{"gene":"NIN","run_date":"2026-06-10T05:19:52","timeline":{"discoveries":[{"year":2004,"finding":"NIN (Ninein) was identified as a centrosomal protein with CEP110-like function. It was found fused to PDGFRB via a t(5;14)(q33;q24) chromosomal translocation in a patient with chronic myeloproliferative disorder with eosinophilia, producing the oncogenic NIN-PDGFRB fusion. The NIN gene was selected as a candidate partner based on the presence of predicted oligomerization domains. Treatment with imatinib produced hematological and cytogenetic remission, consistent with constitutive PDGFRB kinase activation driven by NIN-mediated oligomerization.","method":"Fluorescence in situ hybridization (FISH) to map breakpoints, reverse transcription-PCR to detect NIN-PDGFRB fusion mRNA, candidate gene selection based on oligomerization domain prediction, clinical imatinib response","journal":"Cancer research","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — FISH and RT-PCR confirm fusion gene; oligomerization domain inference is computational; single case report with clinical validation but no reconstitution or direct biochemical assay of NIN oligomerization","pmids":["15087377"],"is_preprint":false},{"year":2012,"finding":"NIN (Ninein) is necessary for maintaining asymmetric, neurogenic divisions of radial glial cells (RGCs). Positive selection on NIN was detected during anthropoid primate evolution, and selection on NIN was significantly associated with neonatal brain size in catarrhines, implicating NIN in the evolution of cortical neuron number through neurogenic RGC divisions.","method":"Molecular evolutionary analysis (dN/dS ratios across primate lineages), correlation of selection signatures with neural phenotypes (neonatal brain size, neuron number estimates)","journal":"Genes, brain, and behavior","confidence":"Low","confidence_rationale":"Tier 4 / Weak — evolutionary/comparative analysis only; no direct cellular experiment on NIN function in RGC divisions performed in this study; mechanistic role in neurogenic divisions referenced from prior literature rather than experimentally established here","pmids":["22937743"],"is_preprint":false},{"year":2013,"finding":"Homozygous missense mutations in NIN (Ninein) were identified in a consanguineous family with a spondyloepimetaphyseal dysplasia with joint laxity (SEMDJL2)-like phenotype. The NIN protein showed a functional relationship with KIF22 and other proteins associated with chromosome congression/movement, centrosomal function, and ciliogenesis, supporting a fundamental role for Ninein in skeletal development. Evidence included cosegregation of the variant with disease phenotype, absence in 500 healthy controls and 1000-genomes database, and comparison with previously identified compound heterozygous NIN mutations in microcephalic primordial dwarfism.","method":"Homozygosity mapping, whole-exome sequencing, cosegregation analysis, population control screening, functional relationship inference from known NIN interactors","journal":"Matrix biology : journal of the International Society for Matrix Biology","confidence":"Low","confidence_rationale":"Tier 3 / Weak — genetic mapping and sequencing establish disease association; no direct biochemical or cell biological experiment performed on the mutant protein; functional relationship with KIF22/centrosome inferred from literature, not tested here","pmids":["23665482"],"is_preprint":false},{"year":2025,"finding":"QKI splicing factor directly binds NIN pre-mRNA and promotes inclusion of exon 18, generating an oncogenic exon-18-included NIN isoform. Depletion of the exon-18-included NIN isoform suppressed proliferation, migration, and invasion of breast cancer cells, induced S-phase arrest via dysregulation of the CDK2/Cyclin A axis, and significantly inhibited tumor growth in vivo.","method":"Multi-omics TCGA analysis, RNA binding protein eCLIP, functional knockdown experiments (cell proliferation, migration, invasion assays), flow cytometry cell cycle analysis, CDK2/Cyclin A western blot, in vivo xenograft tumor model","journal":"Cellular signalling","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct RNA binding (eCLIP) and functional rescue experiments in cells and in vivo; single lab, multiple orthogonal methods; QKI-NIN pre-mRNA interaction and isoform-specific phenotype established","pmids":["41135748"],"is_preprint":false}],"current_model":"NIN (Ninein) is a centrosomal protein with predicted oligomerization domains that, when fused to PDGFRB via chromosomal translocation, constitutively activates PDGFRB kinase signaling; it plays a role in asymmetric neurogenic divisions of radial glial cells relevant to cortical development; biallelic loss-of-function mutations cause microcephalic primordial dwarfism and skeletal dysplasia through disruption of centrosomal function; and the QKI splicing factor directly binds NIN pre-mRNA to promote exon 18 inclusion, generating an oncogenic isoform that drives cell cycle progression via the CDK2/Cyclin A axis in breast cancer."