GIPR Gene - Glucose-Dependent Insulinotropic Polypeptide Receptor
A key regulator of insulin secretion and metabolic homeostasis
Gene Information Card
| Symbol | GIPR |
|---|---|
| Full Name | Glucose-dependent insulinotropic polypeptide receptor |
| Gene Type | protein-coding |
| Chromosomal Location | 19q13.32 |
| NCBI Gene ID | 2696 ncbi.nlm.nih.gov/gene/2696 |
| Ensembl ID | ENSG00000160050 |
| UniProt ID | P48546 |
| OMIM ID | 137020 |
| HGNC ID | 4271 |
| Aliases | GIP-R, GIPR1 |
Description
The GIPR gene encodes the glucose-dependent insulinotropic polypeptide receptor, a G protein-coupled receptor primarily expressed in pancreatic beta cells. Upon binding its ligand GIP, the receptor stimulates insulin secretion in a glucose-dependent manner, playing a critical role in postprandial glucose homeostasis. GIPR is also expressed in adipose tissue, bone, and the central nervous system, where it modulates energy balance and lipid metabolism.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Type 2 Diabetes | Reduced GIPR signaling impairs insulin secretion, contributing to hyperglycemia | ClinVar, NCBI |
| Obesity | GIPR variants (e.g., rs1800437) are associated with altered body mass index and fat distribution | OMIM, NCBI |
| Monogenic Diabetes (MODY) | Rare GIPR loss-of-function mutations cause impaired glucose-stimulated insulin secretion | ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Pancreas | 12.5 | High |
| Adipose Tissue | 3.2 | Medium |
| Stomach | 2.1 | Medium |
| Small Intestine | 1.8 | Low |
| Brain | 0.9 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| INS-1 (rat beta cell) | 15.0 | High expression; used for insulin secretion studies |
| MIN6 (mouse beta cell) | 14.2 | High expression; glucose-responsive |
| 3T3-L1 (adipocyte) | 4.5 | Differentiated adipocytes show moderate expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| rs1800437 (Glu354Gln) | Missense | 5-10% in European populations | Reduced receptor activity; associated with obesity |
| c.205C>T (Arg69Cys) | Missense | Rare | Loss of function; linked to impaired insulin secretion |
| c.1100G>A (Arg367His) | Missense | Rare | Gain of function; increased cAMP signaling |
Mutation functional classification
Loss of Function (LOF)
Mutations such as Arg69Cys reduce GIP binding or receptor activation, leading to diminished insulin secretion and increased risk of type 2 diabetes.
Gain of Function (GOF)
Mutations like Arg367His enhance receptor signaling, potentially increasing insulin secretion but also linked to altered metabolic responses.
Dominant Negative (DN)
No well-characterized dominant-negative mutations reported for GIPR.
View complete mutation data：
Gene Ontology (GO)
| • G protein-coupled receptor activity | • glucose-dependent insulinotropic polypeptide receptor activity |
| • adenylate cyclase-activating G protein-coupled receptor signaling pathway | • positive regulation of insulin secretion |
| • cellular response to glucose stimulus |
Pathways
• GIPR signaling pathway (Reactome: R-HSA-418555)
• Incretin pathway (KEGG: hsa04930)
• GPCR downstream signaling (cAMP/PKA cascade)
Protein Summary
The GIPR protein is a 466-amino acid transmembrane receptor belonging to the secretin receptor family of GPCRs. It consists of a large N-terminal extracellular domain for ligand binding, seven transmembrane helices, and a C-terminal intracellular tail that couples to Gs proteins. Activation by GIP leads to increased cAMP production and downstream activation of PKA and EPAC, promoting insulin granule exocytosis. The receptor is also involved in beta cell proliferation and survival.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| GIPR Knockout HEK293 Cell Line | EDJ-KQ1774 | Human | 2696 | Details Get a Quote |
| GIPR Knockout HCT 116 Cell Line | EDJ-KQ21643 | Human | 2696 | Details Get a Quote |
| GIPR Knockout HeLa Cell Line | EDJ-KQ53343 | Human | 2696 | Details Get a Quote |
| GIPR Knockout A-549 Cell Line | EDJ-KQ61822 | Human | 2696 | Details Get a Quote |
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