KCNJ1

Summary

KCNJ1 (potassium inwardly rectifying channel subfamily J member 1, HGNC:6255) is a protein-coding gene on chromosome 11q24.3, encoding ATP-sensitive inward rectifier potassium channel 1 (P48048). Inward rectifier potassium channels are characterized by a greater tendency to allow potassium to flow into the cell rather than out of it.

Potassium channels are present in most mammalian cells, where they participate in a wide range of physiologic responses. The protein encoded by this gene is an integral membrane protein and inward-rectifier type potassium channel. It is activated by internal ATP and probably plays an important role in potassium homeostasis. The encoded protein has a greater tendency to allow potassium to flow into a cell rather than out of a cell. Mutations in this gene have been associated with antenatal Bartter syndrome, which is characterized by salt wasting, hypokalemic alkalosis, hypercalciuria, and low blood pressure. Multiple transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 3758 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Bartter disease type 2 (Definitive, ClinGen) — +1 more curated relationship
• Clinical variants (ClinVar): 351 total — 29 pathogenic, 36 likely-pathogenic
• Phenotypes (HPO): 49
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity no evidence
• MANE Select transcript: NM_153766

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6255
Approved symbol	KCNJ1
Name	potassium inwardly rectifying channel subfamily J member 1
Location	11q24.3
Locus type	gene with protein product
Status	Approved
Aliases	Kir1.1, ROMK1
Ensembl gene	ENSG00000151704
Ensembl biotype	protein_coding
OMIM	600359
Entrez	3758

Gene structure

Transcript identifiers

Ensembl transcripts: 15 — 14 protein_coding, 1 retained_intron

ENST00000324036, ENST00000392664, ENST00000392665, ENST00000392666, ENST00000440599, ENST00000531562, ENST00000857610, ENST00000857611, ENST00000857612, ENST00000857613, ENST00000857614, ENST00000857615, ENST00000923294, ENST00000923295, ENST00000923296

RefSeq mRNA: 5 — MANE Select: NM_153766 NM_000220, NM_153764, NM_153765, NM_153766, NM_153767

CCDS: CCDS8476, CCDS8477

Canonical transcript exons

ENST00000392666 — 3 exons

Exon	Start	End
ENSE00001384043	128850721	128850890
ENSE00001621272	128838020	128840264
ENSE00002170346	128867173	128867296

Expression profiles

Bgee: expression breadth ubiquitous, 131 present calls, max score 98.07.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.3184 / max 360.7590, expressed in 11 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
123115	0.2452	7
123116	0.0384	5
123114	0.0349	7

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
renal medulla	UBERON:0000362	98.07	gold quality
adult mammalian kidney	UBERON:0000082	96.29	gold quality
nephron tubule	UBERON:0001231	94.75	gold quality
kidney	UBERON:0002113	92.53	gold quality
metanephros cortex	UBERON:0010533	92.13	gold quality
kidney epithelium	UBERON:0004819	89.88	gold quality
metanephros	UBERON:0000081	84.08	gold quality
renal glomerulus	UBERON:0000074	83.78	gold quality
cortex of kidney	UBERON:0001225	83.23	gold quality
metanephric glomerulus	UBERON:0004736	82.96	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	82.28	silver quality
adult organism	UBERON:0007023	79.17	gold quality
choroid plexus epithelium	UBERON:0003911	70.27	gold quality
nucleus accumbens	UBERON:0001882	68.52	gold quality
colonic epithelium	UBERON:0000397	66.15	gold quality
putamen	UBERON:0001874	65.99	gold quality
diaphragm	UBERON:0001103	65.82	gold quality
bone marrow cell	CL:0002092	61.86	silver quality
cauda epididymis	UBERON:0004360	60.84	gold quality
endometrium epithelium	UBERON:0004811	60.53	gold quality
monocyte	CL:0000576	59.75	gold quality
mononuclear cell	CL:0000842	59.65	gold quality
hair follicle	UBERON:0002073	59.55	gold quality
caudate nucleus	UBERON:0001873	58.98	gold quality
granulocyte	CL:0000094	58.23	gold quality
leukocyte	CL:0000738	58.09	gold quality
skin of abdomen	UBERON:0001416	54.84	gold quality
left ventricle myocardium	UBERON:0006566	54.53	gold quality
amygdala	UBERON:0001876	54.02	gold quality
vastus lateralis	UBERON:0001379	53.95	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-HCAD-10	yes	15.96
E-ANND-3	no	2.41

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): NFAT5

miRNA regulators (miRDB)

56 targeting KCNJ1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-4778-3P	99.93	70.40	1818
HSA-MIR-4698	99.84	71.41	4303
HSA-MIR-6844	99.82	70.69	2423
HSA-MIR-6739-5P	99.80	67.87	2806
HSA-MIR-4659A-3P	99.80	72.62	4248
HSA-MIR-4659B-3P	99.80	72.62	4248
HSA-MIR-204-5P	99.79	71.62	2439
HSA-MIR-211-5P	99.79	71.65	2440
HSA-MIR-92A-2-5P	99.75	67.01	2164
HSA-MIR-6733-5P	99.74	67.94	2759
HSA-MIR-4699-3P	99.71	70.15	3142
HSA-MIR-4677-5P	99.70	70.09	1940
HSA-MIR-7154-5P	99.69	70.52	1900
HSA-MIR-646	99.68	67.84	1645
HSA-MIR-587	99.64	70.86	2611
HSA-MIR-3153	99.55	67.59	2337
HSA-MIR-1252-3P	99.55	67.71	2862
HSA-MIR-6507-3P	99.35	67.32	1059
HSA-MIR-1206	99.30	69.32	1016
HSA-MIR-4477B	99.23	70.49	1733
HSA-MIR-323B-3P	99.14	68.89	725
HSA-MIR-4738-3P	98.98	67.98	1846
HSA-MIR-5701	98.97	69.54	1502

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 38)

• ROMK1 is a substrate of PKC and that serine residues 4 and 201 are the two main PKC phosphorylation sites that are essential for the expression of ROMK1 in the cell surface (PMID:12221079)
• One disease-causing mutation in the ROMK channel truncates the extreme COOH-terminus and induces a closed gating conformation. (PMID:12381810)
• In a heterozgous Bartter syndrome patient, AA exchanges Arg338Stop & Met357Thr in ROMK exon 5 alter the C-terminus of the ROMK protein & can affect channel function. (PMID:12589089)
• Findings support the proposed role of ROMK channels in potassium recycling and in the regulation of K+ secretion and present a rationale for the phenotype observed in patients with ROMK deficiency. (PMID:15895241)
• NH(2)-terminal phosphorylation modifying a COOH-terminal ER retention signal in ROMK1 could serve as a checkpoint for proper subunit folding critical to channel gating. (PMID:15987778)
• ROMK is antagonistically regulated by long and kidney-specific WNK1 isoforms (PMID:16428287)
• molecular mechanism for stimulation of endocytosis of ROMK1 by WNK kinases (PMID:17380208)
• A novel mutation in KCNJ1 in a Bartter syndrome case diagnosed as pseudohypoaldosteronism. (PMID:17401586)
• CD63 plays a role in the regulation of ROMK channels through its association with RPTPalpha, which in turn interacts with and activates Src family PTK, thus reducing ROMK activity. (PMID:18211905)
• Members of the Framingham Heart Study were screened for variation in three genes-SLC12A3, SLC12A1 and KCNJ1 causing rare recessive diseases featuring large reductions in blood pressure. (PMID:18391953)
• Five polymorphisms in the KCNJ1 gene coding for the potassium channel, ROMK, showed associations with mean 24-hour systolic or diastolic blood pressure. (PMID:18443236)
• Multiple intra- and/or intermolecular interactions of WNK1 domains are at play for regulation of ROMK1 by WNK1 in the kidney. (PMID:18550644)
• These results confirm the important role of the acidic motif of WNK4 in its protein-protein interaction with the ROMK channel. (PMID:18755144)
• In a large cohort of ante/neonatal Bartter syndrome, deafness, transient hyperkalaemia and severe hypokalaemic hypochloraemic alkalosis orientate molecular investigations to BSND, KCNJ1 and CLCNKB genes, respectively. (PMID:19096086)
• hydrophobic leucines at the cytoplasmic end of the inner transmembrane helices comprise the principal pH gate of Kir1.1, a gate that can be relocated from 160-Kir1.1b to 157-Kir1.1b. (PMID:19170254)
• KS-WNK1 is an important physiological regulator of renal K(+) excretion, likely through its effects on the ROMK1 channel. (PMID:19244242)
• These results suggest that the conformation of the cytoplasmic pore in the Kir1.1 channel changes in response to pHi gating such that the N- and C-termini move apart from each other at pHi 7.4, when the channel is open. (PMID:19272129)
• Regulation of renal outer medullary potassium channel and renal K(+) excretion by Klotho. (PMID:19349416)
• c-Src inhibits SGK1-mediated phosphorylation hereby restoring the WNK4-mediated inhibition of ROMK channels thus suppressing K secretion. (PMID:19706464)
• POSH inhibits ROMK channels by enhancing dynamin-dependent and clathrin-independent endocytosis and by stimulating ubiquitination of ROMK channels. (PMID:19710010)
• KCNJ1 mutations are associated with Bartter syndrome. (PMID:20219833)
• THGP modulation of ROMK function confers a new role of THGP on renal ion transport and may contribute to salt wasting observed in FJHN/MCKD-2/GCKD patients. (PMID:21081491)
• PI3K-activating hormones inhibit ROMK by enhancing its endocytosis via a mechanism that involves phosphorylation of WNK1 by Akt1 and SGK1. (PMID:21355052)
• no mutation in the KCNJ1 gene, among patients suffering from bartter and Gitelman syndromes (PMID:21631963)
• A KCNJ1 SNP was associated with increased FG during HCTZ treatment. (PMID:22907731)
• Findings suggest that 11q24 is a susceptible locus for openness, with KCNJ1 as the possible candidate gene. (PMID:23211697)
• Molecular analysis revealed a compound heterozygous mutation in the KCNJ1 gene, consisting of a novel K76E and an already described V315G mutation, both affecting functional domains of the channel protein. (PMID:23782368)
• The association between polymorphisms in KCNJ1, SLC12A1, and 7 other genes and calcium intake and colorectal neoplasia risk was studied. (PMID:25165391)
• knockdown of KCNJ1 in HK-2 cells promoted cell proliferation. Collectively, these data highlight that KCNJ1, low-expressed in ccRCC and associated with poor prognosis, plays an important role in ccRCC cell growth and metastasis (PMID:25344677)
• WNK4 is a substrate of SFKs and the association of c-Src and PTP-1D with WNK4 at Tyr(1092) and Tyr(1143) plays an important role in modulating the inhibitory effect of WNK4 on ROMK (PMID:25805816)
• Data suggest underlying pathology for some patients with type II Bartter syndrome is linked to stability of ROMK1 in ERAD pathway; using a yeast expression system, cells can be rescued by wild-type (rat) ROMK1 but not by ROMK1 containing any one of four mutations found in (human) type II Bartter syndrome; mutant ROMKs are significantly less stable than wild-type ROMK. (ERAD = endoplasmic reticulum-associated degradation) (PMID:28630040)
• endosomal trafficking factors CORVET and ESCRT suppress plasma membrane residence of the renal outer medullary potassium channel (PMID:29311259)
• The presence of ROMK protein was observed in the inner mitochondrial membrane fraction. Moreover, colocalization of the ROMK protein and a mitochondrial marker in the mitochondria of fibroblast cells was shown by immunofluorescence. (PMID:29458000)
• We replicated the methods in a previous study to detect rare and potentially loss-of-function variants in SLC12A3, SLC12A1, and KCNJ1 reducing blood pressure in variant carriers as compared with noncarriers using whole exome sequencing data. Our study confirmed that SLC12A3, SLC12A1, and KCNJ1 are indeed genes protective of hypertension in the general population. (PMID:30113482)
• Single-Channel Properties of the ROMK-Pore-Forming Subunit of the Mitochondrial ATP-Sensitive Potassium Channel. (PMID:31731540)
• Eight novel KCNJ1 variants and parathyroid hormone overaction or resistance in 5 probands with Bartter syndrome type 2. (PMID:33058840)
• Solubilization, purification, and functional reconstitution of human ROMK potassium channel in copolymer styrene-maleic acid (SMA) nanodiscs. (PMID:33444624)
• Association of polymorphisms of calcium reabsorption genes SLC12A1, KCNJ1 and SLC8A1 with colorectal adenoma. (PMID:37074453)

