KCNJ4

Summary

KCNJ4 (potassium inwardly rectifying channel subfamily J member 4, HGNC:6265) is a protein-coding gene on chromosome 22q13.1, encoding Inward rectifier potassium channel 4 (P48050). Inward rectifier potassium channels are characterized by a greater tendency to allow potassium to flow into the cell rather than out of it.

Several different potassium channels are known to be involved with electrical signaling in the nervous system. One class is activated by depolarization whereas a second class is not. The latter are referred to as inwardly rectifying K+ channels, and they have a greater tendency to allow potassium to flow into the cell rather than out of it. This asymmetry in potassium ion conductance plays a key role in the excitability of muscle cells and neurons. The protein encoded by this gene is an integral membrane protein and member of the inward rectifier potassium channel family. The encoded protein has a small unitary conductance compared to other members of this protein family. Two transcript variants encoding the same protein have been found for this gene.

Source: NCBI Gene 3761 — RefSeq curated summary.

At a glance

• GWAS associations: 6
• Clinical variants (ClinVar): 38 total
• Druggable target: yes
• MANE Select transcript: NM_152868

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6265
Approved symbol	KCNJ4
Name	potassium inwardly rectifying channel subfamily J member 4
Location	22q13.1
Locus type	gene with protein product
Status	Approved
Aliases	Kir2.3, HIR, HRK1, hIRK2, IRK3
Ensembl gene	ENSG00000168135
Ensembl biotype	protein_coding
OMIM	600504
Entrez	3761

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 3 protein_coding

ENST00000303592, ENST00000940563, ENST00000947103

RefSeq mRNA: 2 — MANE Select: NM_152868 NM_004981, NM_152868

CCDS: CCDS13971

Canonical transcript exons

ENST00000303592 — 2 exons

Exon	Start	End
ENSE00001122853	38426327	38428171
ENSE00001246289	38454980	38455199

Expression profiles

Bgee: expression breadth ubiquitous, 119 present calls, max score 99.57.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
endothelial cell	CL:0000115	99.57	gold quality
middle temporal gyrus	UBERON:0002771	98.85	gold quality
Brodmann (1909) area 10	UBERON:0013541	98.70	gold quality
Brodmann (1909) area 23	UBERON:0013554	98.60	gold quality
frontal pole	UBERON:0002795	98.28	gold quality
superior frontal gyrus	UBERON:0002661	97.70	gold quality
postcentral gyrus	UBERON:0002581	97.13	gold quality
Brodmann (1909) area 46	UBERON:0006483	96.91	gold quality
parietal lobe	UBERON:0001872	96.86	gold quality
CA1 field of hippocampus	UBERON:0003881	96.36	gold quality
entorhinal cortex	UBERON:0002728	96.29	gold quality
primary visual cortex	UBERON:0002436	95.93	gold quality
apex of heart	UBERON:0002098	95.48	gold quality
occipital lobe	UBERON:0002021	94.94	gold quality
orbitofrontal cortex	UBERON:0004167	94.54	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	94.53	gold quality
frontal cortex	UBERON:0001870	94.49	gold quality
prefrontal cortex	UBERON:0000451	94.44	gold quality
middle frontal gyrus	UBERON:0002702	94.33	gold quality
neocortex	UBERON:0001950	93.63	gold quality
Brodmann (1909) area 9	UBERON:0013540	93.34	gold quality
cerebral cortex	UBERON:0000956	93.04	gold quality
right frontal lobe	UBERON:0002810	92.63	gold quality
cingulate cortex	UBERON:0003027	92.59	gold quality
anterior cingulate cortex	UBERON:0009835	92.57	gold quality
telencephalon	UBERON:0001893	91.80	gold quality
nucleus accumbens	UBERON:0001882	91.65	gold quality
temporal lobe	UBERON:0001871	91.37	gold quality
putamen	UBERON:0001874	91.25	gold quality
caudate nucleus	UBERON:0001873	90.25	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.65

