MRAP2
protein-codingmelanocortin 2 receptor accessory protein 2
Gene summary
This gene encodes a protein that modulates melanocortin receptor signaling. The encoded protein has been shown to interact with all known melanocortin receptors and may regulate both receptor trafficking and activation in response to ligands. Mice lacking a functional copy of this gene exhibit severe obesity and a mutation in this gene may be associated with severe obesity in human patients. [provided by RefSeq, Oct 2016]
- C6orf117
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~57.1 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
Clinical Genomic Database (CGD)
Manifestation: Endocrine
Intervention: General
Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to MRAP2 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_138409.4. 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 | 22 | 22 | ||||
| missense | 81 | 3 | 84 | |||
| nonsense | 3 | 3 | ||||
| start loss | 0 | |||||
| frameshift | 8 | 8 | ||||
| splice donor/acceptor (+/-2bp) | 2 | 2 | ||||
| Total | 0 | 0 | 94 | 25 | 0 | 119 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_612418.2 | 3 | MANE Select | |
| Ensembl | ENSP00000257776.4 | 3 | MANE Select | |
| RefSeq | NP_001333470.1 | 1 | Standard | |
| RefSeq | NP_001333471.1 | 3 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| mrap2a | Danio rerio | Structure: whole organism Quality: decreased length abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- energy reserve metabolic process
- feeding behavior
- regulation of signaling receptor activity
- protein localization to plasma membrane
- energy homeostasis
Molecular Function
- protein binding
- receptor regulator activity
- corticotropin hormone receptor binding
- type 3 melanocortin receptor binding
- type 4 melanocortin receptor binding
Cellular Component
- endoplasmic reticulum
- endoplasmic reticulum membrane
- plasma membrane
- integral component of membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000257776
- Coding exons
- 3
- Length
- 57126
- Individuals with no LoFs
- 125717
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 30
- Defined
- 125747
- p
- 0.000119
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.309 | 99 | 108 | 0.916 | 0.00000520 | 1355 |
| Missense (PolyPhen) | 38 | 36.723 | 1.0348 | 490 | ||
| Synonymous | -0.249 | 44 | 42.0 | 1.05 | 0.00000221 | 389 |
| Loss of Function | -0.670 | 9 | 7.08 | 1.27 | 2.95e-7 | 96 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.00049 | 0.00043 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.000054 | 0.000054 | rare |
| Finnish | 0.000046 | 0.000046 | rare |
| European (Non-Finnish) | 0.000054 | 0.000053 | rare |
| South Asian | 0.00020 | 0.00020 | rare |
| Other | 0.00016 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Modulator of melanocortin receptor 4 (MC4R), a receptor involved in energy homeostasis. Plays a central role in the control of energy homeostasis and body weight regulation by increasing ligand-sensitivity of MC4R and MC4R-mediated generation of cAMP (By similarity). May also act as a negative regulator of MC2R: competes with MRAP for binding to MC2R and impairs the binding of corticotropin (ACTH) to MC2R. May also regulate activity of other melanocortin receptors (MC1R, MC3R and MC5R); however, additional evidences are required in vivo. {ECO:0000250, ECO:0000269|PubMed:19329486, ECO:0000269|PubMed:20371771}.;
- Disease
- DISEASE: Obesity (OBESITY) [MIM:601665]: A condition characterized by an increase of body weight beyond the limitation of skeletal and physical requirements, as the result of excessive accumulation of body fat. {ECO:0000269|PubMed:23869016}. Note=Disease susceptibility may be associated with variations affecting the gene represented in this entry.;
Recessive Scores
- pRec
- 0.110
Intolerance Scores
- LoFtool
- 0.352
- RVIS EVS
- -0.23
- RVIS percentile EVS
- 36.86
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- S
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.261
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |