Affinage

KCNJ13

Inward rectifier potassium channel 13 · UniProt O60928

Length
360 aa
Mass
40.5 kDa
Annotated
2026-04-28
67 papers in source corpus 44 papers cited in narrative 44 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

KCNJ13 encodes Kir7.1, an inwardly rectifying potassium channel with uniquely low unitary conductance (~2 pS) and an inverse dependence on extracellular K+ concentration, which localizes to the apical membrane of retinal pigment epithelium (RPE) and choroid plexus epithelium and to the basolateral membrane of renal tubular and thyroid cells, where it co-localizes with Na+/K+-ATPase to recycle K+ and sustain pump activity (PMID:10455019, PMID:11179389, PMID:29740340). In the RPE, Kir7.1 is essential for photoreceptor survival and function: conditional RPE-specific knockout causes progressive photoreceptor degeneration with diminished electroretinographic responses, and loss-of-function mutations cause Leber congenital amaurosis (LCA16) while the gain-of-toxic-function R162W mutation causes snowflake vitreoretinal degeneration through dominant-negative disruption of PI(4,5)P2-dependent gating (PMID:30009826, PMID:25921210, PMID:33219695). In hypothalamic paraventricular nucleus neurons, Kir7.1 couples to MC4R in a G-protein-independent manner—closed by α-MSH and opened by AgRP—to regulate energy homeostasis; conditional deletion from MC4R neurons causes late-onset obesity, increased linear growth, and resistance to melanocortin-induced anorexia (PMID:25600267, PMID:30561082). Channel activity is further modulated by PI(4,5)P2 binding at R162/K164, intracellular pH sensing through H26, PKA (S287) and PKC (S201) phosphorylation, N-glycosylation state, SUMO-1 conjugation controlling surface expression, and direct nongenomic activation by progesterone that maintains uterine quiescence (PMID:33219695, PMID:18094146, PMID:18976636, PMID:30257863, PMID:35633059, PMID:40043131).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 1999 High

    Establishing where Kir7.1 resides resolved its likely physiological function: co-localization with Na+/K+-ATPase at epithelial membranes in thyroid and choroid plexus indicated a K+-recycling role to maintain pump activity.

    Evidence Immunohistochemistry and subcellular fractionation in thyroid, choroid plexus, and kidney tissues

    PMID:10455019 PMID:11053473

    Open questions at the time
    • Functional coupling to Na+/K+-ATPase not directly demonstrated
    • No electrophysiological characterization in native epithelia at this stage
  2. 2001 High

    Electrophysiological characterization in RPE and heterologous systems defined Kir7.1's distinctive biophysical fingerprint—mild inward rectification, ~2 pS unitary conductance, and paradoxical inverse K+ dependence—and established it as the dominant apical K+ conductance in RPE.

    Evidence Two-electrode voltage clamp in Xenopus oocytes, cell-attached patch clamp on bovine RPE, immunoelectron microscopy

    PMID:11179389 PMID:11230507

    Open questions at the time
    • Molecular basis of inverse K+ dependence unknown
    • No disease link yet established
  3. 2006 High

    Positional cloning of zebrafish pigmentation mutants (jaguar/obelix) provided the first genetic evidence that Kir7.1 loss-of-function disrupts cellular signaling in vivo, here affecting melanosome transport in response to sympathetic input.

    Evidence Positional cloning, BAC rescue, patch clamp electrophysiology in zebrafish melanophores

    PMID:17121467

    Open questions at the time
    • Relevance to mammalian disease not yet shown
    • Signaling pathway downstream of Kir7.1 in melanophores unclear
  4. 2008 High

    Identification of the R162W mutation in snowflake vitreoretinal degeneration and characterization of PKA/PKC phosphorylation sites revealed that Kir7.1 is both a disease gene and subject to dual kinase regulation, with PKC inhibiting (via S201) and PKA activating (via S287) the channel.

    Evidence Patch clamp of disease mutant in CHO cells; oocyte expression with PKA/PKC modulators and site-directed mutagenesis

    PMID:18179896 PMID:18976636

    Open questions at the time
    • In vivo relevance of PKA/PKC regulation not shown
    • Dominant-negative mechanism of R162W not yet resolved
  5. 2012 High

    Demonstrating that R162W exerts a dominant-negative effect by impairing PI(4,5)P2-dependent gating connected the SVD mutation to a defined regulatory mechanism and explained autosomal dominant inheritance.

