MC1R

melanocortin 1 receptor, the group of Melanocortin receptors

Basic information

Region (hg38): 16:89912118-89920973

Links

ENSG00000258839 ∙ NCBI:4157 ∙ OMIM:155555 ∙ HGNC:6929 ∙ Uniprot:Q01726 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Increased analgesia from kappa-opioid receptor agonist, female specific	AD	Pharmacogenomic	Variants may have pharmacogenomic relevance, as results suggest that women with 2 variant MC1R alleles demonstrate greater analgesia from kappa-opioid pentazocine	General	7581459; 8894704; 11030758; 10631149; 11487574; 11500805; 11500806; 12876664; 12839583; 12663858; 16809487; 17952075; 19578364; 21693730; 21128237; 22095472; 22561518
Skin/hair/eye pigmentation, variation in may not have actionable relevance, though there may be increased risk of skin cancer

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the MC1R gene.

• Melanoma, cutaneous malignant, susceptibility to, 5 (398 variants)
• not provided (39 variants)
• not specified (15 variants)
• Inborn genetic diseases (7 variants)
• Tyrosinase-positive oculocutaneous albinism (7 variants)
• Malignant Melanoma Susceptibility (6 variants)
• Skin and Hair Hypopigmentation (5 variants)
• Skin/hair/eye pigmentation 2, red hair/fair skin (4 variants)
• Melanoma, cutaneous malignant, susceptibility to, 5;Tyrosinase-positive oculocutaneous albinism;Increased analgesia from kappa-opioid receptor agonist, female-specific;Skin/hair/eye pigmentation, variation in, 2 (3 variants)
• Malignant tumor of breast (2 variants)
• Skin/hair/eye pigmentation 2, blond hair/fair skin (2 variants)
• Skin/hair/eye pigmentation, variation in, 2 (2 variants)
• OCULOCUTANEOUS ALBINISM, TYPE II, MODIFIER OF (2 variants)
• Skin/hair/eye pigmentation, variation in, 2;Melanoma, cutaneous malignant, susceptibility to, 5;Tyrosinase-positive oculocutaneous albinism;Increased analgesia from kappa-opioid receptor agonist, female-specific (2 variants)
• Tyrosinase-positive oculocutaneous albinism;Increased analgesia from kappa-opioid receptor agonist, female-specific;Melanoma, cutaneous malignant, susceptibility to, 5;Skin/hair/eye pigmentation, variation in, 2 (2 variants)
• Skin/hair/eye pigmentation, variation in, 2;Tyrosinase-positive oculocutaneous albinism;Increased analgesia from kappa-opioid receptor agonist, female-specific;Melanoma, cutaneous malignant, susceptibility to, 5 (2 variants)
• Increased analgesia from kappa-opioid receptor agonist, female-specific (2 variants)
• Increased analgesia from kappa-opioid receptor agonist, female-specific;Tyrosinase-positive oculocutaneous albinism;Melanoma, cutaneous malignant, susceptibility to, 5;Skin/hair/eye pigmentation, variation in, 2 (1 variants)
• Tyrosinase-positive oculocutaneous albinism;Skin/hair/eye pigmentation, variation in, 2;Increased analgesia from kappa-opioid receptor agonist, female-specific;Melanoma, cutaneous malignant, susceptibility to, 5 (1 variants)
• MC1R-related condition (1 variants)
• Melanoma, cutaneous malignant, susceptibility to, 1 (1 variants)
• Tyrosinase-positive oculocutaneous albinism;Melanoma, cutaneous malignant, susceptibility to, 5;Skin/hair/eye pigmentation, variation in, 2;Increased analgesia from kappa-opioid receptor agonist, female-specific (1 variants)
• bilateral breast cancer (1 variants)
• Skin/hair/eye pigmentation, variation in, 2;Melanoma, cutaneous malignant, susceptibility to, 5;Increased analgesia from kappa-opioid receptor agonist, female-specific;Tyrosinase-positive oculocutaneous albinism (1 variants)
• Melanoma (1 variants)
• Melanoma, cutaneous malignant, susceptibility to, 5;Tyrosinase-positive oculocutaneous albinism;Skin/hair/eye pigmentation, variation in, 2;Increased analgesia from kappa-opioid receptor agonist, female-specific (1 variants)
• UV-induced skin damage, susceptibility to (1 variants)
• Skin/hair/eye pigmentation, variation in, 2;Increased analgesia from kappa-opioid receptor agonist, female-specific;Melanoma, cutaneous malignant, susceptibility to, 5;Tyrosinase-positive oculocutaneous albinism (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MC1R 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			6	89	10	105
missense			181	18	3	202
nonsense			10			10
start loss						0
frameshift		1	15			16
inframe indel			8			8
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding			22	2	14	38
Total	0	1	242	109	27

Variants in MC1R

This is a list of pathogenic ClinVar variants found in the MC1R region.

