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]
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.
| TF | Mean coef | Binding | Outlier | TF→Gene link |
|---|
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 |
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.