GLP2R

Chr 17

glucagon like peptide 2 receptor

NCBI Gene: 9340ENSG00000065325UniProt: O95838

This gene encodes a G protein-coupled receptor that is closely related to the glucagon receptor and binds to glucagon-like peptide-2 (GLP2). Signalling through GLP2 stimulates intestinal growth and increases villus height in the small intestine, concomitant with increased crypt cell proliferation and decreased enterocyte apoptosis. [provided by RefSeq, Dec 2014]

110
ClinVar variants
11
Pathogenic / LP
0.00
pLI score
2
Active trials
Clinical Summary— GLP2R
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
11 Pathogenic / Likely Pathogenic· 85 VUS of 110 total submissions
💊
Clinical Trials
2 active or recruiting trials — potential therapeutic options may be available

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.
0.93LOEUF
pLI 0.000
Z-score 1.88
OE 0.65 (0.47–0.93)
Tolerant

Typical tolerance to LoF variation

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.
1.16Z-score
OE missense 0.81 (0.73–0.90)
251 obs / 308.3 exp
Tolerant

Mild missense constraint

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.0.65 (0.47–0.93)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.81 (0.73–0.90)
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.1.06
0≤1.21.6
LoF obs/exp: 22 / 33.8Missense obs/exp: 251 / 308.3Syn Z: -0.52

ClinVar Variant Classifications

110 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic11
VUS85
Likely Benign6
Benign8
11
Pathogenic
85
VUS
6
Likely Benign
8
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
11
0
11
Likely Pathogenic
0
0
0
0
0
VUS
0
78
7
0
85
Likely Benign
0
5
0
1
6
Benign
0
6
0
2
8
Total089183110

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

View in ClinVar →

Protein Context — Lollipop Plot

GLP2R · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
GLP2-GLP2R signal affects the viability and EGFR-TKIs sensitivity of PC9 and HCC827 cells.
Song B et al.·BMC Pulm Med
2022
A cross-platform approach identifies genetic regulators of human metabolism and health.
Lotta LA et al.·Nat Genet
2021
Methylation Status of GLP2R, LEP and IRS2 in Small for Gestational Age Children with and without Catch-up Growth.
Angulo M et al.·J Clin Res Pediatr Endocrinol
2021
Global glucagon-like peptide-2 receptor activation linked to increased obesity risk in the UK Biobank.
Gerlach PA et al.·Metabolism
2026
Large-Scale Genome-Wide Association Study of East Asians Identifies Loci Associated With Risk for Colorectal Cancer.
Lu Y et al.·Gastroenterology
2019Meta-analysis
Glucagon and glucagon-like peptide receptors as drug targets.
Estall JL et al.·Curr Pharm Des
2006Review
Gut hormones, and short bowel syndrome: the enigmatic role of glucagon-like peptide-2 in the regulation of intestinal adaptation.
Martin GR et al.·World J Gastroenterol
2006Review
Development and verification of a combined immune- and cancer-associated fibroblast related prognostic signature for colon adenocarcinoma.
Wei J et al.·Front Immunol
2024
Review article: a comparison of glucagon-like peptides 1 and 2.
Janssen P et al.·Aliment Pharmacol Ther
2013Review
A Prognostic Model Based on the Immune-related Genes in Colon Adenocarcinoma.
Sun YL et al.·Int J Med Sci
2020Functional
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
Incretin Effect

The Effect of GIP, GLP-1 and GLP-2 in Individuals With Genetically Altered Receptor Function

RECRUITING
NCT06194955Phase NAUniversity of CopenhagenStarted 2023-01-04
GIP(1-42)GLP-1GLP-2
Postural Orthostatic Tachycardia Syndrome (POTS)Healthy

POTS-FLOW: Interplay Between Gut Hormones and Autonomic Postprandial Blood Flow Regulation in Patients With POTS

RECRUITING
NCT07019519Phase NAUniversity of CopenhagenStarted 2025-03-15
Saline/PlaceboGIPR antagonistGLP-1R antagonist

External Resources

Links to major genomics databases and tools