RAMP2
protein-codingreceptor activity modifying protein 2, the group of Receptor (G protein-coupled) activity modifying proteins
Gene summary
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]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~4.6 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AD
Disease ID:MONDO:0005338
Submitter: Ambry Genetics
Inheritance Pattern: AD
Disease ID:MONDO:0005338
Submitter: PanelApp Australia
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to RAMP2 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_005854.3. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 1 | 1 | 2 | |||
| missense | 21 | 2 | 23 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 2 | 2 | ||||
| Total | 0 | 0 | 24 | 3 | 0 | 27 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_005845.2 | 4 | MANE Select | |
| Ensembl | ENSP00000253796.3 | 4 | MANE Select | |
| Ensembl | ENSP00000466455.1 | 4 | Standard | |
| Ensembl | ENSP00000466455.1 | 4 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Vascular smooth muscle contraction - Homo sapiens (human)
- Myometrial Relaxation and Contraction Pathways
- Signaling by GPCR
- Signal Transduction
- G alpha (s) signalling events
Biological Process
- angiogenesis
- vasculogenesis
- response to hypoxia
- sprouting angiogenesis
- calcium ion transport
Molecular Function
- adrenomedullin receptor activity
- protein binding
- protein transporter activity
- coreceptor activity
- amylin receptor activity
Cellular Component
- cytoplasm
- lysosome
- plasma membrane
- integral component of plasma membrane
- clathrin-coated pit
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000253796
- Coding exons
- 4
- Length
- 4595
- Individuals with no LoFs
- 125727
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 7
- Defined
- 125734
- p
- 0.0000278
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.917 | 61 | 84.8 | 0.720 | 0.00000399 | 1127 |
| Missense (PolyPhen) | 18 | 26.387 | 0.68215 | 388 | ||
| Synonymous | 0.552 | 30 | 34.1 | 0.880 | 0.00000180 | 355 |
| Loss of Function | 1.45 | 3 | 7.20 | 0.416 | 3.93e-7 | 75 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.000054 | 0.000054 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000026 | 0.000026 | rare |
| South Asian | 0.000065 | 0.000065 | rare |
| Other | 0.00016 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Transports the calcitonin gene-related peptide type 1 receptor (CALCRL) to the plasma membrane. Acts as a receptor for adrenomedullin (AM) together with CALCRL. {ECO:0000269|PubMed:22102369, ECO:0000269|PubMed:9620797}.;
Recessive Scores
- pRec
- 0.141
Intolerance Scores
- LoFtool
- 0.680
- RVIS EVS
- -0.05
- RVIS percentile EVS
- 49.39
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- S
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.423
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |