GLP2R
protein-codingglucagon like peptide 2 receptor, the group of Glucagon receptor family
Gene summary
This gene encodes a G protein-coupled receptor closely related to the glucagon receptor that binds glucagon-like peptide 2 (GLP-2). Activation of this gene stimulates intestinal growth by increasing villus height, enhancing crypt cell proliferation, and reducing enterocyte apoptosis, thereby promoting nutrient absorption and maintaining gut barrier integrity. Glucagon like protein 2 receptor signaling also regulates intestinal blood flow, supports mucosal healing after injury, and modulates gut hormone secretion. In addition, it has been implicated in metabolic homeostasis and may influence energy balance and glucose metabolism. Dysregulation of this receptor or its signaling pathways is associated with intestinal disorders, including short bowel syndrome and inflammatory bowel disease. This receptor is a potential therapeutic target for enhancing intestinal regeneration and treating gastrointestinal diseases. [provided by RefSeq, Mar 2026]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~69.9 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to GLP2R variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_004246.3. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 1 | 2 | 3 | |||
| missense | 79 | 5 | 6 | 90 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 80 | 6 | 8 | 94 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_004237.1 | 13 | MANE Select | |
| Ensembl | ENSP00000262441.5 | 13 | MANE Select | |
| Ensembl | ENSP00000303605.5 | 3 | Standard | |
| Ensembl | ENSP00000404471.3 | 3 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Neuroactive ligand-receptor interaction - Homo sapiens (human)
- GPCRs, Class B Secretin-like
- Signaling by GPCR
- Signal Transduction
- G alpha (s) signalling events
Biological Process
- cell surface receptor signaling pathway
- G protein-coupled receptor signaling pathway
- adenylate cyclase-modulating G protein-coupled receptor signaling pathway
- positive regulation of cell population proliferation
- cellular response to glucagon stimulus
Molecular Function
- G protein-coupled receptor activity
- glucagon receptor activity
- G protein-coupled peptide receptor activity
- peptide hormone binding
Cellular Component
- plasma membrane
- integral component of membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000262441
- Coding exons
- 13
- Length
- 69897
- Individuals with no LoFs
- 125676
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 71
- Defined
- 125747
- p
- 0.000282
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.16 | 251 | 308 | 0.814 | 0.0000172 | 3551 |
| Missense (PolyPhen) | 67 | 109.19 | 0.61361 | 1321 | ||
| Synonymous | -0.524 | 131 | 124 | 1.06 | 0.00000693 | 1102 |
| Loss of Function | 1.88 | 22 | 33.8 | 0.652 | 0.00000184 | 363 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00025 | 0.00025 | rare |
| Latino/Admixed American | 0.0013 | 0.0012 | notable |
| Ashkenazi Jewish | 0.00011 | 0.000099 | rare |
| East Asian | 0.000054 | 0.000054 | rare |
| Finnish | 0.000046 | 0.000046 | rare |
| European (Non-Finnish) | 0.00014 | 0.00014 | rare |
| South Asian | 0.00014 | 0.00013 | rare |
| Other | 0.00017 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: This is a receptor for glucagon-like peptide 2. The activity of this receptor is mediated by G proteins which activate adenylyl cyclase.;
Recessive Scores
- pRec
- 0.147
Intolerance Scores
- LoFtool
- 0.824
- RVIS EVS
- 1.02
- RVIS percentile EVS
- 91.05
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.354
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |