Duodenal ulcer

Summary

Duodenal ulcer (MONDO:0005412) is a disease with 2 cohort genes (74 GWAS associations across 26 studies) and 47 clinical trials. Top therapeutic interventions include vonoprazan, lansoprazole, and rabeprazole.

At a glance

• Cohort genes: 2
• GWAS associations: 74
• Clinical trials: 47

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	duodenal ulcer
Mondo ID	MONDO:0005412
EFO	EFO:0004607
MeSH	D004381
DOID	DOID:1724
ICD-10-CM	K26
ICD-11	553678663
NCIT	C26755
SNOMED CT	39755000
UMLS	C0013295
MedGen	41670
Is cancer (heuristic)	no

Also known as: duodenal ulcer (disease) · stress Ulcer

Data availability: 74 GWAS associations (26 studies) · 1 HPO phenotype.

Disease family

Classification path: disease › human disease › disease by body system or component › digestive system disorder › intestinal disorder › small intestine disorder › duodenal disorder › duodenal ulcer

Related subtypes (5): duodenal obstruction, duodenitis, biliary dyskinesia, duodenogastric reflux, tumor of duodenum

Genetics & variants

GWAS landscape

74 GWAS associations across 26 studies. Top hits map to 28 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs2294008	8e-189	JRK, PSCA	T	0.41
rs71514093	1e-188	PSCA, JRK	T	0.42
chr8:142678838	1e-22		A	0.15
chr11:6252514	3e-20		C	0.16
rs3805497	1e-18	TTC33	T	0.11
chr19:48703417	1e-18		A	0.13
rs373477888	2e-18	PRKAA1	TG	0.13
rs11665674	3e-17	SEC1P - FUT2	G	0.14
rs8176719	4e-17	ABO	TC	0.1
rs10500661	7e-17	CNGA4 - CCKBR	C	0.14
rs148675590	5e-16	RN7SL272P - FLT3	A	0.15
rs34074411	1e-15	EIF1 - GAST	T	0.1
rs61160304	5e-15	FSCN3 - PAX4	T	0.2
rs573784774	2e-14	UBE2V1P4	G	3.85
chr8:143752994	6e-14		T	0.57
rs5842244	1e-13	GNAS	A	0.11
rs557100015	2e-13	LINC01492 - RNA5SP291	C	1.89
rs78168911	2e-12	NALCN-AS1	C	3.79
rs681343	3e-12	FUT2	?	0.91
chr6:160352346	5e-12		A	0.13
rs6117384	6e-12	CASC20 - LINC01713	C	0.09
chr17:41710996	8e-12		T	0.1
rs141625351	2e-11		G	0.17
rs79928271	2e-11	MECOM	A	0.1
rs2920281	3e-11	JRK, PSCA	?	0.91
rs573250197	3e-11	CYP2A7P2, CYP2G1P, CYP2G1P, CYP2B7P, CYP2B7P	T	3.46
rs551365214	4e-11	ACTG1P19 - GAPDHP26	G	2.12
rs60154219	9e-11	MECOM	G	0.09
rs505922	1e-10	ABO	T	1.32
rs687621	1e-10	ABO	?	0.91

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST90432136	Jiang Y	2023	116,382	213,325	A cross-disorder study to identify causal relationships, shared genetic variants, and genes across 21 digestive disorders.
GCST90270928	He Y	2023	11,964	240,675	East Asian-specific and cross-ancestry genome-wide meta-analyses provide mechanistic insights into peptic ulcer disease.
GCST90270932	He Y	2023	11,964	240,675	East Asian-specific and cross-ancestry genome-wide meta-analyses provide mechanistic insights into peptic ulcer disease.
GCST90473781	UK Biobank Whole-Genome Sequencing Consortium	2025	9,327	449,113	Whole-genome sequencing of 490,640 UK Biobank participants.
GCST90667915	UK Biobank Whole-Genome Sequencing Consortium	2025	9,327	449,113	Whole-genome sequencing of 490,640 UK Biobank participants.
GCST90651854	Liu TY	2025	5,397	202,293	Diversity and longitudinal records: Genetic architecture of disease associations and polygenic risk in the Taiwanese Han population.
GCST90080199	Backman JD	2021	4,256	381,602	Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90084185	Backman JD	2021	4,256	381,602	Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90270929	He Y	2023	3,197	240,675	East Asian-specific and cross-ancestry genome-wide meta-analyses provide mechanistic insights into peptic ulcer disease.
GCST90436314	Zhou W	2018	3,002	401,525	Efficiently controlling for case-control imbalance and sample relatedness in large-scale genetic association studies.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

