ATIC T116S - GET-Evidence

Note: This variant has not been sufficiently evaluated by a GET-Evidence editor.

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Curation:
Currentness:

ATIC T116S

(ATIC Thr116Ser)


Short summary

 

Variant evidence
Computational -
Functional -
Case/Control -
Familial -
 
Clinical importance
Severity -
Treatability -
Penetrance -
 

Impact

Insufficiently evaluated pharmacogenetic

(The "insufficiently evaluated" qualifier is assigned automatically based on the above evidence and importance scores.)

Inheritance pattern

unknown

Summary of published research, and additional commentary

 

Allele frequency

  • G @ chr2:216190020: 24.8% (2664/10758) in EVS
  • G @ chr2:215898264: 19.8% (25/126) in GET-Evidence
  • Frequency shown in summary reports: 24.8% (2664/10758)

Publications
 

Dervieux T, Furst D, Lein DO, Capps R, Smith K, Walsh M, Kremer J. Polyglutamation of methotrexate with common polymorphisms in reduced folate carrier, aminoimidazole carboxamide ribonucleotide transformylase, and thymidylate synthase are associated with methotrexate effects in rheumatoid arthritis. Arthritis Rheum. 2004 Sep;50(9):2766-74. PubMed PMID: 15457444.

 

Dervieux T, Furst D, Lein DO, Capps R, Smith K, Caldwell J, Kremer J. Pharmacogenetic and metabolite measurements are associated with clinical status in patients with rheumatoid arthritis treated with methotrexate: results of a multicentred cross sectional observational study. Ann Rheum Dis. 2005 Aug;64(8):1180-5. Epub 2005 Jan 27. PubMed PMID: 15677700; PubMed Central PMCID: PMC1755602.

 

Warren RB, Smith RL, Campalani E, Eyre S, Smith CH, Barker JN, Worthington J, Griffiths CE. Outcomes of methotrexate therapy for psoriasis and relationship to genetic polymorphisms. Br J Dermatol. 2009 Feb;160(2):438-41. Epub 2008 Oct 25. PubMed PMID: 19016697; PubMed Central PMCID: PMC2680291.

 

Genomes
 

hu0E64A1 - CGI sample GS01173-DNA_B02 from PGP sample 94378523
hom G @ chr2:216190020

 

 

 

hu342A08 - CGI sample GS01175-DNA_B05 from PGP sample 83494370
het G @ chr2:216190020

 

 

 

hu4040B8 - CGI sample GS01175-DNA_D01 from PGP sample 31286272
het G @ chr2:216190020

 

hu4339C0 - CGI sample GS01175-DNA_H01 from PGP sample 94797469
het G @ chr2:216190020

 

hu43860C - CGI sample GS00253-DNA_A01_200_37
het G @ chr2:216190020

 

 

hu72A81D - CGI sample GS01173-DNA_C02 from PGP sample 10366372
het G @ chr2:216190020

 

hu9385BA - CGI sample GS00253-DNA_E01_200_37
het G @ chr2:216190020

 

huAE4A11 - CGI sample GS01669-DNA_F02 from PGP sample 40767107
het G @ chr2:216190020

 

huB1FD55 - CGI sample GS01173-DNA_B07 from PGP sample 61499538
het G @ chr2:216190020

 

huBAAC98 - CGI sample GS01173-DNA_F02 from PGP sample 70008981
het G @ chr2:216190020

 

huBEDA0B - CGI sample GS00253-DNA_C01_200_37
het G @ chr2:216190020

 

huC30901 - CGI sample GS00253-DNA_B01_200_37
het G @ chr2:216190020

 

huCA017E - CGI sample GS01175-DNA_B01 from PGP sample 86206034
het G @ chr2:216190020

 

huD37D14 - CGI sample GS01175-DNA_A04 from PGP sample 13272228
het G @ chr2:216190020

 

huFAF983 - CGI sample GS01175-DNA_F02 from PGP sample 95788191
het G @ chr2:216190020

 

