, carcinoma of the ampulla of vater, carcinoma in situ of extrahepatic bile duct

Genetics & variants

GWAS landscape

2 GWAS associations across 1 studies. Top hits map to 2 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs188273166	1e-08	SLC30A10	?
rs541860626	5e-08	ETV1	?

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST90013662	Ward LD	2021	148	408,035	GWAS of serum ALT and AST reveals an association of SLC30A10 Thr95Ile with hypermanganesemia symptoms.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

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

MAF distribution

Bucket	Variants
common (>=0.05)	0
low_freq (0.01-0.05)	0
rare (<0.01)	0
unknown	2

Functional consequences

Consequence	Count
missense_variant	1
3_prime_UTR_variant	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs188273166	1	219928157	G>A		missense_variant	SLC30A10	1e-08	Tier 1: coding
rs541860626	7	13893201	T>C		3_prime_UTR_variant	ETV1	5e-08	Tier 2: splice/UTR

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 2 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Somatic driver evidence (intOGen + CIViC, cohort fanout)

Gene	intOGen role	Cancer types	CIViC
ETV1	Act	BRCA,COAD	CIViC #1764

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SLC30A10	Orphanet:309854	Cirrhosis-dystonia-polycythemia-hypermanganesemia syndrome
ETV1	Orphanet:319	Skeletal Ewing sarcoma

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
gwas_only	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
SLC30A10	HGNC:25355	ENSG00000196660	Q6XR72	Calcium/manganese antiporter SLC30A10	gwas
ETV1	HGNC:3490	ENSG00000006468	P50549	ETS translocation variant 1	gwas

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SLC30A10	Calcium/manganese antiporter SLC30A10	Calcium:manganese antiporter of the plasma membrane mediating the efflux of intracellular manganese coupled to an active extracellular calcium exchange.
ETV1	ETS translocation variant 1	Transcriptional activator that binds to DNA sequences containing the consensus pentanucleotide 5’-CGGA[AT]-3'.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 2 · 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	2	1.8×	0.312

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SLC30A10	Other/Unknown	no		Cation_efflux, Cation_efflux_TMD_sf, Cation_efflux_CTD
ETV1	Other/Unknown	no		Ets_dom, ETS_PEA3_N, WH-like_DNA-bd_sf

Expression context

Cohort genes with no expression data: 0.

2 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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
jejunal mucosa	1
mucosa of transverse colon	1
right lobe of liver	1
cerebellar vermis	1
cerebellum	1
parotid gland	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SLC30A10	111	broad	marker	jejunal mucosa, right lobe of liver, mucosa of transverse colon
ETV1	250	ubiquitous	marker	cerebellar vermis, parotid gland, cerebellum

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ETV1	2,163
SLC30A10	1,471

Structural data

PDB: 2 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
SLC30A10	Q6XR72	3
ETV1	P50549	3

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 1. Enrichment computed across 2 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
Metal ion SLC transporters	1	601.0×	0.002	SLC30A10

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
manganese ion export across plasma membrane	1	8426.0×	0.001	SLC30A10
mechanosensory behavior	1	4213.0×	0.001	ETV1
detoxification of zinc ion	1	4213.0×	0.001	SLC30A10
intracellular manganese ion homeostasis	1	1685.2×	0.002	SLC30A10
zinc ion import into organelle	1	1685.2×	0.002	SLC30A10
manganese ion transport	1	1053.2×	0.003	SLC30A10
peripheral nervous system neuron development	1	766.0×	0.003	ETV1
cellular response to angiotensin	1	468.1×	0.005	SLC30A10
zinc ion transmembrane transport	1	351.1×	0.006	SLC30A10
intracellular zinc ion homeostasis	1	240.7×	0.007	SLC30A10
epidermal growth factor receptor signaling pathway	1	123.9×	0.013	SLC30A10
muscle organ development	1	83.4×	0.018	ETV1
axon guidance	1	45.3×	0.030	ETV1
positive regulation of ERK1 and ERK2 cascade	1	42.6×	0.030	SLC30A10
transcription by RNA polymerase II	1	35.3×	0.034	ETV1
cell differentiation	1	14.6×	0.076	ETV1
positive regulation of transcription by RNA polymerase II	1	7.4×	0.138	ETV1
regulation of transcription by RNA polymerase II	1	5.8×	0.164	ETV1