},"narrative":{"mechanistic_narrative":"NIN (Ninein) is a centrosomal protein implicated in cell division, oncogenesis, and skeletal and cortical development. Its predicted oligomerization domains underlie its capacity to constitutively activate fused kinases: a t(5;14)(q33;q24) translocation generates a NIN-PDGFRB fusion that drives an imatinib-responsive myeloproliferative disorder through NIN-mediated dimerization and constitutive PDGFRB kinase signaling [PMID:15087377]. Independent of this rearrangement, NIN pre-mRNA is a direct substrate of the splicing factor QKI, which binds it and promotes inclusion of exon 18 to generate an oncogenic isoform that sustains breast cancer cell proliferation, migration, and invasion by engaging the CDK2/Cyclin A axis, with depletion of the exon-18-included isoform inducing S-phase arrest and inhibiting tumor growth in vivo [PMID:41135748]. Beyond these oncogenic and splicing-regulated mechanisms, the structural and biochemical basis of NIN's centrosomal function has not been directly characterized in the available corpus.","teleology":[{"year":2004,"claim":"Established NIN as an oncogenic fusion partner whose oligomerization domains can constitutively activate a receptor tyrosine kinase, explaining why a centrosomal protein contributes to myeloproliferative disease.","evidence":"FISH breakpoint mapping and RT-PCR detection of NIN-PDGFRB fusion mRNA in a chronic myeloproliferative disorder patient, with clinical imatinib response","pmids":["15087377"],"confidence":"Medium","gaps":["NIN oligomerization was inferred computationally, not demonstrated biochemically","single case report without reconstitution of the fusion's kinase activity","wild-type NIN's normal centrosomal mechanism not addressed"]},{"year":2012,"claim":"Linked NIN to the evolutionary expansion of cortical neuron number by associating positive selection on NIN with neurogenic radial glial cell divisions and brain size.","evidence":"Molecular evolutionary analysis (dN/dS across primate lineages) correlated with neonatal brain size in catarrhines","pmids":["22937743"],"confidence":"Low","gaps":["comparative analysis only; no direct cellular experiment on NIN function in RGC divisions","mechanistic role in neurogenic divisions cited from prior literature, not tested here","molecular pathway connecting NIN to division asymmetry undefined"]},{"year":2013,"claim":"Connected NIN loss-of-function to human skeletal dysplasia, implicating centrosomal/ciliogenic function in skeletal development.","evidence":"Homozygosity mapping, whole-exome sequencing, and cosegregation in a consanguineous family with a SEMDJL2-like phenotype, with population control screening","pmids":["23665482"],"confidence":"Low","gaps":["no biochemical or cell biological assay on the mutant protein performed","functional relationship with KIF22 and centrosomal function inferred from literature","causal mechanism linking NIN mutation to skeletal phenotype not established"]},{"year":2025,"claim":"Identified NIN pre-mRNA as a direct QKI splicing target, defining an exon-18-included isoform as an oncogenic driver acting through the CDK2/Cyclin A cell-cycle axis.","evidence":"eCLIP for direct RNA binding, isoform-specific knockdown with proliferation/migration/invasion assays, flow cytometry cell-cycle analysis, CDK2/Cyclin A western blot, and xenograft tumor model in breast cancer","pmids":["41135748"],"confidence":"Medium","gaps":["single-lab study without independent replication","molecular function of the exon-18-included isoform protein not defined","mechanism linking the isoform to CDK2/Cyclin A regulation not resolved"]},{"year":null,"claim":"The direct biochemical and structural basis of NIN's centrosomal activity, and how it mechanistically couples to neurogenic division, skeletal development, and cell-cycle control, remains unresolved.","evidence":"No direct structural or reconstitution study of NIN appears in the corpus","pmids":[],"confidence":"Low","gaps":["no structural model of NIN or its oligomerization domains","no direct demonstration of NIN's molecular activity at the centrosome","mechanism connecting NIN isoform to CDK2/Cyclin A regulation unknown"]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":[],"partners":["PDGFRB","QKI"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q8N4C6","full_name":"Ninein","aliases":["Glycogen synthase kinase 3 beta-interacting protein","GSK3B-interacting protein"],"length_aa":2090,"mass_kda":243.2,"function":"Centrosomal protein required in the positioning and anchorage of the microtubule minus-end in epithelial cells (PubMed:15190203, PubMed:23386061). May also act as a centrosome maturation factor (PubMed:11956314). May play a role in microtubule nucleation, by recruiting the gamma-tubulin ring complex to the centrosome (PubMed:15190203). Overexpression does not perturb nucleation or elongation of microtubules but suppresses release of microtubules (PubMed:15190203). Required for centriole organization and microtubule anchoring at the mother centriole (PubMed:23386061)","subcellular_location":"Cytoplasm","url":"https://www.uniprot.org/uniprotkb/Q8N4C6/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/NIN","classification":"Not Classified","n_dependent_lines":1,"n_total_lines":1208,"dependency_fraction":0.0008278145695364238},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[{"gene":"CCT5","stoichiometry":0.2},{"gene":"CCT6A","stoichiometry":0.2},{"gene":"CLASP1","stoichiometry":0.2},{"gene":"CLASP2","stoichiometry":0.2},{"gene":"CLIP1","stoichiometry":0.2},{"gene":"TUBB4B","stoichiometry":0.2}],"url":"https://opencell.sf.czbiohub.org/search/NIN","total_profiled":1310},"omim":[{"mim_id":"620397","title":"AURORA KINASE A- AND NINEIN-INTERACTING PROTEIN; AUNIP","url":"https://www.omim.org/entry/620397"},{"mim_id":"614851","title":"SECKEL SYNDROME 7; SCKL7","url":"https://www.omim.org/entry/614851"},{"mim_id":"614848","title":"CENTROSOMAL PROTEIN, 164-KD; CEP164","url":"https://www.omim.org/entry/614848"},{"mim_id":"611425","title":"CENTROBIN, CENTRIOLE DUPLICATION AND SPINDLE ASSEMBLY PROTEIN; CNTROB","url":"https://www.omim.org/entry/611425"},{"mim_id":"610858","title":"RNA TRANSCRIPTION, TRANSLATION, AND TRANSPORT FACTOR; RTRAF","url":"https://www.omim.org/entry/610858"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Supported","locations":[{"location":"Centrosome","reliability":"Supported"},{"location":"Basal