======= HMGCR =======


== Gene Information ==
  * **<color #00a2e8>Official Symbol</color>**: HMGCR
  * **<color #00a2e8>Official Name</color>**: 3-hydroxy-3-methylglutaryl-CoA reductase
  * **<color #00a2e8>Aliases and Previous Symbols</color>**: N/A
  * **<color #00a2e8>Entrez ID</color>**: [[https://www.ncbi.nlm.nih.gov/gene/?term=3156|3156]]
  * **<color #00a2e8>UniProt</color>**: [[https://www.uniprot.org/uniprot/P04035|P04035]]
  * **<color #00a2e8>Interactions</color>**: [[https://thebiogrid.org/search.php?search=HMGCR&organism=9606|BioGRID]]
  * **<color #00a2e8>PubMed articles</color>**: [[https://www.ncbi.nlm.nih.gov/pubmed/?term=gene%20HMGCR|Open PubMed]]
  * **<color #00a2e8>OMIM</color>**: [[https://omim.org/entry/142910|Open OMIM]]

== Function Summary ==
  * **<color #00a2e8>Entrez Summary</color>**:  HMG-CoA reductase is the rate-limiting enzyme for cholesterol synthesis and is regulated via a negative feedback mechanism mediated by sterols and non-sterol metabolites derived from mevalonate, the product of the reaction catalyzed by reductase. Normally in mammalian cells this enzyme is suppressed by cholesterol derived from the internalization and degradation of low density lipoprotein (LDL) via the LDL receptor. Competitive inhibitors of the reductase induce the expression of LDL receptors in the liver, which in turn increases the catabolism of plasma LDL and lowers the plasma concentration of cholesterol, an important determinant of atherosclerosis. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2008]. 
  * **<color #00a2e8>UniProt Summary</color>**:  Transmembrane glycoprotein that is the rate-limiting enzyme in cholesterol biosynthesis as well as in the biosynthesis of nonsterol isoprenoids that are essential for normal cell function including ubiquinone and geranylgeranyl proteins.

<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'>
|Patched|
|Sterol-sensing|
|HMG-CoA red|
</modal>

