{"gene":"KATNB1","run_date":"2026-06-10T01:55:23","timeline":{"discoveries":[{"year":2014,"finding":"KATNB1 (katanin p80) is the regulatory subunit of the microtubule-severing enzyme Katanin, and its interaction with KATNA1 (the catalytic subunit) and other microtubule-associated proteins is required for proper mitotic spindle formation; patient-derived fibroblasts carrying KATNB1 mutations show defective mitotic spindle formation due to disrupted KATNB1–KATNA1 interactions.","method":"Exome sequencing of patient cohort; functional analysis of patient-derived fibroblasts (spindle formation assay); loss-of-function in zebrafish (katnb1) and Drosophila (kat80) with microcephaly phenotype; Drosophila neuroblast analysis showing supernumerary centrosomes and spindle abnormalities","journal":"Neuron","confidence":"High","confidence_rationale":"Tier 2 / Strong — reciprocal functional rescue, patient-derived cells, two independent model organisms, multiple orthogonal methods across two independent labs (PMIDs 25521378 and 25521379)","pmids":["25521378"],"is_preprint":false},{"year":2014,"finding":"Loss of KATNB1 causes a remarkable excess of centrioles with supernumerary cilia but deficient Hedgehog signaling, revealing an unexpected role for KATNB1 in regulating centriole number, mother centriole number, and cilia number, as well as in Sonic hedgehog pathway activity during neocortical development.","method":"Katnb1 knockout mouse embryos (hallmarks of aberrant Shh signaling including holoprosencephaly); KATNB1-deficient human cells (proliferation and spindle structure assays); Katnb1 null fibroblasts (centriole counting, cilia quantification, Hedgehog signaling assays); zebrafish katnb1 loss-of-function","journal":"Neuron","confidence":"High","confidence_rationale":"Tier 2 / Strong — multiple orthogonal methods (KO mouse, human cells, zebrafish), multiple independent phenotypic readouts in a single rigorous study","pmids":["25521379"],"is_preprint":false},{"year":2017,"finding":"KATNB1 (p80) regulates microtubule remodeling in combination with NuMA (nuclear mitotic apparatus protein) and cytoplasmic dynein; p80 shuttles between the nucleus and spindle pole in synchrony with the cell cycle (a feature shared with NuMA), and is essential for aster formation and maintenance in vitro. Depletion of p80 and/or NuMA induces abnormal mitotic phenotypes and aberrant neurogenesis/neuronal migration, confirmed in patient-derived iPSCs and brain organoids.","method":"siRNA-mediated depletion of p80 and/or NuMA in mouse embryonic fibroblasts; in vitro aster formation assay; live imaging of cell-cycle-dependent nuclear/spindle pole shuttling; mouse embryonic brain electroporation; patient-derived iPSCs and brain organoids","journal":"Scientific reports","confidence":"High","confidence_rationale":"Tier 2 / Strong — multiple orthogonal methods (in vitro aster assay, siRNA, in vivo brain, patient iPSC organoids), functional epistasis with NuMA and dynein","pmids":["28079116"],"is_preprint":false},{"year":2016,"finding":"KATNB1 interacts with the katanin A-subunits KATNA1 and KATNAL1 (and KATNAL2 in some contexts) as part of the mammalian Katanin family interaction network; proteomic analysis (mass spectrometry) defined the Katanin family interactome (Katan-ome), and KATNB1 was shown to compete with KATNBL1 for binding to KATNA1 and KATNAL1.","method":"Mass spectrometry-based proteomics (pull-down/affinity purification); in vitro microtubule-severing activity assay for KATNBL1; localization studies during cell cycle","journal":"Molecular & cellular proteomics : MCP","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — MS-based interactome plus in vitro severing assay, single lab, multiple orthogonal methods","pmids":["26929214"],"is_preprint":false},{"year":2021,"finding":"KATNB1 is a master regulator of all katanin enzymatic A-subunits (KATNA1, KATNAL1, KATNAL2) during mammalian spermatogenesis; it is required to maintain katanin A-subunit protein abundance, and complete loss of KATNB1 from germ cells is incompatible with sperm production. KATNB1 has essential roles in male meiosis, acrosome formation, sperm tail assembly, regulation of the Sertoli and germ cell cytoskeletons during sperm nuclear remodelling, and maintenance of seminiferous epithelium integrity.","method":"Allelic loss-of-function series (multiple mouse knockout alleles) of KATNB1 in germ cells; histological analysis of seminiferous epithelium; immunostaining for katanin A-subunit abundance; phenotypic readouts across spermatogenesis stages","journal":"Development (Cambridge, England)","confidence":"High","confidence_rationale":"Tier 2 / Strong — allelic series with multiple knockout lines, multiple orthogonal phenotypic readouts, clear epistasis placing KATNB1 upstream of all katanin A-subunits","pmids":["34822718"],"is_preprint":false},{"year":2013,"finding":"The KATNB1 gene is driven by a 518-bp TATA-less promoter containing a critical CpG island and GC boxes; sequential deletion of these elements reduces promoter activity. The transcription factor Elk1 binds the KATNB1 promoter (demonstrated by EMSA) and activates it, increasing both KATNB1 mRNA and protein levels. KCl treatment that increases SUMOylation decreases KATNB1 promoter activity.","method":"Promoter deletion/reporter assays; EMSA (Elk1 binding to KATNB1 promoter); qRT-PCR and western blot for mRNA and protein levels after Elk1 manipulation; KCl/SUMOylation treatment in SH-SY5Y cells","journal":"PloS one","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — EMSA for direct binding plus reporter assays and expression measurement, single lab, two orthogonal methods","pmids":["23894477"],"is_preprint":false},{"year":2014,"finding":"KATNB1 protein localizes to the microtubules of the manchette in human spermatids, a structure required for sperm head shaping, supporting a role in sperm morphogenesis beyond spindle formation.","method":"Immunostaining/immunofluorescence of human testicular biopsy samples; RT-PCR and in situ hybridization for mRNA expression across spermatogenesis stages","journal":"Andrology","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — immunolocalization with stage-specific analysis across multiple samples, single lab, replicated in subsequent studies","pmids":["25280067"],"is_preprint":false},{"year":2016,"finding":"KATNB1 protein is expressed exclusively in germ cells during human spermatogenesis; it