GSTM1 (Glutathione S-transferase M1)

Note	In humans, five GSTM genes are encoded by a 100-kb gene cluster on chromosome 1p13.3 arranged as 5?-GSTM4-GSTM2-GSTM1-GSTM5-GSTM3-3?, known to be highly polymorphic (Pearson et al., 1993).
	GSTM1 gene. The GSTM1 gene spans a region of 21,244 bases, composed of the eights exons (red) and seven introns (green). Exons 1, 2, 3, 4, 5, 6, 7 and 8 are 90bp, 76bp, 65bp, 82bp, 101bp, 96bp, 111bp and 540bp in length, respectively.
Description	The GSTM1 gene is composed of 8 exons spanning a region of 21,244 bases, with transcript length of 1,161 bps and translation length of 218 residues (according to ensembl GRCh37 release 78). The GSTM1 gene is approximately 20 kb in length and is closely flanked by other mu class gene sequences. The end points of the polymorphic GSTM1 deletion are: the left repeated region 5 kb downstream from the 3?-end of the GSTM2 gene and 5 kb upstream from the beginning of the GSTM1 gene; the right repeated region 5 kb downstream from the 3?-end of the GSTM1 and 10 kb upstream from the 5?-end of the GSTM5 gene (Xu et al., 1998). The cDNAs encoded by GSTM1 and GSTM2 share a remarkable 99% sequence identity (Vorachek et al., 1991). The fact that GSTM1 and GSTM2 are physically linked suggests that the frequent deletion of the GSTM1 locus is caused by unequal crossing-over (Pearson et al., 1993). Furthermore, in HeLa cells, it has been confirmed that GSTM2 overexpression, following transient knockdown of GSTM1 and the absence of GSTM1 activity, may be compensated by the overexpression of GSTM2 (Bhattacharjee et al., 2013). Moreover, existence of linkage disequilibrium between GSTM1 and GSTM3 suggests that association between phenotype and GSTM1 genotypes may also reflect polymorphism in GSTM3 or even other GSTM genes (Wu et al., 2012). Polymorphisms: The restriction mapping data revealed the presence of a GST mu cluster with two GSTM1 genes in tandem situated between the GSTM2 and GSTM5 genes (McLellan et al., 1997). The GSTM1 gene contains four different alleles, leading to several M1 class polymorphisms, designated as GSTM1-0, GSTM1-A, GSTM1-B and GSTM1-1x2 alleles (Wu et al., 2012; Board PG, 1981). GSTM1-0 (GSTM1 null allele) arose from a recombination event during evolution between 2 highly homologous regions flanking this locus, resulting in deletion of a 20-kb segment (Xu et al., 1998). This deletion produces a novel 7.4-kb HindIII fragment with the loss of 10.3- and 11.4-kb HindIII fragments, hence homozygotes for GSTM1 null allele produce no GSTM1 protein. The prevalence of GSTM1 deletion polymorphisms varies across ethnic groups, from 18% to 66% (median, 50%), with the exception of Asians, for whom it is 38%-58% (Wu et al., 2012). GSTM1-A and GSTM1-B differ by a single base in exon 7 (Seidegard et al., 1988). Namely, GSTM1-A and GSTM1-B differ by a C?G substitution at base position 534, resulting in a substitution of Lys?Asn at amino acid 172 (Widersten et al., 1991). The substitution further results in formation of monodimers (GSTM1A-1A, GSTM1B-1B) or heterodimers (GSTM1A-1B), although in vitro studies suggest that their activities are similar (Widersten et al., 1991). In Saudi Arabian population, a unique GSTM1 variant dGSTM1-1x2, containing a duplicated GSTM1 gene has been identified (Evans et al., 1996).
Transcription	The 1161-nucleotide transcript encodes a protein of 218 amino acid residues
Pseudogene	At least one other mu class GST gene or pseudogene exists and is found on chromosome 3, probably in the region 3p24-3pter (Pearson et al., 1993; McLellan et al., 1997).

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