Tier	Variants
Tier 1: coding	2
Tier 2: splice/UTR	1
Tier 3: regulatory	2
Tier 4: intronic/intergenic	45

MAF distribution

Bucket	Variants
common (>=0.05)	36
low_freq (0.01-0.05)	0
rare (<0.01)	5
unknown	9

Functional consequences

Consequence	Count
intron_variant	26
unknown	11
intergenic_variant	7
regulatory_region_variant	2
5_prime_UTR_variant	1
frameshift_variant	1
stop_gained	1
synonymous_variant	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs2294008	8	142680513	C>T	0.362	5_prime_UTR_variant	JRK, PSCA	8e-189	Tier 2: splice/UTR
rs71514093	8	142681842	TG>T,TGG	0.365	intron_variant	PSCA, JRK	1e-188	Tier 4: intronic/intergenic
chr8:142678838							1e-22	Tier 4: intronic/intergenic
chr11:6252514							3e-20	Tier 4: intronic/intergenic
rs3805497	5	40746783	A>C,G,T	0.479	intron_variant	TTC33	1e-18	Tier 4: intronic/intergenic
chr19:48703417							1e-18	Tier 4: intronic/intergenic
rs373477888	5	40790539	T>TCTG,TG,TGTTG	0.386	intron_variant	PRKAA1	2e-18	Tier 4: intronic/intergenic
rs11665674	19	48693018	A>G,T	0.448	intergenic_variant	SEC1P - FUT2	3e-17	Tier 4: intronic/intergenic
rs8176719	9	133257522	T>TC	0.449	frameshift_variant	ABO	4e-17	Tier 1: coding
rs10500661	11	6252514	T>C	0.141	intergenic_variant	CNGA4 - CCKBR	7e-17	Tier 4: intronic/intergenic
rs148675590	13	27993672		0.191	intergenic_variant	RN7SL272P - FLT3	5e-16	Tier 4: intronic/intergenic
rs34074411	17	41710996	C>T	0.43	regulatory_region_variant	EIF1 - GAST	1e-15	Tier 3: regulatory
rs61160304	7	127609605	C>T	0.099	intergenic_variant	FSCN3 - PAX4	5e-15	Tier 4: intronic/intergenic
rs573784774	9	129791607	G>A	0	intron_variant	UBE2V1P4	2e-14	Tier 4: intronic/intergenic
chr8:143752994				0.495			6e-14	Tier 4: intronic/intergenic
rs5842244	20	58896229	AT>A,ATT,ATTT,ATTTT	0.288	intron_variant	GNAS	1e-13	Tier 4: intronic/intergenic
rs557100015	9	103352922	C>G	0.001	intergenic_variant	LINC01492 - RNA5SP291	2e-13	Tier 4: intronic/intergenic
rs78168911	13	100874639	C>G,T	0.001	intron_variant	NALCN-AS1	2e-12	Tier 4: intronic/intergenic
rs681343	19	48703205	C>A,T	0.05	stop_gained	FUT2	3e-12	Tier 1: coding
chr6:160352346							5e-12	Tier 4: intronic/intergenic
rs6117384	20	6692895	T>A,C,G	0.266	regulatory_region_variant	CASC20 - LINC01713	6e-12	Tier 3: regulatory
chr17:41710996							8e-12	Tier 4: intronic/intergenic
rs141625351	1	155160590	G>GTGTGTGTGT	0.097			2e-11	Tier 4: intronic/intergenic
rs79928271	3	169421687	T>A,C	0.277	intron_variant	MECOM	2e-11	Tier 4: intronic/intergenic
rs2920281	8	142679026	C>G,T	0.05	intergenic_variant	JRK, PSCA	3e-11	Tier 4: intronic/intergenic
rs573250197	19	40908707	T>C	0	intron_variant	CYP2A7P2, CYP2G1P, CYP2G1P, CYP2B7P, CYP2B7P	3e-11	Tier 4: intronic/intergenic
rs551365214	9	100827515	G>A,C	0.001	intron_variant	ACTG1P19 - GAPDHP26	4e-11	Tier 4: intronic/intergenic
rs60154219	3	169418777	C>G,T	0.268	intron_variant	MECOM	9e-11	Tier 4: intronic/intergenic
rs505922	9	133273813	C>T	0.46	intron_variant	ABO	1e-10	Tier 4: intronic/intergenic
rs687621	9	133261662	G>A,C,T	0.05	intron_variant	ABO	1e-10	Tier 4: intronic/intergenic