localizes to type B spermatogonia entering meiosis, the Golgi complex of pachytene spermatocytes, colocalizes with the cleaving centriole just before the first meiotic division, and is found in early round spermatids in the dictyosome, supporting roles in spindle formation and microtubule-based structures during spermiogenesis.","method":"RT-PCR, RT-qPCR, in situ hybridization, immunohistochemistry/immunofluorescence on 80 human testicular biopsy samples across normal and impaired spermatogenesis","journal":"Fertility and sterility","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — multiple localization methods across large human sample set, single lab","pmids":["27717557"],"is_preprint":false},{"year":2017,"finding":"Katnb1 is ubiquitously expressed during mouse embryonic development with stronger expression in the crown cells of the gastrulation organizer (murine node); null and hypomorphic Katnb1 mutations result in impaired left-right signaling and cardiac malformations, demonstrating a role for katanin in heart development.","method":"Knockin-knockout mouse model of Katnb1 dysfunction; in situ hybridization/expression analysis during embryogenesis; phenotypic characterization of null and hypomorphic embryos","journal":"Developmental dynamics","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — genetic loss-of-function with defined phenotypic readout in mouse model, single lab","pmids":["28791777"],"is_preprint":false},{"year":2022,"finding":"In zebrafish, Katnb1 has an essential role in motile ciliated lineages; katnb1 mutants display defects in ependymal cell cilia and abnormal CSF flow that are associated with scoliosis, uncoupling ependymal cilia and Reissner fiber formation defects from spinal curvature while identifying abnormal CSF flow as a shared pathogenic signature.","method":"Zebrafish katnb1 mutant characterization; cilia motility assays; CSF flow measurement; spine curvature quantification; comparison across multiple scoliosis zebrafish models","journal":"iScience","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — genetic loss-of-function with multiple phenotypic readouts and epistatic uncoupling of phenotypes, single lab","pmids":["36105588"],"is_preprint":false},{"year":2018,"finding":"During Klebsiella pneumoniae infection of lung epithelial cells, KATNB1 and KATNAL1 localize specifically to microtubule cut sites and act as gatekeepers for the microtubule-severing event; knockdown of either protein in infected cells maintained intact microtubules, demonstrating that KATNB1 is required for bacterially-induced host microtubule disassembly.","method":"siRNA knockdown of KATNB1 and KATNAL1 in lung epithelial cells; immunofluorescence localization to microtubule cut sites during K. pneumoniae infection; assessment of microtubule integrity in KD cells","journal":"Cellular microbiology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — siRNA knockdown with specific cellular phenotype readout, localization evidence, single lab","pmids":["30415487"],"is_preprint":false},{"year":2024,"finding":"KATNB1 knockdown in rat primary Sertoli cells disrupts tight junction (TJ) permeability barrier function and causes perturbations in microtubule and actin cytoskeleton organization, leading to improper distribution of TJ and basal ectoplasmic specialization (ES) proteins. Conversely, overexpression of KATNB1 in the testis in vivo blocks cadmium-induced blood-testis barrier (BTB) disruption by maintaining proper cytoskeletal organization.","method":"RNAi knockdown of KATNB1 in primary Sertoli cells (TJ permeability assay); immunofluorescence colocalization with α-tubulin; KATNB1 overexpression in rat testis in vivo (cadmium injury model); western blot and immunostaining for cytoskeletal and junction proteins","journal":"FASEB journal","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — reciprocal gain and loss of function with defined cellular phenotype, single lab, multiple readouts","pmids":["39275889"],"is_preprint":false},{"year":2025,"finding":"KATNB1 works in partnership with KATNAL2 and TUBD1 (delta tubulin) in haploid male germ cells to regulate manchette remodeling and sperm head shaping, as demonstrated in a TUBD1 conditional knockout mouse model.","method":"Conditional knockout mouse model for TUBD1; genetic interaction analysis with KATNAL2 and KATNB1; immunostaining and phenotypic analysis of spermatogenesis","journal":"The Journal of cell biology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — genetic interaction in vivo in conditional KO mouse with defined spermatogenesis phenotype, single lab","pmids":["40586731"],"is_preprint":false},{"year":2017,"finding":"KATNAL2 can partner with KATNB1 or act autonomously depending on cellular context during spermatogenesis; KATNB1 is not universally required for all katanin A-subunit activities.","method":"KATNAL2 knockout mouse model with analysis of spermatogenesis; immunolocalization and co-immunoprecipitation of KATNAL2 with KATNB1","journal":"PLoS genetics","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — genetic KO plus Co-IP, single lab, defined in vivo phenotype","pmids":["29136647"],"is_preprint":false},{"year":2023,"finding":"The mammalian testis KATNB1 interactome (defined by proteomics) includes a network of cytoskeletal and vesicle trafficking proteins, with KATNB1 physically associating with KATNA1 and KATNAL1 in testis.","method":"Affinity purification mass spectrometry (AP-MS) from mouse testis to define KATNB1 interactome","journal":"Development (Cambridge, England)","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — MS-based interactome from native tissue, single lab","pmids":["37882691"],"is_preprint":false}],"current_model":"KATNB1 encodes the noncatalytic regulatory p80 subunit of the Katanin microtubule-severing complex, where it physically interacts with and is required for the stability and localization of the catalytic A-subunits (KATNA1, KATNAL1, KATNAL2); it acts as a master regulator of katanin A-subunit abundance, controls mitotic spindle formation, centriole and cilia number, and microtubule-based structures (manchette, aster, spindle pole), shuttles between nucleus and spindle pole in a cell-cycle-dependent manner in cooperation with NuMA and cytoplasmic dynein, regulates Hedgehog signaling through centriole/cilia control, governs blood-testis barrier integrity through actin and microtubule cytoskeleton organization in Sertoli cells, and is required for left-right axis determination in the embryo via motile cilia at the node."