AGR3

Chr 7

anterior gradient 3, protein disulphide isomerase family member

Also known as: AG-3, AG3, BCMP11, HAG3, PDIA18, hAG-3

NCBI Gene: 155465ENSG00000173467UniProt: Q8TD06

This gene encodes a member of the disulfide isomerase (PDI) family of endoplasmic reticulum (ER) proteins that catalyze protein folding and thiol-disulfide interchange reactions. The encoded protein has an N-terminal ER-signal sequence, a catalytically active thioredoxin domain, and a C-terminal ER-retention sequence. This gene is expressed in ciliated airway epithelial cells and, in mouse, plays a role in ciliary beat frequency in multiciliated cells. This gene is also over-expressed in breast, ovarian, and prostrate cancers. [provided by RefSeq, Dec 2016]

81
ClinVar variants
37
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— AGR3
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
37 Pathogenic / Likely Pathogenic· 36 VUS of 81 total submissions
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
1.98LOEUF
pLI 0.000
Z-score -3.07
OE 2.00 (1.31–1.98)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
-0.90Z-score
OE missense 1.28 (1.09–1.50)
106 obs / 83.0 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.2.00 (1.31–1.98)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.28 (1.09–1.50)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.92
0≤1.21.6
LoF obs/exp: 22 / 11.0Missense obs/exp: 106 / 83.0Syn Z: 0.34

ClinVar Variant Classifications

81 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic34
Likely Pathogenic3
VUS36
Likely Benign6
Benign2
34
Pathogenic
3
Likely Pathogenic
36
VUS
6
Likely Benign
2
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
34
0
34
Likely Pathogenic
0
0
3
0
3
VUS
0
24
12
0
36
Likely Benign
0
1
5
0
6
Benign
0
0
2
0
2
Total02556081

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

AGR3 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype

OMIM

No OMIM entries found.

Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
AGR2 and AGR3 play an important role in the clinical characterization and prognosis of basal like breast cancer.
de Moraes CL et al.·Clin Breast Cancer
2022
Anterior Gradient-3: a novel biomarker for ovarian cancer that mediates cisplatin resistance in xenograft models.
Gray TA et al.·J Immunol Methods
2012Functional
Anterior Gradient 3 Promotes Breast Cancer Development and Chemotherapy Response.
Xu Q et al.·Cancer Res Treat
2020
The Anterior GRadient (AGR) family proteins in epithelial ovarian cancer.
Fessart D et al.·J Exp Clin Cancer Res
2021Review
Combination of TP53 and AGR3 to distinguish ovarian high-grade serous carcinoma from low-grade serous carcinoma.
Qiu C et al.·Int J Oncol
2018
Evaluation of AGR2 and AGR3 as candidate genes for inflammatory bowel disease.
Zheng W et al.·Genes Immun
2006
The anterior gradient homolog 3 (AGR3) gene is associated with differentiation and survival in ovarian cancer.
King ER et al.·Am J Surg Pathol
2011
GWAS of 165,084 Japanese individuals identified nine loci associated with dietary habits.
Matoba N et al.·Nat Hum Behav
2020
A novel triaptosis-related prognostic signature to assess the clinical value in HER2-low breast cancer: evidence from clinical cohorts and experimental validation.
Liu J et al.·Apoptosis
2026Cohort
Community-associated methicillin-resistant and methicillin-sensitive Staphylococcus aureus: skin and soft tissue infections in Hong Kong.
Ho PL et al.·Diagn Microbiol Infect Dis
2008
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools