KRT5 G138E - GET-Evidence

Curation:
Currentness:

KRT5 G138E

(KRT5 Gly138Glu)


Short summary

This variant is associated with 1.25x increased risk of basal cell carcinoma (common skin cancer, rarely malignant).

Variant evidence
Computational 1

Polyphen 2 predicts damaging effect

Functional -
Case/Control 4

equivalent to p=.00067

See Stacey SN et al. 2009 (19578363).

Familial

No familial data

 
Clinical importance
Severity 2

Late onset, rarely malignant, invades surrounding tissue

Treatability 1

Surgically remove if necessary

Penetrance 3

See Stacey SN et al. 2009 (19578363).

 

Impact

Low clinical importance, Likely pathogenic

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

Inheritance pattern

undefined

Summary of published research, and additional commentary

 

Allele frequency

  • T @ chr12:52913668: 5.2% (561/10758) in EVS
  • T @ chr12:51199934: 1.6% (2/128) in GET-Evidence
  • Frequency shown in summary reports: 5.2% (561/10758)

Publications
 

Stacey SN, Sulem P, Masson G, Gudjonsson SA, Thorleifsson G, Jakobsdottir M, Sigurdsson A, Gudbjartsson DF, Sigurgeirsson B, Benediktsdottir KR, Thorisdottir K, Ragnarsson R, Scherer D, Hemminki K, Rudnai P, Gurzau E, Koppova K, Botella-Estrada R, Soriano V, Juberias P, Saez B, Gilaberte Y, Fuentelsaz V, Corredera C, Grasa M, Höiom V, Lindblom A, Bonenkamp JJ, van Rossum MM, Aben KK, de Vries E, Santinami M, Di Mauro MG, Maurichi A, Wendt J, Hochleitner P, Pehamberger H, Gudmundsson J, Magnusdottir DN, Gretarsdottir S, Holm H, Steinthorsdottir V, Frigge ML, Blondal T, Saemundsdottir J, Bjarnason H, Kristjansson K, Bjornsdottir G, Okamoto I, Rivoltini L, Rodolfo M, Kiemeney LA, Hansson J, Nagore E, Mayordomo JI, Kumar R, Karagas MR, Nelson HH, Gulcher JR, Rafnar T, Thorsteinsdottir U, Olafsson JH, Kong A, Stefansson K. New common variants affecting susceptibility to basal cell carcinoma. Nat Genet. 2009 Aug;41(8):909-14. Epub 2009 Jul 5. PubMed PMID: 19578363; PubMed Central PMCID: PMC2973331.

This GWAS study finds the variant is associated with increased risk of basal cell carcinoma (BCC) in the European populations studied — cases had an allele frequency of 10.5%, controls a frequency of 8.4%.

This finding had a p-value of 2.1*10^-9, and the authors report a Bonferroni threshold of 1.6 * 10^-7. This threshold is consistent with a p-value of 0.05 and correcting for 317,00 hypotheses (Illumina HumanHap300). Using this, the p-value can be treated as .00067.

The increased risk of disease can be calculated by making some assumptions — that the 8.4% frequency represents the general population (both people who do and do not get BCC), and that the lifetime risk for BCC in Europeans is 30%. Based on these assumptions, this variant has a BCC rate of 37.5% associated with it (an increased risk of 7.5%).

BCC is rarely malignant, it is typically treated because it is invasive and destroys surrounding tissue.

Genomes
 

hu011C57 - CGI sample GS01669-DNA_B05 from PGP sample 86486261
het T @ chr12:52913668

 

hu9385BA - CGI sample GS00253-DNA_E01_200_37
het T @ chr12:52913668

 

huB1FD55 - CGI sample GS01173-DNA_B07 from PGP sample 61499538
het T @ chr12:52913668

 

huFFAD87 - CGI sample GS01669-DNA_H05 from PGP sample 10971581
het T @ chr12:52913668

 

Other external references
 

    dbSNP
  • rs11170164
    www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi
    GeneTests
  • GeneTests records for the KRT5 gene
    Epidermolysis Bullosa Simplex
    Epidermolysis Bullosa Simplex with Mottled Pigmentation
    Epidermolysis Bullosa Simplex, Dowling-Meara Type
    Epidermolysis Bullosa Simplex, Koebner Type
    Epidermolysis Bullosa Simplex, Weber-Cockayne Type
    www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/KRT5
    PolyPhen-2
  • Score: 0.932 (probably damaging)
    Web search results (119 hits -- see all)
  • Pubget: authors:"Pablo Juberias"
    SNP rs11170164, encoding a G138E substitution in the keratin 5 (KRT5) gene, af... SNP rs11170164, encoding a G138E substitution in the keratin 5 (KRT5) gene, af...
    pubget.com/search?q=authors:"Pablo Juberias"
  • New common variants affecting susceptibility to basal cell ...
    Nature Genetics publishes the very highest quality research in ... SNP rs11170164, encoding a G138E substitution in the keratin 5 (KRT5) gene, affects risk of BCC (OR = 1.35, P ...
    www.nature.com/ng/journal/v41/n8/abs/ng.412.html
  • Gretarsdottir, S (Solveig)
    Gretarsdottir, S (Solveig) :: Localization of a susceptibility gene for common forms of stroke to 5q12. ... encoding a G138E substitution in the keratin 5 (KRT5) gene, affects ...
    lib.bioinfo.pl/auid:23718
  • deCODE Genetics Publications 2009 | Scientific Leadership
    You appear to have disabled Javascript, please enable it to enjoy the full experience of ... encoding a G138E substitution in the keratin 5 (KRT5) gene, affects risk ...
    www.decodeme.com/scientific-leadership/2009
  • New common variants affecting susceptibility to basal cell ...
    New common variants affecting susceptibility to basal cell carcinoma. Stacey SN, Sulem P, Masson G, ... encoding a G138E substitution in the keratin 5 (KRT5) gene, affects risk ...
    www.ncbi.nlm.nih.gov/pubmed/19578363
  • pubget—the blog: Hot off the presses! Aug 01 Nat Genet
    news and updates about the fastest way to search science http: ... SNP rs11170164, encoding a G138E substitution in the keratin 5 (KRT5) gene, affects risk of BCC (OR = 1.35, P ...
    pubget.blogspot.com/2009/07/hot-off-presses-aug-01-nat-ge...
  • FHA - Keratin-5 (Genetics) - Research News and Information
    Mutations in the gene for keratin-5 are associated with EPIDERMOLYSIS BULLOSA SIMPLEX. ... SNP rs11170164, encoding a G138E substitution in the keratin 5 (KRT5) gene, ...
    www.find-health-articles.com/msh-keratin-5--genetics.htm
  • Soriano, V (Virtudes)
    Soriano, V (Virtudes) :: ASIP and TYR pigmentation variants associate with cutaneous ... rs11170164, encoding a G138E substitution in the keratin 5 (KRT5) gene, affects risk of ...
    lib.bioinfo.pl/auid:8475914
  • New common variants affecting susceptibility to basal cell ...
    New common variants affecting susceptibility to basal cell carcinoma. ... encoding a G138E substitution in the keratin 5 (KRT5) gene, affects risk ...
    www.nextbio.com/b/search/article.nb?id=19578363

Other in silico analyses
 

  • NBLOSUM100 score = 6
  • GET-Evidence autoscore = 4

Edit history
 

Gene search

"GENE" or "GENE A123C":

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