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Target intelligence / Profile preview
Disabled homolog 1 (DAB1)
- Target
- DAB1
- Molecular classification
- Signal transduction adaptor protein, Intracellular adaptor protein, Other
01
Overview
Disabled homolog 1 (DAB1) is an intracellular signal transduction adaptor protein essential for mediating the Reelin signaling pathway, which regulates the migration, differentiation, and positioning of neurons during embryonic brain development and neurogenesis in the adult brain. DAB1 becomes tyrosine-phosphorylated in response to Reelin binding its receptors (VLDLR, ApoER2), which drives downstream pathways essential for inside-out laminar organization of the neocortex and cerebellum. Dysregulation or mutation of DAB1 is associated with developmental brain disorders such as spinocerebellar ataxia 37 and may impact susceptibility to neurodegenerative conditions like Alzheimer’s disease[1][2][4][6][7]. While DAB1 performs key roles in neurodevelopment, it is generally not considered a conventional therapeutic target for small-molecule drugs or biologics.
- Other names
- DAB adaptor protein 1YotariSCA37Disabled homolog 1, DAB1Reelin adaptor proteinDab reelin signal transducer 1DabReelin signal transducer, homolog 1Spinocerebellar ataxia 37Yotari, DAB1
02
Biological functions
Signal transduction in Reelin pathwayRegulation of neuronal migrationRegulation of neuronal positioning and cortical layeringBrain development and neurogenesisIntracellular signaling (phosphorylation)
03
Disease associations
Neurodevelopmental disorders (cortical malformations)Spinocerebellar ataxia 37 (SCA37)Spastic ataxiaNeurodegenerative diseases (suggested in Alzheimer’s disease)Potential tumor suppressor in cancer
04
Safety considerations
Genetic dysregulation can cause abnormal neuronal positioning and cerebellar degeneration (e.g., SCA37)Adverse developmental effects from mutations or dysfunction; no known drug-related safety concerns, as DAB1 is not a typical direct drug target
05
Biomarkers
DAB1 expression is associated with neuronal migration disordersAltered DAB1 expression is used in studies of brain development and neurodegenerative diseasesDAB1 mRNA may be a marker of functional reelin signaling in cortical brain tissue
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