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KCNJ6

gene
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Also known as Kir3.2GIRK2KATP2BIR1hiGIRK2

Summary

KCNJ6 (potassium inwardly rectifying channel subfamily J member 6, HGNC:6267) is a protein-coding gene on chromosome 21q22.13, encoding G protein-activated inward rectifier potassium channel 2 (P48051). Inward rectifier potassium channels are characterized by a greater tendency to allow potassium to flow into the cell rather than out of it.

This gene encodes a member of the G protein-coupled inwardly-rectifying potassium channel family of inward rectifier potassium channels. This type of potassium channel allows a greater flow of potassium into the cell than out of it. These proteins modulate many physiological processes, including heart rate in cardiac cells and circuit activity in neuronal cells, through G-protein coupled receptor stimulation. Mutations in this gene are associated with Keppen-Lubinsky Syndrome, a rare condition characterized by severe developmental delay, facial dysmorphism, and intellectual disability.

Source: NCBI Gene 3763 — RefSeq curated summary.

At a glance

  • Gene–disease (curated): Keppen-Lubinsky syndrome (Strong, GenCC)
  • GWAS associations: 6
  • Clinical variants (ClinVar): 131 total — 1 pathogenic, 1 likely-pathogenic
  • Phenotypes (HPO): 52
  • Druggable target: yes
  • Dosage sensitivity (ClinGen): haploinsufficiency no evidence, triplosensitivity no evidence
  • MANE Select transcript: NM_002240

Identifiers

Gene identifiers

FieldValue
HGNC IDHGNC:6267
Approved symbolKCNJ6
Namepotassium inwardly rectifying channel subfamily J member 6
Location21q22.13
Locus typegene with protein product
StatusApproved
AliasesKir3.2, GIRK2, KATP2, BIR1, hiGIRK2
Ensembl geneENSG00000157542
Ensembl biotypeprotein_coding
OMIM600877
Entrez3763

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 3 protein_coding

ENST00000609713, ENST00000645093, ENST00000917423

RefSeq mRNA: 1 — MANE Select: NM_002240 NM_002240

CCDS: CCDS42927

Canonical transcript exons

ENST00000609713 — 4 exons

ExonStartEnd
ENSE000010333133771421137715131
ENSE000015431153784065837840709
ENSE000015431193791588437916457
ENSE000037044853760737337625484

Expression profiles

Bgee: expression breadth ubiquitous, 108 present calls, max score 97.74.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 1.6143 / max 108.3749, expressed in 111 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter IDTPM avgSamples expressed
1904231.6143111
1904160.6430144
1904210.4142120
1904170.183188

Top tissues by expression

260 total, by Bgee expression score (0-100, higher = more expressed):

TissueAnatomy IDExpression scoreQuality
substantia nigra pars reticulataUBERON:000196697.74gold quality
substantia nigra pars compactaUBERON:000196597.65gold quality
middle temporal gyrusUBERON:000277192.97gold quality
Brodmann (1909) area 23UBERON:001355492.01gold quality
frontal poleUBERON:000279589.39gold quality
postcentral gyrusUBERON:000258189.14gold quality
Brodmann (1909) area 46UBERON:000648389.10gold quality
orbitofrontal cortexUBERON:000416788.83gold quality
parietal lobeUBERON:000187288.37gold quality
entorhinal cortexUBERON:000272887.48gold quality
cerebellar vermisUBERON:000472087.12gold quality
Brodmann (1909) area 10UBERON:001354186.34gold quality
superior frontal gyrusUBERON:000266186.21gold quality
ponsUBERON:000098885.46gold quality
CA1 field of hippocampusUBERON:000388184.99gold quality
paraflocculusUBERON:000535184.46gold quality
occipital lobeUBERON:000202183.44gold quality
primary visual cortexUBERON:000243683.40gold quality
buccal mucosa cellCL:000233681.86silver quality
cervix squamous epitheliumUBERON:000692281.80gold quality
type B pancreatic cellCL:000016980.98gold quality
ventral tegmental areaUBERON:000269180.50gold quality
islet of LangerhansUBERON:000000679.74gold quality
olfactory bulbUBERON:000226478.90gold quality
midbrainUBERON:000189177.19gold quality
substantia nigraUBERON:000203876.64gold quality
superior vestibular nucleusUBERON:000722776.58gold quality
Ammon’s hornUBERON:000195476.05gold quality
lateral nuclear group of thalamusUBERON:000273675.66gold quality
cerebral cortexUBERON:000095674.39gold quality

Single-cell (SCXA)

Detected in 7 experiment(s), a significant marker in 7.

ExperimentMarker?Max mean expression
E-GEOD-83139yes589.27
E-MTAB-9154yes425.22
E-MTAB-5061yes29.40
E-GEOD-81547yes23.99
E-HCAD-25yes11.22
E-ANND-3yes6.65
E-GEOD-137537yes4.76

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

130 targeting KCNJ6, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNAMax scoreAvg scoremiRNA target_count
HSA-MIR-4713-3P100.0065.92505
HSA-MIR-4776-3P100.0068.731340
HSA-MIR-4425100.0067.591049
HSA-MIR-5692A100.0074.406850
HSA-MIR-3617-3P99.9867.86918
HSA-MIR-520D-5P99.9873.344883
HSA-MIR-524-5P99.9873.434882
HSA-MIR-493-5P99.9672.472382
HSA-MIR-548AT-5P99.9670.832666
HSA-MIR-391099.9571.132227
HSA-MIR-144-3P99.9473.982698
HSA-MIR-101-3P99.9475.032230
HSA-MIR-9983-3P99.9471.483631
HSA-MIR-6721-5P99.9368.922981
HSA-MIR-7-1-3P99.9171.534384
HSA-MIR-7-2-3P99.9171.404394
HSA-MIR-124-3P99.8973.743043
HSA-MIR-506-3P99.8973.553057
HSA-MIR-4731-5P99.8967.232537
HSA-MIR-6780A-5P99.8866.692776
HSA-MIR-129-5P99.8870.263273
HSA-LET-7A-2-3P99.8770.531921
HSA-LET-7G-3P99.8570.431929
HSA-MIR-576-5P99.8470.462582
HSA-MIR-4799-5P99.8270.602663
HSA-MIR-313399.8170.923506
HSA-MIR-1273H-5P99.7766.322471
HSA-MIR-465899.7764.94514
HSA-MIR-6790-5P99.7765.24505
HSA-MIR-6764-5P99.7567.892304

Functional genomics

ClinGen dosage: haploinsufficiency 0 (no evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 35)