},"narrative":{"mechanistic_narrative":"KATNB1 encodes the noncatalytic regulatory (p80) subunit of the microtubule-severing enzyme katanin, where it binds the catalytic A-subunits KATNA1, KATNAL1, and KATNAL2 and acts as a master regulator that maintains their protein abundance and directs their activity to specific microtubule structures [PMID:25521378, PMID:26929214, PMID:34822718]. Through this regulatory partnership it is required for proper mitotic spindle formation, and patient-derived fibroblasts carrying KATNB1 mutations show defective spindles, linking KATNB1 loss to microcephaly [PMID:25521378]. KATNB1 controls centriole and cilia number and is required for Sonic hedgehog pathway activity during neocortical development, with its loss causing supernumerary centrioles and cilia [PMID:25521379]. It coordinates microtubule remodeling with NuMA and cytoplasmic dynein, shuttling between the nucleus and spindle pole in a cell-cycle-dependent manner and driving aster formation [PMID:28079116]. Beyond mitosis, KATNB1 is essential across spermatogenesis—governing meiosis, manchette remodeling and sperm head shaping (with KATNAL2 and TUBD1), and blood-testis barrier integrity through coordinated actin and microtubule organization in Sertoli cells [PMID:34822718, PMID:39275889, PMID:40586731]—and is required in motile ciliated lineages for left-right axis determination and CSF flow [PMID:28791777, PMID:36105588]. KATNB1 is also recruited to microtubule cut sites with KATNAL1 to mediate bacterially-induced host microtubule disassembly during Klebsiella pneumoniae infection [PMID:30415487].","teleology":[{"year":2013,"claim":"Before its regulation was known, the transcriptional control of KATNB1 was undefined; identifying its promoter and an activating transcription factor established how KATNB1 expression is set.","evidence":"Promoter deletion/reporter assays and EMSA showing Elk1 binding and activation in SH-SY5Y cells","pmids":["23894477"],"confidence":"Medium","gaps":["Physiological contexts in which Elk1 drives KATNB1 are not defined","Link between SUMOylation and promoter repression is correlative"]},{"year":2014,"claim":"It was unknown whether KATNB1 regulatory function is required for spindle assembly in humans; patient mutations disrupting the KATNB1–KATNA1 interaction caused defective spindles and microcephaly, establishing KATNB1 as a spindle regulator and disease gene.","evidence":"Exome sequencing of microcephaly patients, patient-fibroblast spindle assays, and zebrafish/Drosophila loss-of-function","pmids":["25521378"],"confidence":"High","gaps":["Structural basis of the KATNB1–KATNA1 interaction not resolved","Mechanism linking spindle defects to neuronal depletion not detailed"]},{"year":2014,"claim":"Whether katanin regulates centriole and cilia number was unknown; KATNB1 loss produced excess centrioles and cilia yet deficient Hedgehog signaling, revealing a centriole/cilia control function upstream of Shh.","evidence":"Katnb1 knockout mouse embryos, null fibroblast centriole/cilia counting and Hedgehog assays, and zebrafish loss-of-function","pmids":["25521379"],"confidence":"High","gaps":["Molecular mechanism by which katanin limits centriole number unknown","Direct connection between cilia defects and Shh output not mechanistically dissected"]},{"year":2014,"claim":"Whether KATNB1 acts beyond the mitotic spindle in male germ cells was unclear; its localization to the spermatid manchette implicated it in sperm head shaping.","evidence":"Immunostaining and in situ hybridization across stages in human testicular biopsies","pmids":["25280067"],"confidence":"Medium","gaps":["Functional requirement at the manchette not tested in this descriptive study","Catalytic partner at the manchette not identified here"]},{"year":2016,"claim":"The full set of katanin A-subunit partners and how subunit choice is governed were unresolved; interactome proteomics defined the Katan-ome and showed KATNB1 competes with KATNBL1 for binding A-subunits.","evidence":"Mass spectrometry interactome, in vitro severing assay, and cell-cycle localization","pmids":["26929214"],"confidence":"Medium","gaps":["Functional consequence of KATNB1 vs KATNBL1 competition in vivo not established","Single-lab interactome without orthogonal validation of all partners"]},{"year":2016,"claim":"The cellular stages of KATNB1 expression during human spermatogenesis were uncharacterized; expression mapping placed it in meiotic and post-meiotic germ cells at centriole and Golgi/dictyosome structures.","evidence":"RT-PCR, in situ hybridization, and immunohistochemistry across 80 human testicular biopsies","pmids":["27717557"],"confidence":"Medium","gaps":["Localization is descriptive without functional perturbation","Role at the Golgi/dictyosome not defined"]},{"year":2017,"claim":"How KATNB1 is spatially deployed during mitosis was unclear; it was shown to shuttle between nucleus and spindle pole with NuMA and dynein and to be required for aster formation, linking it functionally to neurogenesis.","evidence":"siRNA depletion in MEFs, in vitro aster assay, live imaging, mouse brain electroporation, and patient iPSC organoids","pmids":["28079116"],"confidence":"High","gaps":["Whether KATNB1 shuttling depends on its severing partners is unknown","Direct biochemical interaction with NuMA/dynein not mapped"]},{"year":2017,"claim":"Whether katanin contributes to embryonic left-right patterning was unknown; Katnb1 mutations impaired left-right signaling and caused cardiac malformations, with strong node expression.","evidence":"Knockin-knockout mouse model, embryonic expression analysis, and phenotyping of null/hypomorphic embryos","pmids":["28791777"],"confidence":"Medium","gaps":["Direct demonstration of nodal cilia motility defects not provided","Cell-type-specific requirement at the node not isolated"]},{"year":2017,"claim":"Whether KATNB1 is obligatory for all A-subunit activities was open; KATNAL2 was shown to act with or without KATNB1 depending on context, indicating context-dependent dependence.","evidence":"KATNAL2 knockout mouse with co-immunoprecipitation and immunolocalization with KATNB1","pmids":["29136647"],"confidence":"Medium","gaps":["Determinants of KATNB1-dependent vs autonomous KATNAL2 activity unknown","Co-IP not reciprocally validated"]},{"year":2018,"claim":"Whether