    Evidence Co-expression of mutant and wild-type in Xenopus oocytes with quantitative current analysis

    PMID:23255580

    Open questions at the time
    • Precise PI(4,5)P2 binding residues not yet mapped
    • Structural basis of dominant-negative assembly unknown
  6. 2014 High

    Demonstration that Kir7.1 hyperpolarizes uterine myocytes and maintains quiescence during gestation expanded the channel's physiological repertoire beyond epithelial K+ recycling to a direct role in reproductive physiology.

    Evidence Knockdown, overexpression, patch clamp, and organ bath contractility assays in mouse and human myometrium

    PMID:25056913

    Open questions at the time
    • Upstream signal regulating Kir7.1 in myometrium not identified at this stage
    • Relevance to preterm labor in humans not demonstrated
  7. 2015 High

    Discovery that MC4R couples to Kir7.1 in a G-protein-independent manner—α-MSH closing and AgRP opening the channel—established a novel receptor-channel signaling paradigm in hypothalamic energy homeostasis, while mosaic and global Kcnj13 knockouts proved RPE Kir7.1 is essential for photoreceptor survival and palatogenesis.

    Evidence Brain slice electrophysiology with pharmacological dissection; CRISPR mosaic RPE KO with ERG and histology; global KO mice with cleft palate phenotype; LCA16 mutation electrophysiology

    PMID:25600267 PMID:25666713 PMID:25921210 PMID:26402555

    Open questions at the time
    • In vivo metabolic consequences of MC4R-Kir7.1 coupling not yet tested
    • Whether RPE degeneration mechanism is K+-buffering or phagocytic failure unresolved
  8. 2018 High

    Conditional RPE-specific and tracheal smooth muscle studies, plus discovery that GPCR-modulated N-glycosylation regulates Kir7.1 conductance, deepened understanding of tissue-specific channel regulation and confirmed RPE-autonomous photoreceptor degeneration.

    Evidence Best1-Cre RPE conditional KO with ERG and histology; ENU screen and conditional KO in tracheal SM with AKT rescue; co-expression glycosylation/single-channel recording

    PMID:30009826 PMID:30022023 PMID:30257863

    Open questions at the time
    • How glycosylation state regulates open probability at the structural level unknown
    • Whether AKT pathway is relevant in tissues other than trachea untested
  9. 2019 High

    Conditional deletion of Kcnj13 from MC4R neurons in vivo validated the G-protein-independent MC4R-Kir7.1 pathway as required for melanocortin-induced anorexia and glucose homeostasis, while zebrafish data suggested phagosome clearance failure as an early RPE pathology.

    Evidence MC4R-Cre conditional KO with metabolic phenotyping and brain slice electrophysiology; EM and ATP assays in obelix zebrafish RPE

    PMID:30561082 PMID:30846767

    Open questions at the time
    • Whether phagocytic defect is primary or secondary to ion homeostasis disruption unclear
    • MC4R-Kir7.1 coupling mechanism at the protein level undefined
  10. 2020 High

    Identification of R162, K164, and K159 as the PI(4,5)P2-binding site and demonstration of Kir7.1's role in oligodendrocyte integrity and iPSC-RPE phagocytosis expanded both the molecular understanding of gating and the list of cell types dependent on this channel.

    Evidence Voltage-sensitive phosphatase depletion, cysteine modification, tandem concatemers in oocytes; VU590 block in optic nerve oligodendrocytes; CRISPR KO in hiPSC-RPE phagocytosis assay

    PMID:32086565 PMID:32437550 PMID:33219695

    Open questions at the time
    • Structural basis of PI(4,5)P2 interaction at atomic resolution unknown
    • Whether oligodendrocyte role is relevant to white matter disease in humans untested
  11. 2021 High

    Discovery that progesterone directly activates Kir7.1 independently of classical progesterone receptors revealed a nongenomic steroid-channel mechanism with implications for CSF homeostasis and uterine quiescence.

