RAMP2

Chr 17

receptor activity modifying protein 2

NCBI Gene: 10266ENSG00000131477UniProt: O60895

The protein encoded by this gene is a member of the RAMP family of single-transmembrane-domain proteins, called receptor (calcitonin) activity modifying proteins (RAMPs). RAMPs are type I transmembrane proteins with an extracellular N terminus and a cytoplasmic C terminus. RAMPs are required to transport calcitonin-receptor-like receptor (CRLR) to the plasma membrane. CRLR, a receptor with seven transmembrane domains, can function as either a calcitonin-gene-related peptide (CGRP) receptor or an adrenomedullin receptor, depending on which members of the RAMP family are expressed. In the presence of this (RAMP2) protein, CRLR functions as an adrenomedullin receptor. The RAMP2 protein is involved in core glycosylation and transportation of adrenomedullin receptor to the cell surface. [provided by RefSeq, Jul 2008]

0
Active trials
31
ClinVar variants
6
Pathogenic / LP
0.9
Missense Z
1.07
LOEUF
4
Pubs (2 yr)
Clinical Summary— RAMP2
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.05) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
6 Pathogenic / Likely Pathogenic· 21 VUS of 31 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
1.07LOEUF
pLI 0.051
Z-score 1.45
OE 0.42 (0.19–1.07)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.92Z-score
OE missense 0.72 (0.58–0.89)
61 obs / 84.8 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.42 (0.19–1.07)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.72 (0.58–0.89)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.88
0≤1.21.6
LoF obs/exp: 3 / 7.2Missense obs/exp: 61 / 84.8Syn Z: 0.55

ClinVar Variant Classifications

31 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic6
VUS21
Likely Benign4
6
Pathogenic
21
VUS
4
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
6
0
6
Likely Pathogenic
0
0
0
0
0
VUS
0
21
0
0
21
Likely Benign
0
2
1
1
4
Benign
0
0
0
0
0
Total0237131

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

RAMP2 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Adrenomedullin: Continuing to explore cardioprotection.
Tsuruda T et al.·Peptides
2019Review
RAMP2-AS1 inhibits CXCL11 expression to suppress malignant phenotype of breast cancer by recruiting DNMT1 and DNMT3B.
Li L et al.·Exp Cell Res
2022
Mutant RAMP2 causes primary open-angle glaucoma via the CRLR-cAMP axis.
Gong B et al.·Genet Med
2019
Update on the pharmacology of calcitonin/CGRP family of peptides: IUPHAR Review 25.
Hay DL et al.·Br J Pharmacol
2018Review
Adrenomedullin-RAMP2 system suppresses ER stress-induced tubule cell death and is involved in kidney protection.
Uetake R et al.·PLoS One
2014
Shared and separate functions of the RAMP-based adrenomedullin receptors.
Kuwasako K et al.·Peptides
2011Review
β-arrestins negatively control human adrenomedullin type 1-receptor internalization.
Kuwasako K et al.·Biochem Biophys Res Commun
2017
Modulation of Glucagon Receptor Pharmacology by Receptor Activity-modifying Protein-2 (RAMP2).
Weston C et al.·J Biol Chem
2015
Frequent inactivation of RAMP2, EFEMP1 and Dutt1 in lung cancer by promoter hypermethylation.
Yue W et al.·Clin Cancer Res
2007
Vascular actions of calcitonin gene-related peptide and adrenomedullin.
Brain SD et al.·Physiol Rev
2004Review
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Receptor Activity-Modifying Protein 2 (RAMP2) alters glucagon receptor trafficking in hepatocytes with functional effects on receptor signalling
McGlone ER et al.·Mol Metab
2021Functional
Functional modulation of PTH1R activation and signaling by RAMP2
Nemec K et al.·Proc Natl Acad Sci U S A
2022Functional
RAMP2-AS1 Regulates Endothelial Homeostasis and Aging
Lai CH et al.·Front Cell Dev Biol
2021
Negative allosteric modulation of the glucagon receptor by RAMP2
Krishna Kumar K et al.·Cell
2023
Receptor activity-modifying proteins of adrenomedullin (RAMP2/3): Roles in the pathogenesis of ARDS.
Kasahara T et al.·Peptides
2023
Balance of Gata3 and Ramp2 in hepatocytes regulates hepatic vascular reconstitution in postoperative liver regeneration.
Bibo W et al.·J Hepatol
2023
Adrenomedullin-RAMP2 and -RAMP3 Systems Regulate Cardiac Homeostasis during Cardiovascular Stress.
Cui N et al.·Endocrinology
2021
Top 7 full-text resultsSearch PubTator3 ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients