{"gene":"NPHS1","run_date":"2026-04-29T11:37:57","timeline":{"discoveries":[{"year":1999,"finding":"The NPHS1 gene encodes nephrin, a transmembrane protein expressed on podocyte cell surfaces; the two common Finnish mutations (Fin-major: 2-bp deletion in exon 2; Fin-minor: nonsense mutation in exon 26) and 32 additional novel mutations were identified in the nephrin gene, establishing nephrin as the structural protein mutated in congenital nephrotic syndrome of the Finnish type.","method":"Genomic structure analysis, direct exon sequencing, mutation screening of 35 NPHS1 patients","journal":"American journal of human genetics","confidence":"High","confidence_rationale":"Tier 1-2 — original gene/protein characterization with genomic sequencing, replicated across labs","pmids":["9915943"],"is_preprint":false},{"year":2000,"finding":"The Fin-major and Fin-minor mutations in NPHS1 both result in complete absence of nephrin protein and absence of podocyte slit diaphragms, whereas a patient with the Fin-major/R743C genotype expressed nephrin and had normal slit diaphragms, establishing that nephrin is the principal structural component of the slit diaphragm required for its formation.","method":"Immunohistochemistry, Western blotting, in situ hybridization, electron microscopy of nephrectomized kidneys from 46 Finnish NPHS1 patients","journal":"Kidney international","confidence":"High","confidence_rationale":"Tier 2 — multiple orthogonal methods (IHC, WB, ISH, EM) in a large patient cohort","pmids":["10972661"],"is_preprint":false},{"year":2001,"finding":"Most missense mutations in NPHS1 cause nephrin to be retained in the endoplasmic reticulum and prevent cell surface localization, indicating that ER retention due to protein misfolding is the predominant pathomechanism of missense mutations.","method":"Immunostaining of stable transfected cell lines expressing 21 different nephrin missense mutants, immunoelectron microscopy, subcellular fractionation","journal":"Human molecular genetics","confidence":"High","confidence_rationale":"Tier 1-2 — multiple orthogonal methods (immunostaining, immunoelectron microscopy, subcellular fractionation) for 21 mutants","pmids":["11726550"],"is_preprint":false},{"year":2001,"finding":"Recurrence of nephrotic syndrome after renal transplantation in CNF/NPHS1 patients is caused by autoantibodies against nephrin; increased serum anti-nephrin antibody titers precede nephrotic episodes and drop after successful treatment, demonstrating that nephrin functions as a neoantigen post-transplant and that anti-nephrin antibodies impair glomerular filtration.","method":"Indirect immunofluorescence microscopy, immunoblotting, ELISA assay of serial serum samples before and after recurrence of nephrotic syndrome","journal":"Experimental nephrology","confidence":"High","confidence_rationale":"Tier 2 — multiple orthogonal methods (IIF, immunoblot, ELISA) with serial samples demonstrating temporal correlation","pmids":["11549850"],"is_preprint":false},{"year":2002,"finding":"NPHS1 (nephrin) and NPHS2 (podocin) have a functional inter-relationship in glomerular filtration; digenic inheritance of mutations in both genes results in a 'tri-allelic hit' that modifies the disease phenotype from congenital nephrotic syndrome to congenital focal segmental glomerulosclerosis, demonstrating epistatic interaction between these two slit diaphragm proteins.","method":"Mutational analysis of NPHS1 and NPHS2 in 50 patients with genotype/phenotype correlation analysis","journal":"Human molecular genetics","confidence":"Medium","confidence_rationale":"Tier 3 — genetic epistasis from patient cohort analysis, single lab","pmids":["11854170"],"is_preprint":false},{"year":2000,"finding":"The mouse Nphs1 5' flanking region (8.3-kb and 5.4-kb fragments) drives podocyte-specific transgene expression in vivo, with beta-galactosidase activity confined to podocyte nuclei in kidneys and a discrete brain region, establishing these sequences as functional podocyte-specific promoter/enhancer elements.","method":"BAC clone characterization, transgenic mouse lacZ reporter assay, X-gal staining of kidney sections, chemiluminescence assay","journal":"Journal of the American Society of Nephrology : JASN","confidence":"High","confidence_rationale":"Tier 2 — in vivo transgenic assay with multiple independent founders confirming position-independent podocyte-specific expression","pmids":["11095653"],"is_preprint":false},{"year":2004,"finding":"An endogenous antisense transcript (Nphs1as) originating from the nephrin-encoding locus spans Nphs1 exons 7-12 in reverse orientation and is expressed in brain, thymus, and peripheral lymph nodes but not in kidney or pancreas (major nephrin expression sites), suggesting a role for Nphs1as in tissue-specific regulation of nephrin expression.","method":"Molecular cloning of antisense transcript, RT-PCR, immunoblotting, analysis of nephrin-deficient mouse line generated by insertional mutagenesis","journal":"Genomics","confidence":"Medium","confidence_rationale":"Tier 3 — molecular cloning and expression characterization, single lab","pmids":["15177566"],"is_preprint":false},{"year":2007,"finding":"Anti-nephrin antibodies in NPHS1 patients homozygous for Fin-major mutation (who lack endogenous nephrin expression) effectively impair glomerular function in kidney grafts; plasma exchange alongside cyclophosphamide is effective in treating these antibody-mediated recurrences, confirming nephrin as a functional target of these autoantibodies.","method":"ELISA for serum anti-nephrin antibodies, kidney biopsy immunohistochemistry, clinical outcomes analysis in 65 NPHS1 transplant patients","journal":"Transplantation","confidence":"Medium","confidence_rationale":"Tier 2-3 — ELISA and biopsy with clinical correlation, single institution but large cohort","pmids":["17519780"],"is_preprint":false},{"year":2015,"finding":"Wild-type nephrin suppresses TRPC6 channel current amplitudes in HEK293 cells and podocytes, but this suppression is lost with the NPHS1 c.294C>T synonymous polymorphism, demonstrating that nephrin physically or functionally interacts with TRPC6 to regulate calcium channel activity in podocytes.","method":"Patch-clamp electrophysiology in HEK293 cells and podocytes transfected with TRPC6 and NPHS1 constructs with different genotypes","journal":"American journal of transplantation","confidence":"Medium","confidence_rationale":"Tier 1 — direct electrophysiological assay with defined constructs, single lab","pmids":["26147534"],"is_preprint":false},{"year":2018,"finding":"CNS-associated NPHS1 missense mutations (A419T and C623F) in the nephrin extracellular region reduce surface expression, cause ER retention, impair nephrin tyrosine phosphorylation, and exert dominant negative effects on wild-type nephrin signaling, revealing that extracellular domain mutations can disrupt nephrin's function as a signaling scaffold.","method":"Kidney biopsy localization analysis, cell surface expression assays in cultured cells, phosphorylation assays, dominant negative co-transfection experiments","journal":"PloS one","confidence":"High","confidence_rationale":"Tier 2 — multiple orthogonal methods (localization, surface expression, phosphorylation, dominant negative) in a single study","pmids":["30212551"],"is_preprint":false},{"year":2013,"finding":"All pathogenic NPHS1 mutations identified in Japanese patients impaired nephrin trafficking to the plasma membrane, confirmed using transient transfection with immunostaining with and without detergent permeabilization to distinguish membrane from intracellular protein.","method":"Transient transfection, immunostaining with/without Triton X permeabilization, automated cell counting","journal":"Histology and histopathology","confidence":"Medium","confidence_rationale":"Tier 2 — functional assay for multiple mutations, single lab","pmids":["24142548"],"is_preprint":false},{"year":2024,"finding":"Nphs1 knockout mice exhibit foot process effacement (average FP density 1.0 vs 2.0 FP/µm in controls), reduced filtration slit density (2.64 vs 4.36 µm/µm²), proximal tubular microcysts, proteinuria within the first week of life, and hypoalbuminemia, confirming nephrin is essential for normal podocyte foot process architecture and glomerular filtration barrier integrity.","method":"Conditional Nphs1 knockout mouse model, electron microscopy foot process density measurement, urine albumin-to-creatinine ratio, serum albumin/BUN/creatinine levels","journal":"American journal of physiology. Renal physiology","confidence":"High","confidence_rationale":"Tier 2 — quantitative KO phenotyping with multiple orthogonal structural and functional measures","pmids":["38482553"],"is_preprint":false},{"year":2019,"finding":"An intronic NPHS1 mutation (c.3286+5G>A) causes defective alternative splicing of NPHS1, identifying a splice-site dependent mechanism of disease in congenital nephrotic syndrome.","method":"Functional splicing analysis of the intronic mutation in patient-derived samples","journal":"Italian journal of pediatrics","confidence":"Medium","confidence_rationale":"Tier 2 — direct functional splicing assay for a specific intronic variant, single case","pmids":["31443662"],"is_preprint":false}],"current_model":"NPHS1 encodes nephrin, a podocyte transmembrane protein that is the principal structural component of the glomerular slit diaphragm; nephrin is required for slit diaphragm assembly and foot process architecture, functions as a tyrosine-phosphorylated signaling scaffold that modulates TRPC6 channel activity, and missense mutations predominantly cause disease by inducing ER retention and defective plasma membrane trafficking, while truncating mutations abolish nephrin expression entirely leading to absence of slit diaphragms and massive proteinuria."},"narrative":{"teleology":[{"year":1999,"claim":"Positional cloning of NPHS1 resolved the molecular identity of the gene mutated in congenital nephrotic syndrome of the Finnish type, establishing nephrin as a transmembrane protein and the first defined slit diaphragm component.","evidence":"Genomic structure analysis and direct exon sequencing of 35 CNF patients identifying Fin-major, Fin-minor, and 32 novel mutations","pmids":["9915943"],"confidence":"High","gaps":["Nephrin protein localization and function at the slit diaphragm not yet demonstrated","Mechanism by which specific mutations cause disease not addressed"]},{"year":2000,"claim":"Protein-level analysis demonstrated that truncating NPHS1 mutations abolish nephrin expression and slit diaphragm formation, while a missense allele preserves both, establishing nephrin as the principal structural component of the slit diaphragm.","evidence":"Immunohistochemistry, Western blot, in situ hybridization, and electron microscopy on nephrectomized kidneys from 46 Finnish NPHS1 patients with defined genotypes","pmids":["10972661"],"confidence":"High","gaps":["Mechanism of missense mutation pathogenicity unknown","Whether nephrin has signaling functions beyond structural role not tested"]},{"year":2001,"claim":"Systematic analysis of 21 missense mutants revealed that ER retention due to misfolding is the predominant pathomechanism, shifting understanding from simple loss of expression to a protein quality control defect.","evidence":"Immunostaining of stable cell lines, immunoelectron microscopy, and subcellular fractionation for 21 NPHS1 missense mutants","pmids":["11726550"],"confidence":"High","gaps":["Whether ER-retained mutants can be pharmacologically rescued not tested","Whether some mutants reach the surface but are non-functional not fully resolved"]},{"year":2001,"claim":"The discovery that anti-nephrin autoantibodies cause post-transplant nephrotic syndrome recurrence in CNF patients established that nephrin is a functional neoantigen and that antibody-mediated targeting of nephrin directly impairs glomerular filtration.","evidence":"Indirect immunofluorescence, immunoblotting, and serial ELISA of serum samples in transplanted NPHS1 patients with temporal correlation to nephrotic episodes","pmids":["11549850"],"confidence":"High","gaps":["Precise mechanism by which anti-nephrin antibodies disrupt filtration barrier not defined","Whether antibodies cause complement-mediated injury vs. direct functional blockade unclear"]},{"year":2002,"claim":"Demonstration of digenic inheritance between NPHS1 and NPHS2 (podocin) mutations revealed epistatic interaction between slit diaphragm components, modifying disease phenotype from CNS to FSGS.","evidence":"Mutational analysis of NPHS1 and NPHS2 with genotype-phenotype correlation in 50 patients","pmids":["11854170"],"confidence":"Medium","gaps":["Biochemical basis of nephrin-podocin epistasis not characterized","Not independently replicated in a separate cohort","Whether other slit diaphragm genes contribute to oligogenic inheritance not tested"]},{"year":2015,"claim":"Electrophysiology demonstrated that nephrin suppresses TRPC6 channel currents, establishing a signaling function for nephrin in regulating podocyte calcium homeostasis beyond its structural role.","evidence":"Patch-clamp recordings in HEK293 cells and podocytes co-transfected with TRPC6 and NPHS1 constructs","pmids":["26147534"],"confidence":"Medium","gaps":["Whether nephrin-TRPC6 interaction is direct or mediated through adaptor proteins not determined","In vivo relevance of this channel regulation not tested","Mechanism by which the synonymous c.294C>T variant alters nephrin function unclear"]},{"year":2018,"claim":"CNS-associated extracellular domain missense mutations were shown to reduce surface expression, impair tyrosine phosphorylation, and exert dominant-negative effects on wild-type nephrin, demonstrating that nephrin functions as a tyrosine-phosphorylated signaling scaffold.","evidence":"Cell surface expression assays, phosphorylation assays, and dominant-negative co-transfection experiments for A419T and C623F mutants","pmids":["30212551"],"confidence":"High","gaps":["Identity of the kinase(s) and downstream effectors of nephrin phosphorylation in this context not identified","Whether dominant-negative effects occur in vivo in heterozygous carriers unknown"]},{"year":2024,"claim":"Conditional Nphs1 knockout mice provided definitive in vivo proof that nephrin is essential for foot process architecture and filtration barrier integrity, quantifying the structural and functional consequences of nephrin loss.","evidence":"Conditional Nphs1 KO mice with quantitative EM foot process measurements, urine albumin-to-creatinine ratio, and serum biochemistry","pmids":["38482553"],"confidence":"High","gaps":["Whether adult conditional deletion reproduces neonatal phenotype not reported","Signaling pathways downstream of nephrin loss in vivo not dissected"]},{"year":null,"claim":"The precise mechanism by which nephrin organizes the slit diaphragm at a structural level, its full signaling interactome downstream of tyrosine phosphorylation, and whether ER-retained mutants can be pharmacologically rescued remain unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No high-resolution structural model of the nephrin ectodomain trans-interaction at the slit diaphragm","Full phospho-signaling cascade downstream of nephrin remains unmapped","Pharmacological chaperone rescue of ER-retained nephrin mutants not demonstrated"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0098772","term_label":"molecular function regulator activity","supporting_discovery_ids":[8,9]},{"term_id":"GO:0005198","term_label":"structural molecule activity","supporting_discovery_ids":[1,11]}],"localization":[{"term_id":"GO:0005886","term_label":"plasma membrane","supporting_discovery_ids":[1,2,9,10,11]},{"term_id":"GO:0005783","term_label":"endoplasmic reticulum","supporting_discovery_ids":[2,9,10]}],"pathway":[{"term_id":"R-HSA-162582","term_label":"Signal Transduction","supporting_discovery_ids":[8,9]}],"complexes":[],"partners":["TRPC6","NPHS2"],"other_free_text":[]},"mechanistic_narrative":"NPHS1 encodes nephrin, a podocyte-expressed transmembrane protein that serves as the principal structural and signaling component of the glomerular slit diaphragm, essential for maintaining the kidney filtration barrier. Truncating mutations (e.g., Fin-major, Fin-minor) abolish nephrin protein expression and slit diaphragm formation, causing massive proteinuria characteristic of congenital nephrotic syndrome of the Finnish type, while most missense mutations cause endoplasmic reticulum retention and defective plasma membrane trafficking, with some extracellular domain mutations additionally impairing tyrosine phosphorylation and exerting dominant-negative effects on wild-type nephrin signaling [PMID:9915943, PMID:10972661, PMID:11726550, PMID:30212551]. Nphs1 knockout mice confirm that nephrin is required for podocyte foot process architecture, filtration slit density, and prevention of proteinuria [PMID:38482553]. Nephrin also functions as a signaling scaffold that suppresses TRPC6 calcium channel activity in podocytes, and after transplantation in nephrin-null patients, it acts as a neoantigen whose targeting by autoantibodies causes graft nephrotic syndrome [PMID:26147534, PMID:11549850]."