MC2R melanocortin 2 receptor [Homo sapiens (human)] - Gene

Summary

Official Symbol: MC2Rprovided by HGNC
Official Full Name: melanocortin 2 receptorprovided by HGNC
Primary source: HGNC:HGNC:6930
See related: Ensembl:ENSG00000185231 MIM:607397; AllianceGenome:HGNC:6930
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: ACTHR
Summary: MC2R encodes one member of the five-member G-protein associated melanocortin receptor family. Melanocortins (melanocyte-stimulating hormones and adrenocorticotropic hormone) are peptides derived from pro-opiomelanocortin (POMC). MC2R is selectively activated by adrenocorticotropic hormone, whereas the other four melanocortin receptors recognize a variety of melanocortin ligands. Mutations in MC2R can result in familial glucocorticoid deficiency. Alternate transcript variants have been found for this gene. [provided by RefSeq, May 2014]
Expression: Restricted expression toward adrenal (RPKM 16.0) See more
Orthologs: mouse all
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Genomic context

Location:: 18p11.21

Exon count:: 5

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	18	NC_000018.10 (13882044..13915707, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	18	NC_060942.1 (14044399..14078045, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	18	NC_000018.9 (13882043..13915706, complement)

Chromosome 18 - NC_000018.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

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Expression

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See details

Project title: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

[Clinical characteristics and genetic analysis of two children with Familial glucocorticoid deficiency type 1 due to variants of MC2R gene].
Title: [Clinical characteristics and genetic analysis of two children with Familial glucocorticoid deficiency type 1 due to variants of MC2R gene].
A rare homozygous variant of MC2R gene identified in a Chinese family with familial glucocorticoid deficiency type 1: A case report.
Title: A rare homozygous variant of MC2R gene identified in a Chinese family with familial glucocorticoid deficiency type 1: A case report.
Structural basis of signaling regulation of the human melanocortin-2 receptor by MRAP1.
Title: Structural basis of signaling regulation of the human melanocortin-2 receptor by MRAP1.
Human Melanocortin-2 Receptor: Identifying a Role for Residues in the TM4, EC2, and TM5 Domains in Activation and Trafficking as a Result of Co-Expression with the Accessory Protein, Mrap1 in Chinese Hamster Ovary Cells.
Title: Human Melanocortin-2 Receptor: Identifying a Role for Residues in the TM4, EC2, and TM5 Domains in Activation and Trafficking as a Result of Co-Expression with the Accessory Protein, Mrap1 in Chinese Hamster Ovary Cells.
Delayed retinal vein recovery responses indicate both non-adaptation to stress as well as increased risk for stroke: the SABPA study.
Title: Delayed retinal vein recovery responses indicate both non-adaptation to stress as well as increased risk for stroke: the SABPA study.
Sex-specific association of MC2R polymorphisms and the risk of major depressive disorder in Chinese Southern Han.
Title: Sex-specific association of MC2R polymorphisms and the risk of major depressive disorder in Chinese Southern Han.
A variant in the 3'-untranslated region of the MC2R gene decreases the risk of schizophrenia in a female Han Chinese population.
Title: A variant in the 3'-untranslated region of the MC2R gene decreases the risk of schizophrenia in a female Han Chinese population.
Results indicate that substitution of the amino acid residue leucine to isoleucine in 112 (L112I) of one of the transmembrane domains in the MC2R changes from both DPhe-ACTH1-17 and ACTH1-15 from no activity to agonists. Also, mutation L112I switches alpha-MSH from no activity to agonist, suggesting that this residue plays a key role at MC2R for ligand ACTH or alpha-MSH selectivity.
Title: Amino acid residue L112 in the ACTH receptor plays a key role in ACTH or α-MSH selectivity.
Results show regulation of melanocortin receptors MC2R, MC3R and MC4R gene expressions in CD8(+) cytotoxic T-lymphocytes and CD19(+) B lymphocytes in rheumatoid arthritis (RA) treated with tumor necrosis factor-alpha (TNF-alpha) inhibitor adalimumab.
Title: Melanocortin 2, 3 and 4 Receptor Gene Expressions are Downregulated in CD8(+) T Cytotoxic Lymphocytes and CD19(+) B Lymphocytes in Rheumatoid Arthritis Responding to TNF-α Inhibition.
Four rare missense variants were identified (ACTBL2 rs73757391 (5q11.2), BTD rs200337373 (3p25.1), KRT13 rs150321809 (17q21.2) and MC2R rs104894658 (18p11.21)), but only MC2R rs104894668 had a large effect size (OR = 9.66).
Title: Exome genotyping arrays to identify rare and low frequency variants associated with epithelial ovarian cancer risk.

