Affinage

RELN

Reelin · UniProt P78509

Length
3460 aa
Mass
388.4 kDa
Annotated
2026-06-10
100 papers in source corpus 20 papers cited in narrative 20 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

RELN encodes a large secreted extracellular glycoprotein that governs neuronal migration and cortical lamination, acting on migrating neurons by binding the lipoprotein receptors VLDLR and APOER2 to trigger downstream DAB1 tyrosine phosphorylation (PMID:10973257). Complete loss of Reelin protein causes autosomal recessive lissencephaly with cerebellar hypoplasia in humans, sheep, and the reeler mouse, establishing Reelin as essential for laminar brain architecture (PMID:10973257, PMID:24260534). Beyond cortical neurons, Reelin directs the lateral migration and positioning of substantia nigra dopaminergic neurons (PMID:12724835), and its loss is genetically buffered by the Pafah1b complex during brain development (PMID:18514414). The protein's C-terminal region is required for secretion and confers receptor-binding specificity, being selectively required for VLDLR—but not APOER2—binding and signaling (PMID:9406921, PMID:28123028). Secretion proceeds in part through a specialized axonal bulk-transport route from Cajal-Retzius cells (PMID:11745613), and missense or RXR-motif mutations (e.g., R2290C) impair secretion, provoke ER protein-folding stress, and blunt the Reelin-DAB1 cascade in ASD-associated neural models (PMID:29969175, PMID:28419454, PMID:30022058). Reelin signaling is terminated extracellularly by ADAMTS-3, which cleaves and inactivates the protein (PMID:33388358). RELN expression is controlled transcriptionally by the activator EGR3 (PMID:33113163) and epigenetically through KDM5B-mediated H3K4 demethylation (PMID:26739753) and promoter CpG methylation (PMID:15717292, PMID:24448211). DAB1-dependent signaling also constrains glioblastoma proliferation and migration (PMID:29222813).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 1997 High

    Established that the Reelin C-terminus controls secretion rather than synthesis, separating protein production from delivery to the cell surface.

    Evidence N- vs C-terminal epitope immunohistochemistry and vital surface staining of Cajal-Retzius cells in Orleans reeler vs. normal embryonic cortex

    PMID:9406921

    Open questions at the time
    • Did not define the specific C-terminal motif or trafficking machinery required
    • Mechanism of intracellular retention of truncated protein not resolved
  2. 2000 High

    Answered whether RELN loss-of-function causes human disease, defining RELN as essential for neuronal migration and cortical lamination by linking splice-disrupting mutations and absent protein to lissencephaly with cerebellar hypoplasia.

    Evidence Human genetics, Western blot for protein absence, comparison to reeler mouse

    PMID:10973257

    Open questions at the time
    • Receptor and integrin binding partners listed but not individually dissected in this study
    • Downstream signaling steps not mechanistically resolved here
  3. 2001 High

    Defined how Reelin reaches its extracellular target, identifying an axonal bulk-transport secretory route from Cajal-Retzius cells into the marginal zone.

    Evidence Light and electron microscopy immunohistochemistry in normal vs. Reln(Orl) and Reln(Alb2) mutant mice

    PMID:11745613

    Open questions at the time
    • Molecular sorting machinery for axonal cisterns not identified
    • Whether this route operates in other Reelin-secreting cell types unknown
  4. 2003 Medium

    Extended Reelin's migration function beyond cortex, showing it guides lateral migration and positioning of nigral dopaminergic neurons.

    Evidence CR-50 immunolabeling with anterograde axonal tracing in reeler vs. normal mice

    PMID:12724835

    Open questions at the time
    • Receptor mediating the dopaminergic effect not identified
    • Single-lab observation
  5. 2008 Medium

    Connected the Reelin pathway to the Pafah1b complex genetically, showing alpha-subunit-specific modulation of Reelin-dependent brain development.

    Evidence Genetic epistasis in triple Pafah1b1;Reln;Pafah1b2/b3 mutant mice with histological analysis

    PMID:18514414

    Open questions at the time
    • No biochemical interaction between Reelin and Pafah1b shown
    • Mechanism of opposing alpha-subunit effects unresolved
  6. 2017 High

    Assigned receptor-binding specificity to the C-terminal region, demonstrating it is selectively required for VLDLR but not APOER2 signaling.

    Evidence RelnCTRdel mouse, genetic epistasis with Apoer2null and Vldlrnull alleles, in vitro RELN-receptor binding assay

    PMID:28123028

    Open questions at the time
    • Structural basis of CTR-VLDLR contact not resolved
    • Functional consequences of APOER2-only signaling not fully characterized
  7. 2017 Medium

    Linked ASD RXR-motif missense mutations to a secretion defect that triggers ER folding stress, providing a cell-biological mechanism for partial loss of function.

    Evidence Site-directed mutagenesis (R2290C), secretion assays, neurospheres, heterozygous mouse, PDI upregulation by proteomics/Western

    PMID:28419454

    Open questions at the time
    • Whether ER stress is causal or correlative not established
    • Single lab
  8. 2018 Medium

    Demonstrated that ASD-associated compound heterozygous variants reduce secretion and impair Reelin-DAB1 signaling, with mTORC1 overactivation acting as a modifiable second hit.

    Evidence Patient iPSC-derived neural progenitors, secretion ELISA/Western, DAB1 phosphorylation, rapamycin rescue

    PMID:29969175

    Open questions at the time
    • Mechanistic link between mTORC1 and Reelin-DAB1 not defined
    • Single patient-derived model
  9. 2018 Medium

    Resolved RELN's role in migration at single-cell level, showing a rare variant converts directional to wandering migration in human dopaminergic neurons.

    Evidence CRISPR-edited isogenic iPSC dopaminergic neurons, single-cell trajectory analysis, transcriptomics, patient validation

    PMID:30022058

    Open questions at the time
    • Receptor and cytoskeletal effectors downstream not identified
    • Single lab
  10. 2018 Medium

    Connected RELN haploinsufficiency to neuropsychiatric phenotypes, showing a schizophrenia-associated deletion reduces serum Reelin and produces behavioral, dopaminergic, and GABAergic deficits in mice.

    Evidence Patient Western blot, Reln(rl-Orl/+) mouse behavioral and neurochemical phenotyping, antipsychotic rescue

    PMID:30158644

    Open questions at the time
    • Causal link between serum Reelin and brain phenotype not established
    • Single lab
  11. 2018 Medium

    Showed RELN-DAB1 signaling controls cancer cell behavior, with DAB1 phosphorylation required for Reelin-induced glioblastoma growth arrest.

    Evidence RELN overexpression/silencing, DAB1-5F phosphorylation-null mutant, migration and proliferation assays, proteomics, RELN promoter bisulfite sequencing

    PMID:29222813

    Open questions at the time
    • Receptor used in glioblastoma not identified
    • Substrate-dependent phosphorylation-independent migration mechanism unresolved
  12. 2021 Medium

    Identified ADAMTS-3 as a negative regulator that cleaves and inactivates Reelin, controlling signaling strength at the extracellular level.

    Evidence shRNA knockdown of ADAMTS-3 in cortical neurons, Reelin cleavage assay, DAB1 expression Western

    PMID:33388358

    Open questions at the time
    • Cleavage site sequence and structural consequence not detailed here
    • Single lab
  13. 2020 Medium

    Established transcriptional and epigenetic control of RELN, identifying EGR3 as a direct activator and KDM5B as an H3K4-demethylase repressor.

    Evidence ChIP and luciferase for EGR3 in SH-SY5Y with siRNA epistasis; KDM5B ChIP, knockdown, H3K4me3, extracellular Reelin ELISA and DAB1 phosphorylation in adult NSCs with CR-50 rescue

    PMID:26739753 PMID:33113163

    Open questions at the time
    • Integration of EGR3 and KDM5B inputs at the locus unknown
    • Physiological signals controlling these regulators not defined
  14. 2014 Medium

    Linked RELN promoter methylation to disease and development, showing MeCP2/5-hmC-mediated repression in ASD cerebellum.

    Evidence MeCP2 and TET1 ChIP, MeDIP/hMeDIP, TAB pyrosequencing, qRT-PCR in post-mortem ASD cerebellum

    PMID:24448211

    Open questions at the time
    • Causality of MeCP2 binding for RELN silencing not tested by perturbation
    • Post-mortem correlation only
  15. 2022 Low

    Proposed an epistatic interaction between the APOE locus and the DAB1-RELN pathway in Alzheimer's disease via genetic association.

    Evidence GWAS in APOE-ε4 homozygotes and pathway-level analysis of DAB1-RELN components

    PMID:35977442

    Open questions at the time
    • No direct functional experiment on RELN protein
    • Association does not establish mechanism

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the multiple regulatory layers (EGR3, KDM5B, promoter methylation, ADAMTS-3 cleavage) are integrated to set Reelin dosage at specific developmental and disease states remains unresolved.
  • No unified model connecting transcriptional, epigenetic, and proteolytic control
  • Structural basis of receptor selectivity not solved
  • Mechanism linking partial loss to specific neuropsychiatric phenotypes incompletely defined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 3 GO:0048018 receptor ligand activity 2
Localization
GO:0005576 extracellular region 4
Pathway
R-HSA-1643685 Disease 4 R-HSA-1266738 Developmental Biology 3 R-HSA-162582 Signal Transduction 3
Partners
ADAMTS3APOER2DAB1VLDLR

Evidence

Reading pass · 20 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2000 RELN encodes a large secreted protein (388 kDa) that acts on migrating cortical neurons by binding to VLDLR, ApoER2, α3β1 integrin, and protocadherins. Loss-of-function mutations in RELN (disrupting splicing, resulting in absent/very low protein) cause autosomal recessive lissencephaly with cerebellar hypoplasia (LCH), paralleling the reeler mouse phenotype, establishing RELN as essential for neuronal migration and cortical lamination. Human genetics (identification of splice-disrupting mutations), Western blotting (absent reelin protein), comparison to reeler mouse model Nature genetics High 10973257
1997 The C-terminal region of Reelin is essential for its secretion. In the Orleans reeler allele (Reln[rl-Orl]), a 220-nucleotide deletion causes a frameshift producing a truncated protein that accumulates intracellularly but is not secreted at the cell surface, demonstrating that the C-terminus is required for secretion rather than protein production per se. Immunohistochemistry with multiple antibodies (N-terminal and C-terminal epitopes), vital surface staining of living Cajal-Retzius cells in normal vs. Orleans mutant embryonic cortex Brain research. Molecular brain research High 9406921
2001 Reelin is secreted from Cajal-Retzius cells via an axonal pathway: Reelin-containing smooth cisterns are transported from the axonal cone along axons ('axonal reelin reservoirs') and secreted into the cortical marginal zone, constituting a novel bulk transport secretory mechanism. In Reln(Orl) mutants, failure of this pathway leads to massive accumulation of truncated Reelin in dilated axonal cisterns. Light and electron microscopy immunohistochemistry in normal vs. Reln(Orl) and Reln(Alb2) mutant mice The Journal of comparative neurology High 11745613
2003 Reelin is required for the lateral migration and correct positioning of dopaminergic neurons destined for the substantia nigra. In reeler mutant mice lacking Reelin, nigral dopaminergic neurons cluster medially near the ventral tegmental area rather than migrating laterally, and their axons project to striatal patches forming 'dopamine islands.' Embryonic striatal neurons supply the ventral mesencephalon with Reelin through axonal projections. Comparison of normal vs. Reln(rl) mutant mice; CR-50 (anti-Reelin) immunolabeling combined with anterograde axonal tracing The Journal of comparative neurology Medium 12724835
2017 The C-terminal region (CTR) domain of RELN confers receptor-binding specificity: CTR truncation selectively impairs RELN binding to VLDLR but not to APOER2. Genetic epistasis in RelnCTRdel/Apoer2null double homozygotes (phenotype resembles reeler) vs. RelnCTRdel/Vldlrnull (phenotype does not) confirmed that CTR-dependent signaling operates through VLDLR, while APOER2 signaling remains intact without CTR. A direct RELN-binding assay confirmed significantly decreased RELN–VLDLR binding upon CTR truncation. Chemically induced splice-site mutant mouse (RelnCTRdel), genetic epistasis with Apoer2null and Vldlrnull double homozygotes, in vitro RELN-receptor binding assay The Journal of neuroscience : the official journal of the Society for Neuroscience High 28123028
2018 Rare compound heterozygous missense variants in RELN (identified in an ASD patient) lead to diminished Reelin secretion and impaired Reelin-DAB1 signal transduction in iPSC-derived neural progenitor cells. mTORC1 pathway overactivation acts as a second hit to further downregulate the Reelin-DAB1 cascade; inhibition of mTORC1 by rapamycin partially attenuates this signaling impairment. iPSC-derived neural progenitor cells from ASD patient; functional assays for Reelin secretion (ELISA/Western), DAB1 phosphorylation (Western), mTORC1 signaling; rapamycin rescue experiment Human mutation Medium 29969175
