======= GPX4 =======


== Gene Information ==
  * **<color #00a2e8>Official Symbol</color>**: GPX4
  * **<color #00a2e8>Official Name</color>**: glutathione peroxidase 4
  * **<color #00a2e8>Aliases and Previous Symbols</color>**: N/A
  * **<color #00a2e8>Entrez ID</color>**: [[https://www.ncbi.nlm.nih.gov/gene/?term=2879|2879]]
  * **<color #00a2e8>UniProt</color>**: [[https://www.uniprot.org/uniprot/P36969|P36969]]
  * **<color #00a2e8>Interactions</color>**: [[https://thebiogrid.org/search.php?search=GPX4&organism=9606|BioGRID]]
  * **<color #00a2e8>PubMed articles</color>**: [[https://www.ncbi.nlm.nih.gov/pubmed/?term=gene%20GPX4|Open PubMed]]
  * **<color #00a2e8>OMIM</color>**: [[https://omim.org/entry/138322|Open OMIM]]

== Function Summary ==
  * **<color #00a2e8>Entrez Summary</color>**:  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. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Oct 2016]. 
  * **<color #00a2e8>UniProt Summary</color>**:  Essential antioxidant peroxidase that directly reduces phospholipid hydroperoxide even if they are incorporated in membranes and lipoproteins (By similarity). Can also reduce fatty acid hydroperoxide, cholesterol hydroperoxide and thymine hydroperoxide (By similarity). Plays a key role in protecting cells from oxidative damage by preventing membrane lipid peroxidation (By similarity). Required to prevent cells from ferroptosis, a non-apoptotic cell death resulting from an iron- dependent accumulation of lipid reactive oxygen species (PubMed:24439385). The presence of selenocysteine (Sec) versus Cys at the active site is essential for life: it provides resistance to overoxidation and prevents cells against ferroptosis (By similarity). The presence of Sec at the active site is also essential for the survival of a specific type of parvalbumin- positive interneurons, thereby preventing against fatal epileptic seizures (By similarity). May be required to protect cells from the toxicity of ingested lipid hydroperoxides (By similarity). Required for normal sperm development and male fertility (By similarity). Essential for maturation and survival of photoreceptor cells (By similarity). Plays a role in a primary T- cell response to viral and parasitic infection by protecting T- cells from ferroptosis and by supporting T-cell expansion (By similarity). {ECO:0000250|UniProtKB:O70325, ECO:0000250|UniProtKB:P36968, ECO:0000269|PubMed:24439385}.

<button type='primary' size='sm' modal='Pfam_Domains'>Pfam Domains</button>
<button type='primary' size='sm' modal='GO_terms'>GO Terms</button>


<modal id='Pfam_Domains' size='lg' title='Pfam Domains'>
|GSHPx|
</modal>

<modal id='GO_terms' size='lg' title='GO Terms'>
|negative regulation of ferroptosis|
|phospholipid-hydroperoxide glutathione peroxidase activity|
|regulation of ferroptosis|
|selenium binding|
|lipoxygenase pathway|
|glutathione peroxidase activity|
|long-chain fatty acid biosynthetic process|
|peroxidase activity|
|glutathione metabolic process|
|protein polymerization|
|cellular oxidant detoxification|
|cellular detoxification|
|icosanoid metabolic process|
|long-chain fatty acid metabolic process|
|fatty acid biosynthetic process|
|detoxification|
|response to estradiol|
|fatty acid derivative metabolic process|
|nuclear envelope|
|monocarboxylic acid biosynthetic process|
|cellular modified amino acid metabolic process|
|cellular response to toxic substance|
|aging|
|carboxylic acid biosynthetic process|
|organic acid biosynthetic process|
|fatty acid metabolic process|
|regulation of inflammatory response|
|sulfur compound metabolic process|
|phospholipid metabolic process|
|response to oxidative stress|
|cofactor metabolic process|
|response to toxic substance|
|peptide metabolic process|
|monocarboxylic acid metabolic process|
|spermatogenesis|
|male gamete generation|
|lipid biosynthetic process|
|small molecule biosynthetic process|
|protein-containing complex|
|gamete generation|
|chromatin organization|
|regulation of defense response|
|cellular amide metabolic process|
|multicellular organismal reproductive process|
|sexual reproduction|
|cellular protein-containing complex assembly|
|multicellular organism reproduction|
|response to lipid|
|organophosphate metabolic process|
|negative regulation of programmed cell death|
|carboxylic acid metabolic process|
|response to hormone|
|response to organic cyclic compound|
|cellular lipid metabolic process|
|oxidation-reduction process|
|multi-organism reproductive process|
|negative regulation of cell death|
|oxoacid metabolic process|
|organic acid metabolic process|
|chromosome organization|
|identical protein binding|
|regulation of response to external stimulus|
|lipid metabolic process|
|mitochondrion|
|reproductive process|
|reproduction|
|response to endogenous stimulus|
|regulation of response to stress|
|response to oxygen-containing compound|
|protein-containing complex assembly|
|regulation of programmed cell death|
|regulation of cell death|
|small molecule metabolic process|
|protein-containing complex subunit organization|
</modal>
\\

 === CRISPR Data ===
<button type='primary' size='small' modal='Compound_Hit'>Compound Hit</button>
<button type='primary' size='small' modal='Most_Correlated_Genes'>Most Correlated Genes in Chemogenomics</button>
<button type='primary' size='small' modal='Essential_Avana'>Tissues where Essential in the Avana Dataset (DepMap 20Q1)</button>

<modal id='Compound_Hit' size='lg' title='Compound Hit'>
^Screen^Score^
|[[:results:exp382|Palbociclib 1μM R07 exp382]]|-3.32|
|[[:results:exp450|Artemisinin 50μM R08 exp450]]|-2.85|
|[[:results:exp459|Bleomycin 5μM R08 exp459]]|-2.71|
|[[:results:exp435|JQ1 0.8μM R08 exp435]]|-2.69|
|[[:results:exp97|BI-6727 0.0125μM R03 exp97]]|-2.6|
|[[:results:exp502|Milciclib 2μM R08 exp502]]|-2.58|
|[[:results:exp503|Mitomycin-C 0.06μM R08 exp503]]|-2.44|
|[[:results:exp515|PU-H71 1μM R08 exp515]]|-2.4|
|[[:results:exp529|Thimerosal 0.85μM R08 exp529]]|-2.4|
|[[:results:exp513|ONC212 0.15μM R08 exp513]]|-2.22|
|[[:results:exp416|Tubacin 1.6μM R07 exp416]]|-2.16|
|[[:results:exp524|Staurosporine 0.02μM R08 exp524]]|-2.11|
|[[:results:exp94|Nocodazole 0.1μM R03 exp94]]|-2.1|
|[[:results:exp198|Etoposide 0.1μM R05 exp198]]|-2.08|
|[[:results:exp374|Latrunculin-B 10μM R07 exp374]]|-2.08|
|[[:results:exp532|TIC10 10μM R08 exp532]]|-2.02|
|[[:results:exp106|UM131593 0.2μM R03 exp106]]|-2.01|
|[[:results:exp244|SB743921 0.001μM R05 exp244]]|-1.99|
|[[:results:exp208|Vinblastine 0.015μM R05 exp208]]|-1.97|
|[[:results:exp440|Aphidicolin 0.4μM R08 exp440]]|-1.9|
|[[:results:exp28|Pimelic-diphenylamide-106 5μM R00 exp28]]|-1.89|
|[[:results:exp448|Ammonium tetrathiomolybdate 10μM R08 exp448]]|-1.88|
|[[:results:exp342|Calcium Ionophore 0.4μM R07 exp342]]|-1.86|
|[[:results:exp126|GSK461364A 0.1μM R03 exp126]]|-1.85|
|[[:results:exp24|Nocodazole 0.2μM R00 exp24]]|-1.85|
|[[:results:exp356|Docosahexaenoic-acid 50μM R07 exp356]]|-1.84|
|[[:results:exp539|42°C R08 exp539]]|-1.83|
|[[:results:exp455|Benzoate 10000μM R08 exp455]]|-1.82|
|[[:results:exp199|Etoposide 0.3μM R05 exp199]]|-1.82|
|[[:results:exp507|Monensin 0.3μM R08 exp507]]|-1.82|
|[[:results:exp82|Torin1 0.08μM R02 exp82]]|-1.8|
|[[:results:exp33|Rotenone 2μM R00 exp33]]|-1.78|
|[[:results:exp34|Rotenone 20μM R00 exp34]]|-1.77|
|[[:results:exp3|Actinomycin-D 0.001μM R00 exp3]]|-1.75|
|[[:results:exp335|Aminopterin 0.005μM R07 exp335]]|-1.75|
|[[:results:exp504|MK2206 4μM R08 exp504]]|-1.73|
|[[:results:exp64|Nocodazole 0.2μM R02 exp64]]|-1.72|
|[[:results:exp521|Salinomycin 3.5μM R08 exp521]]|-1.71|
|[[:results:exp295|Pyronaridine 1μM R06 exp295]]|1.87|
|[[:results:exp288|HMS-I2 10μM R06 exp288]]|1.88|
|[[:results:exp362|GSK-J4 1μM R07 exp362]]|1.9|
|[[:results:exp334|All-trans-Retinoic-Acid 40μM R07 exp334]]|2.26|
|[[:results:exp246|UM0011500 10μM R05 exp246]]|2.46|
|[[:results:exp269|Bisphenol A 100μM R06 exp269]]|2.91|
</modal>