Genes & proteins

Mendelian disease overlap and somatic drivers

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

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
ABO	HGNC:79	ENSG00000175164	P16442	Histo-blood group ABO system transferase	gwas
PSCA	HGNC:9500	ENSG00000167653	O43653	Prostate stem cell antigen	gwas

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ABO	Histo-blood group ABO system transferase	This protein is the basis of the ABO blood group system.
PSCA	Prostate stem cell antigen	May be involved in the regulation of cell proliferation.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.5

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
Enzyme (other)	1	6.0×	0.320
Other/Unknown	1	0.9×	0.805

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
ABO	Enzyme (other)	yes	2.4.1.37	Glyco_trans_6, Nucleotide-diphossugar_trans
PSCA	Other/Unknown	no		LY6_UPA_recep-like, Toxin/TOLIP, Snake_toxin-like_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
buccal mucosa cell	1
right lobe of thyroid gland	1
tendon of biceps brachii	1
lower esophagus mucosa	1
mucosa of stomach	1
olfactory segment of nasal mucosa	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ABO	169	broad	marker	tendon of biceps brachii, buccal mucosa cell, right lobe of thyroid gland
PSCA	133	broad	marker	lower esophagus mucosa, mucosa of stomach, olfactory segment of nasal mucosa

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
PSCA	1,273
ABO	227

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
ABO	P16442	151
PSCA	O43653	1

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
Post-translational modification: synthesis of GPI-anchored proteins	1	167.9×	0.006	PSCA

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
regulation of neurotransmitter receptor activity	1	2106.5×	0.002	PSCA
acetylcholine receptor signaling pathway	1	312.1×	0.006	PSCA
negative regulation of ERK1 and ERK2 cascade	1	108.0×	0.012	PSCA
carbohydrate metabolic process	1	68.0×	0.015	ABO

Therapeutics

Drugs indicated for this disease

11 approved, 5 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Amoxicillin	Approved (phase 4)
Bismuth Subcitrate Potassium	Approved (phase 4)
Cimetidine	Approved (phase 4)
Clarithromycin	Approved (phase 4)
Famotidine	Approved (phase 4)
Lansoprazole	Approved (phase 4)
Metronidazole	Approved (phase 4)
Misoprostol	Approved (phase 4)
Nizatidine	Approved (phase 4)
Omeprazole	Approved (phase 4)
Sucralfate	Approved (phase 4)
Esomeprazole	Phase 3 (in late-stage trials)
Gefarnate	Phase 3 (in late-stage trials)
Ilaprazole	Phase 3 (in late-stage trials)
Rabeprazole	Phase 3 (in late-stage trials)
Tegoprazan	Phase 3 (in late-stage trials)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Aspirin, Naproxen, Teprenone.

