GGH T151I - GET-Evidence

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

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(GGH Thr151Ile)

Short summary


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


Insufficiently evaluated pharmacogenetic

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

Inheritance pattern


Summary of published research, and additional commentary


Allele frequency

  • A @ chr8:63938764: 8.3% (889/10758) in EVS
  • A @ chr8:64101317: 14.8% (19/128) in GET-Evidence
  • Frequency shown in summary reports: 8.3% (889/10758)


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PubMed PMID: 15284538


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PubMed PMID: 17286537



hu0D879F - CGI sample GS00253-DNA_G01_200_37
het A @ chr8:63938764













huE80E3D - CGI sample GS00253-DNA_D01_200_37
het A @ chr8:63938764


GS06985 - var-GS06985-1100-36-ASM
het A @ chr8:64101318


GS18526 - var-GS18526-1100-36-ASM
het A @ chr8:64101318


GS18558 - var-GS18558-1100-36-ASM
het A @ chr8:64101318


GS18940 - var-GS18940-1100-36-ASM
het A @ chr8:64101318


GS18956 - var-GS18956-1100-36-ASM
het A @ chr8:64101318


GS19239 - var-GS19239-1100-36-ASM
hom A @ chr8:64101318


GS19240 - var-GS19240-1100-36-ASM
het A @ chr8:64101318


Other external references

  • rs11545078
  • [methotrexate]
    GGH 452C>T has been associated with decreased catalytic activity and higher accumulation of long-chain methotrexate-polyglutamate.
  • [Precursor Cell Lymphoblastic Leukemia-Lymphoma]
    Patients (n= 66) with acute lymphoblastic leukemia showed large individual differences in cellular accumulation of long-chain MTXPG after high-dose methotrexate treatment. The frequency of the rs11545078 (452C>T, Thr127Ile) in GGH was significantly different among patients with low (17.6%), intermediate (9.4%) and high (0%) GGH activity (P = 0.025). Caucasians had a significantly higher frequency of the Ile127 allele (10.0%) than African-Americans (4.4%) (P = 0.033). Rs11545078 was detected in 2 of 4 patients with low GGH activity and none of the five patients with high GGH activity. This missense variant significantly increased Km for long chain polyglutamated methotrexate (MTXPG5) (2.7-fold, P = 0.021), and significantly reduced catalytic efficiency (Vmax/Km) for MTXPG5 (by 67.5%, P = 0.003). The structural impact of this missense variant, based on modelling and enzyme kinetic analysis, indicated a significant reduction GGH binding affinity for long chain MTXPG (MTXPG5).
  • Score: 0.846 (possibly damaging)

Other in silico analyses

  • NBLOSUM100 score = 3
  • GET-Evidence autoscore = 1

Edit history

Gene search

"GENE" or "GENE A123C":

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