DISC1: Disrupted in Schizophrenia 1
A key gene in neurodevelopment and psychiatric disorders
Gene Information Card
| Symbol | DISC1 |
|---|---|
| Full Name | Disrupted in Schizophrenia 1 |
| Gene Type | protein-coding |
| Chromosomal Location | 1q42.2 |
| NCBI Gene ID | 27185 ncbi.nlm.nih.gov/gene/27185 |
| Ensembl ID | ENSG00000162946 |
| UniProt ID | Q9NRI5 |
| OMIM ID | 605210 |
| HGNC ID | 2888 |
| Aliases | SCZD9, C1orf136, FLJ13381, KIAA0457 |
Description
DISC1 (Disrupted in Schizophrenia 1) is a protein-coding gene located on chromosome 1q42.2. It encodes a scaffold protein involved in neurodevelopment, neuronal migration, and synaptic signaling. Disruption of DISC1 by a balanced translocation (1;11)(q42.1;q14.3) was initially linked to major psychiatric disorders including schizophrenia, bipolar disorder, and major depressive disorder. The protein interacts with multiple partners such as NDEL1, PDE4B, and GSK3B, influencing cAMP signaling, cytoskeletal dynamics, and neurogenesis.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Schizophrenia | Translocation disrupts DISC1 leading to altered neurodevelopment and synaptic function | OMIM #181500; multiple family studies |
| Bipolar Disorder | DISC1 variants affect cAMP signaling via PDE4B interaction | OMIM #125480; genetic association studies |
| Major Depressive Disorder | DISC1 missense variants impair neurite outgrowth and stress response | OMIM #608516; case-control studies |
| Autism Spectrum Disorder | Rare DISC1 variants linked to disrupted neuronal connectivity | ClinVar; limited evidence |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain (cerebral cortex) | 12.5 | Medium |
| Brain (hippocampus) | 15.2 | Medium |
| Brain (cerebellum) | 8.9 | Low |
| Testis | 6.3 | Low |
| Heart | 2.1 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 10.8 | Neuronal model |
| HEK293 (embryonic kidney) | 5.2 | Overexpression studies |
| U-87 MG (glioblastoma) | 7.4 | Glial model |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.151C>T (p.Arg51Trp) | Missense | <0.01% | Impaired NDEL1 binding; reduced neurite outgrowth |
| c.704C>T (p.Thr235Ile) | Missense | <0.01% | Altered PDE4B interaction; cAMP signaling dysregulation |
| c.1-? (translocation) | Structural variant | Rare | Complete disruption of gene; linked to psychiatric disorders |
Mutation functional classification
Loss of Function (LOF)
Translocation and truncating mutations reduce DISC1 protein levels or disrupt scaffold function, leading to impaired neurodevelopment.
Gain of Function (GOF)
Not well documented; no clear gain-of-function mutations reported.
Dominant Negative (DN)
Some missense variants (e.g., p.Arg51Trp) may act dominant-negative by sequestering interacting partners.
View complete mutation data：
Gene Ontology (GO)
Pathways
• cAMP signaling pathway (via PDE4B interaction)
• GSK3B signaling pathway
• NDEL1-mediated dynein motor pathway
• Neuronal migration and neurogenesis
Protein Summary
DISC1 is a 854-amino acid scaffold protein predominantly expressed in the brain. It localizes to the cytoplasm, centrosome, and mitochondria, and regulates neuronal migration, axon growth, and synaptic plasticity. Through interactions with NDEL1, PDE4B, and GSK3B, DISC1 modulates cAMP levels, cytoskeletal dynamics, and cell cycle progression. Disruption of DISC1 function is implicated in the pathophysiology of schizophrenia, bipolar disorder, and major depression.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| DISC1 Knockout HEK293 Cell Line | EDJ-KQ8712 | Human | 27185 | Details Get a Quote |
| DISC1 Knockout HeLa Cell Line | EDJ-KQ56027 | Human | 27185 | Details Get a Quote |
| DISC1 Knockout A-549 Cell Line | EDJ-KQ64513 | Human | 27185 | Details Get a Quote |
| DISC1 Knockout HCT 116 Cell Line | EDJ-KQ72971 | Human | 27185 | Details Get a Quote |
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