MRAP: Melanocortin 2 Receptor Accessory Protein
Essential co-receptor for ACTH signaling and adrenal steroidogenesis
Gene Information Card
| Symbol | MRAP |
|---|---|
| Full Name | Melanocortin 2 Receptor Accessory Protein |
| Gene Type | protein-coding |
| Chromosomal Location | 21q22.11 |
| NCBI Gene ID | 56246 ncbi.nlm.nih.gov/gene/56246 |
| Ensembl ID | ENSG00000160218 |
| UniProt ID | Q8TCY5 |
| OMIM ID | 609196 |
| HGNC ID | 1306 |
| Aliases | FALP, B27, C21orf61 |
Description
MRAP encodes a small single-transmembrane domain protein that functions as an accessory factor for the melanocortin 2 receptor (MC2R). MRAP is essential for MC2R trafficking from the endoplasmic reticulum to the cell surface and for ACTH binding and signaling. It forms a unique antiparallel homodimer that is required for receptor function. Mutations in MRAP cause familial glucocorticoid deficiency type 2 (FGD2), an autosomal recessive disorder characterized by isolated glucocorticoid deficiency.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Familial glucocorticoid deficiency type 2 (FGD2) | Loss-of-function mutations in MRAP prevent MC2R cell surface expression and ACTH signaling, leading to impaired cortisol production. | OMIM #609196; multiple homozygous and compound heterozygous mutations reported in patients. |
| Adrenal insufficiency (secondary) | MRAP dysfunction disrupts the hypothalamic-pituitary-adrenal axis, causing low cortisol and high ACTH levels. | ClinVar; case reports. |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Adrenal gland | 12.5 | Medium |
| Adipose tissue | 8.3 | Low |
| Skin | 6.1 | Low |
| Testis | 4.7 | Low |
| Brain | 2.1 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HPA (adrenal cortex) | 15.2 | High expression |
| SW13 (adrenal carcinoma) | 10.8 | Moderate expression |
| HEK293 | 0.5 | Very low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.106C>T (p.Arg36*) | Nonsense | Rare | Loss of function; truncated protein unable to support MC2R trafficking. |
| c.3G>A (p.Met1?) | Start loss | Rare | Loss of function; no protein translation. |
| c.218T>C (p.Leu73Pro) | Missense | Rare | Loss of function; disrupts transmembrane domain. |
| c.IVS1+1G>A | Splice site | Rare | Loss of function; aberrant splicing. |
Mutation functional classification
Loss of Function (LOF)
Most MRAP mutations are loss-of-function, preventing MC2R cell surface expression and ACTH signaling, leading to familial glucocorticoid deficiency type 2.
Gain of Function (GOF)
No gain-of-function mutations have been reported for MRAP.
Dominant Negative (DN)
No dominant-negative effects have been described; inheritance is autosomal recessive.
View complete mutation data：
Gene Ontology (GO)
| • GPCR accessory protein | • melanocortin receptor binding |
| • protein homodimerization activity | • endoplasmic reticulum to plasma membrane transport |
| • ACTH signaling pathway | • adrenal gland development |
Pathways
• GPCR signaling (MC2R pathway)
• Cortisol synthesis and secretion
Protein Summary
MRAP is a 172-amino acid single-pass transmembrane protein that forms antiparallel homodimers. It is essential for the trafficking of MC2R from the endoplasmic reticulum to the plasma membrane and for ACTH binding. MRAP is highly expressed in the adrenal cortex and also in adipose tissue and skin. Without MRAP, MC2R is retained intracellularly and cannot mediate ACTH-induced cortisol production.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| MRAP2 Knockout HEK293 Cell Line | EDJ-KQ7387 | Human | 112609 | Details Get a Quote |
| MRAP Knockout HEK293 Cell Line | EDJ-KQ11965 | Human | 56246 | Details Get a Quote |
| MRAP2 Knockout A-549 Cell Line | EDJ-KQ31161 | Human | 112609 | Details Get a Quote |
| MRAP2 Knockout HCT 116 Cell Line | EDJ-KQ32533 | Human | 112609 | Details Get a Quote |
| MRAP2 Knockout HeLa Cell Line | EDJ-KQ32534 | Human | 112609 | Details Get a Quote |
| MRAP Knockout HeLa Cell Line | EDJ-KQ56725 | Human | 56246 | Details Get a Quote |
| MRAP Knockout A-549 Cell Line | EDJ-KQ65230 | Human | 56246 | Details Get a Quote |
| MRAP Knockout HCT 116 Cell Line | EDJ-KQ73668 | Human | 56246 | Details Get a Quote |
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