Affinage

KLHL3

Kelch-like protein 3 · UniProt Q9UH77

Length
587 aa
Mass
65.0 kDa
Annotated
2026-06-10
45 papers in source corpus 24 papers cited in narrative 23 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

KLHL3 is a BTB-BACK-Kelch substrate adaptor that assembles a CUL3-RING E3 ubiquitin ligase to target the WNK kinases for ubiquitin-dependent degradation, thereby controlling the WNK-SPAK/OSR1-NCC phosphorylation cascade in the distal nephron (PMID:22406640, PMID:23387299, PMID:23453970, PMID:23665031). Its BTB and BACK domains together form the CUL3-binding surface, while its Kelch β-propeller engages an acidic degron motif in WNK1 and WNK4; crystal structures of both the KLHL3 BTB-BACK–CUL3 and Kelch–WNK degron interfaces define these contacts at atomic resolution, and disease mutations mapped onto them abolish either CUL3 association or WNK binding (PMID:23573258, PMID:23387299, PMID:24641320). Knock-in and knockout mouse models confirm WNK1 and WNK4 as bona fide in vivo substrates whose protein levels rise when KLHL3 binding is lost, with WNK4 being indispensable for the downstream NCC-activating phenotype (PMID:24821705, PMID:28052936, PMID:28743496). KLHL3-directed WNK degradation proceeds primarily through the proteasome but is also routed to p62/SQSTM1-mediated selective autophagy (PMID:26349538). The ligase is regulated at multiple levels: phosphorylation of KLHL3 at Ser433 by Akt and PKA weakens Kelch-domain binding to the WNK4 acidic motif and stabilizes WNK4 (PMID:26435498), and CSN-mediated deneddylation of CUL3 is required to maintain KLHL3 stability and proper WNK signaling (PMID:30301860). Beyond the WNK axis, KLHL3 ubiquitinates additional substrates including the tight-junction protein claudin-8 to regulate paracellular chloride transport (PMID:25831548) and, when co-opted by KSHV vIRF1, hnRNP Q1 to reprogram glycolytic metabolism (PMID:35538151). Loss-of-function mutations in KLHL3 cause familial hyperkalemic hypertension (PHAII/FHHt) by stabilizing WNK kinases, with dominant alleles acting through dimerization with wild-type KLHL3 (PMID:22406640, PMID:28052936).

Mechanistic history

Synthesis pass · year-by-year structured walk · 9 steps
  1. 2012 Medium

    Linking KLHL3 to a Cullin3-based ubiquitin system and to NCC regulation established its candidacy as the distal-nephron salt-handling factor mutated in FHHt, framing the question of which substrate it controls.

    Evidence Linkage/exome sequencing in FHHt families plus cell-surface NCC expression assays

    PMID:22406640

    Open questions at the time
    • Direct substrate not yet identified
    • No biochemical demonstration of ligase assembly
  2. 2013 High

    Reconstitution showed KLHL3 bridges CUL3 and WNK kinases as the substrate adaptor of a working E3 ligase, directly explaining how disease mutations elevate WNK protein.

    Evidence Co-IP, in vitro ubiquitination with recombinant CUL3-KLHL3, domain mapping, and crystallography/ITC of the BTB-BACK–CUL3 interface; replicated across labs

    PMID:23387299 PMID:23453970 PMID:23573258 PMID:23665031 PMID:23962426

    Open questions at the time
    • Atomic detail of the Kelch–WNK degron contact not yet resolved
    • In vivo substrate identity not yet confirmed
  3. 2014 High

    Structural definition of the Kelch–WNK4 degron interface and in vivo knock-in models confirmed WNK1/WNK4 as physiological KLHL3 substrates and explained both KLHL3 and CUL3 disease alleles mechanistically.

