HRH3 (Histamine Receptor H3)
G protein-coupled receptor for histamine, involved in neurotransmission and potential therapeutic target for neurological disorders.
Gene Information Card
| Symbol | HRH3 |
|---|---|
| Full Name | Histamine Receptor H3 |
| Gene Type | protein-coding |
| Chromosomal Location | 20q13.33 |
| NCBI Gene ID | 11255 ncbi.nlm.nih.gov/gene/11255 |
| Ensembl ID | ENSG00000101199 |
| UniProt ID | Q9Y5N1 |
| OMIM ID | 604525 |
| HGNC ID | 5184 |
| Aliases | GPCR97, HH3R, H3R |
Description
HRH3 encodes the histamine H3 receptor, a G protein-coupled receptor (GPCR) that inhibits neurotransmitter release in the central and peripheral nervous systems. It is predominantly expressed in the brain and modulates histamine, dopamine, serotonin, and acetylcholine release. The receptor is a target for drugs treating cognitive disorders, sleep-wake disturbances, and obesity.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Attention deficit hyperactivity disorder (ADHD) | HRH3 polymorphisms may alter histaminergic signaling affecting attention and impulse control. | PMID: 19118867 |
| Narcolepsy | HRH3 antagonists promote wakefulness by increasing histamine release. | PMID: 20030577 |
| Obesity | HRH3 regulates appetite via histamine modulation in the hypothalamus. | PMID: 15673519 |
| Schizophrenia | HRH3 variants linked to altered dopamine signaling and cognitive symptoms. | PMID: 20628016 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | High |
| Spinal cord | 5.2 | Medium |
| Adrenal gland | 3.1 | Low |
| Stomach | 2.8 | Low |
| Heart | 1.0 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 8.7 | Neuronal model |
| U-87 MG (glioblastoma) | 6.4 | Astrocytic expression |
| HEK293 (embryonic kidney) | 0.5 | Low endogenous expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.19C>T (p.Arg7Cys) | Missense | <0.01% | Reduced receptor activity |
| c.364G>A (p.Ala122Thr) | Missense | <0.01% | Altered ligand binding |
| c.1069G>A (p.Val357Ile) | Missense | <0.01% | Unknown functional effect |
Mutation functional classification
Loss of Function (LOF)
p.Arg7Cys reduces receptor signaling in vitro.
Gain of Function (GOF)
No confirmed gain-of-function mutations reported.
Dominant Negative (DN)
Not documented for HRH3.
View complete mutation data：
Gene Ontology (GO)
| • G protein-coupled receptor activity | • histamine receptor activity |
| • G protein-coupled receptor signaling pathway | • synaptic transmission |
| • cholinergic | • regulation of neurotransmitter secretion |
| • adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway |
Pathways
• Histamine signaling pathway (Reactome: R-HSA-388479)
• GPCR downstream signaling (Reactome: R-HSA-388396)
• Neurotransmitter release cycle (Reactome: R-HSA-112310)
Protein Summary
The histamine H3 receptor is a 445-amino acid protein with seven transmembrane domains typical of GPCRs. It couples to Gi/o proteins, inhibiting adenylate cyclase and reducing cAMP levels. The receptor is predominantly expressed in the CNS, where it acts as a presynaptic autoreceptor and heteroreceptor, modulating the release of multiple neurotransmitters. Its structure includes an extracellular N-terminus and intracellular C-terminus with phosphorylation sites regulating desensitization.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| HRH3 Knockout HEK293 Cell Line | EDJ-KQ7353 | Human | 11255 | Details Get a Quote |
| HRH3 Knockout HeLa Cell Line | EDJ-KQ55614 | Human | 11255 | Details Get a Quote |
| HRH3 Knockout A-549 Cell Line | EDJ-KQ64113 | Human | 11255 | Details Get a Quote |
| HRH3 Knockout HCT 116 Cell Line | EDJ-KQ72558 | Human | 11255 | Details Get a Quote |
