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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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RAMP3
receptor activity modifying protein 3
Chromosome 7 · 7p13
NCBI Gene: 10268Ensembl: ENSG00000122679.9HGNC: HGNC:9845UniProt: A4D2L1
63PubMed Papers
20Diseases
2Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
ReceptorTransporter
CLINICAL
FDA Approved Target
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
lysosomeplasma membranepositive regulation of cAMP/PKA signal transductionamylin receptor 3 signaling pathwaydiabetes mellitustype 1 diabetes mellitustype 2 diabetes mellitusneurodegenerative disease
✦AI Summary

RAMP3 (receptor activity modifying protein 3) is an accessory protein that modulates G-protein coupled receptor function by forming heteromeric complexes with calcitonin receptors and related proteins. RAMP3 acts as a required co-factor for plasma membrane trafficking of receptors including calcitonin receptor-like receptor (CALCRL) and G-protein coupled estrogen receptor 1 (GPER1) 12. As a structural component, RAMP3 combines with CALCRL to form the adrenomedullin 2 (ADM2) receptor complex 34 and with calcitonin receptor (CTR) to constitute the amylin receptor 3 (AMY3R), where it stabilizes subunit interactions and regulates agonist-dependent signaling dynamics 56. RAMP3-mediated signaling activates downstream cAMP and calcium-dependent pathways 57. Clinically, RAMP3 variants are associated with age-related changes in body composition and increased fracture risk in elderly women 89. The ADM2-RAMP3 pathway promotes tissue-protective responses in intestinal innate lymphoid cells, with altered expression observed in inflammatory bowel disease patients 3. Additionally, RAMP3 participates in cardiovascular regulation through cerebellar adrenomedullinergic signaling, with dysregulation contributing to hypertension 7.

Sources cited
1
RAMP3 forms stable AMY3R heterodimers with CTR that determine cAMP signaling and are modulated by agonists
PMID: 40828907
2
RAMP3 alters calcitonin receptor pharmacology from calcitonin-preferring to amylin-preferring, with CTR+RAMP3 comprising amylin3(a) receptors
PMID: 16492540
3
RAMP3 gene polymorphisms associate with age-related changes in body composition and increased fracture risk in elderly women
PMID: 32550545
4
RAMP3 variation contributes to age-related changes in body composition and fracture risk
PMID: 34530989
5
CALCRL and RAMP3 expression is altered in inflammatory bowel disease patients and the ADM2-RAMP3 pathway promotes tissue-protective ILC2 responses
PMID: 40817416
6
RAMP3 amino acid residues determine adrenomedullin and intermedin binding specificity and potency at AM2 receptors
PMID: 21402116
7
RAMP3 forms AM2 receptors involved in cerebellar cardiovascular regulation with dysregulation during hypertension
PMID: 27614623
8
RAMP3 is required for CALCRL and GPER1 plasma membrane transport and plays cardioprotective roles
PMID: 23674134
9
RAMP3 modulates CALCRL and GPER1 function and is required for receptor transport to plasma membrane
PMID: 9620797
Disease Associationsⓘ20
diabetes mellitusOpen Targets
0.43Moderate
type 1 diabetes mellitusOpen Targets
0.39Weak
type 2 diabetes mellitusOpen Targets
0.36Weak
neurodegenerative diseaseOpen Targets
0.33Weak
neuroinflammatory disorderOpen Targets
0.27Weak
HyperhidrosisOpen Targets
0.26Weak
ulcerative colitisOpen Targets
0.22Weak
pericarditisOpen Targets
0.14Weak
tympanic membrane perforationOpen Targets
0.14Weak
diverticular diseaseOpen Targets
0.12Weak
obesityOpen Targets
0.12Weak
alcohol drinkingOpen Targets
0.07Suggestive
neoplasmOpen Targets
0.06Suggestive
hepatocellular carcinomaOpen Targets
0.06Suggestive
adolescent idiopathic scoliosisOpen Targets
0.05Suggestive
pneumoniaOpen Targets
0.04Suggestive
cancerOpen Targets
0.03Suggestive
gliomaOpen Targets
0.03Suggestive
asthmaOpen Targets
0.03Suggestive
non-small cell lung carcinomaOpen Targets
0.02Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Drug Targets2
PRAMLINTIDEApproved
Amylin receptor AMY2; CALCR/RAMP2 agonist
diabetes mellitus
PRAMLINTIDE ACETATEApproved
Amylin receptor AMY2; CALCR/RAMP2 agonist
Related Genes
ADMProtein interaction100%CALCAProtein interaction100%CALCBProtein interaction100%IAPPProtein interaction100%GRM1Protein interaction90%GNASProtein interaction90%
Tissue Expression6 tissues
Lung
100%
Heart
75%
Liver
17%
Brain
8%
Ovary
6%
Bone Marrow
1%
Gene Interaction Network
Click a node to explore
RAMP3ADMCALCACALCBIAPPGRM1GNAS
PROTEIN STRUCTURE
Preparing viewer…
PDB8F0K · 1.90 Å · EM
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
1.71LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF1.12 [0.74–1.71]
RankingsWhere RAMP3 stands among ~20K protein-coding genes
  • #7,398of 20,598
    Most Researched63
  • #640of 1,025
    FDA-Approved Drug Targets2
  • #16,157of 17,882
    Most Constrained (LOEUF)1.71
Genes detectedRAMP3
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Amylin receptor subunit interactions are modulated by agonists and determine signaling.
PMID: 40828907
Sci Signal · 2025
1.00
2
Receptor pharmacology.
PMID: 16492540
Adv Pharmacol · 2005
0.90
3
Analysis of RAMP3 gene polymorphism with body composition and bone density in young and elderly women.
PMID: 32550545
Gene X · 2019
0.80
4
Analysis of RAMP3 gene polymorphism with body composition and bone density in young and elderly women.
PMID: 34530989
Gene · 2019
0.70
5
CGRP-related neuropeptide adrenomedullin 2 promotes tissue-protective ILC2 responses and limits intestinal inflammation.
PMID: 40817416
Nat Immunol · 2025
0.60