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PsychedeliaDokholyan Laboratory
TargetEnzymes

3-hydroxy-3-methylglutaryl-coenzyme A reductase

Named enzymes, including the metabolising cytochromes and the monoamine oxidases.

Measurements
14
Compounds
7
Binding constants
7
Median pX
—

I · Identity

What this target is

Its function as UniProt states it, where in a cell the protein is found, and which cell types and tissues transcribe its gene.

Protein

HMDH_HUMANHMGCRHomo sapiens

3-hydroxy-3-methylglutaryl-coenzyme A reductase

Catalyzes the conversion of (3S)-hydroxy-3-methylglutaryl-CoA (HMG-CoA) to mevalonic acid, the rate-limiting step in the synthesis of cholesterol and other isoprenoids, thus plays a critical role in cellular cholesterol homeostasis21357570,2991281,36745799,6995544. HMGCR is the main target of statins, a class of cholesterol-lowering drugs11349148,18540668,36745799

Quoted from UniProt’s FUNCTION annotation for P04035 (reviewed). The superscript numbers are UniProt’s own PubMed citations, kept in the sentence and in order, each linking to the paper it names.

What it acts with

STRING’s highest-confidence human functional partners. The combined score mixes several kinds of evidence, so each channel is shown separately — a partner supported by experiment is a different claim from one supported only by text mining, and for a receptor this is where its coupling appears as evidence rather than as assertion.

PartnerCombinedExperimentDatabaseText mining
INSIG10.9990.8400.0000.996
MVK0.9990.0880.9800.964
HMGCS10.9990.0000.9780.974
HMGCS20.9990.0000.9780.937
INSIG20.9900.3730.0000.983
SREBF20.9850.0000.7500.941
SQLE0.9730.0000.0000.863
FDPS0.9670.1320.0000.948
SREBF10.9560.0000.5000.915
FDFT10.9540.0870.0000.926

Where it sits in the cell

UniProt, curated Endoplasmic reticulum membrane · Peroxisome membrane

Expression by cell type

Single cell type RNA, the 5 highest of those the Human Protein Atlas reports for this gene. Transcript, not protein, and a cell type rather than a tissue.

  • Endometrial luminal cells467.8 nCPM
  • Epididymal principal cells260.5 nCPM
  • Endometrial glandular cells197.5 nCPM
  • Retinal ganglion cells197 nCPM
  • Suprabasal keratinocytes176 nCPM

Expression by tissue

The tissues this gene is enriched in, by consensus RNA. A tissue absent from this list is one the Atlas does not call specific for this gene, which is not the same as absent from it.

  • liver98.8 nTPM

II · Anatomy

Where the gene is transcribed

The same two atlases the compound plates use, asked about this gene alone. Brain on the left, peripheral and autonomic tissues on the right.

Brain

cerebral cortex — 47.5 nTPM, from HMGCRcerebellum — 15.9 nTPM, from HMGCRhippocampal formation — 15.7 nTPM, from HMGCRamygdala — 13.1 nTPM, from HMGCRhypothalamus — 18.4 nTPM, from HMGCRthalamus — no resolved target expressed herebasal ganglia — 14.9 nTPM, from HMGCRmedulla oblongata — no resolved target expressed here

basal ganglia: drawn as the caudate nucleus, putamen and globus pallidus.

Measured but not drawn — this anatomogram has no outline for them: retina 17.4, spinal cord 16.3, midbrain 10.0, pituitary gland 7.7.

Body

heart — 6.9 nTPM, from HMGCRsmooth muscle — 11.9 nTPM, from HMGCRlung — 22.8 nTPM, from HMGCRliver — 98.8 nTPM, from HMGCRkidney — 19.7 nTPM, from HMGCRstomach — 25.9 nTPM, from HMGCRduodenum — 35.6 nTPM, from HMGCRsmall intestine — 25.0 nTPM, from HMGCRcolon — 42.4 nTPM, from HMGCRadrenal gland — 38.7 nTPM, from HMGCRthyroid gland — 21.9 nTPM, from HMGCRpancreas — 15.5 nTPM, from HMGCRurinary bladder — 13.2 nTPM, from HMGCRskeletal muscle — 6.0 nTPM, from HMGCRspleen — 14.0 nTPM, from HMGCRsalivary gland — 14.4 nTPM, from HMGCR
099 nTPM

Square-root ramp · shared scale across both plates

Shading is transcript level — not affinity, and not affinity combined with expression. Outlined but unshaded organs hold none of HMGCR transcript above the atlas’s detection threshold. Anatomy from EMBL-EBI Anatomogram (Apache License 2.0); regions identified by Uberon (uberon.org), CC BY 3.0.

