Affinage

KCNJ13

Inward rectifier potassium channel 13 · UniProt O60928

Length
360 aa
Mass
40.5 kDa
Annotated
2026-06-10
67 papers in source corpus 42 papers cited in narrative 42 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

KCNJ13 encodes Kir7.1, an inwardly rectifying K+ channel with a distinctive low (~2 pS) unitary conductance, mild rectification, an inverse dependence on extracellular K+, and a K+≈Rb+>>Cs+>Na+ selectivity that constitutes the apical K+ conductance of polarized epithelia (PMID:11230507, PMID:11179389). Across tissues it localizes to membrane domains adjacent to Na+,K+-ATPase, consistent with a role in recycling K+ to sustain pump-driven transport (PMID:10455019, PMID:11179389). Channel gating is governed by PIP2 binding at R162 (with K159/K164), by intracellular pH via the N-terminal H26, and by dual phosphorylation (PKC-inhibitory Ser201, PKA-stimulatory Ser287); complex glycosylation at its sole N-glycosylation site sets conductance and open probability, and SUMO-1 modification controls surface expression (PMID:33219695, PMID:18094146, PMID:18976636, PMID:30257863, PMID:35633059). C-terminal length is required for plasma-membrane targeting (PMID:16406822), and conserved inner-pore residues (T153, M125) determine both K+ permeation and inhibitor access (PMID:35584325, PMID:28619748, PMID:41212743). In the retinal pigment epithelium Kir7.1 maintains subretinal K+ homeostasis and supports phagocytosis of photoreceptor outer segments, and its loss causes photoreceptor degeneration; this RPE requirement is cell-autonomous as shown by mosaic and tissue-specific deletion (PMID:25666713, PMID:30009826, PMID:32437550, PMID:28878288). Human mutations cause inherited blindness: recessive loss-of-function alleles (e.g. W53X, T153I, L241P) underlie Leber congenital amaurosis type 16, while the dominant R162W allele converts the channel to a nonselective cation conductance and acts dominant-negatively by disrupting PIP2 gating in snowflake vitreoretinal degeneration (PMID:25921210, PMID:35584325, PMID:18179896, PMID:23255580, PMID:33219695). Beyond the eye, Kir7.1 acts as a G-protein-independent effector of MC4R signaling in hypothalamic PVN neurons to regulate energy homeostasis (PMID:25600267, PMID:30561082), is directly activated by progesterone through a nongenomic mechanism to maintain uterine quiescence (PMID:25056913, PMID:34387656, PMID:40043131), and sets cerebrospinal fluid K+ in choroid plexus where it is functionally coupled to NKCC1 and Na+,K+-ATPase (PMID:41212743). Gene-correction strategies including base editing and tRNA suppression restore channel function and vision in LCA16 models [PMID:37561581, PMID:bio_10.1101_2025.07.10.660754].

Mechanistic history

Synthesis pass · year-by-year structured walk · 17 steps
  1. 1999 Medium

    Established where Kir7.1 protein resides in epithelia, linking it to transepithelial ion transport machinery rather than a defined function.

    Evidence Immunohistochemistry and fractionation in thyroid and choroid plexus epithelia

    PMID:10455019

    Open questions at the time
    • No functional reconstitution of channel activity
    • Co-localization does not prove physical or functional coupling to Na+,K+-ATPase
  2. 2001 High

    Defined Kir7.1 as the molecular identity of the RPE apical K+ conductance and characterized its unusual biophysical signature, converting a candidate gene into a functional channel.

    Evidence Two-electrode voltage-clamp in oocytes and patch-clamp of native bovine RPE with noise analysis, plus EM localization and heterologous patch-clamp

    PMID:11179389 PMID:11230507

    Open questions at the time
    • Structural basis of low conductance and inverse K+ dependence unresolved
    • Gating regulators not yet identified
  3. 2006 Medium

    Identified C-terminal length as a trafficking determinant and used a zebrafish pigment mutant to show channel activity governs cellular signaling output, broadening Kir7.1 roles beyond epithelial K+ recycling.

    Evidence Deletion mutagenesis with surface biotinylation in MDCK; positional cloning, patch-clamp and BAC rescue in zebrafish jaguar/obelix

    PMID:16406822 PMID:17121467

    Open questions at the time
    • Trafficking motif within the C-terminus not pinpointed
    • Mechanism linking channel activity to melanosome dispersion downstream of adrenoceptors unresolved
  4. 2008 High

    Defined gating regulators (pH via H26, PKC/PKA phosphorylation) and the molecular pathology of the dominant SVD R162W allele, distinguishing it as a gain-of-toxic-function changing ion selectivity.

    Evidence Oocyte voltage-clamp with site-directed mutagenesis; CHO patch-clamp and molecular modeling of R162W

    PMID:18094146 PMID:18179896 PMID:18976636

    Open questions at the time
    • Physiological kinase signaling inputs in vivo not established
    • Initial selectivity-change interpretation not yet reconciled with later dominant-negative gating model
  5. 2012 High

    Resolved the R162W mechanism as a PIP2-gating-disrupting dominant-negative that still traffics to the membrane, clarifying why SVD is dominant.

    Evidence Co-injection oocyte voltage-clamp and immunostaining; CHO co-expression and homology modeling

    PMID:23255580 PMID:23977131

    Open questions at the time
    • Direct demonstration of PIP2-binding loss awaited
    • Stoichiometry of mutant/WT subunit mixing not quantified
  6. 2014 High

    Extended Kir7.1 function to myometrial physiology, showing it sets membrane potential to enforce gestational quiescence.

    Evidence Bidirectional lentiviral knockdown/overexpression, contractility assays, VU590 pharmacology and patch-clamp

    PMID:25056913

    Open questions at the time
    • Upstream regulator driving labor-associated Kir7.1 downregulation not identified at this stage
    • Direct activator of the channel in myometrium unknown
  7. 2015 High

    Demonstrated a novel G-protein-independent signaling role: MC4R directly couples to Kir7.1 in hypothalamic neurons to control energy balance, with α-MSH closing and AgRP opening the channel.

    Evidence Hypothalamic slice patch-clamp in mice with Gαs pathway dissection and ligand-binding studies

    PMID:25600267

    Open questions at the time
    • Physical nature of the MC4R–Kir7.1 coupling not structurally defined
    • How a single channel produces opposite responses to two ligands unresolved
  8. 2015 High

    Established in vivo that RPE Kir7.1 is required cell-autonomously for photoreceptor survival and explained recessive LCA16 inheritance, distinguishing it from dominant SVD.

    Evidence CRISPR mosaic deletion, Kcnj13 knockout, shRNA knockdown with ERG; heterologous expression of LCA nonsense mutant showing no dominant-negative effect

    PMID:25666713 PMID:25921210 PMID:26402555

    Open questions at the time
    • Complete-knockout postnatal lethality precluded adult retinal analysis
    • Whether degeneration reflects K+ buffering versus other RPE functions unresolved
  9. 2017 High

    Tied RPE Kir7.1 function to whole-retina electrophysiology via subretinal K+ control and mapped the VU590 inhibitor binding mechanism within the pore.

    Evidence In vivo shRNA/VU590 with ERG and isolated-retina controls; native RPE patch-clamp; mutagenesis and modeling of pore residues; OXTR modulation experiments

    PMID:28603013 PMID:28619748 PMID:28878288

    Open questions at the time
    • Whether ERG deficits arise solely from altered subretinal K+ unresolved
    • Physiological role of oxytocin modulation of RPE Kir7.1 unknown
  10. 2018 High

    Revealed glycosylation as a GPCR-tunable modulator of channel activity and uncovered developmental roles in palatogenesis and tracheal smooth-muscle morphogenesis linking ion homeostasis to AKT-dependent actin polymerization.

    Evidence Glycosylation-site mutagenesis with single-channel recording across GPCRs; conditional RPE knockout with ERG/OCT; ENU mutant mouse with AKT pharmacological rescue

    PMID:30009826 PMID:30022023 PMID:30257863

    Open questions at the time
    • Signaling chain from channel activity to AKT phosphorylation not fully defined
    • How GPCRs reduce glycosylation mechanistically unresolved
  11. 2019 High

    Confirmed in vivo that Kir7.1 is the downstream effector of MC4R for energy homeostasis and dissected RPE phagosome/mitochondrial pathology preceding degeneration.

    Evidence MC4R-Cre conditional Kcnj13 knockout with slice electrophysiology and metabolic phenotyping; zebrafish mutant EM, ATP and mitochondrial analysis

    PMID:30561082 PMID:30846767

    Open questions at the time
    • Whether phagosome defect is primary or secondary to ion imbalance unresolved
    • Molecular link between channel activity and phagocytic gene expression unknown
  12. 2020 Medium

    Demonstrated a direct requirement for Kir7.1 in human RPE phagocytosis and identified additional roles in oligodendrocyte integrity under ischemic stress.

    Evidence CRISPR knockout in hiPSC-RPE with phagocytosis assays and qPCR; oligodendrocyte patch-clamp with VU590 in an OGD model

    PMID:32086565 PMID:32437550

    Open questions at the time
    • Mechanism coupling K+ conductance to phagocytic machinery undefined
    • Oligodendrocyte phenotype rests on pharmacology without genetic confirmation
  13. 2021 High

    Identified progesterone as a direct, receptor-independent activator of Kir7.1, providing a molecular basis for hormonal control of channel-dependent tissues.

    Evidence Patch-clamp of native choroid plexus and RPE cells and recombinant channel with receptor antagonists

    PMID:34387656

    Open questions at the time
    • Direct binding site for progesterone on the channel not localized
    • Physiological consequences in choroid plexus and RPE not tested
  14. 2022 High

    Defined pore residue determinants of conductance through disease mutations and identified SUMOylation as a surface-expression regulator relevant to neuropathic pain.

    Evidence Systematic mutagenesis of T153 with patch-clamp; Co-IP, surface fractionation, SUMOylation inhibitors and von Frey behavior; conditional RPE knockout with lentiviral rescue

    PMID:35096838 PMID:35584325 PMID:35633059

    Open questions at the time
    • SUMO-1 acceptor lysine on Kir7.1 not mapped
    • Lentiviral rescue restored only the c-wave, leaving photoreceptor-level rescue unachieved
  15. 2023 High

    Showed that gene correction restores Kir7.1 function and vision, establishing therapeutic tractability of LCA16.

    Evidence Adenine base editing of W53X in patient fibroblasts and hiPSC-RPE with patch-clamp, and in vivo ERG/OCT in an LCA16 mouse

    PMID:37561581

    Open questions at the time
    • Editing efficiency in RPE remained partial
    • Durability and off-target profile not fully resolved
  16. 2024 Medium

    Provided the first structural views of human Kir7.1 gating and the MC4R–Kir7.1 complex, and showed the channel is a clinically relevant target for antipsychotic-associated weight effects.

    Evidence Cryo-EM with mutagenesis and ML418 pharmacology (preprint); MC4R-Cre conditional knockout with electrophysiology, binding/cAMP assays and metabolic phenotyping (preprint)

    PMID:38895206 PMID:38895219

    Open questions at the time
    • Structural data are preprint and not peer-reviewed
    • Assembly stoichiometry of the MC4R–Kir7.1 complex only preliminary
  17. 2025 High

    Distinguished Kir7.1 functions in disease by separating K+-buffering from other roles, extended its physiology to CSF homeostasis, neutrophil chemotaxis and OPN3 modulation, and broadened progesterone activation across reproductive tissues.

    Evidence M125R and conditional knockin/knockout mice with CSF K+ and NKCC1 assays, RPE patch-clamp/ERG; native myometrium and pericyte patch-clamp with progestin panel; OPN3 conditional KO with electrophysiology; voltage-imaging/optogenetics in neutrophils (preprint); ACE-tRNA rescue (preprint)

    PMID:39951488 PMID:40043131 PMID:41212743 PMID:41247777

    Open questions at the time
    • The non-K+-buffering RPE function driving degeneration remains unidentified
    • Mechanism of Kir7.1–NKCC1 coupling not biochemically resolved
    • Neutrophil and tRNA-rescue findings remain preprint

Open questions

Synthesis pass · forward-looking unresolved questions
  • How Kir7.1 physically couples to MC4R and to NKCC1/Na+,K+-ATPase, and which RPE function beyond subretinal K+ buffering drives photoreceptor degeneration, remain the central open mechanistic questions.
  • No peer-reviewed structure of the MC4R–Kir7.1 complex
  • Direct progesterone-binding site on the channel unmapped
  • The disease-relevant non-K+-buffering RPE role unidentified

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005215 transporter activity 4 GO:0060089 molecular transducer activity 2
Localization
GO:0005886 plasma membrane 5
Pathway
R-HSA-162582 Signal Transduction 3 R-HSA-9709957 Sensory Perception 3 R-HSA-382551 Transport of small molecules 2
Partners
MC4RNKCC1OPN3OXTR

