Affinage

KCNJ5

G protein-activated inward rectifier potassium channel 4 · UniProt P48544

Length
419 aa
Mass
47.7 kDa
Annotated
2026-06-10
100 papers in source corpus 39 papers cited in narrative 39 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 10/10 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

KCNJ5 encodes GIRK4 (Kir3.4), an inwardly rectifying K+ channel subunit that assembles with GIRK1 (KCNJ3) into G-protein-gated IKACh channels and also forms functional homotetramers (PMID:9395492, PMID:9765280, PMID:11384974, PMID:30764634). Channel gating is driven by direct binding of Gβγ dimers to two C-terminal regions of GIRK4 (residues 209–245), an interaction characterized in real time and required for activation (PMID:9642257, PMID:8938723), with channel open probability further tuned by PKA phosphorylation and PP2A dephosphorylation (PMID:12547819). The selectivity filter, stabilized by a glutamate–arginine salt bridge that acts as a structural 'bowstring', both restricts permeation to K+ and serves as the agonist-activated gate, coupling ion selectivity to gating (PMID:14504281, PMID:14525972); GIRK4 additionally confers the maturation and plasma-membrane targeting of GIRK1 through a C-terminal domain (PMID:9891030). In the heart, IKACh mediates roughly half of vagal negative chronotropy and beat-to-beat heart rate variability, interacts antagonistically with the HCN4 'funny' current in pacemaking, and drives adenosine-induced atrial fibrillation through localized reentrant drivers (PMID:9459446, PMID:25144323, PMID:27462069). In adrenal glomerulosa cells, basal GIRK4 current maintains a hyperpolarized resting potential and suppresses aldosterone synthesis (PMID:22798349, PMID:25347571); somatic and germline mutations at or near the selectivity filter (e.g. G151R, L168R, T158A) abolish K+ selectivity, permit Na+ influx and depolarization, open voltage-gated Ca2+ channels and impair Na+/Ca2+ exchange, raising cytosolic Ca2+ that activates StAR and the CYP11B2 regulators NURR1/ATF2 to drive aldosterone overproduction and adrenal proliferation in primary aldosteronism (PMID:22203740, PMID:22308486, PMID:22315453, PMID:24506072, PMID:27099398). The magnitude of Na+ conductance determines clinical phenotype, with very high conductance causing Na+-dependent cell lethality that limits hyperplasia (PMID:22308486). A separate loss-of-function mutation (G387R) reduces surface channel and causes long QT syndrome type 13 (PMID:20560207). Beyond the heart and adrenal gland, GIRK4 is expressed in hypothalamic nuclei where its loss produces late-onset obesity and impaired spatial learning (PMID:10908597, PMID:18523006). Macrolide antibiotics selectively inhibit mutant GIRK4, and KCNJ5 expression is repressed by miR-221/222 acting on its 3'-UTR (PMID:28604387, PMID:31312877).

Mechanistic history

Synthesis pass · year-by-year structured walk · 17 steps
  1. 1996 High

    Established the physical basis of G-protein gating by showing Gβγ binds the GIRK4 C-terminus directly, defining the channel as a direct Gβγ effector rather than acting through a diffusible second messenger.

    Evidence Surface plasmon resonance kinetics of recombinant Gβ1γ2 binding to immobilized Kir3.4 C-terminal fusion protein

    PMID:8938723

    Open questions at the time
    • Binding measured on isolated C-terminus, not full-length channel in membrane
    • Did not localize the binding determinants within the C-terminus
  2. 1997 High

    Defined how GIRK4 and GIRK1 cooperate, showing heteromeric assembly proceeds through homologous regions and identifying a selectivity-filter residue critical for inter-subunit synergy.

    Evidence Site-directed mutagenesis and co-expression with G-protein subunits/muscarinic receptors in Xenopus oocytes, two-electrode voltage clamp

    PMID:9395492

    Open questions at the time
    • Stoichiometry of the native heteromer not resolved here
    • Structural model of the assembly interface absent
  3. 1998 High

    Linked GIRK4 to cardiac physiology in vivo, demonstrating IKACh accounts for ~half of vagal/adenosine-mediated heart rate slowing and is required for heart rate variability.

    Evidence GIRK4 knockout mice with ECG telemetry and pharmacological vagal/adenosine challenge

    PMID:9459446

    Open questions at the time
    • Did not address non-cardiac roles
    • Source of the other ~half of vagal chronotropy unresolved
  4. 1998 High

    Mapped the Gβγ-binding determinants and showed GIRK4 forms native homotetramers in addition to heteromers, expanding the functional repertoire of the subunit.

    Evidence Peptide competition/mutagenesis with patch clamp; biochemical purification from bovine atria with single-channel recording

    PMID:9642257 PMID:9765280

    Open questions at the time
    • Physiological function of native homotetramers in heart not established
    • Relative contribution of homomers vs heteromers in vivo unknown
  5. 1999 High

    Identified GIRK4 as a chaperone-like requirement for GIRK1, showing it drives GIRK1 maturation and surface delivery via a discrete C-terminal domain.

    Evidence Flag-tagged GIRK1 pulse-labeling, truncation/chimera analysis, and immunocytochemistry in GIRK4 knockout myocytes

    PMID:9891030

    Open questions at the time
    • Trafficking machinery engaged by the C-terminal domain not identified
    • Whether targeting is ER-exit or post-Golgi unspecified
  6. 2003 High

    Resolved the structural-functional logic of the pore, showing a salt-bridge bowstring stabilizes the selectivity filter and that the filter itself serves as the agonist-activated gate.

    Evidence Systematic selectivity-filter mutagenesis with molecular modeling and voltage clamp in oocytes, correlating selectivity, rectification, and Gβγ activation

    PMID:14504281 PMID:14525972

    Open questions at the time
    • No high-resolution structure of the gated states
    • Coupling pathway from Gβγ binding to filter gate not mapped
  7. 2011 High

    Established the core disease mechanism of primary aldosteronism, showing selectivity-filter mutations abolish K+ selectivity to permit Na+ influx, depolarization, Ca2+ entry, and aldosterone-driving signaling.

    Evidence Sequencing of APA tumors with heterologous expression and patch-clamp measurement of reversal potential/selectivity

    PMID:22203740 PMID:22308486 PMID:22315453

    Open questions at the time
    • Did not fully delineate transcriptional effectors downstream of Ca2+
    • Did not explain phenotypic variability across mutations
  8. 2012 High

    Placed Ca2+/calmodulin signaling downstream of mutant-channel depolarization and showed wild-type basal GIRK4 activity normally suppresses aldosterone, defining both gain- and loss-of-function arms.