  • glutamate residue at the C terminus regulates activity – implications for Andersen Disease (inward rectifier potassium channel 2; IRK2) (PMID:12034888)
  • L344 and G347 play an important functional role in G(betagamma) activation of GIRK2 channels. (PMID:14724209)
  • The potential synergy and consequences of the overexpression of KIR3.2 and KIR4.2 in Down’s syndrome brain development are discussed. (PMID:15068243)
  • GIRK channels are important functional effectors of the P2Y(12) receptor in human platelets. (PMID:15142872)
  • Decreased GRK 2 expression most likely results from reduced cAMP stimulation in cold thyroid nodules. (PMID:15772902)
  • GIRK1 and GIRK2 channels, but not GIRK3 or GIRK4, may may activate signaling pathways in development of lung cancer (PMID:16109170)
  • These data suggest that KCNJ6 could play an important role in altered cardiac regulation in Down syndrome patients. (PMID:18303085)
  • Kir3.2 was capable of interacting with Gbeta1-3 and not Gbeta4 or Gbeta5. These interactions were again fostered by co-expression with Ggamma and were also insensitive to DN Sar 1 or Rab 1. (PMID:19135528)
  • KCNJ6 (GIRK2) gene polymorphisms have roles in postoperative analgesic requirements after major abdominal surgery (PMID:19756153)
  • The KCNJ6 promoter is activated by Trichostatin A (TSA) treatment and by serum depletion according to promoter reporter assays in HEK 293 cells. (PMID:20494980)
  • The overexpression of one particular gene encoding for G-protein-activated inward rectifying potassium type 2 (GIRK2) channel subunit and its coupling to GABA(B) receptors may contribute to a range of mental and functional disabilities in Down syndrome. (PMID:20655490)
  • significant interaction between the TT genotype of rs2070995 (located in KCNJ6) and the GG genotype of rs2253206 (located in CREB1) on rumination were found (PMID:20943350)
  • KCNJ6 is associated with alcohol dependence and may moderate the effect of early psychosocial stress on risky alcohol drinking in adolescents (PMID:21307845)
  • This study is the first to identify the expression of GIRK2-4 subunits in human esophageal smooth muscle cells. (PMID:21637918)
  • GIRK overexpression in Ts65Dn mice has functional consequences affecting balance between GABA(A) and GABA(B) inhibition of CA1 pyramidal neurons in a pathway specific manner, that may contribute to cognitive deficits in Ts65 mouse model of Down syndrome. (PMID:22178330)
  • GIRK2 is expressed in nearly every human pigmented neuron or mouse tyrosine hydroxylase-immunoreactive neuron in both the substantia nigra and ventral tegmental areas. (PMID:22252428)
  • KCNJ6 (or its product GIRK2) accounts for some of the variations in frontal theta; band oscillations. (PMID:22554406)
  • Conformational information encoded by ligand binding to delta-opioid receptors (DORs) is transmitted to Kir3.1/Kir3.2 channels. (PMID:23175530)
  • 3.5 A resolution crystal structure of the mammalian GIRK2 channel in complex with betagamma G-protein subunits, the central signalling complex that links G-protein-coupled receptor stimulation to K(+) channel activity (PMID:23739333)
  • Eight KCNNJ6 single nucleotide polymorphisms(SNPs) are significantly associated with pain-related phenotypes. (PMID:23994450)
  • Ethanol associates directly with the GIRK channel, leading to enhanced interaction with a membrane phospholipid phosphatidylinositol 4,5-bisphosphate and activation of the channel. (PMID:24145411)
  • For KCNJ6, three SNPs (i.e., rs2835914, rs8129919, rs2836050) were associated with the occurrence of preoperative breast pain. (PMID:24392765)
  • KCNJ6 (GIRK2) gene polymorphism rs2835859 could serve as a marker that predicts sensitivity to analgesics and pain and susceptibility to nicotine dependence. (PMID:25346042)
  • The findings of this study suggest that variations in KCNJ6 genes are associated with both mild and severe persistent breast pain after breast cancer surgery. (PMID:25599232)
  • Keppen-Lubinsky syndrome is caused by mutations in the inwardly rectifying K+ channel encoded by KCNJ6. (PMID:25620207)
  • In this transgenic mouse model, GIRK2 plays a major role in the genesis of infantile spasms. (PMID:26032891)
  • The KCNJ6 -1250A and COMT Val alleles are predisposing preterm newborns to diminished opioid-induced pain relief. (PMID:27027462)
  • Three of the four KCNJ6 SNPs studied here were found to be significantly associated with the same theta event related oscillations in adults. (PMID:27847216)
  • The major findings of the current study are 1) an additive genotypic effect of the KCNJ6 SNP on the ERO theta power phenotype during reward processing, increasing significantly across genotypes. (PMID:27993610)
  • Gi/o-coupled muscarinic receptors co-localize with GIRK channel for efficient channel activation (PMID:30240440)
  • These findings suggest that KCNJ6 may contribute to variation of blood pressure responses to dietary sodium interventions. (PMID:30323262)
  • KCNJ6 variants modulate reward-related brain processes and impact executive functions in attention-deficit/hyperactivity disorder. (PMID:31099984)
  • Alcohol reverses the effects of KCNJ6 (GIRK2) noncoding variants on excitability of human glutamatergic neurons. (PMID:36207584)
  • Association of KCNJ6 rs2070995 and methadone response for pain management in advanced cancer at end-of-life. (PMID:36261449)
  • Oxidation Driven Reversal of PIP2-dependent Gating in GIRK2 Channels. (PMID:37168492)

Cross-species orthologs

3 orthologs

OrganismSymbolGene ID
danio_reriokcnj6ENSDARG00000058985
mus_musculusKcnj6ENSMUSG00000043301
rattus_norvegicusKcnj6ENSRNOG00000001658

Paralogs (15): KCNJ13 (ENSG00000115474), KCNJ5 (ENSG00000120457), KCNJ8 (ENSG00000121361), KCNJ2 (ENSG00000123700), KCNJ1 (ENSG00000151704), KCNJ16 (ENSG00000153822), KCNJ15 (ENSG00000157551), KCNJ9 (ENSG00000162728), KCNJ3 (ENSG00000162989), KCNJ4 (ENSG00000168135), KCNJ10 (ENSG00000177807), KCNJ14 (ENSG00000182324), KCNJ12 (ENSG00000184185), KCNJ11 (ENSG00000187486), KCNJ18 (ENSG00000260458)

Protein

Protein identifiers

G protein-activated inward rectifier potassium channel 2 — P48051 (reviewed: P48051)

Alternative names: BIR1, Inward rectifier K(+) channel Kir3.2, KATP-2, Potassium channel, inwardly rectifying subfamily J member 6

All UniProt accessions (1): P48051

UniProt curated annotations — full annotation on UniProt →

Function. 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. This potassium channel may be involved in the regulation of insulin secretion by glucose and/or neurotransmitters acting through G-protein-coupled receptors.

Subunit / interactions. Associates with KCNJ3/GIRK1 or KCNJ5/GRIK4 to form a G-protein-activated heteromultimer pore-forming unit. The resulting inward current is much larger. Interacts (via PDZ-binding motif) with SNX27 (via PDZ domain); the interaction is required when endocytosed to prevent degradation in lysosomes and promote recycling to the plasma membrane.

Subcellular location. Membrane.

Tissue specificity. Most abundant in cerebellum, and to a lesser degree in islets and exocrine pancreas.

Disease relevance. Keppen-Lubinsky syndrome (KPLBS) [MIM:614098] A rare disease characterized by severe developmental delay, intellectual disability, severe generalized lipodystrophy, dysmorphic features including microcephaly, large prominent eyes, narrow nasal bridge, tented upper lip, high palate, open mouth, tightly adherent skin, and aged appearance. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Activated by phosphatidylinositol 4,5 biphosphate (PtdIns(4,5)P2).