    Evidence Patch clamp in native choroid plexus and RPE cells plus recombinant expression

    PMID:34387656

    Open questions at the time
    • Binding site for progesterone on Kir7.1 not identified
    • Whether progesterone regulation is physiologically relevant during pregnancy not yet tested in vivo
  12. 2022 High

    SUMOylation by SUMO-1 was identified as a post-translational mechanism reducing Kir7.1 surface expression in spinal neurons, linking channel regulation to neuropathic pain, while T153 was shown to be structurally required for K+ permeation through pore radius constraints.

    Evidence Co-IP, membrane fractionation, and behavioral testing in SNI pain model; systematic T153 mutagenesis with patch clamp

    PMID:35584325 PMID:35633059

    Open questions at the time
    • SUMO-1 conjugation site on Kir7.1 not mapped
    • Whether T153 disease mutation causes pathology in vivo not tested
  13. 2023 High

    Adenine base editing corrected the KCNJ13 W53X LCA16 mutation in patient-derived cells and preserved vision in a mouse model, providing proof-of-concept for gene therapy targeting Kir7.1 channelopathies.

    Evidence Silica nanocapsule delivery of ABE8e to hiPSC-RPE and mouse retina; patch clamp functional rescue; ERG in vivo

    PMID:37561581

    Open questions at the time
    • Long-term durability and safety of base editing in RPE not established
    • Applicability to other KCNJ13 mutations not tested
  14. 2024 High

    The I120T knockin mouse demonstrated that recessive KCNJ13 mutations produce non-functional monomers that cannot co-assemble with wild-type subunits, leaving heterozygotes with ~50% current and normal vision, explaining haploinsufficiency tolerance.

    Evidence CRISPR knockin mice, native RPE patch clamp, tandem tetramer analysis, ERG and behavioral vision tests

    PMID:38406825

    Open questions at the time
    • Whether all recessive mutations share this non-assembly mechanism is unclear
    • Threshold of Kir7.1 current loss required for pathology not defined
  15. 2025 High

    Recent studies expanded Kir7.1's roles to choroid plexus CSF K+ regulation via an apical complex with Na+/K+-ATPase and NKCC1, confirmed progesterone as a direct nongenomic activator in myometrium and placental pericytes, identified OPN3 as an upstream Gαi/o-coupled modulator of Kir7.1 in MC4R neurons, and challenged the K+-buffering model of RPE disease with M125R knockin data.

    Evidence Conditional KO and M125R knockin mice with CSF measurements; native myometrial/pericyte electrophysiology; MC4R-Cre conditional OPN3 KO with feeding studies; M125R knockin RPE electrophysiology and ERG

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

    Open questions at the time
    • Progesterone binding site on Kir7.1 remains structurally undefined
    • If K+-buffering is not the primary disease mechanism, the critical RPE function of Kir7.1 (phagocytosis support vs. other) is unresolved
    • Whether OPN3-Kir7.1 interaction is direct or mediated by intermediary effectors is unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key open questions include: the atomic-resolution structure of Kir7.1 in complex with PI(4,5)P2 and progesterone, the physical basis of G-protein-independent MC4R-Kir7.1 coupling, and whether phagocytic failure or another non-K+-buffering function is the primary driver of photoreceptor degeneration in KCNJ13 disease.
  • No peer-reviewed high-resolution structure of human Kir7.1 yet published
  • Structural basis of MC4R-Kir7.1 physical coupling undefined
  • Relative contribution of K+ homeostasis vs. phagocytic support to RPE disease pathology unresolved

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005215 transporter activity 7
Localization
GO:0005886 plasma membrane 8 GO:0005829 cytosol 1
Pathway
R-HSA-112316 Neuronal System 4 R-HSA-162582 Signal Transduction 4 R-HSA-9709957 Sensory Perception 4 R-HSA-1643685 Disease 3
Partners
MC4ROPN3OXTRSUMO1