    Evidence Lentiviral mutant/WT KCNJ5 expression in HAC15 cells, aldosterone and membrane-voltage assays, nifedipine/W-7/naringin pharmacology

    PMID:22315453 PMID:22798349

    Open questions at the time
    • In-cell-line model not adrenal tissue context
    • Identity of the calmodulin-dependent steroidogenic step not pinned down here
  9. 2014 High

    Explained clinical heterogeneity by showing the magnitude of Na+ conductance dictates outcome, with extreme conductance causing Na+-dependent cell death that paradoxically limits hyperplasia.

    Evidence Sequencing of kindreds and patch-clamp Na+-conductance/cell-lethality assays in HEK293T cells

    PMID:22308486

    Open questions at the time
    • Mechanism of Na+-dependent lethality not molecularly defined
    • Threshold conductance separating phenotypes only approximated
  10. 2014 Medium

    Refined the ionic mechanism in adrenal cells, showing mutant channels raise Ca2+ through both voltage-gated Ca2+ channel activation and impaired Na+/Ca2+ exchange, and altered the channel's pharmacological profile.

    Evidence Expression in NCI-H295R cells with Na+/Ca2+ imaging and pharmacological profiling (Ba2+, tertiapin-Q, verapamil, amiloride)

    PMID:24506072

    Open questions at the time
    • Single lab, single adrenal cell line
    • Relative contribution of exchanger impairment vs channel opening not quantified
  11. 2010 High

    Extended KCNJ5 pathology to cardiac arrhythmia, showing a loss-of-function surface-expression-reducing mutation causes long QT syndrome type 13.

    Evidence Linkage analysis, sequencing, cardiac-tissue Western blot, heterologous patch-clamp and surface-expression assay in a large family

    PMID:20560207

    Open questions at the time
    • Mechanism by which reduced IKACh prolongs QT not fully explained
    • Single family
  12. 2016 High

    Defined the full transcriptional/steroidogenic output of the gain-of-function lesion, linking Ca2+ entry to both acute (StAR) and chronic (NURR1/ATF2/CYP11B2) regulation of aldosterone.

    Evidence Doxycycline-inducible KCNJ5-T158A HAC15 cells with electrophysiology, qRT-PCR, Western, LC-MS/MS steroid profiling, verapamil dissection

    PMID:27099398

    Open questions at the time
    • Direct molecular link from Ca2+ to NURR1/ATF2 activation not resolved
    • Cell-line model
  13. 2016 High

    Demonstrated cardiac roles for GIRK4 beyond chronotropy, showing antagonism with the HCN4 pacemaker current and a causal contribution to adenosine-induced atrial fibrillation.

    Evidence HCN4 dominant-negative/GIRK4 double-mutant mice with ECG; human-heart optical mapping with regional GIRK4 immunoblotting and tertiapin block

    PMID:25144323 PMID:27462069

    Open questions at the time
    • Molecular basis of the IKACh/If interaction not defined
    • Regional GIRK4 enrichment mechanism unknown
  14. 2017 High

    Provided a therapeutic lever by identifying macrolide antibiotics that selectively inhibit mutant but not wild-type GIRK4 and suppress aldosterone output.

    Evidence High-throughput mutant-lethality rescue screen, patch-clamp inhibition, CYP11B2/aldosterone assays in adrenocortical lines

    PMID:28604387

    Open questions at the time
    • Structural basis of mutant-selective inhibition not solved
    • In vivo efficacy not established in this work
  15. 2008 High

    Revealed a central-nervous-system metabolic role, showing hypothalamic GIRK4 contributes to energy homeostasis with knockout causing late-onset obesity, alongside earlier evidence for spatial learning.

    Evidence Girk4-promoter EGFP reporter localization plus metabolic/behavioral phenotyping of GIRK4 knockout mice; Morris water maze in KO

    PMID:10908597 PMID:18523006

    Open questions at the time
    • Identity of GIRK4 partner subunit and the GPCR driving hypothalamic signaling unknown
    • Circuit-level mechanism not defined
  16. 2019 Medium

    Identified post-transcriptional control of KCNJ5, showing miR-221/222 directly repress its 3'-UTR to reduce channel abundance.

    Evidence Luciferase 3'-UTR reporter, miR overexpression in cardiomyocytes, Western blot, flux and patch-clamp

    PMID:31312877

    Open questions at the time
    • Physiological/pathological context driving miR-221/222 regulation unclear
    • Single lab
  17. 2022 High

    Advanced isoform-selective pharmacology by identifying a small molecule that activates homomeric GIRK4 via a PIP2-proximal site, with a single slide-helix residue determining selectivity.

    Evidence Molecular modeling, mutagenesis, and electrophysiology across GIRK subtypes in oocytes and HEK293 cells

    PMID:35525275

    Open questions at the time
    • Therapeutic relevance in disease models not tested
    • No experimental structure of the activator-bound channel

Open questions

Synthesis pass · forward-looking unresolved questions
  • How Gβγ binding is mechanically transmitted to the selectivity-filter gate, and how mutation-driven Ca2+ entry is molecularly coupled to NURR1/ATF2-dependent CYP11B2 transcription, remain unresolved.
  • No structure of activated/gated GIRK4 states
  • Direct Ca2+-to-transcription-factor link not mapped
  • In vivo validation of mutant-selective therapeutics lacking

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005215 transporter activity 4 GO:0005198 structural molecule activity 2 GO:0060089 molecular transducer activity 2 GO:0098772 molecular function regulator activity 1
Localization
GO:0005886 plasma membrane 4
Pathway
R-HSA-162582 Signal Transduction 3 R-HSA-397014 Muscle contraction 3 R-HSA-1430728 Metabolism 2
Partners
CHRM2GNB1GNG2KCNJ3KIR2.1
Complex memberships
GIRK4 homotetramerIKACh channel (GIRK1/GIRK4 heterotetramer)

Evidence

Reading pass · 39 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1998 GIRK4 knockout mice lack the cardiac IKACh current and show that IKACh mediates approximately half of the negative chronotropic effects of vagal stimulation and adenosine on heart rate, and is necessary for beat-to-beat heart rate variability. Targeted gene disruption (knockout mouse), ECG telemetry, pharmacological manipulation Neuron High 9459446
1997 GIRK4 (Kir3.4) and GIRK1 subunits interact via homologous regions (not divergent termini) to form G-protein-regulated heteromeric channels; the selectivity filter residue Ser143 in GIRK4 (analogous to Phe137 in GIRK1) is critical for synergy between subunits, and both GIRK1(F137S) and GIRK4(S143T) homomeric mutants respond qualitatively similarly to Gβγ, muscarinic receptors, and G-protein subunits. Site-directed mutagenesis, heterologous expression in Xenopus oocytes, co-expression with G-protein subunits and muscarinic receptors, two-electrode voltage clamp The Journal of biological chemistry High 9395492
1998 Gβγ binding to GIRK4 is critical for IKACh activation: two Gβγ-binding regions in the GIRK4 C-terminus (amino acids 209–225 and 226–245) were delineated; a point mutation C216T in GIRK4 reduced Gβγ binding affinity and channel activation, and conversion of five residues in the 226–245 region to those of the Gβγ-insensitive IRK1 completely abolished Gβγ binding to IKACh and channel activation. Purification of native IKACh, peptide competition assays for Gβγ binding, site-directed mutagenesis, functional expression in mammalian cells, patch-clamp electrophysiology The Journal of biological chemistry High 9642257
1996 Gβ1γ2 dimers directly bind the carboxyl-terminal domain of Kir3.4 (GIRK4; residues 186–419) with a dissociation constant of ~800 nM and a slow dissociation rate (~0.003 s⁻¹), as measured in real time by surface plasmon resonance biosensor technology. Surface plasmon resonance biosensor (GST-fusion protein of Kir3.4 C-terminus immobilized on chip, recombinant Gβ1γ2 binding kinetics measured in real time) Neuropharmacology High 8938723
1999 GIRK4 is required for cell surface localization and proper glycosylation of GIRK1: GIRK1 alone is retained intracellularly in immature (core-glycosylated/non-glycosylated) forms, but coexpression with GIRK4 causes GIRK1 to acquire mature glycosylation and reach the plasma membrane. A 25-amino-acid region in the GIRK4 C-terminus is required for cell surface targeting of GIRK1/GIRK4 heterotetramers, and a separate 25-amino-acid region is required for GIRK4 homotetramers. In GIRK4 knockout atrial myocytes, GIRK1 is intracellular and not maturely glycosylated. Extracellularly Flag-tagged GIRK1, [35S]methionine pulse-labeling, truncation and chimeric channel analysis, co-expression in heterologous cells, immunocytochemistry in GIRK4 knockout myocytes The Journal of biological chemistry High 9891030
1998 GIRK4 forms homotetramers in native bovine heart atria: approximately half of total atrial GIRK4 exists as GIRK1/GIRK4 heterotetramers (the classical IKACh), while the remaining half forms SDS-resistant high-molecular-weight complexes (most likely GIRK4 homotetramers) that do not contain GIRK1 and display unusual single-channel behavior. Biochemical purification from bovine heart atria, SDS-PAGE, Western blotting, single-channel patch-clamp recordings The Journal of biological chemistry High 9765280
2001 Overexpression of GIRK4 monomers or concatemers in rat atrial myocytes converts endogenous IKACh to a current with loss of fast desensitization, reduced inward rectification, and slowed activation—properties consistent with functional homomeric GIRK4 channels. Homomeric GIRK4 complexes form functional Gβγ-gated channels when expressed in CHO and HEK293 cells. Transient transfection of GIRK4 monomers/dimers/tetramers in cultured atrial myocytes and heterologous cell lines, whole-cell patch-clamp, two-electrode voltage clamp The Journal of biological chemistry High 11384974
2003 In the Kir3.1/Kir3.4 channel, a salt bridge between a glutamate and arginine residue behind the selectivity filter acts as a 'bowstring' to maintain the rigid structure of the selectivity filter and restrict permeation to K+; mutation of this residue pair reduces or abolishes K+ selectivity and also abolishes polyamine-induced inward rectification because polyamines now permeate rather than block the channel. Site-directed mutagenesis, heterologous expression in Xenopus oocytes, electrophysiology, molecular modeling The Journal of biological chemistry High 14504281
2003 The selectivity filter of Kir3.1/Kir3.4 acts as the agonist-activated gate: disrupting the salt bridge behind the selectivity filter by mutagenesis abolished both K+ selectivity and agonist (Gβγ) activation of the channel. Mutations within the filter that altered selectivity also altered agonist activation, while mutations that did not affect selectivity had little effect on agonist activation, demonstrating a tight correlation between filter structure, selectivity, and gating. Site-directed mutagenesis, heterologous expression in Xenopus oocytes, two-electrode voltage clamp The Journal of biological chemistry High 14525972
2010 A heterozygous loss-of-function mutation Kir3.4-Gly387Arg in KCNJ5 causes long QT syndrome type 13 (LQT13) by reducing plasma membrane expression of the channel, resulting in decreased IKACh current. Genome-wide linkage analysis, Sanger sequencing, Western blotting of human cardiac tissue, heterologous expression with patch-clamp electrophysiology, surface expression assay American journal of human genetics High 20560207
2011 Somatic mutations in KCNJ5 (G151R, L168R) and a germline mutation (T158A) alter the selectivity filter of GIRK4, causing loss of K+ selectivity, Na+ influx, and membrane depolarization, which activates voltage-gated Ca2+ channels, raises cytosolic calcium, and stimulates aldosterone production and adrenal cell proliferation in aldosterone-producing adenomas. Sanger sequencing of APA tumor DNA, heterologous expression in Xenopus oocytes and mammalian cells, patch-clamp electrophysiology measuring reversal potential and ion selectivity Science (referenced via multiple subsequent papers; mechanism first established by Choi et al.); key functional characterization in Hypertension High 22203740 22308486 22315453
2012 Expression of mutant KCNJ5 (T158A) in HAC15 adrenal cortical cells causes a 5.3-fold increase in aldosterone secretion, decreases plasma membrane polarization (depolarization), and allows Na+ and Ca2+ influx. The calcium channel antagonist nifedipine and calmodulin inhibitor W-7 inhibited this effect, placing Ca2+/calmodulin signaling downstream of KCNJ5 mutation-induced depolarization. Lentiviral-mediated expression in HAC15 cells, aldosterone secretion assay, membrane voltage measurements, pharmacological inhibition (nifedipine, W-7) Endocrinology High 22315453
2012 The novel GIRK4 mutation p.Trp126Arg (W126R) found in an APA upregulates CYP11B2 and NR4A2 expression in HAC15 adrenal cells and causes membrane voltage depolarization when overexpressed. Targeted next-generation sequencing, overexpression in HAC15 cells, CYP11B2/NR4A2 gene expression, whole-cell patch clamp Hypertension Medium 24082052
2012 Angiotensin II and a calcium ionophore downregulate KCNJ5 mRNA and protein in HAC15 cells. Overexpression of wild-type KCNJ5 decreases membrane voltage, intracellular calcium, and aldosterone synthesis. Activation of Kir3.4 by naringin inhibits angiotensin II-stimulated membrane depolarization and aldosterone secretion, demonstrating that basal Kir3.4 activity normally suppresses aldosterone production. Lentiviral overexpression in HAC15 cells, naringin pharmacology, membrane voltage and intracellular calcium measurements, aldosterone secretion assay, qRT-PCR Endocrinology Medium 22798349
2012 The novel somatic KCNJ5 mutation delI157 (deletion of isoleucine 157, near but not within the selectivity filter) confers Na+ permeability to the channel and reduced sensitivity to the KCNJ5 inhibitor tertiapin-Q, indicating structural changes around the mouth of the ion channel pore. Site-directed mutagenesis, heterologous expression in Xenopus oocytes, two-electrode voltage clamp, surface expression assay in H295R cells Journal of hypertension Medium 22743686
2013 The novel germline KCNJ5 mutation Y152C causes pathological Na+ permeability, membrane depolarization, and disturbed intracellular Ca2+ homeostasis, leading to increased CYP11B2 and NR4A2 expression in HAC15 cells. This effect is Ca2+-dependent and abolished by the calcium channel blocker nifedipine. Germline sequencing, electrophysiological studies, gene expression studies in HAC15 cells, nifedipine pharmacology The Journal of clinical endocrinology and metabolism Medium 24037882
2014 Mutant KCNJ5 (G151R, L168R, T158A) channels produce a 2-fold increase in intracellular Na+ and a substantial rise in intracellular Ca2+ in NCI-H295R adrenal cells. The Ca2+ increase results from both activation of voltage-gated Ca2+ channels and impairment of Ca2+ extrusion by Na+/Ca2+ exchangers. Mutant KCNJ5 is less sensitive to Ba2+ and tertiapin-Q but inhibited by verapamil and amiloride. Expression in NCI-H295R cells, intracellular Na+ and Ca2+ fluorescent imaging, pharmacological profiling (Ba2+, tertiapin-Q, verapamil, amiloride) Endocrinology Medium 24506072
2014 The KCNJ5 mutation insT149 (novel in-frame insertion near the selectivity filter) causes strong Na+ inward current, membrane depolarization, raised cytosolic Ca2+ via activation of voltage-gated Ca2+ channels and reduced Ca2+ elimination by Na+/Ca2+ exchangers, and increased aldosterone production, as shown in mammalian cells expressing the mutant co-transfected with KCNJ3. Site-directed mutagenesis, whole-cell patch-clamp, Ca2+ imaging, CYP11B2 expression, aldosterone measurement, molecular modeling The Journal of clinical endocrinology and metabolism Medium 25057880
2014 A KCNJ5 mutation (unspecified in abstract) causes Andersen-Tawil syndrome through an inhibitory (dominant-negative) effect on Kir2.1: co-expression of mutant Kir3.4 with Kir2.1 in Xenopus oocytes significantly reduced the inwardly rectifying current compared to wild-type Kir3.4. Exome sequencing, immunoblotting of human tissues, heterologous co-expression in Xenopus oocytes, two-electrode voltage clamp Neurology Medium 24574546
2015 Novel KCNJ5 mutations R115W and E246G reduce Kir3.4 membrane abundance (surface expression) without abolishing K+ selectivity, and exert dominant-negative effects on wild-type channels. Inhibition of endogenous Kir3.4 by tertiapin-Q in human adrenocortical cells depolarizes membrane potential and increases CYP11B2 expression, demonstrating that basal Kir3.4 current is required to maintain resting membrane potential and suppress aldosterone synthesis. Sanger sequencing, heterologous expression in Xenopus oocytes (two-electrode voltage clamp), surface biotinylation assay, tertiapin-Q pharmacology in adrenocortical cells, CYP11B2 expression The Journal of clinical endocrinology and metabolism High 25347571
2015 A novel 12-bp in-frame insertion mutation (A139_F142dup) in the KCNJ5 pore helix upstream of the selectivity filter depolarizes Xenopus oocytes, generates G-protein-sensitive Na+ current with altered K+ selectivity, and increases basal aldosterone release 2.3-fold in H295R cells. The mutant shows reduced tetramer stability and reduced surface expression compared to wild-type, and is insensitive to further stimulation by angiotensin II. Sanger sequencing, heterologous expression in Xenopus oocytes (voltage clamp), H295R cell transfection, aldosterone assay, tetramer stability assay, surface expression Molecular endocrinology Medium 26340408
2016 Mutant KCNJ5 T158A activates both acute and chronic regulatory steps in aldosterone production: it stimulates StAR expression and phosphorylation (acute), upregulates CYP11B2 transcriptional regulators NURR1 and ATF2 (chronic), and increases synthesis of aldosterone, 18-hydroxycortisol, and 18-oxocortisol. All effects are blocked by the L-type Ca2+ channel blocker verapamil, placing Ca2+ entry downstream of KCNJ5-T158A-induced Na+ influx and depolarization. Doxycycline-inducible KCNJ5-T158A expression in HAC15 cells, electrophysiology (loss of inward rectification, Na+ permeability), qRT-PCR, Western blot, LC-MS/MS steroid profiling, verapamil pharmacology Journal of molecular endocrinology High 27099398
2016 Conditional silencing of HCN4 ('funny' current If) in mouse hearts causes impaired pacemaker activity that is rescued by additional genetic deletion of GIRK4 (KCNJ5), demonstrating that GIRK4-mediated IKACh channels and If interact antagonistically in cardiac automaticity—excess parasympathetic GIRK4 activity exacerbates arrhythmia caused by If loss. Cardiac-specific conditional dominant-negative HCN4 expression, genetic deletion of GIRK4 (double mutant mice), ECG and pacemaker activity analysis Nature communications High 25144323
2017 Macrolide antibiotics (e.g., roxithromycin, idremcinal) selectively inhibit mutant KCNJ5 (G151R and L168R) but not wild-type KCNJ5, as demonstrated by electrophysiology (direct channel inhibition) and by suppression of KCNJ5-mutant-induced CYP11B2 expression and aldosterone production in adrenocortical cells. High-throughput screen (KCNJ5-mutant lethality rescue), patch-clamp electrophysiology, CYP11B2 expression assay, aldosterone production assay in human adrenocortical cancer cell lines The Journal of clinical investigation High 28604387
2016 Adenosine-induced atrial fibrillation in human hearts is maintained by localized reentrant drivers in lateral right atrial regions with the highest adenosine A1 receptor and GIRK4 protein expression. Selective GIRK channel blockade with tertiapin counteracted adenosine-induced action potential duration shortening and prevented AF induction, directly implicating GIRK4-containing IKACh channels in this arrhythmia mechanism. Biatrial optical mapping of coronary-perfused human explanted hearts, immunoblot mapping of atrial regions, tertiapin pharmacology Circulation High 27462069
2019 KCNJ5 encodes Kir3.4, which combines with Kir3.1 (KCNJ3) to form the IKACh channel. A gain-of-function KCNJ3 mutation (N83H) increases basal IKACh current even without muscarinic stimulation and causes bradyarrhythmia in transgenic zebrafish; the selective IKACh blocker NIP-151 represses the increased current and improves bradyarrhythmia, confirming the IKACh channel (Kir3.1/Kir3.4 heteromer) as a therapeutic target for bradyarrhythmia. Whole exome sequencing, cellular electrophysiology, transgenic zebrafish model of atrial-specific KCNJ3-N83H expression, NIP-151 pharmacological rescue Circulation Medium 30764634
2014 Germline mutations in KCNJ5 that produce different levels of Na+ conductance lead to different clinical phenotypes: mutations producing very large Na+ conductance (G151E) cause rapid Na+-dependent cell lethality that limits adrenocortical cell mass and aldosterone excess, while mutations with moderate Na+ conductance (G151R) cause massive adrenal hyperplasia without lethality. Sanger sequencing of kindred members, heterologous expression in HEK293T cells, patch-clamp electrophysiology measuring Na+ conductance and cell lethality Proceedings of the National Academy of Sciences of the United States of America High 22308486
2000 GIRK4 (KCNJ5) mRNA is expressed in discrete mouse brain regions including the hypothalamus (ventromedial nucleus), and GIRK4 knockout mice display impaired spatial learning and memory in the Morris water maze but not in passive avoidance, indicating region-specific roles in hippocampal-dependent learning. In situ hybridization using GIRK4 KO as negative control, Morris water maze, passive avoidance, locomotor and pain perception assays The Journal of neuroscience Medium 10908597
2008 GIRK4 (KCNJ5) is expressed in hypothalamic nuclei (ventromedial, paraventricular, and arcuate) involved in energy homeostasis, and GIRK4 knockout mice develop late-onset obesity (~25% heavier by 9 months) attributable to greater body fat, increased food intake tendency, and reduced net energy expenditure. EGFP reporter transgenic mouse (under Girk4 promoter), body weight/composition measurements, metabolic assays, operant food-seeking task in GIRK4 KO mice Proceedings of the National Academy of Sciences of the United States of America High 18523006
2001 Kir3.1 and Kir3.4 proteins are co-localized with m2 muscarinic receptors throughout the outer membrane of atrial and SA node cells in ferret hearts, as shown by immunofluorescence with co-localization analysis. Western blotting and immunofluorescence on tissue sections and isolated single cardiomyocytes from rat, guinea pig, and ferret; double-labeling with anti-m2 muscarinic receptor antibody The journal of histochemistry and cytochemistry Medium 11561006
1998 The Kir3.4 subunit confers mechanosensitivity (stretch inhibition) to the cardiac muscarinic K+ channel: atrial muscarinic K+ channels are rapidly and reversibly inhibited by membrane stretch (hypo-osmolar stress), and homomeric Kir3.4 channels expressed in Xenopus oocytes reproduce this mechanosensitivity, identifying Kir3.4 as the first stretch-inactivated K+ channel identified molecularly. Patch-clamp on rabbit atrial cells and heterologously expressed Kir3.1/Kir3.4 and homomeric Kir3.4 in Xenopus oocytes, hypo-osmolar stretch protocol The Journal of biological chemistry Medium 9430664
2003 GIRK1/GIRK4 channel activity (open probability) is regulated by phosphorylation: PKA phosphorylation of the channel increases open probability by increasing opening frequency and reducing dwell time in a long-closed state, while PP2A dephosphorylation reduces the apparent affinity for Gβγ. The last 20 C-terminal amino acids of GIRK1 are required for PP2A-mediated reduction in Gβγ affinity. Single-channel recordings on isolated membrane patches from Xenopus oocytes, perfusion with PKA catalytic subunit or PP2A, modal gating analysis, C-terminal deletion mutants Biophysical journal Medium 12547819
1997 GIRK4 mRNA expression in the developing mouse begins between embryonic days 7 and 11, consistent with early heart development, and is predominantly expressed in heart with trace levels in brain, kidney, lung, and spleen, but not in skeletal muscle, liver, or testis. Northern blotting and RT-PCR of mouse tissues and embryos, partial genomic structure determination, chromosomal mapping Genomics Low 9073506
2009 Kir2.1 co-immunoprecipitates with Kir3.4 in HEK293T cells, and co-expression of Kir2.1 promotes cell surface localization of Kir3.4 in HEK293T cells. However, co-expression of a dominant-negative Kir2.1 with wild-type Kir3.1/3.4 decreases Kir3.1/3.4 current amplitude in Xenopus oocytes. Co-immunoprecipitation in HEK293T cells, confocal microscopy subcellular localization, two-electrode voltage clamp in Xenopus oocytes with dominant-negative Kir2.1 Biochemical and biophysical research communications Medium 19338762
2007 Overexpression of Kir3.4 in adult atrial myocytes via adenoviral gene transfer generates functional homomeric Kir3.4 channels with Na+-dependent gating (activated at [Na+]pip ≥15 mM, producing receptor-independent basal inward rectifier current Ibir) that is G-protein-independent (insensitive to pertussis toxin and GDP-β-S) and shows higher sensitivity to tertiapin-Q (IC50 0.61 nM) compared to the endogenous Kir3.1/3.4 IKACh (IC50 12 nM). Adenoviral GIRK4 overexpression in rat atrial myocytes, patch-clamp electrophysiology, pertussis toxin and GDP-β-S treatments, PLC activation via α1 adrenergic receptors, tertiapin-Q dose-response The Journal of physiology Medium 17884923
2022 A novel small-molecule (3hi2one-G4) selectively activates homomeric GIRK4 channels but not GIRK2, GIRK1/2, or GIRK1/4. Its binding site involves the transmembrane 1, transmembrane 2, and slide helix regions near the PIP2 binding site, and it activates the channel by strengthening channel-PIP2 interactions. Slide helix residue L77 in GIRK4 (vs. I82 in GIRK2) is a major determinant of isoform-specific selectivity. Molecular modeling, site-directed mutagenesis, electrophysiology (two-electrode voltage clamp in Xenopus oocytes and whole-cell patch clamp in HEK293 cells) The Journal of biological chemistry High 35525275
2018 Targeted disruption of Kcnj5 in female (but not male) mice reduces basal aldosterone levels but produces higher aldosterone after angiotensin II stimulation. RNAseq analysis of KO adrenals revealed sex-specific transcriptional changes, and PPARα pathway was identified as a novel regulatory pathway; the PPARα agonist fenofibrate stimulates aldosterone production and CYP11B2 induction in H295R cells and in vivo in mice. Kcnj5 knockout mice, aldosterone measurement, RNAseq, Ingenuity Pathway Analysis, H295R cell pharmacology, in vivo fenofibrate dosing Clinical science Medium 29222092
2019 miR-221 and miR-222 target the 3'-UTR of Kcnj5 (and Cacna1c), reducing Kcnj5 channel abundance and function as measured by flux assay and Western blot, contributing to altered cardiac ion channel expression. Luciferase 3'-UTR reporter assay, overexpression of miR-221/222 in cardiomyocytes, Western blot, flux measurements, whole-cell patch clamp Cellular and molecular life sciences Medium 31312877
2000 Slow activation of Kir3.1/Kir3.4 is caused principally by unbinding of polyamines from negatively charged residues close to the selectivity filter (in H5, M2, and proximal C-terminus), not by an intrinsic gating mechanism. Ba2+ block involves interaction with the same pore residues; a critical Ba2+-blocking residue was identified in Kir3.4, with the equivalent Kir3.1 residue having less pronounced effect, suggesting pore asymmetry. Site-directed mutagenesis, giant inside-out patch recordings in Xenopus oocytes, polyamine perfusion experiments The Journal of biological chemistry Medium 10956662

