{"gene":"MLPH","run_date":"2026-06-10T02:59:50","timeline":{"discoveries":[{"year":1988,"finding":"The murine leaden (ln) gene (ortholog of human MLPH/melanophilin) controls melanocyte morphology; ln/ln melanocytes are adendritic, and the dilute suppressor gene dsu can partially restore normal dendritic melanocyte morphology in ln/ln mice, indicating genetic epistasis between dsu and ln in the melanocyte morphology pathway. Genetic mapping placed dsu and ln on chromosome 1, approximately 9 cM apart.","method":"Genetic epistasis analysis, coat-color suppression assay, melanocyte morphology examination in double-mutant mice, genetic linkage mapping","journal":"Genetics","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — clean in vivo genetic epistasis with defined cellular phenotype (melanocyte morphology) in multiple mutant combinations; single lab but multiple mutant alleles tested","pmids":["3410303"],"is_preprint":false}],"current_model":"The murine leaden gene (ln), ortholog of human MLPH/melanophilin, is required for normal dendritic melanocyte morphology; loss of ln function produces adendritic melanocytes and a diluted coat color, and this phenotype is partially suppressible by the unlinked dilute suppressor gene dsu, placing ln in a pathway controlling melanocyte morphology and pigment granule distribution."},"narrative":{"mechanistic_narrative":"MLPH (melanophilin), the human ortholog of the murine leaden (ln) gene, functions in the pathway controlling dendritic melanocyte morphology and pigment granule distribution [PMID:3410303]. Loss of ln function produces adendritic melanocytes and a diluted coat color, and this phenotype is partially suppressed by the unlinked dilute suppressor gene dsu, establishing genetic epistasis that places ln downstream within a melanocyte morphology pathway [PMID:3410303]. Beyond this in vivo genetic placement, no molecular mechanism, partners, or biochemical activity for MLPH has been characterized in the available corpus.","teleology":[{"year":1988,"claim":"Established that the leaden gene controls melanocyte dendricity and acts in a defined genetic pathway with the dilute suppressor locus, rather than affecting pigment synthesis alone.","evidence":"Genetic epistasis and coat-color suppression assays with melanocyte morphology examination in single- and double-mutant mice, plus linkage mapping","pmids":["3410303"],"confidence":"Medium","gaps":["No molecular identity of the leaden gene product or its biochemical activity determined","Mechanism by which dsu suppresses the ln phenotype unknown","No direct evidence linking the murine phenotype to human MLPH function"]},{"year":null,"claim":"The molecular function, binding partners, subcellular localization, and biochemical mechanism by which MLPH controls melanocyte morphology and pigment granule distribution remain uncharacterized in the available corpus.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No protein-level mechanism, interactors, or localization data in the timeline","No structural or biochemical characterization","Relationship between ln and dsu gene products at the molecular level unresolved"]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":[],"partners":[],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q9BV36","full_name":"Melanophilin","aliases":["Exophilin-3","Slp homolog lacking C2 domains a","SlaC2-a","Synaptotagmin-like protein 2a"],"length_aa":600,"mass_kda":65.9,"function":"Rab effector protein involved in melanosome transport. Serves as link between melanosome-bound RAB27A and the motor protein MYO5A","subcellular_location":"Cytoplasm","url":"https://www.uniprot.org/uniprotkb/Q9BV36/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/MLPH","classification":"Not Classified","n_dependent_lines":0,"n_total_lines":1208,"dependency_fraction":0.0},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[],"url":"https://opencell.sf.czbiohub.org/search/MLPH","total_profiled":1310},"omim":[{"mim_id":"609227","title":"GRISCELLI SYNDROME, TYPE 3; GS3","url":"https://www.omim.org/entry/609227"},{"mim_id":"609207","title":"MELANOREGULIN; MREG","url":"https://www.omim.org/entry/609207"},{"mim_id":"606526","title":"MELANOPHILIN; MLPH","url":"https://www.omim.org/entry/606526"},{"mim_id":"214450","title":"GRISCELLI SYNDROME, TYPE 1; GS1","url":"https://www.omim.org/entry/214450"},{"mim_id":"160777","title":"MYOSIN VA; MYO5A","url":"https://www.omim.org/entry/160777"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"","locations":[],"tissue_specificity":"Tissue enhanced","tissue_distribution":"Detected in many","driving_tissues":[{"tissue":"prostate","ntpm":133.3},{"tissue":"salivary gland","ntpm":118.7}],"url":"https://www.proteinatlas.org/search/MLPH"},"hgnc":{"alias_symbol":["l1Rk3","l(1)-3Rk","Slac-2a","ln","exophilin-3","SLAC2-A"],"prev_symbol":[]},"alphafold":{"accession":"Q9BV36","domains":[{"cath_id":"3.30.40.10","chopping":"12-144","consensus_level":"medium","plddt":92.172,"start":12,"end":144}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9BV36","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q9BV36-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q9BV36-F1-predicted_aligned_error_v6.png","plddt_mean":60.69},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=MLPH","jax_strain_url":"https://www.jax.org/strain/search?query=MLPH"},"sequence":{"accession":"Q9BV36","fasta_url":"https://rest.uniprot.org/uniprotkb/Q9BV36.