    Evidence Crystal structure of Kelch–WNK4 degron complex, FCS binding with R528H mutant, and KLHL3 R528H knock-in plus nephron-specific Cul3 knockout mice

    PMID:24641320 PMID:24821705 PMID:25250572

    Open questions at the time
    • Relative contribution of WNK1 vs WNK4 to phenotype unresolved
    • Regulatory inputs onto KLHL3 not yet defined
  4. 2015 Medium

    Discovery of phosphoregulation at Ser433 and an alternative autophagic degradation route, plus claudin-8 as a substrate, broadened KLHL3 from a single-substrate adaptor to a hormonally tuned, multi-target ligase.

    Evidence In vitro Akt/PKA kinase assays with MS and phospho-antibody, p62/autophagy perturbation with imaging, and claudin-8 Co-IP/knockout with permeability readouts

    PMID:25831548 PMID:26349538 PMID:26435498

    Open questions at the time
    • In vivo relevance of S433 phosphorylation not established
    • Balance between proteasomal and autophagic routes unquantified
  5. 2017 Medium

    Genetic dissection in mice established the dominant-negative dimerization mechanism of pathogenic alleles and the epistatic requirement of WNK4 for the disease phenotype.

    Evidence KLHL3 knockout/heterozygote mice with dimerization analysis and WNK4-/-/KLHL3R528H double-mutant epistasis

    PMID:28052936 PMID:28743496

    Open questions at the time
    • Stoichiometry of mutant-WT heterodimer inhibition not quantified
    • Why WNK1 cannot compensate for WNK4 not mechanistically resolved
  6. 2018 Medium

    Separation-of-function mutants and CSN manipulation showed that CUL3 binding and KLHL3 stability are distinct vulnerabilities, with deneddylation required to preserve the adaptor.

    Evidence KLHL3 M131V knock-in with Co-IP and immunogold EM, and nephron-specific Jab1 (CSN) knockout mice

    PMID:30148674 PMID:30301860

    Open questions at the time
    • How CUL3 neddylation cycling drives KLHL3 turnover mechanistically unclear
    • Single-lab models
  7. 2021 Medium

    Mapping the KS-WNK1 N-terminal recognition element refined substrate selectivity, explaining why kidney-specific WNK1 is preferentially degraded over full-length WNK1.

    Evidence KLHL3-R528H knock-in mice with KS-WNK1 N-terminal mutagenesis and NCC functional assays

    PMID:33682442

    Open questions at the time
    • Structural basis of KS-WNK1 N-terminal recognition not solved
    • Isoform competition for KLHL3 in vivo not quantified
  8. 2022 High

    A WNK3 degron co-structure defined the complete WNK-family 11-mer binding mode and phospho-degron switching, and a viral-hijack study revealed KLHL3 functions beyond ion transport.

    Evidence Crystal structure of Kelch–WNK3 peptide with fluorescence polarization, and KSHV vIRF1-directed hnRNP Q1 ubiquitination with metabolic assays

    PMID:35179207 PMID:35538151

    Open questions at the time
    • Physiological signals controlling WNK degron phosphorylation unclear
    • Breadth of non-WNK substrate repertoire unknown
  9. 2025 Medium

    Identification of O-GlcNAcylation on KLHL3 and all WNK kinases added a metabolic post-translational layer regulating the axis in osmolarity and ferroptosis contexts.

    Evidence Glycoproteomics/MS with functional osmolarity and ferroptosis assays

    PMID:40796245

    Open questions at the time
    • Specific O-GlcNAc sites and their effect on ligase activity not mapped
    • In vivo physiological consequence not established

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the multiple regulatory inputs (S433 phosphorylation, O-GlcNAcylation, CUL3 neddylation, dimerization) are integrated to set KLHL3 ligase output in different tissues and physiological states remains unresolved.
  • No unified quantitative model of KLHL3 regulation
  • Full non-WNK substrate landscape uncharacterized
  • Tissue-specific substrate preference mechanisms unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 4 GO:0060090 molecular adaptor activity 3 GO:0016874 ligase activity 2
Localization
GO:0005829 cytosol 2
Pathway
R-HSA-382551 Transport of small molecules 2 R-HSA-392499 Metabolism of proteins 2
Partners
CLDN8CUL3MYBPC3SQSTM1SYNCRIPWNK1WNK3WNK4
Complex memberships
CUL3-RING E3 ubiquitin ligase (CRL3)

Evidence

Reading pass · 23 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2012 KLHL3 belongs to the BTB-BACK-kelch family of proteins that recruit substrates for Cullin3-based ubiquitin ligase complexes; KLHL3 is coexpressed with NCC in the distal nephron and downregulates NCC expression at the cell surface. Cell surface expression assay, co-expression analysis, linkage analysis and whole-exome sequencing identifying KLHL3 mutations in FHHt families Nature genetics Medium 22406640
2013 KLHL3 forms a complex with CUL3 (via its BTB-BACK domains) and directly interacts with WNK4 (and WNK1), acting as the substrate adaptor that recruits WNK kinases for CUL3-dependent ubiquitination and proteasomal degradation; disease-causing mutations in KLHL3 reduce WNK4 ubiquitination and increase WNK4 protein levels. Co-immunoprecipitation, in vitro ubiquitination assay with recombinant CUL3-KLHL3 complex, siRNA knockdown of CUL3 in HeLa cells, domain mapping The Biochemical journal High 23387299 23453970 23665031
2013 The KLHL3 BTB and BACK domains together form the CUL3 interaction surface; crystal structure of the KLHL3 BTB-BACK domain dimer in complex with the N-terminal fragment of CUL3 shows both domains contribute to binding, and disease mutations in the BTB-BACK region disrupt CUL3 association as measured by isothermal titration calorimetry. X-ray crystallography, isothermal titration calorimetry (ITC), mutagenesis PloS one High 23573258
2013 KLHL3 interacts with WNK4 through a non-catalytic region of WNK (residues 479-667 in WNK1, equivalent acidic motif in WNK4); Gordon's syndrome-causing mutations E562K and Q565E in WNK4 abolish the interaction with KLHL3. Co-immunoprecipitation, domain mapping, disease-mutant interaction studies The Biochemical journal High 23387299
2013 Multiple disease-causing KLHL3 mutations in the BTB domain reduce CUL3 binding, mutations in the Kelch domain reduce WNK4 binding, and the S410L mutation in the Kelch domain also reduces KLHL3 intracellular stability; all lead to decreased WNK4 ubiquitination and elevated WNK4 levels. Co-immunoprecipitation, cycloheximide chase assay, in vitro and in vivo ubiquitination assays, HEK293T transient expression Biochemical and biophysical research communications Medium 23962426
2014 Crystal structure of the KLHL3 Kelch domain in complex with the WNK4 degron motif (acidic motif) reveals an intricate network of interactions between the Kelch β-propeller surface and WNK4; disease-causing mutations in both WNK4 and KLHL3 disrupt critical interface contacts. KLHL2 binds WNK4 similarly to KLHL3 but with distinct binding mode compared to KEAP1. X-ray crystallography of KLHL3 Kelch domain–WNK4 degron complex; also crystal structure of KLHL2–WNK4 degron complex for comparison The Biochemical journal High 24641320
2014 FHHt-causing CUL3 mutant (CUL3Δ403-459) is more heavily neddylated and activated than WT CUL3; in cells it depletes KLHL3 through enhanced ubiquitylation, thereby preventing WNK degradation despite increased CUL3-mediated WNK ubiquitylation. Cell-based ubiquitylation assays, neddylation analysis, nephron-specific Cul3 knockout mouse model, Western blotting The Journal of clinical investigation High 25250572
2014 In KLHL3(R528H/+) knock-in mice, both WNK1 and WNK4 protein levels are significantly increased in the kidney; fluorescence correlation spectroscopy confirmed that the R528H mutation abolishes binding of KLHL3 to WNK1 and WNK4 peptides, establishing WNK1 and WNK4 as in vivo substrates of KLHL3-CUL3 E3 ligase. KLHL3 R528H knock-in mouse model, fluorescence correlation spectroscopy (FCS) binding assay, Western blotting, NCC phosphorylation analysis Human molecular genetics High 24821705