},"prefetch_data":{"uniprot":{"accession":"O60500","full_name":"Nephrin","aliases":["Renal glomerulus-specific cell adhesion receptor"],"length_aa":1241,"mass_kda":134.7,"function":"Seems to play a role in the development or function of the kidney glomerular filtration barrier. Regulates glomerular vascular permeability. May anchor the podocyte slit diaphragm to the actin cytoskeleton. Plays a role in skeletal muscle formation through regulation of myoblast fusion (By similarity)","subcellular_location":"Cell membrane","url":"https://www.uniprot.org/uniprotkb/O60500/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/NPHS1","classification":"Not Classified","n_dependent_lines":16,"n_total_lines":1208,"dependency_fraction":0.013245033112582781},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[],"url":"https://opencell.sf.czbiohub.org/search/NPHS1","total_profiled":1310},"omim":[{"mim_id":"620049","title":"NEPHROTIC SYNDROME, TYPE 26; NPHS26","url":"https://www.omim.org/entry/620049"},{"mim_id":"619953","title":"TRANSMEMBRANE PROTEIN 63C; TMEM63C","url":"https://www.omim.org/entry/619953"},{"mim_id":"619263","title":"NEPHROTIC SYNDROME, TYPE 24; NPHS24","url":"https://www.omim.org/entry/619263"},{"mim_id":"619201","title":"NEPHROTIC SYNDROME, TYPE 23; NPHS23","url":"https://www.omim.org/entry/619201"},{"mim_id":"619155","title":"NEPHROTIC SYNDROME, TYPE 22; NPHS22","url":"https://www.omim.org/entry/619155"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"","locations":[],"tissue_specificity":"Group enriched","tissue_distribution":"Detected in some","driving_tissues":[{"tissue":"kidney","ntpm":39.8},{"tissue":"pancreas","ntpm":21.5}],"url":"https://www.proteinatlas.org/search/NPHS1"},"hgnc":{"alias_symbol":["CNF","NPHN"],"prev_symbol":[]},"alphafold":{"accession":"O60500","domains":[{"cath_id":"2.60.40.10","chopping":"35-133","consensus_level":"high","plddt":87.3389,"start":35,"end":133},{"cath_id":"2.60.40.10","chopping":"139-238","consensus_level":"high","plddt":88.8725,"start":139,"end":238},{"cath_id":"2.60.40.10","chopping":"242-338","consensus_level":"high","plddt":86.323,"start":242,"end":338},{"cath_id":"2.60.40.10","chopping":"344-436","consensus_level":"high","plddt":85.7101,"start":344,"end":436},{"cath_id":"2.60.40.10","chopping":"444-543","consensus_level":"high","plddt":80.5712,"start":444,"end":543},{"cath_id":"2.60.40.10","chopping":"549-639","consensus_level":"high","plddt":86.7443,"start":549,"end":639},{"cath_id":"2.60.40.10","chopping":"645-737","consensus_level":"medium","plddt":88.4874,"start":645,"end":737},{"cath_id":"2.60.40.10","chopping":"747-836","consensus_level":"medium","plddt":88.2951,"start":747,"end":836},{"cath_id":"2.60.40.10","chopping":"842-938","consensus_level":"high","plddt":87.192,"start":842,"end":938}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/O60500","model_url":"https://alphafold.ebi.ac.uk/files/AF-O60500-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-O60500-F1-predicted_aligned_error_v6.png","plddt_mean":77.25},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=NPHS1","jax_strain_url":"https://www.jax.org/strain/search?query=NPHS1"},"sequence":{"accession":"O60500","fasta_url":"https://rest.uniprot.org/uniprotkb/O60500.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/O60500/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/O60500"}},"corpus_meta":[{"pmid":"17371932","id":"PMC_17371932","title":"Nephrotic syndrome in the first year of life: two thirds of cases are caused by mutations in 4 genes (NPHS1, NPHS2, WT1, and LAMB2).","date":"2007","source":"Pediatrics","url":"https://pubmed.ncbi.nlm.nih.gov/17371932","citation_count":313,"is_preprint":false},{"pmid":"9915943","id":"PMC_9915943","title":"Structure of the gene for congenital nephrotic syndrome of the finnish type (NPHS1) and characterization of mutations.","date":"1999","source":"American journal of human genetics","url":"https://pubmed.ncbi.nlm.nih.gov/9915943","citation_count":302,"is_preprint":false},{"pmid":"10972661","id":"PMC_10972661","title":"Congenital nephrotic syndrome (NPHS1): features resulting from different mutations in Finnish patients.","date":"2000","source":"Kidney international","url":"https://pubmed.ncbi.nlm.nih.gov/10972661","citation_count":213,"is_preprint":false},{"pmid":"11854170","id":"PMC_11854170","title":"Genotype/phenotype correlations of NPHS1 and NPHS2 mutations in nephrotic syndrome advocate a functional inter-relationship in glomerular filtration.","date":"2002","source":"Human molecular genetics","url":"https://pubmed.ncbi.nlm.nih.gov/11854170","citation_count":200,"is_preprint":false},{"pmid":"12538773","id":"PMC_12538773","title":"Constitutive activation of Rho proteins by CNF-1 influences tight junction structure and epithelial barrier function.","date":"2003","source":"Journal of cell science","url":"https://pubmed.ncbi.nlm.nih.gov/12538773","citation_count":172,"is_preprint":false},{"pmid":"11317351","id":"PMC_11317351","title":"Mutation spectrum in the nephrin gene (NPHS1) in congenital nephrotic syndrome.","date":"2001","source":"Human mutation","url":"https://pubmed.ncbi.nlm.nih.gov/11317351","citation_count":137,"is_preprint":false},{"pmid":"11726550","id":"PMC_11726550","title":"Defective nephrin trafficking caused by missense mutations in the NPHS1 gene: insight into the mechanisms of congenital nephrotic syndrome.","date":"2001","source":"Human molecular genetics","url":"https://pubmed.ncbi.nlm.nih.gov/11726550","citation_count":123,"is_preprint":false},{"pmid":"11349064","id":"PMC_11349064","title":"Mutation of the gene encoding cytotoxic necrotizing factor type 1 (cnf(1)) attenuates the virulence of uropathogenic Escherichia coli.","date":"2001","source":"Infection and immunity","url":"https://pubmed.ncbi.nlm.nih.gov/11349064","citation_count":113,"is_preprint":false},{"pmid":"1968978","id":"PMC_1968978","title":"Virulence factors of bacteraemic Escherichia coli with particular reference to production of cytotoxic necrotising factor (CNF) by P-fimbriate strains.","date":"1990","source":"Journal of medical microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/1968978","citation_count":70,"is_preprint":false},{"pmid":"15780077","id":"PMC_15780077","title":"Analysis of NPHS1, NPHS2, ACTN4, and WT1 in Japanese patients with congenital nephrotic syndrome.","date":"2005","source":"Kidney international","url":"https://pubmed.ncbi.nlm.nih.gov/15780077","citation_count":63,"is_preprint":false},{"pmid":"20172850","id":"PMC_20172850","title":"Nineteen novel NPHS1 mutations in a worldwide cohort of patients with congenital nephrotic syndrome (CNS).","date":"2010","source":"Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association","url":"https://pubmed.ncbi.nlm.nih.gov/20172850","citation_count":63,"is_preprint":false},{"pmid":"11095653","id":"PMC_11095653","title":"Evaluation of a new tool for exploring podocyte biology: mouse Nphs1 5' flanking region drives LacZ expression in podocytes.","date":"2000","source":"Journal of the American Society of Nephrology : JASN","url":"https://pubmed.ncbi.nlm.nih.gov/11095653","citation_count":62,"is_preprint":false},{"pmid":"18503012","id":"PMC_18503012","title":"Thirteen novel NPHS1 mutations in a large cohort of children with congenital nephrotic syndrome.","date":"2008","source":"Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association","url":"https://pubmed.ncbi.nlm.nih.gov/18503012","citation_count":60,"is_preprint":false},{"pmid":"32554042","id":"PMC_32554042","title":"Common risk variants in NPHS1 and TNFSF15 are associated with childhood steroid-sensitive nephrotic syndrome.","date":"2020","source":"Kidney international","url":"https://pubmed.ncbi.nlm.nih.gov/32554042","citation_count":46,"is_preprint":false},{"pmid":"9639039","id":"PMC_9639039","title":"Podocyte phenotypes as defined by expression and distribution of GLEPP1 in the developing glomerulus and in nephrotic glomeruli from MCD, CNF, and FSGS. A dedifferentiation hypothesis for the nephrotic syndrome.","date":"1998","source":"Experimental nephrology","url":"https://pubmed.ncbi.nlm.nih.gov/9639039","citation_count":46,"is_preprint":false},{"pmid":"15086927","id":"PMC_15086927","title":"Nephrin gene (NPHS1) in patients with minimal change nephrotic syndrome (MCNS).","date":"2004","source":"Kidney international","url":"https://pubmed.ncbi.nlm.nih.gov/15086927","citation_count":45,"is_preprint":false},{"pmid":"25427594","id":"PMC_25427594","title":"A review: potential usage of cellulose nanofibers (CNF) for enzyme immobilization via covalent interactions.","date":"2014","source":"Applied biochemistry and biotechnology","url":"https://pubmed.ncbi.nlm.nih.gov/25427594","citation_count":42,"is_preprint":false},{"pmid":"15338398","id":"PMC_15338398","title":"No evidence for genotype/phenotype correlation in NPHS1 and NPHS2 mutations.","date":"2004","source":"Pediatric nephrology (Berlin, Germany)","url":"https://pubmed.ncbi.nlm.nih.gov/15338398","citation_count":39,"is_preprint":false},{"pmid":"22565185","id":"PMC_22565185","title":"A spectrum of novel NPHS1 and NPHS2 gene mutations in pediatric nephrotic syndrome patients from Pakistan.","date":"2012","source":"Gene","url":"https://pubmed.ncbi.nlm.nih.gov/22565185","citation_count":36,"is_preprint":false},{"pmid":"15549605","id":"PMC_15549605","title":"CNF and DNT.","date":"2004","source":"Reviews of physiology, biochemistry and