RBCC Red Blood Cell Collection

GPX1 [Confidence: medium (present in either hRBCD or BSc_CH or PM22954596)]
Glutathione peroxidase 1; GPx-1; GSHPx-1; 1.11.1.9 (Cellular glutathione peroxidase)
Note: presumably soluble (membrane word is not in UniProt keywords or features)

UniProt P07203
ID GPX1_HUMAN Reviewed; 203 AA.
AC P07203; E9PAS1; Q7Z5H1; Q9BW12;
DT 01-APR-1988, integrated into UniProtKB/Swiss-Prot.
read moreDT 02-NOV-2010, sequence version 4.
DT 22-JAN-2014, entry version 165.
DE RecName: Full=Glutathione peroxidase 1;
DE Short=GPx-1;
DE Short=GSHPx-1;
DE EC=1.11.1.9;
DE AltName: Full=Cellular glutathione peroxidase;
GN Name=GPX1;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANT 7-ALA-ALA-8 DEL.
RX PubMed=3658677; DOI=10.1093/nar/15.17.7178;
RA Sukenaga Y., Ishida K., Takeda T., Takagi K.;
RT "cDNA sequence coding for human glutathione peroxidase.";
RL Nucleic Acids Res. 15:7178-7178(1987).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1), AND VARIANT 7-ALA-ALA-8
RP DEL.
RX PubMed=3697069; DOI=10.1093/nar/15.23.10051;
RA Ishida K., Morino T., Takagi K., Sukenaga Y.;
RT "Nucleotide sequence of a human gene for glutathione peroxidase.";
RL Nucleic Acids Res. 15:10051-10051(1987).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANT 7-ALA-ALA-8 DEL.
RC TISSUE=Kidney;
RX PubMed=2955287; DOI=10.1093/nar/15.13.5484;
RA Mullenbach G.T., Tabrizi A., Irvine B.D., Bell G.I., Hallewell R.A.;
RT "Sequence of a cDNA coding for human glutathione peroxidase confirms
RT TGA encodes active site selenocysteine.";
RL Nucleic Acids Res. 15:5484-5484(1987).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANT 7-ALA-ALA-8 DEL.
RX PubMed=2307470; DOI=10.1016/0888-7543(90)90566-D;
RA Chada S., le Beau M.M., Casey L., Newburger P.E.;
RT "Isolation and chromosomal localization of the human glutathione
RT peroxidase gene.";
RL Genomics 6:268-271(1990).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1), AND VARIANT ALA-8 DEL.
RX PubMed=1556108;
RA Moscow J.A., Morrow C.S., He R., Mullenbach G.T., Cowan K.H.;
RT "Structure and function of the 5'-flanking sequence of the human
RT cytosolic selenium-dependent glutathione peroxidase gene (hgpx1).";
RL J. Biol. Chem. 267:5949-5958(1992).
RN [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1), AND VARIANTS PRO-5;
RP THR-194 AND LEU-200.
RG NIEHS SNPs program;
RL Submitted (JUN-2003) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16641997; DOI=10.1038/nature04728;
RA Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R.,
RA Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R.,
RA Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V.,
RA Hume J., Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R.,
RA Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Morgan M.B.,
RA Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Wei S.,
RA Wheeler D.A., Wright M.W., Worley K.C., Yuan Y., Zhang Z., Adams C.Q.,
RA Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z.,
RA Clendenning J., Clerc-Blankenburg K.P., Chen R., Chen Z., Davis C.,
RA Delgado O., Dinh H.H., Dong W., Draper H., Ernst S., Fu G.,
RA Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J., Hao B.,
RA Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W., Jackson L.R.,
RA Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B., Liu J.,
RA Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Palmeiri A.,
RA Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B.,
RA Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H.,
RA Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J.,
RA Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J.,
RA Zhang X., Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H.,
RA Reinhardt R., Naylor S.L., Yang H., Olson M., Weinstock G.,
RA Gibbs R.A.;
RT "The DNA sequence, annotation and analysis of human chromosome 3.";
RL Nature 440:1194-1198(2006).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Placenta;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [10]
RP X-RAY CRYSTALLOGRAPHY (1.5 ANGSTROMS) OF 14-198.
RG Structural genomics consortium (SGC);
RT "Crystal structure of the selenocysteine to glycine mutant of human
RT glutathione peroxidase 1.";
RL Submitted (FEB-2009) to the PDB data bank.
RN [11]
RP VARIANT LEU-200.
RX PubMed=10220143;
RX DOI=10.1002/(SICI)1098-1004(1999)13:4<294::AID-HUMU6>3.0.CO;2-5;
RA Forsberg L., de Faire U., Morgenstern R.;
RT "Low yield of polymorphisms from EST blast searching: analysis of
RT genes related to oxidative stress and verification of the P197L
RT polymorphism in GPX1.";
RL Hum. Mutat. 13:294-300(1999).
RN [12]
RP VARIANTS ALA-8 DEL AND 7-ALA-ALA-8 DEL.
RX PubMed=12496980; DOI=10.1038/sj.pcan.4500569;
RA Kote-Jarai Z., Durocher F., Edwards S.M., Hamoudi R., Jackson R.A.,
RA Ardern-Jones A., Murkin A., Dearnaley D.P., Kirby R., Houlston R.,
RA Easton D.F., Eeles R.;
RT "Association between the GCG polymorphism of the selenium dependent
RT GPX1 gene and the risk of young onset prostate cancer.";
RL Prostate Cancer Prostatic Dis. 5:189-192(2002).
RN [13]
RP VARIANTS ALA-8 DEL AND LEU-200.
RX PubMed=15331559; DOI=10.2337/diabetes.53.9.2455;
RA Hamanishi T., Furuta H., Kato H., Doi A., Tamai M., Shimomura H.,
RA Sakagashira S., Nishi M., Sasaki H., Sanke T., Nanjo K.;
RT "Functional variants in the glutathione peroxidase-1 (GPx-1) gene are
RT associated with increased intima-media thickness of carotid arteries
RT and risk of macrovascular diseases in Japanese type 2 diabetic
RT patients.";
RL Diabetes 53:2455-2460(2004).
RN [14]
RP VARIANT LEU-200.
RX PubMed=15247771; DOI=10.1097/01.ju.0000130942.40597.9d;
RA Ichimura Y., Habuchi T., Tsuchiya N., Wang L., Oyama C., Sato K.,
RA Nishiyama H., Ogawa O., Kato T.;
RT "Increased risk of bladder cancer associated with a glutathione
RT peroxidase 1 codon 198 variant.";
RL J. Urol. 172:728-732(2004).
CC -!- FUNCTION: Protects the hemoglobin in erythrocytes from oxidative
CC breakdown.
CC -!- CATALYTIC ACTIVITY: 2 glutathione + H(2)O(2) = glutathione
CC disulfide + 2 H(2)O.
CC -!- SUBUNIT: Homotetramer. Interacts with MIEN1.
CC -!- SUBCELLULAR LOCATION: Cytoplasm.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P07203-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P07203-2; Sequence=VSP_047369, VSP_047370;
CC Note=Gene prediction based on EST data;
CC -!- PTM: During periods of oxidative stress, Sec-49 may react with a
CC superoxide radical, irreversibly lose hydroselenide and be
CC converted to dehydroalanine (By similarity).
CC -!- SIMILARITY: Belongs to the glutathione peroxidase family.
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/gpx1/";
CC -!- WEB RESOURCE: Name=Wikipedia; Note=Glutathione peroxidase entry;
CC URL="http://en.wikipedia.org/wiki/Glutathione_peroxidase";
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DR EMBL; Y00433; CAA68491.1; -; mRNA.
DR EMBL; Y00483; CAB37833.1; -; Genomic_DNA.
DR EMBL; X13709; CAA31992.1; -; mRNA.
DR EMBL; X13710; CAA31993.1; -; mRNA.
DR EMBL; M21304; AAA75389.2; -; mRNA.
DR EMBL; M83094; AAA67540.2; -; Genomic_DNA.
DR EMBL; AY327818; AAP80181.1; -; Genomic_DNA.
DR EMBL; AC121247; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC000742; AAH00742.3; -; mRNA.
DR PIR; A42152; OPHUE.
DR RefSeq; NP_000572.2; NM_000581.2.
DR RefSeq; NP_958799.1; NM_201397.1.
DR UniGene; Hs.76686; -.
DR PDB; 2F8A; X-ray; 1.50 A; A/B=1-198.
DR PDBsum; 2F8A; -.
DR ProteinModelPortal; P07203; -.
DR SMR; P07203; 14-197.
DR IntAct; P07203; 1.
DR STRING; 9606.ENSP00000407375; -.
DR ChEMBL; CHEMBL2163186; -.
DR DrugBank; DB00143; Glutathione.
DR PeroxiBase; 3600; HsGPx01-A.
DR PhosphoSite; P07203; -.
DR DMDM; 311033481; -.
DR OGP; P07203; -.
DR SWISS-2DPAGE; P07203; -.
DR PaxDb; P07203; -.
DR PRIDE; P07203; -.
DR DNASU; 2876; -.
DR Ensembl; ENST00000419349; ENSP00000391316; ENSG00000233276.
DR Ensembl; ENST00000419783; ENSP00000407375; ENSG00000233276.
DR GeneID; 2876; -.
DR KEGG; hsa:2876; -.
DR UCSC; uc021wxx.1; human.
DR CTD; 2876; -.
DR GeneCards; GC03M049369; -.
DR H-InvDB; HIX0003298; -.
DR HGNC; HGNC:4553; GPX1.
DR HPA; CAB011582; -.
DR MIM; 138320; gene+phenotype.
DR neXtProt; NX_P07203; -.
DR PharmGKB; PA28949; -.
DR eggNOG; COG0386; -.
DR HOGENOM; HOG000277055; -.
DR HOVERGEN; HBG004333; -.
DR InParanoid; P07203; -.
DR KO; K00432; -.
DR OMA; CEVNGEK; -.
DR OrthoDB; EOG7KQ23C; -.
DR PhylomeDB; P07203; -.
DR BioCyc; MetaCyc:HS00019-MONOMER; -.
DR Reactome; REACT_111217; Metabolism.
DR ChiTaRS; GPX1; human.
DR EvolutionaryTrace; P07203; -.
DR GeneWiki; GPX1; -.
DR GenomeRNAi; 2876; -.
DR NextBio; 11353; -.
DR PRO; PR:P07203; -.
DR ArrayExpress; P07203; -.
DR Bgee; P07203; -.
DR CleanEx; HS_GPX1; -.
DR Genevestigator; P07203; -.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005739; C:mitochondrion; IDA:BHF-UCL.
DR GO; GO:0004866; F:endopeptidase inhibitor activity; IDA:BHF-UCL.
DR GO; GO:0004602; F:glutathione peroxidase activity; IDA:BHF-UCL.
DR GO; GO:0060055; P:angiogenesis involved in wound healing; IEA:Ensembl.
DR GO; GO:0019369; P:arachidonic acid metabolic process; TAS:Reactome.
DR GO; GO:0043534; P:blood vessel endothelial cell migration; IEA:Ensembl.
DR GO; GO:0045454; P:cell redox homeostasis; IDA:BHF-UCL.
DR GO; GO:0001885; P:endothelial cell development; IEA:Ensembl.
DR GO; GO:0045444; P:fat cell differentiation; IEA:Ensembl.
DR GO; GO:0006749; P:glutathione metabolic process; IDA:BHF-UCL.
DR GO; GO:0060047; P:heart contraction; IMP:BHF-UCL.
DR GO; GO:0042744; P:hydrogen peroxide catabolic process; IDA:BHF-UCL.
DR GO; GO:0051702; P:interaction with symbiont; IEA:Ensembl.
DR GO; GO:0008631; P:intrinsic apoptotic signaling pathway in response to oxidative stress; IEA:Ensembl.
DR GO; GO:0019372; P:lipoxygenase pathway; TAS:Reactome.
DR GO; GO:0051450; P:myoblast proliferation; IEA:Ensembl.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IEA:Ensembl.
DR GO; GO:0043154; P:negative regulation of cysteine-type endopeptidase activity involved in apoptotic process; IMP:BHF-UCL.
DR GO; GO:1902042; P:negative regulation of extrinsic apoptotic signaling pathway via death domain receptors; IMP:BHF-UCL.
DR GO; GO:0002862; P:negative regulation of inflammatory response to antigenic stimulus; IEA:Ensembl.
DR GO; GO:0090201; P:negative regulation of release of cytochrome c from mitochondria; IMP:BHF-UCL.
DR GO; GO:0051897; P:positive regulation of protein kinase B signaling cascade; IEA:Ensembl.
DR GO; GO:0018158; P:protein oxidation; IEA:Ensembl.
DR GO; GO:0006144; P:purine nucleobase metabolic process; TAS:Reactome.
DR GO; GO:0006195; P:purine nucleotide catabolic process; TAS:Reactome.
DR GO; GO:0040029; P:regulation of gene expression, epigenetic; IDA:BHF-UCL.
DR GO; GO:0033599; P:regulation of mammary gland epithelial cell proliferation; IMP:BHF-UCL.
DR GO; GO:0043523; P:regulation of neuron apoptotic process; IEA:Ensembl.
DR GO; GO:0061136; P:regulation of proteasomal protein catabolic process; IDA:BHF-UCL.
DR GO; GO:0010332; P:response to gamma radiation; IEA:Ensembl.
DR GO; GO:0033194; P:response to hydroperoxide; IEA:Ensembl.
DR GO; GO:0010269; P:response to selenium ion; IMP:BHF-UCL.
DR GO; GO:0009609; P:response to symbiotic bacterium; IEA:Ensembl.
DR GO; GO:0009636; P:response to toxic substance; IEA:Ensembl.
DR GO; GO:0009410; P:response to xenobiotic stimulus; IEA:Ensembl.
DR GO; GO:0007605; P:sensory perception of sound; IEA:Ensembl.
DR GO; GO:0048741; P:skeletal muscle fiber development; IEA:Ensembl.
DR GO; GO:0043403; P:skeletal muscle tissue regeneration; IEA:Ensembl.
DR GO; GO:0001659; P:temperature homeostasis; IEA:Ensembl.
DR GO; GO:0006641; P:triglyceride metabolic process; IEA:Ensembl.
DR GO; GO:0009650; P:UV protection; IMP:BHF-UCL.
DR GO; GO:0042311; P:vasodilation; IEA:Ensembl.
DR Gene3D; 3.40.30.10; -; 1.
DR InterPro; IPR000889; Glutathione_peroxidase.
DR InterPro; IPR012336; Thioredoxin-like_fold.
DR PANTHER; PTHR11592; PTHR11592; 1.
DR Pfam; PF00255; GSHPx; 1.
DR PIRSF; PIRSF000303; Glutathion_perox; 1.
DR PRINTS; PR01011; GLUTPROXDASE.
DR SUPFAM; SSF52833; SSF52833; 1.
DR PROSITE; PS00460; GLUTATHIONE_PEROXID_1; 1.
DR PROSITE; PS00763; GLUTATHIONE_PEROXID_2; 1.
DR PROSITE; PS51355; GLUTATHIONE_PEROXID_3; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Complete proteome;
KW Cytoplasm; Oxidoreductase; Peroxidase; Polymorphism;
KW Reference proteome; Selenocysteine.
FT CHAIN 1 203 Glutathione peroxidase 1.
FT /FTId=PRO_0000066610.
FT ACT_SITE 49 49
FT SITE 49 49 Subject to oxidation and hydroselenide
FT loss to dehydroalanine (By similarity).
FT NON_STD 49 49 Selenocysteine.
FT MOD_RES 88 88 N6-acetyllysine (By similarity).
FT MOD_RES 114 114 N6-acetyllysine (By similarity).
FT MOD_RES 148 148 N6-acetyllysine (By similarity).
FT VAR_SEQ 85 98 ENAKNEEILNSLKY -> VRRAERGGAGADVQ (in
FT isoform 2).
FT /FTId=VSP_047369.
FT VAR_SEQ 99 203 Missing (in isoform 2).
FT /FTId=VSP_047370.
FT VARIANT 5 5 R -> P (in dbSNP:rs8179169).
FT /FTId=VAR_020912.
FT VARIANT 7 8 Missing.
FT /FTId=VAR_020913.
FT VARIANT 8 8 Missing.
FT /FTId=VAR_020914.
FT VARIANT 194 194 A -> T (in dbSNP:rs6446261).
FT /FTId=VAR_020915.
FT VARIANT 200 200 P -> L (frequent polymorphism;
FT dbSNP:rs1050450).
FT /FTId=VAR_007904.
FT CONFLICT 93 93 L -> Q (in Ref. 3; CAA31992).
FT HELIX 16 18
FT HELIX 32 35
FT STRAND 38 45
FT STRAND 47 49
FT HELIX 52 66
FT HELIX 67 69
FT STRAND 71 77
FT TURN 82 85
FT HELIX 89 91
FT HELIX 92 98
FT STRAND 108 112
FT HELIX 124 132
FT HELIX 147 149
FT STRAND 152 154
FT STRAND 166 169
FT STRAND 175 179
FT HELIX 185 188
FT HELIX 189 196
SQ SEQUENCE 203 AA; 22088 MW; 5DB11579C66FE8E5 CRC64;
MCAARLAAAA AAAQSVYAFS ARPLAGGEPV SLGSLRGKVL LIENVASLUG TTVRDYTQMN
ELQRRLGPRG LVVLGFPCNQ FGHQENAKNE EILNSLKYVR PGGGFEPNFM LFEKCEVNGA
GAHPLFAFLR EALPAPSDDA TALMTDPKLI TWSPVCRNDV AWNFEKFLVG PDGVPLRRYS
RRFQTIDIEP DIEALLSQGP SCA
//