Submit: New GeneRIF Correction See all GeneRIFs (63)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Glucocorticoid deficiency 1 MedGen: C4049650 OMIM: 202200 GeneReviews: Not available	not available

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

AFMa152wg9 (e-PCR)
- UniSTS:84012

AFMa152wg9 (e-PCR)
- UniSTS:2351

NoName (e-PCR)
- UniSTS:481610

MC2R_927 (e-PCR)
- UniSTS:277481

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables G protein-coupled receptor activity	IBA Inferred from Biological aspect of Ancestor more info
enables corticotropin receptor activity	IEA Inferred from Electronic Annotation more info
enables melanocortin receptor activity	TAS Traceable Author Statement more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
involved_in G protein-coupled receptor signaling pathway	TAS Traceable Author Statement more info	PubMed
involved_in G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger	TAS Traceable Author Statement more info	PubMed
involved_in adenylate cyclase-activating G protein-coupled receptor signaling pathway	IBA Inferred from Biological aspect of Ancestor more info
involved_in adenylate cyclase-activating G protein-coupled receptor signaling pathway	IDA Inferred from Direct Assay more info	PubMed
involved_in neuropeptide signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in regulation of metabolic process	IBA Inferred from Biological aspect of Ancestor more info

Component	Evidence Code	Pubs
is_active_in cytoplasm	IBA Inferred from Biological aspect of Ancestor more info
is_active_in plasma membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in plasma membrane	TAS Traceable Author Statement more info

General protein information

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Preferred Names: adrenocorticotropic hormone receptor

Names: ACTH receptor; MC2 receptor; adrenocorticotropin receptor; corticotropin receptor; melanocortin 2 receptor (adrenocorticotropic hormone)

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_011819.1 RefSeqGene

Range

5001..38493

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_000529.2 → NP_000520.1 adrenocorticotropic hormone receptor

See identical proteins and their annotated locations for NP_000520.1

Status: REVIEWED

Description

Transcript Variant: This variant (1) and variant 2 encode the same protein.

Source sequence(s)

AP001086, BC094710

Consensus CDS

CCDS11869.1

UniProtKB/Swiss-Prot

A8K016, Q01718, Q3MI45, Q504X6

Related

ENSP00000333821.2, ENST00000327606.4

Conserved Domains (1) summary

cd15350
Location:25 → 287

7tmA_MC2R_ACTH_R; melanocortin receptor subtype 2, also called adrenocorticotropic hormone receptor, member of the class A family of seven-transmembrane G protein-coupled receptors
NM_001291911.1 → NP_001278840.1 adrenocorticotropic hormone receptor

See identical proteins and their annotated locations for NP_001278840.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) has an alternate 5' UTR exon, compared to variant 1. Both variants 1 and 2 encode the same protein.

Source sequence(s)

AP001086, BP196054

Consensus CDS

CCDS11869.1

UniProtKB/Swiss-Prot

A8K016, Q01718, Q3MI45, Q504X6

Conserved Domains (1) summary

cd15350
Location:25 → 287

7tmA_MC2R_ACTH_R; melanocortin receptor subtype 2, also called adrenocorticotropic hormone receptor, member of the class A family of seven-transmembrane G protein-coupled receptors

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000018.10 Reference GRCh38.p14 Primary Assembly

Range

13882044..13915707 complement

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_017025781.2 → XP_016881270.1 adrenocorticotropic hormone receptor isoform X1

UniProtKB/Swiss-Prot

A8K016, Q01718, Q3MI45, Q504X6

Conserved Domains (1) summary

cd15350
Location:25 → 287

7tmA_MC2R_ACTH_R; melanocortin receptor subtype 2, also called adrenocorticotropic hormone receptor, member of the class A family of seven-transmembrane G protein-coupled receptors
XM_047437537.1 → XP_047293493.1 adrenocorticotropic hormone receptor isoform X1

UniProtKB/Swiss-Prot

A8K016, Q01718, Q3MI45, Q504X6

Alternate T2T-CHM13v2.0

Genomic

NC_060942.1 Alternate T2T-CHM13v2.0

Range

14044399..14078045 complement

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_054318656.1 → XP_054174631.1 adrenocorticotropic hormone receptor isoform X1

UniProtKB/Swiss-Prot

A8K016, Q01718, Q3MI45, Q504X6
XM_054318657.1 → XP_054174632.1 adrenocorticotropic hormone receptor isoform X1

UniProtKB/Swiss-Prot

A8K016, Q01718, Q3MI45, Q504X6