pharmacology","url":"https://pubmed.ncbi.nlm.nih.gov/15549605","citation_count":33,"is_preprint":false},{"pmid":"19406966","id":"PMC_19406966","title":"Clinical features and long-term outcome of nephrotic syndrome associated with heterozygous NPHS1 and NPHS2 mutations.","date":"2009","source":"Clinical journal of the American Society of Nephrology : CJASN","url":"https://pubmed.ncbi.nlm.nih.gov/19406966","citation_count":33,"is_preprint":false},{"pmid":"16941028","id":"PMC_16941028","title":"Glomerular sclerosis in kidneys with congenital nephrotic syndrome (NPHS1).","date":"2006","source":"Kidney international","url":"https://pubmed.ncbi.nlm.nih.gov/16941028","citation_count":33,"is_preprint":false},{"pmid":"30901196","id":"PMC_30901196","title":"Influence of Cellulose Charge on Bacteria Adhesion and Viability to PVAm/CNF/PVAm-Modified Cellulose Model Surfaces.","date":"2019","source":"Biomacromolecules","url":"https://pubmed.ncbi.nlm.nih.gov/30901196","citation_count":30,"is_preprint":false},{"pmid":"11549850","id":"PMC_11549850","title":"Recurrence of nephrotic syndrome after transplantation in CNF is due to autoantibodies to nephrin.","date":"2001","source":"Experimental nephrology","url":"https://pubmed.ncbi.nlm.nih.gov/11549850","citation_count":30,"is_preprint":false},{"pmid":"31139264","id":"PMC_31139264","title":"Prevalence and pathologic effects of colibactin and cytotoxic necrotizing factor-1 (Cnf 1) in Escherichia coli: experimental and bioinformatics analyses.","date":"2019","source":"Gut pathogens","url":"https://pubmed.ncbi.nlm.nih.gov/31139264","citation_count":30,"is_preprint":false},{"pmid":"17519780","id":"PMC_17519780","title":"Plasma exchange and retransplantation in recurrent nephrosis of patients with congenital nephrotic syndrome of the Finnish type (NPHS1).","date":"2007","source":"Transplantation","url":"https://pubmed.ncbi.nlm.nih.gov/17519780","citation_count":29,"is_preprint":false},{"pmid":"32829853","id":"PMC_32829853","title":"Facile synthesis of a Co/Fe bi-MOFs/CNF membrane nanocomposite and its application in the degradation of tetrabromobisphenol A.","date":"2020","source":"Carbohydrate polymers","url":"https://pubmed.ncbi.nlm.nih.gov/32829853","citation_count":29,"is_preprint":false},{"pmid":"17211152","id":"PMC_17211152","title":"NPHS1 and NPHS2 gene mutations in Chinese children with sporadic nephrotic syndrome.","date":"2007","source":"Pediatric research","url":"https://pubmed.ncbi.nlm.nih.gov/17211152","citation_count":28,"is_preprint":false},{"pmid":"22584503","id":"PMC_22584503","title":"Mutation analysis of NPHS1 in a worldwide cohort of congenital nephrotic syndrome patients.","date":"2012","source":"Nephron. Clinical practice","url":"https://pubmed.ncbi.nlm.nih.gov/22584503","citation_count":25,"is_preprint":false},{"pmid":"30960233","id":"PMC_30960233","title":"Effect of Cellulose Nanofiber (CNF) Surface Treatment on Cellular Structures and Mechanical Properties of Polypropylene/CNF Nanocomposite Foams via Core-Back Foam Injection Molding.","date":"2019","source":"Polymers","url":"https://pubmed.ncbi.nlm.nih.gov/30960233","citation_count":24,"is_preprint":false},{"pmid":"29225701","id":"PMC_29225701","title":"Cytotoxic Escherichia coli strains encoding colibactin and cytotoxic necrotizing factor (CNF) colonize laboratory macaques.","date":"2017","source":"Gut pathogens","url":"https://pubmed.ncbi.nlm.nih.gov/29225701","citation_count":24,"is_preprint":false},{"pmid":"7693621","id":"PMC_7693621","title":"Congenital nephrosis of the Finnish type (CNF): matrix components of the glomerular basement membranes and of cultured mesangial cells.","date":"1993","source":"The Histochemical journal","url":"https://pubmed.ncbi.nlm.nih.gov/7693621","citation_count":24,"is_preprint":false},{"pmid":"26147534","id":"PMC_26147534","title":"Genetic Interactions Between TRPC6 and NPHS1 Variants Affect Posttransplant Risk of Recurrent Focal Segmental Glomerulosclerosis.","date":"2015","source":"American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons","url":"https://pubmed.ncbi.nlm.nih.gov/26147534","citation_count":22,"is_preprint":false},{"pmid":"3894279","id":"PMC_3894279","title":"A randomized multicenter trial of cyclophosphamide, Novantrone and 5-fluorouracil (CNF) versus cyclophosphamide, Adriamycin and 5-fluorouracil (CAF) in patients with metastatic breast cancer.","date":"1985","source":"Investigational new drugs","url":"https://pubmed.ncbi.nlm.nih.gov/3894279","citation_count":19,"is_preprint":false},{"pmid":"24861644","id":"PMC_24861644","title":"Lower prevalence of hlyD, papC and cnf-1 genes in ciprofloxacin-resistant uropathogenic Escherichia coli than their susceptible counterparts isolated from southern India.","date":"2014","source":"Journal of infection and public health","url":"https://pubmed.ncbi.nlm.nih.gov/24861644","citation_count":18,"is_preprint":false},{"pmid":"18048423","id":"PMC_18048423","title":"Glomerular endothelium in kidneys with congenital nephrotic syndrome of the Finnish type (NPHS1).","date":"2007","source":"Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association","url":"https://pubmed.ncbi.nlm.nih.gov/18048423","citation_count":17,"is_preprint":false},{"pmid":"21414970","id":"PMC_21414970","title":"Messenger RNA expression of B7-1 and NPHS1 in urinary sediment could be useful to differentiate between minimal-change disease and focal segmental glomerulosclerosis in adult patients.","date":"2011","source":"Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association","url":"https://pubmed.ncbi.nlm.nih.gov/21414970","citation_count":17,"is_preprint":false},{"pmid":"23325127","id":"PMC_23325127","title":"Glomerulopathy and mutations in NPHS1 and KIRREL2 in soft-coated Wheaten Terrier dogs.","date":"2013","source":"Mammalian genome : official journal of the International Mammalian Genome Society","url":"https://pubmed.ncbi.nlm.nih.gov/23325127","citation_count":16,"is_preprint":false},{"pmid":"31216994","id":"PMC_31216994","title":"A comprehensive analysis of NPHS1 gene mutations in patients with sporadic focal segmental glomerulosclerosis.","date":"2019","source":"BMC medical genetics","url":"https://pubmed.ncbi.nlm.nih.gov/31216994","citation_count":16,"is_preprint":false},{"pmid":"33410511","id":"PMC_33410511","title":"Crystal structure of bacterial cytotoxic necrotizing factor CNFY reveals molecular building blocks for intoxication.","date":"2021","source":"The EMBO journal","url":"https://pubmed.ncbi.nlm.nih.gov/33410511","citation_count":14,"is_preprint":false},{"pmid":"20138859","id":"PMC_20138859","title":"Association between genetic polymorphisms of the NPHS1 gene and membranous glomerulonephritis in the Taiwanese population.","date":"2010","source":"Clinica chimica acta; international journal of clinical chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/20138859","citation_count":13,"is_preprint":false},{"pmid":"16362719","id":"PMC_16362719","title":"Muscular dystonia and athetosis in six patients with congenital nephrotic syndrome of the Finnish type (NPHS1).","date":"2005","source":"Pediatric nephrology (Berlin, Germany)","url":"https://pubmed.ncbi.nlm.nih.gov/16362719","citation_count":13,"is_preprint":false},{"pmid":"17413422","id":"PMC_17413422","title":"Misleading findings of homozygosity mapping resulting from three novel mutations in NPHS1 encoding nephrin in a highly inbred community.","date":"2007","source":"Genetics in medicine : official journal of the American College of Medical Genetics","url":"https://pubmed.ncbi.nlm.nih.gov/17413422","citation_count":13,"is_preprint":false},{"pmid":"8661053","id":"PMC_8661053","title":"Assembly of a 1-Mb restriction-mapped cosmid contig spanning the candidate region for Finnish congenital nephrosis (NPHS1) in 19q13.1.","date":"1996","source":"Genomics","url":"https://pubmed.ncbi.nlm.nih.gov/8661053","citation_count":13,"is_preprint":false},{"pmid":"12920248","id":"PMC_12920248","title":"Genetic polymorphism of NPHS1 modifies the clinical manifestations of Ig A nephropathy.","date":"2003","source":"Laboratory investigation; a journal of technical methods and pathology","url":"https://pubmed.ncbi.nlm.nih.gov/12920248","citation_count":12,"is_preprint":false},{"pmid":"24856380","id":"PMC_24856380","title":"Retrospective mutational analysis of NPHS1, NPHS2, WT1 and LAMB2 in children with steroid-resistant focal segmental glomerulosclerosis - a single-centre experience.","date":"2014","source":"Bosnian journal of basic medical sciences","url":"https://pubmed.ncbi.nlm.nih.gov/24856380","citation_count":12,"is_preprint":false},{"pmid":"10629646","id":"PMC_10629646","title":"Effects on blood coagulation of adjuvant CNF (cyclophosphamide, novantrone, 5-fluorouracil) chemotherapy in stage II breast cancer patients.","date":"1999","source":"Anticancer research","url":"https://pubmed.ncbi.nlm.nih.gov/10629646","citation_count":12,"is_preprint":false},{"pmid":"16316524","id":"PMC_16316524","title":"[NPHS1 mutations in a Chinese