2015 KLHL3 directly binds claudin-8, a tight junction protein in the collecting duct, and promotes its ubiquitination and degradation, thereby regulating paracellular chloride transport; the dominant PHA-II mutation in KLHL3 impairs claudin-8 binding, ubiquitination, and degradation. Tissue-specific claudin-8 knockout mice, Co-immunoprecipitation of KLHL3 and claudin-8, KLHL3 knockdown in collecting duct cells measuring paracellular chloride permeability, ubiquitination assay Proceedings of the National Academy of Sciences of the United States of America Medium 25831548
2015 Akt (downstream of insulin signaling) and PKA (downstream of vasopressin/forskolin signaling) phosphorylate KLHL3 at serine 433 in vitro and in cells; this phosphorylation impairs the interaction between KLHL3 and WNK4, reducing WNK4 degradation and increasing WNK4 protein levels. In vitro kinase assay (Akt and PKA), mass spectrometry identification of phospho-S433, phospho-specific antibody, co-immunoprecipitation, cell-based WNK4 protein level measurement Biochemical and biophysical research communications Medium 26435498
2015 KLHL3 forms a complex with both WNK4 and p62/SQSTM1 via its Kelch repeat domain; under proteasome inhibition, p62-mediated selective autophagy contributes to KLHL3-dependent WNK4 degradation, with WNK4 co-localizing with KLHL3, p62, and LC3 in cytoplasmic puncta. Co-immunoprecipitation, immunofluorescence, 3-methyladenine autophagy inhibition, proteasome inhibitor (epoxomicin) treatment, p62 overexpression and knockdown in HEK293T cells The Biochemical journal Medium 26349538
2016 Phosphorylation of KLHL3 at S433 disrupts hydrogen bonds, hydrophobic, and electrostatic interactions between the Kelch domain of KLHL3 and the acidic motif of WNK4 by making the binding site more negatively charged, as demonstrated by molecular dynamics simulation corroborated by prior experimental data. Molecular dynamics simulation with energetic and structural analysis (computational study validating/explaining prior experimental findings) Protein science Low 27727489
2017 KLHL3 dimerizes, and the dominant-negative effect of pathogenic KLHL3 mutations (causing autosomal dominant FHHt) is explained by dimerization of mutant KLHL3 with wild-type KLHL3, impairing the function of the wild-type subunit; heterozygous KLHL3 deletion alone is insufficient to cause PHAII, whereas homozygous deletion causes PHAII with elevated WNK1 and WNK4 only in the kidney. KLHL3 knockout mouse model (KLHL3-/- and KLHL3+/-), β-galactosidase reporter for expression, Western blot of WNK kinases in multiple organs, dimerization analysis Molecular and cellular biology Medium 28052936
2017 WNK4 is indispensable for PHAII pathogenesis caused by KLHL3 mutation; increased WNK1 protein (due to impaired KLHL3-mediated degradation) cannot compensate for WNK4 deficiency to activate SPAK/OSR1-NCC phosphorylation signaling in vivo. WNK4-/-/KLHL3R528H/+ and WNK4-/-/KLHL3R528H/R528H double-mutant mouse models, Western blot and immunofluorescence of pSPAK, pNCC in distal convoluted tubules Biochemical and biophysical research communications Medium 28743496
2017 KLHL3 ubiquitinates cardiac myosin binding protein C (cMyBP-C) via the ubiquitin-proteasome pathway; KLHL3 interacts with cMyBP-C as shown by co-immunoprecipitation and immunofluorescence, and homocysteine increases KLHL3 expression leading to decreased cMyBP-C. Co-immunoprecipitation, immunofluorescence, Western blotting, MG132 proteasome inhibitor rescue, Western blot (MRM approach) Experimental cell research Low 28315668
