{"gene":"KRT1","run_date":"2026-04-28T18:30:27","timeline":{"discoveries":[{"year":2015,"finding":"KRT1 C-terminal frameshift mutations cause partial collapse of the cytoplasmic intermediate filament network and mislocalization of mutant KRT1 to the nucleus; reversion of these mutations occurs via mitotic recombination, explaining the revertant mosaicism seen in ichthyosis with confetti.","method":"Clinical genetics, histopathology, cell biology (immunofluorescence showing nuclear mislocalization), and molecular analysis of revertant clones demonstrating mitotic recombination","journal":"The Journal of clinical investigation","confidence":"High","confidence_rationale":"Tier 2 — multiple orthogonal methods (molecular genetics, immunofluorescence, revertant clone analysis) in a single rigorous study","pmids":["25774499"],"is_preprint":false},{"year":2003,"finding":"KRT1 and KRT10 form heterodimers that constitute the intermediate filaments in suprabasal keratinocytes committed to terminal differentiation; mutations in the conserved 1A and 2B helical rod domains disrupt this function and cause epidermolytic hyperkeratosis.","method":"Genetic analysis of patients combined with structural domain mapping of mutations; functional inference from dominant-negative phenotypes","journal":"The Journal of investigative dermatology","confidence":"Medium","confidence_rationale":"Tier 3 — genetic/mutational analysis in patients, replicated across multiple studies but no in vitro reconstitution in this specific paper","pmids":["14708600"],"is_preprint":false},{"year":2022,"finding":"Loss of KRT1 via homozygous nonsense mutations (leading to nonsense-mediated mRNA decay and absence of KRT1 protein) results in epidermolytic palmoplantar keratoderma, with compensatory upregulation of keratin 2 (which forms heterodimers with keratin 10), while keratin 9 shows aberrant clumped distribution in palmar skin.","method":"Next-generation sequencing, qRT-PCR, immunofluorescence, Western blot, transmission electron microscopy","journal":"Journal of the European Academy of Dermatology and Venereology : JEADV","confidence":"Medium","confidence_rationale":"Tier 2 — multiple orthogonal methods (molecular, protein, ultrastructural) in a single study; moderate evidence for compensatory heterodimer formation","pmids":["35490383"],"is_preprint":false},{"year":2022,"finding":"The adhesion G-protein-coupled receptor GPR115/ADGRF4 associates with KRT1/KRT10-positive keratin filaments intracellularly and regulates epidermal differentiation; deletion of ADGRF4 in keratinocytes abrogates KRT1 expression and reduces keratinocyte stratification.","method":"Organotypic culture, ADGRF4 CRISPR deletion in HaCaT cells, immunofluorescence colocalization of GPR115 with KRT1/10 filaments","journal":"Cells","confidence":"Medium","confidence_rationale":"Tier 2 — loss-of-function with defined cellular phenotype and direct colocalization, single lab","pmids":["36231117"],"is_preprint":false},{"year":2024,"finding":"CEA (carcinoembryonic antigen) directly binds KRT1, and this interaction activates the PI3K/AKT signaling pathway, contributing to oxaliplatin resistance in gastric cancer; competitive inhibition of the CEA-KRT1 interaction with the small molecule evacetrapib reverses resistance.","method":"Proteomic analysis, Co-IP, GST pull-down, immunofluorescence colocalization, virtual screening, surface plasmon resonance, in vitro and in vivo drug sensitivity assays","journal":"Drug resistance updates","confidence":"Medium","confidence_rationale":"Tier 2 — reciprocal binding confirmed by Co-IP and GST pull-down with functional downstream pathway validation, single lab","pmids":["39644827"],"is_preprint":false},{"year":2025,"finding":"USP28 (a deubiquitinating enzyme) directly interacts with KRT1 and exerts deubiquitination on KRT1, thereby maintaining KRT1 protein stability; USP28 knockdown leads to KRT1 destabilization and decreased IFITM3 expression in hepatocellular carcinoma cells.","method":"IP-MS analysis, co-immunoprecipitation, immunofluorescence, USP28 knockdown/overexpression with functional assays, xenograft mouse model","journal":"Experimental cell research","confidence":"Medium","confidence_rationale":"Tier 2 — interaction confirmed by IP-MS and Co-IP, deubiquitination inferred from protein stability changes upon knockdown, single lab","pmids":["40222446"],"is_preprint":false},{"year":2023,"finding":"CD63 directly interacts with KRT1 (identified by mass spectrometry and co-immunoprecipitation), and this interaction mediates KRT1-dependent cell cycle arrest to suppress metastasis in head and neck squamous cell carcinoma.","method":"Mass spectrometry, co-immunoprecipitation, in vitro and in vivo functional assays (overexpression/knockdown)","journal":"Heliyon","confidence":"Medium","confidence_rationale":"Tier 2 — interaction confirmed by MS and Co-IP with functional phenotype, single lab","pmids":["37455999"],"is_preprint":false},{"year":2018,"finding":"miR-107 directly binds the KRT1 3'UTR (validated by dual-luciferase reporter assay); miR-107-mediated suppression of KRT1 activates the Notch signaling pathway in vascular endothelial cells, reducing inflammation and ER stress in a coronary atherosclerosis model.","method":"Dual-luciferase reporter assay, ectopic expression and depletion experiments, Western blot, ELISA, flow cytometry in mouse atherosclerosis model","journal":"Journal of cellular physiology","confidence":"Medium","confidence_rationale":"Tier 2 — direct binding confirmed by luciferase assay with functional downstream validation, single lab","pmids":["30548623"],"is_preprint":false},{"year":2018,"finding":"KRT1 silencing activates the Notch signaling pathway (increased NICD and Hes1 expression) in myocardial cells, reducing apoptosis and improving cell proliferation; this effect is abolished by Notch pathway inhibition with DAPT, placing KRT1 upstream of Notch in cardiomyocyte injury context.","method":"siRNA-mediated KRT1 knockdown, Notch activator (Jagged1) and inhibitor (DAPT) treatment, Western blot, MTT assay, flow cytometry in mouse MIRI model","journal":"Journal of cellular physiology","confidence":"Low","confidence_rationale":"Tier 3 — epistasis placement using inhibitor/activator without reconstitution; single lab, unusual cell context for a structural keratin","pmids":["30191968"],"is_preprint":false}],"current_model":"KRT1 encodes a type II intermediate filament keratin that heterodimerizes with KRT10 (and KRT9 in palmoplantar skin) to form the 10-nm cytoskeletal filament network in suprabasal keratinocytes; disease-causing mutations in the conserved rod domain act dominantly to collapse this network, while KRT1 protein stability is regulated by USP28-mediated deubiquitination, and KRT1 can also function as a cell-surface binding partner for CEA to activate PI3K/AKT signaling and interact with CD63 to mediate cell cycle arrest."},"narrative":{"teleology":[{"year":2003,"claim":"Establishing KRT1's core function: mapping of patient mutations to the conserved 1A and 2B helical rod domains demonstrated that KRT1/KRT10 heterodimers are essential structural units of suprabasal intermediate filaments and that their disruption causes epidermolytic hyperkeratosis.","evidence":"Genotype–phenotype analysis of multiple epidermolytic hyperkeratosis families with domain mapping of KRT1 mutations","pmids":["14708600"],"confidence":"Medium","gaps":["No in vitro reconstitution of mutant vs. wild-type filament assembly in this study","Quantitative structure–function relationship between specific rod-domain residues and filament stability not resolved"]},{"year":2015,"claim":"Resolving how C-terminal mutations produce a distinct disease: frameshift mutations in the KRT1 tail domain were shown to cause nuclear mislocalization and partial filament collapse rather than complete network disruption, explaining the milder ichthyosis with confetti phenotype and its characteristic revertant mosaicism via mitotic recombination.","evidence":"Immunofluorescence of patient keratinocytes showing nuclear KRT1, molecular analysis of revertant clones demonstrating loss-of-heterozygosity by mitotic recombination","pmids":["25774499"],"confidence":"High","gaps":["Mechanism by which C-terminal frameshift directs nuclear import is unknown","Whether nuclear KRT1 has any functional consequence beyond filament loss is untested"]},{"year":2018,"claim":"Extending KRT1's reach beyond structural roles: miR-107 was shown to directly target the KRT1 3ʹ-UTR, and KRT1 suppression activated Notch signalling in vascular endothelial cells and cardiomyocytes, suggesting KRT1 can modulate signalling pathways in non-epithelial contexts.","evidence":"Dual-luciferase reporter assay confirming miR-107 binding to KRT1 3ʹ-UTR; siRNA knockdown with Notch pathway readouts (NICD, Hes1) and DAPT rescue in mouse atherosclerosis and MIRI models","pmids":["30548623","30191968"],"confidence":"Low","gaps":["KRT1 expression in vascular endothelial cells and cardiomyocytes is atypical for a suprabasal keratin; independent confirmation of endogenous expression in these cell types is lacking","Epistasis with Notch was inferred from inhibitor experiments without direct biochemical mechanism","Single-lab findings not replicated"]},{"year":2022,"claim":"Defining consequences of complete KRT1 loss: homozygous nonsense mutations causing nonsense-mediated decay demonstrated that KRT1 absence triggers compensatory KRT2/KRT10 pairing and aberrant KRT9 distribution, resulting in palmoplantar keratoderma rather than generalised epidermolysis.","evidence":"NGS, qRT-PCR, Western blot, immunofluorescence, and TEM in patient skin biopsies","pmids":["35490383"],"confidence":"Medium","gaps":["Whether KRT2/KRT10 filaments fully substitute mechanically for KRT1/KRT10 is unknown","Why the phenotype is restricted to palmoplantar skin despite widespread KRT1 expression is unexplained"]},{"year":2022,"claim":"Identifying an upstream regulator of KRT1 expression: ADGRF4 (GPR115) was shown to associate with KRT1/KRT10 filaments and to be required for KRT1 expression and keratinocyte stratification.","evidence":"CRISPR deletion of ADGRF4 in HaCaT cells with organotypic culture; immunofluorescence colocalization","pmids":["36231117"],"confidence":"Medium","gaps":["Signal transduction pathway between ADGRF4 and KRT1 transcription is uncharacterised","Physical association versus functional regulation not fully separated"]},{"year":2023,"claim":"Revealing a non-cytoskeletal signalling role: CD63 was identified as a direct KRT1 interactor whose binding mediates KRT1-dependent cell-cycle arrest and metastasis suppression in head and neck squamous cell carcinoma.","evidence":"Mass spectrometry and co-immunoprecipitation with overexpression/knockdown phenotypic assays in vitro and in vivo","pmids":["37455999"],"confidence":"Medium","gaps":["Structural basis of KRT1–CD63 interaction is unknown","Whether this interaction occurs in normal epithelial differentiation or only in carcinoma is untested"]},{"year":2024,"claim":"Defining a signalling axis through which KRT1 promotes chemoresistance: CEA was shown to bind KRT1 directly and activate PI3K/AKT signalling; competitive disruption of this interaction by evacetrapib restored oxaliplatin sensitivity in gastric cancer.","evidence":"Co-IP, GST pull-down, SPR for direct binding; virtual screening and in vivo xenograft drug sensitivity assays","pmids":["39644827"],"confidence":"Medium","gaps":["Binding interface and stoichiometry of CEA–KRT1 complex not determined","Mechanism linking