MIM 138320
*RECORD*
*FIELD* NO
138320
*FIELD* TI
*138320 GLUTATHIONE PEROXIDASE; GPX1
*FIELD* TX

DESCRIPTION

Glutathione peroxidase (EC 1.11.1.9) catalyzes the reduction of organic
read morehydroperoxides and hydrogen peroxide by glutathione and thereby protects
against oxidative damage (summary by Cohen et al., 1989).

CLONING

Paglia and Valentine (1967) characterized red cell glutathione
peroxidase.

Sukenaga et al. (1987) presented the sequence of GPX cDNA. GPX is one of
only a few proteins known in higher vertebrates to contain
selenocysteine. This unusual amino acid occurs at the active site of GPX
and is coded by the nonsense (stop) codon TGA. Sequence analysis of cDNA
clones confirmed previous findings that the unusual amino acid
selenocysteine is encoded by the opal terminator codon UGA (Le Beau,
1989). (Note that TGA = UGA; they represent the cDNA and mRNA code,
respectively.) There appears to be a selenocysteyl-tRNA that donates
selenocysteine to the growing polypeptide chain of GPX, and therefore,
selenocysteine becomes the twenty-first naturally occurring amino acid.
A tRNA molecule that carries selenocysteine has its own translating
factor that delivers it to the translating ribosome (Bock et al., 1991).
Bacterial formate dehydrogenase also contains selenocysteine.

MAPPING

Wijnen et al. (1978) presented evidence that GPX1 is on chromosome 3.
Johannsmann et al. (1979) concluded that the GPX locus is on 3p. In situ
hybridization localized the gene to 3p13-q12 (Johannsmann et al., 1981).
McBride et al. (1988) used a cDNA probe to study DNAs isolated from
human-rodent somatic cell hybrids. A 609-bp probe containing the entire
coding region hybridized to human chromosomes 3, 21, and Xp. An intronic
probe detected only the gene on chromosome 3. The sequences on
chromosomes X and 21 showed equal conservation of the 3-prime
untranslated and coding sequences but did not contain introns,
suggesting that they represent processed pseudogenes.

By fluorescence in situ hybridization and PCR analysis, Kiss et al.
(1997) mapped the GPX1 gene to 3p21.3. Their results were compatible
with the existence of a pseudogene of GPX1 on 3q11-q12 (Chada et al.,
1990).

Mehdizadeh et al. (1996) mapped the Gpx1 gene to mouse chromosome 9 in a
region of known conserved homology between mouse chromosome 9 and human
chromosome 3.

GENE FUNCTION

Using a radioimmunoassay for GSHPx, Takahashi et al. (1986) showed that
there is a direct relationship between GPX enzyme activity and enzyme
protein concentration. Thus, selenium is necessary for the synthesis of
protein. Selenium deficiency (see 614164) results in a decrease not only
in glutathione peroxidase activity but also in GSHPx protein. Only
erythrocytes formed in the presence of selenium contain GSHPx activity.
The possibility of confusing genetic and environmental factors is
indicated. Takahashi et al. (1987) observed a selenium-dependent GPX in
human plasma that is distinct from the one found in erythrocytes.

MOLECULAR GENETICS

By electrophoretic means, Beutler and West (1974) demonstrated
polymorphism of red cell glutathione peroxidase in Afro-Americans. An
electrophoretic polymorphism of glutathione peroxidase was described by
Beutler et al. (1974).

Beutler and Matsumoto (1975) found that persons of Jewish ancestry and
others of Mediterranean origin have a decrease in red cell GPX activity,
but not of leukocyte or fibroblast activity. Oriental populations showed
a significantly lower scatter in red cell enzyme levels in comparison
with Occidental populations. The authors suggested the existence of a
low GPX allele with a frequency of about 0.556 in the Jewish population
and 0.181 in the U.S.-Northern European population. They recommended
caution in assigning a cause-effect relationship to GPX deficiency
(614164) and hemolytic anemia.

