RELN Gene: Reelin – Function, Mutations, and Associated Disorders
Comprehensive biomedical overview of the RELN gene, including its role in neuronal migration, lissencephaly, and psychiatric conditions.
Gene Information Card
| Symbol | RELN |
|---|---|
| Full Name | Reelin |
| Gene Type | Protein coding |
| Chromosomal Location | 7q22.1 |
| NCBI Gene ID | 5649 ncbi.nlm.nih.gov/gene/5649 |
| Ensembl ID | ENSG00000189050 |
| UniProt ID | P78509 |
| OMIM ID | 600514 |
| HGNC ID | 9957 |
| Aliases | RL, LIS2, PRO1598 |
Description
The RELN gene encodes reelin, a large secreted extracellular matrix glycoprotein that regulates neuronal migration and positioning during brain development. Reelin signaling via VLDLR and LRP8 receptors controls layer formation in the cerebral cortex, hippocampus, and cerebellum. Mutations in RELN cause autosomal recessive lissencephaly with cerebellar hypoplasia (LCH) and are associated with increased risk for autism spectrum disorder, schizophrenia, and bipolar disorder.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Lissencephaly 2 (LCH) | Loss-of-function mutations disrupt reelin secretion or signaling, impairing neuronal migration and causing cortical malformation with cerebellar hypoplasia. | OMIM #257320; ClinVar pathogenic variants |
| Autism spectrum disorder | RELN variants (e.g., repeat polymorphisms, missense) alter reelin levels or function, affecting synaptic plasticity and cortical connectivity. | Case-control studies; PMID 16916689 |
| Schizophrenia | Reduced reelin expression in GABAergic interneurons leads to dendritic spine loss and synaptic dysfunction. Epigenetic silencing via promoter hypermethylation reported. | Postmortem brain studies; PMID 12553913 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Cerebral cortex | 12.3 | Medium |
| Cerebellum | 18.7 | High |
| Hippocampus | 15.1 | High |
| Placenta | 0.2 | Not detected |
| Liver | 0.1 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 8.5 | Neuronal model; moderate expression |
| U-87 MG (glioblastoma) | 3.2 | Low expression |
| HEK293 (embryonic kidney) | 0.4 | Not detected |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.2101C>T (p.Arg701Ter) | Nonsense | Rare | Loss of function; truncation of reelin protein |
| c.7461_7462delAG (p.Gly2488fs) | Frameshift | Rare | Loss of function; premature stop codon |
| c.5578G>A (p.Gly1860Arg) | Missense | <0.01% | Impaired secretion; associated with autism |
Mutation functional classification
Loss of Function (LOF)
Nonsense, frameshift, and splice-site mutations that abolish reelin secretion or receptor binding, leading to lissencephaly with cerebellar hypoplasia.
Gain of Function (GOF)
Not reported for RELN.
Dominant Negative (DN)
Not established; RELN mutations are typically recessive.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Reelin signaling pathway (Reactome R-HSA-8867275)
• Neuronal system (Reactome R-HSA-112316)
• Development and migration of neurons (KEGG hsa05200)
Protein Summary
Reelin is a 3461-amino-acid secreted glycoprotein with an N-terminal signal peptide, a F-spondin-like domain, eight reelin repeats, and a C-terminal basic region. It binds to VLDLR and LRP8 receptors on migrating neurons, inducing Dab1 phosphorylation and cytoskeletal rearrangement. Reelin is essential for proper layering of the cerebral cortex, hippocampus, and cerebellum. Reduced reelin expression is linked to psychiatric disorders, while complete loss causes severe brain malformation.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| RELN Knockout HEK293 Cell Line | EDJ-KQ863 | Human | 5649 | Details Get a Quote |
| RELN Knockout HeLa Cell Line | EDJ-KQ54231 | Human | 5649 | Details Get a Quote |
| RELN Knockout A-549 Cell Line | EDJ-KQ62723 | Human | 5649 | Details Get a Quote |
| RELN Knockout HCT 116 Cell Line | EDJ-KQ71195 | Human | 5649 | Details Get a Quote |
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