Cross-species orthologs

15 orthologs

Organism	Symbol	Gene ID
danio_rerio	kcnj1b	ENSDARG00000002666
danio_rerio	kcnj1a.3	ENSDARG00000086248
danio_rerio	kcnj1a.6	ENSDARG00000088484
danio_rerio	kcnj1a.5	ENSDARG00000089060
danio_rerio	kcnj1a.4	ENSDARG00000090635
danio_rerio	kcnj1a.2	ENSDARG00000090866
danio_rerio	kcnj1a.1	ENSDARG00000091232
mus_musculus	Kcnj1	ENSMUSG00000041248
rattus_norvegicus	Kcnj1	ENSRNOG00000059005
drosophila_melanogaster	Irk3	FBGN0032706
drosophila_melanogaster	Irk2	FBGN0039081
drosophila_melanogaster	Irk1	FBGN0265042
caenorhabditis_elegans		WBGENE00002149
caenorhabditis_elegans		WBGENE00002150
caenorhabditis_elegans		WBGENE00002151

Paralogs (15): KCNJ13 (ENSG00000115474), KCNJ5 (ENSG00000120457), KCNJ8 (ENSG00000121361), KCNJ2 (ENSG00000123700), KCNJ16 (ENSG00000153822), KCNJ6 (ENSG00000157542), KCNJ15 (ENSG00000157551), KCNJ9 (ENSG00000162728), KCNJ3 (ENSG00000162989), KCNJ4 (ENSG00000168135), KCNJ10 (ENSG00000177807), KCNJ14 (ENSG00000182324), KCNJ12 (ENSG00000184185), KCNJ11 (ENSG00000187486), KCNJ18 (ENSG00000260458)

Protein

Protein identifiers

ATP-sensitive inward rectifier potassium channel 1 — P48048 (reviewed: P48048)

Alternative names: ATP-regulated potassium channel ROM-K, Inward rectifier K(+) channel Kir1.1, Potassium channel, inwardly rectifying subfamily J member 1

All UniProt accessions (1): P48048

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 channel is activated by internal ATP and can be blocked by external barium. In the kidney, probably plays a major role in potassium homeostasis.

Subunit / interactions. Interacts with SGK1 and SLC9A3R2/NHERF2.

Subcellular location. Cell membrane.

Tissue specificity. In the kidney and pancreatic islets. Lower levels in skeletal muscle, pancreas, spleen, brain, heart and liver.

Post-translational modifications. Phosphorylation at Ser-44 by SGK1 is necessary for its expression at the cell membrane.

Disease relevance. Bartter syndrome 2, antenatal (BARTS2) [MIM:241200] A form of Bartter syndrome, an autosomal recessive disorder characterized by impaired salt reabsorption in the thick ascending loop of Henle with pronounced salt wasting, hypokalemic metabolic alkalosis, and varying degrees of hypercalciuria. BARTS2 is a life-threatening condition beginning in utero, with marked fetal polyuria that leads to polyhydramnios and premature delivery. Another hallmark is a marked hypercalciuria and, as a secondary consequence, the development of nephrocalcinosis and osteopenia. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Inhibited by WNK3. 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. KCNJ1 subfamily.

Isoforms (3)

UniProt ID	Names	Canonical?
P48048-1	1, ROM-K1	yes
P48048-2	2, 2-4-5, ROM-K2, ROM-K4, ROM-K5, ROM-K6
P48048-3	3, ROM-K3

RefSeq proteins (5): NP_000211, NP_722448, NP_722449, NP_722450, NP_722451 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003268	K_chnl_inward-rec_Kir1.1	Family
IPR013518	K_chnl_inward-rec_Kir_cyto	Homologous_superfamily
IPR014756	Ig_E-set	Homologous_superfamily
IPR016449	K_chnl_inward-rec_Kir	Family
IPR040445	Kir_TM	Domain
IPR041647	IRK_C	Domain

Pfam: PF01007, PF17655

Catalyzed reactions (Rhea), 1 shown:

• K(+)(in) = K(+)(out) (RHEA:29463)

UniProt features (32 total): sequence variant 15, topological domain 4, splice variant 2, transmembrane region 2, intramembrane region 2, chain 1, short sequence motif 1, binding site 1, site 1, modified residue 1, glycosylation site 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P48048-F1	84.79	0.56

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): 171 (role in the control of polyamine-mediated channel gating and in the blocking by intracellular magnesium)

Ligand- & substrate-binding residues (1): 223–230

Post-translational modifications (1): 44

Glycosylation sites (1): 117

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-1296067	Potassium transport channels
R-HSA-112316	Neuronal System
R-HSA-1296065	Inwardly rectifying K+ channels
R-HSA-1296071	Potassium Channels

MSigDB gene sets: 251 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_DN, GOBP_POTASSIUM_ION_TRANSPORT, REACTOME_POTASSIUM_CHANNELS, REACTOME_INWARDLY_RECTIFYING_K_CHANNELS, MODULE_511, GOCC_CELL_SURFACE, RACCACAR_AML_Q6, GOBP_MONOATOMIC_CATION_TRANSPORT, AML_Q6, WTGAAAT_UNKNOWN, HNF1_C, RYTTCCTG_ETS2_B, GOBP_MULTICELLULAR_ORGANISMAL_LEVEL_HOMEOSTASIS, AML1_01, PTF1BETA_Q6

GO Biological Process (12): kidney development (GO:0001822), tissue homeostasis (GO:0001894), monoatomic ion transport (GO:0006811), post-embryonic development (GO:0009791), gene expression (GO:0010467), regulation of monoatomic ion transmembrane transport (GO:0034765), renal sodium ion absorption (GO:0070294), circulatory system development (GO:0072359), potassium ion import across plasma membrane (GO:1990573), potassium ion transport (GO:0006813), metal ion transport (GO:0030001), monoatomic ion transmembrane transport (GO:0034220)

GO Molecular Function (6): inward rectifier potassium channel activity (GO:0005242), potassium channel activity (GO:0005267), ATP binding (GO:0005524), phosphatidylinositol-4,5-bisphosphate binding (GO:0005546), ATP-activated inward rectifier potassium channel activity (GO:0015272), nucleotide binding (GO:0000166)

GO Cellular Component (4): plasma membrane (GO:0005886), cell surface (GO:0009986), monoatomic ion channel complex (GO:0034702), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Inwardly rectifying K+ channels	1
Potassium Channels	1
Neuronal System	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
animal organ development	1
renal system development	1
multicellular organismal-level homeostasis	1
anatomical structure homeostasis	1
transport	1
multicellular organism development	1
multicellular organismal process	1
macromolecule biosynthetic process	1
monoatomic ion transmembrane transport	1
regulation of transmembrane transport	1
regulation of monoatomic ion transport	1
renal sodium ion transport	1
renal absorption	1
system development	1
potassium ion transmembrane transport	1
inorganic cation import across plasma membrane	1
metal ion transport	1
monoatomic cation transport	1
monoatomic ion transport	1
transmembrane transport	1
voltage-gated potassium channel activity	1
ligand-gated monoatomic cation channel activity	1
monoatomic cation channel activity	1
potassium ion transmembrane transporter activity	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
phosphatidylinositol phosphate binding	1
phosphatidylinositol bisphosphate binding	1
inward rectifier potassium channel activity	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
membrane	1
cell periphery	1
transmembrane transporter complex	1

Protein interactions and networks

STRING

1054 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
KCNJ1	SLC12A1	Q13621	984
KCNJ1	WNK4	Q96J92	967
KCNJ1	SLC12A3	P55017	959
KCNJ1	CLCNKB	P51801	933
KCNJ1	WNK1	P54963	932
KCNJ1	BSND	Q8WZ55	913
KCNJ1	CFTR	P13569	871
KCNJ1	CASR	P41180	860
KCNJ1	STK39	Q9UEW8	846
KCNJ1	WNK3	Q9BYP7	844
KCNJ1	CLCNKA	P51800	826
KCNJ1	ITSN1	Q15811	811
KCNJ1	KCNMA1	Q12791	803
KCNJ1	SGK1	O00141	770
KCNJ1	OXSR1	O95747	762

IntAct

109 interactions, top by confidence:

A	B	Type	Score
KCNJ1	PDZK1	psi-mi:“MI:0407”(direct interaction)	0.440
KCNJ1	NHERF2	psi-mi:“MI:0407”(direct interaction)	0.440
KCNJ1	MAST2	psi-mi:“MI:0407”(direct interaction)	0.440
KCNJ1	SNX27	psi-mi:“MI:0407”(direct interaction)	0.440
KCNJ1	MAST1	psi-mi:“MI:0407”(direct interaction)	0.440
KCNJ1	SYNJ2BP	psi-mi:“MI:0407”(direct interaction)	0.440
KCNJ1	PDZD7	psi-mi:“MI:0407”(direct interaction)	0.440
KCNJ1	PTPN3	psi-mi:“MI:0407”(direct interaction)	0.440
PICK1	KCNJ1	psi-mi:“MI:0407”(direct interaction)	0.440
KCNJ1	TAX1BP3	psi-mi:“MI:0407”(direct interaction)	0.440
HTRA4	KCNJ1	psi-mi:“MI:0407”(direct interaction)	0.440
KCNJ1	MAGI2	psi-mi:“MI:0407”(direct interaction)	0.440
KCNJ1	ARHGAP21	psi-mi:“MI:0407”(direct interaction)	0.440
KCNJ1	LNX1	psi-mi:“MI:0407”(direct interaction)	0.440
APBA3	KCNJ1	psi-mi:“MI:0407”(direct interaction)	0.440
KCNJ1	MPP2	psi-mi:“MI:0407”(direct interaction)	0.440
LIN7C	KCNJ1	psi-mi:“MI:0407”(direct interaction)	0.440
KCNJ1	PALS2	psi-mi:“MI:0407”(direct interaction)	0.440
KCNJ1	TIAM2	psi-mi:“MI:0407”(direct interaction)	0.440
KCNJ1	RAPGEF6	psi-mi:“MI:0407”(direct interaction)	0.440
KCNJ1	MAGI3	psi-mi:“MI:0407”(direct interaction)	0.440
KCNJ1	NHERF4	psi-mi:“MI:0407”(direct interaction)	0.440
KCNJ1	FRMPD2	psi-mi:“MI:0407”(direct interaction)	0.440
KCNJ1	WHRN	psi-mi:“MI:0407”(direct interaction)	0.440
KCNJ1	DLG4	psi-mi:“MI:0407”(direct interaction)	0.440
KCNJ1	LIMK2	psi-mi:“MI:0407”(direct interaction)	0.440
KCNJ1	GRID2IP	psi-mi:“MI:0407”(direct interaction)	0.440
KCNJ1	CASK	psi-mi:“MI:0407”(direct interaction)	0.440
KCNJ1	FRMPD3	psi-mi:“MI:0407”(direct interaction)	0.440
KCNJ1	PATJ	psi-mi:“MI:0407”(direct interaction)	0.440

BioGRID (10): SLC9A3R1 (Reconstituted Complex), SLC9A3R2 (Reconstituted Complex), KCNJ1 (Affinity Capture-Western), SLC9A3R1 (Two-hybrid), SLC9A3R2 (Two-hybrid), KCNJ1 (Affinity Capture-Western), KCNJ1 (Reconstituted Complex), SH3RF1 (Reconstituted Complex), SH3RF1 (Affinity Capture-Western), KCNJ1 (Biochemical Activity)

ESM2 similar proteins: B7U540, E1BNE9, F1MYR9, F1NHE9, O02670, O18839, O19182, O70339, O88335, O88932, P35560, P35561, P48048, P48050, P48051, P48542, P48543, P48544, P48545, P48548, P48549, P48550, P49655, P49656, P49658, P52185, P52186, P52187, P52188, P52189, P52190, P52191, P63250, P63251, P63252, P63253, P70673, P78508, Q14500, Q4TZY1

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

6 interactions.

A	Effect	B	Mechanism
PRKCD	“up-regulates activity”	KCNJ1
SRC	down-regulates	KCNJ1	phosphorylation
PKC	“up-regulates activity”	KCNJ1	phosphorylation
PRKCA	“down-regulates activity”	KCNJ1	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 74 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Ras activation upon Ca2+ influx through NMDA receptor	5	57.1×	1e-06
Unblocking of NMDA receptors, glutamate binding and activation	5	54.4×	1e-06
Negative regulation of NMDA receptor-mediated neuronal transmission	5	54.4×	1e-06
Long-term potentiation	5	47.6×	2e-06
Assembly and cell surface presentation of NMDA receptors	9	45.7×	4e-11
Neurexins and neuroligins	9	35.4×	2e-10
Protein-protein interactions at synapses	5	26.6×	3e-05

GO biological processes:

GO term	Partners	Fold	FDR
establishment or maintenance of epithelial cell apical/basal polarity	10	81.8×	8e-15
receptor clustering	7	61.5×	4e-09
protein localization to synapse	5	53.9×	2e-06
regulation of postsynaptic membrane neurotransmitter receptor levels	6	41.9×	5e-07
cell-cell adhesion	10	14.3×	2e-07
protein-containing complex assembly	7	11.2×	1e-04
protein localization to plasma membrane	5	7.7×	8e-03
chemical synaptic transmission	7	7.6×	1e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	29
Likely pathogenic	36
Uncertain significance	144
Likely benign	98
Benign	8

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1804660	NM_153766.3(KCNJ1):c.874C>T (p.Arg292Trp)	Pathogenic
2627549	NM_153766.3(KCNJ1):c.514A>C (p.Thr172Pro)	Pathogenic
2697319	NM_153766.3(KCNJ1):c.906G>A (p.Trp302Ter)	Pathogenic
2705732	NM_153766.3(KCNJ1):c.173G>A (p.Trp58Ter)	Pathogenic
2714622	NM_153766.3(KCNJ1):c.808C>T (p.Gln270Ter)	Pathogenic
2719899	NM_153766.3(KCNJ1):c.737del (p.Pro246fs)	Pathogenic
2735789	NM_153766.3(KCNJ1):c.174G>A (p.Trp58Ter)	Pathogenic
2735790	NM_153766.3(KCNJ1):c.163G>T (p.Asp55Tyr)	Pathogenic
2801479	NM_153766.3(KCNJ1):c.194del (p.Phe65fs)	Pathogenic
2821892	NM_153766.3(KCNJ1):c.-6G>T	Pathogenic
2834982	NM_153766.3(KCNJ1):c.499A>T (p.Lys167Ter)	Pathogenic
2840459	NM_153766.3(KCNJ1):c.135del (p.Phe46fs)	Pathogenic
2875630	NM_153766.3(KCNJ1):c.918del (p.Phe306fs)	Pathogenic
2898592	NM_153766.3(KCNJ1):c.485del (p.Lys162fs)	Pathogenic
2996445	NM_153766.3(KCNJ1):c.-21-2117G>A	Pathogenic
3004651	NM_153766.3(KCNJ1):c.659del (p.Gly220fs)	Pathogenic
3646997	NM_153766.3(KCNJ1):c.221_231del (p.Phe74fs)	Pathogenic
3719570	NM_153766.3(KCNJ1):c.644_645del (p.Thr215fs)	Pathogenic
373897	NM_153766.3(KCNJ1):c.262A>T (p.Lys88Ter)	Pathogenic
4700701	NM_153766.3(KCNJ1):c.919del (p.Ala307fs)	Pathogenic
586075	NM_153766.3(KCNJ1):c.1001dup (p.His335fs)	Pathogenic
631655	NM_153766.3(KCNJ1):c.155C>T (p.Thr52Met)	Pathogenic
872042	NM_153766.3(KCNJ1):c.939_942del (p.Glu315fs)	Pathogenic
9153	NM_153766.3(KCNJ1):c.180C>G (p.Tyr60Ter)	Pathogenic
9154	NM_153766.3(KCNJ1):c.42dup (p.Gly15fs)	Pathogenic
9155	NM_153766.3(KCNJ1):c.600C>G (p.Ser200Arg)	Pathogenic
9156	KCNJ1, TRP58TER	Pathogenic
9161	NM_153766.3(KCNJ1):c.265G>C (p.Asp89His)	Pathogenic
9162	NM_153766.3(KCNJ1):c.315T>A (p.Asn105Lys)	Pathogenic
1333621	NM_153766.3(KCNJ1):c.550C>T (p.Arg184Trp)	Likely pathogenic

SpliceAI

679 predictions. Top by Δscore:

Variant	Effect	Δscore
11:128867168:CTTA:C	donor_loss	1.0000
11:128867169:TTAC:T	donor_loss	1.0000
11:128867170:TAC:T	donor_loss	1.0000
11:128867167:TCTTA:T	donor_loss	0.9900
11:128836507:CCCT:C	acceptor_gain	0.9800
11:128836508:CCT:C	acceptor_gain	0.9800
11:128867172:CCT:C	donor_gain	0.9800
11:128867171:A:AC	donor_gain	0.9700
11:128867172:C:CC	donor_gain	0.9700
11:128836506:CCCCT:C	acceptor_gain	0.9600
11:128836510:T:C	acceptor_gain	0.9600
11:128840264:TCTGA:T	acceptor_loss	0.9500
11:128840265:CTGA:C	acceptor_loss	0.9500
11:128842277:C:CA	donor_gain	0.9500
11:128862880:A:AC	donor_gain	0.9500
11:128840260:CTGAT:C	acceptor_gain	0.9400
11:128866663:A:T	acceptor_gain	0.9400
11:128841718:TA:T	donor_gain	0.9300
11:128841719:AA:A	donor_gain	0.9300
11:128841719:AAC:A	donor_gain	0.9300
11:128841725:G:C	donor_gain	0.9300
11:128840261:TGAT:T	acceptor_gain	0.9200
11:128840262:GAT:G	acceptor_gain	0.9200
11:128840265:C:CC	acceptor_gain	0.9100
11:128852755:T:TA	donor_gain	0.9100
11:128841720:A:C	donor_gain	0.9000
11:128840262:GATCT:G	acceptor_gain	0.8900
11:128840263:ATCTG:A	acceptor_gain	0.8900
11:128852756:C:A	donor_gain	0.8900
11:128862890:T:C	donor_gain	0.8700