katanin participates in host responses to infection was unknown; KATNB1 and KATNAL1 were found at microtubule cut sites and required for bacterially-induced microtubule disassembly.","evidence":"siRNA knockdown and immunofluorescence localization in K. pneumoniae-infected lung epithelial cells","pmids":["30415487"],"confidence":"Medium","gaps":["Bacterial signal triggering recruitment unidentified","Consequence for infection outcome not established"]},{"year":2021,"claim":"The hierarchy among katanin subunits in germ cells was unresolved; an allelic series placed KATNB1 upstream of all A-subunits, controlling their abundance and being indispensable for spermatogenesis.","evidence":"Multiple germ-cell Katnb1 knockout alleles with histology, A-subunit immunostaining, and stage-specific phenotyping","pmids":["34822718"],"confidence":"High","gaps":["Mechanism by which KATNB1 stabilizes A-subunit protein unknown","Whether stabilization is direct or via localization not distinguished"]},{"year":2023,"claim":"The native tissue partners of KATNB1 were incompletely defined; testis AP-MS mapped a cytoskeletal and vesicle-trafficking interactome including KATNA1 and KATNAL1.","evidence":"Affinity purification mass spectrometry from mouse testis","pmids":["37882691"],"confidence":"Medium","gaps":["Functional significance of vesicle-trafficking associations untested","Single-lab dataset without orthogonal confirmation"]},{"year":2024,"claim":"Whether KATNB1 contributes to the blood-testis barrier was unknown; reciprocal loss/gain of function showed it maintains tight junction barrier function via actin and microtubule organization in Sertoli cells.","evidence":"RNAi knockdown in primary Sertoli cells with TJ permeability assays and KATNB1 overexpression in a rat cadmium injury model","pmids":["39275889"],"confidence":"Medium","gaps":["How KATNB1 coordinates actin in addition to microtubules is unclear","Catalytic A-subunit mediating this effect not identified"]},{"year":2025,"claim":"How manchette remodeling is controlled in haploid germ cells was incompletely understood; KATNB1 was shown to work with KATNAL2 and TUBD1 to regulate manchette remodeling and sperm head shaping.","evidence":"TUBD1 conditional knockout mouse with genetic interaction analysis and spermatogenesis phenotyping","pmids":["40586731"],"confidence":"Medium","gaps":["Biochemical interaction between KATNB1, KATNAL2, and TUBD1 not mapped","Order of action among the three proteins not resolved"]},{"year":null,"claim":"The structural and biochemical basis by which KATNB1 stabilizes and spatially targets each katanin A-subunit, and how it switches between mitotic, ciliary, and germ-cell functions, remains unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No structure of the KATNB1–A-subunit complex","Mechanism of A-subunit protein stabilization unknown","Determinants of tissue- and context-specific partner selection undefined"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0098772","term_label":"molecular function regulator activity","supporting_discovery_ids":[0,3,4]},{"term_id":"GO:0008092","term_label":"cytoskeletal protein binding","supporting_discovery_ids":[0,2,11]}],"localization":[{"term_id":"GO:0005815","term_label":"microtubule organizing center","supporting_discovery_ids":[2,7]},{"term_id":"GO:0005856","term_label":"cytoskeleton","supporting_discovery_ids":[6,10,11]},{"term_id":"GO:0005634","term_label":"nucleus","supporting_discovery_ids":[2]},{"term_id":"GO:0005929","term_label":"cilium","supporting_discovery_ids":[1,9]},{"term_id":"GO:0005794","term_label":"Golgi apparatus","supporting_discovery_ids":[7]}],"pathway":[{"term_id":"R-HSA-1640170","term_label":"Cell Cycle","supporting_discovery_ids":[0,2]},{"term_id":"R-HSA-1266738","term_label":"Developmental Biology","supporting_discovery_ids":[1,8]},{"term_id":"R-HSA-1474165","term_label":"Reproduction","supporting_discovery_ids":[4,12]},{"term_id":"R-HSA-162582","term_label":"Signal Transduction","supporting_discovery_ids":[1]}],"complexes":["Katanin (p60/p80) microtubule-severing complex"],"partners":["KATNA1","KATNAL1","KATNAL2","KATNBL1","NUMA1","TUBD1"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q9BVA0","full_name":"Katanin p80 WD40 repeat-containing subunit B1","aliases":["p80 katanin"],"length_aa":655,"mass_kda":72.3,"function":"Participates in a complex which severs microtubules in an ATP-dependent manner. May act to target the enzymatic subunit of this complex to sites of action such as the centrosome. Microtubule severing may promote rapid reorganization of cellular microtubule arrays and the release of microtubules from the centrosome following nucleation. Microtubule release from the mitotic spindle poles may allow depolymerization of the microtubule end proximal to the spindle pole, leading to poleward microtubule flux and poleward motion of chromosome. Microtubule release within the cell body of neurons may be required for their transport into neuronal processes by microtubule-dependent motor proteins. This transport is required for axonal growth","subcellular_location":"Cytoplasm; Cytoplasm, cytoskeleton, microtubule organizing center, centrosome; Cytoplasm, cytoskeleton, spindle pole; Cytoplasm, cytoskeleton; Cytoplasm, cytoskeleton, spindle","url":"https://www.uniprot.org/uniprotkb/Q9BVA0/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/KATNB1","classification":"Not Classified","n_dependent_lines":547,"n_total_lines":1208,"dependency_fraction":0.45281456953642385},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[],"url":"https://opencell.sf.czbiohub.org/search/KATNB1","total_profiled":1310},"omim":[{"mim_id":"616235","title":"KATANIN, p80 SUBUNIT, B-LIKE 1; KATNBL1","url":"https://www.omim.org/entry/616235"},{"mim_id":"616212","title":"LISSENCEPHALY 6 WITH MICROCEPHALY; LIS6","url":"https://www.omim.org/entry/616212"},{"mim_id":"610454","title":"LEUCINE ZIPPER, PUTATIVE TUMOR SUPPRESSOR 2; LZTS2","url":"https://www.omim.org/entry/610454"},{"mim_id":"607432","title":"LISSENCEPHALY 1; LIS1","url":"https://www.omim.org/entry/607432"},{"mim_id":"606696","title":"KATANIN, p60 SUBUNIT, A1; KATNA1","url":"https://www.omim.org/entry/606696"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Supported","locations":[{"location":"Cytosol","reliability":"Supported"},{"location":"Plasma membrane","reliability":"Additional"},{"location":"Microtubules","reliability":"Additional"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/KATNB1"},"hgnc":{"alias_symbol":[],"prev_symbol":[]},"alphafold":{"accession":"Q9BVA0","domains":[{"cath_id":"2.130.10.10","chopping":"11-308_372-378","consensus_level":"high","plddt":94.275,"start":11,"end":378},{"cath_id":"-","chopping":"503-652","consensus_level":"high","plddt":89.5606,"start":503,"end":652}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9BVA0","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q9BVA0-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q9BVA0-F1-predicted_aligned_error_v6.png","plddt_mean":79.44},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=KATNB1","jax_strain_url":"https://www.jax.org/strain/search?query=KATNB1"},"sequence":{"accession":"Q9BVA0","fasta_url":"https://rest.uniprot.org/uniprotkb/Q9BVA0.