family with congenital nephrotic syndrome].","date":"2005","source":"Zhonghua er ke za zhi = Chinese journal of pediatrics","url":"https://pubmed.ncbi.nlm.nih.gov/16316524","citation_count":12,"is_preprint":false},{"pmid":"26560236","id":"PMC_26560236","title":"NPHS1 gene mutations confirm congenital nephrotic syndrome in four Brazilian cases: A novel mutation is described.","date":"2016","source":"Nephrology (Carlton, Vic.)","url":"https://pubmed.ncbi.nlm.nih.gov/26560236","citation_count":11,"is_preprint":false},{"pmid":"22009864","id":"PMC_22009864","title":"Two novel NPHS1 mutations in a Chinese family with congenital nephrotic syndrome.","date":"2011","source":"Genetics and molecular research : GMR","url":"https://pubmed.ncbi.nlm.nih.gov/22009864","citation_count":10,"is_preprint":false},{"pmid":"38943949","id":"PMC_38943949","title":"Hydrophobic corn zein-modified cellulose nanofibril (CNF) films with antioxidant properties.","date":"2024","source":"Food chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/38943949","citation_count":10,"is_preprint":false},{"pmid":"29371399","id":"PMC_29371399","title":"Modular domain swapping among the bacterial cytotoxic necrotizing factor (CNF) family for efficient cargo delivery into mammalian cells.","date":"2018","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/29371399","citation_count":10,"is_preprint":false},{"pmid":"30979135","id":"PMC_30979135","title":"Synthesis of Polyaniline (PANI) in Nano-Reaction Field of Cellulose Nanofiber (CNF), and Carbonization.","date":"2016","source":"Polymers","url":"https://pubmed.ncbi.nlm.nih.gov/30979135","citation_count":10,"is_preprint":false},{"pmid":"30924936","id":"PMC_30924936","title":"Cellulose nanofiber (CNF)-sakacin-A active material: production, characterization and application in storage trials of smoked salmon.","date":"2019","source":"Journal of the science of food and agriculture","url":"https://pubmed.ncbi.nlm.nih.gov/30924936","citation_count":10,"is_preprint":false},{"pmid":"30013592","id":"PMC_30013592","title":"Screening of the LAMB2, WT1, NPHS1, and NPHS2 Genes in Pediatric Nephrotic Syndrome.","date":"2018","source":"Frontiers in genetics","url":"https://pubmed.ncbi.nlm.nih.gov/30013592","citation_count":9,"is_preprint":false},{"pmid":"37376399","id":"PMC_37376399","title":"Self-Assembled CNF/rGO/Tannin Composite: Study of the Physicochemical and Wound Healing Properties.","date":"2023","source":"Polymers","url":"https://pubmed.ncbi.nlm.nih.gov/37376399","citation_count":9,"is_preprint":false},{"pmid":"19321760","id":"PMC_19321760","title":"NPHS1 gene mutation in Japanese patients with congenital nephrotic syndrome.","date":"2009","source":"Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association","url":"https://pubmed.ncbi.nlm.nih.gov/19321760","citation_count":9,"is_preprint":false},{"pmid":"2192065","id":"PMC_2192065","title":"Detection of cytotoxic necrotising factor (CNF) in extracts of Escherichia coli strains by enzyme-linked immunosorbent assay.","date":"1990","source":"Journal of medical microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/2192065","citation_count":9,"is_preprint":false},{"pmid":"1510341","id":"PMC_1510341","title":"[Virulence factors and phenotypes of sixty-one strains of Escherichia coli of bovine origin, producing cytotoxic necrotising toxin type 1 (CNF 1)].","date":"1992","source":"Annales de recherches veterinaires. Annals of veterinary research","url":"https://pubmed.ncbi.nlm.nih.gov/1510341","citation_count":9,"is_preprint":false},{"pmid":"35278126","id":"PMC_35278126","title":"Spectrum of NPHS1 and NPHS2 variants in egyptian children with focal segmental glomerular sclerosis: identification of six novel variants and founder effect.","date":"2022","source":"Molecular genetics and genomics : MGG","url":"https://pubmed.ncbi.nlm.nih.gov/35278126","citation_count":8,"is_preprint":false},{"pmid":"31963805","id":"PMC_31963805","title":"Electrospun CNF Supported Ceramics as Electrochemical Catalysts for Water Splitting and Fuel Cell: A Review.","date":"2020","source":"Polymers","url":"https://pubmed.ncbi.nlm.nih.gov/31963805","citation_count":8,"is_preprint":false},{"pmid":"15177566","id":"PMC_15177566","title":"Molecular cloning and characterization of an endogenous antisense transcript of Nphs1.","date":"2004","source":"Genomics","url":"https://pubmed.ncbi.nlm.nih.gov/15177566","citation_count":8,"is_preprint":false},{"pmid":"19878023","id":"PMC_19878023","title":"Prevalence of urovirulence genes cnf, hlyD, sfa/foc, and papGIII in fecal Escherichia coli from healthy dogs and their owners.","date":"2009","source":"American journal of veterinary research","url":"https://pubmed.ncbi.nlm.nih.gov/19878023","citation_count":8,"is_preprint":false},{"pmid":"30212551","id":"PMC_30212551","title":"Characterization of a novel disease-associated mutation within NPHS1 and its effects on nephrin phosphorylation and signaling.","date":"2018","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/30212551","citation_count":8,"is_preprint":false},{"pmid":"25729976","id":"PMC_25729976","title":"Novel NPHS1 splice site mutations in a Chinese child with congenital nephrotic syndrome.","date":"2015","source":"Genetics and molecular research : GMR","url":"https://pubmed.ncbi.nlm.nih.gov/25729976","citation_count":8,"is_preprint":false},{"pmid":"22653594","id":"PMC_22653594","title":"Mutations in NPHS1 in a Chinese child with congenital nephrotic syndrome.","date":"2012","source":"Genetics and molecular research : GMR","url":"https://pubmed.ncbi.nlm.nih.gov/22653594","citation_count":7,"is_preprint":false},{"pmid":"7684711","id":"PMC_7684711","title":"Prenatal diagnosis of congenital nephrosis of the Finnish type (CNF) in the second trimester.","date":"1993","source":"International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics","url":"https://pubmed.ncbi.nlm.nih.gov/7684711","citation_count":7,"is_preprint":false},{"pmid":"32471989","id":"PMC_32471989","title":"Spatio-temporal patterning of different connexins in developing and postnatal human kidneys and in nephrotic syndrome of the Finnish type (CNF).","date":"2020","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/32471989","citation_count":6,"is_preprint":false},{"pmid":"16703378","id":"PMC_16703378","title":"Neonatal nephrotic presentation of a child with heterozygous NPHS1 mutation.","date":"2006","source":"Pediatric nephrology (Berlin, Germany)","url":"https://pubmed.ncbi.nlm.nih.gov/16703378","citation_count":6,"is_preprint":false},{"pmid":"29859279","id":"PMC_29859279","title":"Enzyme treated CNF biofilms: Characterization.","date":"2018","source":"International journal of biological macromolecules","url":"https://pubmed.ncbi.nlm.nih.gov/29859279","citation_count":6,"is_preprint":false},{"pmid":"27882743","id":"PMC_27882743","title":"Congenital nephrotic syndrome with a novel NPHS1 mutation.","date":"2016","source":"Pediatrics international : official journal of the Japan Pediatric Society","url":"https://pubmed.ncbi.nlm.nih.gov/27882743","citation_count":5,"is_preprint":false},{"pmid":"33014689","id":"PMC_33014689","title":"AuNPs/CNF-modified DNA biosensor for early and quick detection of O. tsutsugamushi in patients suffering from scrub typhus.","date":"2020","source":"3 Biotech","url":"https://pubmed.ncbi.nlm.nih.gov/33014689","citation_count":5,"is_preprint":false},{"pmid":"25711261","id":"PMC_25711261","title":"Congenital nephrotic syndrome of NPHS1 associated with cardiac malformation.","date":"2015","source":"Pediatrics international : official journal of the Japan Pediatric Society","url":"https://pubmed.ncbi.nlm.nih.gov/25711261","citation_count":5,"is_preprint":false},{"pmid":"36460143","id":"PMC_36460143","title":"Design of a chimeric protein composed of FimH, FyuA and CNF-1 virulence factors from uropathogenic Escherichia coli and evaluation its biological activity and immunogenicity in vitro and in vivo.","date":"2022","source":"Microbial pathogenesis","url":"https://pubmed.ncbi.nlm.nih.gov/36460143","citation_count":5,"is_preprint":false},{"pmid":"31549796","id":"PMC_31549796","title":"Fe3 SnC@CNF: A 3 D Antiperovskite Intermetallic Carbide System as a New Robust High-Capacity Lithium-Ion Battery Anode.","date":"2019","source":"ChemSusChem","url":"https://pubmed.ncbi.nlm.nih.gov/31549796","citation_count":5,"is_preprint":false},{"pmid":"25599733","id":"PMC_25599733","title":"Association between NPHS1 and NPHS2 gene variants and nephrotic syndrome in children.","date":"2015","source":"Iranian journal of kidney diseases","url":"https://pubmed.ncbi.nlm.nih.gov/25599733","citation_count":4,"is_preprint":false},{"pmid":"36474550","id":"PMC_36474550","title":"The Distribution of Cytotoxic Necrotizing Factors (CNF-1, CNF-2, CNF-3) and Cytolethal Distending Toxins (CDT-1, CDT-2, CDT-3, CDT-4) in Escherichia coli Isolates Isolated from Extraintestinal Infections and the