2018 KLHL3 BTB domain mutation M131V (M78V in human) retains intact interaction with WNK kinases but reduces binding to CUL3, leading to decreased CUL3 in distal convoluted tubule cytosol and increased WNK1/WNK4 abundance in vivo. KLHL3 M131V knock-in mouse model, in vitro co-immunoprecipitation, immunogold-labeling electron microscopy, microdissected renal tubule analysis FASEB journal Medium 30148674
2018 Deficiency of the COP9 signalosome (CSN) catalytic subunit Jab1 in the nephron causes increased neddylated CUL3 and near-complete loss of KLHL3, with consequent accumulation of WNK1, WNK4, and SPAK, and elevated NCC phosphorylation; this indicates that CSN-mediated deneddylation is required for normal KLHL3 stability and CUL3-KLHL3-WNK signaling. Nephron-specific Jab1 knockout mouse model (Pax8/LC1 system), Western blot, immunofluorescence Journal of the American Society of Nephrology Medium 30301860
2019 Multiple disease-causing mutations in the Kelch domain of KLHL3 disrupt binding to the WNK4 acidic motif through two main mechanisms: altering the electrostatic potential of the binding site or disrupting Kelch-acidic motif hydrogen bonds; buried mutations can affect stability or indirect contacts. The L387P mutation causes functional impairment of WNK4 degradation by a mechanism not captured by Kelch-AM interaction simulations alone. Molecular dynamics simulations, Western blot analysis of WNK4 degradation with KLHL3 mutants Biochemistry Low 30931564
2021 The unique 30-amino acid N-terminal fragment of KS-WNK1 (kidney-specific WNK1) is required for both its activating effect on NCC and its recognition by KLHL3; specific residues in this region are critical for KLHL3 sensitivity. Full-length WNK1 is less impacted by CUL3-KLHL3-mediated degradation than KS-WNK1. KLHL3-R528H knock-in mice, mutagenesis of KS-WNK1 N-terminal residues, functional NCC activation assays, Western blotting American journal of physiology. Renal physiology Medium 33682442
2022 Crystal structure of the KLHL3 Kelch domain in complex with a WNK3 degron peptide reveals the complete 11-mer WNK-family degron binding mode; WNK3 Thr541 substitutes for the conserved proline, and phosphorylation of this residue abrogates KLHL3 interaction (shown by fluorescence polarization), revealing isoform-specific regulation. X-ray crystallography of KLHL3 Kelch-WNK3 peptide complex, fluorescence polarization binding assay, structural modelling The Biochemical journal High 35179207
2022 KLHL3 is recruited by KSHV vIRF1 to ubiquitinate and degrade hnRNP Q1 via the ubiquitin-proteasome pathway; vIRF1 upregulates KLHL3 expression and the KLHL3-vIRF1 complex targets hnRNP Q1, leading to destabilization of GDPD1 mRNA and induction of aerobic glycolysis. Co-immunoprecipitation, ubiquitination assay, Western blotting, metabolic assays (glucose uptake, ATP, lactate), mRNA stability assays Cell death and differentiation Medium 35538151
2023 A novel C-terminal motif (CM, residues 1051-1075) in WNK4 rich in negatively charged residues can also mediate KLHL3-dependent WNK4 degradation; this motif responds to PHAII mutations in the KLHL3 Kelch domain similarly to the acidic motif (AM), but AM is dominant; the CM may allow WNK4 degradation when AM is mutated. Co-immunoprecipitation, deletion/mutagenesis mapping in HEK293 cell-based degradation assays Biochemical and biophysical research communications Low 37285722
2025 Human KLHL3 and all four WNK kinases (WNK1-4) are O-GlcNAcylated; O-GlcNAcylation affects WNK4 function in osmolarity control and ferroptosis, demonstrating functional regulation of the KLHL3/WNK axis by this post-translational modification. Glycoproteomics/mass spectrometry, biochemical assays for osmolarity control and ferroptosis, O-GlcNAc-specific detection Glycobiology Medium 40796245