2017 The de novo ASD mutation RELN R2290C (and analogous mutations in RXR motifs) reduces Reelin protein secretion. Heterozygous RELN R2290C neurospheres show up-regulation of Protein Disulfide Isomerase A1 (PDIA1/ERp57), an ER chaperone, suggesting ER protein-folding stress as a consequence of defective Reelin secretion. This phenotype is recapitulated in a heterozygous mouse mutant with defective Reelin secretion. Site-directed mutagenesis of RELN R2290C and analogous RXR-motif mutations, Reelin secretion assays in transfected cells, RELN R2290C heterozygous neurospheres, heterozygous mouse mutant with defective secretion, proteomics/Western for PDI upregulation Journal of neurochemistry Medium 28419454
2018 RELN signaling regulates glioblastoma cell migration in a DAB1 tyrosine-phosphorylation-dependent and -independent manner depending on substrate. RELN stimulation strongly reduces glioblastoma cell proliferation; a DAB1-5F mutant (lacking all RELN-induced tyrosine phosphorylation sites) fails to induce growth arrest, establishing that DAB1 phosphorylation is required for the anti-proliferative effect. Proteomic analysis revealed that RELN-induced growth arrest involves reduction of E2F targets and dephosphorylation of ERK1/2. RELN overexpression and silencing in glioblastoma cells, DAB1-5F phosphorylation-null mutant, cell migration assays on multiple substrates, proliferation assays, proteomics, bisulfite sequencing of RELN promoter, 5-azacytidine/TSA reactivation Brain pathology (Zurich, Switzerland) Medium 29222813
2016 Kdm5b (Jarid1b), a histone H3K4 demethylase, represses Reln expression in adult subventricular zone neural stem cells by binding the proximal Reln promoter. shRNA-mediated Kdm5b depletion increases H3K4me3 at the Reln locus, elevates extracellular Reelin, increases phosphorylation of DAB1 (the downstream Reelin signaling adapter), and enhances NSC migration velocity; sequestration of extracellular Reelin with CR-50 antibody suppresses this enhanced migration. shRNA knockdown of Kdm5b in adult NSCs, ChIP for Kdm5b and H3K4me3 at Reln promoter, extracellular Reelin ELISA, DAB1 phosphorylation Western, migration velocity assay, CR-50 antibody rescue experiment Molecular biology of the cell Medium 26739753
2020 EGR3 is a direct transcriptional activator of RELN: ChIP confirmed EGR3 binding to the RELN promoter, and luciferase reporter assays demonstrated that EGR3 activates RELN transcription. EGR3 overexpression reduces neurite outgrowth, and this effect is partially reversed by RELN knockdown, placing EGR3 upstream of RELN in a neurite-outgrowth regulatory pathway. DNA microarray, ChIP, luciferase reporter assay, EGR3 overexpression and RELN siRNA knockdown in SH-SY5Y cells, neurite outgrowth assay Journal of neurochemistry Medium 33113163
2008 The Pafah1b2 (alpha2 subunit of the Lis1-associated Pafah1b complex) genetically suppresses hydrocephalus in compound Pafah1b1;Reln and Pafah1b1;Dab1 double-mutant mice, whereas Pafah1b3 mutations exacerbate layering defects. This genetic epistasis demonstrates that Reln-pathway components interact with the Pafah1b complex, and that the two alpha subunits have distinct, opposing effects on Reelin-pathway-dependent brain development. Genetic epistasis: triple mouse mutant generation (Pafah1b1;Reln;Pafah1b2 and Pafah1b1;Reln;Pafah1b3), histological analysis of layering defects and hydrocephalus Neuroscience letters Medium 18514414
2021 ADAMTS-3, a metalloprotease, cleaves and inactivates Reelin at the N-terminal site. shRNA knockdown of ADAMTS-3 in primary cultured cortical neurons suppresses Reelin cleavage in conditioned medium and reduces DAB1 expression, indicating enhanced Reelin-DAB1 signaling when ADAMTS-3 is inhibited. This places ADAMTS-3 as a negative regulator of the Reelin signaling pathway. shRNA knockdown of ADAMTS-3 in primary cortical neuron cultures, Reelin cleavage assay in conditioned medium, DAB1 expression by Western blot Neurochemistry international Medium 33388358
2018 A rare RELN deletion (exons 52–58, similar to the Orleans mutation) identified in a schizophrenia patient reduces serum Reelin levels. Heterozygous Reln(rl-Orl/+) mice show anxiety, impaired social behavior, and impaired motor learning; motor learning deficits are ameliorated by antipsychotics. Methamphetamine-induced hyperactivity and dopamine release are reduced, and GABAergic markers are decreased in the brain of these mice, indicating Reelin haploinsufficiency affects dopaminergic and GABAergic systems. Western blot for serum RELN in patient, behavioral analysis of heterozygous Reln(rl-Orl/+) mice, neurochemical measurements (dopamine release, GABAergic markers), antipsychotic rescue experiment Scientific reports Medium 30158644