Determination of their Phylogenetic Relationship by PFGE.","date":"2022","source":"International journal of clinical practice","url":"https://pubmed.ncbi.nlm.nih.gov/36474550","citation_count":4,"is_preprint":false},{"pmid":"22221426","id":"PMC_22221426","title":"Durability test with fuel starvation using a Pt/CNF catalyst in PEMFC.","date":"2012","source":"Nanoscale research letters","url":"https://pubmed.ncbi.nlm.nih.gov/22221426","citation_count":4,"is_preprint":false},{"pmid":"20802786","id":"PMC_20802786","title":"Investigation into Photoconductivity in Single CNF/TiO(2)-Dye Core-Shell Nanowire Devices.","date":"2010","source":"Nanoscale research letters","url":"https://pubmed.ncbi.nlm.nih.gov/20802786","citation_count":4,"is_preprint":false},{"pmid":"39451425","id":"PMC_39451425","title":"Characterization of MSC Growth, Differentiation, and EV Production in CNF Hydrogels Under Static and Dynamic Cultures in Hypoxic and Normoxic Conditions.","date":"2024","source":"Bioengineering (Basel, Switzerland)","url":"https://pubmed.ncbi.nlm.nih.gov/39451425","citation_count":4,"is_preprint":false},{"pmid":"19946311","id":"PMC_19946311","title":"Expanding the spectrum of NPHS1-associated disease.","date":"2009","source":"Kidney international","url":"https://pubmed.ncbi.nlm.nih.gov/19946311","citation_count":3,"is_preprint":false},{"pmid":"30171708","id":"PMC_30171708","title":"Novel variations in NPHS1 gene in children of South Indian population and its association with primary nephrotic syndrome.","date":"2018","source":"Journal of cellular biochemistry","url":"https://pubmed.ncbi.nlm.nih.gov/30171708","citation_count":3,"is_preprint":false},{"pmid":"29663071","id":"PMC_29663071","title":"Cyclosporine A responsive congenital nephrotic syndrome with single heterozygous variants in NPHS1, NPHS2, and PLCE1.","date":"2018","source":"Pediatric nephrology (Berlin, Germany)","url":"https://pubmed.ncbi.nlm.nih.gov/29663071","citation_count":3,"is_preprint":false},{"pmid":"30738309","id":"PMC_30738309","title":"Enhanced photovoltaic properties of dye-sensitized solar cells using three-component CNF/TiO2/Au heterostructure.","date":"2019","source":"Journal of colloid and interface science","url":"https://pubmed.ncbi.nlm.nih.gov/30738309","citation_count":3,"is_preprint":false},{"pmid":"34555552","id":"PMC_34555552","title":"The association of NPHS1 and ACNT4 gene polymorphisms with pre-eclampsia.","date":"2021","source":"European journal of obstetrics, gynecology, and reproductive biology","url":"https://pubmed.ncbi.nlm.nih.gov/34555552","citation_count":2,"is_preprint":false},{"pmid":"38482553","id":"PMC_38482553","title":"Quantitative phenotyping of Nphs1 knockout mice as a prerequisite for gene replacement studies.","date":"2024","source":"American journal of physiology. Renal physiology","url":"https://pubmed.ncbi.nlm.nih.gov/38482553","citation_count":2,"is_preprint":false},{"pmid":"36800604","id":"PMC_36800604","title":"A novel heterozygous mutation of the NPHS1 gene in a Chinese child with congenital nephrotic syndrome: A case report.","date":"2023","source":"Medicine","url":"https://pubmed.ncbi.nlm.nih.gov/36800604","citation_count":2,"is_preprint":false},{"pmid":"40266336","id":"PMC_40266336","title":"The clinical characteristics of patients with congenital nephrotic syndrome secondary to NPHS1 mutation: Is nephrectomy still a therapeutic option for selected cases?","date":"2025","source":"Pediatric nephrology (Berlin, Germany)","url":"https://pubmed.ncbi.nlm.nih.gov/40266336","citation_count":2,"is_preprint":false},{"pmid":"23829269","id":"PMC_23829269","title":"Hsf-1 affects podocyte markers NPHS1, NPHS2 and WT1 in a transgenic mouse model of TTRVal30Met-related amyloidosis.","date":"2013","source":"Amyloid : the international journal of experimental and clinical investigation : the official journal of the International Society of Amyloidosis","url":"https://pubmed.ncbi.nlm.nih.gov/23829269","citation_count":2,"is_preprint":false},{"pmid":"28392951","id":"PMC_28392951","title":"Three Novel Mutations in the NPHS1 Gene in Vietnamese Patients with Congenital Nephrotic Syndrome.","date":"2017","source":"Case reports in genetics","url":"https://pubmed.ncbi.nlm.nih.gov/28392951","citation_count":2,"is_preprint":false},{"pmid":"31443662","id":"PMC_31443662","title":"Congenital nephrotic syndrome associated with 22q11.2 duplication syndrome in a Chinese family and functional analysis of the intronic NPHS1 c. 3286 + 5G > A mutation.","date":"2019","source":"Italian journal of pediatrics","url":"https://pubmed.ncbi.nlm.nih.gov/31443662","citation_count":2,"is_preprint":false},{"pmid":"37220796","id":"PMC_37220796","title":"Integrated enzyme hydrolysis assisted cellulose nanofibril (CNF) fabrication: A sustainable approach to paper mill sludge (PMS) management.","date":"2023","source":"Chemosphere","url":"https://pubmed.ncbi.nlm.nih.gov/37220796","citation_count":2,"is_preprint":false},{"pmid":"39365269","id":"PMC_39365269","title":"Synthesis and Fabrication of Metal Cation Intercalation in Multilayered Ti3C2T Composite CNF Electrode for Asymmetric Coin Cell Supercapacitors.","date":"2024","source":"Langmuir : the ACS journal of surfaces and colloids","url":"https://pubmed.ncbi.nlm.nih.gov/39365269","citation_count":2,"is_preprint":false},{"pmid":"34396835","id":"PMC_34396835","title":"A case report of congenital nephrotic syndrome caused by new mutations of NPHS1.","date":"2021","source":"The Journal of international medical research","url":"https://pubmed.ncbi.nlm.nih.gov/34396835","citation_count":2,"is_preprint":false},{"pmid":"24231487","id":"PMC_24231487","title":"Does NPHS1 polymorphism modulate P118l mutation in NPHS2?","date":"2013","source":"Saudi journal of kidney diseases and transplantation : an official publication of the Saudi Center for Organ Transplantation, Saudi Arabia","url":"https://pubmed.ncbi.nlm.nih.gov/24231487","citation_count":2,"is_preprint":false},{"pmid":"38444459","id":"PMC_38444459","title":"A Case of Congenital Nephrotic Syndrome with Crescents Caused by a Novel Compound Heterozygous Pairing of NPHS1 Genetic Variants.","date":"2024","source":"Case reports in nephrology","url":"https://pubmed.ncbi.nlm.nih.gov/38444459","citation_count":2,"is_preprint":false},{"pmid":"24498843","id":"PMC_24498843","title":"NPHS1 gene mutations in children with Nephrotic Syndrome in northwest Iran.","date":"2013","source":"Pakistan journal of biological sciences : PJBS","url":"https://pubmed.ncbi.nlm.nih.gov/24498843","citation_count":2,"is_preprint":false},{"pmid":"31013750","id":"PMC_31013750","title":"The Role of p.Ser1105Ser (in NPHS1 Gene) and p.Arg548Leu (in PLCE1 Gene) with Disease Status of Vietnamese Patients with Congenital Nephrotic Syndrome: Benign or Pathogenic?","date":"2019","source":"Medicina (Kaunas, Lithuania)","url":"https://pubmed.ncbi.nlm.nih.gov/31013750","citation_count":2,"is_preprint":false},{"pmid":"24142548","id":"PMC_24142548","title":"Functional analysis of NPHS1 mutations in Japanese patients.","date":"2013","source":"Histology and histopathology","url":"https://pubmed.ncbi.nlm.nih.gov/24142548","citation_count":1,"is_preprint":false},{"pmid":"34900253","id":"PMC_34900253","title":"Congenital nephrotic syndrome in a Hispanic Guatemalan newborn associated with a NPHS1 variant: A case report.","date":"2021","source":"Biomedical reports","url":"https://pubmed.ncbi.nlm.nih.gov/34900253","citation_count":1,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":49548,"output_tokens":2979,"usd":0.096665},"stage2":{"model":"claude-opus-4-6","input_tokens":6356,"output_tokens":2267,"usd":0.132683},"total_usd":0.229348,"stage1_batch_id":"msgbatch_012ZiiCUBfB62NCTQd4Bk1Jo","stage2_batch_id":"msgbatch_01Xuqq9aUHoQouS7UVGZNStZ","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 1999,\n      \"finding\": \"The NPHS1 gene encodes nephrin, a transmembrane protein expressed on podocyte cell surfaces; the two common Finnish mutations (Fin-major: 2-bp deletion in exon 2; Fin-minor: nonsense mutation in exon 26) and 32 additional novel mutations were identified in the nephrin gene, establishing nephrin as the structural protein mutated in congenital nephrotic syndrome of the Finnish type.\",\n      \"method\": \"Genomic structure analysis, direct exon sequencing, mutation screening of 35 NPHS1 patients\",\n      \"journal\": \"American journal of human genetics\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1-2 — original gene/protein characterization with genomic sequencing, replicated across labs\",\n      \"pmids\": [\"9915943\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2000,\n      \"finding\": \"The Fin-major and Fin-minor mutations in NPHS1 both result in complete absence of nephrin protein and absence of podocyte slit diaphragms, whereas a patient with the Fin-major/R743C genotype expressed nephrin and had normal slit diaphragms, establishing that nephrin is the principal structural component of the slit diaphragm required for its formation.