<modal id='GO_terms' size='lg' title='GO Terms'>
|hydroxymethylglutaryl-CoA reductase (NADPH) activity|
|hydroxymethylglutaryl-CoA reductase activity|
|negative regulation of amyloid-beta clearance|
|negative regulation of insulin secretion involved in cellular response to glucose stimulus|
|coenzyme binding|
|positive regulation of striated muscle cell apoptotic process|
|positive regulation of cardiac muscle cell apoptotic process|
|coenzyme A metabolic process|
|NADPH binding|
|regulation of amyloid-beta clearance|
|ubiquinone metabolic process|
|negative regulation of striated muscle cell apoptotic process|
|positive regulation of skeletal muscle tissue development|
|positive regulation of muscle cell apoptotic process|
|isoprenoid biosynthetic process|
|quinone metabolic process|
|protein phosphatase 2A binding|
|myoblast differentiation|
|regulation of cardiac muscle cell apoptotic process|
|negative regulation of muscle cell apoptotic process|
|negative regulation of insulin secretion|
|regulation of striated muscle cell apoptotic process|
|negative regulation of blood vessel diameter|
|cholesterol biosynthetic process|
|regulation of sterol biosynthetic process|
|secondary alcohol biosynthetic process|
|regulation of cholesterol biosynthetic process|
|negative regulation of peptide hormone secretion|
|visual learning|
|sterol biosynthetic process|
|regulation of skeletal muscle tissue development|
|oxidoreduction coenzyme metabolic process|
|visual behavior|
|regulation of cholesterol metabolic process|
|peroxisomal membrane|
|regulation of insulin secretion involved in cellular response to glucose stimulus|
|negative regulation of hormone secretion|
|regulation of muscle cell apoptotic process|
|positive regulation of striated muscle tissue development|
|positive regulation of muscle organ development|
|positive regulation of muscle tissue development|
|cellular ketone metabolic process|
|negative regulation of wound healing|
|negative regulation of MAP kinase activity|
|regulation of alcohol biosynthetic process|
|associative learning|
|positive regulation of smooth muscle cell proliferation|
|negative regulation of response to wounding|
|regulation of steroid biosynthetic process|
|alcohol biosynthetic process|
|regulation of steroid metabolic process|
|cholesterol metabolic process|
|response to ethanol|
|steroid biosynthetic process|
|secondary alcohol metabolic process|
|nucleoside bisphosphate metabolic process|
|negative regulation of protein secretion|
|regulation of striated muscle tissue development|
|purine nucleoside bisphosphate metabolic process|
|ribonucleoside bisphosphate metabolic process|
|negative regulation of protein catabolic process|
|regulation of smooth muscle cell proliferation|
|negative regulation of protein serine/threonine kinase activity|
|sterol metabolic process|
|regulation of muscle tissue development|
|regulation of muscle organ development|
|regulation of wound healing|
|isoprenoid metabolic process|
|regulation of blood vessel diameter|
|negative regulation of peptide secretion|
|regulation of tube diameter|
|regulation of tube size|
|learning|
|protein tetramerization|
|positive regulation of stress-activated MAPK cascade|
|regulation of response to wounding|
|negative regulation of MAPK cascade|
|positive regulation of stress-activated protein kinase signaling cascade|
|vascular process in circulatory system|
|regulation of insulin secretion|
|negative regulation of protein transport|
|organic hydroxy compound biosynthetic process|
|negative regulation of establishment of protein localization|
|regulation of lipid biosynthetic process|
|negative regulation of secretion by cell|
|regulation of peptide hormone secretion|
|positive regulation of ERK1 and ERK2 cascade|
|response to nutrient|
|negative regulation of protein kinase activity|
|negative regulation of secretion|
|response to alcohol|
|regulation of stress-activated MAPK cascade|
|regulation of stress-activated protein kinase signaling cascade|
|negative regulation of kinase activity|
|coenzyme metabolic process|
|learning or memory|
|steroid metabolic process|
|regulation of hormone secretion|
|negative regulation of transferase activity|
|aging|
|regulation of ERK1 and ERK2 cascade|
|cognition|
|response to antibiotic|
|response to light stimulus|
|negative regulation of catabolic process|
|purine ribonucleotide metabolic process|
|alcohol metabolic process|
|ribonucleotide metabolic process|
|purine nucleotide metabolic process|
|ribose phosphate metabolic process|
|regulation of MAP kinase activity|
|negative regulation of response to external stimulus|
|purine-containing compound metabolic process|
|regulation of protein catabolic process|
|blood circulation|
|circulatory system process|
|regulation of lipid metabolic process|
|negative regulation of protein phosphorylation|
|regulation of small molecule metabolic process|
|cofactor metabolic process|
|response to radiation|
|negative regulation of phosphorylation|
|nucleotide metabolic process|
|nucleoside phosphate metabolic process|
|organic hydroxy compound metabolic process|
|regulation of protein secretion|
|muscle structure development|
|negative regulation of transport|
|regulation of peptide secretion|
|response to nutrient levels|
|response to toxic substance|
|negative regulation of intracellular signal transduction|
|regulation of anatomical structure size|
|regulation of protein serine/threonine kinase activity|
|protein complex oligomerization|
|response to extracellular stimulus|
|regulation of hormone levels|
|nucleobase-containing small molecule metabolic process|
|positive regulation of MAPK cascade|
|negative regulation of phosphate metabolic process|
|negative regulation of phosphorus metabolic process|
|behavior|
|lipid biosynthetic process|
|small molecule biosynthetic process|
|negative regulation of protein modification process|
|positive regulation of apoptotic process|
|positive regulation of programmed cell death|
|positive regulation of cell death|
|regulation of protein transport|
|regulation of cellular response to stress|
|regulation of peptide transport|
|regulation of establishment of protein localization|
|regulation of secretion by cell|
|regulation of MAPK cascade|
|negative regulation of catalytic activity|
|regulation of protein kinase activity|
|regulation of secretion|
|regulation of kinase activity|
|protein homodimerization activity|
|organophosphate metabolic process|
|negative regulation of apoptotic process|
|negative regulation of programmed cell death|
|positive regulation of cell population proliferation|
|regulation of cellular localization|
|endoplasmic reticulum membrane|
|cellular lipid metabolic process|
|oxidation-reduction process|
|regulation of transferase activity|
|regulation of catabolic process|
|negative regulation of cell death|
|endoplasmic reticulum|
|positive regulation of protein phosphorylation|
|positive regulation of intracellular signal transduction|
|response to drug|
|regulation of protein localization|
|carbohydrate derivative metabolic process|
|negative regulation of cellular protein metabolic process|
|positive regulation of phosphorylation|
|regulation of response to external stimulus|
|negative regulation of protein metabolic process|
|positive regulation of phosphate metabolic process|
|positive regulation of phosphorus metabolic process|
|negative regulation of molecular function|
|response to abiotic stimulus|
|negative regulation of multicellular organismal process|
|lipid metabolic process|
|positive regulation of protein modification process|
|negative regulation of signal transduction|
|organic cyclic compound biosynthetic process|
|negative regulation of cell communication|
|negative regulation of signaling|
|positive regulation of developmental process|
|nervous system process|
|regulation of protein phosphorylation|
|regulation of response to stress|
|regulation of apoptotic process|
|response to oxygen-containing compound|
|protein-containing complex assembly|
|regulation of programmed cell death|
|regulation of phosphorylation|
|positive regulation of cellular protein metabolic process|
|regulation of cell population proliferation|
|negative regulation of response to stimulus|
|positive regulation of signal transduction|
|regulation of cell death|
|positive regulation of protein metabolic process|
|positive regulation of multicellular organismal process|
|small molecule metabolic process|
|regulation of phosphate metabolic process|
|regulation of phosphorus metabolic process|
|positive regulation of cell communication|
|positive regulation of signaling|
|regulation of intracellular signal transduction|
|regulation of protein modification process|
|protein-containing complex subunit organization|
|regulation of transport|
|system process|
</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:exp503|Mitomycin-C 0.06μM R08 exp503]]|-2.93|
|[[:results:exp282|Fluvastatin 2.2μM R06 exp282]]|-2.58|
|[[:results:exp456|Benzoate 20000μM R08 exp456]]|-2.45|
|[[:results:exp521|Salinomycin 3.5μM R08 exp521]]|-2.38|
|[[:results:exp382|Palbociclib 1μM R07 exp382]]|-2.24|
|[[:results:exp34|Rotenone 20μM R00 exp34]]|-2.22|
|[[:results:exp448|Ammonium tetrathiomolybdate 10μM R08 exp448]]|-2.16|
|[[:results:exp66|BI-D1870 3.15μM R02 exp66]]|-1.83|
|[[:results:exp143|Phenformin 20μM R03 exp143]]|-1.8|
|[[:results:exp454|Bafilomycin-A1 0.009μM R08 exp454]]|-1.76|
|[[:results:exp431|Rotenone 0.07μM R08 exp431]]|-1.75|
|[[:results:exp401|SNS-032 25μM R07 exp401]]|-1.75|
|[[:results:exp435|JQ1 0.8μM R08 exp435]]|-1.73|
|[[:results:exp176|Apcin 50 to 100μM on day4 R04 exp176]]|1.7|
|[[:results:exp347|Cyclosporin-A 0.8μM R07 exp347]]|1.7|
|[[:results:exp235|Geldanamycin 0.01μM R05 exp235]]|1.7|
|[[:results:exp223|Cabazitaxel 0.001μM R05 exp223]]|1.71|
|[[:results:exp242|Radicicol 0.16μM R05 exp242]]|1.73|
|[[:results:exp260|ABT-702 0.1μM R06 exp260]]|1.79|
|[[:results:exp212|Phenformin 20μM R05 exp212]]|1.79|
|[[:results:exp359|FK-506 30μM R07 exp359]]|1.97|
|[[:results:exp210|LB-100 2μM R05 exp210]]|1.99|
|[[:results:exp1|5-Fluorouracil 2μM R00 exp1]]|2.06|
|[[:results:exp69|Deguelin 0.05μM R02 exp69]]|2.06|
|[[:results:exp30|Rapamycin 10μM R00 exp30]]|2.07|
|[[:results:exp218|A-395 10μM R05 exp218]]|2.29|
|[[:results:exp228|Demecolcine 0.03μM R05 exp228]]|2.95|
</modal>