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 2

Druggability breadth: 1 of 2 evidence-associated genes (50%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
SLC30A10	0	0
ETV1	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
ETV1	1	Binding:1

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; 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	2	SLC30A10, ETV1

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
SLC30A10	0	—
ETV1	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 69.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE2	34
PHASE1	14
PHASE3	8
Not specified	8
PHASE1/PHASE2	4
PHASE2/PHASE3	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT00253617	PHASE3	WITHDRAWN	Stent Placement With or Without Photodynamic Therapy Using Porfimer Sodium as Palliative Treatment in Treating Patients With Stage III or Stage IV Cholangiocarcinoma That Cannot Be Removed By Surgery
NCT00262769	PHASE3	COMPLETED	Gemcitabine With or Without Cisplatin in Treating Patients With Unresectable Locally Advanced or Metastatic Cholangiocarcinoma or Other Biliary Tract Tumors
NCT00304135	PHASE2/PHASE3	COMPLETED	Fluorouracil, Cisplatin, and Radiation Therapy or Gemcitabine and Oxaliplatin in Treating Patients With Nonmetastatic Biliary Tract Cancer That Cannot Be Removed By Surgery
NCT00363584	PHASE3	COMPLETED	Capecitabine or Observation After Surgery in Treating Patients With Biliary Tract Cancer
NCT00387348	PHASE3	TERMINATED	Escitalopram in Treating Depression in Patients With Advanced Lung or Gastrointestinal Cancer
NCT00513539	PHASE3	COMPLETED	Biliary Stenting With or Without Photodynamic Therapy in Treating Patients With Locally Advanced, Recurrent, or Metastatic Cholangiocarcinoma or Other Biliary Tract Tumors That Cannot Be Removed by Surgery
NCT00658593	PHASE3	TERMINATED	Gemcitabine With/Out Capecitabine in Locally Advanced, Unresectable, or Metastatic Biliary Cancer
NCT01313377	PHASE3	COMPLETED	Gemcitabine Hydrochloride and Oxaliplatin or Observation in Treating Patients With Biliary Tract Cancer That Has Been Removed by Surgery
NCT02349412	PHASE3	COMPLETED	Early Palliative Care With Standard Care or Standard Care Alone in Improving Quality of Life of Patients With Incurable Lung or Non-colorectal Gastrointestinal Cancer and Their Family Caregivers
NCT02834013	PHASE2	ACTIVE_NOT_RECRUITING	Nivolumab and Ipilimumab in Treating Patients With Rare Tumors
NCT00003296	PHASE2	UNKNOWN	Liposomal Doxorubicin in Treating Patients With Liver or Bile Duct Cancer
NCT00003557	PHASE2	COMPLETED	Dolastatin 10 in Treating Patients With Metastatic Or Recurrent Liver, Bile Duct, or Gallbladder Cancer
NCT00003923	PHASE2	COMPLETED	Photodynamic Therapy in Treating Patients With Cancer of the Bile Duct, Gallbladder, or Pancreas
NCT00004895	PHASE2	COMPLETED	Octreotide as Palliative Therapy for Cancer-Related Bowel Obstruction That Cannot Be Removed by Surgery
NCT00004910	PHASE1/PHASE2	COMPLETED	Endoscopic Placement of Metal Stents in Treating Patients With Cancer- Related Duodenal Obstruction
NCT00005938	PHASE2	COMPLETED	DX-8951f in Treating Patients With Biliary Cancer
NCT00005997	PHASE2	TERMINATED	Rebeccamycin Analogue in Treating Patients With Advanced Liver and/or Biliary Cancer
NCT00009893	PHASE2	COMPLETED	Combination Chemotherapy in Treating Patients With Unresectable or Metastatic Biliary Tract or Gallbladder Cancer
NCT00010088	PHASE2	UNKNOWN	Chemotherapy in Treating Patients With Locally Advanced or Metastatic Cancer of the Pancreas or Bile Duct