Evidence

Reading pass · 42 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1999 Kir7.1 (KCNJ13) is localized to the basolateral membrane of thyroid follicular cells and the apical membrane of choroid plexus epithelial cells, co-localizing with Na+,K+-ATPase, consistent with functional coupling to recycle K+ for pump activity. Immunohistochemistry, Northern blot, subcellular fractionation The Biochemical journal Medium 10455019
2001 Kir7.1 is the molecular basis of the apical membrane K+ conductance in retinal pigment epithelium (RPE): it exhibits mild inward rectification, an inverse dependence on extracellular K+ concentration, and a unitary conductance of ~2 pS. The selectivity sequence is K+ ≈ Rb+ >> Cs+ > Na+ ≈ Li+. Xenopus oocyte two-electrode voltage-clamp, whole-cell patch-clamp on bovine RPE, non-stationary noise analysis, Northern/Western blot The Journal of physiology High 11230507
2001 Kir7.1 is localized specifically at the proximal roots of apical processes of RPE cells, co-localizing with Na+,K+-ATPase, and its currents recapitulate the IK(IR) recorded from isolated RPE cells (poor K+-dependence, low Ba2+ sensitivity). Immunohistochemistry including electron microscopy, RT-PCR, immunoblot, patch-clamp in HEK293T cells The Journal of physiology High 11179389
2000 Kir7.1 is localized to the basolateral membrane of distal nephron principal cells (DCT, connecting tubule, cortical collecting duct) co-localizing with Na+,K+-ATPase, where it may function in K+ recycling to sustain pump activity. Western blot, immunohistochemistry, electron microscopic immunocytochemistry, double-labeling immunogold Journal of the American Society of Nephrology Medium 11053473
2003 Kir7.1 constitutes a major component of the apical K+ conductance in bovine RPE, distributed over the length of apical processes, and distinct from Kir4.1, which is absent from RPE. RT-PCR, Northern blot, Western blot, indirect immunofluorescence Investigative ophthalmology & visual science Medium 12824269
2006 Mutations in Kir7.1 in zebrafish jaguar/obelix mutants alter K+ channel activity (demonstrated by patch-clamp), impair the melanophore response to sympathetic neuron-derived melanosome dispersion signals, and constitutively activate melanosome aggregation downstream of the alpha2-adrenoceptor pathway. Positional cloning, patch-clamp electrophysiology, BAC rescue experiment, pigment pattern analysis PLoS genetics High 17121467
2006 The C-terminal length of Kir7.1 is critical for plasma membrane targeting; deletion of 38 or more C-terminal residues causes intracellular retention, an effect rescued by addition of alanine residues to restore C-terminal length. Deletion mutagenesis, immunofluorescence microscopy, cell-surface biotinylation in MDCK cells Cell biology international Medium 16406822
2007 Kir7.1 channels are modulated by intracellular pH in a biphasic manner (maximal activity near pH 7.0, inhibited by acidification or alkalinization), and by extracellular acidification. Histidine 26 (H26) in the NH2-terminus is important for channel activation at physiological pHi. Xenopus oocyte two-electrode voltage-clamp, site-directed mutagenesis of histidine residues American journal of physiology. Cell physiology High 18094146
2008 The R162W mutation in KCNJ13 (SVD-associated) causes Kir7.1 to produce a nonselective cation current instead of selective K+ current, depolarizing transfected cells and increasing cell fragility, establishing a gain-of-toxic-function mechanism for dominant SVD. Overexpression in CHO-K1 cells, whole-cell patch-clamp, molecular modeling American journal of human genetics High 18179896
2008 Kir7.1 channel activity is dually regulated by PKC (inhibition via Ser201) and PKA (stimulation via Ser287) in the C-terminal domain. Xenopus oocyte expression, pharmacological PKC/PKA activation/inhibition, site-directed mutagenesis of consensus phosphorylation sites Biochemical and biophysical research communications Medium 18976636
2012 The R162W mutation causes dominant-negative suppression of Kir7.1: co-expression of mutant and WT Kir7.1 cRNA reduces K+ and Rb+ currents to ~17% of WT alone, while the mutant protein still reaches the plasma membrane. The dominant-negative effect may occur by disruption of PIP2 gating. Xenopus oocyte two-electrode voltage-clamp, immunostaining of oocytes and MDCK cells American journal of physiology. Cell physiology High 23255580
2013 The SVD R162W mutation produces a non-functional Kir channel that depolarizes resting membrane potential upon expression in CHO cells, and co-expression with WT Kir7.1 shows dominant-negative reduction of IKir7.1. Homology modeling suggests loss of hydrogen bonding in the lipid-binding (PIP2) regulatory domain of the cytoplasmic structure. CHO cell expression, whole-cell patch-clamp, co-expression experiments, homology modeling based on bacterial Kir structure PloS one Medium 23977131
2014 Kir7.1 current hyperpolarizes uterine myocytes and promotes myometrial quiescence during gestation. Labor is associated with decreased Kir7.1 expression. Lentiviral miRNA-mediated knockdown of Kir7.1 increased uterine contractile force and duration, while overexpression inhibited contractility. The Kir7.1 inhibitor VU590 induced prolonged uterine contractions. Genome-wide screen, computational modeling, lentiviral miRNA knockdown and overexpression, uterine contractility assays, patch-clamp EMBO molecular medicine High 25056913
2015 MC4R couples to Kir7.1 in hypothalamic PVN neurons in a G-protein (Gαs)-independent manner: α-MSH closes Kir7.1 (depolarizing neurons) and AgRP acts as a biased agonist opening Kir7.1 (hyperpolarizing neurons), independently of blocking α-MSH binding. This Kir7.1 signaling pathway contributes to melanocortin-mediated regulation of energy homeostasis. Hypothalamic slice patch-clamp electrophysiology in mice, pharmacological dissection of Gαs pathway, ligand-binding studies Nature High 25600267
2015 CRISPR-Cas9 mosaic deletion of Kcnj13 in mouse RPE causes photoreceptor degeneration overlying mutant RPE cells, while wild-type RPE cells can rescue photoreceptors overlying mutant RPE; complete loss of Kcnj13 is likely postnatal lethal. This establishes KCNJ13 expression in RPE as required for photoreceptor survival. CRISPR-Cas9 zygote injection, mosaic analysis, immunofluorescence, electroretinography Scientific reports High 25666713
