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PsychedeliaDokholyan Laboratory
TargetIon channels

hERG

Voltage- and ligand-gated channels, including the TRP family and hERG (KCNH2).

Measurements
33
Compounds
16
Binding constants
10
Median pX
6.15

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

KCNH2_HUMANKCNH2Homo sapiens

Voltage-gated inwardly rectifying potassium channel KCNH2

Pore-forming (alpha) subunit of voltage-gated inwardly rectifying potassium channel10219239,10753933,10790218,10837251,11997281,12063277,18559421,22314138,22359612,26363003,27916661,9230439,9351446,9765245. Channel properties are modulated by cAMP and subunit assembly10837251. Characterized by unusual gating kinetics by producing relatively small outward currents during membrane depolarization and large inward currents during subsequent repolarization which reflect a rapid inactivation during depolarization and quick recovery from inactivation but slow deactivation (closing) during repolarization10219239,10753933,10790218,10837251,11997281,12063277,18559421,22314138,22359612,26363003,27916661,9230439,9351446,9765245. Forms a stable complex with KCNE1 or KCNE2, and that this heteromultimerization regulates inward rectifier potassium channel activity10219239,9230439
Has no inward rectifier potassium channel activity by itself, but modulates channel characteristics by forming heterotetramers with other isoforms which are retained intracellularly and undergo ubiquitin-dependent degradation
Has no inward rectifier potassium channel activity by itself, but modulates channel characteristics by forming heterotetramers with other isoforms which are retained intracellularly and undergo ubiquitin-dependent degradation

Quoted from UniProt’s FUNCTION annotation for Q12809 (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
KCNE20.9980.0000.5000.997
KCNE10.9940.2920.5000.985
KCNQ10.9830.0000.0000.983
SCN5A0.9780.0590.0000.978
HSP90AA10.9580.7350.0000.851
KCNE30.9500.0000.5000.906
KCNJ20.9300.0000.0000.930
CACNA1C0.8910.0590.0000.885
KCNH60.8830.8000.4000.077
HSPA40.8740.5100.0000.754

Where it sits in the cell

UniProt, curated Cell membrane

Expression by cell type

Single cell type RNA, the 11 highest of those the Human Protein Atlas reports for this gene. Transcript, not protein, and a cell type rather than a tissue.

  • Erythrocyte progenitors263.5 nCPM
  • Retinal bipolar cells177.1 nCPM
  • Sertoli cells67.5 nCPM
  • Gonadotrophs66.4 nCPM
  • Adrenal medulla cells63.8 nCPM
  • Corticotrophs49.9 nCPM
  • Lactotrophs46.3 nCPM
  • Megakaryocyte-Erythroid progenitors42.7 nCPM
  • Thyrotrophs42.3 nCPM
  • Retinal amacrine cells42.2 nCPM
  • Somatotrophs39.1 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.

  • pituitary gland41.5 nTPM
  • bone marrow39 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 — 10.0 nTPM, from KCNH2cerebellum — 32.4 nTPM, from KCNH2hippocampal formation — 8.9 nTPM, from KCNH2amygdala — 7.5 nTPM, from KCNH2hypothalamus — 14.4 nTPM, from KCNH2thalamus — no resolved target expressed herebasal ganglia — 14.0 nTPM, from KCNH2medulla 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: pituitary gland 41.5, midbrain 6.7, retina 5.3, spinal cord 4.0.

Body

heart — 28.4 nTPM, from KCNH2smooth muscle — 7.0 nTPM, from KCNH2lung — 1.8 nTPM, from KCNH2liver — 0.2 nTPM, from KCNH2kidney — 1.1 nTPM, from KCNH2stomach — 10.6 nTPM, from KCNH2duodenum — 2.4 nTPM, from KCNH2small intestine — 8.1 nTPM, from KCNH2colon — 36.0 nTPM, from KCNH2adrenal gland — 3.4 nTPM, from KCNH2thyroid gland — 0.1 nTPM, from KCNH2pancreas — 3.2 nTPM, from KCNH2urinary bladder — 13.4 nTPM, from KCNH2skeletal muscle — 0.2 nTPM, from KCNH2spleen — 1.7 nTPM, from KCNH2salivary gland — 0.9 nTPM, from KCNH2
042 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 KCNH2 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

  • pituitary gland41.5 nTPM
  • cerebellum32.4 nTPM
  • hypothalamus14.4 nTPM
  • basal ganglia14.0 nTPM
  • cerebral cortex10.0 nTPM
  • hippocampal formation8.9 nTPM
  • amygdala7.5 nTPM
  • midbrain6.7 nTPM
  • retina5.3 nTPM
  • spinal cord4.0 nTPM

Peripheral and autonomic · 16

  • colon36.0 nTPM
  • heart muscle28.4 nTPM
  • urinary bladder13.4 nTPM
  • stomach 110.6 nTPM
  • small intestine8.1 nTPM
  • smooth muscle7.0 nTPM
  • adrenal gland3.4 nTPM
  • pancreas3.2 nTPM
  • duodenum2.4 nTPM
  • lung1.8 nTPM
  • spleen1.7 nTPM
  • kidney1.1 nTPM
  • salivary gland0.9 nTPM
  • liver0.2 nTPM
  • skeletal muscle0.2 nTPM
  • thyroid gland0.1 nTPM

Transcript is not protein. These are RNA levels for KCNH2, 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.