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q9BVA0/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9BVA0"}},"corpus_meta":[{"pmid":"16687443","id":"PMC_16687443","title":"Genome-wide 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interactions.\",\n      \"method\": \"Exome sequencing of patient cohort; functional analysis of patient-derived fibroblasts (spindle formation assay); loss-of-function in zebrafish (katnb1) and Drosophila (kat80) with microcephaly phenotype; Drosophila neuroblast analysis showing supernumerary centrosomes and spindle abnormalities\",\n      \"journal\": \"Neuron\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — reciprocal functional rescue, patient-derived cells, two independent model organisms, multiple orthogonal methods across two independent labs (PMIDs 25521378 and 25521379)\",\n      \"pmids\": [\"25521378\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"Loss of KATNB1 causes a remarkable excess of centrioles with supernumerary cilia but deficient Hedgehog signaling, revealing an unexpected role for KATNB1 in regulating centriole number, mother centriole number, and cilia number, as well as in Sonic hedgehog pathway activity during neocortical development.\",\n      \"method\": \"Katnb1 knockout mouse embryos (hallmarks of aberrant Shh signaling including holoprosencephaly); KATNB1-deficient human cells (proliferation and spindle structure assays); Katnb1 null fibroblasts (centriole counting, cilia quantification, Hedgehog signaling assays); zebrafish katnb1 loss-of-function\",\n      \"journal\": \"Neuron\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — multiple orthogonal methods (KO mouse, human cells, zebrafish), multiple independent phenotypic readouts in a single rigorous study\",\n      \"pmids\": [\"25521379\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"KATNB1 (p80) regulates microtubule remodeling in combination with NuMA (nuclear mitotic apparatus protein) and cytoplasmic dynein; p80 shuttles between the nucleus and spindle pole in synchrony with the cell cycle (a feature shared with NuMA), and is essential for aster formation and maintenance in vitro. Depletion of p80 and/or NuMA induces abnormal mitotic phenotypes and aberrant neurogenesis/neuronal migration, confirmed in patient-derived iPSCs and brain organoids.\",\n      \"method\": \"siRNA-mediated depletion of p80 and/or NuMA in mouse embryonic fibroblasts; in vitro aster formation assay; live imaging of cell-cycle-dependent nuclear/spindle pole shuttling; mouse embryonic brain electroporation; patient-derived iPSCs and brain organoids\",\n      \"journal\": \"Scientific reports\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — multiple orthogonal methods (in vitro aster assay, siRNA, in vivo brain, patient iPSC organoids), functional epistasis with NuMA and dynein\",\n      \"pmids\": [\"28079116\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"KATNB1 interacts with the katanin A-subunits KATNA1 and KATNAL1 (and KATNAL2 in some contexts) as part of the mammalian Katanin family interaction network; proteomic analysis (mass spectrometry) defined the Katanin family interactome (Katan-ome), and KATNB1 was shown to compete with KATNBL1 for binding to KATNA1 and KATNAL1.\",\n      \"method\": \"Mass spectrometry-based proteomics (pull-down/affinity purification); in vitro microtubule-severing activity assay for KATNBL1; localization studies during cell cycle\",\n      \"journal\": \"Molecular & cellular proteomics : MCP\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — MS-based interactome plus in vitro severing assay, single lab, multiple orthogonal methods\",\n      \"pmids\": [\"26929214\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"KATNB1 is a master regulator of all katanin enzymatic A-subunits (KATNA1, KATNAL1, KATNAL2) during mammalian spermatogenesis; it is required to maintain katanin A-subunit protein abundance, and complete loss of KATNB1 from germ cells is incompatible with sperm production. KATNB1 has essential roles in male meiosis, acrosome formation, sperm tail assembly, regulation of the Sertoli and germ cell cytoskeletons during sperm nuclear remodelling, and maintenance of seminiferous epithelium integrity.\",\n      \"method\": \"Allelic loss-of-function series (multiple mouse knockout alleles) of KATNB1 in germ cells; histological analysis of seminiferous epithelium; immunostaining for katanin A-subunit abundance; phenotypic readouts across spermatogenesis stages\",\n      \"journal\": \"Development (Cambridge, England)\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — allelic series with multiple knockout lines, multiple orthogonal phenotypic readouts, clear epistasis placing KATNB1 upstream of all katanin A-subunits\",\n      \"pmids\": [\"34822718\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"The KATNB1 gene is driven by a 518-bp TATA-less promoter containing a critical CpG island and GC boxes; sequential deletion of these elements reduces promoter activity. The transcription factor Elk1 binds the KATNB1 promoter (demonstrated by EMSA) and activates it, increasing both KATNB1 mRNA and protein levels. KCl treatment that increases SUMOylation decreases KATNB1 promoter activity.\",\n      \"method\": \"Promoter deletion/reporter assays; EMSA (Elk1 binding to KATNB1 promoter); qRT-PCR and western blot for mRNA and protein levels after Elk1 manipulation; KCl/SUMOylation treatment in SH-SY5Y cells\",\n      \"journal\": \"PloS one\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — EMSA for direct binding plus reporter assays and expression measurement, single lab, two orthogonal methods\",\n      \"pmids\": [\"23894477\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"KATNB1 protein localizes to the microtubules of the manchette in human spermatids, a structure required for sperm head shaping, supporting a role in sperm morphogenesis beyond spindle formation.