CEA–KRT1 binding to PI3K activation is undefined"]},{"year":2025,"claim":"Establishing post-translational control of KRT1 stability: USP28 was identified as a deubiquitinase that directly interacts with and stabilises KRT1 protein, linking KRT1 turnover to the ubiquitin–proteasome system.","evidence":"IP-MS and co-immunoprecipitation; USP28 knockdown/overexpression with protein stability assays in hepatocellular carcinoma cells and xenografts","pmids":["40222446"],"confidence":"Medium","gaps":["Specific ubiquitin linkage type and lysine residues on KRT1 targeted by USP28 are not mapped","E3 ligase responsible for KRT1 ubiquitination is unknown"]},{"year":null,"claim":"The structural basis of KRT1's non-filament signalling interactions (with CEA, CD63, and Notch pathway components) and how these are coordinated with its primary cytoskeletal role remain unresolved.","evidence":"","pmids":[],"confidence":"Low","gaps":["No atomic-resolution structure of KRT1 in complex with any signalling partner","Whether cytoplasmic soluble KRT1 pool versus filament-incorporated KRT1 mediates signalling is unknown","Interplay between USP28-mediated KRT1 stabilisation and KRT1's signalling functions has not been tested"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0005198","term_label":"structural molecule activity","supporting_discovery_ids":[0,1,2]}],"localization":[{"term_id":"GO:0005856","term_label":"cytoskeleton","supporting_discovery_ids":[0,1,2,3]},{"term_id":"GO:0005634","term_label":"nucleus","supporting_discovery_ids":[0]}],"pathway":[{"term_id":"R-HSA-162582","term_label":"Signal Transduction","supporting_discovery_ids":[4,6]},{"term_id":"R-HSA-1266738","term_label":"Developmental Biology","supporting_discovery_ids":[1,2,3]}],"complexes":["KRT1/KRT10 heterodimer","KRT1/KRT9 heterodimer"],"partners":["KRT10","KRT9","USP28","CD63","CEACAM5","ADGRF4"],"other_free_text":[]},"mechanistic_narrative":"KRT1 is a type II intermediate filament keratin that heterodimerizes with KRT10 to build the 10-nm cytoskeletal network of suprabasal keratinocytes undergoing terminal differentiation, with KRT9 serving as an additional partner in palmoplantar epidermis. Dominant missense mutations in the conserved 1A and 2B rod domains collapse the filament network and cause epidermolytic hyperkeratosis, whereas C-terminal frameshift mutations mislocalise mutant KRT1 to the nucleus and underlie ichthyosis with confetti, in which revertant mosaicism arises through mitotic recombination; homozygous loss-of-function mutations produce epidermolytic palmoplantar keratoderma with compensatory upregulation of keratin 2 [PMID:14708600, PMID:25774499, PMID:35490383]. KRT1 protein stability is maintained by USP28-mediated deubiquitination, and KRT1 can engage non-cytoskeletal signalling partners: binding CEA activates PI3K/AKT signalling and contributes to chemoresistance, while interaction with CD63 mediates cell-cycle arrest in squamous carcinoma cells [PMID:40222446, PMID:39644827, PMID:37455999]. KRT1 expression in suprabasal keratinocytes is regulated in part by the adhesion GPCR ADGRF4, whose deletion abrogates KRT1 expression and impairs epidermal stratification [PMID:36231117]."},"prefetch_data":{"uniprot":{"accession":"P04264","full_name":"Keratin, type II cytoskeletal 1","aliases":["67 kDa cytokeratin","Cytokeratin-1","CK-1","Hair alpha protein","Keratin-1","K1","Type-II keratin Kb1"],"length_aa":644,"mass_kda":66.0,"function":"May regulate the activity of kinases such as PKC and SRC via binding to integrin beta-1 (ITB1) and the receptor of activated protein C kinase 1 (RACK1). In complex with C1QBP is a high affinity receptor for kininogen-1/HMWK","subcellular_location":"Cell membrane; Cytoplasm","url":"https://www.uniprot.org/uniprotkb/P04264/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/KRT1","classification":"Not Classified","n_dependent_lines":4,"n_total_lines":1208,"dependency_fraction":0.0033112582781456954},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[],"url":"https://opencell.sf.czbiohub.org/search/KRT1","total_profiled":1310},"omim":[{"mim_id":"620411","title":"PALMOPLANTAR KERATODERMA, EPIDERMOLYTIC, 2; EPPK2","url":"https://www.omim.org/entry/620411"},{"mim_id":"620150","title":"EPIDERMOLYTIC HYPERKERATOSIS 2A, AUTOSOMAL DOMINANT; EHK2A","url":"https://www.omim.org/entry/620150"},{"mim_id":"620148","title":"ICHTHYOSIS, ANNULAR EPIDERMOLYTIC, 2; AEI2","url":"https://www.omim.org/entry/620148"},{"mim_id":"614594","title":"OLMSTED SYNDROME 1; OLMS1","url":"https://www.omim.org/entry/614594"},{"mim_id":"614428","title":"TRANSCRIPTION FACTOR AP2-EPSILON; TFAP2E","url":"https://www.omim.org/entry/614428"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"","locations":[],"tissue_specificity":"Tissue enriched","tissue_distribution":"Detected in many","driving_tissues":[{"tissue":"skin 1","ntpm":12288.0}],"url":"https://www.proteinatlas.org/search/KRT1"},"hgnc":{"alias_symbol":["KRT1A"],"prev_symbol":["EHK1"]},"alphafold":{"accession":"P04264","domains":[{"cath_id":"1.20.5","chopping":"254-332","consensus_level":"medium","plddt":95.59,"start":254,"end":332}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/P04264","model_url":"https://alphafold.ebi.ac.uk/files/AF-P04264-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-P04264-F1-predicted_aligned_error_v6.png","plddt_mean":63.06},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=KRT1","jax_strain_url":"https://www.jax.org/strain/search?query=KRT1"},"sequence":{"accession":"P04264","fasta_url":"https://rest.uniprot.org/uniprotkb/P04264.