Meera Khan et al. (1986) studied the genetics of red cell GPX1 in the
Djuka of Suriname. This group consists of descendants of captives from
the Gold Coast (Ghana) of Africa brought to Suriname during the 17th
century and of others probably from a wider region of West Africa
transported during the 18th century. During successive waves of revolt
and following the abolition of slavery, the Djuka escaped into the
interior of Suriname and organized themselves into groups which have
lived since then as permanent forest dwellers with little or no
extra-ethnic mixture. Meera Khan et al. (1986) found that the Djuka have
a frequency of the GPX1*2 allele of 0.054 and suggested that the GPX1*2
allele is an African marker. The only non-Africans in whom it is
presently found are Ashkenazi Jews living in the United States and the
Punjabis of the Indian subcontinent. It was proposed that both groups
independently acquired the variant allele through an ancient African
mixture. See Meera Khan et al. (1984).

The catalytic activity of GPX1 enzyme in the 2-1 heterozygote is greater
than that in the 1-1 homozygote. It may be that individuals with the
higher peroxidase activity have an intraerythrocytic environment which
is less favorable for the survival of the falciparum parasite and
therefore that the 2-1 heterozygote enjoys a selective advantage in a
malarious environment. Meera Khan et al. (1986) referred to the
electrophoretic variants as electrotypes.

Shen et al. (1994) reported variation in vivo and instability in vitro
of an in-frame GCG trinucleotide repeat in the GPX1 gene. In a
population study of 110 alleles from 55 unrelated persons, the allele
frequencies for 4, 5, and 6 GCG repeats were 0.40, 0.35, and 0.25,
respectively. No allele was associated with diminished enzyme activity.
Current stocks of HL-60 cells, a human myeloid leukemia cell line, were
found to be homozygous for the 6-repeat allele. The expansion of the
repeat appears to have developed in the course of multiple passages of
the rapidly proliferating cell line because cells frozen in 1976 showed
a 4/6 genotype and 'intermediate' passage cells frozen in 1985 contained
both 4/6 and 5/6 genotypes.

Data on gene frequencies of allelic variants were tabulated by
Roychoudhury and Nei (1988).

ANIMAL MODEL

De Haan et al. (1998) demonstrated a role for GPX1 in protection against
oxidative stress by showing that Gpx1 -/- mice are highly sensitive to
the oxidant paraquat. Lethality was detected within 24 hours in mice
exposed to paraquat at 10 mg/kg(-1), approximately 1/7 of the LD50 of
wildtype controls. The effects of paraquat were dose-related. De Haan et
al. (1998) further demonstrated that paraquat transcriptionally
upregulates Gpx1 in normal cells, reinforcing a role for GPX1 in
protection against paraquat toxicity. Cortical neurons from Gpx1 -/-
mice are more susceptible to peroxide; 30% of neurons from
Gpx1-deficient mice were killed when exposed to 65 micromolar peroxide,
whereas the wildtype controls were unaffected. De Haan et al. (1998)
stated that their data established function for GPX1 in protection
against some oxidative stressors and in protection of neurons against
peroxide.

Reddy et al. (2001) studied the functional role of GPX1 activity in
antioxidant mechanisms of lens in vivo by comparing lens changes of Gpx1
knockout mice with age-matched control animals. Slit-lamp images showed
increased nuclear light scattering (NLS) in Gpx1 knockout mice compared
with control animals. Transmission electron microscopy revealed changes
in the nucleus manifested by waviness of fiber membranes as early as 3
weeks of age. The Gpx1 knockout mice developed mature cataracts after 15
months. Reddy et al. (2001) concluded that their results demonstrated
the critical role of GPX1 in antioxidant defense mechanisms of the lens
nucleus. The increased NLS appeared to be associated with damage to
nuclear fiber membranes, which might have been due to formation of lipid
peroxides, which serve as substrates for GPX1. Cataract formation
appeared to progress from focal opacities, apparent at an early age, to
lamellar cataracts between 6 and 10 months, and finally to complete
opacification in animals older than 15 months.

Shiomi et al. (2004) created myocardial infarction by left coronary
artery ligation in mice overexpressing Gpx1 in the heart and wildtype
mice. Although infarct size was comparable, the transgenic mice had an
increased survival rate with decreased left ventricular dilatation,
dysfunction, and end-diastolic pressure compared to wildtype mice. The
improvement in left ventricular function was accompanied by a decrease
in myocyte hypertrophy, apoptosis, and interstitial fibrosis in the
noninfarcted left ventricle. Shiomi et al. (2004) concluded that
overexpression of Gpx1 protects the heart against post-myocardial
infarction remodeling and heart failure in mice.