\",\n      \"method\": \"Immunostaining/immunofluorescence of human testicular biopsy samples; RT-PCR and in situ hybridization for mRNA expression across spermatogenesis stages\",\n      \"journal\": \"Andrology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — immunolocalization with stage-specific analysis across multiple samples, single lab, replicated in subsequent studies\",\n      \"pmids\": [\"25280067\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"KATNB1 protein is expressed exclusively in germ cells during human spermatogenesis; it localizes to type B spermatogonia entering meiosis, the Golgi complex of pachytene spermatocytes, colocalizes with the cleaving centriole just before the first meiotic division, and is found in early round spermatids in the dictyosome, supporting roles in spindle formation and microtubule-based structures during spermiogenesis.\",\n      \"method\": \"RT-PCR, RT-qPCR, in situ hybridization, immunohistochemistry/immunofluorescence on 80 human testicular biopsy samples across normal and impaired spermatogenesis\",\n      \"journal\": \"Fertility and sterility\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — multiple localization methods across large human sample set, single lab\",\n      \"pmids\": [\"27717557\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"Katnb1 is ubiquitously expressed during mouse embryonic development with stronger expression in the crown cells of the gastrulation organizer (murine node); null and hypomorphic Katnb1 mutations result in impaired left-right signaling and cardiac malformations, demonstrating a role for katanin in heart development.\",\n      \"method\": \"Knockin-knockout mouse model of Katnb1 dysfunction; in situ hybridization/expression analysis during embryogenesis; phenotypic characterization of null and hypomorphic embryos\",\n      \"journal\": \"Developmental dynamics\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — genetic loss-of-function with defined phenotypic readout in mouse model, single lab\",\n      \"pmids\": [\"28791777\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"In zebrafish, Katnb1 has an essential role in motile ciliated lineages; katnb1 mutants display defects in ependymal cell cilia and abnormal CSF flow that are associated with scoliosis, uncoupling ependymal cilia and Reissner fiber formation defects from spinal curvature while identifying abnormal CSF flow as a shared pathogenic signature.\",\n      \"method\": \"Zebrafish katnb1 mutant characterization; cilia motility assays; CSF flow measurement; spine curvature quantification; comparison across multiple scoliosis zebrafish models\",\n      \"journal\": \"iScience\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — genetic loss-of-function with multiple phenotypic readouts and epistatic uncoupling of phenotypes, single lab\",\n      \"pmids\": [\"36105588\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"During Klebsiella pneumoniae infection of lung epithelial cells, KATNB1 and KATNAL1 localize specifically to microtubule cut sites and act as gatekeepers for the microtubule-severing event; knockdown of either protein in infected cells maintained intact microtubules, demonstrating that KATNB1 is required for bacterially-induced host microtubule disassembly.\",\n      \"method\": \"siRNA knockdown of KATNB1 and KATNAL1 in lung epithelial cells; immunofluorescence localization to microtubule cut sites during K. pneumoniae infection; assessment of microtubule integrity in KD cells\",\n      \"journal\": \"Cellular microbiology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — siRNA knockdown with specific cellular phenotype readout, localization evidence, single lab\",\n      \"pmids\": [\"30415487\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"KATNB1 knockdown in rat primary Sertoli cells disrupts tight junction (TJ) permeability barrier function and causes perturbations in microtubule and actin cytoskeleton organization, leading to improper distribution of TJ and basal ectoplasmic specialization (ES) proteins. Conversely, overexpression of KATNB1 in the testis in vivo blocks cadmium-induced blood-testis barrier (BTB) disruption by maintaining proper cytoskeletal organization.\",\n      \"method\": \"RNAi knockdown of KATNB1 in primary Sertoli cells (TJ permeability assay); immunofluorescence colocalization with α-tubulin; KATNB1 overexpression in rat testis in vivo (cadmium injury model); western blot and immunostaining for cytoskeletal and junction proteins\",\n      \"journal\": \"FASEB journal\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal gain and loss of function with defined cellular phenotype, single lab, multiple readouts\",\n      \"pmids\": [\"39275889\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"KATNB1 works in partnership with KATNAL2 and TUBD1 (delta tubulin) in haploid male germ cells to regulate manchette remodeling and sperm head shaping, as demonstrated in a TUBD1 conditional knockout mouse model.\",\n      \"method\": \"Conditional knockout mouse model for TUBD1; genetic interaction analysis with KATNAL2 and KATNB1; immunostaining and phenotypic analysis of spermatogenesis\",\n      \"journal\": \"The Journal of cell biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — genetic interaction in vivo in conditional KO mouse with defined spermatogenesis phenotype, single lab\",\n      \"pmids\": [\"40586731\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"KATNAL2 can partner with KATNB1 or act autonomously depending on cellular context during spermatogenesis; KATNB1 is not universally required for all katanin A-subunit activities.\",\n      \"method\": \"KATNAL2 knockout mouse model with analysis of spermatogenesis; immunolocalization and co-immunoprecipitation of KATNAL2 with KATNB1\",\n      \"journal\": \"PLoS genetics\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — genetic KO plus Co-IP, single lab, defined in vivo phenotype\",\n      \"pmids\": [\"29136647\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"The mammalian testis KATNB1 interactome (defined by proteomics) includes a network of cytoskeletal and vesicle trafficking proteins, with KATNB1 physically associating with KATNA1 and KATNAL1 in testis.