2015 A novel nonsense mutation in KCNJ13 (LCA16) truncates the Kir7.1 C-terminus, alters protein localization, and disrupts potassium currents. Heterozygous co-expression of mutant and WT channel has no negative influence on WT channel function (no dominant-negative effect), consistent with recessive inheritance. shRNA suppression of Kir7.1 in mice reproduces the LCA ERG phenotype. Heterologous expression, patch-clamp electrophysiology, subcellular localization, mouse shRNA knockdown, ERG Human mutation High 25921210
2015 Homozygous Kcnj13 knockout mice die hours after birth and exhibit cleft palate and moderate lung developmental retardation, establishing Kir7.1 roles in palatogenesis and respiratory development. Kcnj13 gene ablation (knockout mouse), histology, developmental analysis PloS one Medium 26402555
2017 Kir7.1 in RPE is required for normal a-, b-, and c-wave ERG responses: shRNA knockdown or pharmacological block with VU590 in vivo reduces all ERG wave amplitudes, whereas VU590 has no effect on isolated retina (without attached RPE), indicating that RPE Kir7.1 controls subretinal K+ homeostasis that is required for photoreceptor and bipolar cell electrophysiology. In vivo shRNA knockdown, pharmacological block (VU590), ERG, ex vivo isolated retina ERG, patch-clamp of native mouse RPE Scientific reports High 28878288
2017 Oxytocin receptor (OXTR) activation in RPE inhibits Kir7.1 channel activity through a PIP2-dependent capacitative Ca2+ entry mechanism. Human RPE cell line, HEK293 heterologous OXTR expression, Ca2+ imaging, pharmacological Ca2+ signaling inhibitors, patch-clamp Cellular signalling Medium 28603013
2017 VU590 inhibits Kir7.1 and Kir1.1 by a voltage- and K+-dependent mechanism within the channel pore. Asparagine 171 (N171) is the key pore residue for high-affinity VU590 block of Kir1.1. For Kir7.1, threonine 153 (T153) creates a polarity barrier that restricts low-affinity ligand access to the pore binding site at E149 and A150. Molecular modeling, site-directed mutagenesis, patch-clamp electrophysiology Molecular pharmacology High 28619748
2018 KCNJ13 is essential for smooth muscle (SM) cell alignment and polarity during mouse tracheal tubulogenesis; loss of KCNJ13 disrupts ion homeostasis in tracheal SM cells, impairing actin polymerization via reduced AKT phosphorylation. Pharmacological increase of AKT phosphorylation ameliorates the tracheal phenotypes. ENU forward genetic screen, Kcnj13 mutant mouse, SM cell imaging, actin staining, AKT pharmacological rescue Nature communications High 30022023
2018 Multiple GPCRs reduce complex glycosylation of Kir7.1, decreasing channel activity without altering its surface expression. Mutagenesis of the sole Kir7.1 glycosylation site reduces conductance and open probability. MC4R is uniquely the only GPCR tested that does not suppress Kir7.1 glycosylation. The LCA-associated L241P mutation has significantly reduced complex glycosylation. Western blotting, mutagenesis, single-channel recording, HEK293T cell expression The Journal of biological chemistry High 30257863
2018 Conditional deletion of Kcnj13 specifically from RPE cells (Best1-cre) causes severe progressive photoreceptor degeneration (outer nuclear layer thinning) and reduced light response, confirming that Kir7.1 expression in RPE is required for photoreceptor survival. CRISPR-generated conditional knockout allele, Best1-cre RPE-specific deletion, histology, OCT, ERG Experimental eye research High 30009826
2019 Deletion of Kcnj13 specifically from MC4R-expressing neurons causes resistance to melanocortin peptide-induced depolarization in PVN brain slices, resistance to the sustained anorexic effect of melanocortin peptides, late-onset obesity, increased linear growth, and glucose intolerance, establishing Kir7.1 as a downstream effector of MC4R signaling in vivo. MC4R-Cre conditional Kcnj13 knockout mouse, hypothalamic slice patch-clamp, pharmacological melanocortin challenge, metabolic phenotyping Journal of neuroendocrinology High 30561082
2019 In kcnj13 mutant zebrafish (obelixtd15), RPE shows reduced phagosome clearance and increased mitochondrial number and size prior to retinal degeneration, with reduced ATP levels; this suggests that KCNJ13 loss primarily disrupts phagosome physiology with secondary mitochondrial dysfunction. Electron microscopy, ATP assay, quantitative RT-PCR, mitochondrial marker analysis in zebrafish mutant RPE Scientific reports Medium 30846767
2020 KCNJ13 knockout in human iPSC-derived RPE impairs cell alignment and phagocytosis of photoreceptor outer segments, with reduced expression of phagocytosis-related genes, establishing Kir7.1 as required for RPE phagocytic function. CRISPR/Cas9 KCNJ13 knockout in hiPSCs, hiPSC-RPE differentiation, phagocytosis assay with fluorescent POS, qPCR Investigative ophthalmology & visual science Medium 32437550
2020 Kir7.1 channels carry a significant proportion of the whole-cell K+ conductance in oligodendrocytes isolated from mouse optic nerves. Pharmacological blockade of Kir7.1 with VU590 compromises oligodendrocyte cell integrity and exacerbates oligodendroglial loss in an oxygen-glucose deprivation model. Patch-clamp electrophysiology of isolated oligodendrocytes, VU590 pharmacological block, OGD ischemia model in isolated optic nerves, immunofluorescence Brain structure & function Medium 32086565
2020 The R162W SVD mutation suppresses Kir7.1 through a dominant-negative mechanism dependent on the large, neutral side chain of Trp, which disrupts PIP2 binding at R162 (and K164/K159). Smaller neutral substitutions at R162 are tolerated or enhance function, confirming R162 as part of the PI(4,5)P2 binding site essential for channel gating. Xenopus oocyte expression, mutagenesis, chemical modification of Cys substitution, DrVSP voltage-dependent phosphatase PIP2 depletion, concatemeric channel constructs The Journal of physiology High 33219695
2021 Progesterone directly activates Kir7.1 channels in choroid plexus epithelial cells and RPE cells, causing membrane hyperpolarization, independently of classical progesterone receptors expressed in these tissues. Whole-cell patch-clamp of murine choroid plexus and RPE cells, current-clamp, recombinant Kir7.1 expression, pharmacological receptor antagonists The Journal of general physiology High 34387656
2022 SUMOylation of Kir7.1 by SUMO-1 (not SUMO-2/3) in spinal cord neurons decreases Kir7.1 membrane expression and contributes to neuropathic pain after spared nerve injury; inhibition of SUMOylation rescues surface Kir7.1 and reduces mechanical allodynia. Co-immunoprecipitation, Western blot (total and membrane fractions), shRNA knockdown, pharmacological inhibitors of SUMOylation (E1 inhibitor GA, UBC9 inhibitor 2-D08), von Frey test CNS neuroscience & therapeutics Medium 35633059