Evidence

Reading pass · 44 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1999 Kir7.1 localizes to the basolateral membrane of thyroid follicular cells and to the apical membrane of choroid plexus epithelial cells, co-localizing with Na+,K+-ATPase, suggesting functional coupling to recycle K+ and maintain pump activity. Northern blot, immunohistochemistry, subcellular fractionation The Biochemical journal High 10455019
2000 Kir7.1 is localized to the basolateral membrane of the distal convoluted tubule and principal cells of the cortical collecting duct in kidney, where it co-localizes with Na+,K+-ATPase and may contribute to K+ recycling and tubular K+ secretion; expression is regulated by dietary K+. Western blot, immunohistochemistry, electron microscopic immunocytochemistry, double-labeling immunogold Journal of the American Society of Nephrology High 11053473
2000 The rat Kir7.1 gene (Kcnj13) promoter contains a CCAAT element through which cAMP regulates channel expression, demonstrated by deletion and mutational analysis of promoter activity in FRTL-5 cells. Promoter deletion analysis, luciferase reporter assay, mutational analysis The Journal of biological chemistry Medium 10871613
2001 Kir7.1 channel subunits form the predominant K+ conductance of the RPE apical membrane; the channel exhibits mild inward rectification, an inverse dependence on extracellular K+ concentration, and a unitary conductance of ~2 pS. Xenopus oocyte expression, two-electrode voltage clamp, non-stationary noise analysis, cell-attached patch clamp on bovine RPE 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 provides the K+ recycling pathway to maintain pump activity. Immunohistochemistry, electron microscopy, RT-PCR, immunoblot, patch clamp in HEK293T cells The Journal of physiology High 11179389
2003 Kir7.1 is the major component of the apical K+ conductance in bovine RPE, distributed over the length of apical processes and co-localizing with Na+,K+-ATPase; it is absent from the basolateral membrane. RT-PCR, Northern blot, Western blot, indirect immunofluorescence Investigative ophthalmology & visual science High 12824269
2006 In zebrafish jaguar/obelix mutants, loss-of-function mutations in Kir7.1 impair K+ channel activity in melanophores, preventing correct response to the melanosome dispersion signal from sympathetic neurons and constitutively activating melanosome aggregation downstream of the alpha2-adrenoceptor. Positional cloning, patch clamp electrophysiology, BAC rescue, in vivo pigment pattern analysis PLoS genetics High 17121467
2006 The C-terminal length of Kir7.1 is essential for plasma membrane targeting; deletions of 38 or more C-terminal residues cause intracellular retention, and restoration of sufficient C-terminal length rescues surface expression. Deletion mutagenesis, immunofluorescence microscopy, cell-surface biotinylation in MDCK cells Cell biology international Medium 16406822
2007 Kir7.1 channel activity is inhibited by strong extracellular acidification and modulated biphasically by intracellular pH, with maximal activity at ~pH 7.0; histidine 26 (H26) in the N-terminus is required for channel activation at physiological intracellular pH. Xenopus oocyte expression, two-electrode voltage clamp, point mutagenesis of histidine residues American journal of physiology. Cell physiology High 18094146
2008 The KCNJ13 R162W mutation in Kir7.1 associated with snowflake vitreoretinal degeneration produces a nonselective cation current instead of selective K+ current, depolarizing transfected cells and increasing their fragility, demonstrating a gain-of-toxic-function mechanism. CHO-K1 cell overexpression, patch clamp electrophysiology, molecular modeling American journal of human genetics Medium 18179896
2008 PKC activation strongly inhibits Kir7.1 currents via phosphorylation at serine 201 (S201), while PKA activation increases Kir7.1 currents via phosphorylation at serine 287 (S287), demonstrating dual kinase regulation. Xenopus oocyte expression, two-electrode voltage clamp, pharmacological PKA/PKC manipulation, site-directed mutagenesis Biochemical and biophysical research communications High 18976636
2011 A pharmacological inhibitor (VU573) inhibits Kir7.1 (IC50 ~1.9 µM for GIRK) with preference over Kir1.1 and Kir2.1, enabling pharmacological dissection of Kir7.1 function; a thallium flux assay for the Kir7.1 M125R pore mutant was established for drug screening. Thallium flux assay, patch clamp electrophysiology in Xenopus oocytes and mammalian cells, structure-activity relationships Frontiers in pharmacology Medium 22275899