Source papers

Stage 0 corpus · 45 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2012 KLHL3 mutations cause familial hyperkalemic hypertension by impairing ion transport in the distal nephron. Nature genetics 265 22406640
2013 Impaired KLHL3-mediated ubiquitination of WNK4 causes human hypertension. Cell reports 181 23453970
2013 The CUL3-KLHL3 E3 ligase complex mutated in Gordon's hypertension syndrome interacts with and ubiquitylates WNK isoforms: disease-causing mutations in KLHL3 and WNK4 disrupt interaction. The Biochemical journal 180 23387299
2014 Hyperkalemic hypertension-associated cullin 3 promotes WNK signaling by degrading KLHL3. The Journal of clinical investigation 123 25250572
2014 Impaired degradation of WNK1 and WNK4 kinases causes PHAII in mutant KLHL3 knock-in mice. Human molecular genetics 72 24821705
2013 Crystal structure of KLHL3 in complex with Cullin3. PloS one 68 23573258
2014 Structural and biochemical characterization of the KLHL3-WNK kinase interaction important in blood pressure regulation. The Biochemical journal 61 24641320
2013 Disease-causing mutations in KLHL3 impair its effect on WNK4 degradation. FEBS letters 58 23665031
2015 KLHL3 regulates paracellular chloride transport in the kidney by ubiquitination of claudin-8. Proceedings of the National Academy of Sciences of the United States of America 53 25831548
2017 KLHL3 Knockout Mice Reveal the Physiological Role of KLHL3 and the Pathophysiology of Pseudohypoaldosteronism Type II Caused by Mutant KLHL3. Molecular and cellular biology 48 28052936
2014 Detection of mutations in KLHL3 and CUL3 in families with FHHt (familial hyperkalaemic hypertension or Gordon's syndrome). Clinical science (London, England : 1979) 42 24266877
2013 Decrease of WNK4 ubiquitination by disease-causing mutations of KLHL3 through different molecular mechanisms. Biochemical and biophysical research communications 34 23962426
2015 Impaired degradation of WNK by Akt and PKA phosphorylation of KLHL3. Biochemical and biophysical research communications 29 26435498
2018 Renal COP9 Signalosome Deficiency Alters CUL3-KLHL3-WNK Signaling Pathway. Journal of the American Society of Nephrology : JASN 25 30301860
2021 Role of KLHL3 and dietary K+ in regulating KS-WNK1 expression. American journal of physiology. Renal physiology 24 33682442
2017 WNK4 is indispensable for the pathogenesis of pseudohypoaldosteronism type II caused by mutant KLHL3. Biochemical and biophysical research communications 23 28743496
2018 Decreased KLHL3 expression is involved in the pathogenesis of pseudohypoaldosteronism type II caused by cullin 3 mutation in vivo. Clinical and experimental nephrology 19 29869755
2000 Molecular characterization of KLHL3, a human homologue of the Drosophila kelch gene. Genomics 19 10843806
2022 A viral interferon regulatory factor degrades RNA-binding protein hnRNP Q1 to enhance aerobic glycolysis via recruiting E3 ubiquitin ligase KLHL3 and decaying GDPD1 mRNA. Cell death and differentiation 18 35538151
2016 Phosphorylation of KLHL3 at serine 433 impairs its interaction with the acidic motif of WNK4: a molecular dynamics study. Protein science : a publication of the Protein Society 16 27727489
2021 Decreased KLHL3 expression is involved in the activation of WNK-OSR1/SPAK-NCC cascade in type 1 diabetic mice. Pflugers Archiv : European journal of physiology 15 33432425
2016 The CUL3/KLHL3-WNK-SPAK/OSR1 pathway as a target for antihypertensive therapy. American journal of physiology. Renal physiology 15 27076645
2017 Three cases of Gordon syndrome with dominant KLHL3 mutations. Journal of pediatric endocrinology & metabolism : JPEM 13 28222034