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q9BV36/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9BV36"}},"corpus_meta":[{"pmid":"6376628","id":"PMC_6376628","title":"Two new monoclonal antibodies (LN-1, LN-2) reactive in B5 formalin-fixed, paraffin-embedded tissues with follicular center and mantle zone human B lymphocytes and derived tumors.","date":"1984","source":"Journal of immunology (Baltimore, Md. : 1950)","url":"https://pubmed.ncbi.nlm.nih.gov/6376628","citation_count":283,"is_preprint":false},{"pmid":"16543232","id":"PMC_16543232","title":"Activation and cross-talk between Akt, NF-kappaB, and unfolded protein response signaling in 1-LN prostate cancer cells consequent to ligation of cell surface-associated GRP78.","date":"2006","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/16543232","citation_count":228,"is_preprint":false},{"pmid":"15908432","id":"PMC_15908432","title":"Binding of activated alpha2-macroglobulin to its cell surface receptor GRP78 in 1-LN prostate cancer cells regulates PAK-2-dependent activation of LIMK.","date":"2005","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/15908432","citation_count":152,"is_preprint":false},{"pmid":"32568362","id":"PMC_32568362","title":"Retrograde migration supplies resident memory T cells to lung-draining LN after influenza infection.","date":"2020","source":"The Journal of experimental medicine","url":"https://pubmed.ncbi.nlm.nih.gov/32568362","citation_count":115,"is_preprint":false},{"pmid":"17692381","id":"PMC_17692381","title":"Synthesis, crystal structure and DNA-binding studies of the Ln(III) complex with 6-hydroxychromone-3-carbaldehyde benzoyl hydrazone.","date":"2007","source":"Journal of inorganic biochemistry","url":"https://pubmed.ncbi.nlm.nih.gov/17692381","citation_count":114,"is_preprint":false},{"pmid":"23243125","id":"PMC_23243125","title":"Ln is a key regulator of leaflet shape and number of seeds per pod in soybean.","date":"2012","source":"The Plant cell","url":"https://pubmed.ncbi.nlm.nih.gov/23243125","citation_count":93,"is_preprint":false},{"pmid":"19281134","id":"PMC_19281134","title":"Isolation of antipodal (-)-versicolamide B and notoamides L-N from a marine-derived Aspergillus sp.","date":"2009","source":"Organic letters","url":"https://pubmed.ncbi.nlm.nih.gov/19281134","citation_count":90,"is_preprint":false},{"pmid":"32724468","id":"PMC_32724468","title":"Self-assembling peptide hydrogels functionalized with LN- and BDNF- mimicking epitopes synergistically enhance peripheral nerve regeneration.","date":"2020","source":"Theranostics","url":"https://pubmed.ncbi.nlm.nih.gov/32724468","citation_count":89,"is_preprint":false},{"pmid":"7211194","id":"PMC_7211194","title":"Characterization of an established human malignant glioma cell line: LN-18.","date":"1981","source":"Acta neuropathologica","url":"https://pubmed.ncbi.nlm.nih.gov/7211194","citation_count":85,"is_preprint":false},{"pmid":"32207913","id":"PMC_32207913","title":"Ultrasensitive Fluorescent miRNA Biosensor Based on a \"Sandwich\" Oligonucleotide Hybridization and Fluorescence Resonance Energy Transfer Process Using an Ln(III)-MOF and Ag Nanoparticles for Early Cancer Diagnosis: Application of Central Composite Design.","date":"2020","source":"ACS applied materials & interfaces","url":"https://pubmed.ncbi.nlm.nih.gov/32207913","citation_count":77,"is_preprint":false},{"pmid":"9179057","id":"PMC_9179057","title":"LN-2 (CD74). A marker to distinguish atypical fibroxanthoma from malignant fibrous histiocytoma.","date":"1997","source":"Cancer","url":"https://pubmed.ncbi.nlm.nih.gov/9179057","citation_count":74,"is_preprint":false},{"pmid":"17083226","id":"PMC_17083226","title":"Equilibrium and formation/dissociation kinetics of some Ln(III)PCTA complexes.","date":"2006","source":"Inorganic chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/17083226","citation_count":67,"is_preprint":false},{"pmid":"23588386","id":"PMC_23588386","title":"Contribution of the PI3K/MMPs/Ln-5γ2 and EphA2/FAK/Paxillin signaling pathways to tumor growth and vasculogenic mimicry of gallbladder carcinomas.","date":"2013","source":"International journal of oncology","url":"https://pubmed.ncbi.nlm.nih.gov/23588386","citation_count":63,"is_preprint":false},{"pmid":"11151500","id":"PMC_11151500","title":"Is ferromagnetism an intrinsic property of the CuII/GdIII couple? 2. Structures and magnetic properties of novel trinuclear complexes with mu-phenolato-mu-oximato (Cu-Ln-Cu) cores (Ln = La, Ce, Gd).","date":"2000","source":"Inorganic chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/11151500","citation_count":63,"is_preprint":false},{"pmid":"23076865","id":"PMC_23076865","title":"Fluoridated HAp:Ln3+ (Ln = Eu or Tb) nanoparticles for cell-imaging.","date":"2012","source":"Nanoscale","url":"https://pubmed.ncbi.nlm.nih.gov/23076865","citation_count":63,"is_preprint":false},{"pmid":"18991275","id":"PMC_18991275","title":"A two-step model for Langerhans cell migration to skin-draining LN.","date":"2008","source":"European journal of immunology","url":"https://pubmed.ncbi.nlm.nih.gov/18991275","citation_count":57,"is_preprint":false},{"pmid":"26260271","id":"PMC_26260271","title":"Phenylbutyrate-a pan-HDAC inhibitor-suppresses proliferation of glioblastoma LN-229 cell line.","date":"2015","source":"Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine","url":"https://pubmed.ncbi.nlm.nih.gov/26260271","citation_count":56,"is_preprint":false},{"pmid":"3410303","id":"PMC_3410303","title":"The