UniProtKB/Swiss-Prot Q01726: Variant p.Val60Leu

Melanocyte-stimulating hormone receptor
Gene: MC1R
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Variant information Variant position:

60 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant:

LB/B The variants are classified into three categories: LP/P, LB/B and US.

LP/P: likely pathogenic or pathogenic.
LB/B: likely benign or benign.
US: uncertain significance

Residue change:

From Valine (V) to Leucine (L) at position 60 (V60L, p.Val60Leu). Indicates the amino acid change of the variant. The one-letter and three-letter codes for amino acids used in UniProtKB/Swiss-Prot are those adopted by the commission on Biochemical Nomenclature of the IUPAC-IUB.
Physico-chemical properties:

Similar physico-chemical property. Both residues are medium size and hydrophobic. The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score:

1 The score within a Blosum matrix for the corresponding wild-type to variant amino acid change. The log-odds score measures the logarithm for the ratio of the likelihood of two amino acids appearing by chance. The Blosum62 substitution matrix is used. This substitution matrix contains scores for all possible exchanges of one amino acid with another:

Lowest score: -4 (low probability of substitution).
Highest score: 11 (high probability of substitution).

More information can be found on the following page
Polymorphism:

Genetic variants in MC1R define the skin/hair/eye pigmentation variation locus 2 (SHEP2) [MIM:266300]. Hair, eye and skin pigmentation are among the most visible examples of human phenotypic variation, with a broad normal range that is subject to substantial geographic stratification. In the case of skin, individuals tend to have lighter pigmentation with increasing distance from the equator, with type I skin being the most lightly pigmented and type IV the most dark pigmented. By contrast, the majority of variation in human eye and hair color is found among individuals of European ancestry, with most other human populations fixed for brown eyes and black hair. Partial loss-of-function mutations are associated with fair skin, poor tanning and increased skin cancer risk.MC1R variants associated with red hair and fair skin, determine female-specific increased analgesia from kappa-opioid receptor agonist [MIM:613098]. - Additional information on the polymorphism described.
Variant description:

Probable risk factor for developing melanoma; unable to stimulate cAMP production as strongly as the wild type receptor in response to alpha-melanocyte-stimulating hormone stimulation. Any additional useful information about the variant.
Other resources:

Links to websites of interest for the variant.

Variant rs1805005 [ dbSNP | Ensembl ]

Sequence information Variant position:

60 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length:

317 The length of the canonical sequence.
Location on the sequence:

ISDGLFLSLGLVSLVENALV V ATIAKNRNLHSPMYCFICCL The residue change on the sequence. Unless the variant is located at the beginning or at the end of the protein sequence, both residues upstream (20) and downstream (20) of the variant will be shown.
Residue conservation:

The multiple alignment of the region surrounding the variant against various orthologous sequences.

Human                         ISDGLFLSLGLVSLVENALVVATIAKNRNLHSPMYCFICCL

Gorilla                       IPDGLFLSLGLVSLVENVLVVATIAKNRNLHSPMYCFICCL

                              IPNGLFLSLGLVSVVENVLVVAAIAKNRNLHSPMYYFIGCL

Rhesus macaque                IPDGLFLSLGLVSLVENVLVVTAIAKNRNLHSPMYCFICCL

Chimpanzee                    IPDGLFLSLGLVSLVENMLVVATIAKNRNLHSPMYCFICCL

Mouse                         IPDGLFLSLGLVSLVENVLVVIAITKNRNLHSPMYYFICCL

Pig                           IPDGLFLSLGLVSLVENVLVVAAIAKNRNLHSPMYYFVCCL

Bovine                        IPDGLFLSLGLVSLVENVLVVAAIAKNRNLHSPMYYFICCL

Goat                          IPDGLFLSLGLVSLVENVLVVAAIAKNRNLHSPMYYFICCL

Sheep                         IPDGLFLSLGLVSLVENVLVVAAIAKNRNLHSPMYYFICCL

Cat                           VPDGLFLGLGLVSVVENVLVVAAIAKNRNLHSPMYYFICCL

Horse                         IPDGLFLSLGLVSLVENVLVVTAIAKNRNLHSPMYYFICCL

Chicken                       IPNELFLTLGLVSLVENLLVVAAILKNRNLHSPTYYFICCL

Sequence annotation in neighborhood:

The regions or sites of interest surrounding the variant. In general the features listed are posttranslational modifications, binding sites, enzyme active sites, local secondary structure or other characteristics reported in the cited references. The "Sequence annotation in neighborhood" lines have a fixed format:

Type: the type of sequence feature.
Positions: endpoints of the sequence feature.
Description: contains additional information about the feature.

Type	Positions	Description
Chain	1 – 317	Melanocyte-stimulating hormone receptor
Transmembrane	38 – 63	Helical; Name=1
Mutagenesis	65 – 65	K -> R. Only minor effect on internalization rate and protein half-life; when associated with R-226; R-238 and R-310.
Helix	42 – 65

Literature citations
Submission
SeattleSNPs variation discovery resource;
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]; VARIANTS LEU-60; MET-92; CYS-151; THR-155; LEU-156; TRP-160; GLN-163 AND LEU-196; Characterization of melanocyte stimulating hormone receptor variant alleles in twins with red hair.
Box N.F.; Wyeth J.R.; O'Gorman L.E.; Martin N.G.; Sturm R.A.;
Hum. Mol. Genet. 6:1891-1897(1997)
Cited for: VARIANTS LEU-60; MET-92; CYS-151; TRP-160 AND HIS-294; Loss of function mutations of the human melanocortin 1 receptor are common and are associated with red hair.
Schioeth H.B.; Phillips S.R.; Rudzish R.; Birch-Machin M.A.; Wikberg J.E.S.; Rees J.L.;
Biochem. Biophys. Res. Commun. 260:488-491(1999)
Cited for: CHARACTERIZATION OF VARIANTS LEU-60; HIS-142; CYS-151; TRP-160 AND HIS-294; MC1R: three novel variants identified in a malignant melanoma association study in the Spanish population.
Fernandez L.; Milne R.; Bravo J.; Lopez J.; Aviles J.; Longo M.; Benitez J.; Lazaro P.; Ribas G.;
Carcinogenesis 28:1659-1664(2007)
Cited for: VARIANTS CMM5 PHE-41 AND THR-128; VARIANTS LEU-60; MET-92; THR-155; TRP-160; GLN-163; SER-281 AND HIS-294; DNA sequencing of a cytogenetically normal acute myeloid leukaemia genome.
Ley T.J.; Mardis E.R.; Ding L.; Fulton B.; McLellan M.D.; Chen K.; Dooling D.; Dunford-Shore B.H.; McGrath S.; Hickenbotham M.; Cook L.; Abbott R.; Larson D.E.; Koboldt D.C.; Pohl C.; Smith S.; Hawkins A.; Abbott S.; Locke D.; Hillier L.W.; Miner T.; Fulton L.; Magrini V.; Wylie T.; Glasscock J.; Conyers J.; Sander N.; Shi X.; Osborne J.R.; Minx P.; Gordon D.; Chinwalla A.; Zhao Y.; Ries R.E.; Payton J.E.; Westervelt P.; Tomasson M.H.; Watson M.; Baty J.; Ivanovich J.; Heath S.; Shannon W.D.; Nagarajan R.; Walter M.J.; Link D.C.; Graubert T.A.; DiPersio J.F.; Wilson R.K.;
Nature 456:66-72(2008)
Cited for: VARIANTS [LARGE SCALE ANALYSIS] LEU-60 AND MET-92;

Disclaimer: Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. They are not in any way intended to be used as a substitute for professional medical advice, diagnostic, treatment or care.