{"gene":"CLTA","run_date":"2026-06-09T22:57:18","timeline":{"discoveries":[{"year":2005,"finding":"CLTA (clathrin light chain A, LCa) and CLTB (LCb) genes arose by localized duplication during chordate evolution (~510-600 million years ago), independently from the heavy chain duplication. CHC17 (the ubiquitous clathrin heavy chain) is bound and regulated by both LCa and LCb, whereas the paralogous CHC22 does not functionally interact with either light chain isoform.","method":"Phylogenetic and sequence analysis; functional interaction assays distinguishing CHC17 vs CHC22 binding to CLCa/CLCb","journal":"Proceedings of the National Academy of Sciences of the United States of America","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — functional interaction data combined with evolutionary sequence analysis, single study","pmids":["15883369"],"is_preprint":false},{"year":1994,"finding":"CLTA maps to chromosome 12q23-q24, and the neuron-specific insertion sequences of CLCa are encoded by two discrete exons (the first homologous to the single neuron-specific exon of LCb), establishing that tissue-specific CLCa isoforms are generated by alternative mRNA splicing.","method":"Chromosomal mapping; isolation and characterization of partial genomic clones; exon structure analysis","journal":"Genomics","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct genomic cloning and exon characterization, single lab","pmids":["7713494"],"is_preprint":false},{"year":2010,"finding":"CLTA (clathrin light chain A) directly interacts with the mitotic arrest deficient protein MAD2B (MAD2L2) during the G2/M phase of the cell cycle. MAD2B and CLTA co-localize at the mitotic spindle, and siRNA-mediated depletion of MAD2B causes CLTA to redistribute away from the spindle and results in a marked increase in misaligned chromosomes.","method":"Yeast two-hybrid screen; GST pull-down; endogenous co-immunoprecipitation; confocal laser scanning microscopy; siRNA knockdown","journal":"PloS one","confidence":"High","confidence_rationale":"Tier 2 / Strong — multiple orthogonal methods (yeast two-hybrid, GST pulldown, reciprocal co-IP, co-localization, siRNA phenotype) in a single study","pmids":["21152103"],"is_preprint":false},{"year":2019,"finding":"CLCa (CLTA), but not CLCb (CLTB), is uniquely required for efficient cell spreading and migration. Selective depletion of CLCa reduced isotropic spreading by 60–80% and wound closure/motility by ~50%. CLCa is required for effective targeting of FAK and paxillin to the adherent surface of spreading cells, for integrin-mediated activation of Src, FAK, and paxillin, and for maturation of focal adhesions. CLCa depletion also blocked the interaction of clathrin with the WAVE nucleation-promoting complex and altered actin distribution. CLCa is preferentially recruited to budding protrusions.","method":"siRNA selective depletion of CLCa vs CLCb; live-cell spreading assays; wound closure/motility assays; immunofluorescence; co-immunoprecipitation (clathrin-WAVE complex); surface integrin quantification","journal":"Journal of cell science","confidence":"High","confidence_rationale":"Tier 2 / Strong — multiple orthogonal methods (selective siRNA, functional assays, co-IP, localization), isoform specificity rigorously demonstrated","pmids":["30975920"],"is_preprint":false},{"year":2020,"finding":"Neuronal clathrin light chain mixtures (nCLCa encoded by CLTA and nCLCb encoded by CLTB) are more effective in membrane deformation than clathrin containing single neuronal isoforms alone. CLC splice variants differentially influence clathrin knee conformation within assemblies. Mice lacking only nCLCa (CLTA-null) show increased synaptic vesicle numbers and restore normal neurotransmission, whereas mice lacking nCLCb have a reduced synaptic vesicle pool and impaired neurotransmission. Both nCLCa-null and nCLCb-null neurons are defective in synaptic vesicle replenishment.","method":"Biophysical characterization of clathrin assemblies with individual CLC variants; electrophysiological recordings in neurons from CLTA-knockout and CLTB-knockout mice; electron microscopy of synaptic vesicle pools","journal":"Proceedings of the National Academy of Sciences of the United States of America","confidence":"High","confidence_rationale":"Tier 1-2 / Strong — in vitro reconstitution of membrane deformation, knockout mouse models, electrophysiology, multiple orthogonal methods","pmids":["32907943"],"is_preprint":false},{"year":2017,"finding":"PFOA exposure in mouse testes affects endocytosis, and CLTA is a direct target of miR-133b-3p as validated by transfection and luciferase activity assay, suggesting post-transcriptional regulation of CLTA by miR-133b-3p.","method":"miRNA array; TaqMan qPCR; immunohistochemistry; Western blot; transfection with miR-133b-3p; luciferase reporter assay","journal":"Toxicology and applied pharmacology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct luciferase reporter validation of miRNA-CLTA interaction, single lab, in mouse testis context","pmids":["28126411"],"is_preprint":false},{"year":2022,"finding":"CPT1A-mediated fatty acid oxidation promotes upregulation of CLTA and CLTC expression in osteoclast precursors through enhanced binding of transcription factor C/EBPβ to the CLTA and CLTC promoters. This drives clathrin-dependent endocytosis, attenuates fusion receptors at the membrane, and contributes to increased podosome formation and osteoclast precursor fusion in rheumatoid arthritis.","method":"ChIP assay (C/EBPβ binding to CLTA/CLTC promoters); Western blot; functional endocytosis assays; podosome and fusion assays in RA patient-derived cells","journal":"Frontiers in immunology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — ChIP for promoter binding and functional assays in disease-relevant cells, single lab","pmids":["35273614"],"is_preprint":false},{"year":2023,"finding":"CLTA in hepatocellular carcinoma (HCC) cells facilitates uptake of small extracellular vesicles (sEVs) by increasing expression of CAPG (capping actin protein gelsolin-like), thereby promoting proliferation, motility, and invasiveness of HCC cells. The CLTA inhibitor Pitstop 2 alone or combined with sorafenib attenuated tumor growth in patient-derived xenografts.","method":"PKH67-sEV uptake assay; MTT; colony formation; transwell assays; mass spectrometry identification of downstream effector CAPG; siRNA knockdown; Pitstop 2 pharmacological inhibition; PDX mouse model","journal":"Hepatology international","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — multiple functional assays and mass spectrometry identification of effector, single lab","pmids":["37354358"],"is_preprint":false},{"year":2023,"finding":"HCC-derived sEV-CLTA remodels the microvascular niche by stabilizing and upregulating basigin (BSG) in endothelial cells, thereby disrupting endothelial integrity and inducing angiogenesis. Circulating sEV CLTA levels were elevated in HCC patients and decreased after surgery.","method":"ELISA of circulating sEVs from HCC patients; tube formation; sprouting; trans-endothelial invasion and vascular leakiness assays; mass spectrometry identification of BSG as downstream effector; PDX mouse model with BSG inhibitor SP-8356","journal":"Journal of extracellular vesicles","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — mass spectrometry effector identification, multiple functional assays in endothelial cells, in vivo PDX model, single lab","pmids":["37606345"],"is_preprint":false},{"year":2018,"finding":"CRISPR/Cas9 was used to fluorescently label the C-terminus of endogenous CLTA in human iPSCs, generating a functional reporter line that maintains normal karyotype and differentiation potential, enabling visualization of endogenous clathrin trafficking in varied cell types derived from iPSCs.","method":"CRISPR/Cas9 genomic editing; fluorescence-activated cell sorting; karyotyping; differentiation assays; live fluorescence imaging of clathrin-coated pits","journal":"Stem cell research","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — endogenous tagging with functional validation in iPSC model, single lab, demonstrates CME function of tagged protein","pmids":["30340091"],"is_preprint":false},{"year":2022,"finding":"An eGFP-Clta fusion knock-in reporter mouse was generated by endogenous tagging of clathrin light chain a. The fusion protein is expressed in all tissues in a cell-specific manner and functionally recruits to nanobeads (validated by TIRF microscopy), enabling intravital 2-photon tracking of endocytic dynamics in living mice.","method":"Endogenous knock-in mouse model; TIRF microscopy nanobead recruitment assay; intravital 2-photon microscopy; fluorescence microscopy across tissues","journal":"PloS one","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — endogenous tagging with functional TIRF validation and in vivo imaging, single lab","pmids":["36149863"],"is_preprint":false},{"year":2025,"finding":"GPN3 interacts directly with CLTA (clathrin light chain A) as well as AP2B1 and AP2S1, and upregulation of GPN3 inhibits clathrin-coated pit invagination. GPN3 regulates co-localization of EGFR with CLTA and EGFR localization in early endosomes upon EGF stimulation, reducing endocytic levels of EGFR and prolonging its membrane-proximal signaling.","method":"Co-immunoprecipitation; clathrin-coated pit invagination assays; co-localization imaging of EGFR and CLTA; early endosome fractionation; GPN3 