body","reliability":"Supported"},{"location":"Nucleoli","reliability":"Additional"},{"location":"Nucleoli rim","reliability":"Additional"}],"tissue_specificity":"Tissue enhanced","tissue_distribution":"Detected in all","driving_tissues":[{"tissue":"bone marrow","ntpm":38.9}],"url":"https://www.proteinatlas.org/search/NIN"},"hgnc":{"alias_symbol":[],"prev_symbol":[]},"alphafold":{"accession":"Q8N4C6","domains":[{"cath_id":"1.10.238.10","chopping":"2-80","consensus_level":"medium","plddt":71.3751,"start":2,"end":80},{"cath_id":"1.10.238","chopping":"184-249","consensus_level":"medium","plddt":71.7952,"start":184,"end":249}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q8N4C6","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q8N4C6-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q8N4C6-F1-predicted_aligned_error_v6.png","plddt_mean":63.97},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=NIN","jax_strain_url":"https://www.jax.org/strain/search?query=NIN"},"sequence":{"accession":"Q8N4C6","fasta_url":"https://rest.uniprot.org/uniprotkb/Q8N4C6.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q8N4C6/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q8N4C6"}},"corpus_meta":[{"pmid":"17369436","id":"PMC_17369436","title":"Medicago truncatula NIN is essential for rhizobial-independent nodule organogenesis induced by autoactive calcium/calmodulin-dependent protein kinase.","date":"2007","source":"Plant physiology","url":"https://pubmed.ncbi.nlm.nih.gov/17369436","citation_count":310,"is_preprint":false},{"pmid":"36137053","id":"PMC_36137053","title":"NIN-like protein 7 transcription factor is a plant nitrate sensor.","date":"2022","source":"Science (New York, N.Y.)","url":"https://pubmed.ncbi.nlm.nih.gov/36137053","citation_count":200,"is_preprint":false},{"pmid":"29403008","id":"PMC_29403008","title":"A NIN-LIKE PROTEIN mediates nitrate-induced control of root nodule symbiosis in Lotus japonicus.","date":"2018","source":"Nature communications","url":"https://pubmed.ncbi.nlm.nih.gov/29403008","citation_count":145,"is_preprint":false},{"pmid":"26672071","id":"PMC_26672071","title":"The NIN Transcription Factor Coordinates Diverse Nodulation Programs in Different Tissues of the Medicago truncatula Root.","date":"2015","source":"The Plant cell","url":"https://pubmed.ncbi.nlm.nih.gov/26672071","citation_count":138,"is_preprint":false},{"pmid":"30297831","id":"PMC_30297831","title":"NIN interacts with NLPs to mediate nitrate inhibition of nodulation in Medicago truncatula.","date":"2018","source":"Nature plants","url":"https://pubmed.ncbi.nlm.nih.gov/30297831","citation_count":131,"is_preprint":false},{"pmid":"12644653","id":"PMC_12644653","title":"The Sym35 gene required for root nodule development in pea is an ortholog of Nin from Lotus japonicus.","date":"2003","source":"Plant physiology","url":"https://pubmed.ncbi.nlm.nih.gov/12644653","citation_count":116,"is_preprint":false},{"pmid":"30610167","id":"PMC_30610167","title":"A Remote cis-Regulatory Region Is Required for NIN Expression in the Pericycle to Initiate Nodule Primordium Formation in Medicago truncatula.","date":"2019","source":"The Plant cell","url":"https://pubmed.ncbi.nlm.nih.gov/30610167","citation_count":106,"is_preprint":false},{"pmid":"34709882","id":"PMC_34709882","title":"NIN-like protein transcription factors regulate leghemoglobin genes in legume nodules.","date":"2021","source":"Science (New York, N.Y.)","url":"https://pubmed.ncbi.nlm.nih.gov/34709882","citation_count":102,"is_preprint":false},{"pmid":"30710053","id":"PMC_30710053","title":"NIN Acts as a Network Hub Controlling a Growth Module Required for Rhizobial Infection.","date":"2019","source":"Plant physiology","url":"https://pubmed.ncbi.nlm.nih.gov/30710053","citation_count":101,"is_preprint":false},{"pmid":"32576831","id":"PMC_32576831","title":"The NIN transcription factor coordinates CEP and CLE signaling peptides that regulate nodulation antagonistically.","date":"2020","source":"Nature communications","url":"https://pubmed.ncbi.nlm.nih.gov/32576831","citation_count":95,"is_preprint":false},{"pmid":"32876985","id":"PMC_32876985","title":"Rice NIN-LIKE PROTEIN 4 plays a pivotal role in nitrogen use efficiency.","date":"2020","source":"Plant biotechnology journal","url":"https://pubmed.ncbi.nlm.nih.gov/32876985","citation_count":91,"is_preprint":false},{"pmid":"32585013","id":"PMC_32585013","title":"Rice NIN-LIKE PROTEIN 1 rapidly responds to nitrogen deficiency and improves yield and nitrogen use efficiency.","date":"2020","source":"Journal of experimental botany","url":"https://pubmed.ncbi.nlm.nih.gov/32585013","citation_count":86,"is_preprint":false},{"pmid":"33826745","id":"PMC_33826745","title":"Different DNA-binding specificities of NLP and NIN transcription factors underlie nitrate-induced control of root nodulation.","date":"2021","source":"The Plant cell","url":"https://pubmed.ncbi.nlm.nih.gov/33826745","citation_count":78,"is_preprint":false},{"pmid":"23869222","id":"PMC_23869222","title":"MicroRNA-326 functions as a tumor suppressor in glioma by targeting the Nin one binding protein 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metabolism","url":"https://pubmed.ncbi.nlm.nih.gov/19519902","citation_count":58,"is_preprint":false},{"pmid":"35150141","id":"PMC_35150141","title":"Rice NIN-LIKE PROTEIN 3 modulates nitrogen use efficiency and grain yield under nitrate-sufficient conditions.","date":"2022","source":"Plant, cell & environment","url":"https://pubmed.ncbi.nlm.nih.gov/35150141","citation_count":57,"is_preprint":false},{"pmid":"31793100","id":"PMC_31793100","title":"The NIN-like protein 5 (ZmNLP5) transcription factor is involved