MC1R gene variants involvement in human OCA phenotype

Abstract

Oculocutaneous albinism (OCA) is a genetic disorder of melanin synthesis that results in hypopigmentation in hair, skin and eyes. OCA has been reported in individuals from all ethnic backgrounds but it is more common among those with Europeans ancestry. OCA is heterogeneous group of disorders and seven types of OCA are caused by mutations in TYR (OCA1), OCA2 (OCA2), TYRP1 (OCA3), SLC45A2 (OCA4), SLC24A5 (OCA6) and C10oRF11 (OCA7) genes. However, MC1R gene variants have been reported that modify OCA2 phenotype but the knowledge about the function ofMC1R gene in melanogenesis, and genotype-phenotype association, in case of OCA, is limited. In this review article we present a comprehensive description of classification of OCA, role of MSH-R in melanin synthesis, the sequence variations in MC1R and their association with OCA. This review will enhance our understanding of MC1R gene variants involved in human OCA2 phenotype.

A genome-wide scan study identifies a single nucleotide substitution in MC1R gene associated with white coat colour in fallow deer (Dama dama)

“…Furthermore, indels and large structural variants would not have been detected by our approach. The MC1R gene is involved in a huge network of colouring genes (for overview see [25]), and thus associated with a broad spectrum of colour variation in human [26], mouse [27] and several other mammalian and bird species, such as horses [28], foxes [29], dogs [30], rabbits [31], chicken [32], alpacas [33], buffalos [20], sheep [34,35], goats [36], and cattle [37,38]. Variants were described together with the prevention of the white winter coat in foxes [39] and increased pigmentation in reindeer [40] and other species (overview by [41]).…”

“…Variants were described together with the prevention of the white winter coat in foxes [39] and increased pigmentation in reindeer [40] and other species (overview by [41]). However, besides oculocutaneous albinism type 2 in humans [26], associations of MC1R variants with white coat colour are rare. They were found in black bears [42], white leghorn chicken [43], martens [44], mice [45], Huskies [46] and the Arabian camel [47].…”

“…MC1R is a seven-pass transmembrane G protein [26] coupled receptor that is especially located on the surface of melanocytes. MC1R is activated by the α-melanocyte stimulating hormone (α-MSH) and competitively inhibited by the agouti signalling protein (ASIP).…”

“…MC1R is activated by the α-melanocyte stimulating hormone (α-MSH) and competitively inhibited by the agouti signalling protein (ASIP). Activation stimulates an adenylate cyclase and increases the amount of cAMP, activating the transcription of enzymes involved in eumelanin production [26], e.g. TYRP1 and TYR, the key enzymes in melanin biosynthesis [2,48].…”

Dysregulation of MITF Leads to Transformation in MC1R-Defective Melanocytes

“…( K ) Frequency of the indicated MC1R mutations in the TCGA melanoma cohort ( n = 471) and in the 73 cases with high expression of MITF. Their associated phenotypes according to [ 48 , 49 , 50 ] are indicated (N/A is not applicable or not known) as well as whether the variant is highly (double arrow), or mildly (single arrow) impairing MC1R function. * indicates the MC1R variants co-occurring in Hermes 4C cell lines; ** indicates the synonymous mutation of the MC1R that does not alter the amino acid sequence of MC1R.…”