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000046652 (11:128846731 C>A), RS1000110955 (11:128855634 T>C), RS1000138089 (11:128851017 A>G), RS1000369898 (11:128839562 T>C), RS1000533330 (11:128841772 A>G), RS1000739852 (11:128840653 G>A,T), RS1000846277 (11:128868679 A>G), RS1000939154 (11:128867966 G>A), RS1001003404 (11:128856081 C>G,T), RS1001054582 (11:128846902 A>G), RS1001116902 (11:128862178 A>G), RS1001136296 (11:128867994 T>C), RS1001337325 (11:128857208 G>A), RS1001463064 (11:128867854 T>C), RS1001477464 (11:128864288 G>A)

Disease associations

OMIM: gene MIM:600359 | disease phenotypes: MIM:241200, MIM:601678

GenCC curated gene-disease

Disease	Classification	Inheritance
Bartter disease type 2	Definitive	Autosomal recessive
antenatal Bartter syndrome	Supportive	Autosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
Bartter disease type 2	Definitive	AR

Mondo (4): Bartter disease type 2 (MONDO:0009424), prostate cancer (MONDO:0008315), Bartter syndrome (MONDO:0015231), (MONDO:0100343)

Orphanet (3): Bartter syndrome (Orphanet:112), Bartter syndrome type 2 (Orphanet:620220), Familial prostate cancer (Orphanet:1331)

HPO phenotypes

49 total (30 of 49 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000103	Polyuria
HP:0000111	Renal juxtaglomerular cell hypertrophy/hyperplasia
HP:0000121	Nephrocalcinosis
HP:0000127	Renal salt wasting
HP:0000128	Renal potassium wasting
HP:0000256	Macrocephaly
HP:0000325	Triangular face
HP:0000400	Macrotia
HP:0000841	Hyperactive renin-angiotensin system
HP:0000848	Increased circulating renin concentration
HP:0000859	Increased circulating aldosterone concentration
HP:0000934	Chondrocalcinosis
HP:0000938	Osteopenia
HP:0001090	Abnormally large globe
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001263	Global developmental delay
HP:0001281	Tetany
HP:0001508	Failure to thrive
HP:0001518	Small for gestational age
HP:0001561	Polyhydramnios
HP:0001563	Fetal polyuria
HP:0001622	Premature birth
HP:0001944	Dehydration
HP:0001945	Fever
HP:0001959	Polydipsia
HP:0001960	Hypokalemic metabolic alkalosis
HP:0002007	Frontal bossing
HP:0002013	Vomiting

GWAS associations

0 associations (top):

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D001477	Bartter Syndrome	C12.050.351.968.419.815.279; C12.200.777.419.815.279; C12.950.419.815.279; C19.053.800.604.249
D011471	Prostatic Neoplasms	C04.588.945.440.770; C12.100.500.260.750; C12.100.500.565.625; C12.200.294.260.750; C12.200.294.565.625; C12.200.758.409.750; C12.900.619.750
C537651	Bartter syndrome, antenatal , type 2 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL1293292 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 8 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL3696475	MK-7145	1	8

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

PharmGKB clinical annotations

3 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs11600347	Toxicity	3	hydrochlorothiazide	Hypertension
rs12795437	Toxicity	3	hydrochlorothiazide	Diabetes Mellitus;Hypertension
rs658903	Toxicity	3	hydrochlorothiazide	Diabetes Mellitus;Hypertension

PharmGKB variants

7 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs658903	KCNJ1	3	3.25	1	hydrochlorothiazide
rs675388	KCNJ1		0.00	0
rs2846680	KCNJ1		0.00	0
rs11600347	KCNJ1	3	3.75	1	hydrochlorothiazide
rs12795437	KCNJ1	3	3.75	1	hydrochlorothiazide
rs17137967	KCNJ1		0.00	0
rs59172778	KCNJ1		0.00	0

GtoPdb / IUPHAR curated pharmacology

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

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

Most potent curated ligand interactions (9 total), top 9:

Ligand	Action	Affinity	Parameter
[125I]tertiapin Y1/K12/Q13	Antagonist	9.2	pKd
tertiapin-Q	Inhibition	8.9	pIC50
MK-8153	Inhibition	8.3	pIC50
MK-7145	Inhibition	8.22	pIC50
H+	Antagonist	6.8	pIC50
VU591	Inhibition	6.6	pKi
Cs+	Antagonist	2.9	pIC50
K+	Activation	2.3	pEC50
Mg2+	Channel blocker	2.2	pKi

Binding affinities (BindingDB)