in modulating the nitrogen response in maize.","date":"2020","source":"The Plant journal : for cell and molecular biology","url":"https://pubmed.ncbi.nlm.nih.gov/31793100","citation_count":57,"is_preprint":false},{"pmid":"26096779","id":"PMC_26096779","title":"The Casuarina NIN gene is transcriptionally activated throughout Frankia root infection as well as in response to bacterial diffusible signals.","date":"2015","source":"The New phytologist","url":"https://pubmed.ncbi.nlm.nih.gov/26096779","citation_count":57,"is_preprint":false},{"pmid":"32664480","id":"PMC_32664480","title":"Evolution of NIN and NIN-like Genes in Relation to Nodule Symbiosis.","date":"2020","source":"Genes","url":"https://pubmed.ncbi.nlm.nih.gov/32664480","citation_count":56,"is_preprint":false},{"pmid":"25760058","id":"PMC_25760058","title":"MicroRNA-326 functions as a tumor suppressor in colorectal cancer by targeting the nin one binding protein.","date":"2015","source":"Oncology reports","url":"https://pubmed.ncbi.nlm.nih.gov/25760058","citation_count":55,"is_preprint":false},{"pmid":"24270631","id":"PMC_24270631","title":"The evolutionary events necessary for the emergence of symbiotic nitrogen fixation in legumes may involve a loss of nitrate responsiveness of the NIN transcription factor.","date":"2013","source":"Plant signaling & 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cell","url":"https://pubmed.ncbi.nlm.nih.gov/35146519","citation_count":45,"is_preprint":false},{"pmid":"33471433","id":"PMC_33471433","title":"NIN is essential for development of symbiosomes, suppression of defence and premature senescence in Medicago truncatula nodules.","date":"2021","source":"The New phytologist","url":"https://pubmed.ncbi.nlm.nih.gov/33471433","citation_count":45,"is_preprint":false},{"pmid":"36440970","id":"PMC_36440970","title":"The small peptide CEP1 and the NIN-like protein NLP1 regulate NRT2.1 to mediate root nodule formation across nitrate concentrations.","date":"2023","source":"The Plant cell","url":"https://pubmed.ncbi.nlm.nih.gov/36440970","citation_count":44,"is_preprint":false},{"pmid":"31863481","id":"PMC_31863481","title":"Mutant analysis in the nonlegume Parasponia andersonii identifies NIN and NF-YA1 transcription factors as a core genetic network in nitrogen-fixing nodule symbioses.","date":"2020","source":"The New 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International Society for Matrix Biology","url":"https://pubmed.ncbi.nlm.nih.gov/23665482","citation_count":19,"is_preprint":false},{"pmid":"34301191","id":"PMC_34301191","title":"Genome-wide survey and expression analysis of NIN-like Protein (NLP) genes reveals its potential roles in the response to nitrate signaling in tomato.","date":"2021","source":"BMC plant biology","url":"https://pubmed.ncbi.nlm.nih.gov/34301191","citation_count":17,"is_preprint":false},{"pmid":"35343248","id":"PMC_35343248","title":"The CYCLOPS Response Element in the NIN Promoter Is Important but Not Essential for Infection Thread Formation During Lotus japonicus-Rhizobia Symbiosis.","date":"2022","source":"Molecular plant-microbe interactions : MPMI","url":"https://pubmed.ncbi.nlm.nih.gov/35343248","citation_count":17,"is_preprint":false},{"pmid":"6277651","id":"PMC_6277651","title":"Effect of Nin-formylation of the tryptophan residue on gastrin (HG-13) binding and on gastric acid 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biology","url":"https://pubmed.ncbi.nlm.nih.gov/37633494","citation_count":15,"is_preprint":false},{"pmid":"2972695","id":"PMC_2972695","title":"Analysis of transcription termination signals in the nin region of bacteriophage lambda: the roc deletion.","date":"1988","source":"Journal of bacteriology","url":"https://pubmed.ncbi.nlm.nih.gov/2972695","citation_count":15,"is_preprint":false},{"pmid":"36139868","id":"PMC_36139868","title":"The NIN-Like Protein OsNLP2 Negatively Regulates Ferroptotic Cell Death and Immune Responses to Magnaporthe oryzae in Rice.","date":"2022","source":"Antioxidants (Basel, Switzerland)","url":"https://pubmed.ncbi.nlm.nih.gov/36139868","citation_count":14,"is_preprint":false},{"pmid":"31880983","id":"PMC_31880983","title":"CLE-HAR1 Systemic Signaling and NIN-Mediated Local Signaling Suppress the Increased Rhizobial Infection in the daphne Mutant of Lotus japonicus.","date":"2019","source":"Molecular plant-microbe interactions : MPMI","url":"https://pubmed.ncbi.nlm.nih.gov/31880983","citation_count":14,"is_preprint":false},{"pmid":"34618055","id":"PMC_34618055","title":"NIN-like protein7 and PROTEOLYSIS6 functional interaction enhances tolerance to sucrose, ABA, and submergence.","date":"2021","source":"Plant physiology","url":"https://pubmed.ncbi.nlm.nih.gov/34618055","citation_count":13,"is_preprint":false},{"pmid":"38199025","id":"PMC_38199025","title":"Genome-wide identification and expression analysis of NIN-like protein (NLP) genes: Exploring their potential roles in nitrate response in tea plant (Camellia sinensis).","date":"2024","source":"Plant physiology and biochemistry : PPB","url":"https://pubmed.ncbi.nlm.nih.gov/38199025","citation_count":13,"is_preprint":false},{"pmid":"39100871","id":"PMC_39100871","title":"NIN-like proteins (NLPs) as crucial nitrate sensors: an overview of their roles in nitrogen signaling, symbiosis, abiotic stress, and beyond.","date":"2024","source":"Physiology and molecular biology of plants : an international journal of functional plant biology","url":"https://pubmed.ncbi.nlm.nih.gov/39100871","citation_count":13,"is_preprint":false},{"pmid":"27899928","id":"PMC_27899928","title":"NIN Is Involved in the Regulation of Arbuscular Mycorrhizal Symbiosis.","date":"2016","source":"Frontiers in plant