2012 The R162W mutation in Kir7.1 causes a dominant-negative effect: the mutant protein does not form functional channels, and coexpression with wild-type Kir7.1 reduces K+/Rb+ currents to ~17% of wild-type levels, likely by impairing gating by membrane PI(4,5)P2. Xenopus oocyte expression, two-electrode voltage clamp, immunostaining in Xenopus oocytes and MDCK cells American journal of physiology. Cell physiology High 23255580
2013 The R162W SVD mutation inactivates Kir7.1 and shifts resting membrane potential toward depolarization; homology modeling based on a bacterial Kir structure suggests loss of hydrogen bonding in the regulatory lipid-binding domain of the cytoplasmic structure. CHO cell expression, patch clamp electrophysiology, homology modeling PloS one Medium 23977131
2014 Kir7.1 current hyperpolarizes uterine myocytes and promotes quiescence during gestation; knockdown via lentiviral miRNA increases uterine contractile force, while overexpression inhibits contractility; Kir7.1 inhibitor VU590 induces sustained uterine contractions. Computational modeling, lentiviral miRNA knockdown, overexpression, patch clamp electrophysiology, organ bath contractility assays in mouse and human myometrium EMBO molecular medicine High 25056913
2015 MC4R couples to Kir7.1 in paraventricular nucleus hypothalamic neurons in a G-protein-independent manner: α-MSH binding closes Kir7.1 causing depolarization, while AgRP acts as a biased agonist that opens Kir7.1 to hyperpolarize neurons independently of blocking α-MSH binding. Whole-cell patch clamp in mouse hypothalamic slices, pharmacological dissection of Gαs signaling, ligand application Nature High 25600267
2015 Loss of Kcnj13 in RPE cells is sufficient to cause photoreceptor degeneration; mosaic CRISPR-Cas9-generated Kcnj13 deletion in mice shows that RPE cells lacking KCNJ13 lose ability to maintain overlying photoreceptors, while wild-type RPE can rescue neighboring photoreceptors above mutant cells. CRISPR-Cas9 zygote injection, electroretinography, histology, immunostaining Scientific reports High 25666713
2015 A novel KCNJ13 nonsense mutation causes LCA16 by truncating the Kir7.1 C-terminus, altering protein localization, and abolishing K+ currents; coexpression of the mutant with wild-type channel has no dominant-negative effect, consistent with recessive inheritance. Patch clamp electrophysiology, protein localization assays, shRNA knockdown in mice, ERG Human mutation High 25921210
2015 Kir7.1-null mice (Kcnj13 knockout) die hours after birth with cleft palate and moderate lung developmental retardation, demonstrating essential roles in palatogenesis and respiratory system development. Gene knockout by Kcnj13 ablation in mice, histology, phenotype characterization PloS one High 26402555
2017 Kir7.1 suppression in RPE (by shRNA or VU590 blocker) reduces ERG a-, b-, and c-wave amplitudes via alterations in subretinal K+ homeostasis; the blocker has no effect on isolated retina lacking attached RPE, demonstrating the RPE K+ channel is required for normal photoreceptor electrophysiology. shRNA knockdown, pharmacological block (VU590), ERG in vivo and ex vivo, patch clamp of native mouse RPE Scientific reports High 28878288
2017 Oxytocin receptor (OXTR) activation inhibits Kir7.1 channel activity in RPE cells through a PIP2-dependent capacitative Ca2+ entry (CCE) mechanism, linking OXTR signaling to subretinal K+ homeostasis. Patch clamp electrophysiology, Ca2+ imaging, pharmacological inhibitors of Ca2+ signaling, HEK293 heterologous expression Cellular signalling Medium 28603013
2017 VU590 inhibits Kir7.1 by binding within the pore in a voltage- and K+-dependent manner; pore-lining threonine 153 (T153) creates a polar barrier that limits low-affinity ligand access to the binding site formed by E149 and A150. Molecular modeling, site-directed mutagenesis, patch clamp electrophysiology Molecular pharmacology High 28619748
2018 KCNJ13 is required for smooth muscle cell alignment and actin polymerization during mouse tracheal tubulogenesis; KCNJ13 maintains ion homeostasis in SM cells, activating AKT to regulate the actin cytoskeleton, and pharmacological AKT activation rescues the mutant phenotype. ENU forward genetic screen, conditional KO, histology, immunostaining, pharmacological rescue with AKT activator Nature communications High 30022023
2018 Multiple GPCRs reduce complex glycosylation of Kir7.1 and decrease its channel activity without altering surface expression; mutagenesis of the sole glycosylation site reduces conductance and open probability; the LCA-associated L241P mutation has significantly reduced glycosylation; MC4R is the only tested GPCR that does not suppress Kir7.1 glycosylation. Western blot, single-channel recording, mutagenesis of glycosylation site, HEK293T co-expression with GPCRs The Journal of biological chemistry High 30257863
