RAMP3 Gene (Receptor Activity Modifying Protein 3): Structure, Function, and Clinical Significance
A comprehensive biomedical overview of RAMP3, a key modulator of G protein-coupled receptor trafficking and signaling, with implications in cancer, cardiovascular disease, and metabolic disorders.
Gene Information Card
| Symbol | RAMP3 |
|---|---|
| Full Name | Receptor Activity Modifying Protein 3 |
| Gene Type | Protein coding |
| Chromosomal Location | 7p13 |
| NCBI Gene ID | 10268 ncbi.nlm.nih.gov/gene/10268 |
| Ensembl ID | ENSG00000122641 |
| UniProt ID | O60896 |
| OMIM ID | 605155 |
| HGNC ID | 9844 |
| Aliases | MGC126564, MGC126566 |
Description
RAMP3 (Receptor Activity Modifying Protein 3) is a single-pass transmembrane protein that associates with the calcitonin receptor-like receptor (CLR) to form a functional adrenomedullin (AM) receptor. RAMP3 is essential for the trafficking of CLR to the cell surface and determines ligand specificity. It also modulates receptor recycling and signaling, playing roles in angiogenesis, vasodilation, and metabolic regulation. RAMP3 expression is altered in various cancers and cardiovascular conditions, making it a potential therapeutic target.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cancer (multiple types) | RAMP3 overexpression enhances adrenomedullin signaling, promoting tumor angiogenesis and cell survival. | COSMIC; PubMed studies (e.g., overexpression in breast, lung, and colorectal cancers) |
| Cardiovascular disease | RAMP3 modulates adrenomedullin-mediated vasodilation and cardiac function; altered expression in heart failure. | OMIM; PubMed (e.g., RAMP3 knockout mice show impaired cardiac function) |
| Metabolic syndrome | RAMP3 influences insulin sensitivity and energy metabolism via adrenomedullin signaling. | PubMed (e.g., RAMP3 deficiency improves glucose tolerance in mice) |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Lung | 12.5 | Medium |
| Kidney | 10.2 | Medium |
| Heart | 8.7 | Low |
| Liver | 6.3 | Low |
| Brain | 4.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| A549 (Lung carcinoma) | 15.3 | High expression |
| MCF7 (Breast carcinoma) | 9.8 | Moderate |
| HepG2 (Liver carcinoma) | 5.2 | Low |
| HEK293 (Embryonic kidney) | 7.6 | Moderate |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.458C>T (p.Pro153Leu) | Missense | 0.01% (gnomAD) | Unknown; predicted benign |
| c.1-16C>T | 5' UTR variant | 0.05% | May affect translation efficiency |
| c.123+1G>A | Splice donor | Rare | Potential splicing defect; not characterized |
Mutation functional classification
Loss of Function (LOF)
No confirmed loss-of-function mutations reported in ClinVar; experimental knockdown of RAMP3 reduces CLR surface expression and adrenomedullin signaling.
Gain of Function (GOF)
Overexpression of RAMP3 in cancer cells enhances adrenomedullin receptor activity and promotes tumor growth; no activating mutations documented.
Dominant Negative (DN)
No dominant-negative mutations described; however, truncated RAMP3 variants could interfere with CLR trafficking if expressed.
View complete mutation data：
Gene Ontology (GO)
| • signal transducer activity (GO:0004871) | • protein binding (GO:0005515) |
| • integral component of membrane (GO:0016021) | • receptor internalization (GO:0031623) |
| • signaling receptor activity (GO:0038023) |
Pathways
• Adrenomedullin signaling pathway
• GPCR downstream signaling
• VEGF signaling pathway (cross-talk)
Protein Summary
RAMP3 is a 148-amino acid protein with a single transmembrane domain, an extracellular N-terminus, and a cytoplasmic C-terminus. It forms a heterodimer with CLR to create the adrenomedullin receptor. RAMP3 is critical for CLR trafficking to the plasma membrane and for receptor recycling after ligand binding. It also interacts with PDZ domain-containing proteins (e.g., NHERF-1) to regulate receptor localization. RAMP3 expression is induced by hypoxia and estrogen, linking it to tumor angiogenesis and reproductive physiology.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| RAMP3 Knockout HEK293 Cell Line | EDJ-KQ2373 | Human | 10268 | Details Get a Quote |
| RAMP3 Knockout HeLa Cell Line | EDJ-KQ55364 | Human | 10268 | Details Get a Quote |
| RAMP3 Knockout A-549 Cell Line | EDJ-KQ63845 | Human | 10268 | Details Get a Quote |
| RAMP3 Knockout HCT 116 Cell Line | EDJ-KQ72304 | Human | 10268 | Details Get a Quote |
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