2018 A rare RELN variant (RELN-del) introduced into human iPSC-derived dopaminergic neurons by genome editing impairs Reelin signaling and decreases expression of genes relevant for cell movement. Single-cell trajectory analysis reveals that RELN-del neurons exhibit wandering (non-directional) migration in vitro, compared to directional migration in control neurons, directly linking RELN function to neuronal migration dynamics at single-cell resolution. CRISPR/Cas9 genome editing of RELN-del into iPSCs, differentiation to dopaminergic neurons, single-cell trajectory analysis of migration, Reelin signaling assay, transcriptomic analysis; confirmed in patient-derived neurons Translational psychiatry Medium 30022058
2013 A 31-bp deletion (c.5410_5440del) in ovine RELN exon 36 causes a premature stop codon, leading to absent Reelin protein in brain cortex and blood of affected lambs and a lissencephaly with cerebellar hypoplasia phenotype in a recessive pattern, establishing that complete loss of Reelin protein causes LCH in sheep as in humans and mice. GWAS and homozygosity mapping, RELN sequencing, RT-PCR (mRNA quantification), Western blot (protein absence in brain cortex and blood), segregation analysis in flock PloS one Medium 24260534
2010 RELN promoter hypermethylation is associated with silenced RELN expression in gastric cancer cell lines and primary gastric tumors. In non-tumor gastric epithelia RELN is strongly expressed. Treatment with demethylating/HDAC-inhibiting agents was not tested but methylation-specific PCR demonstrated correlation of promoter methylation with absent expression, suggesting epigenetic silencing as a mechanism for RELN downregulation in gastric carcinogenesis. Methylation-specific PCR of RELN promoter in GC cell lines and primary tumors; RT-PCR/immunohistochemistry for expression International journal of oncology Low 19956836
2005 RELN promoter CpG islands flanking a CRE and SP1 binding site are hypermethylated at significantly higher levels in post-mortem frontal lobe brains of schizophrenic patients compared to controls, and this hypermethylation is inversely correlated with RELN mRNA expression, suggesting promoter methylation as a mechanism for RELN downregulation in schizophrenia. Methylation-specific PCR (MSP) of post-mortem brain DNA; semi-quantitative RT-PCR for expression correlation American journal of medical genetics. Part B, Neuropsychiatric genetics Low 15717292
2014 In ASD cerebellum, MeCP2 binding to the RELN promoter is significantly increased, coinciding with enrichment of 5-hydroxymethylcytosine (5-hmC, not 5-mC) at the RELN promoter, increased TET1 expression, and reduced RELN mRNA. This suggests MeCP2 preferentially binds 5-hmC to repress RELN in ASD, mediated by TET1-driven 5-mC oxidation. ChIP for MeCP2 and TET1 binding; MeDIP and hMeDIP for 5-mC and 5-hmC; TET-assisted bisulfite (TAB) pyrosequencing; qRT-PCR for mRNA Translational psychiatry Medium 24448211
2010 RELN promoter methylation increases significantly after puberty in normal human neocortex (Brodmann Area 41/42): prepuberal individuals show very little or no methylation, while most postpuberal individuals are heavily methylated, especially at CpG positions between -131 and -98 bp, suggesting sex hormone-driven DNA methylation as a developmental regulatory mechanism for RELN. Bisulfite pyrosequencing of post-mortem temporocortical tissue from prepuberal (n=3) and postpuberal (n=6) normal individuals Neuroreport Low 19952965
2022 Whole-genome association in APOE-ε4 homozygotes identified a genome-wide significant association with DAB1 (rs112437613) in Alzheimer's disease, and pathway analysis of the DAB1-RELN pathway showed the entire pathway is associated with AD, suggesting epistatic interaction between the APOE locus and the DAB1-RELN signaling pathway in AD pathogenesis. GWAS in 5,390 APOE-ε4 homozygous UK Biobank individuals; pathway-level analysis of DAB1-RELN components Neurobiology of aging Low 35977442