\",\n      \"method\": \"Affinity purification mass spectrometry (AP-MS) from mouse testis to define KATNB1 interactome\",\n      \"journal\": \"Development (Cambridge, England)\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — MS-based interactome from native tissue, single lab\",\n      \"pmids\": [\"37882691\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"KATNB1 encodes the noncatalytic regulatory p80 subunit of the Katanin microtubule-severing complex, where it physically interacts with and is required for the stability and localization of the catalytic A-subunits (KATNA1, KATNAL1, KATNAL2); it acts as a master regulator of katanin A-subunit abundance, controls mitotic spindle formation, centriole and cilia number, and microtubule-based structures (manchette, aster, spindle pole), shuttles between nucleus and spindle pole in a cell-cycle-dependent manner in cooperation with NuMA and cytoplasmic dynein, regulates Hedgehog signaling through centriole/cilia control, governs blood-testis barrier integrity through actin and microtubule cytoskeleton organization in Sertoli cells, and is required for left-right axis determination in the embryo via motile cilia at the node.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"KATNB1 encodes the noncatalytic regulatory (p80) subunit of the microtubule-severing enzyme katanin, where it binds the catalytic A-subunits KATNA1, KATNAL1, and KATNAL2 and acts as a master regulator that maintains their protein abundance and directs their activity to specific microtubule structures [#0, #3, #4]. Through this regulatory partnership it is required for proper mitotic spindle formation, and patient-derived fibroblasts carrying KATNB1 mutations show defective spindles, linking KATNB1 loss to microcephaly [#0]. KATNB1 controls centriole and cilia number and is required for Sonic hedgehog pathway activity during neocortical development, with its loss causing supernumerary centrioles and cilia [#1]. It coordinates microtubule remodeling with NuMA and cytoplasmic dynein, shuttling between the nucleus and spindle pole in a cell-cycle-dependent manner and driving aster formation [#2]. Beyond mitosis, KATNB1 is essential across spermatogenesis—governing meiosis, manchette remodeling and sperm head shaping (with KATNAL2 and TUBD1), and blood-testis barrier integrity through coordinated actin and microtubule organization in Sertoli cells [#4, #11, #12]—and is required in motile ciliated lineages for left-right axis determination and CSF flow [#8, #9]. KATNB1 is also recruited to microtubule cut sites with KATNAL1 to mediate bacterially-induced host microtubule disassembly during Klebsiella pneumoniae infection [#10].\",\n  \"teleology\": [\n    {\n      \"year\": 2013,\n      \"claim\": \"Before its regulation was known, the transcriptional control of KATNB1 was undefined; identifying its promoter and an activating transcription factor established how KATNB1 expression is set.\",\n      \"evidence\": \"Promoter deletion/reporter assays and EMSA showing Elk1 binding and activation in SH-SY5Y cells\",\n      \"pmids\": [\"23894477\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Physiological contexts in which Elk1 drives KATNB1 are not defined\", \"Link between SUMOylation and promoter repression is correlative\"]\n    },\n    {\n      \"year\": 2014,\n      \"claim\": \"It was unknown whether KATNB1 regulatory function is required for spindle assembly in humans; patient mutations disrupting the KATNB1–KATNA1 interaction caused defective spindles and microcephaly, establishing KATNB1 as a spindle regulator and disease gene.\",\n      \"evidence\": \"Exome sequencing of microcephaly patients, patient-fibroblast spindle assays, and zebrafish/Drosophila loss-of-function\",\n      \"pmids\": [\"25521378\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Structural basis of the KATNB1–KATNA1 interaction not resolved\", \"Mechanism linking spindle defects to neuronal depletion not detailed\"]\n    },\n    {\n      \"year\": 2014,\n      \"claim\": \"Whether katanin regulates centriole and cilia number was unknown; KATNB1 loss produced excess centrioles and cilia yet deficient Hedgehog signaling, revealing a centriole/cilia control function upstream of Shh.\",\n      \"evidence\": \"Katnb1 knockout mouse embryos, null fibroblast centriole/cilia counting and Hedgehog assays, and zebrafish loss-of-function\",\n      \"pmids\": [\"25521379\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Molecular mechanism by which katanin limits centriole number unknown\", \"Direct connection between cilia defects and Shh output not mechanistically dissected\"]\n    },\n    {\n      \"year\": 2014,\n      \"claim\": \"Whether KATNB1 acts beyond the mitotic spindle in male germ cells was unclear; its localization to the spermatid manchette implicated it in sperm head shaping.\",\n      \"evidence\": \"Immunostaining and in situ hybridization across stages in human testicular biopsies\",\n      \"pmids\": [\"25280067\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Functional requirement at the manchette not tested in this descriptive study\", \"Catalytic partner at the manchette not identified here\"]\n    },\n    {\n      \"year\": 2016,\n      \"claim\": \"The full set of katanin A-subunit partners and how subunit choice is governed were unresolved; interactome proteomics defined the Katan-ome and showed KATNB1 competes with KATNBL1 for binding A-subunits.\",\n      \"evidence\": \"Mass spectrometry interactome, in vitro severing assay, and cell-cycle localization\",\n      \"pmids\": [\"26929214\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Functional consequence of KATNB1 vs KATNBL1 competition in vivo not established\", \"Single-lab interactome without orthogonal validation of all partners\"]\n    },\n    {\n      \"year\": 2016,\n      \"claim\": \"The cellular stages of KATNB1 expression during human spermatogenesis were uncharacterized; expression mapping placed it in meiotic and post-meiotic germ cells at centriole and Golgi/dictyosome structures.