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1998 Abnormal heart rate regulation in GIRK4 knockout mice. Neuron 307 9459446
2001 Molecular basis of downregulation of G-protein-coupled inward rectifying K(+) current (I(K,ACh) in chronic human atrial fibrillation: decrease in GIRK4 mRNA correlates with reduced I(K,ACh) and muscarinic receptor-mediated shortening of action potentials. Circulation 265 11714649
2012 Prevalence, clinical, and molecular correlates of KCNJ5 mutations in primary aldosteronism. Hypertension (Dallas, Tex. : 1979) 229 22275527
2012 Hypertension with or without adrenal hyperplasia due to different inherited mutations in the potassium channel KCNJ5. Proceedings of the National Academy of Sciences of the United States of America 192 22308486
2012 Microarray, qPCR, and KCNJ5 sequencing of aldosterone-producing adenomas reveal differences in genotype and phenotype between zona glomerulosa- and zona fasciculata-like tumors. The Journal of clinical endocrinology and metabolism 162 22442279
2012 Comprehensive re-sequencing of adrenal aldosterone producing lesions reveal three somatic mutations near the KCNJ5 potassium channel selectivity filter. PloS one 152 22848660
2012 Expression and mutations of KCNJ5 mRNA in Japanese patients with aldosterone-producing adenomas. The Journal of clinical endocrinology and metabolism 147 22278422
2011 KCNJ5 mutations in European families with nonglucocorticoid remediable familial hyperaldosteronism. Hypertension (Dallas, Tex. : 1979) 147 22203740
1997 Probing the G-protein regulation of GIRK1 and GIRK4, the two subunits of the KACh channel, using functional homomeric mutants. The Journal of biological chemistry 145 9395492
2010 Identification of a Kir3.4 mutation in congenital long QT syndrome. American journal of human genetics 142 20560207
2012 Potassium channel mutant KCNJ5 T158A expression in HAC-15 cells increases aldosterone synthesis. Endocrinology 141 22315453
2013 Somatic ATP1A1, ATP2B3, and KCNJ5 mutations in aldosterone-producing adenomas. Hypertension (Dallas, Tex. : 1979) 135 24082052
2012 Somatic mutations affecting the selectivity filter of KCNJ5 are frequent in 2 large unselected collections of adrenal aldosteronomas. Hypertension (Dallas, Tex. : 1979) 127 22252394
2000 Brain localization and behavioral impact of the G-protein-gated K+ channel subunit GIRK4. The Journal of neuroscience : the official journal of the Society for Neuroscience 99 10908597
2012 A novel point mutation in the KCNJ5 gene causing primary hyperaldosteronism and early-onset autosomal dominant hypertension. The Journal of clinical endocrinology and metabolism 94 22628607
2012 Role of KCNJ5 in familial and sporadic primary aldosteronism. Nature reviews. Endocrinology 91 23229280
1996 A G-protein-activated inwardly rectifying K+ channel (GIRK4) from human hippocampus associates with other GIRK channels. The Journal of neuroscience : the official journal of the Society for Neuroscience 89 8558261
2001 Distribution of the muscarinic K+ channel proteins Kir3.1 and Kir3.4 in the ventricle, atrium, and sinoatrial node of heart. The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society 87 11561006
1998 Identification of native atrial G-protein-regulated inwardly rectifying K+ (GIRK4) channel homomultimers. The Journal of biological chemistry 84 9765280
2016 Adenosine-Induced Atrial Fibrillation: Localized Reentrant Drivers in Lateral Right Atria due to Heterogeneous Expression of Adenosine A1 Receptors and GIRK4 Subunits in the Human Heart. Circulation 82 27462069
2013 a Novel Y152C KCNJ5 mutation responsible for familial hyperaldosteronism type III. The Journal of clinical endocrinology and metabolism 77 24037882
2014 Comparison of cardiovascular complications in patients with and without KCNJ5 gene mutations harboring aldosterone-producing adenomas. Journal of atherosclerosis and thrombosis 76 25253161
1997 An immunocytochemical study on the distribution of two G-protein-gated inward rectifier potassium channels (GIRK2 and GIRK4) in the adult rat brain. Neuroscience 76 9284339
2019 Mutant KCNJ3 and KCNJ5 Potassium Channels as Novel Molecular Targets in Bradyarrhythmias and Atrial Fibrillation. Circulation 74 30764634
1999 GIRK4 confers appropriate processing and cell surface localization to G-protein-gated potassium channels. The Journal of biological chemistry 74 9891030
1998 Gbeta binding to GIRK4 subunit is critical for G protein-gated K+ channel activation. The Journal of biological chemistry 71 9642257
2014 Cardiac arrhythmia induced by genetic silencing of 'funny' (f) channels is rescued by GIRK4 inactivation. Nature communications 67 25144323
2012 Visinin-like 1 is upregulated in aldosterone-producing adenomas with KCNJ5 mutations and protects from calcium-induced apoptosis. Hypertension (Dallas, Tex. : 1979) 65 22331379
2014 A Kir3.4 mutation causes Andersen-Tawil syndrome by an inhibitory effect on Kir2.1. Neurology 63 24574546
2019 KCNJ5 Somatic Mutation Is a Predictor of Hypertension Remission After Adrenalectomy for Unilateral Primary Aldosteronism. The Journal of clinical endocrinology and metabolism 59 31216002
2017 Macrolides selectively inhibit mutant KCNJ5 potassium channels that cause aldosterone-producing adenoma. The Journal of clinical investigation 59 28604387
2014 Pharmacology and pathophysiology of mutated KCNJ5 found in adrenal aldosterone-producing adenomas. Endocrinology 59 24506072
2003 Molecular basis of ion selectivity, block, and rectification of the inward rectifier Kir3.1/Kir3.4 K(+) channel. The Journal of biological chemistry 57 14504281