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
ABO	0	0
PSCA	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
ABO	6	Binding:6

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
ABO	2.4.1.37, 2.4.1.40, 2.4.1.88	fucosylgalactoside 3-alpha-galactosyltransferase, glycoprotein-fucosylgalactoside alpha-N-acetylgalactosaminyltransferase, globoside alpha-N-acetylgalactosaminyltransferase

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).

Chemical tractability of cohort targets

0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

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	1	ABO
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	PSCA

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)
ABO	6	—
PSCA	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 47.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE3	19
Not specified	17
PHASE1	4
PHASE4	3
PHASE2/PHASE3	2
PHASE2	2

Top trials by phase / activity

NCT	Phase	Status	Title
NCT00854451	PHASE4	COMPLETED	Relation of Metabolic Rate of Omeprazole and Eradication of Helicobacter Pylori Infection
NCT02467621	PHASE4	COMPLETED	Stress Ulcer Prophylaxis in the Intensive Care Unit
NCT03667703	PHASE4	COMPLETED	Stress Ulcer Prophylaxis Versus Placebo in Critically Ill Infants With Congenital Heart Disease
NCT00132171	PHASE3	COMPLETED	Helicobacter Pylori Eradication With a New Sequential Treatment
NCT00149084	PHASE3	UNKNOWN	Tailored Treatment of H. Pylori Infection Based Polymorphisms of CYP2C19 and 23S rRNA of H. Pylori
NCT00197418	PHASE2/PHASE3	UNKNOWN	Second Line Therapy for the Cure of Helicobacter Pylori (H. Pylori) Infection
NCT00441727	PHASE3	COMPLETED	Study of Esomeprazole 20 mg or 40 mg vs Placebo Effectiveness on the Occurrence of Peptic Ulcers in Subjects on Low Dose Acetylsalicylic Acid (LDA)
NCT00542789	PHASE3	COMPLETED	Comparative Efficacy & Safety Study of Esomeprazole Versus Placebo for the Prevention of Gastric and Duodenal Ulcers With NSAID
NCT00595517	PHASE3	COMPLETED	Long Term Study to Investigate the Efficacy & Safety of D961H (Esomeprazole) for the Prevention of NSAIDs-induced Ulcer
NCT00762359	PHASE3	TERMINATED	A Safety and Efficacy Study of Lansoprazole in Preventing Aspirin-Induced Gastric and Duodenal Ulcers
NCT00787254	PHASE3	COMPLETED	Efficacy and Safety of Lansoprazole on Gastric and Duodenal Ulcers in Patients Taking Nonsteroidal Anti-Inflammatory Drugs
NCT00952978	PHASE3	COMPLETED	Ilaprazole for the Treatment of Duodenal Ulcer in Chinese Patients (Phase 3)
NCT01452724	PHASE3	COMPLETED	Efficacy and Safety of TAK-438 Compared to AG-1749 (Lansoprazole) in the Treatment of Duodenal Ulcer
NCT01452750	PHASE3	COMPLETED	Efficacy and Safety of TAK-438 for the Prevention of Recurrent Gastric or Duodenal Ulcers During Therapy of Non-steroidal Anti-inflammatory Drug (NSAID)
NCT01452763	PHASE3	COMPLETED	Efficacy and Safety of TAK-438 for the Prevention of Recurrent Gastric or Duodenal Ulcers During Therapy of Low-dose Aspirin
NCT01456247	PHASE3	COMPLETED	Long-term Extension Study of TAK-438 for the Prevention of Recurrent Gastric or Duodenal Ulcers During Therapy of Low-dose Aspirin
NCT01456260	PHASE3	COMPLETED	Long-term Extension Study of TAK-438 for the Prevention of Recurrent Gastric or Duodenal Ulcers During Therapy of Non-steroidal Anti-inflammatory Drug (NSAID)