Similarity. Belongs to the inward rectifier-type potassium channel (TC 1.A.2.1) family. KCNJ6 subfamily.

RefSeq proteins (1): NP_002231* (*=MANE)

Domains & families (InterPro)

IDNameType
IPR003275K_chnl_inward-rec_Kir3.2Family
IPR013518K_chnl_inward-rec_Kir_cytoHomologous_superfamily
IPR014756Ig_E-setHomologous_superfamily
IPR016449K_chnl_inward-rec_KirFamily
IPR040445Kir_TMDomain
IPR041647IRK_CDomain

Pfam: PF01007, PF17655

Catalyzed reactions (Rhea), 1 shown:

  • K(+)(in) = K(+)(out) (RHEA:29463)

UniProt features (17 total): topological domain 4, short sequence motif 2, modified residue 2, sequence variant 2, transmembrane region 2, intramembrane region 2, chain 1, site 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

ModelpLDDTFraction very-high
AF-P48051-F183.830.69

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (1): 182 (role in the control of polyamine-mediated channel gating and in the blocking by intracellular magnesium)

Post-translational modifications (2): 16, 23

Function

Pathways and Gene Ontology

Reactome pathways

11 pathways

IDPathway
R-HSA-1296041Activation of G protein gated Potassium channels
R-HSA-997272Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits
R-HSA-112314Neurotransmitter receptors and postsynaptic signal transmission
R-HSA-112315Transmission across Chemical Synapses
R-HSA-112316Neuronal System
R-HSA-1296059G protein gated Potassium channels
R-HSA-1296065Inwardly rectifying K+ channels
R-HSA-1296071Potassium Channels
R-HSA-977443GABA receptor activation
R-HSA-977444GABA B receptor activation
R-HSA-991365Activation of GABAB receptors

MSigDB gene sets: 242 (showing top): GOBP_POTASSIUM_ION_TRANSPORT, REACTOME_POTASSIUM_CHANNELS, REACTOME_INWARDLY_RECTIFYING_K_CHANNELS, MODULE_64, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, GOBP_MONOATOMIC_CATION_TRANSPORT, ONDER_CDH1_TARGETS_2_UP, ONDER_CDH1_SIGNALING_VIA_CTNNB1, REACTOME_TRANSMISSION_ACROSS_CHEMICAL_SYNAPSES, GOBP_IMPORT_INTO_CELL, chr21q22, GOBP_TRANSMEMBRANE_TRANSPORT, GOCC_POTASSIUM_CHANNEL_COMPLEX, GOCC_CATION_CHANNEL_COMPLEX, GOCC_TRANSPORTER_COMPLEX

GO Biological Process (5): potassium ion transport (GO:0006813), regulation of monoatomic ion transmembrane transport (GO:0034765), potassium ion import across plasma membrane (GO:1990573), monoatomic ion transport (GO:0006811), monoatomic ion transmembrane transport (GO:0034220)

GO Molecular Function (3): inward rectifier potassium channel activity (GO:0005242), G-protein activated inward rectifier potassium channel activity (GO:0015467), protein binding (GO:0005515)

GO Cellular Component (5): Golgi apparatus (GO:0005794), plasma membrane (GO:0005886), voltage-gated potassium channel complex (GO:0008076), membrane (GO:0016020), monoatomic ion channel complex (GO:0034702)

Reactome top-level categories

Rollup of top-9 pathways:

CategoryPathways
Neuronal System2
G protein gated Potassium channels1
Activation of GABAB receptors1
Transmission across Chemical Synapses1
Inwardly rectifying K+ channels1
Potassium Channels1
Neurotransmitter receptors and postsynaptic signal transmission1
GABA receptor activation1
GABA B receptor activation1

GO top-level categories

Rollup of top GO terms by namespace:

CategoryTerms
metal ion transport1
monoatomic ion transmembrane transport1
regulation of transmembrane transport1
regulation of monoatomic ion transport1
potassium ion transmembrane transport1
inorganic cation import across plasma membrane1
transport1
monoatomic ion transport1
transmembrane transport1
voltage-gated potassium channel activity1
ligand-gated monoatomic cation channel activity1
inward rectifier potassium channel activity1
binding1
cytoplasm1
endomembrane system1
intracellular membrane-bounded organelle1
membrane1
cell periphery1
potassium channel complex1
plasma membrane protein complex1
cellular anatomical structure1
transmembrane transporter complex1

Protein interactions and networks

STRING

1488 interactions, top by confidence (×1000):

Protein AProtein BPartner UniProtScore
KCNJ6INCENPQ9NQS7990
KCNJ6KCNJ9Q92806982
KCNJ6KCNJ3P48549978
KCNJ6CDCA8Q53HL2927
KCNJ6AURKBQ96GD4904
KCNJ6NBL1P41271879
KCNJ6KCNJ5P48544876
KCNJ6TMEM63CQ9P1W3844
KCNJ6TAB1Q15750795
KCNJ6XIAPP98170779
KCNJ6DRD2P14416768
KCNJ6SLC18A2Q05940693
KCNJ6SUCLG2Q96I99687
KCNJ6LMX1AQ8TE12685
KCNJ6BIRC2Q13490678

IntAct

181 interactions, top by confidence:

ABTypeScore
BET1KCNJ6psi-mi:“MI:0915”(physical association)0.560
PEX16KCNJ6psi-mi:“MI:0915”(physical association)0.560
THSD7BKCNJ6psi-mi:“MI:0915”(physical association)0.560
LEPROTL1KCNJ6psi-mi:“MI:0915”(physical association)0.560
LPCAT2KCNJ6psi-mi:“MI:0915”(physical association)0.560
STRIT1KCNJ6psi-mi:“MI:0915”(physical association)0.560
STATHKCNJ6psi-mi:“MI:0915”(physical association)0.560
MYO15BKCNJ6psi-mi:“MI:0915”(physical association)0.560
KCNJ6TMEM208psi-mi:“MI:0915”(physical association)0.560
FAM20BKCNJ6psi-mi:“MI:0915”(physical association)0.560
KCNJ6VSTM1psi-mi:“MI:0915”(physical association)0.560
KCNJ6SCAMP4psi-mi:“MI:0915”(physical association)0.560
KCNJ6ZDHHC24psi-mi:“MI:0915”(physical association)0.560
TMEM120BKCNJ6psi-mi:“MI:0915”(physical association)0.560
KCNJ6RTP2psi-mi:“MI:0915”(physical association)0.560
KCNJ6NRACpsi-mi:“MI:0915”(physical association)0.560
KCNJ6ERG28psi-mi:“MI:0915”(physical association)0.560
KCNJ6EDDM3Bpsi-mi:“MI:0915”(physical association)0.560
ITGAMKCNJ6psi-mi:“MI:0915”(physical association)0.560
APODKCNJ6psi-mi:“MI:0915”(physical association)0.560
HMOX2KCNJ6psi-mi:“MI:0915”(physical association)0.560
KCNJ6ORMDL2psi-mi:“MI:0915”(physical association)0.560
KCNJ6TMPPEpsi-mi:“MI:0915”(physical association)0.560

