Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTEO25X)

• DTT Name: Inward rectifier potassium channel Kir3.4 (KCNJ5)
• Synonyms: Potassium channel, inwardly rectifying, subfamily J, member 5; KCNJ5; KATP-1; KATP channel; Inward rectifier K+ channel Kir3.4; Heart KATP channel; GIRK4; Cardiac inward rectifier; CIR
• Gene Name: KCNJ5
• DTT Type: Clinical trial target; [1]
• Related Disease:
  Acute myeloid leukaemia [ICD-11: 2A60]
  Hodgkin lymphoma [ICD-11: 2B30]
• BioChemical Class: Inward rectifier potassium channel
• UniProt ID: KCNJ5_HUMAN
• TTD ID: T78692
• Sequence:
  MAGDSRNAMNQDMEIGVTPWDPKKIPKQARDYVPIATDRTRLLAEGKKPRQRYMEKSGKC
  NVHHGNVQETYRYLSDLFTTLVDLKWRFNLLVFTMVYTVTWLFFGFIWWLIAYIRGDLDH
  VGDQEWIPCVENLSGFVSAFLFSIETETTIGYGFRVITEKCPEGIILLLVQAILGSIVNA
  FMVGCMFVKISQPKKRAETLMFSNNAVISMRDEKLCLMFRVGDLRNSHIVEASIRAKLIK
  SRQTKEGEFIPLNQTDINVGFDTGDDRLFLVSPLIISHEINQKSPFWEMSQAQLHQEEFE
  VVVILEGMVEATGMTCQARSSYMDTEVLWGHRFTPVLTLEKGFYEVDYNTFHDTYETNTP
  SCCAKELAEMKREGRLLQYLPSPPLLGGCAEAGLDAEAEQNEEDEPKGLGGSREARGSV
• Function: This potassium channel is controlled by G proteins. Inward rectifier potassium channels are characterized by a greater tendency to allow potassium to flow into the cell rather than out of it. Their voltage dependence is regulated by the concentration of extracellular potassium; as external potassium is raised, the voltage range of the channel opening shifts to more positive voltages. The inward rectification is mainly due to the blockage of outward current by internal magnesium. Can be blocked by external barium.
• KEGG Pathway:
  Circadian entrainment (hsa04713)
  Retrograde endocannabinoid signaling (hsa04723)
  Serotonergic synapse (hsa04726)
  Dopaminergic synapse (hsa04728)
  Estrogen signaling pathway (hsa04915)
  Oxytocin signaling pathway (hsa04921)
  Morphine addiction (hsa05032)
• Reactome Pathway:
  Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits (R-HSA-997272)
  Activation of G protein gated Potassium channels (R-HSA-1296041)

Molecular Interaction Atlas (MIA) of This DTT

1 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
phorbol 12-myristate 13-acetate	DMJWD62	Acute myeloid leukaemia	2A60	Phase 2	[1]

1 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
PIP2	DMOZV7N	Discovery agent	N.A.	Investigative	[2]

Molecular Expression Atlas (MEA) of This DTT

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Chronic obstructive pulmonary disease	CA23	Lung tissue	1.18E-01	0.08	0.47
Chronic obstructive pulmonary disease	CA23	Small airway epithelium	1.73E-03	0.08	0.43

References

• [1] Molecular basis for the inhibition of G protein-coupled inward rectifier K(+) channels by protein kinase C. Proc Natl Acad Sci U S A. 2004 Jan 27;101(4):1087-92.
• [2] PIP2 and PIP as determinants for ATP inhibition of KATP channels. Science. 1998 Nov 6;282(5391):1141-4.