<modal id='Most_Correlated_Genes' size='lg' title='Most Correlated Genes in Chemogenomics'>
^Gene^Correlation^
|[[:human genes:h:hgc6.3|HGC6.3]]|0.546|
|[[:human genes:n:npipb5|NPIPB5]]|0.495|
|[[:human genes:p:pcf11|PCF11]]|0.487|
|[[:human genes:t:terf1|TERF1]]|0.468|
|[[:human genes:s:ssh2|SSH2]]|0.455|
|[[:human genes:s:scaf1|SCAF1]]|0.452|
|[[:human genes:n:nupl1|NUPL1]]|0.451|
|[[:human genes:a:akirin2|AKIRIN2]]|0.449|
|[[:human genes:c:chd4|CHD4]]|0.445|
|[[:human genes:s:supt6h|SUPT6H]]|0.441|
|[[:human genes:o:orc1|ORC1]]|0.436|
|[[:human genes:c:ccna2|CCNA2]]|0.434|
|[[:human genes:c:copb1|COPB1]]|0.434|
|[[:human genes:n:nup54|NUP54]]|0.428|
|[[:human genes:l:lrr1|LRR1]]|0.428|
|[[:human genes:m:myo18a|MYO18A]]|0.417|
|[[:human genes:p:polr2j3|POLR2J3]]|0.417|
|[[:human genes:m:myo1h|MYO1H]]|0.413|
|[[:human genes:p:psmc6|PSMC6]]|0.41|
|[[:human genes:s:sec13|SEC13]]|0.408|
|[[:human genes:m:med29|MED29]]|0.407|
|[[:human genes:d:dtl|DTL]]|0.407|
|[[:human genes:m:mt1e|MT1E]]|0.407|
</modal>

