Chronic atrophic gastritis

Summary

Chronic atrophic gastritis (MONDO:0006665) is a disease with 1 cohort gene (10 GWAS associations across 10 studies) and 53 clinical trials. Top therapeutic interventions include blood, whole, curcumin, and netazepide.

At a glance

• Cohort genes: 1
• GWAS associations: 10
• Clinical trials: 53

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	chronic atrophic gastritis
Mondo ID	MONDO:0006665
EFO	EFO:1000826
MeSH	D005757
DOID	DOID:8929
ICD-10-CM	K29.4
NCIT	C7405
SNOMED CT	84568007
UMLS	C0017154
MedGen	42157
MedDRA	10003685
Is cancer (heuristic)	no

Also known as: atrophic Gastritides · atrophic gastritis · gastric atrophy · Gastritides, atrophic

Data availability: 10 GWAS associations (10 studies).

Disease family

Classification path: disease › human disease › disease by body system or component › digestive system disorder › stomach disorder › gastritis › chronic gastritis › chronic atrophic gastritis

Genetics & variants

GWAS landscape

10 GWAS associations across 10 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
rs572995086	5e-14	GREM2	G	2.52
rs2920283	2e-13	PSCA, JRK	T	0.63
rs182777447	2e-12	AXDND1	T	2.24
rs979521322	1e-11	M1AP	G	4.21
rs557016087	3e-11	VPS13D	G	2.92
rs2294008	4e-11	JRK, PSCA	C	0.43
rs150816279	9e-09	RFLNA	?
chr6:100062740	2e-07		A	0.17
rs35591543	1e-06	CREG1	G	0.17
rs2664153	1e-06	KLK4 - PPIAP59	A	0.19

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST90478351	Verma A	2024	2,236	439,071	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90478350	Verma A	2024	866	117,460	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90480301	Verma A	2024	866	117,460	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST008714	Hishida A	2019	479	0	GWAS analysis reveals a significant contribution of PSCA to the risk of Heliobacter pylori-induced gastric atrophy.
GCST90436319	Zhou W	2018	370	378,124	Efficiently controlling for case-control imbalance and sample relatedness in large-scale genetic association studies.
GCST90482143	Verma A	2024	338	58,242	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90651459	Liu TY	2025	203	197,546	Diversity and longitudinal records: Genetic architecture of disease associations and polygenic risk in the Taiwanese Han population.
GCST90044136	Jiang L	2021	180	456,168	A generalized linear mixed model association tool for biobank-scale data.
GCST008713	Hishida A	2019	120	0	GWAS analysis reveals a significant contribution of PSCA to the risk of Heliobacter pylori-induced gastric atrophy.
GCST90104151	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	1
Tier 3: regulatory	2
Tier 4: intronic/intergenic	7

MAF distribution

Bucket	Variants
common (>=0.05)	5
low_freq (0.01-0.05)	0
rare (<0.01)	4
unknown	1

Functional consequences

Consequence	Count
intron_variant	4
regulatory_region_variant	2
5_prime_UTR_variant	1
non_coding_transcript_exon_variant	1
unknown	1
intergenic_variant	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs572995086	1	240593002	G>A,T	0.001	intron_variant	GREM2	5e-14	Tier 4: intronic/intergenic
rs2920283	8	142675619	T>A,C,G	0.388	regulatory_region_variant	PSCA, JRK	2e-13	Tier 3: regulatory
rs182777447	1	179406133	T>C	0.002	intron_variant	AXDND1	2e-12	Tier 4: intronic/intergenic
rs979521322	2	74571387	G>A	0	intron_variant	M1AP	1e-11	Tier 4: intronic/intergenic
rs557016087	1	12275577	G>A	0.001	intron_variant	VPS13D	3e-11	Tier 4: intronic/intergenic
rs2294008	8	142680513	C>T	0.389	5_prime_UTR_variant	JRK, PSCA	4e-11	Tier 2: splice/UTR
rs150816279	12	124203424	C>T		non_coding_transcript_exon_variant	RFLNA	9e-09	Tier 4: intronic/intergenic
chr6:100062740				0.499			2e-07	Tier 4: intronic/intergenic
rs35591543	1	167540326	A>C,G,T	0.31	regulatory_region_variant	CREG1	1e-06	Tier 3: regulatory
rs2664153	19	50911996	G>A,C	0.199	intergenic_variant	KLK4 - PPIAP59	1e-06	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

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
gwas_only	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
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)
PSCA	Prostate stem cell antigen	May be involved in the regulation of cell proliferation.

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)
PSCA	Other/Unknown	no		LY6_UPA_recep-like, Toxin/TOLIP, Snake_toxin-like_sf

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
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
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

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
PSCA	O43653	1

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 1. 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
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 1 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	4213.0×	7e-04	PSCA
acetylcholine receptor signaling pathway	1	624.1×	0.002	PSCA
negative regulation of ERK1 and ERK2 cascade	1	216.1×	0.005	PSCA

Therapeutics

Drugs indicated for this disease

No approved or late-stage (phase ≥3) drug is indicated for this disease; the following are in earlier-phase trials only.

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

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
PSCA	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).