murine dilute suppressor gene dsu suppresses the coat-color phenotype of three pigment mutations that alter melanocyte morphology, d, ash and ln.","date":"1988","source":"Genetics","url":"https://pubmed.ncbi.nlm.nih.gov/3410303","citation_count":56,"is_preprint":false},{"pmid":"3261214","id":"PMC_3261214","title":"Age- and sex-specific pediatric reference intervals: study design and methods illustrated by measurement of serum proteins with the Behring LN Nephelometer.","date":"1988","source":"Clinical chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/3261214","citation_count":55,"is_preprint":false},{"pmid":"36302567","id":"PMC_36302567","title":"Safety and Efficacy of Belimumab in Patients with Lupus Nephritis: Open-Label Extension of BLISS-LN Study.","date":"2022","source":"Clinical journal of the American Society of Nephrology : CJASN","url":"https://pubmed.ncbi.nlm.nih.gov/36302567","citation_count":54,"is_preprint":false},{"pmid":"18430779","id":"PMC_18430779","title":"A single point mutation in the LN domain of LAMA2 causes muscular dystrophy and peripheral amyelination.","date":"2008","source":"Journal of cell science","url":"https://pubmed.ncbi.nlm.nih.gov/18430779","citation_count":51,"is_preprint":false},{"pmid":"17083231","id":"PMC_17083231","title":"Heterobimetallic Zn(II)-Ln(III) phenylene-bridged schiff base complexes, computational studies, and evidence for singlet energy transfer as the main pathway in the sensitization of near-infrared Nd3+ luminescence.","date":"2006","source":"Inorganic chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/17083231","citation_count":51,"is_preprint":false},{"pmid":"22330721","id":"PMC_22330721","title":"Interleukin-1β and transforming growth factor-β cooperate to induce neurosphere formation and increase tumorigenicity of adherent LN-229 glioma cells.","date":"2012","source":"Stem cell research & therapy","url":"https://pubmed.ncbi.nlm.nih.gov/22330721","citation_count":48,"is_preprint":false},{"pmid":"16612623","id":"PMC_16612623","title":"Genetic similarities and differences between lobular in situ neoplasia (LN) and invasive lobular carcinoma of the breast.","date":"2006","source":"Virchows Archiv : an international journal of pathology","url":"https://pubmed.ncbi.nlm.nih.gov/16612623","citation_count":48,"is_preprint":false},{"pmid":"12203324","id":"PMC_12203324","title":"Unequivocal synthetic pathway to heterodinuclear (4f,4f') complexes: magnetic study of relevant (Ln(III), Gd(III)) and (Gd(III), Ln(III)) complexes.","date":"2002","source":"Chemistry (Weinheim an der Bergstrasse, Germany)","url":"https://pubmed.ncbi.nlm.nih.gov/12203324","citation_count":48,"is_preprint":false},{"pmid":"24628713","id":"PMC_24628713","title":"Norcantharidin inhibits tumor growth and vasculogenic mimicry of human gallbladder carcinomas by suppression of the PI3-K/MMPs/Ln-5γ2 signaling pathway.","date":"2014","source":"BMC cancer","url":"https://pubmed.ncbi.nlm.nih.gov/24628713","citation_count":47,"is_preprint":false},{"pmid":"16781158","id":"PMC_16781158","title":"Synthesis, characterization, and DNA-binding properties of the Ln(III) complexes with 6-hydroxy chromone-3-carbaldehyde-(2'-hydroxy) benzoyl hydrazone.","date":"2006","source":"Bioorganic & medicinal chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/16781158","citation_count":46,"is_preprint":false},{"pmid":"24935095","id":"PMC_24935095","title":"Distinct functions of the laminin β LN domain and collagen IV during cardiac extracellular matrix formation and stabilization of alary muscle attachments revealed by EMS mutagenesis in Drosophila.","date":"2014","source":"BMC developmental biology","url":"https://pubmed.ncbi.nlm.nih.gov/24935095","citation_count":45,"is_preprint":false},{"pmid":"20809608","id":"PMC_20809608","title":"Para-derivatized pybox ligands as sensitizers in highly luminescent Ln(III) complexes.","date":"2010","source":"Inorganic chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/20809608","citation_count":44,"is_preprint":false},{"pmid":"15877435","id":"PMC_15877435","title":"Syntheses, structures, and magnetic properties of diphenoxo-bridged M(II)Ln(III) complexes derived from N,N'-ethylenebis(3-ethoxysalicylaldiimine) (M = Cu or Ni; Ln = Ce-Yb): observation of surprisingly strong exchange interactions.","date":"2005","source":"Inorganic chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/15877435","citation_count":43,"is_preprint":false},{"pmid":"19585996","id":"PMC_19585996","title":"[Ln(DPA)(3)](3-) is a convenient paramagnetic shift reagent for protein NMR studies.","date":"2009","source":"Journal of the American Chemical Society","url":"https://pubmed.ncbi.nlm.nih.gov/19585996","citation_count":42,"is_preprint":false},{"pmid":"21527980","id":"PMC_21527980","title":"Molecular and Biological Characterization of Chinese Sacbrood Virus LN Isolate.","date":"2011","source":"Comparative and functional genomics","url":"https://pubmed.ncbi.nlm.nih.gov/21527980","citation_count":41,"is_preprint":false},{"pmid":"19038478","id":"PMC_19038478","title":"Synthesis, crystal structure, antioxidant activities and DNA-binding studies of the Ln(III) complexes with 7-methoxychromone-3-carbaldehyde-(4'-hydroxy) benzoyl hydrazone.","date":"2008","source":"European journal of medicinal chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/19038478","citation_count":39,"is_preprint":false},{"pmid":"2476034","id":"PMC_2476034","title":"Astrocytes and microglia in human brain share an epitope recognized by a B-lymphocyte-specific monoclonal antibody (LN-1).","date":"1989","source":"The American journal of pathology","url":"https://pubmed.ncbi.nlm.nih.gov/2476034","citation_count":38,"is_preprint":false},{"pmid":"28766195","id":"PMC_28766195","title":"Association of LN Evaluation with Survival in Women Aged 70 Years or Older With Clinically Node-Negative Hormone Receptor Positive Breast Cancer.","date":"2017","source":"Annals of surgical oncology","url":"https://pubmed.ncbi.nlm.nih.gov/28766195","citation_count":38,"is_preprint":false},{"pmid":"2973428","id":"PMC_2973428","title":"Antigenic phenotype of Langerhans cell histiocytosis: an immunohistochemical study demonstrating the value of LN-2, LN-3, and vimentin.","date":"1988","source":"Human pathology","url":"https://pubmed.ncbi.nlm.nih.gov/2973428","citation_count":37,"is_preprint":false},{"pmid":"20509606","id":"PMC_20509606","title":"Syntheses, crystal and electronic structures, and physical properties of quaternary semiconductors: Ln2Mn3Sb4S12 (Ln = Pr, Nd, Sm, Gd).","date":"2010","source":"Inorganic chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/20509606","citation_count":37,"is_preprint":false},{"pmid":"21714501","id":"PMC_21714501","title":"Stability and structural evolution of Ce(IV)(1-x)Ln(III)(x)O(2-x/2) solid solutions: a coupled μ-Raman/XRD approach.","date":"2011","source":"Inorganic chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/21714501","citation_count":35,"is_preprint":false},{"pmid":"19615791","id":"PMC_19615791","title":"Synthesis, characterization, DNA binding properties and antioxidant activity of Ln(III) complexes with hesperetin-4-one-(benzoyl) hydrazone.","date":"2009","source":"European journal of medicinal chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/19615791","citation_count":33,"is_preprint":false},{"pmid":"3281719","id":"PMC_3281719","title":"Immunohistochemical characterization of two new monoclonal antibodies (LN-4, LN-5) reactive with human macrophage subsets and derived malignancies in B5-fixed, paraffin-embedded tissues.","date":"1988","source":"Blood","url":"https://pubmed.ncbi.nlm.nih.gov/3281719","citation_count":33,"is_preprint":false},{"pmid":"27125555","id":"PMC_27125555","title":"LN-1-255, a penicillanic acid sulfone able to inhibit the class D carbapenemase OXA-48.","date":"2016","source":"The Journal of antimicrobial chemotherapy","url":"https://pubmed.ncbi.nlm.nih.gov/27125555","citation_count":32,"is_preprint":false},{"pmid":"28106189","id":"PMC_28106189","title":"Microsolvation of the pyrrole cation (Py+) with nonpolar and polar ligands: infrared spectra of Py+-Ln with L = Ar, N2, and H2O (n ≤ 3).","date":"2017","source":"Physical chemistry chemical physics : PCCP","url":"https://pubmed.ncbi.nlm.nih.gov/28106189","citation_count":31,"is_preprint":false},{"pmid":"14709337","id":"PMC_14709337","title":"Potentiation of signal transduction mitogenesis and cellular proliferation upon binding of receptor-recognized forms of alpha2-macroglobulin to 1-LN prostate cancer cells.","date":"2004","source":"Cellular signalling","url":"https://pubmed.ncbi.nlm.nih.gov/14709337","citation_count":30,"is_preprint":false},{"pmid":"24863948","id":"PMC_24863948","title":"Prediction of thyroid extracapsular extension with cervical lymph node metastases (ECE-LN) by CEUS and BRAF expression in papillary thyroid carcinoma.","date":"2014","source":"Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine","url":"https://pubmed.ncbi.nlm.nih.gov/24863948","citation_count":27,"is_preprint":false},{"pmid":"16633312","id":"PMC_16633312","title":"Diagnostic value of two reagent strips (Multistix 8 SG and Combur 2 LN) in cirrhotic patients with spontaneous bacterial peritonitis and symptomatic bacterascites.","date":"2006","source":"Gastroenterologie clinique et biologique","url":"https://pubmed.ncbi.nlm.nih.gov/16633312","citation_count":27,"is_preprint":false},{"pmid":"7951414","id":"PMC_7951414","title":"Plasminogen activator and metalloprotease activities of Du-145, PC-3, and 1-LN-PC-3-1A human prostate tumors grown in nude mice: correlation with tumor invasive behavior.","date":"1993","source":"Cellular & molecular biology research","url":"https://pubmed.ncbi.nlm.nih.gov/7951414","citation_count":26,"is_preprint":false},{"pmid":"32795593","id":"PMC_32795593","title":"MiRNA-200c, MiRNA-139 and ln RNA H19; new predictors of treatment response in H-pylori- induced gastric ulcer or progression to gastric cancer.","date":"2020","source":"Microbial pathogenesis","url":"https://pubmed.ncbi.nlm.nih.gov/32795593","citation_count":25,"is_preprint":false},{"pmid":"22424613","id":"PMC_22424613","title":"A novel anti-tumor agent, Ln(III) 2-thioacetate benzothiazole induces anti-angiogenic effect and cell death in cancer cell lines.","date":"2012","source":"European journal of medicinal chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/22424613","citation_count":25,"is_preprint":false},{"pmid":"30870791","id":"PMC_30870791","title":"High in vitro and in vivo antitumor activities of Ln(III) complexes with mixed 5,7-dichloro-2-methyl-8-quinolinol and 4,4'-dimethyl-2,2'-bipyridyl chelating ligands.","date":"2019","source":"European journal of medicinal chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/30870791","citation_count":24,"is_preprint":false},{"pmid":"11097186","id":"PMC_11097186","title":"Selective upregulated expression of the alpha2-macroglobulin signaling receptor in highly metastatic 1-LN prostate carcinoma cells.","date":"2000","source":"Archives of biochemistry and biophysics","url":"https://pubmed.ncbi.nlm.nih.gov/11097186","citation_count":24,"is_preprint":false},{"pmid":"12036889","id":"PMC_12036889","title":"Tissue factor is the receptor for plasminogen type 1 on 1-LN human prostate cancer cells.","date":"2002","source":"Blood","url":"https://pubmed.ncbi.nlm.nih.gov/12036889","citation_count":23,"is_preprint":false},{"pmid":"24821384","id":"PMC_24821384","title":"Di-ethylhexylphthalate (DEHP) modulates cell invasion, migration and anchorage independent growth through targeting S100P in LN-229 glioblastoma cells.","date":"2014","source":"International journal of environmental research and public health","url":"https://pubmed.ncbi.nlm.nih.gov/24821384","citation_count":20,"is_preprint":false},{"pmid":"15911629","id":"PMC_15911629","title":"Association of plasminogen with dipeptidyl peptidase IV and Na+/H+ exchanger isoform NHE3 regulates invasion of human 1-LN prostate tumor cells.","date":"2005","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/15911629","citation_count":20,"is_preprint":false},{"pmid":"17430262","id":"PMC_17430262","title":"Establishment and characterization of androgen-independent human prostate cancer cell lines, LN-REC4 and LNCaP-SF, from LNCaP.","date":"2007","source":"International journal of urology : official journal of the Japanese Urological Association","url":"https://pubmed.ncbi.nlm.nih.gov/17430262","citation_count":19,"is_preprint":false},{"pmid":"29085246","id":"PMC_29085246","title":"Confirmation of the pleiotropic control of leaflet shape and number of seeds per pod by the Ln gene in induced soybean mutants.","date":"2017","source":"Breeding science","url":"https://pubmed.ncbi.nlm.nih.gov/29085246","citation_count":19,"is_preprint":false},{"pmid":"27185264","id":"PMC_27185264","title":"Correlative near-infrared light and cathodoluminescence microscopy using Y2O3:Ln, Yb (Ln = Tm, Er) nanophosphors for multiscale, multicolour bioimaging.","date":"2016","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/27185264","citation_count":19,"is_preprint":false},{"pmid":"35907913","id":"PMC_35907913","title":"Curcumin piperidone derivatives induce anti-proliferative and anti-migratory effects in LN-18 human glioblastoma cells.","date":"2022","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/35907913","citation_count":18,"is_preprint":false},{"pmid":"37047269","id":"PMC_37047269","title":"Lanthanides as Calcium Mimetic Species in Calcium-Signaling/Buffering Proteins: The Effect of Lanthanide Type on the Ca2+/Ln3+ Competition.","date":"2023","source":"International journal of molecular sciences","url":"https://pubmed.ncbi.nlm.nih.gov/37047269","citation_count":18,"is_preprint":false},{"pmid":"21786031","id":"PMC_21786031","title":"Engineering [Ln(DPA)3] 3- binding sites in proteins: a widely applicable method for tagging proteins with lanthanide ions.","date":"2011","source":"Journal of biomolecular NMR","url":"https://pubmed.ncbi.nlm.nih.gov/21786031","citation_count":18,"is_preprint":false},{"pmid":"11313826","id":"PMC_11313826","title":"Death receptor-independent cytochrome c release and caspase activation mediate thymidine kinase plus ganciclovir-mediated cytotoxicity in LN-18 and LN-229 human malignant glioma cells.","date":"2001","source":"Gene therapy","url":"https://pubmed.ncbi.nlm.nih.gov/11313826","citation_count":18,"is_preprint":false},{"pmid":"27366822","id":"PMC_27366822","title":"Perovskite-Like Polar Lanthanide Formate Frameworks of [NH2NH3][Ln(HCOO)4] (Ln = Tb-Lu and Y): Synthesis, Structures, Magnetism, and Anisotropic Thermal Expansion.","date":"2016","source":"Inorganic chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/27366822","citation_count":18,"is_preprint":false},{"pmid":"7150347","id":"PMC_7150347","title":"Mode of action of LN 1643 (a triphenylbromoethylene antiestrogen): probable mediation by the estrogen receptor and high affinity metabolite.","date":"1982","source":"Biochemical pharmacology","url":"https://pubmed.ncbi.nlm.nih.gov/7150347","citation_count":18,"is_preprint":false},{"pmid":"26190155","id":"PMC_26190155","title":"Ln(3+)-doped hydroxyapatite nanocrystals: controllable synthesis and cell imaging.","date":"2015","source":"Physical chemistry chemical physics : PCCP","url":"https://pubmed.ncbi.nlm.nih.gov/26190155","citation_count":17,"is_preprint":false},{"pmid":"31500216","id":"PMC_31500216","title":"Multifunctional NaLnF4@MOF-Ln Nanocomposites with Dual-Mode Luminescence for Drug Delivery and Cell Imaging.","date":"2019","source":"Nanomaterials (Basel, Switzerland)","url":"https://pubmed.ncbi.nlm.nih.gov/31500216","citation_count":17,"is_preprint":false},{"pmid":"34335030","id":"PMC_34335030","title":"SQLE Mediates Metabolic Reprogramming to Promote LN Metastasis in Castration-Resistant Prostate Cancer.","date":"2021","source":"OncoTargets and therapy","url":"https://pubmed.ncbi.nlm.nih.gov/34335030","citation_count":17,"is_preprint":false},{"pmid":"22742732","id":"PMC_22742732","title":"Naphthomycins L-N, ansamycin antibiotics from Streptomyces sp. CS.","date":"2012","source":"Journal of natural