2022 The T153I disease mutation in Kir7.1 produces a full-length protein that reaches the cell membrane but exhibits negligible K+ conductance, failing to hyperpolarize the membrane. Side-chain polarity and length at position 153 (within the inner pore) govern K+ permeation: polar residues with pore radii comparable to WT (Cys, Ser) maintain conductance, while nonpolar substitutions (Ile, Leu, Ala, Gly) do not. Whole-cell patch-clamp, chord conductance analysis, site-directed mutagenesis, subcellular localization imaging American journal of physiology. Cell physiology High 35584325
2022 Conditional knockout of Kcnj13 in RPE (VMD2-Cre) results in loss of outer nuclear layer photoreceptors, thinning of inner nuclear layer, and loss of bipolar cells with extinguished ERG, while RPE is preserved but morphologically disrupted. Lentiviral replacement of Kcnj13 restored ERG c-wave but not a- or b-waves. Conditional knockout mouse (gene-trap + Cre), fundoscopy, OCT, ERG, histology, lentiviral gene replacement Frontiers in cell and developmental biology High 35096838
2023 Base editing delivery to RPE via silica nanocapsules corrected the KCNJ13 W53X mutation in patient fibroblasts (47%) and hiPSC-RPE (17%), restoring functional Kir7.1 channels in edited LCA16-iPSC-RPE. In vivo delivery in an LCA16 mouse model preserved normal vision by ERG and OCT. Adenine base editor (ABE8e) delivery, patch-clamp of edited hiPSC-RPE, full-field ERG, multifocal ERG, OCT The Journal of clinical investigation High 37561581
2024 Clozapine inhibits MC4R-expressing PVN neurons by enhancing MC4R–Kir7.1 coupling, opening the channel independently of canonical Gαs signaling; neither clozapine nor risperidone affects MC4R ligand binding or Gαs signaling. Deletion of Kir7.1 in Mc4r-Cre neurons prevents clozapine-induced weight gain. MC4R-Cre conditional Kcnj13 knockout, hypothalamic slice electrophysiology, radioligand binding, cAMP assay, metabolic phenotyping, Kir7.1 blocker pharmacology bioRxivpreprint Medium 38895206
2024 The first cryo-EM/structural characterization of human Kir7.1 revealed conformational changes associated with pathogenic mutations R162Q and E276A that illuminate the gating pathway. ML418 blockade was structurally resolved within the pore. Preliminary structural data on an MC4R–Kir7.1 tandem fusion suggest the complex forms a homotetrameric channel that retains MC4R ligand regulation. Channel block in vivo with ML418 activates PVN MC4R neurons, inhibiting food intake and inducing weight loss. Cryo-EM structure determination, mutagenesis, pharmacological in vivo blockade, patch-clamp bioRxivpreprint Medium 38895219
2024 The I120T mutation in Kir7.1 produces a full-length but completely inactive channel that reaches the plasma membrane; in heterozygous WT/I120T mice, RPE Kir7.1 current is reduced ~50% proportional to WT gene dosage with no dominant-negative effect, and vision is normal. Mutant I120T channels do not form heterotetramers with WT in vitro. CRISPR knockin mice, RPE patch-clamp with Rb+ charge carrier, mixed transfection and tandem tetrameric constructs, ERG, behavioral vision testing American journal of physiology. Cell physiology High 38406825
2025 Progesterone and synthetic progestins (17α-hydroxyprogesterone caproate, dydrogesterone) directly activate Kir7.1 in myometrial and placental pericyte cells through a nongenomic mechanism, hyperpolarizing these cells and maintaining uterine quiescence during gestation. Patch-clamp electrophysiology of human and murine myometrium and placental pericytes, pharmacological progestin panel, subcellular localization Science advances High 40043131
2025 Kir7.1 is the primary K+-independent conductance in choroid plexus epithelial (CPE) cells and is critical for setting CSF K+ concentration: conditional knockout reduces [K+]CSF while M125R knock-in (converting K+-independence to K+-dependence) increases it. Kir7.1 loss also strongly inhibits NKCC1 activity in CPE despite unchanged expression, suggesting Kir7.1 functions as part of an apical complex with Na+-K+-ATPase and NKCC1. Conditional KO and M125R knockin mice, patch-clamp of CPE cells, in vivo CSF collection and K+ measurement, NKCC1 activity assay, Western blot for NKCC1 phosphorylation Acta physiologica High 41212743
2025 Kir7.1-M125R mice, in which the channel loses its inverse K+-dependence, show altered RPE cell membrane potential relative to controls but normal photoreceptor and bipolar cell ERG responses (normal a- and b-waves), indicating that altered subretinal K+ buffering alone does not impair light signal processing; other Kir7.1 functions (such as photoreceptor outer segment recycling) are implicated in disease pathogenesis. Kir7.1-M125R knockin mouse, RPE patch-clamp, full-field ERG American journal of physiology. Cell physiology Medium 41247777
2025 OPN3 (opsin 3) in PVN hypothalamic neurons coexpressed with MC4R potentiates Kir7.1 channel activity via Gαi/o signaling under baseline conditions, opposing MC4R-mediated channel closure, and thereby promotes food intake. Patch-clamp electrophysiology, Gαi/o pharmacological inhibition, Opn3 conditional knockout in Mc4r neurons, cAMP assay, feeding behavior Proceedings of the National Academy of Sciences Medium 39951488
2025 Kir7.1 maintains resting membrane potential in neutrophils and is required for directional sensing (but not cell polarization) during chemotaxis. Oscillating membrane potential depolarizations occur in pseudopods toward chemokine sources, and Kir7.1 is required for this polarized depolarization. Focal depolarization biases pseudopod selection and Kir7.1 regulates GPCR signaling activation. Pharmacological and genetic Kir7.1 inhibition in neutrophils, genetically encoded voltage indicators in zebrafish neutrophils, optogenetic focal depolarization, chemotaxis assays bioRxivpreprint Medium bio_10.1101_2025.03.06.641746
2025 Anticodon-engineered tRNA (ACE-tRNA) targeting the W53X premature stop codon in KCNJ13 restores full-length Kir7.1 protein and channel function in patient hiPSC-RPE cells, and HDAd delivery in a W53X LCA16 mouse model durably restores vision as measured by retinography. ACE-tRNA suppression, HDAd viral delivery, patch-clamp of hiPSC-RPE, retinography in mouse model bioRxivpreprint Medium bio_10.1101_2025.07.10.660754

