MC2R (Melanocortin 2 Receptor) Gene
Key regulator of adrenal steroidogenesis and stress response
Gene Information Card
| Symbol | MC2R |
|---|---|
| Full Name | Melanocortin 2 Receptor |
| Gene Type | protein-coding |
| Chromosomal Location | 18p11.21 |
| NCBI Gene ID | 4158 ncbi.nlm.nih.gov/gene/4158 |
| Ensembl ID | ENSG00000185231 |
| UniProt ID | Q01718 |
| OMIM ID | 607397 |
| HGNC ID | 6930 |
| Aliases | ACTH receptor, ACTHR, MC2 |
Description
The MC2R gene encodes the melanocortin 2 receptor, a G protein-coupled receptor that specifically binds adrenocorticotropic hormone (ACTH). This receptor is primarily expressed in the adrenal cortex and mediates ACTH-stimulated cortisol production. Mutations in MC2R are a major cause of familial glucocorticoid deficiency type 1 (FGD1), an autosomal recessive disorder characterized by cortisol deficiency and elevated ACTH levels.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Familial glucocorticoid deficiency type 1 (FGD1) | Loss-of-function mutations impair ACTH binding or signaling, leading to adrenal unresponsiveness and cortisol deficiency. | ClinVar, OMIM |
| Isolated glucocorticoid deficiency | Similar mechanism as FGD1; defective MC2R prevents normal adrenal steroidogenesis. | OMIM, NCBI |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Adrenal gland | 12.5 | High |
| Skin | 0.3 | Low |
| Brain | 0.1 | Very low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| NCI-H295R (adrenocortical) | 15.2 | High endogenous expression |
| HEK293 | 0.0 | No detectable expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.560C>T (p.Thr187Ile) | Missense | Rare | Loss of function; impaired cell surface expression |
| c.710T>C (p.Phe237Ser) | Missense | Rare | Loss of function; defective ACTH binding |
| c.1A>G (p.Met1Val) | Start loss | Rare | Complete loss of protein translation |
Mutation functional classification
Loss of Function (LOF)
Most MC2R mutations cause loss of function by disrupting receptor trafficking, ligand binding, or signal transduction, leading to familial glucocorticoid deficiency.
Gain of Function (GOF)
No gain-of-function mutations have been reported in MC2R.
Dominant Negative (DN)
No dominant-negative effects have been described for MC2R mutations.
View complete mutation data：
Gene Ontology (GO)
| • G protein-coupled receptor activity (GO:0004930) | • melanocortin receptor activity (GO:0004977) |
| • ACTH receptor activity (GO:0016500) | • plasma membrane (GO:0005886) |
| • cAMP-mediated signaling (GO:0019933) | • response to corticotropin (GO:0043401) |
Pathways
• GPCR downstream signaling (cAMP/PKA cascade)
• Adrenal steroidogenesis (cortisol production)
Protein Summary
The melanocortin 2 receptor (MC2R) is a 297-amino acid G protein-coupled receptor with seven transmembrane domains. It is the specific receptor for ACTH and is essential for adrenal glucocorticoid synthesis. Upon ACTH binding, MC2R activates the cAMP/PKA signaling pathway, leading to increased transcription of steroidogenic enzymes. The receptor requires accessory protein MRAP for proper trafficking and function.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| MC2R Knockout HEK293 Cell Line | EDJ-KQ1772 | Human | 4158 | Details Get a Quote |
| MC2R Knockout HeLa Cell Line | EDJ-KQ53849 | Human | 4158 | Details Get a Quote |
| MC2R Knockout A-549 Cell Line | EDJ-KQ62335 | Human | 4158 | Details Get a Quote |
| MC2R Knockout HCT 116 Cell Line | EDJ-KQ70810 | Human | 4158 | Details Get a Quote |
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