science","url":"https://pubmed.ncbi.nlm.nih.gov/27899928","citation_count":11,"is_preprint":false},{"pmid":"33775367","id":"PMC_33775367","title":"Functional analyses unveil the involvement of moso bamboo (Phyllostachys edulis) group I and II NIN-LIKE PROTEINS in nitrate signaling regulation.","date":"2021","source":"Plant science : an international journal of experimental plant biology","url":"https://pubmed.ncbi.nlm.nih.gov/33775367","citation_count":11,"is_preprint":false},{"pmid":"33779265","id":"PMC_33779265","title":"Three Common Symbiotic ABC Subfamily B Transporters in Medicago truncatula Are Regulated by a NIN-Independent Branch of the Symbiosis Signaling Pathway.","date":"2021","source":"Molecular plant-microbe interactions : MPMI","url":"https://pubmed.ncbi.nlm.nih.gov/33779265","citation_count":11,"is_preprint":false},{"pmid":"28720806","id":"PMC_28720806","title":"Heteroborospherene clusters Nin ∈ B40 (n = 1-4) and heteroborophene monolayers Ni2 ∈ B14 with planar heptacoordinate transition-metal centers in η7-B7 heptagons.","date":"2017","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/28720806","citation_count":10,"is_preprint":false},{"pmid":"36226899","id":"PMC_36226899","title":"NiN-Passivated NiO Hole-Transport Layer Improves Halide Perovskite-Based Solar Cell.","date":"2022","source":"ACS applied materials & interfaces","url":"https://pubmed.ncbi.nlm.nih.gov/36226899","citation_count":9,"is_preprint":false},{"pmid":"34135927","id":"PMC_34135927","title":"Phylogenetic and Structural Analysis of NIN-Like Proteins With a Type I/II PB1 Domain That Regulates Oligomerization for Nitrate Response.","date":"2021","source":"Frontiers in plant science","url":"https://pubmed.ncbi.nlm.nih.gov/34135927","citation_count":9,"is_preprint":false},{"pmid":"11154043","id":"PMC_11154043","title":"Effects of qian-kun-nin, a Chinese herbal medicine formulation, on HIV positive subjects: a pilot study.","date":"2000","source":"The American journal of Chinese medicine","url":"https://pubmed.ncbi.nlm.nih.gov/11154043","citation_count":9,"is_preprint":false},{"pmid":"27645388","id":"PMC_27645388","title":"The Topology of the l-Arginine Exporter ArgO Conforms to an Nin-Cout Configuration in Escherichia coli: Requirement for the Cytoplasmic N-Terminal Domain, Functional Helical Interactions, and an Aspartate Pair for ArgO Function.","date":"2016","source":"Journal of bacteriology","url":"https://pubmed.ncbi.nlm.nih.gov/27645388","citation_count":8,"is_preprint":false},{"pmid":"35294329","id":"PMC_35294329","title":"Overexpression of microRNA-107 suppressed proliferation, migration, invasion, and the PI3K/Akt signaling pathway and induced apoptosis by targeting Nin one binding (NOB1) protein in a hypopharyngeal squamous cell carcinoma cell line (FaDu).","date":"2022","source":"Bioengineered","url":"https://pubmed.ncbi.nlm.nih.gov/35294329","citation_count":7,"is_preprint":false},{"pmid":"25420906","id":"PMC_25420906","title":"Evaluation of NIN/RPN12 binding protein inhibits proliferation and growth in human renal cancer cells.","date":"2014","source":"Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine","url":"https://pubmed.ncbi.nlm.nih.gov/25420906","citation_count":6,"is_preprint":false},{"pmid":"37358766","id":"PMC_37358766","title":"Identification and expression characteristics of NLP (NIN-like protein) gene family in pepper (Capsicum annuum L.).","date":"2023","source":"Molecular biology 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behavior","url":"https://pubmed.ncbi.nlm.nih.gov/29215953","citation_count":3,"is_preprint":false},{"pmid":"39905670","id":"PMC_39905670","title":"Distinct domain regions of NIN and NLP1 mediate symbiotic and nitrate signalling in Medicago truncatula.","date":"2025","source":"Journal of experimental botany","url":"https://pubmed.ncbi.nlm.nih.gov/39905670","citation_count":2,"is_preprint":false},{"pmid":"41213871","id":"PMC_41213871","title":"GRAS51 promotes legume symbiotic nitrogen fixation and salt tolerance of nodulation by directly regulating NIN expression.","date":"2025","source":"Plant physiology","url":"https://pubmed.ncbi.nlm.nih.gov/41213871","citation_count":2,"is_preprint":false},{"pmid":"40885889","id":"PMC_40885889","title":"Identification and expression characteristics of NIN-like protein (NLP) gene family in cucumber plant (Cucumis sativus L.).","date":"2025","source":"BMC plant biology","url":"https://pubmed.ncbi.nlm.nih.gov/40885889","citation_count":1,"is_preprint":false},{"pmid":"38790169","id":"PMC_38790169","title":"The Satellite DNA PcH-Sat, Isolated and Characterized in the Limpet Patella caerulea (Mollusca, Gastropoda), Suggests the Origin from a Nin-SINE Transposable Element.","date":"2024","source":"Genes","url":"https://pubmed.ncbi.nlm.nih.gov/38790169","citation_count":1,"is_preprint":false},{"pmid":"39899489","id":"PMC_39899489","title":"The auxin phenylacetic acid induces NIN expression in the actinorhizal plant Datisca glomerata, whereas cytokinin acts antagonistically.","date":"2025","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/39899489","citation_count":1,"is_preprint":false},{"pmid":"41616063","id":"PMC_41616063","title":"The root nodule symbiosis regulator NIN exhibits broad DNA binding specificity conferred by an NLP-inherited motif.","date":"2026","source":"Science 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physiology","url":"https://pubmed.ncbi.nlm.nih.gov/41269885","citation_count":0,"is_preprint":false},{"pmid":"40159793","id":"PMC_40159793","title":"Natural Variation in NIN-LIKE PROTEIN 4 Associated With Spike-Response to Nitrogen in Barley.","date":"2025","source":"Plant, cell & environment","url":"https://pubmed.ncbi.nlm.nih.gov/40159793","citation_count":0,"is_preprint":false},{"pmid":"41942423","id":"PMC_41942423","title":"Ancestral functionality and symbiotic refinement of NIN in root nodule symbiosis.","date":"2026","source":"Nature communications","url":"https://pubmed.ncbi.nlm.nih.gov/41942423","citation_count":0,"is_preprint":false},{"pmid":"41135748","id":"PMC_41135748","title":"Multi-omics reveals that QKI-mediated NIN exon 18 splicing drives breast cancer cell progression.","date":"2025","source":"Cellular signalling","url":"https://pubmed.ncbi.nlm.nih.gov/41135748","citation_count":0,"is_preprint":false},{"pmid":"41174857","id":"PMC_41174857","title":"RSD-mediated suppression of NIN and NLP2 transcription is crucial for symbiotic nitrogen fixation.","date":"2025","source":"The New phytologist","url":"https://pubmed.ncbi.nlm.nih.gov/41174857","citation_count":0,"is_preprint":false},{"pmid":"40751525","id":"PMC_40751525","title":"Expanding the Clinical Phenotype Associated with the NIN Gene; Report of a Patient with Short Stature, Microcephaly and Hearing Loss.","date":"2025","source":"Archives of Iranian medicine","url":"https://pubmed.ncbi.nlm.nih.gov/40751525","citation_count":0,"is_preprint":false},{"pmid":"42251962","id":"PMC_42251962","title":"MaWRKY76 enhances symbiotic nodulation and salt tolerance of nodulation by activating NIN in Melilotus albus.","date":"2026","source":"Journal of genetics and genomics = Yi chuan xue bao","url":"https://pubmed.ncbi.nlm.nih.gov/42251962","citation_count":0,"is_preprint":false},{"pmid":"2397540","id":"PMC_2397540","title":"[Clinical and experimental study of wei-nin granules in the treatment of chronic superficial gastritis].","date":"1990","source":"Zhong xi yi jie he za zhi = Chinese journal of modern developments in traditional medicine","url":"https://pubmed.ncbi.nlm.nih.gov/2397540","citation_count":0,"is_preprint":false},{"pmid":"24936165","id":"PMC_24936165","title":"Simplified ZrTiO x -based RRAM cell structure with rectifying characteristics by integrating Ni/n + -Si diode.","date":"2014","source":"Nanoscale research letters","url":"https://pubmed.ncbi.nlm.nih.gov/24936165","citation_count":0,"is_preprint":false},{"pmid":null,"id":"bio_10.1101_2025.08.21.671612","title":"Evolutionary predisposition of NIN to function in nitrogen-fixing nodules","date":"2025-08-25","source":"bioRxiv","url":"https://doi.org/10.1101/2025.08.21.671612","citation_count":0,"is_preprint":true},{"pmid":null,"id":"bio_10.1101_2025.07.20.665785","title":"An NLP-inherited motif confers broad DNA-binding specificity to NIN in root nodule symbiosis","date":"2025-07-23","source":"bioRxiv","url":"https://doi.org/10.1101/2025.07.20.665785","citation_count":0,"is_preprint":true},{"pmid":null,"id":"bio_10.1101_2025.11.16.25340343","title":"Artificial Intelligence for Significant Mitral Regurgitation Screening and Diagnosis: A Systematic Review and Meta-analysis","date":"2025-11-17","source":"bioRxiv","url":"https://doi.org/10.1101/2025.11.16.25340343","citation_count":0,"is_preprint":true},{"pmid":null,"id":"bio_10.1101_2025.11.03.684091","title":"Nitrate restricts the expression of non-symbiotic leghemoglobin through inhibition of nodule inception protein in nodules of peanut (  <i>Arachis hypogaea</i>  )","date":"2025-11-05","source":"bioRxiv","url":"https://doi.org/10.1101/2025.11.03.684091","citation_count":0,"is_preprint":true},{"pmid":null,"id":"bio_10.1101_2025.10.10.681601","title":"A hierarchical nickel organic framework confers high conductivity over long distances in cable bacteria","date":"2025-10-11","source":"bioRxiv","url":"https://doi.org/10.1101/2025.10.10.681601","citation_count":0,"is_preprint":true},{"pmid":null,"id":"bio_10.1101_2025.09.04.674271","title":"QKI ensures splicing fidelity during cardiogenesis by engaging the U6 tri-snRNP to activate splicing at weak 5ʹ splice sites","date":"2025-09-07","source":"bioRxiv","url":"https://doi.org/10.1101/2025.09.04.674271","citation_count":0,"is_preprint":true},{"pmid":null,"id":"bio_10.1101_2025.11.04.25339356","title":"Macronutrient Intake and Dietary Patterns in Indian Adults with and without Type 2 Diabetes: Findings From the Multicentric I-STARCH-1 Study","date":"2025-11-13","source":"bioRxiv","url":"https://doi.org/10.1101/2025.11.04.25339356","citation_count":0,"is_preprint":true},{"pmid":null,"id":"bio_10.1101_2025.09.05.674380","title":"Cytokinin receptor AHK3 influences leaf size by modulating  <i>trans</i>  -zeatin-type cytokinin levels in xylem","date":"2025-09-05","source":"bioRxiv","url":"https://doi.org/10.1101/2025.09.05.674380","citation_count":0,"is_preprint":true},{"pmid":null,"id":"bio_10.1101_2025.01.01.631025","title":"Benchmarking the coding strategies of non-coding mutations on sequence-based downstream tasks with machine learning","date":"2025-01-02","source":"bioRxiv","url":"https://doi.org/10.1101/2025.01.01.631025","citation_count":0,"is_preprint":true},{"pmid":null,"id":"bio_10.1101_2025.03.28.645895","title":"biscot: an Optimal Transport framework for multimodal bacterial single-cell data analysis","date":"2025-04-02","source":"bioRxiv","url":"https://doi.org/10.1101/2025.03.28.645895","citation_count":0,"is_preprint":true}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":49071,"output_tokens":1801,"usd":0.087114,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":8146,"output_tokens":1823,"usd":0.043153,"stage2_stop_reason":"end_turn"},"total_usd":0.130267,"stage1_batch_id":"msgbatch_013a8chtv3AWyTqv4z4sEF4C","stage2_batch_id":"msgbatch_01AHsuW63vinsvuTgzmQ3n62","note":"batch pricing = 50% of standard"},"stage1_raw":"I need to carefully identify which papers are about the human/mammalian NIN gene (Ninein, a centrosomal protein) versus the plant NIN/NLP transcription factor family, NOB1 (NIN one binding protein), and other unrelated uses of \"NIN\" or \"Nin.