*FIELD* AV
.0001
GLUTATHIONE PEROXIDASE POLYMORPHISM
GPX1, PRO197LEU

Forsberg et al. (1999) searched the human EST database to determine new
polymorphisms in the antioxidant enzymes superoxide dismutase (see
147450), glutathione peroxidases, catalase (115500), and microsomal
glutathione transferase-1 (138330). When any mutation, indicated by the
search, gave rise to a nonconservative amino acid change, they performed
PCR restriction analysis and/or sequence analysis of genomic DNA from
human subjects in order to verify these potential polymorphisms. In this
way, they identified a pro197-to-leu substitution in the GPX1 gene,
resulting from a C-to-T transition at nucleotide 593. The corresponding
allele frequencies were approximately 70% for pro197 and 30% for leu197.

*FIELD* SA
Blankenberg et al. (2003); Board (1983); Boivin et al. (1969); Golan
et al. (1980)
*FIELD* RF
1. Beutler, E.; Matsumoto, F.: Ethnic variation in red cell glutathione
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2. Beutler, E.; West, C.: Red cell glutathione peroxidase polymorphism
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3. Beutler, E.; West, C.; Beutler, B.: Electrophoretic polymorphism
of glutathione peroxidase. Ann. Hum. Genet. 38: 163-169, 1974.

4. Blankenberg, S.; Rupprecht, H. J.; Bickel, C.; Torzewski, M.; Hafner,
G; Tiret, L.; Smieja, M.; Cambien, F.; Meyer, J.; Lackner, K. J.:
Glutathione peroxidase 1 activity and cardiovascular events in patients
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5. Board, P. G.: Further electrophoretic studies of erythrocyte glutathione
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6. Bock, A.; Forchhammer, K.; Heider, J.; Leinfelder, W.; Sawers,
G.; Veprek, B.; Zinoni, F.: Selenocysteine: the 21st amino acid. Molec.
Microbiol. 5: 515-520, 1991.

7. Boivin, P.; Galand, C.; Hakim, J.: Anemie hemolytique avec deficit
en glutathion-peroxydase chez un adulte. Enzym. Biol. Clin. 10:
68-80, 1969.

8. Chada, S.; Le Beau, M. M.; Casey, L.; Newburger, P. E.: Isolation
and chromosomal localization of the human glutathione peroxidase gene. Genomics 6:
268-271, 1990.

9. Cohen, H. J.; Brown, M. R.; Hamilton, D.; Lyons-Patterson, J.;
Avissar, N.; Liegey, P.: Glutathione peroxidase and selenium deficiency
in patients receiving home parenteral nutrition: time course for development
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10. de Haan, J. B.; Bladier, C.; Griffiths, P.; Kelner, M.; O'Shea,
R. D.; Cheung, N. S.; Bronson, R. T.; Silvestro, M. J.; Wild, S.;
Zheng, S. S.; Beart, P. M.; Hertzog, P. J.; Kola, I.: Mice with a
homozygous null mutation for the most abundant glutathione peroxidase,
Gpx1, show increased susceptibility to the oxidative stress-inducing
agents paraquat and hydrogen peroxide. J. Biol. Chem. 273: 22528-22536,
1998.

11. Forsberg, L.; de Faire, U.; Morgenstern, R.: Low yield of polymorphisms
from EST Blast searching: analysis of genes related to oxidative stress
and verification of the P197L polymorphism in GPX1. Hum. Mutat. 13:
294-300, 1999.

12. Golan, R.; Ezzer, J. B.; Szeinberg, A.: Red cell glutathione
peroxidase in various Jewish ethnic groups in Israel. Hum. Hered. 30:
136-141, 1980.

13. Johannsmann, R.; Hellkuhl, B.; Grzeschik, K.-H.: Regional mapping
of human chromosome 3: assignment of a glutathione peroxidase-1 gene
to 3p13-3q12. Hum. Genet. 56: 361-363, 1981.

14. Johannsmann, R.; Hellkuhl, B.; Grzeschik, K.-H.: Regional assignment
of a gene for glutathione peroxidase on human chromosome 3. (Abstract) Cytogenet.
Cell Genet. 25: 167 only, 1979.