products","url":"https://pubmed.ncbi.nlm.nih.gov/22742732","citation_count":17,"is_preprint":false},{"pmid":"24849287","id":"PMC_24849287","title":"(BMI)3LnCl6 crystals as models for the coordination environment of LnCl3 (Ln = Sm, Eu, Dy, Er, Yb) in 1-butyl-3-methylimidazolium chloride ionic-liquid solution.","date":"2014","source":"Inorganic chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/24849287","citation_count":17,"is_preprint":false},{"pmid":"36102042","id":"PMC_36102042","title":"A novel regulatory complex mediated by Lanata (Ln) controls multicellular trichome formation in tomato.","date":"2022","source":"The New phytologist","url":"https://pubmed.ncbi.nlm.nih.gov/36102042","citation_count":16,"is_preprint":false},{"pmid":"19913499","id":"PMC_19913499","title":"PFT-alpha inhibits antibody-induced activation of p53 and pro-apoptotic signaling in 1-LN prostate cancer cells.","date":"2009","source":"Biochemical and biophysical research communications","url":"https://pubmed.ncbi.nlm.nih.gov/19913499","citation_count":16,"is_preprint":false},{"pmid":"15016824","id":"PMC_15016824","title":"Cell surface adenosine deaminase binds and stimulates plasminogen activation on 1-LN human prostate cancer cells.","date":"2004","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/15016824","citation_count":16,"is_preprint":false},{"pmid":"17407099","id":"PMC_17407099","title":"Mature DC from skin and skin-draining LN retain the ability to acquire and efficiently present targeted antigen.","date":"2007","source":"European journal of immunology","url":"https://pubmed.ncbi.nlm.nih.gov/17407099","citation_count":16,"is_preprint":false},{"pmid":"20812685","id":"PMC_20812685","title":"Syntheses, structures, and magnetic properties of diphenoxo-bridged Cu(II)Ln(III) and Ni(II)(low-spin)Ln(III) compounds derived from a compartmental ligand (Ln = Ce-Yb).","date":"2010","source":"Inorganic chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/20812685","citation_count":16,"is_preprint":false},{"pmid":"26896612","id":"PMC_26896612","title":"High glucose regulates LN expression in human liver sinusoidal endothelial cells through ROS/integrin αvβ3 pathway.","date":"2016","source":"Environmental toxicology and pharmacology","url":"https://pubmed.ncbi.nlm.nih.gov/26896612","citation_count":15,"is_preprint":false},{"pmid":"36194725","id":"PMC_36194725","title":"Ln2 (SeO3 )2 (SO4 )(H2 O)2 (Ln=Sm, Dy, Yb): A Mixed-Ligand Pathway to New Lanthanide(III) Multifunctional Materials Featuring Nonlinear Optical and Magnetic Anisotropy Properties.","date":"2022","source":"Angewandte Chemie (International ed. in English)","url":"https://pubmed.ncbi.nlm.nih.gov/36194725","citation_count":15,"is_preprint":false},{"pmid":"38233574","id":"PMC_38233574","title":"GC/MS and LC/MS serum metabolomic analysis of Chinese LN patients.","date":"2024","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/38233574","citation_count":14,"is_preprint":false},{"pmid":"34786067","id":"PMC_34786067","title":"ln RNA LINC01234 promotes triple-negative breast cancer progression through regulating the miR-429/SYNJ1 axis.","date":"2021","source":"American journal of translational research","url":"https://pubmed.ncbi.nlm.nih.gov/34786067","citation_count":14,"is_preprint":false},{"pmid":"34691085","id":"PMC_34691085","title":"LN Monocytes Limit DC-Poly I:C Induced Cytotoxic T Cell Response via IL-10 and Induction of Suppressor CD4 T Cells.","date":"2021","source":"Frontiers in immunology","url":"https://pubmed.ncbi.nlm.nih.gov/34691085","citation_count":14,"is_preprint":false},{"pmid":"19658092","id":"PMC_19658092","title":"Homeostatic proliferation of naïve CD8+ T cells depends on CD62L/L-selectin-mediated homing to peripheral LN.","date":"2009","source":"European journal of immunology","url":"https://pubmed.ncbi.nlm.nih.gov/19658092","citation_count":14,"is_preprint":false},{"pmid":"19404747","id":"PMC_19404747","title":"Crystal structures, DNA-binding studies and antioxidant activities of the Ln(III) complexes with 7-methoxychromone- 3-carbaldehyde-isonicotinoyl hydrazone.","date":"2009","source":"Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine","url":"https://pubmed.ncbi.nlm.nih.gov/19404747","citation_count":14,"is_preprint":false},{"pmid":"11195372","id":"PMC_11195372","title":"Heteroleptic lanthanide compounds with chalcogenolate ligands: reduction of PhNNPh/PhEEPh (E = Se or Te) mixtures with Ln (Ln = Ho, Er, Tm, Yb). Thermolysis can give LnN or LnE.","date":"2001","source":"Inorganic chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/11195372","citation_count":13,"is_preprint":false},{"pmid":"18615212","id":"PMC_18615212","title":"Towards inert and preorganized d-block-containing receptors for trivalent lanthanides: the synthesis and characterization of triple-helical monometallic Os(II) and bimetallic Os(II)-Ln(III) complexes.","date":"2008","source":"Dalton transactions (Cambridge, England : 2003)","url":"https://pubmed.ncbi.nlm.nih.gov/18615212","citation_count":13,"is_preprint":false},{"pmid":"20683527","id":"PMC_20683527","title":"Grafting of peralkylated Ln(II)Al(III) heterobimetallic complexes onto periodic mesoporous silica KIT-6.","date":"2010","source":"Dalton transactions (Cambridge, England : 2003)","url":"https://pubmed.ncbi.nlm.nih.gov/20683527","citation_count":13,"is_preprint":false},{"pmid":"26741116","id":"PMC_26741116","title":"Expression of Tim4 in Glioma and its Regulatory Role in LN-18 Glioma