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/P04264/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/P04264"}},"corpus_meta":[{"pmid":"7504232","id":"PMC_7504232","title":"Ehk-1 and Ehk-2: two novel members of the Eph receptor-like tyrosine kinase family with distinctive structures and neuronal expression.","date":"1993","source":"Oncogene","url":"https://pubmed.ncbi.nlm.nih.gov/7504232","citation_count":99,"is_preprint":false},{"pmid":"7523376","id":"PMC_7523376","title":"Characterization and chromosomal localization of the cornea-specific murine keratin gene Krt1.12.","date":"1994","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/7523376","citation_count":96,"is_preprint":false},{"pmid":"16789827","id":"PMC_16789827","title":"Allele-specific KRT1 expression is a complex trait.","date":"2006","source":"PLoS genetics","url":"https://pubmed.ncbi.nlm.nih.gov/16789827","citation_count":62,"is_preprint":false},{"pmid":"25774499","id":"PMC_25774499","title":"Frequent somatic reversion of KRT1 mutations in ichthyosis with confetti.","date":"2015","source":"The Journal of clinical investigation","url":"https://pubmed.ncbi.nlm.nih.gov/25774499","citation_count":54,"is_preprint":false},{"pmid":"26581228","id":"PMC_26581228","title":"Expanding the Clinical and Genetic Spectrum of KRT1, KRT2 and KRT10 Mutations in Keratinopathic Ichthyosis.","date":"2016","source":"Acta dermato-venereologica","url":"https://pubmed.ncbi.nlm.nih.gov/26581228","citation_count":48,"is_preprint":false},{"pmid":"30548623","id":"PMC_30548623","title":"microRNA-107 protects against inflammation and endoplasmic reticulum stress of vascular endothelial cells via KRT1-dependent Notch signaling pathway in a mouse model of coronary atherosclerosis.","date":"2018","source":"Journal of cellular physiology","url":"https://pubmed.ncbi.nlm.nih.gov/30548623","citation_count":42,"is_preprint":false},{"pmid":"7898646","id":"PMC_7898646","title":"Expression and developmental regulation of Ehk-1, a neuronal Elk-like receptor tyrosine kinase in brain.","date":"1994","source":"Neuroscience","url":"https://pubmed.ncbi.nlm.nih.gov/7898646","citation_count":31,"is_preprint":false},{"pmid":"14708600","id":"PMC_14708600","title":"Splice site and deletion mutations in keratin (KRT1 and KRT10) genes: unusual phenotypic alterations in Scandinavian patients with epidermolytic hyperkeratosis.","date":"2003","source":"The Journal of investigative dermatology","url":"https://pubmed.ncbi.nlm.nih.gov/14708600","citation_count":29,"is_preprint":false},{"pmid":"30191968","id":"PMC_30191968","title":"KRT1 gene silencing ameliorates myocardial ischemia-reperfusion injury via the activation of the Notch signaling pathway in mouse models.","date":"2018","source":"Journal of cellular physiology","url":"https://pubmed.ncbi.nlm.nih.gov/30191968","citation_count":23,"is_preprint":false},{"pmid":"17668073","id":"PMC_17668073","title":"In vitro human keratinocyte migration rates are associated with SNPs in the KRT1 interval.","date":"2007","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/17668073","citation_count":23,"is_preprint":false},{"pmid":"11951085","id":"PMC_11951085","title":"Cis-regulatory elements of the mouse Krt1.12 gene.","date":"2002","source":"Molecular vision","url":"https://pubmed.ncbi.nlm.nih.gov/11951085","citation_count":18,"is_preprint":false},{"pmid":"39644827","id":"PMC_39644827","title":"CEA-induced PI3K/AKT pathway activation through the binding of CEA to KRT1 contributes to oxaliplatin resistance in gastric cancer.","date":"2024","source":"Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy","url":"https://pubmed.ncbi.nlm.nih.gov/39644827","citation_count":14,"is_preprint":false},{"pmid":"30021014","id":"PMC_30021014","title":"Analysis of KRT1, KRT10, KRT19, TP53 and MMP9 expression in pediatric and adult cholesteatoma.","date":"2018","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/30021014","citation_count":11,"is_preprint":false},{"pmid":"15663507","id":"PMC_15663507","title":"Epidermolytic hyperkeratosis type PS-1 caused by aberrant splicing of KRT1.","date":"2005","source":"Clinical and experimental dermatology","url":"https://pubmed.ncbi.nlm.nih.gov/15663507","citation_count":10,"is_preprint":false},{"pmid":"9191074","id":"PMC_9191074","title":"Extensive splice variation and localization of the EHK-1 receptor tyrosine kinase in adult human brain and glial tumors.","date":"1997","source":"Brain research. Molecular brain research","url":"https://pubmed.ncbi.nlm.nih.gov/9191074","citation_count":8,"is_preprint":false},{"pmid":"10754100","id":"PMC_10754100","title":"Whiskers amiss, a new vibrissae and hair mutation near the Krt1 cluster on mouse chromosome 11.","date":"2000","source":"Mammalian genome : official journal of the International Mammalian Genome Society","url":"https://pubmed.ncbi.nlm.nih.gov/10754100","citation_count":6,"is_preprint":false},{"pmid":"36231117","id":"PMC_36231117","title":"The Adhesion G-Protein-Coupled Receptor GPR115/ADGRF4 Regulates Epidermal Differentiation and Associates with Cytoskeletal KRT1.","date":"2022","source":"Cells","url":"https://pubmed.ncbi.nlm.nih.gov/36231117","citation_count":5,"is_preprint":false},{"pmid":"30152556","id":"PMC_30152556","title":"A p.478I>T KRT1 mutation in a case of annular epidermolytic ichthyosis.","date":"2018","source":"Pediatric dermatology","url":"https://pubmed.ncbi.nlm.nih.gov/30152556","citation_count":5,"is_preprint":false},{"pmid":"1380418","id":"PMC_1380418","title":"Localization by in situ hybridization of a type I keratin intermediate filament gene (Krt-1.14) to band D of mouse chromosome 11.","date":"1992","source":"Cytogenetics and cell genetics","url":"https://pubmed.ncbi.nlm.nih.gov/1380418","citation_count":5,"is_preprint":false},{"pmid":"35490383","id":"PMC_35490383","title":"Nonsense mutations in KRT1 caused recessive epidermolytic palmoplantar keratoderma with knuckle pads.","date":"2022","source":"Journal of the European Academy of Dermatology and Venereology : JEADV","url":"https://pubmed.ncbi.nlm.nih.gov/35490383","citation_count":4,"is_preprint":false},{"pmid":"35126011","id":"PMC_35126011","title":"Bullous diseases caused by KRT1 gene mutations: from epidermolytic hyperkeratosis to a novel variant of epidermolysis bullosa simplex.","date":"2020","source":"Postepy dermatologii i alergologii","url":"https://pubmed.ncbi.nlm.nih.gov/35126011","citation_count":4,"is_preprint":false},{"pmid":"33363884","id":"PMC_33363884","title":"A novel KRT1 c.1433A>G p.