\",\n      \"method\": \"Immunohistochemistry, Western blotting, in situ hybridization, electron microscopy of nephrectomized kidneys from 46 Finnish NPHS1 patients\",\n      \"journal\": \"Kidney international\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — multiple orthogonal methods (IHC, WB, ISH, EM) in a large patient cohort\",\n      \"pmids\": [\"10972661\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2001,\n      \"finding\": \"Most missense mutations in NPHS1 cause nephrin to be retained in the endoplasmic reticulum and prevent cell surface localization, indicating that ER retention due to protein misfolding is the predominant pathomechanism of missense mutations.\",\n      \"method\": \"Immunostaining of stable transfected cell lines expressing 21 different nephrin missense mutants, immunoelectron microscopy, subcellular fractionation\",\n      \"journal\": \"Human molecular genetics\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1-2 — multiple orthogonal methods (immunostaining, immunoelectron microscopy, subcellular fractionation) for 21 mutants\",\n      \"pmids\": [\"11726550\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2001,\n      \"finding\": \"Recurrence of nephrotic syndrome after renal transplantation in CNF/NPHS1 patients is caused by autoantibodies against nephrin; increased serum anti-nephrin antibody titers precede nephrotic episodes and drop after successful treatment, demonstrating that nephrin functions as a neoantigen post-transplant and that anti-nephrin antibodies impair glomerular filtration.\",\n      \"method\": \"Indirect immunofluorescence microscopy, immunoblotting, ELISA assay of serial serum samples before and after recurrence of nephrotic syndrome\",\n      \"journal\": \"Experimental nephrology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — multiple orthogonal methods (IIF, immunoblot, ELISA) with serial samples demonstrating temporal correlation\",\n      \"pmids\": [\"11549850\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2002,\n      \"finding\": \"NPHS1 (nephrin) and NPHS2 (podocin) have a functional inter-relationship in glomerular filtration; digenic inheritance of mutations in both genes results in a 'tri-allelic hit' that modifies the disease phenotype from congenital nephrotic syndrome to congenital focal segmental glomerulosclerosis, demonstrating epistatic interaction between these two slit diaphragm proteins.\",\n      \"method\": \"Mutational analysis of NPHS1 and NPHS2 in 50 patients with genotype/phenotype correlation analysis\",\n      \"journal\": \"Human molecular genetics\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 — genetic epistasis from patient cohort analysis, single lab\",\n      \"pmids\": [\"11854170\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2000,\n      \"finding\": \"The mouse Nphs1 5' flanking region (8.3-kb and 5.4-kb fragments) drives podocyte-specific transgene expression in vivo, with beta-galactosidase activity confined to podocyte nuclei in kidneys and a discrete brain region, establishing these sequences as functional podocyte-specific promoter/enhancer elements.\",\n      \"method\": \"BAC clone characterization, transgenic mouse lacZ reporter assay, X-gal staining of kidney sections, chemiluminescence assay\",\n      \"journal\": \"Journal of the American Society of Nephrology : JASN\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — in vivo transgenic assay with multiple independent founders confirming position-independent podocyte-specific expression\",\n      \"pmids\": [\"11095653\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2004,\n      \"finding\": \"An endogenous antisense transcript (Nphs1as) originating from the nephrin-encoding locus spans Nphs1 exons 7-12 in reverse orientation and is expressed in brain, thymus, and peripheral lymph nodes but not in kidney or pancreas (major nephrin expression sites), suggesting a role for Nphs1as in tissue-specific regulation of nephrin expression.\",\n      \"method\": \"Molecular cloning of antisense transcript, RT-PCR, immunoblotting, analysis of nephrin-deficient mouse line generated by insertional mutagenesis\",\n      \"journal\": \"Genomics\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 — molecular cloning and expression characterization, single lab\",\n      \"pmids\": [\"15177566\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2007,\n      \"finding\": \"Anti-nephrin antibodies in NPHS1 patients homozygous for Fin-major mutation (who lack endogenous nephrin expression) effectively impair glomerular function in kidney grafts; plasma exchange alongside cyclophosphamide is effective in treating these antibody-mediated recurrences, confirming nephrin as a functional target of these autoantibodies.\",\n      \"method\": \"ELISA for serum anti-nephrin antibodies, kidney biopsy immunohistochemistry, clinical outcomes analysis in 65 NPHS1 transplant patients\",\n      \"journal\": \"Transplantation\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2-3 — ELISA and biopsy with clinical correlation, single institution but large cohort\",\n      \"pmids\": [\"17519780\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"Wild-type nephrin suppresses TRPC6 channel current amplitudes in HEK293 cells and podocytes, but this suppression is lost with the NPHS1 c.294C>T synonymous polymorphism, demonstrating that nephrin physically or functionally interacts with TRPC6 to regulate calcium channel activity in podocytes.\",\n      \"method\": \"Patch-clamp electrophysiology in HEK293 cells and podocytes transfected with TRPC6 and NPHS1 constructs with different genotypes\",\n      \"journal\": \"American journal of transplantation\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1 — direct electrophysiological assay with defined constructs, single lab\",\n      \"pmids\": [\"26147534\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"CNS-associated NPHS1 missense mutations (A419T and C623F) in the nephrin extracellular region reduce surface expression, cause ER retention, impair nephrin tyrosine phosphorylation, and exert dominant negative effects on wild-type nephrin signaling, revealing that extracellular domain mutations can disrupt nephrin's function as a signaling scaffold.\",\n      \"method\": \"Kidney biopsy localization analysis, cell surface expression assays in cultured cells, phosphorylation assays, dominant negative co-transfection experiments\",\n      \"journal\": \"PloS one\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — multiple orthogonal methods (localization, surface expression, phosphorylation, dominant negative) in a single study\",\n      \"pmids\": [\"30212551\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"All pathogenic NPHS1 mutations identified in Japanese patients impaired nephrin trafficking to the plasma membrane, confirmed using transient transfection with immunostaining with and without detergent permeabilization to distinguish membrane from intracellular protein.\",\n      \"method\": \"Transient transfection, immunostaining with/without Triton X permeabilization, automated cell counting\",\n      \"journal\": \"Histology and histopathology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — functional assay for multiple mutations, single lab\",\n      \"pmids\": [\"24142548\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"Nphs1 knockout mice exhibit foot process effacement (average FP density 1.0 vs 2.0 FP/µm in controls), reduced filtration slit density (2.64 vs 4.36 µm/µm²), proximal tubular microcysts, proteinuria within the first week of life, and hypoalbuminemia, confirming nephrin is essential for normal podocyte foot process architecture and glomerular filtration barrier integrity.\",\n      \"method\": \"Conditional Nphs1 knockout mouse model, electron microscopy foot process density measurement, urine albumin-to-creatinine ratio, serum albumin/BUN/creatinine levels\",\n      \"journal\": \"American journal of physiology. Renal physiology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — quantitative KO phenotyping with multiple orthogonal structural and functional measures\",\n      \"pmids\": [\"38482553\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"An intronic NPHS1 mutation (c.3286+5G>A) causes defective alternative splicing of NPHS1, identifying a splice-site dependent mechanism of disease in congenital nephrotic syndrome.