RAMP3

Chr 7

receptor activity modifying protein 3

NCBI Gene: 10268ENSG00000122679UniProt: O60896

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 (RAMP3) protein, CRLR functions as an adrenomedullin receptor. [provided by RefSeq, Jul 2008]

47
ClinVar variants
25
Pathogenic / LP
0.02
pLI score
0
Active trials
Clinical Summary— RAMP3
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.02) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
25 Pathogenic / Likely Pathogenic· 17 VUS of 47 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.
1.57LOEUF
pLI 0.016
Z-score 0.71
OE 0.64 (0.29–1.57)
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.
0.56Z-score
OE missense 0.83 (0.69–1.01)
74 obs / 88.8 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.0.64 (0.29–1.57)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.83 (0.69–1.01)
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.1.15
0≤1.21.6
LoF obs/exp: 3 / 4.7Missense obs/exp: 74 / 88.8Syn Z: -0.75

ClinVar Variant Classifications

47 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic24
Likely Pathogenic1
VUS17
Likely Benign3
Benign2
24
Pathogenic
1
Likely Pathogenic
17
VUS
3
Likely Benign
2
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
24
0
24
Likely Pathogenic
0
0
1
0
1
VUS
0
12
5
0
17
Likely Benign
0
1
1
1
3
Benign
0
2
0
0
2
Total01531147

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

View in ClinVar →

Protein Context — Lollipop Plot

RAMP3 · 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
Integrated GMPS and RAMP3 as a signature to predict prognosis and immune heterogeneity in hepatocellular carcinoma.
Chen Z et al.·Gene
2025
Regulation of the chemokine receptors CXCR4 and ACKR3 by receptor activity-modifying proteins.
Pfersdorf F et al.·J Biol Chem
2025
Update on the pharmacology of calcitonin/CGRP family of peptides: IUPHAR Review 25.
Hay DL et al.·Br J Pharmacol
2018Review
Shared and separate functions of the RAMP-based adrenomedullin receptors.
Kuwasako K et al.·Peptides
2011Review
Functional characterization of two human receptor activity-modifying protein 3 variants.
Bailey RJ et al.·Peptides
2010Functional
Vascular actions of calcitonin gene-related peptide and adrenomedullin.
Brain SD et al.·Physiol Rev
2004Review
Effects of adrenomedullin on endothelial cells in the multistep process of angiogenesis: involvement of CRLR/RAMP2 and CRLR/RAMP3 receptors.
Fernandez-Sauze S et al.·Int J Cancer
2004
The role of peptides and receptors of the calcitonin family in the regulation of bone metabolism.
Naot D et al.·Bone
2008Review
RAMP and MRAP accessory proteins have selective effects on expression and signalling of the CB(1), CB(2), GPR18 and GPR55 cannabinoid receptors.
Glenn NAK et al.·Br J Pharmacol
2024
Identification and analysis of necroptosis-associated signatures for prognostic and immune microenvironment evaluation in hepatocellular carcinoma.
Lu J et al.·Front Immunol
2022
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

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