III · Ranking

Compounds by strongest binding constant

One bar per compound: its strongest Ki or Kd at this target, expressed as pX. Compounds measured here only by a functional assay do not appear — they are in the table below.

  1. 01Voacangine6.41
  2. 02Ibogaine6.15
  3. 03Noribogaine5.71

IV · Evidence

Every measurement at this target

Each row links to the ChEMBL assay it came from.

Equilibrium binding constants 10

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

TargetClassTypeValue (nM)pXOrganismAssay
hERGIon channelsKi3896.41HAMSTERPMID 25636206
hERGIon channelsKi7106.15HAMSTERPMID 25636206
hERGIon channelsKi1,9605.71HAMSTERPMID 25636206
hERGIon channelsKi— no normalized value— value does not convert to pXHomo sapiensCHEMBL1909190
hERGIon channelsKi— no normalized value— value does not convert to pXHomo sapiensCHEMBL1909190
hERGIon channelsKi— no normalized value— value does not convert to pXHomo sapiensCHEMBL1909190
hERGIon channelsKi— no normalized value— value does not convert to pXHomo sapiensCHEMBL1909190
hERGIon channelsKi— no normalized value— value does not convert to pXHomo sapiensCHEMBL1909190
hERGIon channelsKi— no normalized value— value does not convert to pXHomo sapiensCHEMBL1909190
hERGIon channelsKi— no normalized value— value does not convert to pXHomo sapiensCHEMBL1909190

Functional readouts 23

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

TargetClassTypeValue (nM)pXOrganismAssay
hERGIon channelsIC504,8005.32Homo sapiensCHEMBL1227232
hERGIon channelsAC50— no normalized value— value does not convert to pXHomo sapiensCHEMBL5291828
hERGIon channelsAC50— no normalized value— value does not convert to pXHomo sapiensCHEMBL5291828
hERGIon channelsIC50— no normalized value— value does not convert to pXHomo sapiensCHEMBL1909190
hERGIon channelsIC50— no normalized value— value does not convert to pXHomo sapiensCHEMBL1909190
hERGIon channelsIC50— no normalized value— value does not convert to pXHomo sapiensCHEMBL1909190
hERGIon channelsIC50— no normalized value— value does not convert to pXHomo sapiensCHEMBL1909190
hERGIon channelsIC50— no normalized value— value does not convert to pXHomo sapiensCHEMBL1909190
hERGIon channelsIC50— no normalized value— value does not convert to pXHomo sapiensCHEMBL1909190
hERGIon channelsIC50— no normalized value— value does not convert to pXHomo sapiensCHEMBL1909190
hERGIon channelsIC50— no normalized value— value does not convert to pXHomo sapiensCHEMBL6080247
hERGIon channelsIC50— no normalized value— value does not convert to pXHomo sapiensCHEMBL4707280
hERGIon channelsIC50— no normalized value— value does not convert to pXHomo sapiensCHEMBL1816994
hERGIon channelsIC50— no normalized value— value does not convert to pXHomo sapiensCHEMBL6117187
hERGIon channelsAC50— no normalized value— value does not convert to pXHomo sapiensCHEMBL5291828
hERGIon channelsAC50— no normalized value— value does not convert to pXHomo sapiensCHEMBL5291828
hERGIon channelsAC50— no normalized value— value does not convert to pXHomo sapiensCHEMBL5291828
hERGIon channelsAC50— no normalized value— value does not convert to pXHomo sapiensCHEMBL5291828
hERGIon channelsAC50— no normalized value— value does not convert to pXHomo sapiensCHEMBL5291828
hERGIon channelsAC50— no normalized value— value does not convert to pXHomo sapiensCHEMBL5291828
hERGIon channelsAC50— no normalized value— value does not convert to pXHomo sapiensCHEMBL5291828
hERGIon channelsAC50— no normalized value— value does not convert to pXHomo sapiensCHEMBL5291828
hERGIon channelsAC50— no normalized value— value does not convert to pXHomo sapiensCHEMBL5291828
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