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

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)
PSCA	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 53.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	45
PHASE2	4
PHASE4	2
EARLY_PHASE1	2

Top trials by phase / activity

NCT	Phase	Status	Title
NCT02047994	PHASE4	RECRUITING	Multicentric Randomized Study of H. Pylori Eradication and Pepsinogen Testing for Prevention of Gastric Cancer Mortality
NCT01474044	PHASE4	COMPLETED	To Evaluate the Efficacy and Safety of Vitamin B12 Contains Extract of Lamb’s Stomach in Treatment of Chronic Atrophic Gastritis (CAG)
NCT02782949	PHASE2	ACTIVE_NOT_RECRUITING	Curcumin in Preventing Gastric Cancer in Patients With Chronic Atrophic Gastritis or Gastric Intestinal Metaplasia
NCT01339169	PHASE2	COMPLETED	YF476 and Type I Gastric Carcinoids
NCT01444014	PHASE2	TERMINATED	YF476 and Type I Gastric Carcinoids (Norway)
NCT05209633	PHASE2	UNKNOWN	Efficacy and Safety of Using Granules Dendrobii for the Treatment of Chronic Atrophic Gastritis
NCT04251403	EARLY_PHASE1	UNKNOWN	Novel Approach to Surveillance of Gastric Lesions
NCT05493124	EARLY_PHASE1	UNKNOWN	Clinical Study of Manpixiao in the Treatment of Chronic Atrophic Gastritis
NCT03250091	Not specified	RECRUITING	Surveillance of Patients With Precancerous Lesions of the Stomach
NCT04022109	Not specified	RECRUITING	Screening of Gastric Cancer Via Breath Volatile Organic Compounds by Hybrid Sensing Approach
NCT04191551	Not specified	RECRUITING	The GAstric Precancerous Conditions Study
NCT04613570	Not specified	RECRUITING	SUrveillance of PREMalignant Stomach - Individualized Endoscopic Follow-up
NCT04840056	Not specified	RECRUITING	Prediction of Gastric Cancer in Intestinal Metaplasia and Atrophic Gastritis
NCT05021029	Not specified	ENROLLING_BY_INVITATION	UC Davis Cohort of Pre-Malignant and Malignant Gastro-Intestinal DisEases Study
NCT05053945	Not specified	RECRUITING	Helicobacter Pylori, Atrophic Gastritis and Intestinal Metaplasia Registry and Prospective Study
NCT05657080	Not specified	RECRUITING	Cytosponge for Gastric Intestinal Metaplasia
NCT06203327	Not specified	RECRUITING	Atrophic Gastritis Predicts the Risk of Gastric Cancer
NCT06267703	Not specified	ACTIVE_NOT_RECRUITING	Multi-omics Analyses on Etiology and Early Detection of Stomach Cancer Precursor Lesions
NCT06370143	Not specified	RECRUITING	A Study Collecting Health Information to Understand and Prevent Gastric Cancer
NCT06489132	Not specified	NOT_YET_RECRUITING	Objective Study on Tongue Diagnosis of Chronic Atrophic Gastritis
NCT06707701	Not specified	NOT_YET_RECRUITING	Correlation Among Various OLGA and OLGIM Stages, Digestive Symptom Scores, and Acupuncture Treatment in Patients with Chronic Atrophic Gastritis
NCT06751212	Not specified	NOT_YET_RECRUITING	Observation on the Efficacy of Radiofrequency Ablation for Patients With Moderate to Severe Gastric Atrophy With Enterosis With or Without Atrophy of Intraepithelial Neoplasia: An Observational Study
NCT06912178	Not specified	NOT_YET_RECRUITING	Association of Sleep Quality With Pathologic Staging, Acupuncture Treatment in Patients With Chronic Atrophic Gastritis: a Cross-sectional Study
NCT07060482	Not specified	NOT_YET_RECRUITING	Gastrin, Anti-helicobacter Pylori and Pepsinogen Diagnostic Accuracy Study
NCT07152860	Not specified	NOT_YET_RECRUITING	Evaluation of the Efficacy of Electroacupuncture in the Treatment of Chronic Atrophic Gastritis
NCT07250308	Not specified	RECRUITING	Correlation Study of Atrophic Gastritis and Dyspepsia Symptoms
NCT07319338	Not specified	NOT_YET_RECRUITING	Objective Vascular Biomarkers as Triage for Depression in Chronic Atrophic Gastritis
NCT07388459	Not specified	RECRUITING	Natural History, Evolution, and Clinical Features of Autoimmune Atrophic Gastritis
NCT07605312	Not specified	NOT_YET_RECRUITING	AI-Based Risk Prediction Model for Upper Digestive Tract Cancer
NCT01824953	Not specified	COMPLETED	Long-term Follow-up Prognosis of Atrophic Gastritis After 3 Years
NCT01896310	Not specified	COMPLETED	New Classification of Stomach Using Probe-based Confocal Laser Endomicroscopy
NCT02184910	Not specified	UNKNOWN	Usefulness of Serum Pepsinogen and Gastrin as the Predictive Biomarker of Atrophic Gastritis, Intestinal Metaplasia and Gastric Cancer in Korea
NCT02332213	Not specified	COMPLETED	Volatile Markers in Digestive Cancer
NCT02351154	Not specified	COMPLETED	Grading Atrophic Gastritis by Confocal Laser Endomicroscopy Probe (p-CLE)
NCT02597517	Not specified	COMPLETED	New Technology to Differentiate Normal Gastric Mucosa From Helicobacter Pylori Associated Gastritis and Gastric Atrophy
NCT02691637	Not specified	COMPLETED	Effect of H. Pylori Eradication on the Reversibility of Atrophic Gastritis and Intestinal Metaplasia in Korean Patients
NCT02724280	Not specified	COMPLETED	Linked Color Imaging to Differentiate H. Pylori Associated Gastritis and Gastric Atrophy
NCT02833363	Not specified	UNKNOWN	Difference of Gastric Microbiota in the Process of Correa’s Model.
NCT02955134	Not specified	COMPLETED	The Study of Chinese Medicine for the Treatment of Chronic Atrophic Gastritis
NCT03228095	Not specified	UNKNOWN	Volatiles in Breath and Headspace Analysis - Diagnostic Markers

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
BLOOD, WHOLE	3	1
CURCUMIN	3	1
NETAZEPIDE	2	2
GASTRIN	2	1