2014 Role for germline mutations and a rare coding single nucleotide polymorphism within the KCNJ5 potassium channel in a large cohort of sporadic cases of primary aldosteronism. Hypertension (Dallas, Tex. : 1979) 56 24420545
2019 18-Oxocortisol Synthesis in Aldosterone-Producing Adrenocortical Adenoma and Significance of KCNJ5 Mutation Status. Hypertension (Dallas, Tex. : 1979) 52 31006333
2001 Overexpression of monomeric and multimeric GIRK4 subunits in rat atrial myocytes removes fast desensitization and reduces inward rectification of muscarinic K(+) current (I(K(ACh))). Evidence for functional homomeric GIRK4 channels. The Journal of biological chemistry 52 11384974
2014 A novel KCNJ5-insT149 somatic mutation close to, but outside, the selectivity filter causes resistant hypertension by loss of selectivity for potassium. The Journal of clinical endocrinology and metabolism 50 25057880
2012 Characterization of a novel somatic KCNJ5 mutation delI157 in an aldosterone-producing adenoma. Journal of hypertension 46 22743686
2012 The potassium channel, Kir3.4 participates in angiotensin II-stimulated aldosterone production by a human adrenocortical cell line. Endocrinology 46 22798349
2015 Novel KCNJ5 mutations in sporadic aldosterone-producing adenoma reduce Kir3.4 membrane abundance. The Journal of clinical endocrinology and metabolism 45 25347571
2018 KCNJ5 mutation as a predictor for resolution of hypertension after surgical treatment of aldosterone-producing adenoma. Journal of hypertension 44 29016532
2015 A case of severe hyperaldosteronism caused by a de novo mutation affecting a critical salt bridge Kir3.4 residue. The Journal of clinical endocrinology and metabolism 43 25322277
2008 Predisposition to late-onset obesity in GIRK4 knockout mice. Proceedings of the National Academy of Sciences of the United States of America 42 18523006
2016 Aldosterone-Producing Adenoma With a Somatic KCNJ5 Mutation Revealing APC-Dependent Familial Adenomatous Polyposis. The Journal of clinical endocrinology and metabolism 39 27648962
2019 Primary Aldosteronism: KCNJ5 Mutations and Adrenocortical Cell Growth. Hypertension (Dallas, Tex. : 1979) 38 31446799
2014 KCNJ5 gene somatic mutations affect cardiac remodelling but do not preclude cure of high blood pressure and regression of left ventricular hypertrophy in primary aldosteronism. Journal of hypertension 38 24759126
2012 KCNJ5 mutations in the National Institutes of Health cohort of patients with primary hyperaldosteronism: an infrequent genetic cause of Conn's syndrome. Endocrine-related cancer 37 22323562
1996 Time resolved kinetics of direct G beta 1 gamma 2 interactions with the carboxyl terminus of Kir3.4 inward rectifier K+ channel subunits. Neuropharmacology 37 8938723
2012 KCNJ5 mutations in aldosterone- and cortisol-co-secreting adrenal adenomas. Endocrine journal 36 22863749
1998 Mechanosensitivity of the cardiac muscarinic potassium channel. A novel property conferred by Kir3.4 subunit. The Journal of biological chemistry 36 9430664
2016 Mutated KCNJ5 activates the acute and chronic regulatory steps in aldosterone production. Journal of molecular endocrinology 34 27099398
2016 Double adrenocortical adenomas harboring independent KCNJ5 and PRKACA somatic mutations. European journal of endocrinology 34 27165862
2013 New insights into aldosterone-producing adenomas and hereditary aldosteronism: mutations in the K+ channel KCNJ5. Current opinion in nephrology and hypertension 33 23318698
2013 KCNJ5 mutations in aldosterone producing adenoma and relationship with adrenal cortex remodeling. Molecular and cellular endocrinology 33 23376008
2013 Outcome after surgery for primary hyperaldosteronism may depend on KCNJ5 tumor mutation status: a population-based study from Western Norway. Langenbeck's archives of surgery 33 23778974
2018 Tumor Cell Subtypes Based on the Intracellular Hormonal Activity in KCNJ5-Mutated Aldosterone-Producing Adenoma. Hypertension (Dallas, Tex. : 1979) 32 30354756
2016 Characteristics of Japanese aldosterone-producing adenomas with KCNJ5 mutations. Endocrine journal 31 27681703
2007 Characterizations of a loss-of-function mutation in the Kir3.4 channel subunit. Biochemical and biophysical research communications 31 17967416
2018 Aldosterone Suppression by Dexamethasone in Patients With KCNJ5-Mutated Aldosterone-Producing Adenoma. The Journal of clinical endocrinology and metabolism 30 30020487
2019 miR-221 and -222 target CACNA1C and KCNJ5 leading to altered cardiac ion channel expression and current density. Cellular and molecular life sciences : CMLS 28 31312877
2017 Macrolides Blunt Aldosterone Biosynthesis: A Proof-of-Concept Study in KCNJ5 Mutated Adenoma Cells Ex Vivo. Hypertension (Dallas, Tex. : 1979) 28 28993452
2016 Somatic KCNJ5 mutation occurring early in adrenal development may cause a novel form of juvenile primary aldosteronism. Molecular and cellular endocrinology 28 27514282
2014 Discordant genotype-phenotype correlation in familial hyperaldosteronism type III with KCNJ5 gene mutation: a patient report and review of the literature. Hormone research in paediatrics 28 24819081
2012 Somatic mutations in the KCNJ5 gene raise the lateralization index: implications for the diagnosis of primary aldosteronism by adrenal vein sampling. The Journal of clinical endocrinology and metabolism 28 23012392
2020 KCNJ5 Somatic Mutations in Aldosterone-Producing Adenoma Are Associated With a Worse Baseline Status and Better Recovery of Left Ventricular Remodeling and Diastolic Function. Hypertension (Dallas, Tex. : 1979) 27 33249859
