GPX4
glutathione peroxidase 4 | MCSP, PHGPx

The protein encoded by this gene belongs to the glutathione peroxidase family, members of which catalyze the reduction of hydrogen peroxide, organic hydroperoxides and lipid hydroperoxides, and thereby protect cells against oxidative damage. Several isozymes of this gene family exist in vertebrates, which vary in cellular location and substrate specificity. This isozyme has a high preference for lipid hydroperoxides and protects cells against membrane lipid peroxidation and cell death. It is also required for normal sperm development; thus, it has been identified as a 'moonlighting' protein because of its ability to serve dual functions as a peroxidase, as well as a structural protein in mature spermatozoa. Mutations in this gene are associated with Sedaghatian type of spondylometaphyseal dysplasia (SMDS). This isozyme is also a selenoprotein, containing the rare amino acid selenocysteine (Sec) at its active site. Sec is encoded by the UGA codon, which normally signals translation termination. The 3' UTRs of selenoprotein mRNAs contain a conserved stem-loop structure, designated the Sec insertion sequence (SECIS) element, that is necessary for the recognition of UGA as a Sec codon, rather than as a stop signal. Transcript variants resulting from alternative splicing or use of alternate promoters have been described to encode isoforms with different subcellular localization. [provided by RefSeq, Dec 2018]

Member of: DE-1 DE-1.29 Developmental clusters: GC2
Biological processes 40 terms
arachidonate metabolic process (GO:0019369)cellular oxidant detoxification (GO:0098869)cellular response to oxidative stress (GO:0034599)cytoplasm (GO:0005737)cytosol (GO:0005829)cytosol (GO:0005829)cytosol (GO:0005829)extracellular exosome (GO:0070062)glutathione peroxidase activity (GO:0004602)glutathione peroxidase activity (GO:0004602)glutathione peroxidase activity (GO:0004602)glutathione peroxidase activity (GO:0004602)identical protein binding (GO:0042802)lipoxygenase pathway (GO:0019372)lipoxygenase pathway (GO:0019372)long-chain fatty acid biosynthetic process (GO:0042759)mitochondrion (GO:0005739)mitochondrion (GO:0005739)mitochondrion (GO:0005739)negative regulation of ferroptosis (GO:0110076)negative regulation of ferroptosis (GO:0110076)nuclear envelope (GO:0005635)nucleus (GO:0005634)nucleus (GO:0005634)nucleus (GO:0005634)peroxidase activity (GO:0004601)phospholipid metabolic process (GO:0006644)phospholipid-hydroperoxide glutathione peroxidase activity (GO:0047066)phospholipid-hydroperoxide glutathione peroxidase activity (GO:0047066)phospholipid-hydroperoxide glutathione peroxidase activity (GO:0047066)phospholipid-hydroperoxide glutathione peroxidase activity (GO:0047066)phospholipid-hydroperoxide glutathione peroxidase activity (GO:0047066)protein binding (GO:0005515)protein polymerization (GO:0051258)protein-containing complex (GO:0032991)response to estradiol (GO:0032355)response to oxidative stress (GO:0006979)response to oxidative stress (GO:0006979)selenium binding (GO:0008430)spermatogenesis (GO:0007283)
Expression (TPM)
GPX4 — as a Regulated Gene

TFs regulating GPX4 0 TFs

Transcription factors with Perturb-seq knockdown data for GPX4. The Binding column indicates whether any binding evidence exists for this TF–gene pair (ChIP-seq or motif footprint peaks). The Mean coef is the average Perturb-seq regression coefficient across active gRNAs (positive = GPX4 upregulated upon KD; negative = downregulated). The Outlier column indicates whether this gene is in the top or bottom 5% of all TF knockdown effects.

Data: Effect:
TF Mean coef Binding Outlier TF→Gene link

Elements linked to GPX4

Open chromatin peaks (ATAC-seq) in the genomic neighbourhood of GPX4, linked by TSS proximity or chromatin conformation (Multiome / HiCAR). Each element overlaps at least one TF ChIP-seq binding site — the TFs column shows how many distinct TFs bind that element.

