RAMP1: Receptor Activity Modifying Protein 1 – Structure, Function, and Clinical Relevance
A comprehensive biomedical overview of RAMP1, a key regulator of GPCR signaling, with emphasis on its role in CGRP receptor function, disease associations, and tissue-specific expression.
Gene Information Card
| Symbol | RAMP1 |
|---|---|
| Full Name | Receptor Activity Modifying Protein 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 2q36.3 |
| NCBI Gene ID | 10267 ncbi.nlm.nih.gov/gene/10267 |
| Ensembl ID | ENSG00000132329 |
| UniProt ID | O60894 |
| OMIM ID | 605153 |
| HGNC ID | 9842 |
| Aliases | RAMP1; receptor (calcitonin) activity modifying protein 1 |
Description
RAMP1 encodes receptor activity modifying protein 1, a single-pass transmembrane protein that forms heterodimers with calcitonin receptor-like receptor (CALCRL) to create the CGRP receptor. RAMP1 is essential for ligand specificity, receptor trafficking, and signaling. It is widely expressed in the nervous system, cardiovascular tissues, and immune cells, and is implicated in pain transmission, vasodilation, and inflammatory responses.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Migraine | RAMP1 modulates CGRP receptor function; elevated CGRP levels and receptor activity contribute to neurogenic inflammation and vasodilation in migraine pathogenesis. | Genetic association studies and clinical efficacy of CGRP receptor antagonists (gepants) confirm RAMP1's role. |
| Hypertension | RAMP1-mediated CGRP signaling influences vascular tone; altered RAMP1 expression may affect blood pressure regulation. | Animal models and expression studies in vascular tissues. |
| Osteoarthritis | RAMP1 is involved in CGRP signaling in joint innervation, contributing to pain and inflammation in osteoarthritis. | Expression studies in synovial tissue and animal models. |
| Cancer | RAMP1 expression in tumor microenvironment may modulate angiogenesis and tumor growth via CGRP signaling. | Preclinical studies in various cancer cell lines and xenografts. |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Lung | 12.3 | Medium |
| Brain | 8.5 | Low |
| Heart | 6.2 | Low |
| Kidney | 4.1 | Low |
| Liver | 1.0 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 15.2 | High expression; used in CGRP receptor studies. |
| A549 (lung carcinoma) | 8.7 | Moderate expression; relevant to lung cancer studies. |
| HUVEC (endothelial) | 5.3 | Low expression; vascular function studies. |
| HEK293 (embryonic kidney) | 2.1 | Low endogenous; often used for transfection. |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| rs3754701 | SNP (intronic) | Minor allele frequency ~0.3 | Associated with altered RAMP1 expression and migraine susceptibility in some populations. |
| rs7590387 | SNP (5' UTR) | Minor allele frequency ~0.2 | Potential effect on translation efficiency; linked to hypertension risk. |
| c.458C>T (p.Pro153Leu) | Missense | Rare (<0.01) | May affect protein stability; clinical significance uncertain. |
Mutation functional classification
Loss of Function (LOF)
RAMP1 loss-of-function mutations are rare; complete knockout in mice leads to reduced CGRP receptor function and altered pain responses.
Gain of Function (GOF)
No clear gain-of-function mutations reported; overexpression of RAMP1 can enhance CGRP receptor signaling in vitro.
Dominant Negative (DN)
No dominant-negative mutations described; however, truncated RAMP1 variants could interfere with receptor assembly.
View complete mutation data：
Gene Ontology (GO)
| • signal transducer activity (GO:0004871) | • protein binding (GO:0005515) |
| • integral component of membrane (GO:0016021) | • plasma membrane (GO:0005886) |
| • receptor activity (GO:0031623) | • signal transduction (GO:0007165) |
Pathways
• CGRP receptor signaling pathway
• GPCR downstream signaling (cAMP production)
• Neurogenic inflammation pathway
• Vasodilation pathway
Protein Summary
RAMP1 is a 148-amino acid single-pass type I transmembrane protein with a large extracellular N-terminal domain. It associates with CALCRL to form a functional CGRP receptor. RAMP1 is critical for ligand binding and receptor trafficking to the cell surface. Upon CGRP binding, the receptor activates Gαs, increasing cAMP levels and downstream signaling. RAMP1 is also involved in receptor for adrenomedullin (AM1) when paired with CALCRL, but with lower affinity. Its expression is regulated in response to inflammatory stimuli and is a target for migraine therapeutics.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| RAMP1 Knockout HEK293 Cell Line | EDJ-KQ6353 | Human | 10267 | Details Get a Quote |
| CRAMP1 Knockout HEK293 Cell Line | EDJ-KQ13000 | Human | 57585 | Details Get a Quote |
| RAMP1 Knockout HCT 116 Cell Line | EDJ-KQ31687 | Human | 10267 | Details Get a Quote |
| CRAMP1 Knockout A-549 Cell Line | EDJ-KQ42253 | Human | 57585 | Details Get a Quote |
| CRAMP1 Knockout HCT 116 Cell Line | EDJ-KQ42254 | Human | 57585 | Details Get a Quote |
| CRAMP1 Knockout HeLa Cell Line | EDJ-KQ42255 | Human | 57585 | Details Get a Quote |
| RAMP1 Knockout HeLa Cell Line | EDJ-KQ55363 | Human | 10267 | Details Get a Quote |
| RAMP1 Knockout A-549 Cell Line | EDJ-KQ63844 | Human | 10267 | Details Get a Quote |
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