overexpression and knockdown; GTP-dependence testing","journal":"Cell death discovery","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — reciprocal Co-IP and functional co-localization assays showing CLTA-GPN3 interaction with defined endocytic phenotype, single lab","pmids":["39893205"],"is_preprint":false},{"year":2025,"finding":"CLTA silencing by siRNA in osteosarcoma cell lines (MG63 and U2OS) led to significant reductions in cell proliferation, colony formation, and migration, establishing a direct functional role for CLTA in osteosarcoma cell behavior.","method":"siRNA knockdown; MTT/cell proliferation assay; colony formation assay; wound healing migration assay","journal":"The journal of gene medicine","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single lab, standard functional knockdown assays without mechanistic pathway placement beyond phenotype description","pmids":["41236100"],"is_preprint":false},{"year":2026,"finding":"In a rat controlled cortical impact (CCI) TBI model, hippocampal abundance of clathrin light chain (including CLTA-associated protein complex) was decreased at 14 days post-injury, temporally associated with neurobehavioral impairments. In severe TBI patients, a CLTA SNP minor allele (rs4879960) was associated with improved outcomes on the Glasgow Outcome Scale and Disability Rating Scale.","method":"Western blot of hippocampal CME proteins in CCI rats; neurobehavioral testing; human SNP genotyping correlated with clinical outcomes","journal":"Molecular neurobiology","confidence":"Low","confidence_rationale":"Tier 3 / Weak — associational protein abundance changes in rat model with behavioral correlation; human SNP association without mechanistic dissection","pmids":["41673368"],"is_preprint":false}],"current_model":"CLTA encodes clathrin light chain A (CLCa), a structural and regulatory subunit of the clathrin triskelion that associates with the ubiquitous clathrin heavy chain CHC17; CLCa has isoform-specific functions distinct from CLCb, including a unique role in promoting cell spreading, migration, and focal adhesion maturation through FAK/Src/paxillin signaling and interaction with the WAVE actin nucleation complex, a role in synaptic vesicle replenishment where balanced co-expression of neuronal CLCa and CLCb isoforms optimizes membrane deformation and neurotransmission, a mitotic function via direct interaction with MAD2B at the spindle to maintain chromosome alignment, and roles in clathrin-mediated endocytosis that impact EGFR trafficking, sEV uptake (via CAPG upregulation in HCC), and microvascular niche remodeling (via BSG stabilization); additionally, CLTA expression is transcriptionally regulated by C/EBPβ downstream of fatty acid oxidation and post-transcriptionally targeted by miR-133b-3p."},"narrative":{"mechanistic_narrative":"CLTA encodes clathrin light chain A (CLCa), a regulatory subunit of the clathrin triskelion that binds and regulates the ubiquitous clathrin heavy chain CHC17, an interaction that arose by light-chain gene duplication independent of heavy-chain duplication during chordate evolution; the paralogous CHC22 does not engage either light chain [PMID:15883369]. Tissue-specific CLCa isoforms are generated by alternative splicing of discrete neuron-specific exons [PMID:7713494]. CLCa has functions distinct from its paralog CLCb: it is uniquely required for cell spreading and migration, controlling targeting of FAK and paxillin to the adherent surface, integrin-mediated activation of Src/FAK/paxillin, focal adhesion maturation, and the interaction of clathrin with the WAVE actin nucleation-promoting complex [PMID:30975920]. In neurons, balanced co-assembly of CLCa and CLCb isoforms tunes clathrin knee conformation and membrane deformation, with CLTA-null mice showing increased synaptic vesicle numbers, and both isoforms required for synaptic vesicle replenishment [PMID:32907943]. Beyond endocytosis, CLCa directly interacts with MAD2B (MAD2L2) at the mitotic spindle during G2/M, where MAD2B depletion redistributes CLCa from the spindle and produces chromosome misalignment [PMID:21152103]. In clathrin-mediated endocytosis, CLCa cooperates with the AP2 complex and is regulated by GPN3, which controls EGFR co-localization with CLCa and EGFR endocytic trafficking [PMID:39893205]. CLTA expression is transcriptionally driven by C/EBPβ downstream of fatty acid oxidation [PMID:35273614] and post-transcriptionally targeted by miR-133b-3p [PMID:28126411]. CLTA contributes to tumor cell behavior in hepatocellular carcinoma, where it promotes small extracellular vesicle uptake via CAPG upregulation [PMID:37354358] and remodels the microvascular niche by stabilizing basigin (BSG) [PMID:37606345].","teleology":[{"year":1994,"claim":"Establishing the genomic architecture of CLTA defined how a single gene produces tissue-specific light chain isoforms, a prerequisite for understanding functional divergence.","evidence":"Chromosomal mapping and genomic exon-structure analysis of CLTA","pmids":["7713494"],"confidence":"Medium","gaps":["Functional consequences of the neuron-specific exons not addressed","No protein-level activity assigned to splice variants at this stage"]},{"year":2005,"claim":"Tracing the evolutionary origin of CLTA/CLTB and their heavy-chain binding specificity established which heavy chain CLCa actually regulates, separating it from the non-interacting CHC22 paralog.","evidence":"Phylogenetic/sequence analysis with CHC17-vs-CHC22 functional interaction assays","pmids":["15883369"],"confidence":"Medium","gaps":["Does not resolve isoform-specific functional differences between CLCa and CLCb","Structural basis of selective heavy-chain binding not defined"]},{"year":2010,"claim":"Identifying a direct CLCa-MAD2B interaction at the spindle answered whether clathrin light chain has a dedicated mitotic role beyond membrane trafficking.","evidence":"Yeast two-hybrid, GST pull-down, reciprocal co-IP, confocal co-localization, and siRNA in cultured cells","pmids":["21152103"],"confidence":"High","gaps":["Molecular mechanism by which the CLCa-MAD2B complex maintains chromosome alignment unknown","Whether this requires heavy-chain-assembled clathrin not established"]},{"year":2019,"claim":"Selective depletion of CLCa versus CLCb demonstrated that CLCa carries a non-redundant role in adhesion and motility signaling, defining the first clearly isoform-specific cellular function.","evidence":"Isoform-selective siRNA with spreading/migration assays, immunofluorescence, integrin quantification, and clathrin-WAVE co-IP","pmids":["30975920"],"confidence":"High","gaps":["Direct binding interface between CLCa and the WAVE complex not mapped","How CLCa selectively directs FAK/paxillin targeting mechanistically unresolved"]},{"year":2020,"claim":"Reconstitution and knockout-mouse work showed that balanced neuronal CLCa/CLCb co-assembly tunes membrane deformation and synaptic vesicle cycling, explaining why both isoforms are retained.","evidence":"Biophysical assembly assays, electrophysiology and EM in CLTA-null and CLTB-null mice","pmids":["32907943"],"confidence":"High","gaps":["Structural determinant of knee-conformation control by each variant not fully defined","Molecular link between vesicle replenishment defect and isoform identity unresolved"]},{"year":2017,"claim":"Validation of CLTA as a miR-133b-3p target introduced a post-transcriptional layer controlling CLTA abundance in an endocytosis-relevant tissue context.","evidence":"miRNA array, qPCR, and luciferase reporter assay in mouse testis","pmids":["28126411"],"confidence":"Medium","gaps":["Physiological extent of miR-133b-3p control over CLTA in other tissues unknown","Downstream endocytic consequence of CLTA repression not directly tested"]},{"year":2022,"claim":"Linking C/EBPβ to CLTA promoter binding downstream of fatty acid oxidation established a transcriptional input coupling metabolism to clathrin-dependent endocytosis in disease.","evidence":"ChIP, Western blot, and endocytosis/fusion assays in RA patient-derived osteoclast precursors","pmids":["35273614"],"confidence":"Medium","gaps":["Direct demonstration that CLTA induction alone drives the fusion phenotype not isolated from CLTC","Generality beyond osteoclast precursors unknown"]},{"year":2023,"claim":"Two studies defined CLTA-dependent mechanisms in hepatocellular carcinoma — sEV uptake via CAPG and microvascular remodeling via BSG — placing CLTA in tumor progression and providing pharmacological entry points.","evidence":"sEV uptake and invasion assays, mass spectrometry effector identification, Pitstop 2/SP-8356 inhibition, and PDX models","pmids":["37354358","37606345"],"confidence":"Medium","gaps":["Whether CLTA acts as classical clathrin subunit or moonlights in these contexts not resolved","Mechanism of sEV-CLTA cargo delivery to recipient endothelial cells not detailed"]},{"year":2025,"claim":"Identification of GPN3 as a direct CLTA/AP2 interactor that restrains pit invagination connected CLCa to regulated control of EGFR endocytosis and signaling duration.","evidence":"Reciprocal co-IP, pit invagination assays, EGFR-CLTA co-localization and endosome fractionation with GPN3 perturbation","pmids":["39893205"],"confidence":"Medium","gaps":["How GPN3 mechanistically inhibits invagination at the molecular level unclear","Specificity for CLCa versus CLCb-containing coats not tested"]},{"year":2025,"claim":"Functional knockdown in osteosarcoma lines extended CLTA's pro-tumor role to a second cancer type at the phenotypic level.","evidence":"siRNA knockdown with proliferation, colony formation, and migration assays in MG63 and U2OS cells","pmids":["41236100"],"confidence":"Low","gaps":["Standard knockdown phenotype without mechanistic pathway placement","No effector or signaling axis identified in this context"]},{"year":2026,"claim":"Associational data linked clathrin light chain abundance and a CLTA SNP to TBI outcomes, raising clathrin trafficking as a candidate factor in neural injury recovery.","evidence":"Western blot in rat CCI model with behavioral testing and human CLTA SNP-outcome genotyping","pmids":["41673368"],"confidence":"Low","gaps":["Associational only; no causal mechanism for the rs4879960 effect","CLTA-specific contribution not separated from general clathrin complex changes"]},{"year":null,"claim":"How CLCa's distinct functions — adhesion signaling, mitotic spindle activity, neuronal membrane deformation, and cancer-associated trafficking — are molecularly partitioned through isoform-specific sequence features and binding partners remains unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No structural model linking CLCa-specific exons to its unique functions","Whether mitotic and adhesion roles depend on assembled clathrin coats versus free light chain unknown"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0005198","term_label":"structural molecule activity","supporting_discovery_ids":[0,4]},{"term_id":"GO:0060090","term_label":"molecular adaptor activity","supporting_discovery_ids":[3,11]},{"term_id":"GO:0008092","term_label":"cytoskeletal protein binding","supporting_discovery_ids":[3]}],"localization":[{"term_id":"GO:0005886","term_label":"plasma membrane","supporting_discovery_ids":[3,10,11]},{"term_id":"GO:0005815","term_label":"microtubule organizing center","supporting_discovery_ids":[2]},{"term_id":"GO:0031410","term_label":"cytoplasmic vesicle","supporting_discovery_ids":[4,9]},{"term_id":"GO:0005768","term_label":"endosome","supporting_discovery_ids":[11]}],"pathway":[{"term_id":"R-HSA-5653656","term_label":"Vesicle-mediated transport","supporting_discovery_ids":[4,9,11]},{"term_id":"R-HSA-1640170","term_label":"Cell Cycle","supporting_discovery_ids":[2]},{"term_id":"R-HSA-112316","term_label":"Neuronal System","supporting_discovery_ids":[4]}],"complexes":["clathrin triskelion (CHC17/clathrin coat)"],"partners":["CLTC","MAD2L2","GPN3","AP2B1","AP2S1"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"P09496","full_name":"Clathrin light chain A","aliases":[],"length_aa":248,"mass_kda":27.1,"function":"Clathrin is the major protein of the polyhedral coat of coated pits and vesicles. Acts as a component of the TACC3/ch-TOG/clathrin complex proposed to contribute to stabilization of kinetochore fibers of the mitotic spindle by acting as inter-microtubule bridge (PubMed:15858577, PubMed:21297582)","subcellular_location":"Cytoplasmic vesicle membrane; Membrane, coated pit; Cytoplasm, cytoskeleton, spindle","url":"https://www.uniprot.org/uniprotkb/P09496/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/CLTA","classification":"Not Classified","n_dependent_lines":3,"n_total_lines":1208,"dependency_fraction":0.0024834437086092716},"opencell":{"profiled":true,"resolved_as":"","ensg_id":"ENSG00000122705","cell_line_id":"CID000401","localizations":[{"compartment":"vesicles","grade":3},{"compartment":"cytoplasmic","grade":2},{"compartment":"golgi","grade":2},{"compartment":"membrane","grade":2}],"interactors":[{"gene":"SCYL2","stoichiometry":10.0},{"gene":"CLTC","stoichiometry":10.0},{"gene":"CLTB","stoichiometry":10.0},{"gene":"EDC4","stoichiometry":4.0},{"gene":"CLINT1","stoichiometry":4.0},{"gene":"ARHGAP18","stoichiometry":0.2},{"gene":"CAPZB","stoichiometry":0.2},{"gene":"HSPH1","stoichiometry":0.2},{"gene":"STX10","stoichiometry":0.2},{"gene":"MLK4","stoichiometry":0.2}],"url":"https://opencell.sf.czbiohub.org/target/CID000401","total_profiled":1310},"omim":[{"mim_id":"620664","title":"RHO GUANINE NUCLEOTIDE EXCHANGE FACTOR 37; ARHGEF37","url":"https://www.omim.org/entry/620664"},{"mim_id":"612064","title":"GRB10-INTERACTING GYF PROTEIN 1; GIGYF1","url":"https://www.omim.org/entry/612064"},{"mim_id":"612003","title":"GRB10-INTERACTING GYF PROTEIN 2; GIGYF2","url":"https://www.omim.org/entry/612003"},{"mim_id":"604647","title":"CALCYON; CALY","url":"https://www.omim.org/entry/604647"},{"mim_id":"604464","title":"INTERSECTIN 2; ITSN2","url":"https://www.omim.org/entry/604464"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Supported","locations":[{"location":"Endosomes","reliability":"Supported"},{"location":"Lysosomes","reliability":"Supported"},{"location":"Golgi apparatus","reliability":"Additional"},{"location":"Plasma membrane","reliability":"Additional"},{"location":"Mitotic spindle","reliability":"Additional"},{"location":"Primary cilium","reliability":"Additional"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/CLTA"},"hgnc":{"alias_symbol":["Lca"],"prev_symbol":[]},"alphafold":{"accession":"P09496","domains":[{"cath_id":"-","chopping":"218-248","consensus_level":"medium","plddt":75.3942,"start":218,"end":248},{"cath_id":"1.20.5","chopping":"103-170","consensus_level":"medium","plddt":93.3419,"start":103,"end":170}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/P09496","model_url":"https://alphafold.ebi.ac.uk/files/AF-P09496-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-P09496-F1-predicted_aligned_error_v6.png","plddt_mean":70.12},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=CLTA","jax_strain_url":"https://www.jax.org/strain/search?query=CLTA"},"sequence":{"accession":"P09496","fasta_url":"https://rest.uniprot.org/uniprotkb/P09496.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/P09496/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/P09496"}},"corpus_meta":[{"pmid":"24829760","id":"PMC_24829760","title":"Mechanism of tumor rejection with doublets of CTLA-4, PD-1/PD-L1, or IDO blockade involves restored IL-2 production and proliferation of CD8(+) T cells directly within the tumor microenvironment.","date":"2014","source":"Journal for immunotherapy of cancer","url":"https://pubmed.ncbi.nlm.nih.gov/24829760","citation_count":483,"is_preprint":false},{"pmid":"25642417","id":"PMC_25642417","title":"CTLA-4 and PD-1 Pathway Blockade: Combinations in the Clinic.","date":"2015","source":"Frontiers in oncology","url":"https://pubmed.ncbi.nlm.nih.gov/25642417","citation_count":187,"is_preprint":false},{"pmid":"11807776","id":"PMC_11807776","title":"CTLA-4 regulates cell cycle progression during a primary immune response.","date":"2002","source":"European journal of immunology","url":"https://pubmed.ncbi.nlm.nih.gov/11807776","citation_count":101,"is_preprint":false},{"pmid":"27249713","id":"PMC_27249713","title":"Immune Checkpoint Inhibitors in Brain Metastases: From Biology to Treatment.","date":"2016","source":"American Society of Clinical Oncology educational book. American Society of Clinical Oncology. Annual Meeting","url":"https://pubmed.ncbi.nlm.nih.gov/27249713","citation_count":79,"is_preprint":false},{"pmid":"15841095","id":"PMC_15841095","title":"Association of the CTLA-4 gene with rheumatoid arthritis in Chinese Han population.","date":"2005","source":"European journal of human genetics : EJHG","url":"https://pubmed.ncbi.nlm.nih.gov/15841095","citation_count":74,"is_preprint":false},{"pmid":"25761764","id":"PMC_25761764","title":"Loss of muscleblind-like 1 results in cardiac pathology and persistence of embryonic splice isoforms.","date":"2015","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/25761764","citation_count":69,"is_preprint":false},{"pmid":"32596376","id":"PMC_32596376","title":"High-Throughput Sequencing and Exploration of the lncRNA-circRNA-miRNA-mRNA Network in Type 2 Diabetes Mellitus.","date":"2020","source":"BioMed research international","url":"https://pubmed.ncbi.nlm.nih.gov/32596376","citation_count":62,"is_preprint":false},{"pmid":"18474104","id":"PMC_18474104","title":"Global analysis of aberrant pre-mRNA splicing in glioblastoma using exon expression arrays.","date":"2008","source":"BMC genomics","url":"https://pubmed.ncbi.nlm.nih.gov/18474104","citation_count":57,"is_preprint":false},{"pmid":"28337964","id":"PMC_28337964","title":"Targeting CD47 Enhances the Efficacy of Anti-PD-1 and CTLA-4 in an Esophageal Squamous Cell Cancer Preclinical Model.","date":"2017","source":"Oncology research","url":"https://pubmed.ncbi.nlm.nih.gov/28337964","citation_count":54,"is_preprint":false},{"pmid":"21272569","id":"PMC_21272569","title":"Consequences of metaphase II oocyte cryopreservation on mRNA content.","date":"2011","source":"Cryobiology","url":"https://pubmed.ncbi.nlm.nih.gov/21272569","citation_count":53,"is_preprint":false},{"pmid":"15883369","id":"PMC_15883369","title":"Clathrin heavy and light chain isoforms originated by independent mechanisms of gene duplication during chordate evolution.","date":"2005","source":"Proceedings of the National Academy of Sciences of the United States of America","url":"https://pubmed.ncbi.nlm.nih.gov/15883369","citation_count":52,"is_preprint":false},{"pmid":"16882704","id":"PMC_16882704","title":"CTLA-4 dysregulation of self/tumor-reactive CD8+ T-cell function is CD4+ T-cell dependent.","date":"2006","source":"Blood","url":"https://pubmed.ncbi.nlm.nih.gov/16882704","citation_count":51,"is_preprint":false},{"pmid":"27708711","id":"PMC_27708711","title":"Identification