885 measured of 886 human assays (886 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
2-(4-methyl-5-oxo-2H-furan-3-yl)-8-[[4-(tetrazol-1-yl)phenyl]methylamino]-2-azaspiro[4.5]decan-1-one	IC50	3.1 nM	US-9718808: Inhibitors of the renal outer medullary potassium channel
2-(4-methyl-5-oxo-2H-furan-3-yl)-8-[[4-(tetrazol-2-yl)phenyl]methylamino]-2-azaspiro[4.5]decan-1-one	IC50	3.3 nM	US-9718808: Inhibitors of the renal outer medullary potassium channel
2-(4-methyl-5-oxo-2H-furan-3-yl)-8-[methyl-[[4-(tetrazol-2-yl)phenyl]methyl]amino]-2-azaspiro[4.5]decan-1-one	IC50	3.4 nM	US-9718808: Inhibitors of the renal outer medullary potassium channel
9-[(2S)-2-hydroxy-2-[6-(tetrazol-1-yl)-3-pyridinyl]ethyl]-4-(4-methyl-5-oxo-2H-furan-3-yl)-1-oxa-4,9-diazaspiro[5.5]undecan-5-one	IC50	3.8 nM	US-9850245: Inhibitors of the renal outer medullary potassium channel
8-(4,5-dihydrotetrazolo[1,5-a]quinolin-7-ylmethylamino)-2-(4-methyl-5-oxo-2H-furan-3-yl)-2-azaspiro[4.5]decan-1-one	IC50	4.3 nM	US-9718808: Inhibitors of the renal outer medullary potassium channel
5-[8-[(2R)-2-hydroxy-2-(4-methyl-1-oxo-3H-2-benzofuran-5-yl)ethyl]-2,8-diazaspiro[4.5]decan-2-yl]pyrazine-2-carbonitrile	IC50	4.7 nM	US-9751881: Inhibitors of the renal outer medullary potassium channel
9-[2-hydroxy-2-[4-(tetrazol-1-yl)phenyl]ethyl]-4-(4-methyl-5-oxo-2H-furan-3-yl)-1-oxa-4,9-diazaspiro[5.5]undecan-5-one	IC50	4.8 nM	US-9850245: Inhibitors of the renal outer medullary potassium channel
8-[(6-fluoro-5H-tetrazolo[5,1-a]isoindol-7-yl)methylamino]-2-(4-methyl-5-oxo-2H-furan-3-yl)-2-azaspiro[4.5]decan-1-one	IC50	6 nM	US-9718808: Inhibitors of the renal outer medullary potassium channel
2-(4-methyl-5-oxo-2H-furan-3-yl)-8-[2-(5H-tetrazolo[5,1-a]isoindol-7-yl)ethyl]-2,8-diazaspiro[4.5]decan-1-one	IC50	6 nM	US-10208064: Inhibitors of the renal outer medullary potassium channel
9-[(2R)-2-hydroxy-2-(4-methyl-1-oxo-3H-2-benzofuran-5-yl)ethyl]-4-(4-methyl-5-oxo-2H-furan-3-yl)-1-oxa-4,9-diazaspiro[5.5]undecan-5-one	IC50	6.4 nM	US-9850245: Inhibitors of the renal outer medullary potassium channel
9-[(2S)-2-fluoro-2-[6-(tetrazol-1-yl)-3-pyridinyl]ethyl]-4-(4-methyl-5-oxo-2H-furan-3-yl)-1-oxa-4,9-diazaspiro[5.5]undecan-5-one	IC50	6.6 nM	US-9850245: Inhibitors of the renal outer medullary potassium channel
2-[8-[(2R)-2-hydroxy-2-(4-methyl-1-oxo-3H-2-benzofuran-5-yl)ethyl]-2,8-diazaspiro[4.5]decan-2-yl]-1,3-thiazole-5-carbonitrile	IC50	6.7 nM	US-9751881: Inhibitors of the renal outer medullary potassium channel
(3S)-3-methyl-2-(5-oxo-2H-furan-3-yl)-8-[[5-(tetrazol-1-yl)pyrazin-2-yl]methylamino]-2-azaspiro[4.5]decan-1-one	IC50	7 nM	US-9718808: Inhibitors of the renal outer medullary potassium channel
2-(4-methyl-5-oxo-2H-furan-3-yl)-8-[methyl-[[5-(tetrazol-1-yl)-2-pyridinyl]methyl]amino]-2-azaspiro[4.5]decan-1-one	IC50	7 nM	US-9718808: Inhibitors of the renal outer medullary potassium channel
(3R)-8-[(2S)-2-hydroxy-2-(tetrazolo[1,5-a]quinolin-7-yl)ethyl]-3-methyl-2-(5-oxo-2H-furan-3-yl)-2,8-diazaspiro[4.5]decan-1-one	IC50	7 nM	US-10208064: Inhibitors of the renal outer medullary potassium channel
4-(4-methyl-5-oxo-2H-furan-3-yl)-9-[2-[6-(tetrazol-1-yl)pyridazin-3-yl]ethyl]-1-oxa-4,9-diazaspiro[5.5]undecan-5-one	IC50	7.3 nM	US-9850245: Inhibitors of the renal outer medullary potassium channel
8-methyl-2-(4-methyl-5-oxo-2H-furan-3-yl)-8-[[6-(tetrazol-1-yl)pyridazin-3-yl]methylamino]-2-azaspiro[4.5]decan-1-one	IC50	7.7 nM	US-9718808: Inhibitors of the renal outer medullary potassium channel
6-fluoro-5H-tetrazolo[5,1-a]isoindole-7-carbaldehyde	IC50	8.3 nM	US-9718808: Inhibitors of the renal outer medullary potassium channel
2-(4-methyl-5-oxo-2H-furan-3-yl)-8-[[5-methyl-6-(tetrazol-1-yl)pyridazin-3-yl]methylamino]-2-azaspiro[4.5]decan-1-one	IC50	8.4 nM	US-9718808: Inhibitors of the renal outer medullary potassium channel
(3S)-3-methyl-2-(5-oxo-2H-furan-3-yl)-8-[[6-(tetrazol-1-yl)pyridazin-3-yl]methylamino]-2-azaspiro[4.5]decan-1-one	IC50	8.4 nM	US-9718808: Inhibitors of the renal outer medullary potassium channel
8-[(2S)-2-(6-chloro-5H-tetrazolo[5,1-a]isoindol-7-yl)-2-hydroxyethyl]-2-(4-methyl-5-oxo-2H-furan-3-yl)-2,8-diazaspiro[4.5]decan-1-one	IC50	9 nM	US-10208064: Inhibitors of the renal outer medullary potassium channel
(5r,8r)-8-(((6-(2H-tetrazol-2-yl)pyridazin-3-yl)methyl)amino)-2-(4-methyl-5-oxo-2,5-dihydrofuran-3-yl)-2-azaspiro[4.5]decan-1-one	IC50	9.3 nM	US-9718808: Inhibitors of the renal outer medullary potassium channel
5-[9-[2-hydroxy-2-(4-methyl-1-oxo-3H-2-benzofuran-5-yl)ethyl]-3,9-diazaspiro[5.5]undecan-3-yl]pyrazine-2-carbonitrile	IC50	9.62 nM	US-9751881: Inhibitors of the renal outer medullary potassium channel
8-[methyl-[(6-methyl-5H-tetrazolo[5,1-a]isoindol-7-yl)methyl]amino]-2-(4-methyl-5-oxo-2H-furan-3-yl)-2-azaspiro[4.5]decan-1-one	IC50	9.7 nM	US-9718808: Inhibitors of the renal outer medullary potassium channel
8-[2-(4-methyl-1-oxo-3H-2-benzofuran-5-yl)ethyl]-2-(4-methyl-5-oxo-2H-furan-3-yl)-2,8-diazaspiro[4.5]decan-1-one	IC50	10 nM	US-9206198: Inhibitors of the renal outer medullary potassium channel
(3S)-8-[(2R)-2-hydroxy-2-(4-methyl-1-oxo-3H-2-benzofuran-5-yl)ethyl]-3-methyl-2-(5-oxo-2H-furan-3-yl)-2,8-diazaspiro[4.5]decan-1-one	IC50	10 nM	US-9206198: Inhibitors of the renal outer medullary potassium channel
8-[(2R)-2-hydroxy-2-(4-methyl-1-oxo-3H-2-benzofuran-5-yl)ethyl]-2-(4-methyl-5-oxo-2H-furan-3-yl)-2,8-diazaspiro[4.5]decan-1-one	IC50	10 nM	US-9206198: Inhibitors of the renal outer medullary potassium channel
9-[(2R)-2-hydroxy-2-(4-methyl-1-oxo-3H-2-benzofuran-5-yl)ethyl]-2-(4-methyl-5-oxo-2H-furan-3-yl)-2,9-diazaspiro[5.5]undecan-1-one	IC50	10 nM	US-9206198: Inhibitors of the renal outer medullary potassium channel
8-[(2R)-2-methoxy-2-(4-methyl-1-oxo-3H-2-benzofuran-5-yl)ethyl]-1’-(4-methyl-5-oxo-2H-furan-3-yl)spiro[8-azabicyclo[3.2.1]octane-3,3’-pyrrolidine]-2’-one	IC50	10 nM	US-9206198: Inhibitors of the renal outer medullary potassium channel
9-[(2R)-2-hydroxy-2-(4-methyl-1-oxo-3H-2-benzofuran-5-yl)ethyl]-2-(5-oxo-2H-furan-3-yl)-2,9-diazaspiro[5.5]undecan-1-one	IC50	10 nM	US-9206198: Inhibitors of the renal outer medullary potassium channel
2-(4-chloro-5-oxo-2H-furan-3-yl)-8-[(2R)-2-hydroxy-2-(4-methyl-1-oxo-3H-2-benzofuran-5-yl)ethyl]-2,8-diazaspiro[4.5]decan-1-one	IC50	10 nM	US-9206198: Inhibitors of the renal outer medullary potassium channel
8-[(1S,2R)-1-hydroxy-1-(4-methyl-1-oxo-3H-2-benzofuran-5-yl)propan-2-yl]-2-(4-methyl-5-oxo-2H-furan-3-yl)-2,8-diazaspiro[4.5]decan-1-one	IC50	10 nM	US-9206198: Inhibitors of the renal outer medullary potassium channel
3-ethyl-8-[(2R)-2-hydroxy-2-(4-methyl-1-oxo-3H-2-benzofuran-5-yl)ethyl]-2-(5-oxo-2H-furan-3-yl)-2,8-diazaspiro[4.5]decan-1-one	IC50	10 nM	US-9206198: Inhibitors of the renal outer medullary potassium channel
8-[2-(4-ethyl-1-oxo-3H-2-benzofuran-5-yl)-2-hydroxyethyl]-2-(4-methyl-5-oxo-2H-furan-3-yl)-2,8-diazaspiro[4.5]decan-1-one	IC50	10 nM	US-9206198: Inhibitors of the renal outer medullary potassium channel
8-[2-(4-cyclopropyl-1-oxo-3H-2-benzofuran-5-yl)-2-hydroxyethyl]-2-(4-methyl-5-oxo-2H-furan-3-yl)-2,8-diazaspiro[4.5]decan-1-one	IC50	10 nM	US-9206198: Inhibitors of the renal outer medullary potassium channel
8-[2-(4-chloro-1-oxo-3H-2-benzofuran-5-yl)-2-hydroxyethyl]-2-(4-methyl-5-oxo-2H-furan-3-yl)-2,8-diazaspiro[4.5]decan-1-one	IC50	10 nM	US-9206198: Inhibitors of the renal outer medullary potassium channel
8-[2-(4-fluoro-1-oxo-3H-2-benzofuran-5-yl)-2-hydroxyethyl]-2-(4-methyl-5-oxo-2H-furan-3-yl)-2,8-diazaspiro[4.5]decan-1-one	IC50	10 nM	US-9206198: Inhibitors of the renal outer medullary potassium channel
8-[1-hydroxy-2-methyl-1-(4-methyl-1-oxo-3H-2-benzofuran-5-yl)propan-2-yl]-2-(4-methyl-5-oxo-2H-furan-3-yl)-2,8-diazaspiro[4.5]decan-1-one	IC50	10 nM	US-9206198: Inhibitors of the renal outer medullary potassium channel
8-[(1R,2S)-1-hydroxy-1-(4-methyl-1-oxo-3H-2-benzofuran-5-yl)propan-2-yl]-2-(4-methyl-5-oxo-2H-furan-3-yl)-2,8-diazaspiro[4.5]decan-1-one	IC50	10 nM	US-9206198: Inhibitors of the renal outer medullary potassium channel
2-(4-methyl-5-oxo-2H-furan-3-yl)-8-[[6-(tetrazol-1-yl)pyridazin-3-yl]methylamino]-2-azaspiro[4.5]decan-1-one	IC50	10 nM	US-9718808: Inhibitors of the renal outer medullary potassium channel
(3S)-8-[(2S)-2-hydroxy-2-(tetrazolo[1,5-a]quinolin-7-yl)ethyl]-3-methyl-2-(5-oxo-2H-furan-3-yl)-2,8-diazaspiro[4.5]decan-1-one	IC50	10 nM	US-10208064: Inhibitors of the renal outer medullary potassium channel
6-[8-[(2R)-2-hydroxy-2-(4-methyl-1-oxo-3H-2-benzofuran-5-yl)ethyl]-2,8-diazaspiro[4.5]decan-2-yl]pyridine-3-carbonitrile	IC50	10 nM	US-9751881: Inhibitors of the renal outer medullary potassium channel
5-[8-[(2R)-2-hydroxy-2-(4-methyl-1-oxo-3H-2-benzofuran-5-yl)ethyl]-2,8-diazaspiro[4.5]decan-2-yl]-3-methylpyridine-2-carbonitrile	IC50	10.1 nM	US-9751881: Inhibitors of the renal outer medullary potassium channel
6-[8-[(2R)-2-hydroxy-2-(4-methyl-1-oxo-3H-2-benzofuran-5-yl)ethyl]-3-oxo-2,8-diazaspiro[4.5]decan-2-yl]pyridine-3-carbonitrile	IC50	10.5 nM	US-9751881: Inhibitors of the renal outer medullary potassium channel
5-[(1R)-1-hydroxy-2-[1-[(2R)-2-hydroxy-2-(4-methyl-1-oxo-3H-2-benzofuran-5-yl)ethyl]-1,7-diazaspiro[4.4]nonan-7-yl]ethyl]-4-methyl-3H-2-benzofuran-1-one	IC50	11 nM	US-9493474: Inhibitors of the renal outer medullary potassium channel
2-(4-methyl-5-oxo-2H-furan-3-yl)-8-[methyl-[(1R)-1-[6-(tetrazol-1-yl)-3-pyridinyl]ethyl]amino]-2-azaspiro[4.5]decan-1-one	IC50	11 nM	US-9718808: Inhibitors of the renal outer medullary potassium channel
8-[(2R)-2-hydroxy-2-(tetrazolo[1,5-a]quinolin-7-yl)ethyl]-2-(4-methyl-5-oxo-2H-furan-3-yl)-2,8-diazaspiro[4.5]decan-1-one	IC50	11 nM	US-10208064: Inhibitors of the renal outer medullary potassium channel
3-[9-[2-hydroxy-2-[2-methyl-6-(tetrazol-1-yl)-3-pyridinyl]ethyl]-1-oxa-4,9-diazaspiro[5.5]undecan-4-yl]-4-methyl-2H-furan-5-one	IC50	11 nM	US-9850245: Inhibitors of the renal outer medullary potassium channel
4-methyl-5-[2-[4-[2-(4-methyl-1-oxo-3H-2-benzofuran-5-yl)propyl]piperazin-1-yl]ethyl]-3H-2-benzofuran-1-one	IC50	12 nM	US-9073882: Inhibitors of the renal outer medullary potassium channel
9-[2-hydroxy-2-[5-(tetrazol-1-yl)pyrazin-2-yl]ethyl]-4-(4-methyl-5-oxo-2H-furan-3-yl)-1-oxa-4,9-diazaspiro[5.5]undecan-5-one	IC50	12 nM	US-9850245: Inhibitors of the renal outer medullary potassium channel