2018 Conditional deletion of Kcnj13 specifically in RPE (Best1-Cre) causes severe progressive thinning of the outer nuclear layer and reduced ERG responses, confirming that Kcnj13 expression in the RPE is required for photoreceptor function and survival. CRISPR-generated floxed allele, Best1-Cre conditional KO, ERG, histology, OCT Experimental eye research High 30009826
2018 Kir7.1 is expressed at the apical membrane of choroid plexus epithelial cells and produces characteristically large Rb+ currents; in mice, it is found in inner medullary collecting ducts (basolateral), respiratory tract epithelium (basolateral), eye, and ileum. Kir7.1-HA knock-in mouse, anti-HA Western blot, immunolocalization, patch clamp electrophysiology Frontiers in physiology High 29740340
2019 Deletion of Kcnj13 specifically from MC4R-expressing neurons causes resistance to melanocortin-induced depolarization of PVN neurons, resistance to sustained anorexic effects of melanocortin peptides, late-onset obesity, increased linear growth, and glucose intolerance, demonstrating that MC4R→Kir7.1 signaling is required in vivo for a subset of MC4R-mediated metabolic phenotypes. Conditional KO (MC4R-Cre × Kcnj13-flox), brain slice electrophysiology, metabolic phenotyping, feeding behavior analysis Journal of neuroendocrinology High 30561082
2019 Kcnj13 mutant zebrafish (obelixtd15) RPE shows reduced phagosome clearance, increased mitochondrial number and size, and altered ATP levels prior to retinal degeneration, suggesting that primary phagosome physiology failure with secondary mitochondrial dysfunction underlies KCNJ13-related retinal degeneration. Electron microscopy, ATP assay, quantitative RT-PCR, GFAP/HSP60 immunostaining Scientific reports Medium 30846767
2020 KCNJ13 knockout in human iPSC-derived RPE impairs phagocytosis of photoreceptor outer segments and reduces expression of phagocytosis-related genes, establishing a functional role for Kir7.1 in RPE phagocytic activity. CRISPR/Cas9 KO in hiPSCs, RPE differentiation, fluorescent POS phagocytosis assay, qPCR Investigative ophthalmology & visual science Medium 32437550
2020 Kir7.1 carries a significant proportion of whole-cell K+ conductance in oligodendrocytes of the mouse optic nerve; Kir7.1 blockade with VU590 compromises oligodendrocyte integrity and compounds oligodendroglial loss in oxygen-glucose deprivation. qRT-PCR, immunofluorescence in optic nerve, patch clamp electrophysiology with VU590, OGD model Brain structure & function Medium 32086565
2020 R162 and K164 (and possibly K159) in Kir7.1 form the PI(4,5)P2 binding site essential for channel activity; the SVD R162W mutation exerts a dominant-negative effect reducing activity to less than one-fifth of wild-type when equal amounts of mutant and wild-type channels are co-expressed. Heterologous expression, voltage-dependent phosphatase (DrVSP) PI(4,5)P2 depletion, cysteine chemical modification, tandem tetrameric concatemers, two-electrode voltage clamp The Journal of physiology High 33219695
2021 Progesterone directly and specifically potentiates Kir7.1 channel activity in choroid plexus and RPE cells, independently of known progesterone receptors, causing hyperpolarization of choroid plexus cells. Whole-cell patch clamp in native murine choroid plexus cells and RPE cells, current-clamp studies, recombinant Kir7.1 expression The Journal of general physiology High 34387656
2022 SUMOylation of Kir7.1 by SUMO-1 (not SUMO-2/3) decreases its surface expression in spinal cord neurons; SNI-induced neuropathic pain upregulates Kir7.1 SUMOylation, reducing membrane Kir7.1, and inhibiting SUMOylation restores surface expression and reduces mechanical allodynia. Co-immunoprecipitation, Western blot of total and membrane fractions, siRNA knockdown, pharmacological E1/UBC9 inhibitors, von Frey behavioral test CNS neuroscience & therapeutics Medium 35633059
2022 The T153I disease mutation in Kir7.1 abolishes K+ conductance despite normal membrane localization, due to alteration of inner pore radius; polar side-chain substitutions (Cys, Ser) with pore radii comparable to wild-type restore normal K+ conductance, revealing the structural requirement of T153 for K+ permeation. Whole-cell patch clamp, chord conductance analysis, mutagenesis of T153 to multiple amino acids, protein localization assay American journal of physiology. Cell physiology High 35584325