(Glu478Gly) mutation in a newborn with epidermolytic ichthyosis.","date":"2020","source":"Clinical case reports","url":"https://pubmed.ncbi.nlm.nih.gov/33363884","citation_count":4,"is_preprint":false},{"pmid":"37455999","id":"PMC_37455999","title":"Tetraspanin CD63 reduces the progression and metastasis of head and neck squamous cell carcinoma via KRT1-mediated cell cycle arrest.","date":"2023","source":"Heliyon","url":"https://pubmed.ncbi.nlm.nih.gov/37455999","citation_count":4,"is_preprint":false},{"pmid":"36251712","id":"PMC_36251712","title":"A de novo variant in the keratin 1 gene (KRT1) in a Chinese shar-pei dog with severe congenital cornification disorder and non-epidermolytic ichthyosis.","date":"2022","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/36251712","citation_count":3,"is_preprint":false},{"pmid":"25429721","id":"PMC_25429721","title":"Next-generation sequencing detection and characterization of a heterozygous novel splice junction mutation in the 2B domain of KRT1 in a family with diffuse palmoplantar keratoderma.","date":"2015","source":"Experimental dermatology","url":"https://pubmed.ncbi.nlm.nih.gov/25429721","citation_count":3,"is_preprint":false},{"pmid":"25808222","id":"PMC_25808222","title":"A KRT1 gene mutation related to epidermolytic ichthyosis in a Chinese family.","date":"2015","source":"Clinical and experimental dermatology","url":"https://pubmed.ncbi.nlm.nih.gov/25808222","citation_count":2,"is_preprint":false},{"pmid":"37170713","id":"PMC_37170713","title":"Two cases of KRT1 mutation-associated epidermolytic ichthyosis without typical epidermolytic hyperkeratosis in the neonatal skin lesions.","date":"2023","source":"Pediatric dermatology","url":"https://pubmed.ncbi.nlm.nih.gov/37170713","citation_count":2,"is_preprint":false},{"pmid":"40222446","id":"PMC_40222446","title":"USP28 knockdown and small molecule inhibitors promote KRT1 destabilization and sensitize hepatocellular carcinoma cells to sorafenib.","date":"2025","source":"Experimental cell research","url":"https://pubmed.ncbi.nlm.nih.gov/40222446","citation_count":1,"is_preprint":false},{"pmid":"32049370","id":"PMC_32049370","title":"A novel frameshift truncation mutation in the V2 tail domain of KRT1 causes mild ichthyosis hystrix of Curth-Macklin.","date":"2020","source":"Clinical and experimental dermatology","url":"https://pubmed.ncbi.nlm.nih.gov/32049370","citation_count":1,"is_preprint":false},{"pmid":"32898404","id":"PMC_32898404","title":"A de novo mutation of KRT1 in a baby girl causing epidermolytic ichthyosis with impressive epidermolytic palmoplantar keratoderma.","date":"2020","source":"Dermatology online journal","url":"https://pubmed.ncbi.nlm.nih.gov/32898404","citation_count":1,"is_preprint":false},{"pmid":"39619568","id":"PMC_39619568","title":"ABHD1 Facilitates Intermediate Filament-Mediated Endothelial Cell Chemotaxis by Regulating KRT1 and KRT2 in Diabetic Retinopathy.","date":"2024","source":"Journal of diabetes research","url":"https://pubmed.ncbi.nlm.nih.gov/39619568","citation_count":0,"is_preprint":false},{"pmid":"41186844","id":"PMC_41186844","title":"CircPPP1CB subtype, hsa_circ_0007439, promotes nasopharyngeal carcinoma progression by upregulating KRT1.","date":"2025","source":"Discover oncology","url":"https://pubmed.ncbi.nlm.nih.gov/41186844","citation_count":0,"is_preprint":false},{"pmid":"30452289","id":"PMC_30452289","title":"Novel Splice-Site Mutation of KRT1 Underlies Diffuse Palmoplantar Keratoderma in a Large Chinese Pedigree.","date":"2018","source":"Genetic testing and molecular biomarkers","url":"https://pubmed.ncbi.nlm.nih.gov/30452289","citation_count":0,"is_preprint":false},{"pmid":"37566479","id":"PMC_37566479","title":"De Novo Mutation in KRT1 Leads to Epidermolytic Palmoplantar Keratoderma: from Chinese Traditional Treatment to Prenatal Diagnosis Using Whole-Exome Sequencing-Plus.","date":"2023","source":"DNA and cell biology","url":"https://pubmed.ncbi.nlm.nih.gov/37566479","citation_count":0,"is_preprint":false},{"pmid":"37443844","id":"PMC_37443844","title":"Correction: Winkler et al. The Adhesion G-Protein-Coupled Receptor GPR115/ADGRF4 Regulates Epidermal Differentiation and Associates with Cytoskeletal KRT1. Cells 2022, 11, 3151.","date":"2023","source":"Cells","url":"https://pubmed.ncbi.nlm.nih.gov/37443844","citation_count":0,"is_preprint":false},{"pmid":null,"id":"bio_10.1101_2025.09.15.676359","title":"Under Pressure: A unique mechanoresponsive mechanism of body site-specific keratin regulation in palmoplantar epidermis","date":"2025-09-17","source":"bioRxiv","url":"https://doi.org/10.1101/2025.09.15.676359","citation_count":0,"is_preprint":true},{"pmid":null,"id":"bio_10.1101_2025.05.01.651662","title":"Modeling epithelial and endothelial cell tropism for SARS-CoV-2 through restricted transgenic hACE2 expression in mice","date":"2025-05-02","source":"bioRxiv","url":"https://doi.org/10.1101/2025.05.01.651662","citation_count":0,"is_preprint":true},{"pmid":null,"id":"bio_10.1101_2025.01.16.633456","title":"A Single-Cell Atlas of the Upper Respiratory Epithelium Reveals Heterogeneity in Cell Types and Patterning Strategies","date":"2025-01-21","source":"bioRxiv","url":"https://doi.org/10.1101/2025.01.16.633456","citation_count":0,"is_preprint":true},{"pmid":null,"id":"bio_10.1101_2024.12.27.630544","title":"Keratin 