SLC45A2 L374F - GET-Evidence

Curation:
Currentness:

SLC45A2 L374F

(SLC45A2 Leu374Phe)


Short summary

Pigmentation allele for non-black hair, and consequently, possible increased susceptibility to malignant melanoma.

Variant evidence
Computational -
Functional -
Case/Control 5

See Graf J et al. 2005 (15714523).

Familial -
 
Clinical importance
Severity

See Graf J et al. 2005 (15714523), Fernandez LP et al. 2008 (18563784).

Treatability

See Graf J et al. 2005 (15714523), Fernandez LP et al. 2008 (18563784).

Penetrance -
 

Impact

Low clinical importance, Likely benign

(The "low clinical importance, likely" qualifier is assigned automatically based on the above evidence and importance scores.)

Inheritance pattern

unknown

Summary of published research, and additional commentary

 

Total cases/controls case+ case– control+ control– p-value odds ratio
Skin pigmentation
2253 117 303 63 0.0000 4.004

 

Allele frequency

  • G @ chr5:33951693: 69.2% (7442/10758) in EVS
  • G @ chr5:33987449: 40.6% (52/128) in GET-Evidence
  • Frequency shown in summary reports: 69.2% (7442/10758)

Publications
 

Graf J, Hodgson R, van Daal A. Single nucleotide polymorphisms in the MATP gene are associated with normal human pigmentation variation. Hum Mutat. 2005 Mar;25(3):278-84. PubMed PMID: 15714523.

The reverse of this variant, F374L, of the SLC45A2 gene (a.k.a. MATP) is significantly correlated with dark hair, skin and eye color in Caucasions. However, this variant (L374F) appears to be prevalent in all phenotypes for the Caucasion population under investigation.

Cases/controls case+ case– control+ control– p-value odds ratio
Skin pigmentation
2253 117 303 63 0.0000 4.004

 

Yuasa I, Umetsu K, Harihara S, Kido A, Miyoshi A, Saitou N, Dashnyam B, Jin F, Lucotte G, Chattopadhyay PK, Henke L, Henke J. Distribution of the F374 allele of the SLC45A2 (MATP) gene and founder-haplotype analysis. Ann Hum Genet. 2006 Nov;70(Pt 6):802-11. PubMed PMID: 17044855.

 

Fernandez LP, Milne RL, Pita G, Avilés JA, Lázaro P, Benítez J, Ribas G. SLC45A2: a novel malignant melanoma-associated gene. Hum Mutat. 2008 Sep;29(9):1161-7. PubMed PMID: 18563784.

The reverse variant, F374L , is shown to be protective against melanoma, further establishing the association with darker pigmentation (and conversely, lighter pigmentation for this variant, L374F).

Branicki W, Brudnik U, Draus-Barini J, Kupiec T, Wojas-Pelc A. Association of the SLC45A2 gene with physiological human hair colour variation. J Hum Genet. 2008;53(11-12):966-71. Epub 2008 Sep 20. PubMed PMID: 18806926.

 

Genomes
 

 

 

hu034DB1 - CGI sample GS00253-DNA_A02_200_37
hom G @ chr5:33951693

 

hu04FD18 - CGI sample GS00253-DNA_F01_200_37
hom G @ chr5:33951693

 

hu0D879F - CGI sample GS00253-DNA_G01_200_37
hom G @ chr5:33951693

 

 

 

 

 

 

 

 

 

 

 

 

 

hu43860C - CGI sample GS00253-DNA_A01_200_37
hom G @ chr5:33951693

 

 

 

 

 

 

 

 

 

hu9385BA - CGI sample GS00253-DNA_E01_200_37
hom G @ chr5:33951693

 

 

 

 

huAE6220 - CGI sample GS00253-DNA_H01_200_37
hom G @ chr5:33951693

 

 

 

huBEDA0B - CGI sample GS00253-DNA_C01_200_37
hom G @ chr5:33951693

 

huC30901 - CGI sample GS00253-DNA_B01_200_37
hom G @ chr5:33951693

 

 

 

huE80E3D - CGI sample GS00253-DNA_D01_200_37
het G @ chr5:33951693

 

 

 

GS06985 - var-GS06985-1100-36-ASM
hom G @ chr5:33987450

 

GS06994 - var-GS06994-1100-36-ASM
hom G @ chr5:33987450

 

GS07357 - var-GS07357-1100-36-ASM
hom G @ chr5:33987450

 