BioGRID (88): MB21D2 (Affinity Capture-MS), C4orf27 (Affinity Capture-MS), KCNJ6 (Affinity Capture-MS), KCNJ6 (Affinity Capture-MS), C1orf43 (Affinity Capture-MS), UFSP2 (Affinity Capture-MS), LRRC1 (Affinity Capture-MS), HSDL1 (Affinity Capture-MS), KCNJ6 (Reconstituted Complex), KCNJ6 (Two-hybrid), KCNJ6 (Two-hybrid), KCNJ6 (Two-hybrid), KCNJ6 (Two-hybrid), KCNJ6 (Two-hybrid), KCNJ6 (Two-hybrid)

ESM2 similar proteins: B7U540, E1BNE9, F1MYR9, F1NHE9, O02670, O02822, O18839, O19182, O70617, P35561, P48050, P48051, P48542, P48543, P48544, P48545, P48548, P48549, P48550, P49656, P49658, P52185, P52186, P52187, P52188, P52189, P52190, P52191, P52192, P63250, P63251, P63252, P63253, P70673, P97794, Q14500, Q14654, Q15842, Q4TZY1, Q5NVJ6

Diamond homologs: B7U540, E1BN00, E1BNE9, F1MYR9, F1NHE9, O02670, O02822, O18839, O19182, O60928, O70339, O70596, O70617, O88335, O88932, P35560, P35561, P48048, P48050, P48051, P48542, P48543, P48544, P48545, P48548, P48549, P48550, P49655, P49656, P49658, P52185, P52186, P52187, P52188, P52189, P52190, P52191, P52192, P63250, P63251

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

131 variants total. Per-class counts are floors (≥ shown; pagination cap):

ClassificationCount (floor)
Pathogenic1
Likely pathogenic1
Uncertain significance69
Likely benign42
Benign11

Top pathogenic / likely-pathogenic (2)

Variant IDHGVSClassification
189254NM_002240.5(KCNJ6):c.452CCA[1] (p.Thr152del)Pathogenic
189255NM_002240.5(KCNJ6):c.460G>A (p.Gly154Ser)Likely pathogenic

SpliceAI

2398 predictions. Top by Δscore:

VariantEffectΔscore
21:37625485:C:CAacceptor_loss1.0000
21:37625486:T:Aacceptor_loss1.0000
21:37715140:T:TCacceptor_gain1.0000
21:37840649:GCTAC:Gdonor_loss1.0000
21:37840650:CTACT:Cdonor_loss1.0000
21:37840652:ACT:Adonor_loss1.0000
21:37840653:C:CGdonor_loss1.0000
21:37840654:TCACT:Tdonor_loss1.0000
21:37840655:CACTC:Cdonor_loss1.0000
21:37840656:A:ACdonor_gain1.0000
21:37840656:A:Cdonor_loss1.0000
21:37840656:ACT:Adonor_gain1.0000
21:37840657:C:Adonor_loss1.0000
21:37840657:C:CAdonor_gain1.0000
21:37840657:CT:Cdonor_gain1.0000
21:37840657:CTC:Cdonor_gain1.0000
21:37840657:CTCA:Cdonor_gain1.0000
21:37840657:CTCAT:Cdonor_gain1.0000
21:37840710:C:CCacceptor_gain1.0000
21:37840716:G:Cacceptor_gain1.0000
21:37840716:G:GCacceptor_gain1.0000
21:37916393:AATT:Adonor_gain1.0000
21:37625163:A:Cdonor_gain0.9900
21:37625232:T:TAdonor_gain0.9900
21:37625480:CATCC:Cacceptor_gain0.9900
21:37625481:ATCC:Aacceptor_gain0.9900
21:37625482:TCC:Tacceptor_gain0.9900
21:37625483:CC:Cacceptor_gain0.9900
21:37625483:CCC:Cacceptor_gain0.9900
21:37625484:CC:Cacceptor_gain0.9900

AlphaMissense

2800 scored. Top likely-pathogenic:

VariantProtein changeam_pathogenicity
21:37625370:A:GF354S1.000
21:37625424:A:GF336S1.000
21:37625427:C:GR335P1.000
21:37625437:A:GW332R1.000
21:37625437:A:TW332R1.000
21:37625445:T:AE329V1.000
21:37625458:A:CY325D1.000
21:37625460:G:AS324F1.000
21:37625460:G:TS324Y1.000
21:37625461:A:GS324P1.000
21:37714211:C:AG316W1.000
21:37714228:C:TG310E1.000
21:37714229:C:GG310R1.000
21:37714229:C:TG310R1.000
21:37714234:A:GL308P1.000
21:37714234:A:TL308Q1.000
21:37714240:A:TV306D1.000
21:37714250:C:TE303K1.000
21:37714296:A:CS287R1.000
21:37714296:A:TS287R1.000
21:37714298:T:GS287R1.000
21:37714327:A:GL277P1.000
21:37714330:G:CP276R1.000
21:37714330:G:TP276Q1.000
21:37714331:G:AP276S1.000
21:37714331:G:TP276T1.000
21:37714339:A:GL273P1.000
21:37714342:A:GF272S1.000
21:37714370:C:AG263W1.000
21:37714441:G:TA239D1.000

dbSNP variants (sampled 300 via entrez): RS1000000128 (21:37863069 G>A), RS1000006159 (21:37838089 C>G,T), RS1000010589 (21:37855143 A>G), RS1000012826 (21:37721773 A>G), RS1000013330 (21:37903816 T>A,C), RS1000017007 (21:37903449 G>A), RS1000017213 (21:37901805 G>A), RS1000032368 (21:37875021 G>A), RS1000033927 (21:37665053 C>T), RS1000064337 (21:37715116 C>A), RS1000065534 (21:37780766 G>A), RS1000069592 (21:37821145 G>A), RS1000077733 (21:37910656 T>C), RS1000103884 (21:37754519 G>A,T), RS1000114270 (21:37792312 C>T)

Disease associations

OMIM: gene MIM:600877 | disease phenotypes: MIM:614098, MIM:181500

GenCC curated gene-disease

DiseaseClassificationInheritance
Keppen-Lubinsky syndromeStrongAutosomal dominant

Mondo (2): Keppen-Lubinsky syndrome (MONDO:0013572), schizophrenia (MONDO:0005090)

Orphanet (2): Keppen-Lubinsky syndrome (Orphanet:435628), NON RARE IN EUROPE: Schizophrenia (Orphanet:3140)

HPO phenotypes

52 total (30 of 52 shown, HPO-id order):