Source papers

Stage 0 corpus · 67 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2015 G-protein-independent coupling of MC4R to Kir7.1 in hypothalamic neurons. Nature 154 25600267
2011 Recessive mutations in KCNJ13, encoding an inwardly rectifying potassium channel subunit, cause leber congenital amaurosis. American journal of human genetics 113 21763485
2006 Pigment pattern in jaguar/obelix zebrafish is caused by a Kir7.1 mutation: implications for the regulation of melanosome movement. PLoS genetics 112 17121467
1999 Inwardly rectifying K+ channel Kir7.1 is highly expressed in thyroid follicular cells, intestinal epithelial cells and choroid plexus epithelial cells: implication for a functional coupling with Na+,K+-ATPase. The Biochemical journal 98 10455019
2008 Mutations in KCNJ13 cause autosomal-dominant snowflake vitreoretinal degeneration. American journal of human genetics 84 18179896
2015 CRISPR-engineered mosaicism rapidly reveals that loss of Kcnj13 function in mice mimics human disease phenotypes. Scientific reports 80 25666713
2001 Expression and permeation properties of the K(+) channel Kir7.1 in the retinal pigment epithelium. The Journal of physiology 70 11230507
2003 Expression and localization of the inwardly rectifying potassium channel Kir7.1 in native bovine retinal pigment epithelium. Investigative ophthalmology & visual science 67 12824269
2000 Localization of inward rectifier potassium channel Kir7.1 in the basolateral membrane of distal nephron and collecting duct. Journal of the American Society of Nephrology : JASN 59 11053473
2014 The inwardly rectifying K+ channel KIR7.1 controls uterine excitability throughout pregnancy. EMBO molecular medicine 57 25056913
2001 Functional Kir7.1 channels localized at the root of apical processes in rat retinal pigment epithelium. The Journal of physiology 56 11179389
2018 The potassium channel KCNJ13 is essential for smooth muscle cytoskeletal organization during mouse tracheal tubulogenesis. Nature communications 50 30022023
2015 A Novel KCNJ13 Nonsense Mutation and Loss of Kir7.1 Channel Function Causes Leber Congenital Amaurosis (LCA16). Human mutation 48 25921210
2001 Cellular localization of the potassium channel Kir7.1 in guinea pig and human kidney. Kidney international 46 11380822
2011 Discovery, characterization, and structure-activity relationships of an inhibitor of inward rectifier potassium (Kir) channels with preference for Kir2.3, Kir3.x, and Kir7.1. Frontiers in pharmacology 36 22275899
2014 Focus on Kir7.1: physiology and channelopathy. Channels (Austin, Tex.) 34 25558901
2013 Snowflake vitreoretinal degeneration (SVD) mutation R162W provides new insights into Kir7.1 ion channel structure and function. PloS one 34 23977131
2015 Cleft Palate, Moderate Lung Developmental Retardation and Early Postnatal Lethality in Mice Deficient in the Kir7.1 Inwardly Rectifying K+ Channel. PloS one 31 26402555
2023 Nonviral base editing of KCNJ13 mutation preserves vision in a model of inherited retinal channelopathy. The Journal of clinical investigation 27 37561581
2017 Abnormal Electroretinogram after Kir7.1 Channel Suppression Suggests Role in Retinal Electrophysiology. Scientific reports 27 28878288
2014 A distinct vitreo-retinal dystrophy with early-onset cataract from recessive KCNJ13 mutations. Ophthalmic genetics 26 25475713
2007 Expression of Kir7.1 and a novel Kir7.1 splice variant in native human retinal pigment epithelium. Experimental eye research 25 18035352
2020 Evolution of the potassium channel gene Kcnj13 underlies colour pattern diversification in Danio fish. Nature communications 24 33277491
2017 Oxytocin (OXT)-stimulated inhibition of Kir7.1 activity is through PIP2-dependent Ca2+ response of the oxytocin receptor in the retinal pigment epithelium in vitro. Cellular signalling 24 28603013
2012 Characterization of the R162W Kir7.1 mutation associated with snowflake vitreoretinopathy. American journal of physiology. Cell physiology 24 23255580
2019 Phagosomal and mitochondrial alterations in RPE may contribute to KCNJ13 retinopathy. Scientific reports 23 30846767
2018 Conditional loss of Kcnj13 in the retinal pigment epithelium causes photoreceptor degeneration. Experimental eye research 22 30009826
2019 Late onset obesity in mice with targeted deletion of potassium inward rectifier Kir7.1 from cells expressing the melanocortin-4 receptor. Journal of neuroendocrinology 20 30561082
2020 A critical role for the inward rectifying potassium channel Kir7.1 in oligodendrocytes of the mouse optic nerve. Brain structure & function 19 32086565
2007 Modulation of the Kir7.1 potassium channel by extracellular and intracellular pH. American journal of physiology. Cell physiology 19 18094146
2020 KCNJ13 Gene Deletion Impairs Cell Alignment and Phagocytosis in Retinal Pigment Epithelium Derived from Human-Induced Pluripotent Stem Cells. Investigative ophthalmology & visual science 17 32437550
1998 Partial gene structure and assignment to chromosome 2q37 of the human inwardly rectifying K+ channel (Kir7.1) gene (KCNJ13). Genomics 17 9878260
2003 Expression of the K+ channel Kir7.1 in the developing rat kidney: role in K+ excretion. Kidney international 16 12631077
2018 G protein-coupled receptors differentially regulate glycosylation and activity of the inwardly rectifying potassium channel Kir7.1. The Journal of biological chemistry 15 30257863