and characterization of putative xylose and cellobiose transporters in Aspergillus nidulans.","date":"2016","source":"Biotechnology for biofuels","url":"https://pubmed.ncbi.nlm.nih.gov/27708711","citation_count":50,"is_preprint":false},{"pmid":"30123922","id":"PMC_30123922","title":"Monitoring of patients with metastatic melanoma treated with immune checkpoint inhibitors using PET-CT.","date":"2018","source":"Cancer immunology, immunotherapy : CII","url":"https://pubmed.ncbi.nlm.nih.gov/30123922","citation_count":50,"is_preprint":false},{"pmid":"20154110","id":"PMC_20154110","title":"Identification and analysis of the biosynthetic gene cluster encoding the thiopeptide antibiotic cyclothiazomycin in Streptomyces hygroscopicus 10-22.","date":"2010","source":"Applied and environmental microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/20154110","citation_count":46,"is_preprint":false},{"pmid":"26019284","id":"PMC_26019284","title":"Induction of Inhibitory Receptors on T Cells During Plasmodium vivax Malaria Impairs Cytokine Production.","date":"2015","source":"The Journal of infectious diseases","url":"https://pubmed.ncbi.nlm.nih.gov/26019284","citation_count":45,"is_preprint":false},{"pmid":"30846179","id":"PMC_30846179","title":"The effects of checkpoint inhibition on head and neck squamous cell carcinoma: A systematic review.","date":"2019","source":"Oral oncology","url":"https://pubmed.ncbi.nlm.nih.gov/30846179","citation_count":39,"is_preprint":false},{"pmid":"34923342","id":"PMC_34923342","title":"The potential role of vitamin C in empowering cancer immunotherapy.","date":"2021","source":"Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie","url":"https://pubmed.ncbi.nlm.nih.gov/34923342","citation_count":38,"is_preprint":false},{"pmid":"19075789","id":"PMC_19075789","title":"Regulatory T cells and allergic disease.","date":"2008","source":"Inflammation & allergy drug targets","url":"https://pubmed.ncbi.nlm.nih.gov/19075789","citation_count":38,"is_preprint":false},{"pmid":"32850353","id":"PMC_32850353","title":"Biological Landscape of Triple Negative Breast Cancers Expressing CTLA-4.","date":"2020","source":"Frontiers in oncology","url":"https://pubmed.ncbi.nlm.nih.gov/32850353","citation_count":35,"is_preprint":false},{"pmid":"30763573","id":"PMC_30763573","title":"Proteomic characterization of early lung response to breast cancer metastasis in mice.","date":"2019","source":"Experimental and molecular pathology","url":"https://pubmed.ncbi.nlm.nih.gov/30763573","citation_count":35,"is_preprint":false},{"pmid":"19952852","id":"PMC_19952852","title":"Novel immunotherapies as potential therapeutic partners for traditional or targeted agents: cytotoxic T-lymphocyte antigen-4 blockade in advanced melanoma.","date":"2010","source":"Melanoma research","url":"https://pubmed.ncbi.nlm.nih.gov/19952852","citation_count":32,"is_preprint":false},{"pmid":"18025169","id":"PMC_18025169","title":"A novel approach to specific allergy treatment: the recombinant allergen-S-layer fusion protein rSbsC-Bet v 1 matures dendritic cells that prime Th0/Th1 and IL-10-producing regulatory T cells.","date":"2007","source":"Journal of immunology (Baltimore, Md. : 1950)","url":"https://pubmed.ncbi.nlm.nih.gov/18025169","citation_count":31,"is_preprint":false},{"pmid":"7512030","id":"PMC_7512030","title":"Expression and function of the costimulatory molecule B7 on murine Langerhans cells: evidence for an alternative CTLA-4 ligand.","date":"1994","source":"European journal of immunology","url":"https://pubmed.ncbi.nlm.nih.gov/7512030","citation_count":30,"is_preprint":false},{"pmid":"32907943","id":"PMC_32907943","title":"Clathrin light chain diversity regulates membrane deformation in vitro and synaptic vesicle formation in vivo.","date":"2020","source":"Proceedings of the National Academy of Sciences of the United States of America","url":"https://pubmed.ncbi.nlm.nih.gov/32907943","citation_count":29,"is_preprint":false},{"pmid":"21152103","id":"PMC_21152103","title":"The mitotic arrest deficient protein MAD2B interacts with the clathrin light chain A during mitosis.","date":"2010","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/21152103","citation_count":28,"is_preprint":false},{"pmid":"31442209","id":"PMC_31442209","title":"A disparate role of RP11-424C20.2/UHRF1 axis through control of tumor immune escape in liver hepatocellular carcinoma and thymoma.","date":"2019","source":"Aging","url":"https://pubmed.ncbi.nlm.nih.gov/31442209","citation_count":27,"is_preprint":false},{"pmid":"23597029","id":"PMC_23597029","title":"The associations between the polymorphisms in the CTLA-4 gene and the risk of Graves' disease in the Chinese population.","date":"2013","source":"BMC medical genetics","url":"https://pubmed.ncbi.nlm.nih.gov/23597029","citation_count":26,"is_preprint":false},{"pmid":"27496128","id":"PMC_27496128","title":"Genome-wide association study revealed genomic regions related to white/red earlobe color trait in the Rhode Island Red chickens.","date":"2016","source":"BMC genetics","url":"https://pubmed.ncbi.nlm.nih.gov/27496128","citation_count":23,"is_preprint":false},{"pmid":"35795667","id":"PMC_35795667","title":"Autoimmune Cytopenias in Common Variable Immunodeficiency Are a Diagnostic and Therapeutic Conundrum: An Update.","date":"2022","source":"Frontiers in immunology","url":"https://pubmed.ncbi.nlm.nih.gov/35795667","citation_count":21,"is_preprint":false},{"pmid":"30975920","id":"PMC_30975920","title":"A unique role for clathrin light chain A in cell spreading and migration.","date":"2019","source":"Journal of cell science","url":"https://pubmed.ncbi.nlm.nih.gov/30975920","citation_count":21,"is_preprint":false},{"pmid":"37606345","id":"PMC_37606345","title":"Clathrin light chain A-enriched small extracellular vesicles remodel microvascular niche to induce hepatocellular carcinoma metastasis.","date":"2023","source":"Journal of extracellular vesicles","url":"https://pubmed.ncbi.nlm.nih.gov/37606345","citation_count":20,"is_preprint":false},{"pmid":"12135671","id":"PMC_12135671","title":"Reduced CTLA-4 protein and messenger RNA expression in umbilical cord blood T lymphocytes.","date":"2002","source":"Experimental hematology","url":"https://pubmed.ncbi.nlm.nih.gov/12135671","citation_count":20,"is_preprint":false},{"pmid":"35273614","id":"PMC_35273614","title":"CPT1A-Mediated Fatty Acid Oxidation Promotes Precursor Osteoclast Fusion in Rheumatoid Arthritis.","date":"2022","source":"Frontiers in immunology","url":"https://pubmed.ncbi.nlm.nih.gov/35273614","citation_count":20,"is_preprint":false},{"pmid":"35488304","id":"PMC_35488304","title":"HOXC6 impacts epithelial-mesenchymal transition and the immune microenvironment through gene transcription in gliomas.","date":"2022","source":"Cancer cell international","url":"https://pubmed.ncbi.nlm.nih.gov/35488304","citation_count":19,"is_preprint":false},{"pmid":"33668701","id":"PMC_33668701","title":"CLTA-4 Expression is Associated with the Maintenance of Chronic Inflammation in Endometriosis and Infertility.","date":"2021","source":"Cells","url":"https://pubmed.ncbi.nlm.nih.gov/33668701","citation_count":18,"is_preprint":false},{"pmid":"33996698","id":"PMC_33996698","title":"Different Apples, Same Tree: Visualizing Current Biological and Clinical Insights into CTLA-4 Insufficiency and LRBA and DEF6 Deficiencies.","date":"2021","source":"Frontiers in pediatrics","url":"https://pubmed.ncbi.nlm.nih.gov/33996698","citation_count":18,"is_preprint":false},{"pmid":"34745002","id":"PMC_34745002","title":"The Upregulation of Molecules Related to Tumor Immune Escape in Human Pituitary Adenomas.","date":"2021","source":"Frontiers in endocrinology","url":"https://pubmed.ncbi.nlm.nih.gov/34745002","citation_count":18,"is_preprint":false},{"pmid":"28155012","id":"PMC_28155012","title":"Immune Checkpoint Blockade and Hematopoietic Stem Cell Transplant.","date":"2017","source":"Current hematologic malignancy reports","url":"https://pubmed.ncbi.nlm.nih.gov/28155012","citation_count":16,"is_preprint":false},{"pmid":"37243227","id":"PMC_37243227","title":"The Role of CTLA-4 in T Cell Exhaustion in Chronic Hepatitis B Virus Infection.","date":"2023","source":"Viruses","url":"https://pubmed.ncbi.nlm.nih.gov/37243227","citation_count":16,"is_preprint":false},{"pmid":"20429425","id":"PMC_20429425","title":"Foxp3 expressing regulatory T-cells in allergic disease.","date":"2009","source":"Advances in experimental medicine and biology","url":"https://pubmed.ncbi.nlm.nih.gov/20429425","citation_count":16,"is_preprint":false},{"pmid":"23289635","id":"PMC_23289635","title":"CTLA-4 polymorphisms and systemic lupus erythematosus: a comprehensive meta-analysis.","date":"2013","source":"Genetic testing and molecular biomarkers","url":"https://pubmed.ncbi.nlm.nih.gov/23289635","citation_count":15,"is_preprint":false},{"pmid":"31435659","id":"PMC_31435659","title":"Immune checkpoint inhibitor-based combinations: is dose escalation mandatory for phase I trials?","date":"2019","source":"Annals of oncology : official journal of the European Society for Medical Oncology","url":"https://pubmed.ncbi.nlm.nih.gov/31435659","citation_count":15,"is_preprint":false},{"pmid":"21620962","id":"PMC_21620962","title":"Cytotoxic T lymphocyte antigen-2 alpha induces apoptosis of murine T-lymphoma cells and cardiac fibroblasts and is regulated by cAMP/PKA.","date":"2011","source":"Cellular