2013 The phenotype characteristics of type 13 long QT syndrome with mutation in KCNJ5 (Kir3.4-G387R). Heart rhythm 25 23872692
2000 Residues and mechanisms for slow activation and Ba2+ block of the cardiac muscarinic K+ channel, Kir3.1/Kir3.4. The Journal of biological chemistry 24 10956662
2007 Generation of a constitutive Na+-dependent inward-rectifier current in rat adult atrial myocytes by overexpression of Kir3.4. The Journal of physiology 23 17884923
2020 Mosaicism for KCNJ5 Causing Early-Onset Primary Aldosteronism due to Bilateral Adrenocortical Hyperplasia. American journal of hypertension 22 31637427
2018 Macrolides for KCNJ5-mutated aldosterone-producing adenoma (MAPA): design of a study for personalized diagnosis of primary aldosteronism. Blood pressure 22 29409357
2017 Molecular characteristics of the KCNJ5 mutated aldosterone-producing adenomas. Endocrine-related cancer 21 28747387
2015 Functional histopathological markers of aldosterone producing adenoma and somatic KCNJ5 mutations. Molecular and cellular endocrinology 21 25617716
2013 Mutations in KCNJ5 determines presentation and likelihood of cure in primary hyperaldosteronism. ANZ journal of surgery 21 24274318
2003 Single channel analysis of the regulation of GIRK1/GIRK4 channels by protein phosphorylation. Biophysical journal 21 12547819
2022 A novel small-molecule selective activator of homomeric GIRK4 channels. The Journal of biological chemistry 20 35525275
2003 The selectivity filter may act as the agonist-activated gate in the G protein-activated Kir3.1/Kir3.4 K+ channel. The Journal of biological chemistry 20 14525972
1997 Partial structure, chromosome localization, and expression of the mouse Girk4 gene. Genomics 20 9073506
2004 K+ activation of kir3.1/kir3.4 and kv1.4 K+ channels is regulated by extracellular charges. Biophysical journal 19 15454439
2015 KCNJ5 Mutations: Sex, Salt and Selection. Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme 18 26566104
2016 Functional characterization of two novel germline mutations of the KCNJ5 gene in hypertensive patients without primary aldosteronism but with ACTH-dependent aldosterone hypersecretion. Clinical endocrinology 17 27293068
2015 Novel Insertion Mutation in KCNJ5 Channel Produces Constitutive Aldosterone Release From H295R Cells. Molecular endocrinology (Baltimore, Md.) 16 26340408
2020 Primary aldosteronism diagnostics: KCNJ5 mutations and hybrid steroid synthesis in aldosterone-producing adenomas. Gland surgery 15 32206594
2017 Arterial stiffness and blood pressure improvement in aldosterone-producing adenoma harboring KCNJ5 mutations after adrenalectomy. Oncotarget 15 28415786
2013 Genetic variations in the KCNJ5 gene in primary aldosteronism patients from Xinjiang, China. PloS one 15 23382865
2013 Regulation of aldosterone biosynthesis by the Kir3.4 (KCNJ5) potassium channel. Clinical and experimental pharmacology & physiology 15 23829355
2009 The single nucleotide polymorphisms of Kir3.4 gene and their correlation with lone paroxysmal atrial fibrillation in Chinese Han population. Heart, lung & circulation 15 19208499
2023 Cardiovascular and metabolic characters of KCNJ5 somatic mutations in primary aldosteronism. Frontiers in endocrinology 14 36950676
2021 KCNJ5 Mutation Contributes to Complete Clinical Success in Aldosterone-Producing Adenoma: A Study From a Single Center. Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists 14 33678553
2021 Aldosterone-producing adenoma-harbouring KCNJ5 mutations is associated with lower prevalence of metabolic disorders and abdominal obesity. Journal of hypertension 14 34313632
2018 Prevalence of Somatic KCNJ5 Mutations in Thai Patients With Aldosterone-Producing Adrenal Adenomas. Journal of the Endocrine Society 14 30283826
2025 Multiomics analysis unveils the cellular ecosystem with clinical relevance in aldosterone-producing adenomas with KCNJ5 mutations. Proceedings of the National Academy of Sciences of the United States of America 13 40009643
2009 Heteromeric assembly of inward rectifier channel subunit Kir2.1 with Kir3.1 and with Kir3.4. Biochemical and biophysical research communications 13 19338762
2000 Expression of GIRK (Kir3.1/Kir3.4) channels in mouse fibroblast cells with and without beta1 integrins. FEBS letters 12 10682853
1997 ATP-dependent regulation of a G protein-coupled K+ channel (GIRK1/GIRK4) expressed in oocytes. The American journal of physiology 12 9038938
2018 GSTA1 Expression Is Correlated With Aldosterone Level in KCNJ5-Mutated Adrenal Aldosterone-Producing Adenoma. The Journal of clinical endocrinology and metabolism 11 29165597
2018 Targeted disruption of the Kcnj5 gene in the female mouse lowers aldosterone levels. Clinical science (London, England : 1979) 11 29222092
2014 Association of the KCNJ5 gene with Tourette Syndrome and Attention-Deficit/Hyperactivity Disorder. Genes, brain, and behavior 11 24840790
2001 Evidence of involvement of GIRK1/GIRK4 in long-term desensitization of cardiac muscarinic K+ channels. American journal of physiology. Heart and circulatory physiology 10 11356610
2023 Generation of sheep with defined FecBB and TBXT mutations and porcine blastocysts with KCNJ5G151R/+ mutation using prime editing. BMC genomics 9 37308830
2012 G-protein-gated inwardly rectifying K+ channel 4 (GIRK4) immunoreactivity in chemically defined neurons of the hypothalamic arcuate nucleus that control body weight. Journal of chemical neuroanatomy 9 22465809

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