{{Rsnum
|rsid=11545078
|Gene=GGH
|Chromosome=8
|position=63026205
|Orientation=minus
|GMAF=0.07117
|Assembly=GRCh38
|GenomeBuild=38.1
|dbSNPBuild=141
|geno1=(C;C)
|geno2=(C;T)
|geno3=(T;T)
|Gene_s=GGH
}}{{ population diversity
| geno1=(C;C)
| geno2=(C;T)
| geno3=(T;T)
| CEU | 77.6 | 20.6 | 1.9
| HCB | 0.0 | 0.0 | 0.0
| JPT | 76.9 | 22.2 | 0.9
| YRI | 83.6 | 15.7 | 0.7
| ASW | 87.5 | 12.5 | 0.0
| CHB | 0.0 | 0.0 | 0.0
| CHD | 86.9 | 12.1 | 0.9
| GIH | 72.2 | 21.6 | 6.2
| LWK | 86.0 | 13.1 | 0.9
| MEX | 0.0 | 0.0 | 0.0
| MKK | 85.3 | 14.1 | 0.6
| TSI | 83.8 | 14.1 | 2.0
| HapMapRevision=28
}}{{PharmGKB
|RSID=rs11545078
|Name_s=GGH: c.452C>T, p.Thr151Ile; p.Thr127Ile
|Gene_s=GGH
|Feature=Exon/NonSyn
|Evidence=PubMed ID:15284538
|Annotation=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).
|Drugs=methotrexate
|Drug Classes=
|Diseases=Precursor Cell Lymphoblastic Leukemia-Lymphoma
|Curation Level=Curated
|PharmGKB Accession ID=PA165109543
}}

{{PharmGKB
|RSID=rs11545078
|Name_s=GGH: 452C>T
|Gene_s=GGH
|Feature=Exon/NonSyn
|Evidence=PubMed ID:17286537
|Annotation=GGH 452C>T has been associated with decreased catalytic activity and higher accumulation of long-chain methotrexate-polyglutamate.
|Drugs=methotrexate
|Drug Classes=
|Diseases=
|Curation Level=Curated
|PharmGKB Accession ID=PA165106757
}}

{{PMID Auto
|PMID=22018726
|Title=Genetic variation in folylpolyglutamate synthase and gamma-glutamyl hydrolase and plasma homocysteine levels in the Singapore Chinese Health Study
|OA=1
}}

{{PMID|16826517|OA=1
}} Epigenetic regulation of human gamma-glutamyl hydrolase activity in acute lymphoblastic leukemia cells.

{{GET Evidence
|gene=GGH
|aa_change=Thr151Ile
|aa_change_short=T151I
|impact=pharmacogenetic
|qualified_impact=Insufficiently evaluated pharmacogenetic
|inheritance=unknown
|quality_scores=Array
|dbsnp_id=rs11545078
|overall_frequency_n=889
|overall_frequency_d=10758
|overall_frequency=0.0826362
|n_genomes=12
|n_genomes_annotated=0
|n_haplomes=13
|n_articles=2
|n_articles_annotated=2
|in_pharmgkb=Y
|pph2_score=0.846
|nblosum100=3
|autoscore=1
|webscore=N
}}

{{on chip | 23andMe v3}}
{{on chip | 23andMe v4}}
{{on chip | FTDNA2}}
{{on chip | HumanOmni1Quad}}
{{on chip | Illumina Human 1M}}