MC2R

melanocortin 2 receptor, the group of Melanocortin receptors

Basic information

Region (hg38): 18:13882043-13915707

Links

ENSG00000185231 ∙ ∙ OMIM:607397 ∙ HGNC:6930 ∙ Uniprot:Q01718 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• glucocorticoid deficiency 1 (Strong), mode of inheritance: AR
• glucocorticoid deficiency 1 (Definitive), mode of inheritance: AR
• familial glucocorticoid deficiency (Supportive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Glucocorticoid deficiency 1	AR	Endocrine	Early recognition and preventive measures and treatment related to hypoglycemia (as well as to potential infectious episodes) can be effective	Endocrine	13616862; 4302512; 4312011; 4342294; 4349230; 238474; 2539720; 8094489; 8227361; 7627261; 12851305; 21823545; 22337906; 22814974

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the MC2R gene.

• Glucocorticoid deficiency 1 (111 variants)
• Glucocorticoid Deficiency (30 variants)
• not provided (20 variants)
• Inborn genetic diseases (6 variants)
• not specified (3 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MC2R gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			3	3		6
missense	5	5	14	4	2	30
nonsense	1					1
start loss						0
frameshift	3	1				4
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding			71	8	24	103
Total	9	6	88	15	26

Highest pathogenic variant AF is 0.000296

Variants in MC2R

This is a list of pathogenic ClinVar variants found in the MC2R region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
18-13882053-C-T		Glucocorticoid deficiency 1	Uncertain significance (Jan 13, 2018)
18-13882097-A-C		Glucocorticoid deficiency 1	Benign (Jan 13, 2018)
18-13882193-T-G		Glucocorticoid deficiency 1	Likely benign (Jan 13, 2018)
18-13882197-TA-T		Glucocorticoid Deficiency	Likely benign (Jun 14, 2016)
18-13882198-A-G		Glucocorticoid deficiency 1	Uncertain significance (Jan 13, 2018)
18-13882199-A-G		Glucocorticoid deficiency 1	Benign (Jan 12, 2018)
18-13882216-T-C		Glucocorticoid deficiency 1	Uncertain significance (Jan 12, 2018)
18-13882231-G-C		Glucocorticoid deficiency 1	Benign (Jan 12, 2018)
18-13882302-G-A		Glucocorticoid deficiency 1	Likely benign (Jan 12, 2018)
18-13882401-T-G		Glucocorticoid deficiency 1	Likely benign (Jan 13, 2018)
18-13882487-C-A		Glucocorticoid deficiency 1	Benign (Jan 13, 2018)
18-13882560-C-T		Glucocorticoid deficiency 1	Likely benign (Jan 13, 2018)
18-13882651-G-GT		Glucocorticoid Deficiency	Uncertain significance (Jun 14, 2016)
18-13882680-TCA-T		Glucocorticoid Deficiency	Uncertain significance (Jun 14, 2016)
18-13882705-A-T		Glucocorticoid deficiency 1	Benign (Jan 13, 2018)
18-13882708-G-T		Glucocorticoid deficiency 1	Uncertain significance (Jan 13, 2018)
18-13882729-G-A		Glucocorticoid deficiency 1	Benign (Jan 13, 2018)
18-13882740-A-G		Glucocorticoid deficiency 1	Benign (Jan 13, 2018)
18-13882748-T-C		Glucocorticoid deficiency 1	Benign (Jan 13, 2018)
18-13882755-T-C		Glucocorticoid deficiency 1	Uncertain significance (Jan 12, 2018)
18-13882769-A-G		Glucocorticoid deficiency 1	Uncertain significance (Jan 13, 2018)
18-13882866-G-T		Glucocorticoid deficiency 1	Benign (Jan 12, 2018)
18-13882958-C-T		Glucocorticoid deficiency 1	Uncertain significance (Jan 12, 2018)
18-13883006-C-T		Glucocorticoid deficiency 1	Likely benign (Jan 12, 2018)
18-13883021-C-G		Glucocorticoid deficiency 1	Benign (Jan 12, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
MC2R	protein_coding	protein_coding	ENST00000327606	1	33664

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.000307	0.369	125721	0	24	125745	0.0000954

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.00651	174	174	0.999	0.0000107	1974
Missense in Polyphen		58	69.001	0.84056		842
Synonymous	-1.04	85	73.6	1.15	0.00000506	609
Loss of Function	-0.156	5	4.64	1.08	2.63e-7	60

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000210	0.000210
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000544	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.000132	0.000132
Middle Eastern	0.0000544	0.0000544
South Asian	0.0000653	0.0000653
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Receptor for corticotropin (ACTH). This receptor is mediated by G proteins (G(s)) which activate adenylate cyclase (cAMP). {ECO:0000269|PubMed:19329486, ECO:0000269|PubMed:20371771}.
• Pathway: Cortisol synthesis and secretion - Homo sapiens (human);Aldosterone synthesis and secretion - Homo sapiens (human);Cushing,s syndrome - Homo sapiens (human);cAMP signaling pathway - Homo sapiens (human);Neuroactive ligand-receptor interaction - Homo sapiens (human);Corticotropin Activation of Cortisol Production;Peptide GPCRs;GPCRs, Class A Rhodopsin-like;Signaling by GPCR;Signal Transduction;G alpha (s) signalling events;Peptide ligand-binding receptors;Class A/1 (Rhodopsin-like receptors);GPCR ligand binding;GPCR downstream signalling (Consensus)

Recessive Scores

• pRec: 0.524

Intolerance Scores

• loftool: 0.371
• rvis_EVS: 0.26
• rvis_percentile_EVS: 70.44

Haploinsufficiency Scores

• pHI: 0.175
• hipred: N
• hipred_score: 0.267
• ghis: 0.413

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.210

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Mc2r
• Phenotype: immune system phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); hematopoietic system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); homeostasis/metabolism phenotype; growth/size/body region phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); endocrine/exocrine gland phenotype

Gene ontology

• Biological process: placenta development;G protein-coupled receptor signaling pathway;G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger;adenylate cyclase-activating G protein-coupled receptor signaling pathway;neuropeptide signaling pathway
• Cellular component: cytoplasm;plasma membrane;integral component of plasma membrane
• Molecular function: melanocortin receptor activity;corticotropin receptor activity;protein binding