ChEMBL bioactivities

1723 potent at pChembl≥5 of 1729 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.82	IC50	0.15	nM	CHEMBL5804346
9.24	IC50	0.57	nM	CHEMBL5804346
9.00	IC50	1	nM	CHEMBL5557617
8.96	IC50	1.1	nM	CHEMBL5944778
8.70	Ki	2	nM	CHEMBL4559408
8.68	IC50	2.1	nM	CHEMBL5824262
8.62	IC50	2.4	nM	CHEMBL5924058
8.52	IC50	3	nM	CHEMBL3935296
8.51	IC50	3.1	nM	CHEMBL5961641
8.48	IC50	3.3	nM	CHEMBL5821982
8.47	IC50	3.4	nM	CHEMBL5909398
8.44	IC50	3.6	nM	CHEMBL5879257
8.44	IC50	3.6	nM	CHEMBL5824262
8.42	IC50	3.8	nM	CHEMBL5851002
8.40	IC50	4	nM	CHEMBL3895661
8.40	IC50	4	nM	CHEMBL4115897
8.40	IC50	4	nM	CHEMBL3967802
8.40	IC50	4	nM	CHEMBL4062753
8.40	IC50	4	nM	CHEMBL5999603
8.37	IC50	4.3	nM	CHEMBL5812834
8.33	IC50	4.7	nM	CHEMBL5561980
8.33	IC50	4.7	nM	CHEMBL5944311
8.33	IC50	4.7	nM	CHEMBL5860041
8.33	IC50	4.7	nM	CHEMBL5757596
8.32	IC50	4.8	nM	CHEMBL5793852
8.32	IC50	4.8	nM	CHEMBL5957552
8.31	IC50	4.9	nM	CHEMBL5786106
8.30	IC50	5	nM	CHEMBL4103004
8.30	IC50	5	nM	CHEMBL3913475
8.24	IC50	5.7	nM	CHEMBL5560640
8.22	IC50	6	nM	MK-7145
8.22	IC50	6	nM	CHEMBL3962588
8.22	IC50	6	nM	CHEMBL6045925
8.22	IC50	6	nM	CHEMBL4456154
8.21	IC50	6.2	nM	CHEMBL4548110
8.21	IC50	6.2	nM	CHEMBL6011409
8.21	IC50	6.1	nM	CHEMBL5797888
8.19	IC50	6.4	nM	CHEMBL5845647
8.19	IC50	6.4	nM	CHEMBL5877653
8.18	IC50	6.6	nM	CHEMBL4563446
8.18	IC50	6.6	nM	CHEMBL4549009
8.18	IC50	6.6	nM	CHEMBL5560084
8.18	IC50	6.6	nM	CHEMBL5939153
8.17	IC50	6.8	nM	CHEMBL5563848
8.17	IC50	6.7	nM	CHEMBL5827294
8.17	IC50	6.8	nM	CHEMBL6007651
8.15	IC50	7	nM	CHEMBL3808666
8.15	IC50	7	nM	CHEMBL5205738
8.15	IC50	7	nM	CHEMBL5767256
8.15	IC50	7	nM	CHEMBL5741219

PubChem BioAssay actives

381 with measured affinity, of 435 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.