Cells.","date":"2016","source":"Medical science monitor : international medical journal of experimental and clinical research","url":"https://pubmed.ncbi.nlm.nih.gov/26741116","citation_count":12,"is_preprint":false},{"pmid":"37768278","id":"PMC_37768278","title":"Stabilization Of The CN3 5- Anion In Recoverable High-pressure Ln3 O2 (CN3 ) (Ln=La, Eu, Gd, Tb, Ho, Yb) Oxoguanidinates.","date":"2023","source":"Angewandte Chemie (International ed. in English)","url":"https://pubmed.ncbi.nlm.nih.gov/37768278","citation_count":12,"is_preprint":false},{"pmid":"34015217","id":"PMC_34015217","title":"Na-Ln Heterometallic Coordination Polymers: Structure Modulation by Na+ Concentration and Efficient Detection to Tetracycline Antibiotics and 4-(Phenylazo)aniline.","date":"2021","source":"Inorganic chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/34015217","citation_count":12,"is_preprint":false},{"pmid":"33434986","id":"PMC_33434986","title":"Targeted Stealth Polymer Capsules Encapsulating Ln3+-Doped LaVO4 Nanoparticles for Bioimaging Applications.","date":"2016","source":"ACS biomaterials science & engineering","url":"https://pubmed.ncbi.nlm.nih.gov/33434986","citation_count":12,"is_preprint":false},{"pmid":"25359551","id":"PMC_25359551","title":"LaF3:Ln mesoporous spheres: controllable synthesis, tunable luminescence and application for dual-modal chemo-/photo-thermal therapy.","date":"2014","source":"Nanoscale","url":"https://pubmed.ncbi.nlm.nih.gov/25359551","citation_count":12,"is_preprint":false},{"pmid":"31290880","id":"PMC_31290880","title":"Novel NIR LaGaO3:Cr3+,Ln3+ (Ln = Yb, Nd, Er) phosphors via energy transfer for C-Si-based solar cells.","date":"2019","source":"Dalton transactions (Cambridge, England : 2003)","url":"https://pubmed.ncbi.nlm.nih.gov/31290880","citation_count":11,"is_preprint":false},{"pmid":"30522103","id":"PMC_30522103","title":"Down-Regulation of Laminin (LN)- α5 is Associated with Preeclampsia and Impairs Trophoblast Cell Viability and Invasiveness Through PI3K Signaling Pathway.","date":"2018","source":"Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology","url":"https://pubmed.ncbi.nlm.nih.gov/30522103","citation_count":11,"is_preprint":false},{"pmid":"24138134","id":"PMC_24138134","title":"Polar and magnetic layered A-site and rock salt B-site-ordered NaLnFeWO6 (Ln = La, Nd) perovskites.","date":"2013","source":"Inorganic chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/24138134","citation_count":11,"is_preprint":false},{"pmid":"32554851","id":"PMC_32554851","title":"CTRP13 attenuates the expression of LN and CAV-1 Induced by high glucose via CaMKKβ/AMPK pathway in rLSECs.","date":"2020","source":"Aging","url":"https://pubmed.ncbi.nlm.nih.gov/32554851","citation_count":10,"is_preprint":false},{"pmid":"32175553","id":"PMC_32175553","title":"Mitochondria-localizing dicarbohydrazide Ln complexes and their mechanism of in vitro anticancer activity.","date":"2020","source":"Dalton transactions (Cambridge, England : 2003)","url":"https://pubmed.ncbi.nlm.nih.gov/32175553","citation_count":10,"is_preprint":false},{"pmid":"19370403","id":"PMC_19370403","title":"Synthesis, characterization and DNA-binding properties of Ln(III) complexes with 6-ethoxy chromone-3-carbaldehyde benzoyl hydrazone.","date":"2009","source":"Journal of fluorescence","url":"https://pubmed.ncbi.nlm.nih.gov/19370403","citation_count":10,"is_preprint":false},{"pmid":"29632639","id":"PMC_29632639","title":"Reduced expression of α-L-Fucosidase-1 (FUCA-1) predicts recurrence and shorter cancer specific survival in luminal B LN+ breast cancer patients.","date":"2018","source":"Oncotarget","url":"https://pubmed.ncbi.nlm.nih.gov/29632639","citation_count":10,"is_preprint":false},{"pmid":"18074203","id":"PMC_18074203","title":"Synthesis, characterization, DNA-binding properties of the Ln(III) complexes with 6-hydroxy chromone-3-carbaldehyde-(4'-hydroxy) benzoyl hydrazone.","date":"2007","source":"Journal of fluorescence","url":"https://pubmed.ncbi.nlm.nih.gov/18074203","citation_count":10,"is_preprint":false},{"pmid":"32966771","id":"PMC_32966771","title":"Development of Sentinel LN Imaging with a Combination of HAase Based on a Comprehensive Analysis of the Intra-lymphatic Kinetics of LPs.","date":"2020","source":"Molecular therapy : the journal of the American Society of Gene Therapy","url":"https://pubmed.ncbi.nlm.nih.gov/32966771","citation_count":10,"is_preprint":false},{"pmid":"28009880","id":"PMC_28009880","title":"Ln polyoxocations: yttrium oxide solution speciation & solution deposited thin films.","date":"2017","source":"Dalton transactions (Cambridge, England : 2003)","url":"https://pubmed.ncbi.nlm.nih.gov/28009880","citation_count":10,"is_preprint":false},{"pmid":"34068712","id":"PMC_34068712","title":"LN-Derived Fibroblastic Reticular Cells and Their Impact on T Cell Response-A Systematic Review.","date":"2021","source":"Cells","url":"https://pubmed.ncbi.nlm.nih.gov/34068712","citation_count":9,"is_preprint":false},{"pmid":"31252209","id":"PMC_31252209","title":"Well-tuned white-light-emitting behaviours in multicenter-Ln polyoxometalate derivatives: A photoluminescence property and energy transfer pathway study.","date":"2019","source":"Spectrochimica acta. Part A, Molecular and biomolecular spectroscopy","url":"https://pubmed.ncbi.nlm.nih.gov/31252209","citation_count":9,"is_preprint":false},{"pmid":"24838313","id":"PMC_24838313","title":"Caspase-activated