16 spatially inhibits type I interferon responses in stressed and diseased skin","date":"2024-12-28","source":"bioRxiv","url":"https://doi.org/10.1101/2024.12.27.630544","citation_count":0,"is_preprint":true},{"pmid":null,"id":"bio_10.1101_2024.07.13.603037","title":"Differential expression of keratin and keratin associated proteins are linked with hair loss condition in spontaneously mutated inbred mice","date":"2024-07-17","source":"bioRxiv","url":"https://doi.org/10.1101/2024.07.13.603037","citation_count":0,"is_preprint":true},{"pmid":null,"id":"bio_10.1101_2024.08.10.607363","title":"Single cell RNA sequencing reveals shifts in cell maturity and function of endogenous and infiltrating cell types in response to acute intervertebral disc injury","date":"2024-08-10","source":"bioRxiv","url":"https://doi.org/10.1101/2024.08.10.607363","citation_count":0,"is_preprint":true}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":20249,"output_tokens":2150,"usd":0.046498},"stage2":{"model":"claude-opus-4-6","input_tokens":5438,"output_tokens":2583,"usd":0.137648},"total_usd":0.184146,"stage1_batch_id":"msgbatch_01Mgbec4vM6c9vXht7JVJzss","stage2_batch_id":"msgbatch_01JkuuH5RB2BdJNsgnhjbC6s","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2015,\n      \"finding\": \"KRT1 C-terminal frameshift mutations cause partial collapse of the cytoplasmic intermediate filament network and mislocalization of mutant KRT1 to the nucleus; reversion of these mutations occurs via mitotic recombination, explaining the revertant mosaicism seen in ichthyosis with confetti.\",\n      \"method\": \"Clinical genetics, histopathology, cell biology (immunofluorescence showing nuclear mislocalization), and molecular analysis of revertant clones demonstrating mitotic recombination\",\n      \"journal\": \"The Journal of clinical investigation\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — multiple orthogonal methods (molecular genetics, immunofluorescence, revertant clone analysis) in a single rigorous study\",\n      \"pmids\": [\"25774499\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2003,\n      \"finding\": \"KRT1 and KRT10 form heterodimers that constitute the intermediate filaments in suprabasal keratinocytes committed to terminal differentiation; mutations in the conserved 1A and 2B helical rod domains disrupt this function and cause epidermolytic hyperkeratosis.\",\n      \"method\": \"Genetic analysis of patients combined with structural domain mapping of mutations; functional inference from dominant-negative phenotypes\",\n      \"journal\": \"The Journal of investigative dermatology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 — genetic/mutational analysis in patients, replicated across multiple studies but no in vitro reconstitution in this specific paper\",\n      \"pmids\": [\"14708600\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"Loss of KRT1 via homozygous nonsense mutations (leading to nonsense-mediated mRNA decay and absence of KRT1 protein) results in epidermolytic palmoplantar keratoderma, with compensatory upregulation of keratin 2 (which forms heterodimers with keratin 10), while keratin 9 shows aberrant clumped distribution in palmar skin.\",\n      \"method\": \"Next-generation sequencing, qRT-PCR, immunofluorescence, Western blot, transmission electron microscopy\",\n      \"journal\": \"Journal of the European Academy of Dermatology and Venereology : JEADV\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — multiple orthogonal methods (molecular, protein, ultrastructural) in a single study; moderate evidence for compensatory heterodimer formation\",\n      \"pmids\": [\"35490383\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"The adhesion G-protein-coupled receptor GPR115/ADGRF4 associates with KRT1/KRT10-positive keratin filaments intracellularly and regulates epidermal differentiation; deletion of ADGRF4 in keratinocytes abrogates KRT1 expression and reduces keratinocyte stratification.\",\n      \"method\": \"Organotypic culture, ADGRF4 CRISPR deletion in HaCaT cells, immunofluorescence colocalization of GPR115 with KRT1/10 filaments\",\n      \"journal\": \"Cells\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — loss-of-function with defined cellular phenotype and direct colocalization, single lab\",\n      \"pmids\": [\"36231117\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"CEA (carcinoembryonic antigen) directly binds KRT1, and this interaction activates the PI3K/AKT signaling pathway, contributing to oxaliplatin resistance in gastric cancer; competitive inhibition of the CEA-KRT1 interaction with the small molecule evacetrapib reverses resistance.\",\n      \"method\": \"Proteomic analysis, Co-IP, GST pull-down, immunofluorescence colocalization, virtual screening, surface plasmon resonance, in vitro and in vivo drug sensitivity assays\",\n      \"journal\": \"Drug resistance updates\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — reciprocal binding confirmed by Co-IP and GST pull-down with functional downstream pathway validation, single lab\",\n      \"pmids\": [\"39644827\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"USP28 (a deubiquitinating enzyme) directly interacts with KRT1 and exerts deubiquitination on KRT1, thereby maintaining KRT1 protein stability; USP28 knockdown leads to KRT1 destabilization and decreased IFITM3 expression in hepatocellular carcinoma cells.