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

29 targeting KCNJ4, 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-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-548AJ-5P	99.78	71.12	3085
HSA-MIR-548F-5P	99.78	71.02	3093
HSA-MIR-548G-5P	99.78	71.12	3085
HSA-MIR-548X-5P	99.78	71.12	3085
HSA-MIR-4699-3P	99.71	70.15	3142
HSA-MIR-4729	99.69	72.18	4233
HSA-MIR-4472	99.56	66.08	1478
HSA-MIR-136-5P	99.50	67.26	1153
HSA-MIR-361-3P	99.19	66.45	1381
HSA-MIR-6734-3P	99.15	66.27	1627
HSA-MIR-6814-5P	99.03	66.68	1273
HSA-MIR-4709-3P	98.88	68.04	1594
HSA-MIR-3145-3P	98.85	69.07	2031
HSA-MIR-4635	98.74	67.63	1339
HSA-MIR-6761-5P	98.71	68.03	1504
HSA-MIR-3135B	98.61	65.33	1470
HSA-MIR-10397-3P	97.78	65.70	601
HSA-MIR-2467-5P	97.36	67.71	991
HSA-MIR-194-3P	97.36	65.96	1027
HSA-MIR-3616-3P	96.96	65.45	983
HSA-MIR-5702	96.68	68.21	958
HSA-MIR-152-5P	96.42	66.59	960
HSA-MIR-4296	96.35	63.55	1233
HSA-MIR-4265	96.18	64.68	557
HSA-MIR-4322	96.18	64.85	539

Literature-anchored findings (GeneRIF, showing 9)

• Kir2.2 and Kir2.1 are primary determinants of endogenous K(+) conductance in HAECs under resting conditions and that Kir2.2 provides the dominant conductance in these cells. (PMID:15958527)
• Results describe the regulation of inwardly rectifying potassium current and its main molecular correlates, Kir2.1, Kir2.2 and Kir2.3 channels, by endothelin-1 in human atrial cardiomyocytes. (PMID:16258766)
• In conclusion, the data are consistent with the universal mechanism of rectification in Kir2 channels, but also point to significant, and physiologically important, quantitative differences between Kir2 isoforms. (PMID:16373386)
• Kir2.3 is internalized by an AP-2 clathrin-dependent mechanism. (PMID:18180291)
• possibility of intramolecular interactions of the residue Kir2.3(H117) with conserved cysteines in close proximity to the selectivity filter (PMID:18453743)
• The data suggest that Kir2.3 plays a potentially important role in I(K1) currents in neonatal rat cardiomyocytes. (PMID:18503768)
• TIP-1 may act as an important regulator for the endocytic pathway of Kir2.3. (PMID:19635485)
• Increased excitability and decreased dendritic arborization are associated with downregulation of inward rectifier potassium channels (Kir2.1/2.3). (PMID:22396414)
• results shed some light on the contribution of KCNJ4 functioning as a significant player in LADC, implying that KCNJ4 might be a valuable prognostic biomarker and a potential therapeutic target for LADC treatment (PMID:30512237)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio		ENSDARG00000068110
mus_musculus	Kcnj4	ENSMUSG00000044216
rattus_norvegicus	Kcnj4	ENSRNOG00000013869

Paralogs (15): KCNJ13 (ENSG00000115474), KCNJ5 (ENSG00000120457), KCNJ8 (ENSG00000121361), KCNJ2 (ENSG00000123700), KCNJ1 (ENSG00000151704), KCNJ16 (ENSG00000153822), KCNJ6 (ENSG00000157542), KCNJ15 (ENSG00000157551), KCNJ9 (ENSG00000162728), KCNJ3 (ENSG00000162989), KCNJ10 (ENSG00000177807), KCNJ14 (ENSG00000182324), KCNJ12 (ENSG00000184185), KCNJ11 (ENSG00000187486), KCNJ18 (ENSG00000260458)

Protein

Protein identifiers

Inward rectifier potassium channel 4 — P48050 (reviewed: P48050)

Alternative names: HIRK2, HRK1, Hippocampal inward rectifier, Inward rectifier K(+) channel Kir2.3, Potassium channel, inwardly rectifying subfamily J member 4

All UniProt accessions (1): P48050

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. Can be blocked by extracellular barium and cesium.

Subunit / interactions. Homomultimeric and heteromultimeric association with KCNJ2 and KCNJ12. Interacts with DLG2 and DLG4. Associates, via its PDZ-recognition domain, with a complex containing LIN7A, LIN7B, LIN7C, DLG1, CASK and APBA1. Interacts with TAX1BP3. TAX1BP3 competes with LIN7 family members for KCNJ4 binding.

Subcellular location. Cell membrane. Postsynaptic cell membrane. Cytoplasmic vesicle membrane.

Tissue specificity. Heart, skeletal muscle, and several different brain regions including the hippocampus.

Domain organisation. The Val/Gly/Ala/Pro stretch may have a functional role in the conductance or permeation properties.

Similarity. Belongs to the inward rectifier-type potassium channel (TC 1.A.2.1) family. KCNJ4 subfamily.

RefSeq proteins (2): NP_004972, NP_690607* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003273	K_chnl_inward-rec_Kir2.3	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 (21 total): sequence conflict 7, topological domain 4, short sequence motif 2, transmembrane region 2, intramembrane region 2, chain 1, site 1, mutagenesis site 1, region of interest 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
3GJ9	X-RAY DIFFRACTION	2.8

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P48050-F1	79.90	0.61

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

Mutagenesis-validated functional residues (1):

Position	Phenotype
117	abolishes inwardly rectifying potassium currents and ph-sensitivity.

Function

Pathways and Gene Ontology

Reactome pathways

15 pathways

ID	Pathway
R-HSA-1296041	Activation of G protein gated Potassium channels
R-HSA-1296053	Classical Kir channels
R-HSA-5576886	Phase 4 - resting membrane potential
R-HSA-997272	Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits
R-HSA-112314	Neurotransmitter receptors and postsynaptic signal transmission
R-HSA-112315	Transmission across Chemical Synapses
R-HSA-112316	Neuronal System
R-HSA-1296059	G protein gated Potassium channels
R-HSA-1296065	Inwardly rectifying K+ channels
R-HSA-1296071	Potassium Channels
R-HSA-397014	Muscle contraction
R-HSA-5576891	Cardiac conduction
R-HSA-977443	GABA receptor activation
R-HSA-977444	GABA B receptor activation
R-HSA-991365	Activation of GABAB receptors

MSigDB gene sets: 133 (showing top): GSE18804_BRAIN_VS_COLON_TUMORAL_MACROPHAGE_UP, GOBP_POTASSIUM_ION_TRANSPORT, BENPORATH_ES_WITH_H3K27ME3, GRUETZMANN_PANCREATIC_CANCER_DN, REACTOME_POTASSIUM_CHANNELS, REACTOME_INWARDLY_RECTIFYING_K_CHANNELS, MODULE_45, MODULE_64, DACOSTA_UV_RESPONSE_VIA_ERCC3_UP, MODULE_16, GOBP_MONOATOMIC_CATION_TRANSPORT, MODULE_66, SHETH_LIVER_CANCER_VS_TXNIP_LOSS_PAM5, MODULE_157, DACOSTA_UV_RESPONSE_VIA_ERCC3_COMMON_UP

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), PDZ domain binding (GO:0030165), protein binding (GO:0005515)

GO Cellular Component (9): plasma membrane (GO:0005886), voltage-gated potassium channel complex (GO:0008076), basolateral plasma membrane (GO:0016323), cytoplasmic vesicle membrane (GO:0030659), postsynaptic membrane (GO:0045211), membrane (GO:0016020), cytoplasmic vesicle (GO:0031410), monoatomic ion channel complex (GO:0034702), synapse (GO:0045202)

Reactome top-level categories

Rollup of top-11 pathways:

Category	Pathways
Inwardly rectifying K+ channels	2
Neuronal System	2
G protein gated Potassium channels	1
Cardiac conduction	1
Activation of GABAB receptors	1
Transmission across Chemical Synapses	1
Potassium Channels	1
Muscle contraction	1
Neurotransmitter receptors and postsynaptic signal transmission	1
GABA receptor activation	1
GABA B receptor activation	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
metal ion transport	1
monoatomic ion transmembrane transport	1
regulation of transmembrane transport	1
regulation of monoatomic ion transport	1
potassium ion transmembrane transport	1
inorganic cation import across plasma membrane	1
transport	1
monoatomic ion transport	1
transmembrane transport	1
voltage-gated potassium channel activity	1
ligand-gated monoatomic cation channel activity	1
protein domain specific binding	1
binding	1
membrane	1
cell periphery	1
potassium channel complex	1
plasma membrane protein complex	1
basal plasma membrane	1
plasma membrane region	1
vesicle membrane	1
cytoplasmic vesicle	1
synaptic membrane	1
postsynapse	1
cellular anatomical structure	1
cytoplasm	1
intracellular vesicle	1
transmembrane transporter complex	1
cell junction	1