Accessibility Element Dist. to TSS Link type TFs
chr19:821,294–822,728 281.9 kb Distal (>10kb) Multiome 254
chr19:861,664–863,223 241.8 kb Distal (>10kb) Multiome 530
chr19:892,703–893,746 210.8 kb Distal (>10kb) Multiome 715
chr19:917,038–918,169 186.2 kb Distal (>10kb) Multiome 711
chr19:924,743–926,242 178.3 kb Distal (>10kb) Multiome 796
chr19:927,058–927,629 176.7 kb Distal (>10kb) Multiome 362
chr19:982,565–983,215 121.2 kb Distal (>10kb) Multiome 590
chr19:984,046–985,154 119.5 kb Distal (>10kb) Multiome 829
chr19:1,000,142–1,000,881 103.7 kb Distal (>10kb) Multiome 399
chr19:1,020,611–1,022,069 82.6 kb Distal (>10kb) Multiome 1017
chr19:1,026,155–1,026,856 77.5 kb Distal (>10kb) Multiome 598
chr19:1,027,770–1,028,926 75.5 kb Distal (>10kb) Multiome 584
chr19:1,039,648–1,040,400 64.0 kb Distal (>10kb) Multiome 684
chr19:1,040,481–1,041,402 62.8 kb Distal (>10kb) Multiome 556
chr19:1,044,758–1,045,598 58.7 kb Distal (>10kb) Multiome 402
chr19:1,061,840–1,062,923 41.5 kb Distal (>10kb) Multiome 204
chr19:1,063,045–1,065,722 39.2 kb Distal (>10kb) Multiome 681
chr19:1,066,682–1,067,587 36.8 kb Distal (>10kb) Multiome 489
chr19:1,071,107–1,071,721 32.9 kb Distal (>10kb) Multiome 178
chr19:1,081,317–1,083,172 21.6 kb Distal (>10kb) Multiome 484
chr19:1,094,985–1,095,654 8.6 kb Proximal (<10kb) Multiome 671
chr19:1,101,840–1,102,266 1.7 kb Proximal (<10kb) 571
chr19:1,103,487–1,105,654 12 bp At TSS Multiome 849
chr19:1,112,029–1,112,884 8.3 kb Proximal (<10kb) Multiome 294
chr19:1,113,014–1,114,139 9.5 kb Proximal (<10kb) Multiome 690
chr19:1,122,934–1,123,720 19.2 kb Distal (>10kb) Multiome 231
chr19:1,173,441–1,174,438 70.2 kb Distal (>10kb) Multiome 682
chr19:1,194,370–1,194,985 90.6 kb Distal (>10kb) Multiome 531
chr19:1,205,175–1,206,374 101.6 kb Distal (>10kb) Multiome HiCAR 746
chr19:1,237,080–1,238,434 134.1 kb Distal (>10kb) Multiome 430
chr19:1,239,513–1,242,539 137.7 kb Distal (>10kb) Multiome 889
chr19:1,244,253–1,244,857 140.6 kb Distal (>10kb) Multiome 590
chr19:1,247,981–1,252,501 147.0 kb Distal (>10kb) Multiome 1136
chr19:1,259,185–1,262,955 155.4 kb Distal (>10kb) Multiome 1070
chr19:1,265,280–1,270,235 165.3 kb Distal (>10kb) Multiome 1171
chr19:1,274,423–1,276,502 171.7 kb Distal (>10kb) Multiome 967
chr19:1,285,317–1,286,108 181.8 kb Distal (>10kb) Multiome 277
chr19:1,354,303–1,355,411 250.9 kb Distal (>10kb) Multiome 688
chr19:1,383,122–1,384,333 279.7 kb Distal (>10kb) Multiome 1228
chr19:1,401,101–1,401,839 297.5 kb Distal (>10kb) Multiome 540

Genome Browser

Genomic view of the GPX4 locus showing ATAC-seq accessibility and RNA-seq expression across the ESC → DE time course, together with TF binding peaks and element-to-TSS loop connections.

chr19:811,294 – 1,411,839
Proximal 1 kb Distal 10 kb Multiome HiCAR ATAC-seq RNA-seq