signalling","url":"https://pubmed.ncbi.nlm.nih.gov/21620962","citation_count":15,"is_preprint":false},{"pmid":"37354358","id":"PMC_37354358","title":"Clathrin light chain A facilitates small extracellular vesicle uptake to promote hepatocellular carcinoma progression.","date":"2023","source":"Hepatology international","url":"https://pubmed.ncbi.nlm.nih.gov/37354358","citation_count":14,"is_preprint":false},{"pmid":"24138302","id":"PMC_24138302","title":"Kinase inhibitors and immune check-point blockade for the treatment of metastatic melanoma and advanced cancer: synergistic or antagonistic?","date":"2013","source":"Expert opinion on pharmacotherapy","url":"https://pubmed.ncbi.nlm.nih.gov/24138302","citation_count":14,"is_preprint":false},{"pmid":"27012236","id":"PMC_27012236","title":"Lipoteichoic Acid Isolated from Weissella cibaria Increases Cytokine Production in Human Monocyte-Like THP-1 Cells and Mouse Splenocytes.","date":"2016","source":"Journal of microbiology and biotechnology","url":"https://pubmed.ncbi.nlm.nih.gov/27012236","citation_count":13,"is_preprint":false},{"pmid":"7713494","id":"PMC_7713494","title":"Chromosomal location and some structural features of human clathrin light-chain genes (CLTA and CLTB).","date":"1994","source":"Genomics","url":"https://pubmed.ncbi.nlm.nih.gov/7713494","citation_count":12,"is_preprint":false},{"pmid":"15138696","id":"PMC_15138696","title":"Cloning and sequence analysis of a low temperature-induced gene from trifoliate orange with unusual pre-mRNA processing.","date":"2004","source":"Plant cell reports","url":"https://pubmed.ncbi.nlm.nih.gov/15138696","citation_count":12,"is_preprint":false},{"pmid":"28126411","id":"PMC_28126411","title":"Perfluorooctanoic acid affects endocytosis involving clathrin light chain A and microRNA-133b-3p in mouse testes.","date":"2017","source":"Toxicology and applied pharmacology","url":"https://pubmed.ncbi.nlm.nih.gov/28126411","citation_count":12,"is_preprint":false},{"pmid":"15466588","id":"PMC_15466588","title":"Cloning and expression of clt genes encoding milk-clotting proteases from Myxococcus xanthus 422.","date":"2004","source":"Applied and environmental microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/15466588","citation_count":12,"is_preprint":false},{"pmid":"29476189","id":"PMC_29476189","title":"The synergic effects of CTLA-4/Foxp3-related genotypes and chromosomal aberrations on the risk of recurrent spontaneous abortion among a Chinese Han population.","date":"2018","source":"Journal of human genetics","url":"https://pubmed.ncbi.nlm.nih.gov/29476189","citation_count":11,"is_preprint":false},{"pmid":"34224794","id":"PMC_34224794","title":"Genome-wide association study identified INSC gene associated with Trail Making Test Part A and Alzheimer's disease related cognitive phenotypes.","date":"2021","source":"Progress in neuro-psychopharmacology & biological psychiatry","url":"https://pubmed.ncbi.nlm.nih.gov/34224794","citation_count":11,"is_preprint":false},{"pmid":"40127814","id":"PMC_40127814","title":"Pancreatic cancer precursor lesions - Can immunotherapy prevent progression into pancreatic ductal adenocarcinoma?","date":"2025","source":"Cancer letters","url":"https://pubmed.ncbi.nlm.nih.gov/40127814","citation_count":10,"is_preprint":false},{"pmid":"33867351","id":"PMC_33867351","title":"A novel comprehensive immune-related gene signature as a promising survival predictor for the patients with head and neck squamous cell carcinoma.","date":"2021","source":"Aging","url":"https://pubmed.ncbi.nlm.nih.gov/33867351","citation_count":10,"is_preprint":false},{"pmid":"38072196","id":"PMC_38072196","title":"Aberrant follicular regulatory T cells associate with immunoglobulin hyperproduction in nasal polyps with ectopic lymphoid tissues.","date":"2023","source":"The Journal of allergy and clinical immunology","url":"https://pubmed.ncbi.nlm.nih.gov/38072196","citation_count":9,"is_preprint":false},{"pmid":"36467654","id":"PMC_36467654","title":"Transcriptome-based selection and validation of optimal reference genes in perirenal adipose developing of goat (Capra hircus).","date":"2022","source":"Frontiers in veterinary science","url":"https://pubmed.ncbi.nlm.nih.gov/36467654","citation_count":9,"is_preprint":false},{"pmid":"30258189","id":"PMC_30258189","title":"The two phases of the clinical validation of preclinical translational mechanistic research on PDE5 inhibitors since Viagra's advent. A personal perspective.","date":"2018","source":"International journal of impotence research","url":"https://pubmed.ncbi.nlm.nih.gov/30258189","citation_count":8,"is_preprint":false},{"pmid":"40346769","id":"PMC_40346769","title":"Treg Control of CD80/CD86 Expression Mediates Immune System Homeostasis.","date":"2025","source":"European journal of immunology","url":"https://pubmed.ncbi.nlm.nih.gov/40346769","citation_count":7,"is_preprint":false},{"pmid":"32960139","id":"PMC_32960139","title":"Bispecific anti-PD-1/CTLA-4 antibody for advanced solid tumors.","date":"2020","source":"Pharmaceutical patent analyst","url":"https://pubmed.ncbi.nlm.nih.gov/32960139","citation_count":7,"is_preprint":false},{"pmid":"29335768","id":"PMC_29335768","title":"CTLA-4 polymorphisms: influence on transplant-related mortality and survival in children undergoing allogeneic hematopoietic stem cell transplantation.","date":"2018","source":"Journal of cancer research and clinical oncology","url":"https://pubmed.ncbi.nlm.nih.gov/29335768","citation_count":7,"is_preprint":false},{"pmid":"10956161","id":"PMC_10956161","title":"Influence of the hapten conjugation site on the characteristics of antibodies generated against metabolites of clostebol acetate.","date":"2000","source":"Journal of agricultural and food chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/10956161","citation_count":7,"is_preprint":false},{"pmid":"35254172","id":"PMC_35254172","title":"Association of CTLA-4 gene polymorphisms and alopecia areata: a systematic review and meta-analysis.","date":"2022","source":"Biomarkers : biochemical indicators of exposure, response, and susceptibility to chemicals","url":"https://pubmed.ncbi.nlm.nih.gov/35254172","citation_count":6,"is_preprint":false},{"pmid":"37406177","id":"PMC_37406177","title":"Management and outcome of COVID-19 in CTLA-4 insufficiency.","date":"2023","source":"Blood advances","url":"https://pubmed.ncbi.nlm.nih.gov/37406177","citation_count":6,"is_preprint":false},{"pmid":"40075698","id":"PMC_40075698","title":"Current Advances in Immunotherapy Management of Esophageal Cancer.","date":"2025","source":"Cancers","url":"https://pubmed.ncbi.nlm.nih.gov/40075698","citation_count":6,"is_preprint":false},{"pmid":"37371778","id":"PMC_37371778","title":"Proteome Analysis of the Antiproliferative Activity of the Novel Chitooligosaccharide-Gallic Acid Conjugate against the SW620 Colon Cancer Cell Line.","date":"2023","source":"Biomedicines","url":"https://pubmed.ncbi.nlm.nih.gov/37371778","citation_count":6,"is_preprint":false},{"pmid":"31333044","id":"PMC_31333044","title":"Reference Gene Validation for Quantitative Real-time PCR Studies in Amphibian Kidney-derived A6 Epithelial Cells.","date":"2019","source":"Alternatives to laboratory animals : ATLA","url":"https://pubmed.ncbi.nlm.nih.gov/31333044","citation_count":6,"is_preprint":false},{"pmid":"30340091","id":"PMC_30340091","title":"Generation of a CLTA reporter human induced pluripotent stem cell line, CRMi001-A-1, using the CRISPR/Cas9 system to monitor endogenous clathrin trafficking.","date":"2018","source":"Stem cell research","url":"https://pubmed.ncbi.nlm.nih.gov/30340091","citation_count":4,"is_preprint":false},{"pmid":"19187432","id":"PMC_19187432","title":"CLTA-4 blockade in vivo promotes the generation of short-lived effector CD8 T cells and a more persistent central memory CD4 T cell response.","date":"2008","source":"Journal of medical primatology","url":"https://pubmed.ncbi.nlm.nih.gov/19187432","citation_count":4,"is_preprint":false},{"pmid":"41097667","id":"PMC_41097667","title":"A Review of Immunotherapy in Renal Cell Carcinoma: Current Landscape and Future Directions.","date":"2025","source":"Cancers","url":"https://pubmed.ncbi.nlm.nih.gov/41097667","citation_count":4,"is_preprint":false},{"pmid":"36149863","id":"PMC_36149863","title":"A Clathrin light chain A reporter mouse for in vivo imaging of endocytosis.","date":"2022","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/36149863","citation_count":4,"is_preprint":false},{"pmid":"35144391","id":"PMC_35144391","title":"Identification of differentially expressed genes associated with coronary in-stent restenosis by integrated bioinformatics approaches.","date":"2022","source":"Annals of palliative medicine","url":"https://pubmed.ncbi.nlm.nih.gov/35144391","citation_count":4,"is_preprint":false},{"pmid":"14970690","id":"PMC_14970690","title":"Improving the comparative map of porcine chromosome 10 with respect to human chromosomes 1, 9 and 10.","date":"2003","source":"Cytogenetic and genome research","url":"https://pubmed.ncbi.nlm.nih.gov/14970690","citation_count":4,"is_preprint":false},{"pmid":"40372556","id":"PMC_40372556","title":"Identification and functional characterization of hub genes CLTA, EDIL3, HAPLN1, and HIP1 as diagnostic biomarkers and therapeutic targets in thyroid cancer and Hashimoto's thyroiditis.","date":"2025","source":"Clinical and experimental medicine","url":"https://pubmed.ncbi.nlm.nih.gov/40372556","citation_count":3,"is_preprint":false},{"pmid":"24854867","id":"PMC_24854867","title":"Cloning