UniProtKB/Swiss-Prot Q71RS6: Variant p.Thr111Ala

Sodium/potassium/calcium exchanger 5
Gene: SLC24A5
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Variant information Variant position:

111 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 Threonine (T) to Alanine (A) at position 111 (T111A, p.Thr111Ala). 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 polar (T) to small size and hydrophobic (A) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score:

0 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 SLC24A5 define the skin/hair/eye pigmentation variation locus 4 (SHEP4) [MIM:113750]. 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. 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.The Ala-111 allele predominates (93 to 100%) in African and East Asian populations. In contrast, the Thr-111 allele is nearly fixed (98.7 to 100%) in European populations, is associated with a substantial reduction in regional heterozygosity, and correlates with lighter skin pigmentation in admixed populations. - Additional information on the polymorphism described.
Variant description:

Greatly reduced exchange activity. Any additional useful information about the variant.
Other resources:

Links to websites of interest for the variant.

Variant rs1426654 [ dbSNP | Ensembl ]

Sequence information Variant position:

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

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

FLPSLEIISESLGLSQDVAG T TFMAAGSSAPELVTAFLGVF 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                         FLPSLEIISESLGLSQDVAGTTFMAAGSSAPELVTAFLGVF

Mouse                         FLPSLEIISDSLGLSQDVAGATFMAAGSSAPELVTAFLGVF

Zebrafish                     FLPSLEVISERLGLSQDVAGATFMAAGSSAPELVTAFLGVF

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	30 – 500	Sodium/potassium/calcium exchanger 5
Topological domain	88 – 111	Cytoplasmic

Literature citations
SLC24A5, a putative cation exchanger, affects pigmentation in zebrafish and humans.
Lamason R.L.; Mohideen M.-A.P.K.; Mest J.R.; Wong A.C.; Norton H.L.; Aros M.C.; Jurynec M.J.; Mao X.; Humphreville V.R.; Humbert J.E.; Sinha S.; Moore J.L.; Jagadeeswaran P.; Zhao W.; Ning G.; Makalowska I.; McKeigue P.M.; O'Donnell D.; Kittles R.; Parra E.J.; Mangini N.J.; Grunwald D.J.; Shriver M.D.; Canfield V.A.; Cheng K.C.;
Science 310:1782-1786(2005)
Cited for: FUNCTION; VARIANT ALA-111; SLC24A5 encodes a trans-Golgi network protein with potassium-dependent sodium-calcium exchange activity that regulates human epidermal melanogenesis.
Ginger R.S.; Askew S.E.; Ogborne R.M.; Wilson S.; Ferdinando D.; Dadd T.; Smith A.M.; Kazi S.; Szerencsei R.T.; Winkfein R.J.; Schnetkamp P.P.; Green M.R.;
J. Biol. Chem. 283:5486-5495(2008)
Cited for: FUNCTION; TRANSPORTER ACTIVITY; SUBCELLULAR LOCATION; CHARACTERIZATION OF VARIANT ALA-111; A genomewide association study of skin pigmentation in a South Asian population.
Stokowski R.P.; Pant P.V.K.; Dadd T.; Fereday A.; Hinds D.A.; Jarman C.; Filsell W.; Ginger R.S.; Green M.R.; van der Ouderaa F.J.; Cox D.R.;
Am. J. Hum. Genet. 81:1119-1132(2007)
Cited for: VARIANT ALA-111; INVOLVEMENT IN SHEP4; POLYMORPHISM;

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.