<modal id='Essential_Avana' size='lg' title='Tissues where Essential in the Avana Dataset (DepMap 20Q1)'>
Global Fraction of Cell Lines Where Essential: 169/739
^Tissue^Fraction Of Cell Lines Where Essential^
|1290807.0|0/1|
|909776.0|0/1|
|bile duct|9/28|
|blood|7/28|
|bone|4/26|
|breast|9/33|
|central nervous system|4/56|
|cervix|1/4|
|colorectal|2/17|
|esophagus|0/13|
|fibroblast|0/1|
|gastric|4/16|
|kidney|4/21|
|liver|2/20|
|lung|24/75|
|lymphocyte|7/16|
|ovary|7/26|
|pancreas|7/24|
|peripheral nervous system|1/16|
|plasma cell|4/15|
|prostate|1/1|
|skin|9/24|
|soft tissue|2/9|
|thyroid|0/2|
|upper aerodigestive|4/22|
|urinary tract|4/29|
|uterus|2/5|
</modal>

== Essentiality in NALM6  ==
    * **<color #00a2e8>Essentiality Rank</color>**: 683
    * **<color #00a2e8>Expression level (log2 read counts)</color>**: 8.35 
<button type='primary' size='small' modal='Dist_expr'>Expression Distribution</button>
<modal id='Dist_expr' size='lg' title='HMGCR Expression in NALM6 Cells: 8.35'>
{{:chemogenomics:nalm6 dist.png?nolink |}}
</modal>