of cDNAs for H1F0, TOP1, CLTA and CDK1 and the effects of cryopreservation on the expression of their mRNA transcripts in yak (Bos grunniens) oocytes.","date":"2014","source":"Cryobiology","url":"https://pubmed.ncbi.nlm.nih.gov/24854867","citation_count":3,"is_preprint":false},{"pmid":"36091483","id":"PMC_36091483","title":"Association of CLTA-4 Gene Polymorphisms with Diabetes Mellitus: A Study Based on the Han Population of Northern China.","date":"2022","source":"Diabetes, metabolic syndrome and obesity : targets and therapy","url":"https://pubmed.ncbi.nlm.nih.gov/36091483","citation_count":3,"is_preprint":false},{"pmid":"39893205","id":"PMC_39893205","title":"GTPase GPN3 facilitates cell proliferation and migration in non-small cell lung cancer by impeding clathrin-mediated endocytosis of EGFR.","date":"2025","source":"Cell death discovery","url":"https://pubmed.ncbi.nlm.nih.gov/39893205","citation_count":3,"is_preprint":false},{"pmid":"38990251","id":"PMC_38990251","title":"Synaptic Vesicle-Related Proteins and Ubiquilin 2 in Cortical Synaptosomes Mediate Cognitive Impairment in Vascular Dementia Rats.","date":"2024","source":"Molecular neurobiology","url":"https://pubmed.ncbi.nlm.nih.gov/38990251","citation_count":3,"is_preprint":false},{"pmid":"33684103","id":"PMC_33684103","title":"A computational study of co-inhibitory immune complex assembly at the interface between T cells and antigen presenting cells.","date":"2021","source":"PLoS computational biology","url":"https://pubmed.ncbi.nlm.nih.gov/33684103","citation_count":3,"is_preprint":false},{"pmid":"16151814","id":"PMC_16151814","title":"Expression analysis of a cold responsive transcript from trifoliate orange by real-time PCR and RT-PCR.","date":"2005","source":"Plant cell reports","url":"https://pubmed.ncbi.nlm.nih.gov/16151814","citation_count":2,"is_preprint":false},{"pmid":"37128592","id":"PMC_37128592","title":"Meta-analysis of the rs231775 locus polymorphism in the CTLA-4 gene and the susceptibility to Graves' disease in children.","date":"2023","source":"Open life sciences","url":"https://pubmed.ncbi.nlm.nih.gov/37128592","citation_count":2,"is_preprint":false},{"pmid":"38674386","id":"PMC_38674386","title":"Early Chronic Fluoxetine Treatment of Ts65Dn Mice Rescues Synaptic Vesicular Deficits and Prevents Aberrant Proteomic Alterations.","date":"2024","source":"Genes","url":"https://pubmed.ncbi.nlm.nih.gov/38674386","citation_count":2,"is_preprint":false},{"pmid":"38401943","id":"PMC_38401943","title":"A simplified protocol for deep quantitative proteomic analysis of gingival crevicular fluid for skeletal maturity indicators.","date":"2024","source":"Analytica chimica acta","url":"https://pubmed.ncbi.nlm.nih.gov/38401943","citation_count":2,"is_preprint":false},{"pmid":"38801311","id":"PMC_38801311","title":"Assessment of differentially expressed genes from in vitro matured human oocytes: A bioinformatics approach.","date":"2024","source":"JBRA assisted reproduction","url":"https://pubmed.ncbi.nlm.nih.gov/38801311","citation_count":1,"is_preprint":false},{"pmid":"21528289","id":"PMC_21528289","title":"Effective introduction of T cell costimulatory molecules into virus modified tumor cell vaccines by modification with bispecific antibodies.","date":"1997","source":"International journal of oncology","url":"https://pubmed.ncbi.nlm.nih.gov/21528289","citation_count":1,"is_preprint":false},{"pmid":"40791155","id":"PMC_40791155","title":"Identification and validation of TUBB, CLTA, and FBXL5 as potential diagnostic markers of postmenopausal osteoporosis.","date":"2025","source":"Biomolecules & biomedicine","url":"https://pubmed.ncbi.nlm.nih.gov/40791155","citation_count":0,"is_preprint":false},{"pmid":"41236100","id":"PMC_41236100","title":"Molecular Crosstalk Between Osteoporosis and Osteosarcoma: Identification of Common Diagnostic Markers and Therapeutic Targets.","date":"2025","source":"The journal of gene medicine","url":"https://pubmed.ncbi.nlm.nih.gov/41236100","citation_count":0,"is_preprint":false},{"pmid":"41673368","id":"PMC_41673368","title":"Traumatic Brain Injury and Endocytosis: Reduced Rodent Hippocampal Endocytosis Proteins and Human Clathrin Light Chain Polymorphisms Are Associated with Impaired Neurological Outcomes After TBI.","date":"2026","source":"Molecular neurobiology","url":"https://pubmed.ncbi.nlm.nih.gov/41673368","citation_count":0,"is_preprint":false},{"pmid":"41483743","id":"PMC_41483743","title":"Optimizing the resolution-fidelity trade-off in SRRF nanoscopy for live-cell clathrin imaging.","date":"2026","source":"Acta histochemica","url":"https://pubmed.ncbi.nlm.nih.gov/41483743","citation_count":0,"is_preprint":false},{"pmid":null,"id":"bio_10.1101_2024.08.10.607237","title":"Long-read transcriptomic identification of synaptic adaptation to amyloid pathology in the  <i>  App  <sup>NL-G-F</sup>  </i>  knock-in mouse model of the earliest phase of Alzheimer’s disease","date":"2024-08-10","source":"bioRxiv","url":"https://doi.org/10.1101/2024.08.10.607237","citation_count":0,"is_preprint":true}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":47865,"output_tokens":3839,"usd":0.10059,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":11563,"output_tokens":3900,"usd":0.077658,"stage2_stop_reason":"end_turn"},"total_usd":0.178248,"stage1_batch_id":"msgbatch_01ACAxJQabDsht39JXeWG22d","stage2_batch_id":"msgbatch_01QEU22A9U5sbPTgsMzTmvSf","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2005,\n      \"finding\": \"CLTA (clathrin light chain A, LCa) and CLTB (LCb) genes arose by localized duplication during chordate evolution (~510-600 million years ago), independently from the heavy chain duplication. CHC17 (the ubiquitous clathrin heavy chain) is bound and regulated by both LCa and LCb, whereas the paralogous CHC22 does not functionally interact with either light chain isoform.\",\n      \"method\": \"Phylogenetic and sequence analysis; functional interaction assays distinguishing CHC17 vs CHC22 binding to CLCa/CLCb\",\n      \"journal\": \"Proceedings of the National Academy of Sciences of the United States of America\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — functional interaction data combined with evolutionary sequence analysis, single study\",\n      \"pmids\": [\"15883369\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 1994,\n      \"finding\": \"CLTA maps to chromosome 12q23-q24, and the neuron-specific insertion sequences of CLCa are encoded by two discrete exons (the first homologous to the single neuron-specific exon of LCb), establishing that tissue-specific CLCa isoforms are generated by alternative mRNA splicing.\",\n      \"method\": \"Chromosomal mapping; isolation and characterization of partial genomic clones; exon structure analysis\",\n      \"journal\": \"Genomics\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct genomic cloning and exon characterization, single lab\",\n      \"pmids\": [\"7713494\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2010,\n      \"finding\": \"CLTA (clathrin light chain A) directly interacts with the mitotic arrest deficient protein MAD2B (MAD2L2) during the G2/M phase of the cell cycle. MAD2B and CLTA co-localize at the mitotic spindle, and siRNA-mediated depletion of MAD2B causes CLTA to redistribute away from the spindle and results in a marked increase in misaligned chromosomes.\",\n      \"method\": \"Yeast two-hybrid screen; GST pull-down; endogenous co-immunoprecipitation; confocal laser scanning microscopy; siRNA knockdown\",\n      \"journal\": \"PloS one\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — multiple orthogonal methods (yeast two-hybrid, GST pulldown, reciprocal co-IP, co-localization, siRNA phenotype) in a single study\",\n      \"pmids\": [\"21152103\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"CLCa (CLTA), but not CLCb (CLTB), is uniquely required for efficient cell spreading and migration. Selective depletion of CLCa reduced isotropic spreading by 60–80% and wound closure/motility by ~50%. CLCa is required for effective targeting of FAK and paxillin to the adherent surface of spreading cells, for integrin-mediated activation of Src, FAK, and paxillin, and for maturation of focal adhesions. CLCa depletion also blocked the interaction of clathrin with the WAVE nucleation-promoting complex and altered actin distribution. CLCa is preferentially recruited to budding protrusions.\",\n      \"method\": \"siRNA selective depletion of CLCa vs CLCb; live-cell spreading assays; wound closure/motility assays; immunofluorescence; co-immunoprecipitation (clathrin-WAVE complex); surface integrin quantification\",\n      \"journal\": \"Journal of cell science\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — multiple orthogonal methods (selective siRNA, functional assays, co-IP, localization), isoform specificity rigorously demonstrated\",\n      \"pmids\": [\"30975920\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"Neuronal clathrin light chain mixtures (nCLCa encoded by CLTA and nCLCb encoded by CLTB) are more effective in membrane deformation than clathrin containing single neuronal isoforms alone. CLC splice variants differentially influence clathrin knee conformation within assemblies. Mice lacking only nCLCa (CLTA-null) show increased synaptic vesicle numbers and restore normal neurotransmission, whereas mice lacking nCLCb have a reduced synaptic vesicle pool and impaired neurotransmission. Both nCLCa-null and nCLCb-null neurons are defective in synaptic vesicle replenishment.