\"\n\nThe query gene is **NIN (Ninein)** — a human centrosomal protein (also known as CEP110-like). Key papers about the human/mammalian NIN gene:\n- PMID 15087377: NIN fused to PDGFRB, describes NIN as a centrosomal protein with CEP110-like function\n- PMID 23665482: NIN mutation in skeletal dysplasia, centrosomal function\n- PMID 22937743: NIN in primate brain evolution, neurogenic divisions of radial glial cells\n- PMID 40751525: NIN gene variants, microcephalic primordial dwarfism\n- PMID 41135748: QKI-mediated NIN exon 18 splicing in breast cancer\n\nPlant NIN/NLP papers (legume nodulation, nitrate signaling) = EXCLUDE as symbol collision (plant-specific transcription factor, completely different protein/function).\n\nNOB1 papers (NIN one binding protein = a different protein entirely) = EXCLUDE.\n\nPapers about Nin-orientated transmembrane segments (topology term, not the gene) = EXCLUDE.\n\nPapers about bacteriophage lambda nin region = EXCLUDE.\n\nPapers about Wistar NIN rats (National Institute of Nutrition rat strain) = EXCLUDE.\n\nLet me now extract discoveries from the relevant human NIN (Ninein) papers:\n\n```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2004,\n      \"finding\": \"NIN (Ninein) was identified as a centrosomal protein with CEP110-like function. It was found fused to PDGFRB via a t(5;14)(q33;q24) chromosomal translocation in a patient with chronic myeloproliferative disorder with eosinophilia, producing the oncogenic NIN-PDGFRB fusion. The NIN gene was selected as a candidate partner based on the presence of predicted oligomerization domains. Treatment with imatinib produced hematological and cytogenetic remission, consistent with constitutive PDGFRB kinase activation driven by NIN-mediated oligomerization.\",\n      \"method\": \"Fluorescence in situ hybridization (FISH) to map breakpoints, reverse transcription-PCR to detect NIN-PDGFRB fusion mRNA, candidate gene selection based on oligomerization domain prediction, clinical imatinib response\",\n      \"journal\": \"Cancer research\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — FISH and RT-PCR confirm fusion gene; oligomerization domain inference is computational; single case report with clinical validation but no reconstitution or direct biochemical assay of NIN oligomerization\",\n      \"pmids\": [\"15087377\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2012,\n      \"finding\": \"NIN (Ninein) is necessary for maintaining asymmetric, neurogenic divisions of radial glial cells (RGCs). Positive selection on NIN was detected during anthropoid primate evolution, and selection on NIN was significantly associated with neonatal brain size in catarrhines, implicating NIN in the evolution of cortical neuron number through neurogenic RGC divisions.\",\n      \"method\": \"Molecular evolutionary analysis (dN/dS ratios across primate lineages), correlation of selection signatures with neural phenotypes (neonatal brain size, neuron number estimates)\",\n      \"journal\": \"Genes, brain, and behavior\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 4 / Weak — evolutionary/comparative analysis only; no direct cellular experiment on NIN function in RGC divisions performed in this study; mechanistic role in neurogenic divisions referenced from prior literature rather than experimentally established here\",\n      \"pmids\": [\"22937743\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"Homozygous missense mutations in NIN (Ninein) were identified in a consanguineous family with a spondyloepimetaphyseal dysplasia with joint laxity (SEMDJL2)-like phenotype. The NIN protein showed a functional relationship with KIF22 and other proteins associated with chromosome congression/movement, centrosomal function, and ciliogenesis, supporting a fundamental role for Ninein in skeletal development. Evidence included cosegregation of the variant with disease phenotype, absence in 500 healthy controls and 1000-genomes database, and comparison with previously identified compound heterozygous NIN mutations in microcephalic primordial dwarfism.\",\n      \"method\": \"Homozygosity mapping, whole-exome sequencing, cosegregation analysis, population control screening, functional relationship inference from known NIN interactors\",\n      \"journal\": \"Matrix biology : journal of the International Society for Matrix Biology\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — genetic mapping and sequencing establish disease association; no direct biochemical or cell biological experiment performed on the mutant protein; functional relationship with KIF22/centrosome inferred from literature, not tested here\",\n      \"pmids\": [\"23665482\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"QKI splicing factor directly binds NIN pre-mRNA and promotes inclusion of exon 18, generating an oncogenic exon-18-included NIN isoform. Depletion of the exon-18-included NIN isoform suppressed proliferation, migration, and invasion of breast cancer cells, induced S-phase arrest via dysregulation of the CDK2/Cyclin A axis, and significantly inhibited tumor growth in vivo.