UniProtKB/Swiss-Prot Q01726: Variant p.Asp294His

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

294 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 Aspartate (D) to Histidine (H) at position 294 (D294H, p.Asp294His). 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:

Change from medium size and acidic (D) to medium size and polar (H) 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 rs1805009 [ dbSNP | Ensembl ]

Sequence information Variant position:

294 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:

GCIFKNFNLFLALIICNAII D PLIYAFHSQELRRTLKEVLT 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                         GCIFKNFNLFLALIICNAIIDPLIYAFHSQELRRTLKEVLT

Gorilla                       GCIFKNFNLFLALIICNAIIDPLIYAFHSQELRRTLKEVLT

                              GCVFQNFNLFLTLIICNSIIDPFIYAFRSQELRKTLQEVVL

Rhesus macaque                SCIFKNFNLFLALIICNAIIDPLIYAFRSQELRRTLKEVLL

Chimpanzee                    GCIFKNFNLFLALIICNAIIDPLIYAFHSQELRRTLKEVLT

Mouse                         SCIFKNFNLFLLLIVLSSTVDPLIYAFRSQELRMTLKEVLL

Pig                           GCVFKNVNLFLALVICNSIVDPLIYAFRSQELRKTLQEVLQ

Bovine                        GCIFKNFNLFLALIICNAIVDPLIYAFRSQELRKTLQEVLQ

Goat                          GCIFKNFNLFLALIICNAIVDPLIYAFRSQELRKTLQEVLQ

Sheep                         GCIFKNFNLFLALIICNAIVDPLIYAFRSQELRKTLQEVLQ

Cat                           GCVFKNFNLFLTLIICNSIVDPFIYAFRSQELRKTLQEVLL

Horse                         GCVFKNFKLFLTLILCSAIVDPLIYAFRSQELRKTLQEVLL

Chicken                       TCFFSYFNLFLILIICNSVVDPLIYAFRSQELRRTLREVVL

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	280 – 300	Helical; Name=7
Mutagenesis	310 – 310	K -> R. Only minor effect on internalization rate and protein half-life; when associated with R-65; R-226 and R-238.
Helix	280 – 298

Literature citations
Variants of the melanocyte-stimulating hormone receptor gene are associated with red hair and fair skin in humans.
Valverde P.; Healy F.; Jackson I.; Rees J.L.; Thody A.J.;
Nat. Genet. 11:328-330(1995)
Cited for: VARIANT HIS-294; 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;

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.