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2000 Autosomal recessive lissencephaly with cerebellar hypoplasia is associated with human RELN mutations. Nature genetics 638 10973257
2005 Hypermethylation of the reelin (RELN) promoter in the brain of schizophrenic patients: a preliminary report. American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics 299 15717292
1992 Rapid induction in regenerating liver of RL/IF-1 (an I kappa B that inhibits NF-kappa B, RelB-p50, and c-Rel-p50) and PHF, a novel kappa B site-binding complex. Molecular and cellular biology 164 1588976
2005 Analysis of the RELN gene as a genetic risk factor for autism. Molecular psychiatry 132 15558079
2014 Increased binding of MeCP2 to the GAD1 and RELN promoters may be mediated by an enrichment of 5-hmC in autism spectrum disorder (ASD) cerebellum. Translational psychiatry 114 24448211
1997 A truncated Reelin protein is produced but not secreted in the 'Orleans' reeler mutation (Reln[rl-Orl]). Brain research. Molecular brain research 109 9406921
2003 Behavioral phenotype of the reeler mutant mouse: effects of RELN gene dosage and social isolation. Behavioral neuroscience 99 14674845
1995 Growth inhibition and apoptosis of RL human B lymphoma cells by vitamin E succinate and retinoic acid: role for transforming growth factor beta. Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research 85 7669719
2004 Lack of evidence for an association between WNT2 and RELN polymorphisms and autism. American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics 84 15048648
2024 Peptide Cy RL-QN15 accelerates hair regeneration in diabetic mice by binding to the Frizzled-7 receptor. Zoological research 71 39479995
2016 RELN Mutations in Autism Spectrum Disorder. Frontiers in cellular neuroscience 68 27064498
1996 The protein hydrolysate, Primatone RL, is a cost-effective multiple growth promoter of mammalian cell culture in serum-containing and serum-free media and displays anti-apoptosis properties. Journal of immunological methods 67 8765172
1979 Definition of a unique cell surface antigen of mouse leukemia RL male 1 by cell-mediated cytotoxicity. Proceedings of the National Academy of Sciences of the United States of America 66 91166
2016 Epigenetic RELN Dysfunction in Schizophrenia and Related Neuropsychiatric Disorders. Frontiers in cellular neuroscience 64 27092053
2012 Rhamnolipid (RL) from Pseudomonas aeruginosa OBP1: a novel chemotaxis and antibacterial agent. Colloids and surfaces. B, Biointerfaces 64 23261573
2004 Robust-LongSAGE (RL-SAGE): a substantially improved LongSAGE method for gene discovery and transcriptome analysis. Plant physiology 64 15020752
2022 Zn2+ Cross-Linked Alginate Carrying Hollow Silica Nanoparticles Loaded with RL-QN15 Peptides Provides Promising Treatment for Chronic Skin Wounds. ACS applied materials & interfaces 59 35731847
2011 The genetic variation of RELN expression in schizophrenia and bipolar disorder. PloS one 57 21603580
2009 A genome-wide analysis identifies genetic variants in the RELN gene associated with otosclerosis. American journal of human genetics 55 19230858
2010 Epigenetic silencing of RELN in gastric cancer. International journal of oncology 52 19956836
2008 The RELN locus in Alzheimer's disease. Journal of Alzheimer's disease : JAD 52 18599960
2019 In Vitro Modeling of the Bipolar Disorder and Schizophrenia Using Patient-Derived Induced Pluripotent Stem Cells with Copy Number Variations of PCDH15 and RELN. eNeuro 51 31540999
2010 Reduced expression of reelin (RELN) gene is associated with high recurrence rate of hepatocellular carcinoma. Annals of surgical oncology 51 20734148
2001 Axonal secretion of Reelin by Cajal-Retzius cells: evidence from comparison of normal and Reln(Orl) mutant mice. The Journal of comparative neurology 51 11745613
2007 The role of RELN in lissencephaly and neuropsychiatric disease. American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics 50 16958033
2003 Lack of Reelin causes malpositioning of nigral dopaminergic neurons: evidence from comparison of normal and Reln(rl) mutant mice. The Journal of comparative neurology 50 12724835
2017 Epigenetic regulation of RELN and GAD1 in the frontal cortex (FC) of autism spectrum disorder (ASD) subjects. International journal of developmental neuroscience : the official journal of the International Society for Developmental Neuroscience 49 28229923
2008 The association analysis of RELN and GRM8 genes with autistic spectrum disorder in Chinese Han population. American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics 48 17955477
2018 Genetic and animal model analyses reveal the pathogenic role of a novel deletion of RELN in schizophrenia. Scientific reports 46 30158644
2017 Reelin (RELN) DNA methylation in the peripheral blood of schizophrenia. Journal of psychiatric research 46 28086126
2025 Ultra-short cyclic peptide Cy RL-QN15 acts as a TLR4 antagonist to expedite oral ulcer healing. Zoological research 45 41017403
2020 Bioremediation of di-(2-ethylhexyl) phthalate contaminated red soil by Gordonia terrae RL-JC02: Characterization, metabolic pathway and kinetics. The Science of the total environment 44 32446058
2006 Deep and comparative analysis of the mycelium and appressorium transcriptomes of Magnaporthe grisea using MPSS, RL-SAGE, and oligoarray methods. BMC genomics 44 17156450
2015 5-, 12- and 15-Hydroxyeicosatetraenoic acids induce cellular hypertrophy in the human ventricular cardiomyocyte, RL-14 cell line, through MAPK- and NF-κB-dependent mechanism. Archives of toxicology 37 25600587
1999 Cycloheximide and 4-OH-TEMPO suppress chloramphenicol-induced apoptosis in RL-34 cells via the suppression of the formation of megamitochondria. Biochimica et biophysica acta 36 10076048