\",\n      \"method\": \"Biophysical characterization of clathrin assemblies with individual CLC variants; electrophysiological recordings in neurons from CLTA-knockout and CLTB-knockout mice; electron microscopy of synaptic vesicle pools\",\n      \"journal\": \"Proceedings of the National Academy of Sciences of the United States of America\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1-2 / Strong — in vitro reconstitution of membrane deformation, knockout mouse models, electrophysiology, multiple orthogonal methods\",\n      \"pmids\": [\"32907943\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"PFOA exposure in mouse testes affects endocytosis, and CLTA is a direct target of miR-133b-3p as validated by transfection and luciferase activity assay, suggesting post-transcriptional regulation of CLTA by miR-133b-3p.\",\n      \"method\": \"miRNA array; TaqMan qPCR; immunohistochemistry; Western blot; transfection with miR-133b-3p; luciferase reporter assay\",\n      \"journal\": \"Toxicology and applied pharmacology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct luciferase reporter validation of miRNA-CLTA interaction, single lab, in mouse testis context\",\n      \"pmids\": [\"28126411\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"CPT1A-mediated fatty acid oxidation promotes upregulation of CLTA and CLTC expression in osteoclast precursors through enhanced binding of transcription factor C/EBPβ to the CLTA and CLTC promoters. This drives clathrin-dependent endocytosis, attenuates fusion receptors at the membrane, and contributes to increased podosome formation and osteoclast precursor fusion in rheumatoid arthritis.\",\n      \"method\": \"ChIP assay (C/EBPβ binding to CLTA/CLTC promoters); Western blot; functional endocytosis assays; podosome and fusion assays in RA patient-derived cells\",\n      \"journal\": \"Frontiers in immunology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — ChIP for promoter binding and functional assays in disease-relevant cells, single lab\",\n      \"pmids\": [\"35273614\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"CLTA in hepatocellular carcinoma (HCC) cells facilitates uptake of small extracellular vesicles (sEVs) by increasing expression of CAPG (capping actin protein gelsolin-like), thereby promoting proliferation, motility, and invasiveness of HCC cells. The CLTA inhibitor Pitstop 2 alone or combined with sorafenib attenuated tumor growth in patient-derived xenografts.\",\n      \"method\": \"PKH67-sEV uptake assay; MTT; colony formation; transwell assays; mass spectrometry identification of downstream effector CAPG; siRNA knockdown; Pitstop 2 pharmacological inhibition; PDX mouse model\",\n      \"journal\": \"Hepatology international\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — multiple functional assays and mass spectrometry identification of effector, single lab\",\n      \"pmids\": [\"37354358\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"HCC-derived sEV-CLTA remodels the microvascular niche by stabilizing and upregulating basigin (BSG) in endothelial cells, thereby disrupting endothelial integrity and inducing angiogenesis. Circulating sEV CLTA levels were elevated in HCC patients and decreased after surgery.\",\n      \"method\": \"ELISA of circulating sEVs from HCC patients; tube formation; sprouting; trans-endothelial invasion and vascular leakiness assays; mass spectrometry identification of BSG as downstream effector; PDX mouse model with BSG inhibitor SP-8356\",\n      \"journal\": \"Journal of extracellular vesicles\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — mass spectrometry effector identification, multiple functional assays in endothelial cells, in vivo PDX model, single lab\",\n      \"pmids\": [\"37606345\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"CRISPR/Cas9 was used to fluorescently label the C-terminus of endogenous CLTA in human iPSCs, generating a functional reporter line that maintains normal karyotype and differentiation potential, enabling visualization of endogenous clathrin trafficking in varied cell types derived from iPSCs.\",\n      \"method\": \"CRISPR/Cas9 genomic editing; fluorescence-activated cell sorting; karyotyping; differentiation assays; live fluorescence imaging of clathrin-coated pits\",\n      \"journal\": \"Stem cell research\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — endogenous tagging with functional validation in iPSC model, single lab, demonstrates CME function of tagged protein\",\n      \"pmids\": [\"30340091\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"An eGFP-Clta fusion knock-in reporter mouse was generated by endogenous tagging of clathrin light chain a. The fusion protein is expressed in all tissues in a cell-specific manner and functionally recruits to nanobeads (validated by TIRF microscopy), enabling intravital 2-photon tracking of endocytic dynamics in living mice.\",\n      \"method\": \"Endogenous knock-in mouse model; TIRF microscopy nanobead recruitment assay; intravital 2-photon microscopy; fluorescence microscopy across tissues\",\n      \"journal\": \"PloS one\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — endogenous tagging with functional TIRF validation and in vivo imaging, single lab\",\n      \"pmids\": [\"36149863\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"GPN3 interacts directly with CLTA (clathrin light chain A) as well as AP2B1 and AP2S1, and upregulation of GPN3 inhibits clathrin-coated pit invagination. GPN3 regulates co-localization of EGFR with CLTA and EGFR localization in early endosomes upon EGF stimulation, reducing endocytic levels of EGFR and prolonging its membrane-proximal signaling.\",\n      \"method\": \"Co-immunoprecipitation; clathrin-coated pit invagination assays; co-localization imaging of EGFR and CLTA; early endosome fractionation; GPN3 overexpression and knockdown; GTP-dependence testing\",\n      \"journal\": \"Cell death discovery\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal Co-IP and functional co-localization assays showing CLTA-GPN3 interaction with defined endocytic phenotype, single lab\",\n      \"pmids\": [\"39893205\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"CLTA silencing by siRNA in osteosarcoma cell lines (MG63 and U2OS) led to significant reductions in cell proliferation, colony formation, and migration, establishing a direct functional role for CLTA in osteosarcoma cell behavior.\",\n      \"method\": \"siRNA knockdown; MTT/cell proliferation assay; colony formation assay; wound healing migration assay\",\n      \"journal\": \"The journal of gene medicine\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single lab, standard functional knockdown assays without mechanistic pathway placement beyond phenotype description\",\n      \"pmids\": [\"41236100\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2026,\n      \"finding\": \"In a rat controlled cortical impact (CCI) TBI model, hippocampal abundance of clathrin light chain (including CLTA-associated protein complex) was decreased at 14 days post-injury, temporally associated with neurobehavioral impairments. In severe TBI patients, a CLTA SNP minor allele (rs4879960) was associated with improved outcomes on the Glasgow Outcome Scale and Disability Rating Scale.\",\n      \"method\": \"Western blot of hippocampal CME proteins in CCI rats; neurobehavioral testing; human SNP genotyping correlated with clinical outcomes\",\n      \"journal\": \"Molecular neurobiology\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — associational protein abundance changes in rat model with behavioral correlation; human SNP association without mechanistic dissection\",\n      \"pmids\": [\"41673368\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"CLTA encodes clathrin light chain A (CLCa), a structural and regulatory subunit of the clathrin triskelion that associates with the ubiquitous clathrin heavy chain CHC17; CLCa has isoform-specific functions distinct from CLCb, including a unique role in promoting cell spreading, migration, and focal adhesion maturation through FAK/Src/paxillin signaling and interaction with the WAVE actin nucleation complex, a role in synaptic vesicle replenishment where balanced co-expression of neuronal CLCa and CLCb isoforms optimizes membrane deformation and neurotransmission, a mitotic function via direct interaction with MAD2B at the spindle to maintain chromosome alignment, and roles in clathrin-mediated endocytosis that impact EGFR trafficking, sEV uptake (via CAPG upregulation in HCC), and microvascular niche remodeling (via BSG stabilization); additionally, CLTA expression is transcriptionally regulated by C/EBPβ downstream of fatty acid oxidation and post-transcriptionally targeted by miR-133b-3p.