Compound	Assay	Type	Value	Unit
6-[4-[[[(2R)-2-hydroxy-2-(4-methyl-1-oxo-3H-2-benzofuran-5-yl)ethyl]amino]methyl]-5-methoxypyrazol-1-yl]-4-methylpyridine-3-carbonitrile	2077483: Inhibition of human ROMK expressed in T-REX-CHO cells incubated for 30 mins by thallium flux assay	ic50	0.0010	uM
(1R,4S,7S,10S,16S,19S,22S,25R,28S,31R,36R,39S,42S,45S,52R,55S)-39,42-bis(4-aminobutyl)-N-[2-[[(2S)-6-amino-1-[[(2S)-1,6-diamino-1-oxohexan-2-yl]amino]-1-oxohexan-2-yl]amino]-2-oxoethyl]-28,55-bis(2-amino-2-oxoethyl)-52-[[(2S)-2-[[(2S)-2-aminopropanoyl]amino]-4-methylpentanoyl]amino]-16,19,22-tris[(2S)-butan-2-yl]-25-(3-carbamimidamidopropyl)-7-(1H-imidazol-5-ylmethyl)-45-(1H-indol-3-ylmethyl)-4-(2-methylsulfanylethyl)-3,6,9,15,18,21,24,27,30,38,41,44,47,53,56-pentadecaoxo-33,34,49,50-tetrathia-2,5,8,14,17,20,23,26,29,37,40,43,46,54,57-pentadecazatricyclo[29.16.10.010,14]heptapentacontane-36-carboxamide	1525457: Inhibition of ROMK (unknown origin)	ki	0.0020	uM
8-[(2R)-2-hydroxy-2-(4-methyl-1-oxo-3H-2-benzofuran-5-yl)ethyl]-2-(1,2-thiazol-5-yl)-2,8-diazaspiro[4.5]decan-1-one	1474849: Inhibition of human ROMK expressed in CHO cells at -70 mV holding potential after 6 mins by whole cell patch clamp Qpatch method	ic50	0.0040	uM
8-[(2R)-2-hydroxy-2-(4-methyl-1-oxo-3H-2-benzofuran-5-yl)ethyl]-2-(5-oxo-2H-furan-3-yl)-2,8-diazaspiro[4.5]decan-1-one	1817294: Inhibition of human ROMK expressed in CHO cells by whole cell voltage clamp electrophysiology assay	ic50	0.0040	uM
6-[4-[[[(2R)-2-hydroxy-2-(4-methyl-1-oxo-3H-2-benzofuran-5-yl)ethyl]amino]methyl]pyrazol-1-yl]-4-methylpyridine-3-carbonitrile	2077484: Inhibition of human ROMK expressed in T-REX-CHO cells incubated for 3 to 8 mins by whole cell manual patch clamp assay	ic50	0.0047	uM
8-[(2R)-2-hydroxy-2-(4-methyl-1-oxo-3H-2-benzofuran-5-yl)ethyl]-2-(2-methoxypyrimidin-4-yl)-2,8-diazaspiro[4.5]decan-1-one	1474849: Inhibition of human ROMK expressed in CHO cells at -70 mV holding potential after 6 mins by whole cell patch clamp Qpatch method	ic50	0.0050	uM
8-[(2R)-2-hydroxy-2-(4-methyl-1-oxo-3H-2-benzofuran-5-yl)ethyl]-2-(4-methyl-5-oxo-2H-furan-3-yl)-2,8-diazaspiro[4.5]decan-1-one	1817294: Inhibition of human ROMK expressed in CHO cells by whole cell voltage clamp electrophysiology assay	ic50	0.0050	uM
4-methyl-6-[4-[[(3R)-3-(4-methyl-1-oxo-3H-2-benzofuran-5-yl)piperazin-1-yl]methyl]pyrazol-1-yl]pyridine-3-carbonitrile	2077484: Inhibition of human ROMK expressed in T-REX-CHO cells incubated for 3 to 8 mins by whole cell manual patch clamp assay	ic50	0.0057	uM
5-[(1R)-1-hydroxy-2-[4-[(2R)-2-hydroxy-2-(4-methyl-1-oxo-3H-2-benzofuran-5-yl)ethyl]piperazin-1-yl]ethyl]-4-methyl-3H-2-benzofuran-1-one	1627531: Inhibition of ROMK (unknown origin) after 30 mins by Tl+ influx assay	ic50	0.0060	uM
2-(4-chloro-5-oxo-2H-furan-3-yl)-8-[(2R)-2-hydroxy-2-(4-methyl-1-oxo-3H-2-benzofuran-5-yl)ethyl]-2,8-diazaspiro[4.5]decan-1-one	1817294: Inhibition of human ROMK expressed in CHO cells by whole cell voltage clamp electrophysiology assay	ic50	0.0060	uM
2-ethoxy-4-[4-[[[(2R)-2-hydroxy-2-(4-methyl-1-oxo-3H-2-benzofuran-5-yl)ethyl]amino]methyl]pyrazol-1-yl]benzonitrile	1525475: Inhibition of human ROMK1 expressed in CHO cells by Tl+ flux assay	ic50	0.0062	uM
4-methyl-6-[5-[[(3S,5R)-3-methyl-5-(4-methyl-1-oxo-3H-2-benzofuran-5-yl)piperazin-1-yl]methyl]-1,2-oxazol-3-yl]pyridine-3-carbonitrile	1525475: Inhibition of human ROMK1 expressed in CHO cells by Tl+ flux assay	ic50	0.0066	uM
6-[5-[[[(2R)-2-hydroxy-2-(4-methyl-1-oxo-3H-2-benzofuran-5-yl)ethyl]amino]methyl]-1,3-thiazol-2-yl]-4-methylpyridine-3-carbonitrile	2077483: Inhibition of human ROMK expressed in T-REX-CHO cells incubated for 30 mins by thallium flux assay	ic50	0.0066	uM
4-[5-[[[(2R)-2-hydroxy-2-(4-methyl-1-oxo-3H-2-benzofuran-5-yl)ethyl]amino]methyl]-1,3-thiazol-2-yl]-2-methylbenzonitrile	1525475: Inhibition of human ROMK1 expressed in CHO cells by Tl+ flux assay	ic50	0.0066	uM
4-methyl-6-[4-[[(3S,5R)-3-methyl-5-(4-methyl-1-oxo-3H-2-benzofuran-5-yl)piperazin-1-yl]methyl]triazol-2-yl]pyridine-3-carbonitrile	2077484: Inhibition of human ROMK expressed in T-REX-CHO cells incubated for 3 to 8 mins by whole cell manual patch clamp assay	ic50	0.0068	uM
(3R)-8-[(2S)-2-hydroxy-2-(5H-tetrazolo[5,1-a]isoindol-8-yl)ethyl]-3-methyl-2-(5-oxo-2H-furan-3-yl)-2,8-diazaspiro[4.5]decan-1-one	1304039: Inhibition of human Kir1.1 expressed in HEK293 cells after 30 mins by thallium flux assay	ic50	0.0070	uM
5-[(1S)-2-[3-(4-fluoro-5-oxo-2H-furan-3-yl)-3,9-diazaspiro[5.5]undecan-9-yl]-1-hydroxyethyl]-4-methyl-3H-2-benzofuran-1-one	1850572: Inhibition of ROMK (unknown origin) by Thallium Efflux assay	ic50	0.0070	uM
6-[4-[[(5R)-3,3-dimethyl-5-(4-methyl-1-oxo-3H-2-benzofuran-5-yl)piperazin-1-yl]methyl]triazol-2-yl]-4-methylpyridine-3-carbonitrile	2077484: Inhibition of human ROMK expressed in T-REX-CHO cells incubated for 3 to 8 mins by whole cell manual patch clamp assay	ic50	0.0079	uM
8-[(2R)-2-hydroxy-2-(4-methyl-1-oxo-3H-2-benzofuran-5-yl)ethyl]-2-(3-methyl-1,2,4-thiadiazol-5-yl)-2,8-diazaspiro[4.5]decan-1-one	1474849: Inhibition of human ROMK expressed in CHO cells at -70 mV holding potential after 6 mins by whole cell patch clamp Qpatch method	ic50	0.0080	uM
6-[4-[[[(2R)-2-hydroxy-2-(4-methyl-1-oxo-3H-2-benzofuran-5-yl)ethyl]amino]methyl]triazol-2-yl]-4-methylpyridine-3-carbonitrile	2077484: Inhibition of human ROMK expressed in T-REX-CHO cells incubated for 3 to 8 mins by whole cell manual patch clamp assay	ic50	0.0081	uM
1-[6-[[(3R)-3-(4-methyl-1-oxo-3H-2-benzofuran-5-yl)piperazin-1-yl]methyl]-3-pyridinyl]pyrazole-4-carbonitrile	1525475: Inhibition of human ROMK1 expressed in CHO cells by Tl+ flux assay	ic50	0.0088	uM
2-fluoro-4-[6-[(2R)-2-hydroxy-2-(4-methyl-1-oxo-3H-2-benzofuran-5-yl)ethyl]-7,8-dihydro-5H-pyrido[4,3-d]pyrimidin-2-yl]benzonitrile	2077483: Inhibition of human ROMK expressed in T-REX-CHO cells incubated for 30 mins by thallium flux assay	ic50	0.0088	uM
5-[9-[(2R)-2-hydroxy-2-(4-methyl-1-oxo-3H-2-benzofuran-5-yl)ethyl]-3,9-diazaspiro[5.5]undecan-3-yl]pyrazine-2-carbonitrile	1249741: Inhibition of human Kir1.1 expressed in HEK293 cells by thallium flux assay	ic50	0.0090	uM
8-[(2S)-2-(7-chloro-5H-tetrazolo[5,1-a]isoindol-8-yl)-2-hydroxyethyl]-2-(4-methyl-5-oxo-2H-furan-3-yl)-2,8-diazaspiro[4.5]decan-1-one	1304039: Inhibition of human Kir1.1 expressed in HEK293 cells after 30 mins by thallium flux assay	ic50	0.0090	uM
5-[(1S)-1-hydroxy-2-[4-[(2R)-2-hydroxy-2-(4-methyl-1-oxo-3H-2-benzofuran-5-yl)ethyl]piperazin-1-yl]ethyl]-4-methyl-3H-2-benzofuran-1-one	1627528: Inhibition of ROMK (unknown origin) expressed in CHO cells after 6 mins by electrophysiological assay	ic50	0.0090	uM
6-[8-[(2R)-2-hydroxy-2-(4-methyl-1-oxo-3H-2-benzofuran-5-yl)ethyl]-2,8-diazaspiro[4.5]decan-2-yl]pyridine-3-carbonitrile	1249741: Inhibition of human Kir1.1 expressed in HEK293 cells by thallium flux assay	ic50	0.0100	uM
6-[8-[(2R)-2-hydroxy-2-(4-methyl-1-oxo-3H-2-benzofuran-5-yl)ethyl]-3-oxo-2,8-diazaspiro[4.5]decan-2-yl]pyridine-3-carbonitrile	1436988: Inhibition of human ROMK expressed in HEK293 cells after 30 mins by thallium flux assay	ic50	0.0100	uM
5-[8-[(2R)-2-hydroxy-2-(4-methyl-1-oxo-3H-2-benzofuran-5-yl)ethyl]-2,8-diazaspiro[4.5]decan-2-yl]pyridine-3-carbonitrile	1436988: Inhibition of human ROMK expressed in HEK293 cells after 30 mins by thallium flux assay	ic50	0.0100	uM
5-[8-[(2R)-2-hydroxy-2-(4-methyl-1-oxo-3H-2-benzofuran-5-yl)ethyl]-3-oxo-2,8-diazaspiro[4.5]decan-2-yl]pyridine-3-carbonitrile	1436988: Inhibition of human ROMK expressed in HEK293 cells after 30 mins by thallium flux assay	ic50	0.0100	uM
8-[(1R,2S)-1-hydroxy-1-(4-methyl-1-oxo-3H-2-benzofuran-5-yl)propan-2-yl]-2-(4-methyl-5-oxo-2H-furan-3-yl)-2,8-diazaspiro[4.5]decan-1-one	1850572: Inhibition of ROMK (unknown origin) by Thallium Efflux assay	ic50	0.0100	uM
5-[8-[(2R)-2-hydroxy-2-(4-methyl-1-oxo-3H-2-benzofuran-5-yl)ethyl]-2,8-diazaspiro[4.5]decan-2-yl]-3-methylpyridine-2-carbonitrile	1249741: Inhibition of human Kir1.1 expressed in HEK293 cells by thallium flux assay	ic50	0.0101	uM
8-[(2R)-2-hydroxy-2-(4-methyl-1-oxo-3H-2-benzofuran-5-yl)ethyl]-2-pyridin-4-yl-2,8-diazaspiro[4.5]decan-1-one	1474849: Inhibition of human ROMK expressed in CHO cells at -70 mV holding potential after 6 mins by whole cell patch clamp Qpatch method	ic50	0.0110	uM
8-[(2R)-2-hydroxy-2-(4-methyl-1-oxo-3H-2-benzofuran-5-yl)ethyl]-2-(3-oxocyclopenten-1-yl)-2,8-diazaspiro[4.5]decan-1-one	1817294: Inhibition of human ROMK expressed in CHO cells by whole cell voltage clamp electrophysiology assay	ic50	0.0110	uM
8-[(2R)-2-hydroxy-2-(5H-tetrazolo[5,1-a]isoindol-8-yl)ethyl]-2-(4-methyl-5-oxo-2H-furan-3-yl)-2,8-diazaspiro[4.5]decan-1-one	1304039: Inhibition of human Kir1.1 expressed in HEK293 cells after 30 mins by thallium flux assay	ic50	0.0110	uM
4-methyl-6-[4-[[(2R)-2-(4-methyl-1-oxo-3H-2-benzofuran-5-yl)morpholin-4-yl]methyl]pyrazol-1-yl]pyridine-3-carbonitrile	2077484: Inhibition of human ROMK expressed in T-REX-CHO cells incubated for 3 to 8 mins by whole cell manual patch clamp assay	ic50	0.0110	uM
6-[8-[2-(4-methyl-1-oxo-3H-2-benzofuran-5-yl)ethyl]-3-oxo-2,8-diazaspiro[4.5]decan-2-yl]pyridine-3-carbonitrile	1249741: Inhibition of human Kir1.1 expressed in HEK293 cells by thallium flux assay	ic50	0.0120	uM
8-[(2R)-2-hydroxy-2-(4-methyl-1-oxo-3H-2-benzofuran-5-yl)ethyl]-2-(3-methyl-1,2-thiazol-5-yl)-2,8-diazaspiro[4.5]decan-1-one	1474849: Inhibition of human ROMK expressed in CHO cells at -70 mV holding potential after 6 mins by whole cell patch clamp Qpatch method	ic50	0.0120	uM
6-[5-[[[(2R)-2-hydroxy-2-(4-methyl-1-oxo-3H-2-benzofuran-5-yl)ethyl]amino]methyl]-2-pyridinyl]-4-methylpyridine-3-carbonitrile	2077484: Inhibition of human ROMK expressed in T-REX-CHO cells incubated for 3 to 8 mins by whole cell manual patch clamp assay	ic50	0.0120	uM
6-[1-hydroxy-2-[4-[(2R)-2-hydroxy-2-(4-methyl-1-oxo-3H-2-benzofuran-5-yl)ethyl]piperazin-1-yl]ethyl]-2-methylpyridine-3-carbonitrile	1244095: Inhibition of ROMK (unknown origin) expressed in HEK293 cells by electrophysiology assay	ic50	0.0120	uM
5-[(1S)-1-hydroxy-2-[4-[(2S)-2-hydroxy-2-(4-methyl-1-oxo-3H-2-benzofuran-5-yl)ethyl]piperazin-1-yl]ethyl]-4-methyl-3H-2-benzofuran-1-one	1627528: Inhibition of ROMK (unknown origin) expressed in CHO cells after 6 mins by electrophysiological assay	ic50	0.0120	uM
6-[9-[(2R)-2-hydroxy-2-(4-methyl-1-oxo-3H-2-benzofuran-5-yl)ethyl]-3,9-diazaspiro[5.5]undecan-3-yl]pyridazine-3-carbonitrile	1249741: Inhibition of human Kir1.1 expressed in HEK293 cells by thallium flux assay	ic50	0.0130	uM
6-[1-hydroxy-2-[4-[(2R)-2-hydroxy-2-(4-methyl-1-oxo-3H-2-benzofuran-5-yl)ethyl]piperazin-1-yl]ethyl]-4-(trideuteriomethoxy)pyridine-3-carbonitrile	1244095: Inhibition of ROMK (unknown origin) expressed in HEK293 cells by electrophysiology assay	ic50	0.0130	uM
2-fluoro-4-[2-[2-(1-oxo-3H-2-benzofuran-5-yl)ethyl]-3,4-dihydro-1H-isoquinolin-6-yl]benzonitrile	2077484: Inhibition of human ROMK expressed in T-REX-CHO cells incubated for 3 to 8 mins by whole cell manual patch clamp assay	ic50	0.0130	uM
6-[8-[(2R)-2-hydroxy-2-(4-methyl-1-oxo-3H-2-benzofuran-5-yl)ethyl]-2,8-diazaspiro[4.5]decan-2-yl]-2-methylpyridine-3-carbonitrile	1249741: Inhibition of human Kir1.1 expressed in HEK293 cells by thallium flux assay	ic50	0.0140	uM
6-[8-[(2R)-2-amino-2-(4-methyl-1-oxo-3H-2-benzofuran-5-yl)ethyl]-3-oxo-2,8-diazaspiro[4.5]decan-2-yl]pyridine-3-carbonitrile	1249741: Inhibition of human Kir1.1 expressed in HEK293 cells by thallium flux assay	ic50	0.0140	uM
2-[9-[(2R)-2-hydroxy-2-(4-methyl-1-oxo-3H-2-benzofuran-5-yl)ethyl]-3,9-diazaspiro[5.5]undecan-3-yl]pyrimidine-5-carbonitrile	1249741: Inhibition of human Kir1.1 expressed in HEK293 cells by thallium flux assay	ic50	0.0140	uM
(3S)-8-[(2S)-2-hydroxy-2-(5H-tetrazolo[5,1-a]isoindol-8-yl)ethyl]-3-methyl-2-(5-oxo-2H-furan-3-yl)-2,8-diazaspiro[4.5]decan-1-one	1304039: Inhibition of human Kir1.1 expressed in HEK293 cells after 30 mins by thallium flux assay	ic50	0.0140	uM
4-[8-[(2R)-2-hydroxy-2-(4-methyl-1-oxo-3H-2-benzofuran-5-yl)ethyl]-2,8-diazaspiro[4.5]decan-2-yl]benzonitrile	1249741: Inhibition of human Kir1.1 expressed in HEK293 cells by thallium flux assay	ic50	0.0150	uM
8-[(2R)-2-hydroxy-2-(4-methyl-1-oxo-3H-2-benzofuran-5-yl)ethyl]-2-(2-methyl-3-oxocyclopenten-1-yl)-2,8-diazaspiro[4.5]decan-1-one	1817294: Inhibition of human ROMK expressed in CHO cells by whole cell voltage clamp electrophysiology assay	ic50	0.0150	uM
6-[3-(difluoromethyl)-4-[[[(2R)-2-hydroxy-2-(4-methyl-1-oxo-3H-2-benzofuran-5-yl)ethyl]amino]methyl]pyrazol-1-yl]-4-methylpyridine-3-carbonitrile	2077483: Inhibition of human ROMK expressed in T-REX-CHO cells incubated for 30 mins by thallium flux assay	ic50	0.0150	uM