\",\n      \"method\": \"Functional splicing analysis of the intronic mutation in patient-derived samples\",\n      \"journal\": \"Italian journal of pediatrics\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — direct functional splicing assay for a specific intronic variant, single case\",\n      \"pmids\": [\"31443662\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"NPHS1 encodes nephrin, a podocyte transmembrane protein that is the principal structural component of the glomerular slit diaphragm; nephrin is required for slit diaphragm assembly and foot process architecture, functions as a tyrosine-phosphorylated signaling scaffold that modulates TRPC6 channel activity, and missense mutations predominantly cause disease by inducing ER retention and defective plasma membrane trafficking, while truncating mutations abolish nephrin expression entirely leading to absence of slit diaphragms and massive proteinuria.\"\n}\n```","stage2_raw":"```json\n{\n  \"mechanistic_narrative\": \"NPHS1 encodes nephrin, a podocyte-expressed transmembrane protein that serves as the principal structural and signaling component of the glomerular slit diaphragm, essential for maintaining the kidney filtration barrier. Truncating mutations (e.g., Fin-major, Fin-minor) abolish nephrin protein expression and slit diaphragm formation, causing massive proteinuria characteristic of congenital nephrotic syndrome of the Finnish type, while most missense mutations cause endoplasmic reticulum retention and defective plasma membrane trafficking, with some extracellular domain mutations additionally impairing tyrosine phosphorylation and exerting dominant-negative effects on wild-type nephrin signaling [PMID:9915943, PMID:10972661, PMID:11726550, PMID:30212551]. Nphs1 knockout mice confirm that nephrin is required for podocyte foot process architecture, filtration slit density, and prevention of proteinuria [PMID:38482553]. Nephrin also functions as a signaling scaffold that suppresses TRPC6 calcium channel activity in podocytes, and after transplantation in nephrin-null patients, it acts as a neoantigen whose targeting by autoantibodies causes graft nephrotic syndrome [PMID:26147534, PMID:11549850].\",\n  \"teleology\": [\n    {\n      \"year\": 1999,\n      \"claim\": \"Positional cloning of NPHS1 resolved the molecular identity of the gene mutated in congenital nephrotic syndrome of the Finnish type, establishing nephrin as a transmembrane protein and the first defined slit diaphragm component.\",\n      \"evidence\": \"Genomic structure analysis and direct exon sequencing of 35 CNF patients identifying Fin-major, Fin-minor, and 32 novel mutations\",\n      \"pmids\": [\"9915943\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Nephrin protein localization and function at the slit diaphragm not yet demonstrated\",\n        \"Mechanism by which specific mutations cause disease not addressed\"\n      ]\n    },\n    {\n      \"year\": 2000,\n      \"claim\": \"Protein-level analysis demonstrated that truncating NPHS1 mutations abolish nephrin expression and slit diaphragm formation, while a missense allele preserves both, establishing nephrin as the principal structural component of the slit diaphragm.\",\n      \"evidence\": \"Immunohistochemistry, Western blot, in situ hybridization, and electron microscopy on nephrectomized kidneys from 46 Finnish NPHS1 patients with defined genotypes\",\n      \"pmids\": [\"10972661\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Mechanism of missense mutation pathogenicity unknown\",\n        \"Whether nephrin has signaling functions beyond structural role not tested\"\n      ]\n    },\n    {\n      \"year\": 2001,\n      \"claim\": \"Systematic analysis of 21 missense mutants revealed that ER retention due to misfolding is the predominant pathomechanism, shifting understanding from simple loss of expression to a protein quality control defect.\",\n      \"evidence\": \"Immunostaining of stable cell lines, immunoelectron microscopy, and subcellular fractionation for 21 NPHS1 missense mutants\",\n      \"pmids\": [\"11726550\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Whether ER-retained mutants can be pharmacologically rescued not tested\",\n        \"Whether some mutants reach the surface but are non-functional not fully resolved\"\n      ]\n    },\n    {\n      \"year\": 2001,\n      \"claim\": \"The discovery that anti-nephrin autoantibodies cause post-transplant nephrotic syndrome recurrence in CNF patients established that nephrin is a functional neoantigen and that antibody-mediated targeting of nephrin directly impairs glomerular filtration.\",\n      \"evidence\": \"Indirect immunofluorescence, immunoblotting, and serial ELISA of serum samples in transplanted NPHS1 patients with temporal correlation to nephrotic episodes\",\n      \"pmids\": [\"11549850\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Precise mechanism by which anti-nephrin antibodies disrupt filtration barrier not defined\",\n        \"Whether antibodies cause complement-mediated injury vs. direct functional blockade unclear\"\n      ]\n    },\n    {\n      \"year\": 2002,\n      \"claim\": \"Demonstration of digenic inheritance between NPHS1 and NPHS2 (podocin) mutations revealed epistatic interaction between slit diaphragm components, modifying disease phenotype from CNS to FSGS.\",\n      \"evidence\": \"Mutational analysis of NPHS1 and NPHS2 with genotype-phenotype correlation in 50 patients\",\n      \"pmids\": [\"11854170\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Biochemical basis of nephrin-podocin epistasis not characterized\",\n        \"Not independently replicated in a separate cohort\",\n        \"Whether other slit diaphragm genes contribute to oligogenic inheritance not tested\"\n      ]\n    },\n    {\n      \"year\": 2015,\n      \"claim\": \"Electrophysiology demonstrated that nephrin suppresses TRPC6 channel currents, establishing a signaling function for nephrin in regulating podocyte calcium homeostasis beyond its structural role.\",\n      \"evidence\": \"Patch-clamp recordings in HEK293 cells and podocytes co-transfected with TRPC6 and NPHS1 constructs\",\n      \"pmids\": [\"26147534\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Whether nephrin-TRPC6 interaction is direct or mediated through adaptor proteins not determined\",\n        \"In vivo relevance of this channel regulation not tested\",\n        \"Mechanism by which the synonymous c.294C>T variant alters nephrin function unclear\"\n      ]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"CNS-associated extracellular domain missense mutations were shown to reduce surface expression, impair tyrosine phosphorylation, and exert dominant-negative effects on wild-type nephrin, demonstrating that nephrin functions as a tyrosine-phosphorylated signaling scaffold.\",\n      \"evidence\": \"Cell surface expression assays, phosphorylation assays, and dominant-negative co-transfection experiments for A419T and C623F mutants\",\n      \"pmids\": [\"30212551\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Identity of the kinase(s) and downstream effectors of nephrin phosphorylation in this context not identified\",\n        \"Whether dominant-negative effects occur in vivo in heterozygous carriers unknown\"\n      ]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Conditional Nphs1 knockout mice provided definitive in vivo proof that nephrin is essential for foot process architecture and filtration barrier integrity, quantifying the structural and functional consequences of nephrin loss.\",\n      \"evidence\": \"Conditional Nphs1 KO mice with quantitative EM foot process measurements, urine albumin-to-creatinine ratio, and serum biochemistry\",\n      \"pmids\": [\"38482553\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Whether adult conditional deletion reproduces neonatal phenotype not reported\",\n        \"Signaling pathways downstream of nephrin loss in vivo not dissected\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The precise mechanism by which nephrin organizes the slit diaphragm at a structural level, its full signaling interactome downstream of tyrosine phosphorylation, and whether ER-retained mutants can be pharmacologically rescued remain unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No high-resolution structural model of the nephrin ectodomain trans-interaction at the slit diaphragm\",\n        \"Full phospho-signaling cascade downstream of nephrin remains unmapped\",\n        \"Pharmacological chaperone rescue of ER-retained nephrin mutants not demonstrated\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0098772\", \"supporting_discovery_ids\": [8, 9]},\n      {\"term_id\": \"GO:0005198\", \"supporting_discovery_ids\": [1, 11]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005886\", \"supporting_discovery_ids\": [1, 2, 9, 10, 11]},\n      {\"term_id\": \"GO:0005783\", \"supporting_discovery_ids\": [2, 9, 10]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0005198\", \"supporting_discovery_ids\": []},\n      {\"term_id\": \"R-HSA-162582\", \"supporting_discovery_ids\": [8, 9]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\n      \"TRPC6\",\n      \"NPHS2\"\n    ],\n    \"other_free_text\": []\n  }\n}\n```"}