GS06994 - var-GS06994-1100-36-ASM
het G @ chr2:215898265

 

GS12004 - var-GS12004-1100-36-ASM
het G @ chr2:215898265

 

GS18517 - var-GS18517-1100-36-ASM
het G @ chr2:215898265

 

GS18526 - var-GS18526-1100-36-ASM
het G @ chr2:215898265

 

GS18558 - var-GS18558-1100-36-ASM
het G @ chr2:215898265

 

GS18942 - var-GS18942-1100-36-ASM
het G @ chr2:215898265

 

GS18956 - var-GS18956-1100-36-ASM
hom G @ chr2:215898265

 

GS19648 - var-GS19648-1100-36-ASM
het G @ chr2:215898265

 

GS19649 - var-GS19649-1100-36-ASM
het G @ chr2:215898265

 

GS19704 - var-GS19704-1100-36-ASM
het G @ chr2:215898265

 

GS19735 - var-GS19735-1100-36-ASM
hom G @ chr2:215898265

 

GS20509 - var-GS20509-1100-36-ASM
het G @ chr2:215898265

 

NA12878

 

Other external references
 

    dbSNP
  • rs2372536
    www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi
    PharmGKB
  • [Arthritis, Rheumatoid]
    [methotrexate]
    Rheumatoid arthritis patients taking methotrexate (MTX) >3 months who carry the ATIC 347GG (116Ser/Ser) genotype showed lower disease activity as assessed by the physician (p = 0.02) and fewer swollen joints (p = 0.06) compared with carriers of combined ATIC CG and CC genotypes; and a pharmacogenetic index of the combined variant alleles for MTX pathway gene variants, TYMS *2, ATIC 347C>G (116Ser), and SLC19A1 (RFC-1) 80A>G (27Arg), was associated with less tender joints (p = 0.012), less swollen joints (p = 0.004), less physician-assessed disease activity (p = 0.0004), and less patient-assessed difficulty with physical tasks (p = 0.001).
    www.ncbi.nlm.nih.gov/pubmed/15457444
  • [Psoriasis]
    [folic acid; methotrexate]
    In 330 patients who completed 3 months methotrexate treatment for psoriasis, no significant genotypic associations were found between clinical outcome (e.g. efficacy, toxicity) and 50 SNPs in pathway genes for methotrexate metabolism (ATIC, FPGS, GGH, MTHFR), including 47 common ( >5% minor allele frequency) haplotype-tagging SNPs (r(2) > 0.8) plus 3 additional SNPs.
    www.ncbi.nlm.nih.gov/pubmed/19016697
  • [Arthritis, Rheumatoid]
    [methotrexate]
    Risk or phenotype-associated allele: ATIC 347CC (116Thr/Thr) > GC (116Thr/Ser) > GG (116Ser/Ser) Phenotype: A composite pharmacogenetic index (additive from zero to five) was calculated using the following values: ATIC 347CC or TSER*3/*3 or SLC19A1 80GG or SLC19A1 80GA genotypes were valued as 0, ATIC 347CG or TSER*2/*3 or SLC19A1 80AA genotypes were valued as 1, and ATIC 347GG or TSER*2/*2 genotypes were valued as 2. The sum originating from each component (ATIC + TSER + SLC19A1) was calculated and constitutes the pharmacogenetic index for the patient. There was a significant association between smaller pharmacolgical index and greater number of tender joints (p = 0.002), swollen joints (p = 0.003), greater physician's global assessment of disease activity (p = 0.032), and higher modified Health Assessment Questionnaire (mHAQ) (p = 0.047). Study size: Study population/ethnicity: Significance metric(s): p < 0.05. Type of association: PD; PK; GN; FA
    www.ncbi.nlm.nih.gov/pubmed/15677700
    PolyPhen-2
  • Score: 0.001 (benign)

Other in silico analyses
 

  • NBLOSUM100 score = –2
  • GET-Evidence autoscore = 1

Edit history
 

Gene search

"GENE" or "GENE A123C":

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