CTD chemical–gene interactions

18 total (human), top 18 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
ochratoxin A	decreases expression, increases expression	2
Benzo(a)pyrene	affects methylation, decreases expression	2
antibiotic G 418	increases expression	1
perfluorooctanoic acid	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	decreases expression	1
CGP 52608	increases reaction, affects binding	1
perfluoro-n-nonanoic acid	decreases expression	1
Zoledronic Acid	decreases expression	1
Allergens	increases expression	1
Calcitriol	increases expression, affects cotreatment	1
Gentamicins	increases expression	1
Potassium	decreases transport, increases transport	1
Tamoxifen	increases expression	1
Testosterone	affects cotreatment, increases expression	1
Tobacco Smoke Pollution	increases expression	1
Aflatoxin B1	increases methylation	1
Antirheumatic Agents	increases expression	1

ChEMBL screening assays

61 unique, capped per target: 59 binding, 1 functional, 1 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1614332	Functional	PUBCHEM_BIOASSAY: High throughput discovery of novel modulators of ROMK K+ channel activity: Analog Library Testing. (Class of assay: confirmatory)	PubChem BioAssay data set
CHEMBL2148625	Binding	Inhibition of human ROMK1 channel expressed in CHO cells coexpressing DHFR assessed as inhibition of 86Rb+ efflux after 35 mins by TopCount method	Discovery of Selective Small Molecule ROMK Inhibitors as Potential New Mechanism Diuretics. — ACS Med Chem Lett
CHEMBL4407434	ADMET	Inhibition of Kir1.1 (unknown origin) at 3 uM relative to control	Discovery of 3,4,6-Trisubstituted Piperidine Derivatives as Orally Active, Low hERG Blocking Akt Inhibitors via Conformational Restriction and Structure-Based Design. — J Med Chem

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00029224	PHASE4	COMPLETED	Treatment With Zoledronic Acid in Patients With Breast Cancer, Multiple Myeloma, and Prostate Cancer With Cancer Related Bone Lesions
NCT00035997	PHASE4	COMPLETED	Open-label Trial on the Effect of I.V. Zoledronic Acid 4 mg on Bone Density in Hormone Sensitive Prostate Cancer Patients With Bone Metastasis
NCT00063609	PHASE4	COMPLETED	The Effect of Zoledronic Acid on Bone Loss in Prostate Cancer Patients Undergoing Androgen Deprivation Therapy
NCT00103623	PHASE4	SUSPENDED	The Plenaxis® Experience Study
NCT00106392	PHASE4	COMPLETED	A Safety and Efficacy Study of Prograf in the Prevention of Erectile Dysfunction After Radical Prostatectomy
NCT00185029	PHASE4	UNKNOWN	MR-Lymphography and Lymph Node Staging in Prostate Cancer
NCT00199485	PHASE4	COMPLETED	Angelica Sinensis for the Treatment of Hot Flashes in Men Undergoing LHRH Therapy for Prostate Cancer
NCT00219219	PHASE4	COMPLETED	Zoledronic Acid in the Prevention of Skeletal-related Events in Hormone Refractory and Hormone-sensitive Prostate Cancer Patients With Bone Metastases
NCT00219271	PHASE4	COMPLETED	Effect Of Zoledronic Acid On Circulating And Bone Marrow-Residing Prostate Cancer Cells In Patients With Clinically Localized Prostate Cancer
NCT00237146	PHASE4	COMPLETED	Study to Evaluate Zoledronic Acid on Quality of Life and Skeletal-related Events as Adjuvant Treatment in Patients With Hormone-naïve Prostate Cancer and Bone Metastasis Who Have Undergone Orchiectomy
NCT00242554	PHASE4	COMPLETED	Open-label Phase IV Clinical Trial to Evaluate the Safety and Tolerability of Zoledronic Acid in Patients With Prostate Cancer and Bone Metastases
NCT00280098	PHASE4	COMPLETED	Docetaxel in the Treatment of Hormone Refractory Prostate Cancer
NCT00293696	PHASE4	COMPLETED	Casodex/Zoladex Biomarkers in Localised Prostate Cancer
NCT00334139	PHASE4	COMPLETED	Effect of Zoledronic Acid on Bone Metabolism in Patients With Bone Metastasis and Prostate or Breast Cancer
NCT00375765	PHASE4	COMPLETED	Effects On Dihydrotestosterone Regulated Gene Expression In Benign Prostatic Hyperplasia Or Prostate Cancer
NCT00391690	PHASE4	COMPLETED	Evaluation of Bone Markers as Diagnostic Tools for Early Detection of Bone Metastases in Patients With High Risk Prostate Cancer
NCT00422708	PHASE4	COMPLETED	Local Anesthesia for Prostate Biopsy
NCT00526331	PHASE4	COMPLETED	Evaluation of Arterial Pressure Based Cardiac Output for Goal-Directed Perioperative Therapy
NCT00590213	PHASE4	COMPLETED	Compare the Value of Prophylactic Versus Therapeutic Breast Radiotherapy in CASODEX
NCT00629330	PHASE4	TERMINATED	Dissemination of Prostate Cancer Screening to PCP’s in African American Communities
NCT00771966	PHASE4	COMPLETED	Radical Prostatectomy and Perioperative Fluid Therapy
NCT00805701	PHASE4	COMPLETED	Study Assessing The Efficacy And Safety Of Avodart (Dutasteride) At Improving Urinary Symptoms In Men With Prostate Cancer Who Are Undergoing Seed Implantation
NCT00859027	PHASE4	COMPLETED	Effect Of Risedronate On Bone Mass In Older Men Receiving Neoadjuvant Therapy For Prostate Cancer
NCT00906269	PHASE4	UNKNOWN	Can Hyperbaric Oxygen Improve Erectile Function Following Surgery for Prostate Cancer
NCT00953277	PHASE4	COMPLETED	Study of Nerve Reconstruction Using AVANCE in Subjects Who Undergo Robotic Assisted Prostatectomy for Treatment of Prostate Cancer
NCT00982800	PHASE4	COMPLETED	Does Postoperative Gabapentin Reduce Pain, Opioid Consumption and Anxiety and Have a Positive Effect on Health Related Quality of Life After Radical Prostatectomy?
NCT01083199	PHASE4	COMPLETED	Global Performance Evaluation of the AMS CONTINUUM™ Device
NCT01136226	PHASE4	COMPLETED	Evaluate Recovery of Testosterone for Patients Using Eligard
NCT01161563	PHASE4	COMPLETED	Randomized Crossover Trial to Assess the Tolerability of Gonadotropin Releasing Hormone (GnRH) Analogue Administration
NCT01230905	PHASE4	COMPLETED	Study to Monitor the Effects of Androgen Suppression Treatment on the Heart
NCT01296672	PHASE4	COMPLETED	3 Month Finasteride Challenge Test Can Significantly Improve the Performance of Screening for Prostate Cancer
NCT01365143	PHASE4	TERMINATED	Prospective Randomized Trial Comparing Robotic Versus Open Radical Prostatectomy
NCT01379742	PHASE4	UNKNOWN	Comparison of Between ThinSeed™ and OncoSeed™ for Permanent Prostate Brachytherapy
NCT01486563	PHASE4	COMPLETED	Hydroxyethyl Starch and Renal Function After Radical Prostatectomy
NCT01511874	PHASE4	COMPLETED	Efficacy and Safety Study of ELIGARD 22.5mg With Prostate Cancer
NCT01512472	PHASE4	TERMINATED	Firmagon (Degarelix) Intermittent Therapy
NCT01547416	PHASE4	COMPLETED	The Effect of Combined General/Epidural Anesthesia Versus General Anesthesia on Diaphragmatic Function
NCT01571544	PHASE4	COMPLETED	The Use of Thermal Suits as Preventing Hypothermia During Surgery
NCT01581749	PHASE4	UNKNOWN	Evaluation of Truebeam for Low-Intermediate Risk Prostate Cancer
NCT01649635	PHASE4	COMPLETED	Study of Cabazitaxel Combined With Prednisone and Prophylaxis of Neutropenia Complications in the Treatment of Patients With Metastatic Castration-resistant Prostate Cancer