<modal id='Most_Correlated_Genes' size='lg' title='Most Correlated Genes in Chemogenomics'>
^Gene^Correlation^
|[[:human genes:e:eefsec|EEFSEC]]|0.515|
|[[:human genes:p:pstk|PSTK]]|0.491|
|[[:human genes:s:sephs2|SEPHS2]]|0.472|
|[[:human genes:c:chd4|CHD4]]|0.447|
|[[:human genes:r:rrm1|RRM1]]|0.437|
|[[:human genes:r:rpl35|RPL35]]|0.43|
|[[:human genes:p:psmc6|PSMC6]]|0.43|
|[[:human genes:o:orc1|ORC1]]|0.429|
|[[:human genes:f:fbxw9|FBXW9]]|0.426|
|[[:human genes:p:pole|POLE]]|0.426|
|[[:human genes:c:cln6|CLN6]]|0.424|
|[[:human genes:p:psmd3|PSMD3]]|0.422|
|[[:human genes:p:psmc5|PSMC5]]|0.421|
|[[:human genes:p:polr2a|POLR2A]]|0.414|
|[[:human genes:p:prim1|PRIM1]]|0.414|
|[[:human genes:d:dnttip2|DNTTIP2]]|0.411|
|[[:human genes:c:ccna2|CCNA2]]|0.407|
|[[:human genes:c:cdc73|CDC73]]|0.407|
|[[:human genes:r:rad21|RAD21]]|0.406|
|[[:human genes:p:psmb2|PSMB2]]|0.403|
|[[:human genes:p:psmb4|PSMB4]]|0.401|
|[[:human genes:c:chmp2a|CHMP2A]]|0.4|
</modal>

<modal id='Essential_Avana' size='lg' title='Tissues where Essential in the Avana Dataset (DepMap 20Q1)'>
Global Fraction of Cell Lines Where Essential: 143/739
^Tissue^Fraction Of Cell Lines Where Essential^
|1290807.0|1/1|
|909776.0|1/1|
|bile duct|1/28|
|blood|11/28|
|bone|9/26|
|breast|8/33|
|central nervous system|16/56|
|cervix|0/4|
|colorectal|0/17|
|esophagus|1/13|
|fibroblast|0/1|
|gastric|1/16|
|kidney|6/21|
|liver|8/20|
|lung|13/75|
|lymphocyte|5/16|
|ovary|6/26|
|pancreas|4/24|
|peripheral nervous system|6/16|
|plasma cell|3/15|
|prostate|0/1|
|skin|4/24|
|soft tissue|3/9|
|thyroid|0/2|
|upper aerodigestive|0/22|
|urinary tract|1/29|
|uterus|2/5|
</modal>

== Essentiality in NALM6  ==
    * **<color #00a2e8>Essentiality Rank</color>**: 1341
    * **<color #00a2e8>Expression level (log2 read counts)</color>**: 6.01 
<button type='primary' size='small' modal='Dist_expr'>Expression Distribution</button>
<modal id='Dist_expr' size='lg' title='GPX4 Expression in NALM6 Cells: 6.01'>
{{:chemogenomics:nalm6 dist.png?nolink |}}
</modal>