DNase is necessary and sufficient for oligonucleosomal DNA breakdown, but not for chromatin disassembly during caspase-dependent apoptosis of LN-18 glioblastoma cells.","date":"2014","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/24838313","citation_count":9,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":55494,"output_tokens":684,"usd":0.088371,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":6648,"output_tokens":782,"usd":0.026395,"stage2_stop_reason":"end_turn"},"total_usd":0.114766,"stage1_batch_id":"msgbatch_01BbTCMyrRPyhtEq6b1MdwCN","stage2_batch_id":"msgbatch_011dEed5bbxYvTAaQWKJevxu","note":"batch pricing = 50% of standard"},"stage1_raw":"Looking through all 100 abstracts, I need to find papers about MLPH (melanophilin, also known as Slac-2a, exophilin-3, leaden/ln). \n\nThe gene MLPH encodes melanophilin, a Rab27a effector protein involved in melanosome transport. The aliases include \"ln\" (leaden) which is a mouse coat color gene.\n\nLet me identify relevant papers:\n\n- Paper [18] discusses the murine \"leaden (ln)\" coat color gene and its relationship to melanocyte morphology and the dilute suppressor gene dsu. This is directly relevant to MLPH/leaden.\n\nAll other papers are clearly unrelated (lanthanide chemistry, lymph node biology, glioma cell lines, prostate cancer, soybean narrow leaflet, etc.). The \"ln\" symbol appears frequently as an abbreviation for lanthanide or lymph node, and \"LN\" appears as various abbreviations (lymph node, laminin, cell line names). None of these are MLPH.\n\nPaper [18] describes genetic epistasis experiments showing that dsu suppresses the coat-color phenotype of leaden (ln) mice by partially restoring normal (dendritic) melanocyte morphology, and provides genetic mapping data establishing that dsu and ln are separate but interacting loci on chromosome 1.\n\n```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 1988,\n      \"finding\": \"The murine leaden (ln) gene (ortholog of human MLPH/melanophilin) controls melanocyte morphology; ln/ln melanocytes are adendritic, and the dilute suppressor gene dsu can partially restore normal dendritic melanocyte morphology in ln/ln mice, indicating genetic epistasis between dsu and ln in the melanocyte morphology pathway. Genetic mapping placed dsu and ln on chromosome 1, approximately 9 cM apart.\",\n      \"method\": \"Genetic epistasis analysis, coat-color suppression assay, melanocyte morphology examination in double-mutant mice, genetic linkage mapping\",\n      \"journal\": \"Genetics\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — clean in vivo genetic epistasis with defined cellular phenotype (melanocyte morphology) in multiple mutant combinations; single lab but multiple mutant alleles tested\",\n      \"pmids\": [\"3410303\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"The murine leaden gene (ln), ortholog of human MLPH/melanophilin, is required for normal dendritic melanocyte morphology; loss of ln function produces adendritic melanocytes and a diluted coat color, and this phenotype is partially suppressible by the unlinked dilute suppressor gene dsu, placing ln in a pathway controlling melanocyte morphology and pigment granule distribution.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"MLPH (melanophilin), the human ortholog of the murine leaden (ln) gene, functions in the pathway controlling dendritic melanocyte morphology and pigment granule distribution [#0]. Loss of ln function produces adendritic melanocytes and a diluted coat color, and this phenotype is partially suppressed by the unlinked dilute suppressor gene dsu, establishing genetic epistasis that places ln downstream within a melanocyte morphology pathway [#0]. Beyond this in vivo genetic placement, no molecular mechanism, partners, or biochemical activity for MLPH has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 1988,\n      \"claim\": \"Established that the leaden gene controls melanocyte dendricity and acts in a defined genetic pathway with the dilute suppressor locus, rather than affecting pigment synthesis alone.\",\n      \"evidence\": \"Genetic epistasis and coat-color suppression assays with melanocyte morphology examination in single- and double-mutant mice, plus linkage mapping\",\n      \"pmids\": [\n        \"3410303\"\n      ],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No molecular identity of the leaden gene product or its biochemical activity determined\",\n        \"Mechanism by which dsu suppresses the ln phenotype unknown\",\n        \"No direct evidence linking the murine phenotype to human MLPH function\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The molecular function, binding partners, subcellular localization, and biochemical mechanism by which MLPH controls melanocyte morphology and pigment granule distribution remain uncharacterized in the available corpus.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No protein-level mechanism, interactors, or localization data in the timeline\",\n        \"No structural or biochemical characterization\",\n        \"Relationship between ln and dsu gene products at the molecular level unresolved\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [],\n    \"localization\": [],\n    \"pathway\": [],\n    \"complexes\": [],\n    \"partners\": [],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":2,"faith_total":2,"faith_pct":100.0}}