According to hg19/GRCh37-Feb_2009:
- Start: chr3:49394609 bp from pter
- End: chr3:49395791 bp from pter
- Size: 1183 bases
- Orientation: minus strand

Two alternatively spliced transcript variants encoding distinct isoforms have been shown for this gene Nucleotide.
Isoform 1 represents the shorter transcript (921 bases), RefSeq: NM_000581.2, which is comprised of 2 exons and coding the longer isoform (Figure 2A).
Isoform 2 is 1200 bases, RefSeq: NM_201397.1, also this variant is intronless. Due to the fact that this variant is not spliced the open reading frame is shifted and the protein is shorter from C-terminus compared to isoform 1 (Figure 2B).

Two pseudogenes have been found so far. GPX1P1 glutathione peroxidase pseudogene 1 (other names: GPXL2, GPXP1) is located at the locus Xp22.2 (HGNC:4560). GPX1P2 glutathione peroxidase pseudogene 2 (other names: GPXP2, GPXP2P) is located at the locus 21q21.3 (HGNC:4561).

203 aa (Accession: NM_000581.2) isoform 1; 98 aa (Accession: NM_201397.1) isoform 2.
GPX1 belongs to the family of glutathione peroxidases (Kryukov et al., 2003). GPX1, GPX2, GPX3, GPX4 and GPX6 utilize a UGA codon that specifies insertion of a selenocysteine residue which is critical to protein function (Arthur, 2000). Both isoforms contain selenocysteine at the position 49 (Mullenbach et al., 1988).

GPX1 is found at high levels in tissues exposed to high oxygen tensions such as in the lungs, at the cellular elements of blood, liver, kidney and pancreas, and also at moderate levels in heart, muscle and brain (Esposito et al., 2000; Moscow et al., 1992).
Regulation: Aberrant promotor methylation and consequence silencing has been shown for GPX1 expression during several pathological conditions in breast (Kulak et al., 2012) and gastric cancer (Min et al., 2012); whereas, induction of GPX1 gene expression was associated with transcription factors such TFAP2C in breast cancer (Kulak et al., 2012) and ZNF143 transcription factor under the mitochondrial respiratory dysfunction (Lu et al., 2012).

The protein is detected in cytoplasm and mitochondria but the ratio may vary and be dependent on cellular function (Chiu et al., 1976; Timcenko-Youssef et al., 1985; Reeves et al., 2009).

GPX1 is an enzyme of mammals and birds which protects against the damaging effects of various endogenously formed hydroperoxides and hydrogen peroxide as follows: H2O2+ 2 GSH - 2 H2O + GSS and RGOH + 2 GSH - GSSG + ROH + H2O where ROOH represents lipid hydroperoxides, membrane associated phospholipid hydroperoxides (Ursini et al., 1985; Reeves et al., 2009).

The GPX1 gene is present in vertebrates and across all mammals demonstrates homology of about 70% at the nucleotide level (Mariotti et al., 2012).

Single nucleotide and ALA polymorphism have been shown for GPX1.
The 5-UTR of GPX1 was found to contain a single nucleotide C/T polymorphism rs 1800668 located at the position ch3:49395757. The CC genotype demonstrates relatively high activity of GPX1 compared to CT or TT variant of alleles; however, the polymorphism does not alter the protein structure so differences in activity might be associated with transcriptional regulation since rs 1080668 site is located within promoter of GPX1 (Najafi et al., 2012).
A single nucleotide polymorphism rs 1050450 at the position ch3:49394834 leads to Pro198->Leu (C->T) substitution in GPX1. Many publications suggested an associated increased risk of cancer with the TT (Leu) genotype. However, extended meta-analysis failed to find a significant correlation of the polymorphism (rs 1050450) with cancer risk, although the TT GPX1 genotype examined in erythrocytes demonstrated significantly lower functional activity (Hong et al., 2012).
ALA N-terminal polymorphism has been shown for the GPX1 gene. In this variant, the number of GCG repeats is altered resulting in a protein with a variable number of alanines 5, 6, or 7 (Shen et al., 1994). Some association between 5-ALA genotype and high risk of breast cancer have been shown (Knight et al., 2004). However, associations between specific genotypes and the risk of prostate cancer have not been found (Kote-Jarai et al., 2002).