GS10851 - var-GS10851-1100-36-ASM
hom G @ chr5:33987450

 

GS12004 - var-GS12004-1100-36-ASM
hom G @ chr5:33987450

 

GS19648 - var-GS19648-1100-36-ASM
hom G @ chr5:33987450

 

GS19649 - var-GS19649-1100-36-ASM
hom G @ chr5:33987450

 

GS19670 - var-GS19670-1100-36-ASM
het G @ chr5:33987450

 

GS19701 - var-GS19701-1100-36-ASM
het G @ chr5:33987450

 

GS19704 - var-GS19704-1100-36-ASM
het G @ chr5:33987450

 

GS20502 - var-GS20502-1100-36-ASM
hom G @ chr5:33987450

 

Other external references
 

    dbSNP
  • rs16891982
    www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi
    GWAS
  • Skin pigmentation (rs16891982-C)
    Stokowski 15-Oct-07 in Am J Hum Genet
    OR or beta: 4.86 [2.88-8.21]
    Risk allele frequency: 0.83
    p-value: 3.00E-11
    Initial sample: 363 with maxL* < 56 and 374 with maxL* > 63; 20% tails of distribution
    Replication sample: 116 low maxL*, 115 high maxL* individuals
    www.ncbi.nlm.nih.gov/pubmed/17999355
    PolyPhen-2
  • Score: 0.947 (probably damaging)
    Web search results (160 hits -- see all)
  • BioPortfolio - p.L374F
    P.L374F Pages on BioPortfolio: Results from other life science and pharmaceutical sites: ... An L374F substitution in SLC45A2 is at 100% frequency in the European sample .
    www.bioportfolio.com/search/p.L374F.html
  • Distribution of the F374 Allele of the SLC45A2 (MATP) Gene ...
    The L374F. mutation in the SLC45A2 gene encoding MATP has been suggested to be associated ... that the L374F mutation occurred only once in the ancestry of ...
    sayer.lab.nig.ac.jp/.../paper-pdf/Yuasa_AnnHumGenet06.pdf
  • Journal of Human Genetics - Abstract of article: Association ...
    Association of the SLC45A2 gene with physiological human hair colour variation ... Pigmentation, SLC45A2, Association study, E272K, L374F, Phenotype prediction ...
    www.nature.com/doifinder/10.1007/s10038-008-0338-3
  • Sengupta, Mol Vis 2007; 13:1406-1411.
    ... identified which included E272K and L374F polymorphisms that have been reported ... mutation in SLC45A2 and a defect in another locus, or SLC45A2 is not ...
    www.molvis.org/molvis/v13/a155
  • Gretarsdottir, S (Solveig)
    A melanoma- and pigmentation-associated variant in the SLC45A2 gene, L374F, is associated with risk of both BCC and squamous cell carcinoma. ...
    lib.bioinfo.pl/auid:23718
  • New common variants affecting susceptibility to basal cell ...
    Nature Genetics publishes the very highest quality research in ... melanoma- and pigmentation-associated variant in the SLC45A2 gene, L374F, is associated with risk of both BCC ...
    www.nature.com/ng/journal/v41/n8/abs/ng.412.html
  • deCODE Genetics Publications 2009 | Scientific Leadership
    A melanoma- and pigmentation-associated variant in the SLC45A2 gene, L374F, is associated with risk of both BCC and squamous cell carcinoma. ...
    www.decodeme.com/scientific-leadership/2009
  • Pubget: authors:"Pablo Juberias"
    A melanoma- and pigmentation-associated variant in the SLC45A2 gene, L374F, is associated with risk of both BCC and squamous cell carcinoma. ...
    pubget.com/search?q=authors:"Pablo Juberias"
  • SLC45A2 variations in Indian oculocutaneous albinism patients.
    SLC45A2 variations in Indian oculocutaneous albinism patients. ... tyrosinase gene (TYR) were screened further for nucleotide variants in SLC45A2. ...
    www.ncbi.nlm.nih.gov/pubmed/17768386
  • SLC45A2/MATP & The Genetics Of Human Hair Color ...
    SLC45A2 stands for solute carrier family 45, member 2. It is found on ... The leucine residue on position 374 is thus changed to a phenylalanine (annotated as L374F) ...
    anthropology.net/2008/10/09/slc45a2matp-the-genetics-of-h...

Other in silico analyses
 

  • NBLOSUM100 score = 0
  • GET-Evidence autoscore = 5

Edit history
 

Gene search

"GENE" or "GENE A123C":

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