\",\n      \"evidence\": \"RT-PCR, in situ hybridization, and immunohistochemistry across 80 human testicular biopsies\",\n      \"pmids\": [\"27717557\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Localization is descriptive without functional perturbation\", \"Role at the Golgi/dictyosome not defined\"]\n    },\n    {\n      \"year\": 2017,\n      \"claim\": \"How KATNB1 is spatially deployed during mitosis was unclear; it was shown to shuttle between nucleus and spindle pole with NuMA and dynein and to be required for aster formation, linking it functionally to neurogenesis.\",\n      \"evidence\": \"siRNA depletion in MEFs, in vitro aster assay, live imaging, mouse brain electroporation, and patient iPSC organoids\",\n      \"pmids\": [\"28079116\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Whether KATNB1 shuttling depends on its severing partners is unknown\", \"Direct biochemical interaction with NuMA/dynein not mapped\"]\n    },\n    {\n      \"year\": 2017,\n      \"claim\": \"Whether katanin contributes to embryonic left-right patterning was unknown; Katnb1 mutations impaired left-right signaling and caused cardiac malformations, with strong node expression.\",\n      \"evidence\": \"Knockin-knockout mouse model, embryonic expression analysis, and phenotyping of null/hypomorphic embryos\",\n      \"pmids\": [\"28791777\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Direct demonstration of nodal cilia motility defects not provided\", \"Cell-type-specific requirement at the node not isolated\"]\n    },\n    {\n      \"year\": 2017,\n      \"claim\": \"Whether KATNB1 is obligatory for all A-subunit activities was open; KATNAL2 was shown to act with or without KATNB1 depending on context, indicating context-dependent dependence.\",\n      \"evidence\": \"KATNAL2 knockout mouse with co-immunoprecipitation and immunolocalization with KATNB1\",\n      \"pmids\": [\"29136647\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Determinants of KATNB1-dependent vs autonomous KATNAL2 activity unknown\", \"Co-IP not reciprocally validated\"]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"Whether katanin participates in host responses to infection was unknown; KATNB1 and KATNAL1 were found at microtubule cut sites and required for bacterially-induced microtubule disassembly.\",\n      \"evidence\": \"siRNA knockdown and immunofluorescence localization in K. pneumoniae-infected lung epithelial cells\",\n      \"pmids\": [\"30415487\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Bacterial signal triggering recruitment unidentified\", \"Consequence for infection outcome not established\"]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"The hierarchy among katanin subunits in germ cells was unresolved; an allelic series placed KATNB1 upstream of all A-subunits, controlling their abundance and being indispensable for spermatogenesis.\",\n      \"evidence\": \"Multiple germ-cell Katnb1 knockout alleles with histology, A-subunit immunostaining, and stage-specific phenotyping\",\n      \"pmids\": [\"34822718\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Mechanism by which KATNB1 stabilizes A-subunit protein unknown\", \"Whether stabilization is direct or via localization not distinguished\"]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"The native tissue partners of KATNB1 were incompletely defined; testis AP-MS mapped a cytoskeletal and vesicle-trafficking interactome including KATNA1 and KATNAL1.\",\n      \"evidence\": \"Affinity purification mass spectrometry from mouse testis\",\n      \"pmids\": [\"37882691\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Functional significance of vesicle-trafficking associations untested\", \"Single-lab dataset without orthogonal confirmation\"]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Whether KATNB1 contributes to the blood-testis barrier was unknown; reciprocal loss/gain of function showed it maintains tight junction barrier function via actin and microtubule organization in Sertoli cells.\",\n      \"evidence\": \"RNAi knockdown in primary Sertoli cells with TJ permeability assays and KATNB1 overexpression in a rat cadmium injury model\",\n      \"pmids\": [\"39275889\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"How KATNB1 coordinates actin in addition to microtubules is unclear\", \"Catalytic A-subunit mediating this effect not identified\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"How manchette remodeling is controlled in haploid germ cells was incompletely understood; KATNB1 was shown to work with KATNAL2 and TUBD1 to regulate manchette remodeling and sperm head shaping.\",\n      \"evidence\": \"TUBD1 conditional knockout mouse with genetic interaction analysis and spermatogenesis phenotyping\",\n      \"pmids\": [\"40586731\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Biochemical interaction between KATNB1, KATNAL2, and TUBD1 not mapped\", \"Order of action among the three proteins not resolved\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The structural and biochemical basis by which KATNB1 stabilizes and spatially targets each katanin A-subunit, and how it switches between mitotic, ciliary, and germ-cell functions, remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No structure of the KATNB1–A-subunit complex\", \"Mechanism of A-subunit protein stabilization unknown\", \"Determinants of tissue- and context-specific partner selection undefined\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0098772\", \"supporting_discovery_ids\": [0, 3, 4]},\n      {\"term_id\": \"GO:0008092\", \"supporting_discovery_ids\": [0, 2, 11]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005815\", \"supporting_discovery_ids\": [2, 7]},\n      {\"term_id\": \"GO:0005856\", \"supporting_discovery_ids\": [6, 10, 11]},\n      {\"term_id\": \"GO:0005634\", \"supporting_discovery_ids\": [2]},\n      {\"term_id\": \"GO:0005929\", \"supporting_discovery_ids\": [1, 9]},\n      {\"term_id\": \"GO:0005794\", \"supporting_discovery_ids\": [7]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-1640170\", \"supporting_discovery_ids\": [0, 2]},\n      {\"term_id\": \"R-HSA-1266738\", \"supporting_discovery_ids\": [1, 8]},\n      {\"term_id\": \"R-HSA-1474165\", \"supporting_discovery_ids\": [4, 12]},\n      {\"term_id\": \"R-HSA-162582\", \"supporting_discovery_ids\": [1]}\n    ],\n    \"complexes\": [\"Katanin (p60/p80) microtubule-severing complex\"],\n    \"partners\": [\"KATNA1\", \"KATNAL1\", \"KATNAL2\", \"KATNBL1\", \"NUMA1\", \"TUBD1\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":6,"faith_total":6,"faith_pct":100.0}}