NCT00012246	PHASE2	TERMINATED	Vaccine Therapy in Treating Patients With Cancer of the Gastrointestinal Tract
NCT00019474	PHASE2	COMPLETED	Combination Chemotherapy Plus Interferon Alfa Followed by Filgrastim in Treating Patients With Gastrointestinal Tract Cancer
NCT00021047	PHASE1/PHASE2	COMPLETED	Epirubicin, Carboplatin, and Capecitabine in Treating Patients With Unresectable Locally Advanced, Metastatic, or Recurrent Solid Tumor
NCT00023946	PHASE2	TERMINATED	BMS-247550 in Treating Patients With Liver or Gallbladder Cancer
NCT00030511	PHASE2	TERMINATED	Radiation Therapy and Fluorouracil Before Surgery in Treating Patients With Primary or Recurrent Bile Duct Cancer
NCT00033462	PHASE2	COMPLETED	Erlotinib in Treating Patients With Unresectable Liver, Bile Duct, or Gallbladder Cancer
NCT00033540	PHASE2	COMPLETED	S0202 Gemcitabine and Capecitabine for Unresectable Locally Advanced Metastatic Gallbladder Cancer or Cholangiocarcinoma
NCT00059865	PHASE1/PHASE2	COMPLETED	Gemcitabine Plus Pemetrexed Disodium in Treating Patients With Unresectable or Metastatic Biliary Tract or Gallbladder Cancer
NCT00073905	PHASE2	COMPLETED	Adjuvant Palliative Capecitabine and Gemcitabine in Treating Patients With Locally Advanced or Metastatic Biliary Tract Cancer
NCT00084942	PHASE2	COMPLETED	Gemcitabine and Capecitabine in Treating Patients With Advanced and/or Inoperable Cholangiocarcinoma or Carcinoma of the Gallbladder
NCT00085410	PHASE2	TERMINATED	Bortezomib in Treating Patients With Unresectable Locally Advanced or Metastatic Adenocarcinoma of the Bile Duct or Gallbladder
NCT00101036	PHASE2	COMPLETED	Lapatinib in Treating Patients With Locally Advanced or Metastatic Biliary Tract or Liver Cancer That Cannot Be Removed By Surgery
NCT00107536	PHASE2	COMPLETED	Lapatinib Ditosylate in Treating Patients With Unresectable Liver or Biliary Tract Cancer
NCT00238212	PHASE2	COMPLETED	S0514 Sorafenib in Treating Patients With Unresectable or Metastatic Gallbladder Cancer or Cholangiocarcinoma
NCT00356889	PHASE2	COMPLETED	Bevacizumab and Erlotinib Hydrochloride in Treating Patients With Metastatic or Unresectable Biliary Tumors
NCT00478140	PHASE2	TERMINATED	Trastuzumab in Treating Patients With Locally Advanced or Metastatic Gallbladder Cancer or Bile Duct Cancer That Cannot Be Removed by Surgery
NCT00553332	PHASE2	COMPLETED	Selumetinib in Treating Patients With Biliary Cancer That Cannot Be Removed By Surgery
NCT00789958	PHASE2	COMPLETED	S0809: Capecitabine, Gemcitabine, and RT in Patients w/Cholangiocarcinoma of the Gallbladder or Bile Duct
NCT00832637	PHASE2	TERMINATED	Gemcitabine, Oxaliplatin, Tarceva &/or Cisplatin in HCC & Biliary Tree Cancers
NCT00903396	PHASE2	TERMINATED	Palonosetron Hydrochloride in Preventing Nausea and Vomiting Caused by Radiation Therapy in Patients With Primary Abdominal Cancer
NCT00919061	PHASE2	COMPLETED	Gemcitabine and Cisplatin Plus Sorafenib in Patients With Advanced Biliary Tract Carcinomas Naive to Systemic Therapy

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
LAPATINIB	4	6
CISPLATIN	4	5
GEMCITABINE	4	4
PORFIMER SODIUM	4	3
EPIRUBICIN HYDROCHLORIDE	4	2
ERLOTINIB	4	2
OXALIPLATIN	4	2
SELUMETINIB	4	2
SORAFENIB	4	2
APREPITANT	4	1
CAPECITABINE	4	1
CITALOPRAM	4	1
ESCITALOPRAM	4	1
HYDROXYUREA	4	1
IXABEPILONE	4	1
OCTREOTIDE ACETATE	4	1
PALONOSETRON HYDROCHLORIDE	4	1
SARGRAMOSTIM	4	1
TRAMETINIB	4	1
EXATECAN	3	2
BECATECARIN	3	1
CEDIRANIB MALEATE	3	1
CPI 613	3	1
INCOMPLETE FREUND’S ADJUVANT	3	1
MOTEXAFIN GADOLINIUM	3	1
DOLASTATIN-10	2	1
EDODEKIN ALFA	2	1
CHEMBL4463209	0	2
CHEMBL5433950	0	1