2022 Conditional Kcnj13 knockout in RPE (VMD2-Cre) causes loss of photoreceptors, inner nuclear layer thinning with loss of bipolar cells, disruption of outer plexiform layer, and decreased ERG amplitudes; lentiviral Kcnj13 replacement selectively rescues the ERG c-wave but not a- or b-waves. Conditional KO with VMD2-Cre, histology, fundoscopy, OCT, ERG, lentiviral gene replacement Frontiers in cell and developmental biology High 35096838
2023 Nonviral delivery of adenine base editor (ABE8e) corrects the KCNJ13 W53X mutation in patient fibroblasts and hiPSC-RPE, restoring functional Kir7.1 channels; in a LCA16 mouse model, RPE-targeted base editing preserves vision as measured by ERG. Silica nanocapsule delivery of ABE8e mRNA + sgRNA, patch clamp electrophysiology in edited hiPSC-RPE, ERG in vivo, OCT The Journal of clinical investigation High 37561581
2024 The Kir7.1 I120T mutation produces a full-length, membrane-localized but completely non-functional channel that does not form heterotetramers with wild-type Kir7.1 in vitro; heterozygous WT/I120T mice have ~50% of normal RPE Rb+ current (proportional to WT gene dosage) and normal vision, explaining the recessive nature of this disease mutation. Heterologous expression, patch clamp in native RPE cells from knockin mice, CRISPR knockin mouse generation, ERG, behavioral vision tests, tandem tetramer analysis American journal of physiology. Cell physiology High 38406825
2024 Crystal/cryo-EM structures of human Kir7.1 reveal the conformational basis of channel gating; pathogenic mutations R162Q and E276A display distinct conformational biases explaining disease; the small molecule ML418 blocks the channel at a defined structural site; a tandem MC4R-Kir7.1 fusion forms a homotetrameric channel that retains regulation by liganded MC4R. Cryo-EM structural determination, mutagenesis, pharmacological characterization, in vivo ML418 administration with ERG/feeding studies bioRxivpreprint High 38895219
2024 Clozapine enhances functional coupling between MC4R and Kir7.1 in PVN neurons, causing Kir7.1 opening and neuronal inhibition independently of MC4R Gαs signaling or ligand binding; deletion of Kir7.1 in MC4R neurons prevents clozapine-induced weight gain; Kir7.1 blocker mitigates clozapine-induced overeating. Brain slice electrophysiology, conditional KO (Mc4r-Cre × Kcnj13-flox), pharmacological Kir7.1 blockade, metabolic phenotyping in mice bioRxivpreprint High 38895206
2025 Progesterone and selective synthetic progestins (17α-hydroxyprogesterone caproate, dydrogesterone) directly activate Kir7.1 in myometrium and placental pericytes through a nongenomic mechanism, maintaining uterine quiescence during gestation. Patch clamp electrophysiology in native myometrial and placental pericyte cells, pharmacological profiling of steroid analogs Science advances High 40043131
2025 OPN3 in MC4R-expressing PVN neurons acts via Gαi/o to potentiate baseline Kir7.1 activity and suppress MC4R-mediated cAMP signaling, promoting food intake; conditional deletion of OPN3 in MC4R neurons reduces food consumption. Brain slice electrophysiology, cAMP assays, conditional KO (Mc4r-Cre), pharmacological Gαi/o inhibition, feeding behavior analysis Proceedings of the National Academy of Sciences High 39951488
2025 Kir7.1 is the primary K+-independent conductance in choroid plexus epithelial cells, setting membrane potential; its inactivation reduces CSF K+ concentration and impairs NKCC1 cotransporter function, suggesting Kir7.1 forms part of an apical complex with Na+,K+-ATPase and NKCC1. Conditional KO and M125R knockin mice, patch clamp of choroid plexus cells, in vivo CSF K+ measurement, NKCC1 activity/phosphorylation assays Acta physiologica High 41212743
2025 The Kir7.1 M125R mutation (which disrupts the extracellular K+-independent conductance property) does not abolish retinal responses to light in vivo, suggesting that K+ buffering of the subretinal space by Kir7.1 is not the primary mechanism underlying disease from Kir7.1 mutations; instead, other functions (e.g., photoreceptor outer segment recycling support) must underlie pathology. CRISPR knockin M125R mice, patch clamp of native RPE cells, in vivo ERG American journal of physiology. Cell physiology Medium 41247777
2025 Kir7.1 in neutrophils maintains resting membrane potential and is required for directional sensing during chemotaxis; Kir7.1 mediates oscillating depolarization in protrusions toward a chemokine source and regulates GPCR signaling activation during chemotaxis. Pharmacological inhibition and genetic KO of Kir7.1 in neutrophil models, genetically encoded voltage indicators in zebrafish neutrophils, optogenetic focal depolarization bioRxivpreprint Medium bio_10.1101_2025.03.06.641746