2015 Hypercalciuria in familial hyperkalemia and hypertension with KLHL3 mutations. Nephron 11 25925082
2016 A patient with pseudohypoaldosteronism type II complicated by congenital hypopituitarism carrying a KLHL3 mutation. Clinical pediatric endocrinology : case reports and clinical investigations : official journal of the Japanese Society for Pediatric Endocrinology 10 27780982
2015 Involvement of selective autophagy mediated by p62/SQSTM1 in KLHL3-dependent WNK4 degradation. The Biochemical journal 10 26349538
2018 Generation and analysis of a mouse model of pseudohypoaldosteronism type II caused by KLHL3 mutation in BTB domain. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 9 30148674
2017 Familial Hyperkalemia and Hypertension (FHHt) and KLHL3: Description of a Family with a New Recessive Mutation (S553L) Compared to a Family with a Dominant Mutation, Q309R, with Analysis of Urinary Sodium Chloride Cotransporter. Nephron 9 28511177
2022 A Novel Homozygous KLHL3 Mutation as a Cause of Autosomal Recessive Pseudohypoaldosteronism Type II Diagnosed Late in Life. Nephron 8 35093948
2017 cMyBP-C was decreased via KLHL3-mediated proteasomal degradation in congenital heart diseases. Experimental cell research 8 28315668
2019 Unveiling the Distinct Mechanisms by which Disease-Causing Mutations in the Kelch Domain of KLHL3 Disrupt the Interaction with the Acidic Motif of WNK4 through Molecular Dynamics Simulation. Biochemistry 7 30931564
2021 A case report of pseudohypoaldosteronism type II with a homozygous KLHL3 variant accompanied by hyperthyroidism. BMC endocrine disorders 6 34022862
2022 KLHL3 deficiency in mice ameliorates obesity, insulin resistance, and nonalcoholic fatty liver disease by regulating energy expenditure. Experimental & molecular medicine 5 36028759
2022 Sequence and structural variations determining the recruitment of WNK kinases to the KLHL3 E3 ligase. The Biochemical journal 4 35179207
2023 KLHL3-dependent WNK4 degradation affected by potassium through the neddylation and autophagy pathway. BMC nephrology 3 37481568
2025 The functional study of novel KLHL3 missense mutations associated with pseudohypoaldosteronism type II. Endocrine 2 41091294
2024 Pseudohypoaldosteronism type II and sensory neuropathy associated with a heterozygous pathogenic variant in KLHL3 gene, a case report. Heliyon 1 39553548
2023 Identification of a novel KLHL3-interacting motif in the C-terminal region of WNK4. Biochemical and biophysical research communications 1 37285722
2022 Generation and analysis of pseudohypoaldosteronism type II knock-in mice caused by a nonsense KLHL3 mutation in the Kelch domain. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 1 35621709
2019 KLHL3 single-nucleotide polymorphism is associated with essential hypertension in Chinese Han population. Medicine 1 31096542
2025 Camk2n1 deficiency reduces the NaCl cotransporter activity through the CUL3/KLHL3/WNK4 complex in the kidney. European journal of pharmacology 0 39798916
2025 Evidence for Functional Regulation of the KLHL3/WNK Pathway by O-GlcNAcylation. bioRxiv : the preprint server for biology 0 40060460
2025 Evidence for functional regulation of the KLHL3/WNK pathway by O-GlcNAcylation. Glycobiology 0 40796245
2025 Pseudo-Hypoaldosteronism Type 2 due to New Variants of KLHL3 Gene Diagnosed in an Adult Woman With Very High Sensitivity to Hydrochlorothiazide. Clinical case reports 0 40964474
2021 [A Case of Pseudohypoaldosteronism Type Ⅱ (PHA2) Caused by a Novel Mutation of KLHL3]. Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition 0 34622611

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