2021 Phthalic acid esters degradation by a novel marine bacterial strain Mycolicibacterium phocaicum RL-HY01: Characterization, metabolic pathway and bioaugmentation. The Science of the total environment 34 34118676
2017 Meta-analyses of RELN variants in neuropsychiatric disorders. Behavioural brain research 34 28506622
2016 Differential methylation at the RELN gene promoter in temporal cortex from autistic and typically developing post-puberal subjects. Journal of neurodevelopmental disorders 34 27134686
2015 Development of cellular hypertrophy by 8-hydroxyeicosatetraenoic acid in the human ventricular cardiomyocyte, RL-14 cell line, is implicated by MAPK and NF-κB. Cell biology and toxicology 33 26493311
1995 Suppressed T cell and macrophage function in the "reeler" (rl/rl) mutant, a murine strain with elevated cerebellar norepinephrine concentration. Brain, behavior, and immunity 33 7620210
2020 RETRACTED: MicroRNA-381 facilitates autophagy and apoptosis in prostate cancer cells via inhibiting the RELN-mediated PI3K/AKT/mTOR signaling pathway. Life sciences 32 32304760
2016 RELN and VLDLR mutations underlie two distinguishable clinico-radiological phenotypes. Clinical genetics 32 27000652
2010 Neocortical RELN promoter methylation increases significantly after puberty. Neuroreport 32 19952965
2007 Investigation of potential gene-gene interactions between APOE and RELN contributing to autism risk. Psychiatric genetics 32 17621165
2004 Neurobehavioral evaluation of Reln-rl-orl mutant mice and correlations with cytochrome oxidase activity. Neuroscience research 32 15196778
2023 Peptide RL-QN15 promotes wound healing of diabetic foot ulcers through p38 mitogen-activated protein kinase and smad3/miR-4482-3p/vascular endothelial growth factor B axis. Burns & trauma 31 38026443
2018 RELN signaling modulates glioblastoma growth and substrate-dependent migration. Brain pathology (Zurich, Switzerland) 31 29222813
2016 Recombinant Newcastle disease virus (rL-RVG) triggers autophagy and apoptosis in gastric carcinoma cells by inducing ER stress. American journal of cancer research 30 27293989
2018 Rare RELN variants affect Reelin-DAB1 signal transduction in autism spectrum disorder. Human mutation 29 29969175
2011 Analysis of common genetic variants identifies RELN as a risk gene for schizophrenia in Chinese population. The world journal of biological psychiatry : the official journal of the World Federation of Societies of Biological Psychiatry 29 21745129
2021 Cloning and expression analysis of fused holin-endolysin from RL bacteriophage; Exhibits broad activity against multi drug resistant pathogens. Enzyme and microbial technology 28 34311883
2018 Single-cell trajectory analysis of human homogenous neurons carrying a rare RELN variant. Translational psychiatry 28 30022058
2016 Deletion of the Distal Tnfsf11 RL-D2 Enhancer That Contributes to PTH-Mediated RANKL Expression in Osteoblast Lineage Cells Results in a High Bone Mass Phenotype in Mice. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 28 26332516
2016 Identification of RELN variation p.Thr3192Ser in a Chinese family with schizophrenia. Scientific reports 27 27071546
2022 Whole genome analysis in APOE4 homozygotes identifies the DAB1-RELN pathway in Alzheimer's disease pathogenesis. Neurobiology of aging 26 35977442
2018 11β-HSD1 Inhibition by RL-118 Promotes Autophagy and Correlates with Reduced Oxidative Stress and Inflammation, Enhancing Cognitive Performance in SAMP8 Mouse Model. Molecular neurobiology 26 29611102
1981 Endogenous and cholera toxin-catalyzed ADP-ribosylation of a plasma membrane protein by RL-PR-C cloned rat hepatocytes. Biochimica et biophysica acta 26 7225428
2016 MicroRNA-340 Inhibits Tumor Cell Proliferation and Induces Apoptosis in Endometrial Carcinoma Cell Line RL 95-2. Medical science monitor : international medical journal of experimental and clinical research 25 27153225
2014 Human fetal ventricular cardiomyocyte, RL-14 cell line, is a promising model to study drug metabolizing enzymes and their associated arachidonic acid metabolites. Journal of pharmacological and toxicological methods 25 25454080
2008 Genetic analysis of reelin gene (RELN) SNPs: no association with autism spectrum disorder in the Indian population. Neuroscience letters 25 18597938
2017 The de novo autism spectrum disorder RELN R2290C mutation reduces Reelin secretion and increases protein disulfide isomerase expression. Journal of neurochemistry 24 28419454
2011 Association study of RELN polymorphisms with schizophrenia in Han Chinese population. Progress in neuro-psychopharmacology & biological psychiatry 24 21549172
2016 Inhibition of the histone demethylase Kdm5b promotes neurogenesis and derepresses Reln (reelin) in neural stem cells from the adult subventricular zone of mice. Molecular biology of the cell 23 26739753
2020 Generation and analysis of novel Reln-deleted mouse model corresponding to exonic Reln deletion in schizophrenia. Psychiatry and clinical neurosciences 22 32065683
2018 Protective effects of antioxidin-RL from Odorrana livida against ultraviolet B-irradiated skin photoaging. Peptides 22 29341894
2005 The RL-ET-14 cell line mediates expression of glutamine synthetase through the upstream enhancer/promoter region. Journal of hepatology 22 15876469
2015 RELN rare variants in myoclonus-dystonia. Movement disorders : official journal of the Movement Disorder Society 21 25648840
2015 Genetic analysis of the RELN gene: Gender specific association with Alzheimer's disease. Psychiatry research 21 26384575
2017 C-Terminal Region Truncation of RELN Disrupts an Interaction with VLDLR, Causing Abnormal Development of the Cerebral Cortex and Hippocampus. The Journal of neuroscience : the official journal of the Society for Neuroscience 20 28123028