HPOTerm
HP:0000006Autosomal dominant inheritance
HP:0000194Open mouth
HP:0000212Gingival overgrowth
HP:0000218High palate
HP:0000252Microcephaly
HP:0000290Abnormal forehead morphology
HP:0000292Loss of facial adipose tissue
HP:0000298Mask-like facies
HP:0000322Short philtrum
HP:0000347Micrognathia
HP:0000430Underdeveloped nasal alae
HP:0000446Narrow nasal bridge
HP:0000496Abnormality of eye movement
HP:0000520Proptosis
HP:0000586Shallow orbits
HP:0001090Abnormally large globe
HP:0001249Intellectual disability
HP:0001250Seizure
HP:0001263Global developmental delay
HP:0001276Hypertonia
HP:0001285Spastic tetraparesis
HP:0001347Hyperreflexia
HP:0001371Flexion contracture
HP:0001508Failure to thrive
HP:0001561Polyhydramnios
HP:0002093Respiratory insufficiency
HP:0002094Dyspnea
HP:0002179Opisthotonus
HP:0002187Profound intellectual disability
HP:0002373Febrile seizure (within the age range of 3 months to 6 years)

GWAS associations

6 associations (top):

StudyTraitp-value
GCST001503_2Electroencephalographic traits in alcoholism5.000000e-10
GCST005790_45Rosacea symptom severity5.000000e-06
GCST009276_11Response to placebo treatment in childhood asthma (FVC change)9.000000e-06
GCST010989_161Body size at age 102.000000e-08
GCST011536_9Intestinal permeability measurement8.000000e-06
GCST012277_14Clostridioides difficle infection3.000000e-06

EFO canonical traits (7, from GWAS)

EFO IDTrait name
EFO:0004800frontal theta oscillation measurement
EFO:0009180rosacea severity measurement
EFO:0008344response to placebo
EFO:0010339FVC change measurement
EFO:0009819comparative body size at age 10, self-reported
EFO:0011031intestinal permeability measurement
EFO:0009130clostridium difficile infection

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (3): CHEMBL2406895 (SINGLE PROTEIN), CHEMBL3038489 (PROTEIN COMPLEX), CHEMBL3038490 (PROTEIN COMPLEX)

PharmGKB: 1 entry (VIP=true, CPIC=false)

PharmGKB clinical annotations

5 annotations.

VariantTypeLevelDrugsPhenotypes
rs2070995Other3methadoneHeroin Dependence
rs2070995Efficacy3AnalgesicsPain
rs2835859Dosage3fentanylPain;Postoperative
rs6517442Efficacy3morphinePain
rs6517442Dosage3opioidsLow Back Pain

PharmGKB variants

3 variants.

VariantGenesLevelScore#Clin annotsDrugs
rs2070995KCNJ633.252methadone;Analgesics
rs2835859KCNJ632.751fentanyl
rs6517442KCNJ635.002opioids;morphine

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: vgic — Inwardly rectifying potassium channels (KIR)

Most potent curated ligand interactions (20 total), top 20:

LigandActionAffinityParameter
PIP2Agonist6.3pKd
pimozideAntagonist5.5pEC50
SCH-23390Antagonist5.1pIC50
fluoxetineAntagonist4.8pIC50
desipramineAntagonist4.4pIC50
clomipramineAntagonist4.4pIC50
imipramineAntagonist4.3pIC50
thioridazineAntagonist4.2pEC50
bupivacaineAntagonist4.2pIC50
halothaneAntagonist4.2pIC50
F3Antagonist4.1pIC50
haloperidolAntagonist4.1pEC50
amitriptylineAntagonist4.0pIC50
maprotilineAntagonist4.0pIC50
verapamilAntagonist3.9pIC50
nortriptylineAntagonist3.9pIC50
clozapineAntagonist3.8pEC50
dizocilpineAntagonist3.7pIC50
QX-314Antagonist3.7pIC50
Na+Agonist1.6pEC50

ChEMBL bioactivities

181 potent at pChembl≥5 of 187 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChemblTypeValueUnitMolecule
7.48EC5033nMCHEMBL5178783
7.19EC5065nMCHEMBL4453299
7.19EC5064nMCHEMBL5192713
7.16EC5070nMCHEMBL2409110
7.09EC5081nMCHEMBL4461542
7.08EC5084nMCHEMBL4435859
7.06EC5088nMCHEMBL5206362
7.04EC5091nMCHEMBL5199523
7.02EC5096nMCHEMBL4453946
7.00IC50100nMCHEMBL5272051
6.96EC50111nMCHEMBL4529550
6.94EC50116nMCHEMBL4549232
6.94EC50116nMCHEMBL4458146
6.93EC50117nMCHEMBL4447978
6.89EC50129nMCHEMBL4530409
6.88EC50132nMCHEMBL5202704
6.88EC50133nMCHEMBL5192503
6.86EC50137nMCHEMBL5182581
6.84EC50146nMCHEMBL5187664
6.82EC50150nMCHEMBL3339145
6.82EC50150nMCHEMBL5186323
6.80EC50160nMCHEMBL2409106
6.79EC50163nMCHEMBL4473433
6.78EC50165nMCHEMBL5189637
6.76EC50175nMCHEMBL4543208
6.75EC50180nMCHEMBL4450006
6.75EC50176nMCHEMBL4457178
6.74EC50183nMCHEMBL4518000
6.74EC50183nMCHEMBL4536665
6.73EC50187nMCHEMBL4522066
6.73EC50187nMCHEMBL5209446
6.72EC50190nMCHEMBL2409108
6.70IC50200nMCHEMBL5286246
6.68EC50210nMCHEMBL2409132
6.62EC50241nMCHEMBL4529580
6.62EC50239nMCHEMBL5180586
6.57EC50270nMCHEMBL3339128
6.57EC50270nMCHEMBL3339144
6.57EC50271nMCHEMBL4586820
6.52EC50300nMCHEMBL4533916
6.51EC50310nMCHEMBL3339146
6.51EC50310nMCHEMBL3339147
6.47EC50340nMCHEMBL2409127
6.46EC50350nMCHEMBL2409131
6.43EC50375nMCHEMBL4451814
6.43EC50370nMCHEMBL4476625
6.42EC50380nMCHEMBL2409129
6.39EC50410nMCHEMBL2409113
6.36EC50440nMCHEMBL3339120
6.36EC50441nMCHEMBL4553987

PubChem BioAssay actives

181 with measured affinity, of 474 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