Protein interactions and networks

STRING

1736 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
KCNJ4	DLG4	P78352	798
KCNJ4	KCNJ12	Q14500	762
KCNJ4	TAX1BP3	O14907	740
KCNJ4	LIN7A	O14910	627
KCNJ4	DLG1	Q12959	620
KCNJ4	KCNA5	P22460	599
KCNJ4	KCND3	Q9UK17	598
KCNJ4	KCNA4	P22459	594
KCNJ4	KCNJ2	P48049	591
KCNJ4	KCNK5	O95279	572
KCNJ4	SCN5A	Q14524	556
KCNJ4	KCND2	Q9NZV8	550
KCNJ4	KCNH2	Q12809	539
KCNJ4	IQSEC2	Q5JU85	520
KCNJ4	DLG2	Q15700	514

IntAct

132 interactions, top by confidence:

A	B	Type	Score
SCRIB	KCNJ4	psi-mi:“MI:0915”(physical association)	0.720
SCRIB	KCNJ4	psi-mi:“MI:0407”(direct interaction)	0.720
KCNJ4	SCRIB	psi-mi:“MI:0407”(direct interaction)	0.720
KCNJ4	Dlg1	psi-mi:“MI:0914”(association)	0.560
Dlg1	KCNJ4	psi-mi:“MI:0915”(physical association)	0.560
KCNJ4	LIN7B	psi-mi:“MI:0915”(physical association)	0.510
LIN7B	KCNJ4	psi-mi:“MI:0915”(physical association)	0.510
KCNJ4	MAGI3	psi-mi:“MI:0407”(direct interaction)	0.440
KCNJ4	SYNJ2BP	psi-mi:“MI:0407”(direct interaction)	0.440
KCNJ4	TAX1BP3	psi-mi:“MI:0407”(direct interaction)	0.440
KCNJ4	MAGI2	psi-mi:“MI:0407”(direct interaction)	0.440
KCNJ4	MAST2	psi-mi:“MI:0407”(direct interaction)	0.440
KCNJ4	PTPN3	psi-mi:“MI:0407”(direct interaction)	0.440
KCNJ4	DLG1	psi-mi:“MI:0407”(direct interaction)	0.440
PDZRN3	KCNJ4	psi-mi:“MI:0407”(direct interaction)	0.440
KCNJ4	PDZD2	psi-mi:“MI:0407”(direct interaction)	0.440
KCNJ4	DLG2	psi-mi:“MI:0407”(direct interaction)	0.440
KCNJ4	DLG3	psi-mi:“MI:0407”(direct interaction)	0.440
KCNJ4	WHRN	psi-mi:“MI:0407”(direct interaction)	0.440
KCNJ4	PDZRN4	psi-mi:“MI:0407”(direct interaction)	0.440
KCNJ4	DLG4	psi-mi:“MI:0407”(direct interaction)	0.440
KCNJ4	TIAM2	psi-mi:“MI:0407”(direct interaction)	0.440
KCNJ4	MAST1	psi-mi:“MI:0407”(direct interaction)	0.440
KCNJ4	PDZD7	psi-mi:“MI:0407”(direct interaction)	0.440
SNTB1	KCNJ4	psi-mi:“MI:0407”(direct interaction)	0.440
APBA3	KCNJ4	psi-mi:“MI:0407”(direct interaction)	0.440

BioGRID (26): KCNJ4 (Two-hybrid), DLG1 (Affinity Capture-Western), CASK (Affinity Capture-Western), LIN7C (Affinity Capture-Western), DMD (Affinity Capture-Western), SNTA1 (Affinity Capture-Western), DLG1 (Affinity Capture-Western), CASK (Affinity Capture-Western), DLG4 (Affinity Capture-Western), LIN7A (Affinity Capture-Western), LIN7C (Affinity Capture-Western), DLG4 (Affinity Capture-Western), DLG2 (Affinity Capture-Western), KCNJ4 (Two-hybrid), LIN7B (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

3 interactions.