2014 RELN-expressing neuron density in layer I of the superior temporal lobe is similar in human brains with autism and in age-matched controls. Neuroscience letters 20 25067827
2014 Anti-proliferative effects of Siegesbeckia orientalis ethanol extract on human endometrial RL-95 cancer cells. Molecules (Basel, Switzerland) 19 25470271
2011 No significant association between RELN polymorphism and autism in case-control and family-based association study in Chinese Han population. Psychiatry research 19 20554015
2011 A new single-nucleotide mutation (rs362719) of the reelin (RELN) gene associated with schizophrenia in female Chinese Han. Genetics and molecular research : GMR 19 21863557
2019 Migration of gastric cancer is suppressed by recombinant Newcastle disease virus (rL-RVG) via regulating α7-nicotinic acetylcholine receptors/ERK- EMT. BMC cancer 18 31640627
2015 Thermus parvatiensis RL(T) sp. nov., Isolated from a Hot Water Spring, Located Atop the Himalayan Ranges at Manikaran, India. Indian journal of microbiology 18 26543260
2010 Genetic variants in RELN are associated with otosclerosis in a non-European population from Tunisia. Annals of human genetics 18 20642811
2023 Peptide RL-QN15 promotes regeneration of epidermal nerve fibers and recovery of sensory function in diabetic skin wounds. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 17 36951647
2017 Recombinant Newcastle disease virus rL-RVG enhances the apoptosis and inhibits the migration of A549 lung adenocarcinoma cells via regulating alpha 7 nicotinic acetylcholine receptors in vitro. Virology journal 17 28974241
2014 Genetic association analysis in a clinically and histologically confirmed otosclerosis population confirms association with the TGFB1 gene but suggests an association of the RELN gene with a clinically indistinguishable otosclerosis-like phenotype. Otology & neurotology : official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology 17 24643032
2006 Tanacetum parthenium and Salix alba (Mig-RL) combination in migraine prophylaxis: a prospective, open-label study. Clinical drug investigation 17 17163262
2002 Synaptic inputs of class III and class V interneurons in the cat pulvinar nucleus: differential integration of RS and RL inputs. Visual neuroscience 17 12180859
2020 Identification of RELN variant p.(Ser2486Gly) in an Iranian family with ankylosing spondylitis; the first association of RELN and AS. European journal of human genetics : EJHG 16 32001840
2022 Monoallelic and biallelic mutations in RELN underlie a graded series of neurodevelopmental disorders. Brain : a journal of neurology 15 35769015
2020 Schizophrenia risk candidate EGR3 is a novel transcriptional regulator of RELN and regulates neurite outgrowth via the Reelin signal pathway in vitro. Journal of neurochemistry 15 33113163
2015 Autophagy is involved in recombinant Newcastle disease virus (rL-RVG)-induced cell death of stomach adenocarcinoma cells in vitro. International journal of oncology 15 26058483
2010 The Reelin (RELN) gene is associated with executive function in healthy individuals. Neurobiology of learning and memory 15 20727978
1999 Mathematical modeling and optimization of cellulase protein production using Trichoderma reesei RL-P37. Biotechnology and bioengineering 15 10556790
2012 Association analysis of two single-nucleotide polymorphisms of the RELN gene with autism in the South African population. Genetic testing and molecular biomarkers 14 23216241
2008 Pafah1b2 mutations suppress the development of hydrocephalus in compound Pafah1b1; Reln and Pafah1b1; Dab1 mutant mice. Neuroscience letters 14 18514414
2021 Analysis of Reelin signaling and neurodevelopmental trajectory in primary cultured cortical neurons with RELN deletion identified in schizophrenia. Neurochemistry international 13 33388358
2019 Female gender specific association of the Reelin (RELN) gene rs7341475 variant with schizophrenia. Molecular biology reports 13 30980267
2014 [The association of polymorphisms in SLC18A1, TPH1 and RELN genes with risk of paranoid schizophrenia]. Molekuliarnaia biologiia 13 25842846
2021 Mice with exonic RELN deletion identified from a patient with schizophrenia have impaired visual discrimination learning and reversal learning in touchscreen operant tasks. Behavioural brain research 12 34499931
2020 Multifunctional Nanostructure RAP-RL Rescues Alzheimer's Cognitive Deficits through Remodeling the Neurovascular Unit. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 12 33511002
2018 Recombinant Newcastle disease virus expressing human IFN-λ1 (rL-hIFN-λ1)-induced apoptosis of A549 cells is connected to endoplasmic reticulum stress pathways. Thoracic cancer 12 30246439
2010 Identification of RL-TGR, a coreceptor involved in aversive chemical signaling. Proceedings of the National Academy of Sciences of the United States of America 12 20566865
1990 The permeability of EUDRAGIT RL and HEMA-MMA microcapsules to glucose and inulin. Biotechnology and bioengineering 12 18597256
2018 Evidence of distinct RELN and TGFB1 genetic associations in familial and non-familial otosclerosis in a British population. Human genetics 11 29728750
2018 Two single-nucleotide polymorphisms of the RELN gene and symptom-based and developmental deficits among children and adolescents with autistic spectrum disorders in the Tianjin, China. Behavioural brain research 11 29753726
2013 Identification of a 31-bp deletion in the RELN gene causing lissencephaly with cerebellar hypoplasia in sheep. PloS one 11 24260534

Missed literature

Know a paper Affinage missed for RELN? Flag it for the maintainers and the community.

No submissions yet.