CompoundAssayTypeValueUnit
2-(2,4-dichlorophenoxy)-N-[2-(4,4-difluorocyclohexyl)-5-methylpyrazol-3-yl]acetamide1865719: Activation of GIRK1/2 channel (unknown origin) expressed in HEK293 cells incubated for 6 mins by thallium flux assayec500.0330uM
2-(2,4-dibromophenoxy)-N-[2-(1,1-dioxothiolan-3-yl)-5-methylpyrazol-3-yl]acetamide1865719: Activation of GIRK1/2 channel (unknown origin) expressed in HEK293 cells incubated for 6 mins by thallium flux assayec500.0640uM
N-(2-cyclohexyl-5-methylpyrazol-3-yl)-2-(4-phenylpyrazol-1-yl)acetamide1624836: Activation of human GIRK1/2 expressed in HEK293 cells co-expressing rat mGlu8 by thallium flux assayec500.0650uM
1-(2-benzyl-5-methylpyrazol-3-yl)-3-(3,4-difluorophenyl)urea762439: Activation of GIRK1/2 (unknown origin)ec500.0700uM
N-(2-cyclohexyl-5-methylpyrazol-3-yl)-2-[5-(3-fluorophenyl)tetrazol-2-yl]acetamide1624836: Activation of human GIRK1/2 expressed in HEK293 cells co-expressing rat mGlu8 by thallium flux assayec500.0810uM
N-[2-(4,4-difluorocyclohexyl)-5-methylpyrazol-3-yl]-2-(5-phenyltetrazol-2-yl)acetamide1624836: Activation of human GIRK1/2 expressed in HEK293 cells co-expressing rat mGlu8 by thallium flux assayec500.0840uM
2-(2,4-dichlorophenoxy)-N-[5-methyl-2-(oxan-4-yl)pyrazol-3-yl]acetamide1865719: Activation of GIRK1/2 channel (unknown origin) expressed in HEK293 cells incubated for 6 mins by thallium flux assayec500.0880uM
N-(2-cyclohexyl-5-methylpyrazol-3-yl)-2-(2,4-dichlorophenoxy)acetamide1865719: Activation of GIRK1/2 channel (unknown origin) expressed in HEK293 cells incubated for 6 mins by thallium flux assayec500.0910uM
N-(2-cyclohexyl-5-methylpyrazol-3-yl)-2-(5-phenyltetrazol-2-yl)acetamide1624836: Activation of human GIRK1/2 expressed in HEK293 cells co-expressing rat mGlu8 by thallium flux assayec500.0960uM
8-chloro-1-(2,6-dichlorophenyl)-5-[(2R)-2,3-dihydroxypropoxy]-2-(hydroxymethyl)-1,6-naphthyridin-4-one1952009: Inhibition of GIRK1/2 (unknown origin) channelic500.1000uM
N-(2-cyclohexyl-5-methylpyrazol-3-yl)-2-[5-(4-methylphenyl)tetrazol-2-yl]acetamide1624836: Activation of human GIRK1/2 expressed in HEK293 cells co-expressing rat mGlu8 by thallium flux assayec500.1110uM
N-(2-cyclohexyl-5-methylpyrazol-3-yl)-2-(4-phenyltriazol-1-yl)acetamide1624836: Activation of human GIRK1/2 expressed in HEK293 cells co-expressing rat mGlu8 by thallium flux assayec500.1160uM
N-(2-cyclohexyl-5-methylpyrazol-3-yl)-2-[5-(3,4-difluorophenyl)tetrazol-2-yl]acetamide1624836: Activation of human GIRK1/2 expressed in HEK293 cells co-expressing rat mGlu8 by thallium flux assayec500.1160uM
N-(2-cyclohexyl-5-methylpyrazol-3-yl)-2-[5-(3-methoxyphenyl)tetrazol-2-yl]acetamide1624836: Activation of human GIRK1/2 expressed in HEK293 cells co-expressing rat mGlu8 by thallium flux assayec500.1170uM
N-(2-cyclohexyl-5-methylpyrazol-3-yl)-2-[5-(3-methylphenyl)tetrazol-2-yl]acetamide1624836: Activation of human GIRK1/2 expressed in HEK293 cells co-expressing rat mGlu8 by thallium flux assayec500.1290uM
2-(4-bromo-2-chlorophenoxy)-N-[2-(1,1-dioxothiolan-3-yl)-5-methylpyrazol-3-yl]acetamide1865719: Activation of GIRK1/2 channel (unknown origin) expressed in HEK293 cells incubated for 6 mins by thallium flux assayec500.1320uM
2-(2,4-dichlorophenoxy)-N-(5-methyl-2-propan-2-ylpyrazol-3-yl)acetamide1865719: Activation of GIRK1/2 channel (unknown origin) expressed in HEK293 cells incubated for 6 mins by thallium flux assayec500.1330uM
2-(2,4-dichlorophenoxy)-N-[2-(1,1-dioxothiolan-3-yl)-5-methylpyrazol-3-yl]acetamide1865719: Activation of GIRK1/2 channel (unknown origin) expressed in HEK293 cells incubated for 6 mins by thallium flux assayec500.1370uM
2-[2,4-bis(trifluoromethyl)phenoxy]-N-[2-(1,1-dioxothiolan-3-yl)-5-methylpyrazol-3-yl]acetamide1865719: Activation of GIRK1/2 channel (unknown origin) expressed in HEK293 cells incubated for 6 mins by thallium flux assayec500.1460uM
1-(4-chlorophenyl)-3-[3-(2-methylcyclopropyl)-1-(2,2,2-trifluoroethyl)pyrazol-5-yl]urea1166626: Activation of GIRK1/2 (unknown origin) by thallium-flux based assayec500.1500uM
2-(2,5-dichlorophenoxy)-N-[2-(1,1-dioxothiolan-3-yl)-5-methylpyrazol-3-yl]acetamide1865719: Activation of GIRK1/2 channel (unknown origin) expressed in HEK293 cells incubated for 6 mins by thallium flux assayec500.1500uM
1-(3,4-difluorophenyl)-3-(5-methyl-2-phenylpyrazol-3-yl)urea1166626: Activation of GIRK1/2 (unknown origin) by thallium-flux based assayec500.1600uM
N-(2-cyclopentyl-5-methylpyrazol-3-yl)-2-(5-phenyltetrazol-2-yl)acetamide1624836: Activation of human GIRK1/2 expressed in HEK293 cells co-expressing rat mGlu8 by thallium flux assayec500.1630uM
2-(3-chloro-4-fluorophenyl)-N-(2-cyclohexyl-5-methylpyrazol-3-yl)acetamide1865719: Activation of GIRK1/2 channel (unknown origin) expressed in HEK293 cells incubated for 6 mins by thallium flux assayec500.1650uM
N-(2-cyclohexyl-5-methylpyrazol-3-yl)-2-[5-(4-methoxyphenyl)tetrazol-2-yl]acetamide1624836: Activation of human GIRK1/2 expressed in HEK293 cells co-expressing rat mGlu8 by thallium flux assayec500.1750uM
N-[2-(cyclohexylmethyl)-5-methylpyrazol-3-yl]-2-(5-phenyltetrazol-2-yl)acetamide1624836: Activation of human GIRK1/2 expressed in HEK293 cells co-expressing rat mGlu8 by thallium flux assayec500.1760uM
N-(2-cyclohexyl-5-methylpyrazol-3-yl)-2-[5-(4-fluorophenyl)tetrazol-2-yl]acetamide1624836: Activation of human GIRK1/2 expressed in HEK293 cells co-expressing rat mGlu8 by thallium flux assayec500.1800uM
N-(2-cyclohexyl-5-methylpyrazol-3-yl)-2-[5-[3-(trifluoromethyl)phenyl]tetrazol-2-yl]acetamide1624836: Activation of human GIRK1/2 expressed in HEK293 cells co-expressing rat mGlu8 by thallium flux assayec500.1830uM
2-[5-(3-cyanophenyl)tetrazol-2-yl]-N-(2-cyclohexyl-5-methylpyrazol-3-yl)acetamide1624836: Activation of human GIRK1/2 expressed in HEK293 cells co-expressing rat mGlu8 by thallium flux assayec500.1830uM
N-(2-cyclohexyl-5-methylpyrazol-3-yl)-2-[5-(2-fluorophenyl)tetrazol-2-yl]acetamide1624836: Activation of human GIRK1/2 expressed in HEK293 cells co-expressing rat mGlu8 by thallium flux assayec500.1870uM
2-(2,4-dichlorophenoxy)-N-[1-(1,1-dioxothiolan-3-yl)-3-ethylpyrazol-5-yl]acetamide1865719: Activation of GIRK1/2 channel (unknown origin) expressed in HEK293 cells incubated for 6 mins by thallium flux assayec500.1870uM
1-(3,4-difluorophenyl)-3-[2-(4-fluorophenyl)-5-methylpyrazol-3-yl]urea762439: Activation of GIRK1/2 (unknown origin)ec500.1900uM
3,5-dichloro-4-(5-fluoro-2-methyl-4-oxo-1,7-naphthyridin-1-yl)benzonitrile1951994: Inhibition of recombinant human GIRK1/2 channelic500.2000uM
1-(1-benzyl-3-cyclopropylpyrazol-5-yl)-3-(3-chloro-4-fluorophenyl)urea762439: Activation of GIRK1/2 (unknown origin)ec500.2100uM
2-(2,3-dichlorophenoxy)-N-[2-(1,1-dioxothiolan-3-yl)-5-methylpyrazol-3-yl]acetamide1865719: Activation of GIRK1/2 channel (unknown origin) expressed in HEK293 cells incubated for 6 mins by thallium flux assayec500.2390uM
N-(2-cyclohexyl-5-methylpyrazol-3-yl)-2-[5-[4-(trifluoromethyl)phenyl]tetrazol-2-yl]acetamide1624836: Activation of human GIRK1/2 expressed in HEK293 cells co-expressing rat mGlu8 by thallium flux assayec500.2410uM
1-[1-benzyl-3-(2-methylcyclopropyl)pyrazol-5-yl]-3-(3-fluorophenyl)urea1166626: Activation of GIRK1/2 (unknown origin) by thallium-flux based assayec500.2700uM
1-[3-(2-methylcyclopropyl)-1-(2,2,2-trifluoroethyl)pyrazol-5-yl]-3-(4-methylphenyl)urea1166626: Activation of GIRK1/2 (unknown origin) by thallium-flux based assayec500.2700uM
N-(1-cyclohexyl-3-cyclopropylpyrazol-5-yl)-2-(5-phenyltetrazol-2-yl)acetamide1624836: Activation of human GIRK1/2 expressed in HEK293 cells co-expressing rat mGlu8 by thallium flux assayec500.2710uM
2-[5-(3-chlorophenyl)tetrazol-2-yl]-N-(2-cyclohexyl-5-methylpyrazol-3-yl)acetamide1624836: Activation of human GIRK1/2 expressed in HEK293 cells co-expressing rat mGlu8 by thallium flux assayec500.3000uM
1-[3-(2-methylcyclopropyl)-1-(2,2,2-trifluoroethyl)pyrazol-5-yl]-3-[4-(trifluoromethyl)phenyl]urea1166626: Activation of GIRK1/2 (unknown origin) by thallium-flux based assayec500.3100uM
1-(3-fluorophenyl)-3-[3-(2-methylcyclopropyl)-1-(2,2,2-trifluoroethyl)pyrazol-5-yl]urea1166626: Activation of GIRK1/2 (unknown origin) by thallium-flux based assayec500.3100uM
1-(1-benzyl-3-cyclopropylpyrazol-5-yl)-3-[3-(trifluoromethyl)phenyl]urea762439: Activation of GIRK1/2 (unknown origin)ec500.3400uM
1-(1-benzyl-3-cyclopropylpyrazol-5-yl)-3-(4-fluorophenyl)urea762439: Activation of GIRK1/2 (unknown origin)ec500.3500uM
N-(2-cyclohexyl-5-methylpyrazol-3-yl)-2-(3-phenylphenyl)acetamide1624836: Activation of human GIRK1/2 expressed in HEK293 cells co-expressing rat mGlu8 by thallium flux assayec500.3700uM
N-(2-cyclohexyl-5-methylpyrazol-3-yl)-2-(5-phenyltriazol-1-yl)acetamide1624836: Activation of human GIRK1/2 expressed in HEK293 cells co-expressing rat mGlu8 by thallium flux assayec500.3750uM
1-(1-benzyl-3-cyclopropylpyrazol-5-yl)-3-(3-bromophenyl)urea762439: Activation of GIRK1/2 (unknown origin)ec500.3800uM
1-(3-cyclopropyl-1-phenylpyrazol-5-yl)-3-(3,4-difluorophenyl)urea762439: Activation of GIRK1/2 (unknown origin)ec500.4100uM
N-[5-methyl-2-(oxan-4-yl)pyrazol-3-yl]-2-(5-phenyltetrazol-2-yl)acetamide1624836: Activation of human GIRK1/2 expressed in HEK293 cells co-expressing rat mGlu8 by thallium flux assayec500.4350uM
1-(3,4-difluorophenyl)-3-[3-(2-methylcyclopropyl)-1-phenylpyrazol-5-yl]urea1166626: Activation of GIRK1/2 (unknown origin) by thallium-flux based assayec500.4400uM