A	Effect	B	Mechanism
PKA	“up-regulates activity”	KCNJ4	phosphorylation
PRKCA	“down-regulates activity”	KCNJ4	phosphorylation
EGFR	“up-regulates activity”	KCNJ4	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 87 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	50.1×	2e-06
Unblocking of NMDA receptors, glutamate binding and activation	5	47.7×	2e-06
Negative regulation of NMDA receptor-mediated neuronal transmission	5	47.7×	2e-06
Assembly and cell surface presentation of NMDA receptors	10	44.5×	1e-12
Dopamine Neurotransmitter Release Cycle	5	43.5×	3e-06
Long-term potentiation	5	41.7×	3e-06
Neurexins and neuroligins	11	38.0×	8e-13
Protein-protein interactions at synapses	7	32.6×	1e-07

GO biological processes:

GO term	Partners	Fold	FDR
establishment or maintenance of epithelial cell apical/basal polarity	11	77.0×	3e-16
protein localization to synapse	6	55.4×	1e-07
receptor clustering	7	52.6×	1e-08
regulation of postsynaptic membrane neurotransmitter receptor levels	7	41.8×	5e-08
protein-containing complex assembly	9	12.3×	3e-06
cell-cell adhesion	10	12.2×	7e-07
regulation of small GTPase mediated signal transduction	5	8.7×	5e-03
chemical synaptic transmission	7	6.5×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	34
Likely benign	1
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

377 predictions. Top by Δscore:

Variant	Effect	Δscore
22:38454974:GCTTA:G	donor_loss	1.0000
22:38454975:CTTA:C	donor_loss	1.0000
22:38454976:TTACC:T	donor_loss	1.0000
22:38454977:TA:T	donor_loss	1.0000
22:38454978:A:AC	donor_gain	1.0000
22:38454979:C:CC	donor_gain	1.0000
22:38454979:C:CT	donor_loss	1.0000
22:38454979:CCG:C	donor_gain	1.0000
22:38428169:GGCC:G	acceptor_loss	0.9900
22:38428171:CCT:C	acceptor_loss	0.9900
22:38428172:C:CC	acceptor_gain	0.9900
22:38452536:A:AC	donor_gain	0.9900
22:38452537:C:CC	donor_gain	0.9900
22:38452543:T:A	donor_gain	0.9900
22:38454978:ACCG:A	donor_gain	0.9800
22:38454979:CCGC:C	donor_gain	0.9800
22:38428167:AGGGC:A	acceptor_gain	0.9700
22:38428168:GGGC:G	acceptor_gain	0.9700
22:38428169:GGC:G	acceptor_gain	0.9700
22:38428170:GC:G	acceptor_gain	0.9700
22:38428171:CC:C	acceptor_gain	0.9700
22:38452532:C:A	donor_gain	0.9700
22:38452537:CTGCT:C	donor_gain	0.9700
22:38428169:GGCCT:G	acceptor_gain	0.9600
22:38428170:GCC:G	acceptor_gain	0.9600
22:38428171:CCTGC:C	acceptor_gain	0.9600
22:38454978:AC:A	donor_gain	0.9600
22:38454979:CC:C	donor_gain	0.9600
22:38454979:CCGCT:C	donor_gain	0.9600
22:38428168:GGGCC:G	acceptor_gain	0.9500