NCT01568385	PHASE3	COMPLETED	A Unblinded Study of TAK-438 (20 mg) for Prevention of Recurrence of Gastric or Duodenal Ulcer During Long-Term Non-Steroid Anti-Inflammatory Drug (NSAID) Therapy
NCT01568398	PHASE3	COMPLETED	A Unblinded Study of TAK-438 (20 mg) for Prevention of Recurrence of Gastric or Duodenal Ulcer During Long-Term Low-Dose Aspirin Therapy
NCT02153398	PHASE3	COMPLETED	A Phase I/III Study of D961H 10 mg and 20 mg in Japanese Paediatric Patients With Gastrointestinal Acid Related Diseases
NCT02847455	PHASE2/PHASE3	COMPLETED	Ilaprazole for the Treatment of Duodenal Ulcer in Chinese Patients
NCT03050359	PHASE3	COMPLETED	Comparison of TAK-438 (Vonoprazan) to Lansoprazole in the Treatment of Duodenal Ulcer Participants With or Without Helicobacter Pylori Infection
NCT03553563	PHASE3	COMPLETED	A Study of Esomeplazole (D961H) in Japanese Paediatric Patients With Reflux Esophagitis, Gastric Ulcer or Duodenal Ulcer
NCT05010954	PHASE3	COMPLETED	Efficacy and Safety of LXI-15028 Comparing With Lansoprazole in the Treatment of Duodenal Ulcer
NCT00543868	PHASE2	COMPLETED	MK0782 + Low-Dose Aspirin 7-Day Erosion Endoscopy Study (0782-001)
NCT00953381	PHASE2	COMPLETED	Ilaprazole for the Treatment of Duodenal Ulcer in Chinese Patients (Phase 2)
NCT00284908	PHASE1	COMPLETED	Dose-Effect of S-Tenatoprazole-Na(STU-Na) 30 mg, 60 mg, 90 mg and 120 mg in Healthy Volunteers
NCT01964131	PHASE1	COMPLETED	BE Study Between a Capsule and a Sachet Formulation of D961H by Pharmacodynamics in Japanese Healthy Male Subjects
NCT05959499	PHASE1	COMPLETED	A Study to Evaluate the Pharmacokinetics and Safety Between Single Administration of BR6002 and Coadministration of BR6002A and BR6002B Under Fed Conditions in Healthy Adult Volunteers
NCT06165237	PHASE1	COMPLETED	A Study to Evaluate the Drug-drug Interaction and Safety Between BR6001-1 and BR6001-2
NCT04702542	Not specified	ACTIVE_NOT_RECRUITING	To Develop Methods for the Rehabilitation of Chronic Gastroduodenal Pathology in Children.
NCT07399054	Not specified	NOT_YET_RECRUITING	Efficacy and Safety of Esomeprazole 40 mg IV in Post-Surgical Patients Admitted to the ICU
NCT00173953	Not specified	COMPLETED	Lymphocytic Subsets and Cytokine Production With H. Pylori Infection
NCT00197470	Not specified	UNKNOWN	Cytokine Gene Polymorphisms in Gastric Diseases
NCT01037491	Not specified	UNKNOWN	Comparison of Ulcer Healing in Patients Taking Rabeprazole With Different Antiplatelets
NCT01199536	Not specified	COMPLETED	Helicobacter Pylori Eradication Treatment in Patients With Duodenal Ulcers
NCT01435525	Not specified	COMPLETED	Nexium Capsules Helicobacter Pylori Specific Clinical Experience Investigation
NCT01562600	Not specified	COMPLETED	Nexium Capsules Non-steroidal Anti-inflammatory Drug (NSAID) Specific Clinical Experience Investigation
NCT01729182	Not specified	COMPLETED	Nexium Capsules LDA Specific Clinical Experience Investigation
NCT01926600	Not specified	UNKNOWN	Sublingual Administration of PPI

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
VONOPRAZAN	4	24
LANSOPRAZOLE	4	9
RABEPRAZOLE	4	3
CLARITHROMYCIN	4	2
FAMOTIDINE	4	1
OMEPRAZOLE	4	1
PANTOPRAZOLE	4	1
SODIUM CHLORIDE	4	1
ILAPRAZOLE	3	3
GEFARNATE	3	2
INTERLEUKIN-10	2	1
TNF-ALPHA	0	1