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

Position	Type	Phenotype	Significance	ClinVar
16-89917679-CAT-C		Macular degeneration, age-related, neovascular type	Benign (Jan 10, 2019)
16-89917760-C-A			Benign (Jun 21, 2019)
16-89917888-C-G		Melanoma, cutaneous malignant, susceptibility to, 5	Benign (Jan 13, 2018)
16-89917952-A-C		Melanoma, cutaneous malignant, susceptibility to, 5	Uncertain significance (Jan 12, 2018)
16-89917962-T-C		Melanoma, cutaneous malignant, susceptibility to, 5	Benign (Jan 10, 2019)
16-89917970-C-T		Melanoma, cutaneous malignant, susceptibility to, 5	Benign/Likely benign (Mar 24, 2019)
16-89917985-G-C		Melanoma, cutaneous malignant, susceptibility to, 5	Uncertain significance (Jan 13, 2018)
16-89917996-G-A		Melanoma, cutaneous malignant, susceptibility to, 5	Uncertain significance (Jan 13, 2018)
16-89918008-C-T		Melanoma, cutaneous malignant, susceptibility to, 5	Benign (Jan 12, 2018)
16-89918016-G-A		Melanoma, cutaneous malignant, susceptibility to, 5	Uncertain significance (Jan 13, 2018)
16-89918024-A-T		Melanoma, cutaneous malignant, susceptibility to, 5	Uncertain significance (Jan 12, 2018)
16-89918025-C-T		Melanoma, cutaneous malignant, susceptibility to, 5	Benign (Jan 12, 2018)
16-89918029-C-T		Melanoma, cutaneous malignant, susceptibility to, 5	Uncertain significance (Jan 13, 2018)
16-89918050-C-T		Melanoma, cutaneous malignant, susceptibility to, 5	Uncertain significance (Jan 12, 2018)
16-89918082-G-C		Melanoma, cutaneous malignant, susceptibility to, 5	Uncertain significance (Jan 13, 2018)
16-89918089-C-G			Likely benign (May 24, 2021)
16-89918102-A-C		Melanoma, cutaneous malignant, susceptibility to, 5	Uncertain significance (Jan 13, 2018)
16-89918116-C-T		Melanoma, cutaneous malignant, susceptibility to, 5	Uncertain significance (Jan 12, 2018)
16-89918117-G-A		Melanoma, cutaneous malignant, susceptibility to, 5	Uncertain significance (Jan 13, 2018)
16-89918134-C-T		Melanoma, cutaneous malignant, susceptibility to, 5	Uncertain significance (Jan 13, 2018)
16-89918161-C-T		Melanoma, cutaneous malignant, susceptibility to, 5	Uncertain significance (Jan 13, 2018)
16-89918167-G-A		Melanoma, cutaneous malignant, susceptibility to, 5	Benign (Jan 13, 2018)
16-89918196-T-C		Melanoma, cutaneous malignant, susceptibility to, 5	Benign (Jan 10, 2019)
16-89918243-C-G		Melanoma, cutaneous malignant, susceptibility to, 5	Benign (Jan 13, 2018)
16-89918253-G-T		Melanoma, cutaneous malignant, susceptibility to, 5	Uncertain significance (Jan 12, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
MC1R	protein_coding	protein_coding	ENST00000555147	1	8859

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
8.11e-11	0.00581	0	0	0	0	0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-2.34	299	205	1.46	0.0000141	2000
Missense in Polyphen		98	54.866	1.7862		702
Synonymous	-3.14	146	105	1.39	0.00000820	720
Loss of Function	-2.21	12	6.10	1.97	3.47e-7	58

LoF frequencies by population

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

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Receptor for MSH (alpha, beta and gamma) and ACTH. The activity of this receptor is mediated by G proteins which activate adenylate cyclase.
• Disease: DISEASE: Melanoma, cutaneous malignant 5 (CMM5) [MIM:613099]: A malignant neoplasm of melanocytes, arising de novo or from a pre- existing benign nevus, which occurs most often in the skin but also may involve other sites. {ECO:0000269|PubMed:17434924, ECO:0000269|PubMed:19338054}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.
• Pathway: Neuroactive ligand-receptor interaction - Homo sapiens (human);Melanogenesis - Homo sapiens (human);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: 0.689

Intolerance Scores

• rvis_EVS: 0.34
• rvis_percentile_EVS: 73.73

Haploinsufficiency Scores

• hipred: N
• hipred_score: 0.204

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.781

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Mc1r
• Phenotype: growth/size/body region phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); cellular phenotype; craniofacial phenotype; hearing/vestibular/ear phenotype; limbs/digits/tail phenotype; pigmentation phenotype; neoplasm; hematopoietic system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); immune system phenotype

Gene ontology

• Biological process: 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;multicellular organism development;UV protection;positive regulation of protein kinase A signaling;sensory perception of pain;negative regulation of tumor necrosis factor production;intracellular signal transduction;melanin biosynthetic process;pigmentation;positive regulation of transcription by RNA polymerase II;positive regulation of protein kinase B signaling;UV-damage excision repair;positive regulation of protein kinase C signaling
• Cellular component: plasma membrane;integral component of plasma membrane
• Molecular function: melanocortin receptor activity;melanocyte-stimulating hormone receptor activity;protein binding;G protein-coupled peptide receptor activity;ubiquitin protein ligase binding