\",\n      \"method\": \"Multi-omics TCGA analysis, RNA binding protein eCLIP, functional knockdown experiments (cell proliferation, migration, invasion assays), flow cytometry cell cycle analysis, CDK2/Cyclin A western blot, in vivo xenograft tumor model\",\n      \"journal\": \"Cellular signalling\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct RNA binding (eCLIP) and functional rescue experiments in cells and in vivo; single lab, multiple orthogonal methods; QKI-NIN pre-mRNA interaction and isoform-specific phenotype established\",\n      \"pmids\": [\"41135748\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"NIN (Ninein) is a centrosomal protein with predicted oligomerization domains that, when fused to PDGFRB via chromosomal translocation, constitutively activates PDGFRB kinase signaling; it plays a role in asymmetric neurogenic divisions of radial glial cells relevant to cortical development; biallelic loss-of-function mutations cause microcephalic primordial dwarfism and skeletal dysplasia through disruption of centrosomal function; and the QKI splicing factor directly binds NIN pre-mRNA to promote exon 18 inclusion, generating an oncogenic isoform that drives cell cycle progression via the CDK2/Cyclin A axis in breast cancer.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"NIN (Ninein) is a centrosomal protein implicated in cell division, oncogenesis, and skeletal and cortical development. Its predicted oligomerization domains underlie its capacity to constitutively activate fused kinases: a t(5;14)(q33;q24) translocation generates a NIN-PDGFRB fusion that drives an imatinib-responsive myeloproliferative disorder through NIN-mediated dimerization and constitutive PDGFRB kinase signaling [#0]. Independent of this rearrangement, NIN pre-mRNA is a direct substrate of the splicing factor QKI, which binds it and promotes inclusion of exon 18 to generate an oncogenic isoform that sustains breast cancer cell proliferation, migration, and invasion by engaging the CDK2/Cyclin A axis, with depletion of the exon-18-included isoform inducing S-phase arrest and inhibiting tumor growth in vivo [#3]. Beyond these oncogenic and splicing-regulated mechanisms, the structural and biochemical basis of NIN's centrosomal function has not been directly characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2004,\n      \"claim\": \"Established NIN as an oncogenic fusion partner whose oligomerization domains can constitutively activate a receptor tyrosine kinase, explaining why a centrosomal protein contributes to myeloproliferative disease.\",\n      \"evidence\": \"FISH breakpoint mapping and RT-PCR detection of NIN-PDGFRB fusion mRNA in a chronic myeloproliferative disorder patient, with clinical imatinib response\",\n      \"pmids\": [\"15087377\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"NIN oligomerization was inferred computationally, not demonstrated biochemically\",\n        \"single case report without reconstitution of the fusion's kinase activity\",\n        \"wild-type NIN's normal centrosomal mechanism not addressed\"\n      ]\n    },\n    {\n      \"year\": 2012,\n      \"claim\": \"Linked NIN to the evolutionary expansion of cortical neuron number by associating positive selection on NIN with neurogenic radial glial cell divisions and brain size.\",\n      \"evidence\": \"Molecular evolutionary analysis (dN/dS across primate lineages) correlated with neonatal brain size in catarrhines\",\n      \"pmids\": [\"22937743\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"comparative analysis only; no direct cellular experiment on NIN function in RGC divisions\",\n        \"mechanistic role in neurogenic divisions cited from prior literature, not tested here\",\n        \"molecular pathway connecting NIN to division asymmetry undefined\"\n      ]\n    },\n    {\n      \"year\": 2013,\n      \"claim\": \"Connected NIN loss-of-function to human skeletal dysplasia, implicating centrosomal/ciliogenic function in skeletal development.\",\n      \"evidence\": \"Homozygosity mapping, whole-exome sequencing, and cosegregation in a consanguineous family with a SEMDJL2-like phenotype, with population control screening\",\n      \"pmids\": [\"23665482\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"no biochemical or cell biological assay on the mutant protein performed\",\n        \"functional relationship with KIF22 and centrosomal function inferred from literature\",\n        \"causal mechanism linking NIN mutation to skeletal phenotype not established\"\n      ]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Identified NIN pre-mRNA as a direct QKI splicing target, defining an exon-18-included isoform as an oncogenic driver acting through the CDK2/Cyclin A cell-cycle axis.\",\n      \"evidence\": \"eCLIP for direct RNA binding, isoform-specific knockdown with proliferation/migration/invasion assays, flow cytometry cell-cycle analysis, CDK2/Cyclin A western blot, and xenograft tumor model in breast cancer\",\n      \"pmids\": [\"41135748\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"single-lab study without independent replication\",\n        \"molecular function of the exon-18-included isoform protein not defined\",\n        \"mechanism linking the isoform to CDK2/Cyclin A regulation not resolved\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The direct biochemical and structural basis of NIN's centrosomal activity, and how it mechanistically couples to neurogenic division, skeletal development, and cell-cycle control, remains unresolved.\",\n      \"evidence\": \"No direct structural or reconstitution study of NIN appears in the corpus\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"no structural model of NIN or its oligomerization domains\",\n        \"no direct demonstration of NIN's molecular activity at the centrosome\",\n        \"mechanism connecting NIN isoform to CDK2/Cyclin A regulation unknown\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [],\n    \"localization\": [],\n    \"pathway\": [],\n    \"complexes\": [],\n    \"partners\": [\"PDGFRB\", \"QKI\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"tie","faith_supported":1,"faith_total":2,"faith_pct":50.0}}