Brain · 10

  • cerebral cortex47.5 nTPM
  • hypothalamus18.4 nTPM
  • retina17.4 nTPM
  • spinal cord16.3 nTPM
  • cerebellum15.9 nTPM
  • hippocampal formation15.7 nTPM
  • basal ganglia14.9 nTPM
  • amygdala13.1 nTPM
  • midbrain10.0 nTPM
  • pituitary gland7.7 nTPM

Peripheral and autonomic · 16

  • liver98.8 nTPM
  • colon42.4 nTPM
  • adrenal gland38.7 nTPM
  • duodenum35.6 nTPM
  • stomach 125.9 nTPM
  • small intestine25.0 nTPM
  • lung22.8 nTPM
  • thyroid gland21.9 nTPM
  • kidney19.7 nTPM
  • pancreas15.5 nTPM
  • salivary gland14.4 nTPM
  • spleen14.0 nTPM
  • urinary bladder13.2 nTPM
  • smooth muscle11.9 nTPM
  • heart muscle6.9 nTPM
  • skeletal muscle6.0 nTPM

Transcript is not protein. These are RNA levels for HMGCR, shaded on √nTPM so that a three-order range stays legible — on a linear ramp every region but the strongest would read as blank, which looks like absence rather than less. A region carrying no shading is one the atlas reports no consensus value for, not one where the gene is silent. And a gene being transcribed somewhere is not evidence that any compound reaches it. Human Protein Atlas, RNA expression, nTPM (normalized transcripts per million), consensus tissue dataset.

IV · Evidence

Every measurement at this target

Each row links to the ChEMBL assay it came from.

Equilibrium binding constants 7

Ki and Kd — a concentration at equilibrium. Directly comparable across rows at the same target.

TargetClassTypeValue (nM)pXOrganismAssay
3-hydroxy-3-methylglutaryl-coenzyme A reductaseEnzymesKi— no normalized value— value does not convert to pXHomo sapiensCHEMBL1909158
3-hydroxy-3-methylglutaryl-coenzyme A reductaseEnzymesKi— no normalized value— value does not convert to pXHomo sapiensCHEMBL1909158
3-hydroxy-3-methylglutaryl-coenzyme A reductaseEnzymesKi— no normalized value— value does not convert to pXHomo sapiensCHEMBL1909158
3-hydroxy-3-methylglutaryl-coenzyme A reductaseEnzymesKi— no normalized value— value does not convert to pXHomo sapiensCHEMBL1909158
3-hydroxy-3-methylglutaryl-coenzyme A reductaseEnzymesKi— no normalized value— value does not convert to pXHomo sapiensCHEMBL1909158
3-hydroxy-3-methylglutaryl-coenzyme A reductaseEnzymesKi— no normalized value— value does not convert to pXHomo sapiensCHEMBL1909158
3-hydroxy-3-methylglutaryl-coenzyme A reductaseEnzymesKi— no normalized value— value does not convert to pXHomo sapiensCHEMBL1909158

Functional readouts 7

IC₅₀, EC₅₀, AC₅₀ and potency. Assay-dependent, and not interchangeable with a binding constant.

TargetClassTypeValue (nM)pXOrganismAssay
3-hydroxy-3-methylglutaryl-coenzyme A reductaseEnzymesIC50— no normalized value— value does not convert to pXHomo sapiensCHEMBL1909158
3-hydroxy-3-methylglutaryl-coenzyme A reductaseEnzymesIC50— no normalized value— value does not convert to pXHomo sapiensCHEMBL1909158
3-hydroxy-3-methylglutaryl-coenzyme A reductaseEnzymesIC50— no normalized value— value does not convert to pXHomo sapiensCHEMBL1909158
3-hydroxy-3-methylglutaryl-coenzyme A reductaseEnzymesIC50— no normalized value— value does not convert to pXHomo sapiensCHEMBL1909158
3-hydroxy-3-methylglutaryl-coenzyme A reductaseEnzymesIC50— no normalized value— value does not convert to pXHomo sapiensCHEMBL1909158
3-hydroxy-3-methylglutaryl-coenzyme A reductaseEnzymesIC50— no normalized value— value does not convert to pXHomo sapiensCHEMBL1909158
3-hydroxy-3-methylglutaryl-coenzyme A reductaseEnzymesIC50— no normalized value— value does not convert to pXHomo sapiensCHEMBL1909158
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