CTD chemical–gene interactions

29 total (human), top 29 by PubMed support.

ChemicalActions (top 5)PubMed papers
Benzo(a)pyrenedecreases expression, increases methylation, affects methylation3
perfluorooctane sulfonic acidaffects cotreatment, decreases expression2
Copperaffects cotreatment, decreases expression, affects binding2
ammonium 2,3,3,3-tetrafluoro-2-(heptafluoropropoxy)-propanoateaffects cotreatment, decreases expression1
methylmercuric chloridedecreases expression1
bisphenol Aaffects cotreatment, increases methylation1
butyraldehydedecreases expression1
perfluorooctanoic acidaffects cotreatment, decreases expression1
Grape Seed Proanthocyanidinsaffects cotreatment, decreases expression1
perfluorobutanesulfonic aciddecreases expression, affects cotreatment1
bisphenol Sdecreases methylation1
jinfukangaffects cotreatment, decreases expression1
NSC 689534affects binding, decreases expression1
theaflavin-3,3’-digallateaffects expression1
Resveratrolaffects cotreatment, decreases expression1
Fulvestrantaffects cotreatment, increases methylation1
Catechinaffects cotreatment, decreases expression1
Cisplatinaffects cotreatment, decreases expression1
Cocainedecreases expression1
Leadincreases expression1
Potassiumincreases transport1
Smokeincreases expression1
Tetrachlorodibenzodioxinincreases expression1
Thalliumaffects binding, increases activity, increases transport1
Tobacco Smoke Pollutionincreases methylation1
Valproic Acidaffects expression1
1-Methyl-4-phenylpyridiniumincreases reaction, increases response to substance1
Crack Cocaineincreases expression1
Aflatoxin B1decreases methylation1

ChEMBL screening assays

25 unique, capped per target: 25 binding

Representative assays (with source publication via chembl_document):

Assay IDTypeDescriptionSource paper
CHEMBL2411640BindingActivation of GIRK2 (unknown origin)Discovery of ‘molecular switches’ within a GIRK activator scaffold that afford selective GIRK inhibitors. — Bioorg Med Chem Lett

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

First 10 cell lines (id-ordered, not curated):

CellosaurusNameCategorySex
CVCL_D1TBAbcam U-87MG KCNJ6 KOCancer cell lineMale

Clinical trials (associated diseases)

300 trials via MONDO — disease-level, not drug-specific.