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
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
2011 Recessive mutations in KCNJ13, encoding an inwardly rectifying potassium channel subunit, cause leber congenital amaurosis. American journal of human genetics 111 21763485
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 82 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 69 11230507
2003 Expression and localization of the inwardly rectifying potassium channel Kir7.1 in native bovine retinal pigment epithelium. Investigative ophthalmology & visual science 66 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 46 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.) 33 25558901
2013 Snowflake vitreoretinal degeneration (SVD) mutation R162W provides new insights into Kir7.1 ion channel structure and function. PloS one 32 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
2017 Abnormal Electroretinogram after Kir7.1 Channel Suppression Suggests Role in Retinal Electrophysiology. Scientific reports 26 28878288
2023 Nonviral base editing of KCNJ13 mutation preserves vision in a model of inherited retinal channelopathy. The Journal of clinical investigation 25 37561581
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
2007 Expression of Kir7.1 and a novel Kir7.1 splice variant in native human retinal pigment epithelium. Experimental eye research 24 18035352
2020 Evolution of the potassium channel gene Kcnj13 underlies colour pattern diversification in Danio fish. Nature communications 23 33277491
2019 Phagosomal and mitochondrial alterations in RPE may contribute to KCNJ13 retinopathy. Scientific reports 23 30846767
2014 A distinct vitreo-retinal dystrophy with early-onset cataract from recessive KCNJ13 mutations. Ophthalmic genetics 23 25475713
2012 Characterization of the R162W Kir7.1 mutation associated with snowflake vitreoretinopathy. American journal of physiology. Cell physiology 23 23255580
2018 Conditional loss of Kcnj13 in the retinal pigment epithelium causes photoreceptor degeneration. Experimental eye research 21 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
2007 Modulation of the Kir7.1 potassium channel by extracellular and intracellular pH. American journal of physiology. Cell physiology 19 18094146
2020 A critical role for the inward rectifying potassium channel Kir7.1 in oligodendrocytes of the mouse optic nerve. Brain structure & function 18 32086565
2020 KCNJ13 Gene Deletion Impairs Cell Alignment and Phagocytosis in Retinal Pigment Epithelium Derived from Human-Induced Pluripotent Stem Cells. Investigative ophthalmology & visual science 16 32437550
2003 Expression of the K+ channel Kir7.1 in the developing rat kidney: role in K+ excretion. Kidney international 16 12631077
1998 Partial gene structure and assignment to chromosome 2q37 of the human inwardly rectifying K+ channel (Kir7.1) gene (KCNJ13). Genomics 16 9878260
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
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
2019 Missense variants in the conserved transmembrane M2 protein domain of KCNJ13 associated with retinovascular changes in humans and zebrafish. Experimental eye research 11 31647904
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
2007 Functional diversification of kir7.1 in cichlids accelerated by gene duplication. Gene 6 17553638
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 5 39951488
2022 Retinal Development and Pathophysiology in Kcnj13 Knockout Mice. Frontiers in cell and developmental biology 5 35096838
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
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 Phenotypic expansion of KCNJ13-associated snowflake vitreoretinal degeneration. Ophthalmic genetics 2 36440807
2025 Role of the Choroid Plexus Kir7.1 Channel in the Regulation of Mouse Cerebrospinal Fluid K+ Concentration. Acta physiologica (Oxford, England) 1 41212743
2022 A novel phenotype associated with the R162W variant in the KCNJ13 gene. Ophthalmic genetics 1 35477418
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