HRH2 (Histamine Receptor H2)
G protein-coupled receptor for histamine; key target in gastric acid regulation and antihistamine therapy
Gene Information Card
| Symbol | HRH2 |
|---|---|
| Full Name | Histamine Receptor H2 |
| Gene Type | protein-coding |
| Chromosomal Location | 5q35.2 |
| NCBI Gene ID | 3274 ncbi.nlm.nih.gov/gene/3274 |
| Ensembl ID | ENSG00000168765 |
| UniProt ID | P25021 |
| OMIM ID | 142703 |
| HGNC ID | 5183 |
| Aliases | H2R, H2-R, H2RB, H2R_HUMAN |
Description
The HRH2 gene encodes the histamine H2 receptor, a G protein-coupled receptor (GPCR) that mediates histamine signaling. It is primarily expressed in gastric parietal cells, where it stimulates gastric acid secretion, and also in cardiac, smooth muscle, and immune cells. The receptor couples to Gs proteins, activating adenylate cyclase and increasing intracellular cAMP. HRH2 is a major pharmacological target for H2 receptor antagonists (e.g., ranitidine, famotidine) used to treat peptic ulcer disease and gastroesophageal reflux.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Gastric ulcer / GERD | HRH2 activation increases gastric acid secretion; antagonists block this effect | ClinVar, OMIM |
| Schizophrenia | HRH2 polymorphisms associated with altered histamine signaling in CNS | NCBI Gene, OMIM |
| Allergic rhinitis | HRH2 modulates histamine-induced vasodilation and bronchoconstriction | NCBI Gene |
| Cardiovascular effects | HRH2 activation in heart may contribute to positive inotropic and chronotropic effects | UniProt |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Stomach | 12.5 | Medium |
| Heart | 8.3 | Medium |
| Lung | 5.1 | Low |
| Brain | 3.2 | Low |
| Spleen | 2.8 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 15.2 | Recombinant expression |
| K562 | 1.5 | Endogenous low expression |
| A549 | 2.1 | Endogenous low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.314A>G (p.Asn105Ser) | Missense | <0.01% | Altered ligand binding; reduced cAMP response |
| c.649G>A (p.Gly217Arg) | Missense | <0.01% | Impaired receptor activation |
| c.1076C>T (p.Pro359Leu) | Missense | <0.01% | Unknown functional effect |
Mutation functional classification
Loss of Function (LOF)
p.Asn105Ser and p.Gly217Arg reduce receptor signaling and cAMP production.
Gain of Function (GOF)
No confirmed gain-of-function mutations reported.
Dominant Negative (DN)
No dominant-negative mutations reported.
View complete mutation data：
Gene Ontology (GO)
| • G protein-coupled receptor activity | • histamine receptor activity |
| • adenylate cyclase-activating G protein-coupled receptor signaling pathway | • positive regulation of gastric acid secretion |
| • plasma membrane |
Pathways
• Histamine signaling pathway (Reactome: R-HSA-375280)
• GPCR downstream signaling (Reactome: R-HSA-388396)
• cAMP-mediated signaling (KEGG: hsa04024)
Protein Summary
The HRH2 protein is a 359-amino acid GPCR with seven transmembrane domains. It binds histamine with high affinity and couples to Gs proteins to stimulate cAMP production. The receptor is expressed in stomach, heart, lung, and brain. It plays a central role in gastric acid secretion and is a therapeutic target for H2 antagonists. Mutations affecting ligand binding or signaling are rare but can alter receptor function.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| HRH2 Knockout HEK293 Cell Line | EDJ-KQ1556 | Human | 3274 | Details Get a Quote |
| HRH2 Knockout A-549 Cell Line | EDJ-KQ21230 | Human | 3274 | Details Get a Quote |
| HRH2 Knockout HeLa Cell Line | EDJ-KQ53572 | Human | 3274 | Details Get a Quote |
| HRH2 Knockout HCT 116 Cell Line | EDJ-KQ70520 | Human | 3274 | Details Get a Quote |
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