15. Kiss, C.; Li, J.; Szeles, A.; Gizatullin, R. Z.; Kashuba, V. I.;
Lushnikova, T.; Protopopov, A. I.; Kelve, M.; Kiss, H.; Kholodnyuk,
I. D.; Imreh, S.; Klein, G.; Zabarovsky, E. R.: Assignment of the
ARHA and GPX1 genes to human chromosome bands 3p21.3 by in situ hybridization
and with somatic cell hybrids. Cytogenet. Cell Genet. 79: 228-230,
1997.

16. Le Beau, M. M.: Personal Communication. Chicago, Ill. 1/23/1989.

17. McBride, O. W.; Mitchell, A.; Lee, B. J.; Mullenbach, G.; Hatfield,
D.: Gene for selenium-dependent glutathione peroxidase maps to human
chromosomes 3, 21 and X. BioFactors 1: 285-292, 1988.

18. Meera Khan, P.; Verma, C.; Wijnen, L. M. M.; Jairaj, S.: Red
cell glutathione peroxidase (GPX1) variation in Afro-Jamaican, Asiatic
Indian, and Dutch populations: is the GPX1*2 allele of 'Thomas' variant
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19. Meera Khan, P.; Verma, C.; Wijnen, L. M. M.; Wijnen, J. T.; Prins,
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Hum. Genet. 38: 712-723, 1986.

20. Mehdizadeh, S.; Warden, C. H.; Wen, P.-Z.; Xia, Y.-R.; Mehrabian,
M.; Lusis, A. J.: The glutathione peroxidase gene, Gpx1, maps to
mouse chromosome 9. Mammalian Genome 7: 465-466, 1996.

21. Paglia, D. E.; Valentine, W. N.: Studies on the quantitative
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Lab. Clin. Med. 70: 158-169, 1967.

22. Reddy, V. N.; Giblin, F. J.; Lin, L.-R.; Dang, L.; Unakar, N.
J.; Musch, D. C.; Boyle, D. L.; Takemoto, L. J.; Ho, Y.-S.; Knoernschild,
T.; Juenemann, A.; Lutjen-Drecoll, E.: Glutathione peroxidase-1 deficiency
leads to increased nuclear light scattering, membrane damage, and
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23. Roychoudhury, A. K.; Nei, M.: Human Polymorphic Genes: World
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24. Shen, Q.; Townes, P. L.; Padden, C.; Newburger, P. E.: An in-frame
trinucleotide repeat in the coding region of the human cellular glutathione
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25. Shiomi, T.; Tsutsui, H.; Matsusaka, H.; Murakami, K.; Hayashidani,
S.; Ikeuchi, M.; Wen, J.; Kubota, T.; Utsumi, H.; Takeshita, A.:
Overexpression of glutathione peroxidase prevents left ventricular
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26. Sukenaga, Y.; Ishida, K.; Takeda, T.; Takagi, K.: cDNA sequence
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27. Takahashi, K.; Avissar, N.; Whitin, J.; Cohen, H.: Purification
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28. Takahashi, K.; Newburger, P. E.; Cohen, H. J.: Glutathione peroxidase
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29. Wijnen, L. M.; Monteba-van Heuvel, M.; Pearson, P. L.; Meera Khan,
P.: Assignment of a gene for glutathione peroxidase (GPX-1) to human
chromosome 3. Cytogenet. Cell Genet. 22: 232-238, 1978.

*FIELD* CN
Marla J. F. O'Neill - updated: 11/3/2005
Victor A. McKusick - updated: 11/3/2003
Jane Kelly - updated: 7/2/2002
Ada Hamosh - updated: 7/28/2000
Victor A. McKusick - updated: 5/14/1999
Victor A. McKusick - updated: 5/28/1998

*FIELD* CD
Victor A. McKusick: 3/9/1989

*FIELD* ED
carol: 11/03/2011
carol: 8/12/2011
carol: 1/8/2010
wwang: 12/28/2009
wwang: 11/3/2005
terry: 4/6/2005
mgross: 3/17/2004
tkritzer: 11/6/2003
tkritzer: 11/4/2003
terry: 11/3/2003
mgross: 7/2/2002
carol: 6/22/2001
alopez: 8/1/2000
terry: 7/28/2000
mgross: 6/3/1999
mgross: 5/26/1999
terry: 5/14/1999
terry: 4/30/1999
terry: 6/1/1998
terry: 5/28/1998
joanna: 6/20/1997
mark: 10/11/1996
terry: 9/20/1996
terry: 1/11/1995
mimadm: 9/24/1994
warfield: 4/8/1994
pfoster: 2/18/1994
carol: 7/8/1992
carol: 3/31/1992