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"CLTA encodes clathrin light chain A (CLCa), a regulatory subunit of the clathrin triskelion that binds and regulates the ubiquitous clathrin heavy chain CHC17, an interaction that arose by light-chain gene duplication independent of heavy-chain duplication during chordate evolution; the paralogous CHC22 does not engage either light chain [#0]. Tissue-specific CLCa isoforms are generated by alternative splicing of discrete neuron-specific exons [#1]. CLCa has functions distinct from its paralog CLCb: it is uniquely required for cell spreading and migration, controlling targeting of FAK and paxillin to the adherent surface, integrin-mediated activation of Src/FAK/paxillin, focal adhesion maturation, and the interaction of clathrin with the WAVE actin nucleation-promoting complex [#3]. In neurons, balanced co-assembly of CLCa and CLCb isoforms tunes clathrin knee conformation and membrane deformation, with CLTA-null mice showing increased synaptic vesicle numbers, and both isoforms required for synaptic vesicle replenishment [#4]. Beyond endocytosis, CLCa directly interacts with MAD2B (MAD2L2) at the mitotic spindle during G2/M, where MAD2B depletion redistributes CLCa from the spindle and produces chromosome misalignment [#2]. In clathrin-mediated endocytosis, CLCa cooperates with the AP2 complex and is regulated by GPN3, which controls EGFR co-localization with CLCa and EGFR endocytic trafficking [#11]. CLTA expression is transcriptionally driven by C/EBPβ downstream of fatty acid oxidation [#6] and post-transcriptionally targeted by miR-133b-3p [#5]. CLTA contributes to tumor cell behavior in hepatocellular carcinoma, where it promotes small extracellular vesicle uptake via CAPG upregulation [#7] and remodels the microvascular niche by stabilizing basigin (BSG) [#8].\",\n  \"teleology\": [\n    {\n      \"year\": 1994,\n      \"claim\": \"Establishing the genomic architecture of CLTA defined how a single gene produces tissue-specific light chain isoforms, a prerequisite for understanding functional divergence.\",\n      \"evidence\": \"Chromosomal mapping and genomic exon-structure analysis of CLTA\",\n      \"pmids\": [\"7713494\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Functional consequences of the neuron-specific exons not addressed\", \"No protein-level activity assigned to splice variants at this stage\"]\n    },\n    {\n      \"year\": 2005,\n      \"claim\": \"Tracing the evolutionary origin of CLTA/CLTB and their heavy-chain binding specificity established which heavy chain CLCa actually regulates, separating it from the non-interacting CHC22 paralog.\",\n      \"evidence\": \"Phylogenetic/sequence analysis with CHC17-vs-CHC22 functional interaction assays\",\n      \"pmids\": [\"15883369\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Does not resolve isoform-specific functional differences between CLCa and CLCb\", \"Structural basis of selective heavy-chain binding not defined\"]\n    },\n    {\n      \"year\": 2010,\n      \"claim\": \"Identifying a direct CLCa-MAD2B interaction at the spindle answered whether clathrin light chain has a dedicated mitotic role beyond membrane trafficking.\",\n      \"evidence\": \"Yeast two-hybrid, GST pull-down, reciprocal co-IP, confocal co-localization, and siRNA in cultured cells\",\n      \"pmids\": [\"21152103\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Molecular mechanism by which the CLCa-MAD2B complex maintains chromosome alignment unknown\", \"Whether this requires heavy-chain-assembled clathrin not established\"]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"Selective depletion of CLCa versus CLCb demonstrated that CLCa carries a non-redundant role in adhesion and motility signaling, defining the first clearly isoform-specific cellular function.\",\n      \"evidence\": \"Isoform-selective siRNA with spreading/migration assays, immunofluorescence, integrin quantification, and clathrin-WAVE co-IP\",\n      \"pmids\": [\"30975920\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Direct binding interface between CLCa and the WAVE complex not mapped\", \"How CLCa selectively directs FAK/paxillin targeting mechanistically unresolved\"]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Reconstitution and knockout-mouse work showed that balanced neuronal CLCa/CLCb co-assembly tunes membrane deformation and synaptic vesicle cycling, explaining why both isoforms are retained.\",\n      \"evidence\": \"Biophysical assembly assays, electrophysiology and EM in CLTA-null and CLTB-null mice\",\n      \"pmids\": [\"32907943\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Structural determinant of knee-conformation control by each variant not fully defined\", \"Molecular link between vesicle replenishment defect and isoform identity unresolved\"]\n    },\n    {\n      \"year\": 2017,\n      \"claim\": \"Validation of CLTA as a miR-133b-3p target introduced a post-transcriptional layer controlling CLTA abundance in an endocytosis-relevant tissue context.\",\n      \"evidence\": \"miRNA array, qPCR, and luciferase reporter assay in mouse testis\",\n      \"pmids\": [\"28126411\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Physiological extent of miR-133b-3p control over CLTA in other tissues unknown\", \"Downstream endocytic consequence of CLTA repression not directly tested\"]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Linking C/EBPβ to CLTA promoter binding downstream of fatty acid oxidation established a transcriptional input coupling metabolism to clathrin-dependent endocytosis in disease.\",\n      \"evidence\": \"ChIP, Western blot, and endocytosis/fusion assays in RA patient-derived osteoclast precursors\",\n      \"pmids\": [\"35273614\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Direct demonstration that CLTA induction alone drives the fusion phenotype not isolated from CLTC\", \"Generality beyond osteoclast precursors unknown\"]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Two studies defined CLTA-dependent mechanisms in hepatocellular carcinoma — sEV uptake via CAPG and microvascular remodeling via BSG — placing CLTA in tumor progression and providing pharmacological entry points.\",\n      \"evidence\": \"sEV uptake and invasion assays, mass spectrometry effector identification, Pitstop 2/SP-8356 inhibition, and PDX models\",\n      \"pmids\": [\"37354358\", \"37606345\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Whether CLTA acts as classical clathrin subunit or moonlights in these contexts not resolved\", \"Mechanism of sEV-CLTA cargo delivery to recipient endothelial cells not detailed\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Identification of GPN3 as a direct CLTA/AP2 interactor that restrains pit invagination connected CLCa to regulated control of EGFR endocytosis and signaling duration.\",\n      \"evidence\": \"Reciprocal co-IP, pit invagination assays, EGFR-CLTA co-localization and endosome fractionation with GPN3 perturbation\",\n      \"pmids\": [\"39893205\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"How GPN3 mechanistically inhibits invagination at the molecular level unclear\", \"Specificity for CLCa versus CLCb-containing coats not tested\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Functional knockdown in osteosarcoma lines extended CLTA's pro-tumor role to a second cancer type at the phenotypic level.\",\n      \"evidence\": \"siRNA knockdown with proliferation, colony formation, and migration assays in MG63 and U2OS cells\",\n      \"pmids\": [\"41236100\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"Standard knockdown phenotype without mechanistic pathway placement\", \"No effector or signaling axis identified in this context\"]\n    },\n    {\n      \"year\": 2026,\n      \"claim\": \"Associational data linked clathrin light chain abundance and a CLTA SNP to TBI outcomes, raising clathrin trafficking as a candidate factor in neural injury recovery.\",\n      \"evidence\": \"Western blot in rat CCI model with behavioral testing and human CLTA SNP-outcome genotyping\",\n      \"pmids\": [\"41673368\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"Associational only; no causal mechanism for the rs4879960 effect\", \"CLTA-specific contribution not separated from general clathrin complex changes\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How CLCa's distinct functions — adhesion signaling, mitotic spindle activity, neuronal membrane deformation, and cancer-associated trafficking — are molecularly partitioned through isoform-specific sequence features and binding partners remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No structural model linking CLCa-specific exons to its unique functions\", \"Whether mitotic and adhesion roles depend on assembled clathrin coats versus free light chain unknown\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0005198\", \"supporting_discovery_ids\": [0, 4]},\n      {\"term_id\": \"GO:0060090\", \"supporting_discovery_ids\": [3, 11]},\n      {\"term_id\": \"GO:0008092\", \"supporting_discovery_ids\": [3]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005886\", \"supporting_discovery_ids\": [3, 10, 11]},\n      {\"term_id\": \"GO:0005815\", \"supporting_discovery_ids\": [2]},\n      {\"term_id\": \"GO:0031410\", \"supporting_discovery_ids\": [4, 9]},\n      {\"term_id\": \"GO:0005768\", \"supporting_discovery_ids\": [11]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-5653656\", \"supporting_discovery_ids\": [4, 9, 11]},\n      {\"term_id\": \"R-HSA-1640170\", \"supporting_discovery_ids\": [2]},\n      {\"term_id\": \"R-HSA-112316\", \"supporting_discovery_ids\": [4]}\n    ],\n    \"complexes\": [\n      \"clathrin triskelion (CHC17/clathrin coat)\"\n    ],\n    \"partners\": [\n      \"CLTC\",\n      \"MAD2L2\",\n      \"GPN3\",\n      \"AP2B1\",\n      \"AP2S1\"\n    ],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":7,"faith_total":8,"faith_pct":87.5}}