TrialPhaseStatusTitle
NCT00000374PHASE4COMPLETEDTreatment for First-Episode Schizophrenia
NCT00001656PHASE4COMPLETEDComparison of Clozapine vs Olanzapine in Childhood-Onset Psychotic Disorders
NCT00007774PHASE4COMPLETEDTo Determine if Olanzapine is More Cost Effective Than Haloperidol for the Treatment of Schizophrenia
NCT00014001PHASE4COMPLETEDCATIE- Schizophrenia Trial
NCT00018668PHASE4COMPLETEDAntipsychotic Response in Schizophrenia
NCT00034801PHASE4COMPLETEDOlanzapine Versus Active Comparator in the Treatment of Depression in Patients With Schizophrenia
NCT00034905PHASE4COMPLETEDA Comparison of Seroquel vs. Risperidone in Schizophrenia
NCT00036088PHASE4COMPLETEDOlanzapine Versus An Active Comparator in the Treatment of Schizophrenia
NCT00044187PHASE4COMPLETEDThe Assessment of a Weight-Gain Agent for the Treatment of Olanzapine-Associated Anti-Obesity Agent in Patients With Schizophrenia, Schizophreniform Disorder, Schizoaffective Disorder, and Bipolar I Disorder
NCT00044655PHASE4COMPLETEDSwitching Medication to Treat Schizophrenia
NCT00048828PHASE4COMPLETEDTreating Drug-Resistant Childhood Schizophrenia
NCT00053703PHASE4COMPLETEDTreatment of Early Onset Schizophrenia Spectrum Disorders (TEOSS)
NCT00056498PHASE4COMPLETEDRisperidone Treatment in Schizophrenia Patients Who Are Currently Taking Clozapine
NCT00061802PHASE4COMPLETEDEfficacy and Safety of Two Atypical Antipsychotics vs. Placebo in Patients With an Acute Exacerbation of Either Schizophrenia or Schizoaffective Disorder
NCT00080327PHASE4COMPLETEDStudy of Three Doses of Aripiprazole in Patients With Acute Schizophrenia
NCT00088049PHASE4COMPLETEDStudy of Olanzapine vs. Aripiprazole in the Treatment of Schizophrenia
NCT00090012PHASE4COMPLETEDComparison of Continuing Olanzapine to Switching to Quetiapine in Overweight or Obese Patients With Schizophrenia and Schizoaffective Disorder
NCT00100776PHASE4COMPLETEDEfficacy of High Dose Olanzapine for the Treatment of Schizophrenia and Schizoaffective Disorder
NCT00103571PHASE4COMPLETEDOlanzapine Versus Aripiprazole in the Treatment of Acutely Ill Patients With Schizophrenia
NCT00108368PHASE4COMPLETEDThe Effects of Risperidone and Olanzapine on Thinking
NCT00114595PHASE4COMPLETEDEthyl-Eicosapentaenoic Acid and Tardive Dyskinesia
NCT00130923PHASE4COMPLETEDRisperidone Long-acting Versus Oral Risperidone in Patients With Schizophrenia and Alcohol Use Disorder
NCT00137020PHASE4COMPLETEDClinical Effect Of Cross Titration Of Antipsychotics With Ziprasidone In Schizophrenia Or Schizoaffective Disorder
NCT00140166PHASE4COMPLETEDTreatment of Acute Schizophrenia With Vitamin Therapy
NCT00145847PHASE4COMPLETEDNaltrexone Treatment of Alcohol Abuse in Schizophrenia
NCT00148564PHASE4COMPLETEDEnergy Homeostasis Under Treatment With Atypical Antipsychotics
NCT00156715PHASE4COMPLETEDEfficacy of Quetiapine in the Treatment of Patients With Schizophrenia and a Comorbid Substance Use Disorder
NCT00158223PHASE4COMPLETEDEffectiveness of Pimozide in Augmenting the Effects of Clozapine in the Treatment of Schizophrenia
NCT00159081PHASE4COMPLETEDOne Year Drug Treatment in First-Episode Schizophrenia
NCT00159120PHASE4COMPLETEDMaintenance Treatment vs. Stepwise Drug Discontinuation in First-Episode Schizophrenia
NCT00159133PHASE4COMPLETEDProdrome-Based Early Intervention With Antipsychotics vs. Benzodiazepines in First-Episode Schizophrenia
NCT00159757PHASE4TERMINATED12 Week Open, Non-Comparative Switch Study Of Oral Ziprazidone In Previously Treated Schizophrenic Patients
NCT00167817PHASE4COMPLETEDEffect of Switch to Aripiprazole on Health and Smoking Parameters in Patients With Schizophrenia: A Pilot Study
NCT00169026PHASE4TERMINATEDAlcoholism and Schizophrenia: Effects of Clozapine
NCT00169039PHASE4TERMINATEDClozapine Versus Chlorpromazine for Treatment-Unresponsive Schizophrenia
NCT00169065PHASE4COMPLETEDEffectiveness of Clozapine Versus Olanzapine for Treatment-resistant Schizophrenia
NCT00169091PHASE4TERMINATEDClozapine Versus Haloperidol for Treating the First Episode of Schizophrenia
NCT00176423PHASE4COMPLETEDEfficacy Study of Galantamine for Cognitive Impairments in Schizophrenia
NCT00176436PHASE4COMPLETEDAtomoxetine for Treatment of Weight Gain in Olanzapine or Clozapine Patients
NCT00177008PHASE4COMPLETEDAripiprazole for the Treatment of Schizophrenia With Co-Morbid Social Anxiety

About this page

Generated deterministically by Sugi Atlas from primary biomedical databases via BioBTree. Every record on this page traces to a primary source.

Generated
Atlas version
v1.1.2
BioBTree
v2.0.2

Sources 79

This page pulls from 79 datasets indexed by BioBTree:

alphafoldalphamissenseantibodybgeebgee_evidencebindingdbbiogrid_interactionbrendabrenda_kineticsccdscellosauruschembl_activitychembl_assaychembl_documentchembl_moleculechembl_targetciviccivic_evidenceclingen_dosageclingen_gene_validityclinical_trialsclinvarcollectrictd_gene_interactiondbsnpdepmapdiamond_similarityefoensemblentrezesm2_similarityexonfantom5_genefantom5_promotergenccgenerifgogoparentgtopdbgtopdb_interactiongwasgwas_studyhgnchpointactinterprointogenjasparmeshmimmirdbmondomsigdborphanetorthologparalogpdbpfampharmgkb_clinicalpharmgkb_genepharmgkb_guidelinepharmgkb_variantpubchempubchem_activitypubchem_assaypubmedreactomereactomeparentrefseqrhearnacentralscxa_expressionscxa_gene_experimentsignorspliceaistring_interactiontranscriptufeatureuniprot