\",\n      \"method\": \"IP-MS analysis, co-immunoprecipitation, immunofluorescence, USP28 knockdown/overexpression with functional assays, xenograft mouse model\",\n      \"journal\": \"Experimental cell research\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — interaction confirmed by IP-MS and Co-IP, deubiquitination inferred from protein stability changes upon knockdown, single lab\",\n      \"pmids\": [\"40222446\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"CD63 directly interacts with KRT1 (identified by mass spectrometry and co-immunoprecipitation), and this interaction mediates KRT1-dependent cell cycle arrest to suppress metastasis in head and neck squamous cell carcinoma.\",\n      \"method\": \"Mass spectrometry, co-immunoprecipitation, in vitro and in vivo functional assays (overexpression/knockdown)\",\n      \"journal\": \"Heliyon\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — interaction confirmed by MS and Co-IP with functional phenotype, single lab\",\n      \"pmids\": [\"37455999\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"miR-107 directly binds the KRT1 3'UTR (validated by dual-luciferase reporter assay); miR-107-mediated suppression of KRT1 activates the Notch signaling pathway in vascular endothelial cells, reducing inflammation and ER stress in a coronary atherosclerosis model.\",\n      \"method\": \"Dual-luciferase reporter assay, ectopic expression and depletion experiments, Western blot, ELISA, flow cytometry in mouse atherosclerosis model\",\n      \"journal\": \"Journal of cellular physiology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — direct binding confirmed by luciferase assay with functional downstream validation, single lab\",\n      \"pmids\": [\"30548623\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"KRT1 silencing activates the Notch signaling pathway (increased NICD and Hes1 expression) in myocardial cells, reducing apoptosis and improving cell proliferation; this effect is abolished by Notch pathway inhibition with DAPT, placing KRT1 upstream of Notch in cardiomyocyte injury context.\",\n      \"method\": \"siRNA-mediated KRT1 knockdown, Notch activator (Jagged1) and inhibitor (DAPT) treatment, Western blot, MTT assay, flow cytometry in mouse MIRI model\",\n      \"journal\": \"Journal of cellular physiology\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 — epistasis placement using inhibitor/activator without reconstitution; single lab, unusual cell context for a structural keratin\",\n      \"pmids\": [\"30191968\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"KRT1 encodes a type II intermediate filament keratin that heterodimerizes with KRT10 (and KRT9 in palmoplantar skin) to form the 10-nm cytoskeletal filament network in suprabasal keratinocytes; disease-causing mutations in the conserved rod domain act dominantly to collapse this network, while KRT1 protein stability is regulated by USP28-mediated deubiquitination, and KRT1 can also function as a cell-surface binding partner for CEA to activate PI3K/AKT signaling and interact with CD63 to mediate cell cycle arrest.\"\n}\n```","stage2_raw":"```json\n{\n  \"mechanistic_narrative\": \"KRT1 is a type II intermediate filament keratin that heterodimerizes with KRT10 to build the 10-nm cytoskeletal network of suprabasal keratinocytes undergoing terminal differentiation, with KRT9 serving as an additional partner in palmoplantar epidermis. Dominant missense mutations in the conserved 1A and 2B rod domains collapse the filament network and cause epidermolytic hyperkeratosis, whereas C-terminal frameshift mutations mislocalise mutant KRT1 to the nucleus and underlie ichthyosis with confetti, in which revertant mosaicism arises through mitotic recombination; homozygous loss-of-function mutations produce epidermolytic palmoplantar keratoderma with compensatory upregulation of keratin 2 [PMID:14708600, PMID:25774499, PMID:35490383]. KRT1 protein stability is maintained by USP28-mediated deubiquitination, and KRT1 can engage non-cytoskeletal signalling partners: binding CEA activates PI3K/AKT signalling and contributes to chemoresistance, while interaction with CD63 mediates cell-cycle arrest in squamous carcinoma cells [PMID:40222446, PMID:39644827, PMID:37455999]. KRT1 expression in suprabasal keratinocytes is regulated in part by the adhesion GPCR ADGRF4, whose deletion abrogates KRT1 expression and impairs epidermal stratification [PMID:36231117].\",\n  \"teleology\": [\n    {\n      \"year\": 2003,\n      \"claim\": \"Establishing KRT1's core function: mapping of patient mutations to the conserved 1A and 2B helical rod domains demonstrated that KRT1/KRT10 heterodimers are essential structural units of suprabasal intermediate filaments and that their disruption causes epidermolytic hyperkeratosis.\",\n      \"evidence\": \"Genotype–phenotype analysis of multiple epidermolytic hyperkeratosis families with domain mapping of KRT1 mutations\",\n      \"pmids\": [\"14708600\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No in vitro reconstitution of mutant vs. wild-type filament assembly in this study\",\n        \"Quantitative structure–function relationship between specific rod-domain residues and filament stability not resolved\"\n      ]\n    },\n    {\n      \"year\": 2015,\n      \"claim\": \"Resolving how C-terminal mutations produce a distinct disease: frameshift mutations in the KRT1 tail domain were shown to cause nuclear mislocalization and partial filament collapse rather than complete network disruption, explaining the milder ichthyosis with confetti phenotype and its characteristic revertant mosaicism via mitotic recombination.\",\n      \"evidence\": \"Immunofluorescence of patient keratinocytes showing nuclear KRT1, molecular analysis of revertant clones demonstrating loss-of-heterozygosity by mitotic recombination\",\n      \"pmids\": [\"25774499\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Mechanism by which C-terminal frameshift directs nuclear import is unknown\",\n        \"Whether nuclear KRT1 has any functional consequence beyond filament loss is untested\"\n      ]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"Extending KRT1's reach beyond structural roles: miR-107 was shown to directly target the KRT1 3ʹ-UTR, and KRT1 suppression activated Notch signalling in vascular endothelial cells and cardiomyocytes, suggesting KRT1 can modulate signalling pathways in non-epithelial contexts.