2022 SUMOylation of Kir7.1 participates in neuropathic pain through regulating its membrane expression in spinal cord neurons. CNS neuroscience & therapeutics 14 35633059
2017 Pore Polarity and Charge Determine Differential Block of Kir1.1 and Kir7.1 Potassium Channels by Small-Molecule Inhibitor VU590. Molecular pharmacology 14 28619748
2012 Diagnostic value of EAAT-1 and Kir7.1 for distinguishing endolymphatic sac tumors from choroid plexus tumors. American journal of clinical pathology 13 22706862
2006 Role of C-terminus of Kir7.1 potassium channel in cell-surface expression. Cell biology international 13 16406822
2000 Complex structure and regulation of expression of the rat gene for inward rectifier potassium channel Kir7.1. The Journal of biological chemistry 13 10871613
2019 Missense variants in the conserved transmembrane M2 protein domain of KCNJ13 associated with retinovascular changes in humans and zebrafish. Experimental eye research 12 31647904
2018 Tissue Distribution of Kir7.1 Inwardly Rectifying K+ Channel Probed in a Knock-in Mouse Expressing a Haemagglutinin-Tagged Protein. Frontiers in physiology 12 29740340
2019 Glial and neuronal expression of the Inward Rectifying Potassium Channel Kir7.1 in the adult mouse brain. Journal of anatomy 11 31309576
2003 Expression and functional properties of unique inward rectifier K+ channel Kir7.1 in the porcine iris and retinal pigment epithelium. Current eye research 11 14562164
2008 Dual regulation of renal Kir7.1 potassium channels by protein Kinase A and protein Kinase C. Biochemical and biophysical research communications 10 18976636
2022 Kir7.1 disease mutant T153I within the inner pore affects K+ conduction. American journal of physiology. Cell physiology 9 35584325
2021 The epithelial potassium channel Kir7.1 is stimulated by progesterone. The Journal of general physiology 9 34387656
2016 Kir7.1 immunoreactivity in canine choroid plexus tumors. Journal of veterinary diagnostic investigation : official publication of the American Association of Veterinary Laboratory Diagnosticians, Inc 9 27216721
2015 A High-Throughput Electrophysiology Assay Identifies Inhibitors of the Inwardly Rectifying Potassium Channel Kir7.1. Journal of biomolecular screening 9 25656238
2019 A novel Kir7.1 splice variant expressed in various mouse tissues shares organisational and functional properties with human Leber amaurosis-causing mutations of this K+ channel. Biochemical and biophysical research communications 8 31056263
2018 Characterization of MC4R Regulation of the Kir7.1 Channel Using the Tl+ Flux Assay. Methods in molecular biology (Clifton, N.J.) 8 29058194
2025 Hypothalamic opsin 3 suppresses MC4R signaling and potentiates Kir7.1 to promote food consumption. Proceedings of the National Academy of Sciences of the United States of America 6 39951488
2022 Retinal Development and Pathophysiology in Kcnj13 Knockout Mice. Frontiers in cell and developmental biology 6 35096838
2007 Functional diversification of kir7.1 in cichlids accelerated by gene duplication. Gene 6 17553638
2020 Altered phosphatidylinositol regulation of mutant inwardly rectifying K+ Kir7.1 channels associated with inherited retinal degeneration disease. The Journal of physiology 5 33219695
2024 Normal vision and development in mice with low functional expression of Kir7.1 in heterozygosis for a blindness-producing mutation inactivating the channel. American journal of physiology. Cell physiology 4 38406825
2022 Protrusion of KCNJ13 Gene Knockout Retinal Pigment Epithelium Due to Oxidative Stress-Induced Cell Death. Investigative ophthalmology & visual science 4 36413373
2022 Phenotypic expansion of KCNJ13-associated snowflake vitreoretinal degeneration. Ophthalmic genetics 4 36440807
2019 Kir7.1 inwardly rectifying K+ channel is expressed in ciliary body non pigment epithelial cells and might contribute to intraocular pressure regulation. Experimental eye research 4 31319081
2023 kcnj13 regulates pigment cell shapes in zebrafish and has diverged by cis-regulatory evolution between Danio species. Development (Cambridge, England) 3 37530080
2000 Genomic structure and promoter analysis of the rat kir7.1 potassium channel gene (Kcnj13). FEBS letters 3 11042260
2025 Kir7.1 is the physiological target for hormones and steroids that regulate uteroplacental function. Science advances 2 40043131
2024 Functional coupling between MC4R and Kir7.1 contributes to clozapine-induced hyperphagia. bioRxiv : the preprint server for biology 2 38895206
2024 Structure of the Ion Channel Kir7.1 and Implications for its Function in Normal and Pathophysiologic States. bioRxiv : the preprint server for biology 2 38895219
2022 A novel phenotype associated with the R162W variant in the KCNJ13 gene. Ophthalmic genetics 2 35477418
2025 Role of the Choroid Plexus Kir7.1 Channel in the Regulation of Mouse Cerebrospinal Fluid K+ Concentration. Acta physiologica (Oxford, England) 1 41212743
2025 Role of Kir7.1 K+ channel in retinal pigment epithelium probed in a Kir7.1-M125R-expressing mutant mouse. American journal of physiology. Cell physiology 0 41247777
2024 Automated Patch Clamp Recordings of GPCR-Gated Ion Channels: Targeting the MC4-R/Kir7.1 Potassium Channel Complex. Methods in molecular biology (Clifton, N.J.) 0 38856905

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