AlphaMissense

2933 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
22:38427125:A:C	F336L	1.000
22:38427125:A:T	F336L	1.000
22:38427126:A:C	F336C	1.000
22:38427126:A:G	F336S	1.000
22:38427127:A:G	F336L	1.000
22:38427179:A:C	F318L	1.000
22:38427179:A:T	F318L	1.000
22:38427180:A:C	F318C	1.000
22:38427180:A:G	F318S	1.000
22:38427181:A:C	F318V	1.000
22:38427181:A:G	F318L	1.000
22:38427181:A:T	F318I	1.000
22:38427183:C:G	R317P	1.000
22:38427189:C:A	G315V	1.000
22:38427189:C:T	G315D	1.000
22:38427190:C:G	G315R	1.000
22:38427191:C:A	W314C	1.000
22:38427191:C:G	W314C	1.000
22:38427192:C:G	W314S	1.000
22:38427193:A:G	W314R	1.000
22:38427193:A:T	W314R	1.000
22:38427201:T:A	E311V	1.000
22:38427213:T:G	Y307S	1.000
22:38427214:A:C	Y307D	1.000
22:38427214:A:G	Y307H	1.000
22:38427214:A:T	Y307N	1.000
22:38427216:G:A	S306F	1.000
22:38427216:G:T	S306Y	1.000
22:38427217:A:G	S306P	1.000
22:38427222:C:G	R304P	1.000

dbSNP variants (sampled 300 via entrez): RS1000189807 (22:38436695 T>C), RS1000271425 (22:38454849 G>A,C,T), RS1000299562 (22:38434726 CCTCA>C), RS1000382819 (22:38448796 G>A), RS1000382913 (22:38446400 G>A), RS1000496289 (22:38436631 C>T), RS1000524137 (22:38438407 G>T), RS1000602169 (22:38456216 T>G), RS1000633360 (22:38444535 T>A), RS1000633737 (22:38436303 A>G), RS1000699763 (22:38443321 C>A), RS1000796533 (22:38442168 C>A,T), RS1001067483 (22:38444239 G>A), RS1001104474 (22:38442404 A>C,G), RS1001122061 (22:38438852 G>A,T)

Disease associations

OMIM: gene MIM:600504 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): prostate cancer (MONDO:0008315)

Orphanet (1): Familial prostate cancer (Orphanet:1331)

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST002438_10	Conotruncal heart defects	1.000000e-06
GCST007329_23	Automobile speeding propensity	2.000000e-08
GCST007576_168	Chronotype	2.000000e-08
GCST010346_3	TPE interval (resting)	1.000000e-20
GCST010346_36	TPE interval (resting)	1.000000e-11
GCST010346_51	TPE interval (resting)	7.000000e-10

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0008579	risk-taking behaviour
EFO:0008328	chronotype measurement
EFO:0004644	TPE interval measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
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

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2146347 (SINGLE PROTEIN)

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

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 (7 total), top 7:

Ligand	Action	Affinity	Parameter
H+	Antagonist	6.77	pKi
tenidap	Agonist	6.4	pEC50
arachidonic acid	Agonist	6.35	pEC50
Mg2+	Antagonist	5.0	pKd
Ba2+	Antagonist	4.99	pIC50
Cs+	Antagonist	4.52	pKi
tetraethylammonium	Antagonist	4.21	pKi

CTD chemical–gene interactions

30 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression, affects expression, increases expression	4
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
sotorasib	affects cotreatment, decreases expression	1
trichostatin A	decreases expression	1
CGP 52608	affects binding, increases reaction	1
entinostat	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
bis-N,N-dimethylamino-2-(N-methylpyrrolyl)methyl cyclopentadienyl titanium (IV)	increases expression	1
trametinib	decreases expression, affects cotreatment	1
(+)-JQ1 compound	decreases expression	1
NVP-BKM120	affects cotreatment, decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Decitabine	affects expression	1
Carvedilol	affects binding, decreases activity, decreases reaction	1
Acetaminophen	decreases expression	1
Atrazine	increases expression	1
Barium	decreases activity	1
Benzo(a)pyrene	decreases methylation	1
Cisplatin	affects expression	1
Diethylhexyl Phthalate	decreases expression	1
Lead	affects expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Potassium	increases transport	1
Silicon Dioxide	decreases expression	1
Thallium	increases transport	1
1-Methyl-4-phenylpyridinium	increases expression	1
Cyclosporine	decreases methylation	1
Aflatoxin B1	decreases methylation	1
Phosphatidylinositol Phosphates	decreases reaction, affects binding, decreases activity	1

ChEMBL screening assays

7 unique, capped per target: 7 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL2148628	Binding	Inhibition of human Kir2.3 expressed in CHO cells assessed as inhibition of 86Rb+ efflux	Discovery of Selective Small Molecule ROMK Inhibitors as Potential New Mechanism Diuretics. — ACS Med Chem Lett

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