\",\n      \"evidence\": \"Dual-luciferase reporter assay confirming miR-107 binding to KRT1 3ʹ-UTR; siRNA knockdown with Notch pathway readouts (NICD, Hes1) and DAPT rescue in mouse atherosclerosis and MIRI models\",\n      \"pmids\": [\"30548623\", \"30191968\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"KRT1 expression in vascular endothelial cells and cardiomyocytes is atypical for a suprabasal keratin; independent confirmation of endogenous expression in these cell types is lacking\",\n        \"Epistasis with Notch was inferred from inhibitor experiments without direct biochemical mechanism\",\n        \"Single-lab findings not replicated\"\n      ]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Defining consequences of complete KRT1 loss: homozygous nonsense mutations causing nonsense-mediated decay demonstrated that KRT1 absence triggers compensatory KRT2/KRT10 pairing and aberrant KRT9 distribution, resulting in palmoplantar keratoderma rather than generalised epidermolysis.\",\n      \"evidence\": \"NGS, qRT-PCR, Western blot, immunofluorescence, and TEM in patient skin biopsies\",\n      \"pmids\": [\"35490383\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Whether KRT2/KRT10 filaments fully substitute mechanically for KRT1/KRT10 is unknown\",\n        \"Why the phenotype is restricted to palmoplantar skin despite widespread KRT1 expression is unexplained\"\n      ]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Identifying an upstream regulator of KRT1 expression: ADGRF4 (GPR115) was shown to associate with KRT1/KRT10 filaments and to be required for KRT1 expression and keratinocyte stratification.\",\n      \"evidence\": \"CRISPR deletion of ADGRF4 in HaCaT cells with organotypic culture; immunofluorescence colocalization\",\n      \"pmids\": [\"36231117\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Signal transduction pathway between ADGRF4 and KRT1 transcription is uncharacterised\",\n        \"Physical association versus functional regulation not fully separated\"\n      ]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Revealing a non-cytoskeletal signalling role: CD63 was identified as a direct KRT1 interactor whose binding mediates KRT1-dependent cell-cycle arrest and metastasis suppression in head and neck squamous cell carcinoma.\",\n      \"evidence\": \"Mass spectrometry and co-immunoprecipitation with overexpression/knockdown phenotypic assays in vitro and in vivo\",\n      \"pmids\": [\"37455999\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Structural basis of KRT1–CD63 interaction is unknown\",\n        \"Whether this interaction occurs in normal epithelial differentiation or only in carcinoma is untested\"\n      ]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Defining a signalling axis through which KRT1 promotes chemoresistance: CEA was shown to bind KRT1 directly and activate PI3K/AKT signalling; competitive disruption of this interaction by evacetrapib restored oxaliplatin sensitivity in gastric cancer.\",\n      \"evidence\": \"Co-IP, GST pull-down, SPR for direct binding; virtual screening and in vivo xenograft drug sensitivity assays\",\n      \"pmids\": [\"39644827\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Binding interface and stoichiometry of CEA–KRT1 complex not determined\",\n        \"Mechanism linking CEA–KRT1 binding to PI3K activation is undefined\"\n      ]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Establishing post-translational control of KRT1 stability: USP28 was identified as a deubiquitinase that directly interacts with and stabilises KRT1 protein, linking KRT1 turnover to the ubiquitin–proteasome system.\",\n      \"evidence\": \"IP-MS and co-immunoprecipitation; USP28 knockdown/overexpression with protein stability assays in hepatocellular carcinoma cells and xenografts\",\n      \"pmids\": [\"40222446\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Specific ubiquitin linkage type and lysine residues on KRT1 targeted by USP28 are not mapped\",\n        \"E3 ligase responsible for KRT1 ubiquitination is unknown\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The structural basis of KRT1's non-filament signalling interactions (with CEA, CD63, and Notch pathway components) and how these are coordinated with its primary cytoskeletal role remain unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No atomic-resolution structure of KRT1 in complex with any signalling partner\",\n        \"Whether cytoplasmic soluble KRT1 pool versus filament-incorporated KRT1 mediates signalling is unknown\",\n        \"Interplay between USP28-mediated KRT1 stabilisation and KRT1's signalling functions has not been tested\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0005198\", \"supporting_discovery_ids\": [0, 1, 2]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005856\", \"supporting_discovery_ids\": [0, 1, 2, 3]},\n      {\"term_id\": \"GO:0005634\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-162582\", \"supporting_discovery_ids\": [4, 6]},\n      {\"term_id\": \"R-HSA-1266738\", \"supporting_discovery_ids\": [1, 2, 3]}\n    ],\n    \"complexes\": [\n      \"KRT1/KRT10 heterodimer\",\n      \"KRT1/KRT9 heterodimer\"\n    ],\n    \"partners\": [\n      \"KRT10\",\n      \"KRT9\",\n      \"USP28\",\n      \"CD63\",\n      \"CEACAM5\",\n      \"ADGRF4\"\n    ],\n    \"other_free_text\": []\n  }\n}\n```"}