| BIN1 — Bridging Integrator 1 | |
|---|---|
| Symbol | BIN1 |
| Full Name | Bridging Integrator 1 (Amphiphysin 2) |
| Chromosome | 2q14.3 |
| NCBI Gene | 274 |
| Ensembl | ENSG00000136717 |
| OMIM | 601248 |
| UniProt | O00499 |
| Diseases | Alzheimer's Disease |
| Expression | Cerebral cortex, Hippocampus, White matter, Cerebellum |
| Key Variants | |
| rs744373 (AD risk, OR ~1.17-1.19) rs6733839 (AD risk, OR ~1.20) rs4663105 (AD risk, LD with rs744373) |
|
Bin1 — Bridging Integrator 1 is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.
BIN1 (Bridging Integrator 1, also known as Amphiphysin 2, Myc box-dependent-interacting protein 1, or AMPH2) is a gene located on chromosome 2q14.3 that encodes a member of the BAR (Bin/Amphiphysin/Rvs) adapter
protein family [1].
BIN1 is the second most significant genetic risk locus for late-onset [Alzheimer's disease[/diseases/alzheimers (LOAD) after [APOE[/genes/apoe is enriched in [neurons[/entities/neurons and plays critical roles in synaptic vesicle endocytosis, membrane dynamics,
and cytoskeletal organization [3][4].
Unlike [APOE[/Amyloid-Beta pathology, BIN1 appears to modulate [Alzheimer's disease[/diseases/alzheimers risk primarily through effects on tau[/proteins/tau-protein pathology and synaptic function [2][5].
The BIN1 protein contains several functional domains that mediate its diverse cellular roles [3]:
In the brain, BIN1 participates in multiple critical processes [3][4]:
BIN1 is expressed throughout the brain, with highest levels in:
Expression data is available from the Allen Human Brain Atlas.
BIN1 was first identified as an AD risk locus in large-scale GWAS meta-analyses published in 2010–2011 [1]. The association has been replicated across multiple independent cohorts and populations. Key risk variants include:
These variants are located in regulatory regions upstream of BIN1 and are thought to influence BIN1 expression levels rather than protein structure [2].
A growing body of evidence links BIN1 specifically to tau[/proteins/tau-protein pathology rather than [Amyloid-Beta[/proteins/Amyloid-Beta deposition [2][5][6]:
In [Alzheimer's disease[/diseases/alzheimers brain tissue, BIN1 protein is lost from the cytoplasmic fraction of cortical [neurons[/entities/neurons, and this loss is accompanied by progressive mislocalization of phosphorylated tau[/proteins/tau-protein
to synapses [5].
This suggests that BIN1 normally acts to restrain pathological tau accumulation at synapses, and its loss contributes to synaptic tau pathology and cognitive decline [5].
BIN1 risk allele carriers show faster rates of cognitive decline compared to non-carriers, and this effect is mediated by accelerated global tau-PET accumulation in the presence of
[Amyloid-Beta[/proteins/Amyloid-Beta pathology [8]. Importantly, BIN1 effects on tau accumulation are amyloid-dependent, consistent with the amyloid cascade model
where amyloid pathology triggers downstream tau spread [8].
The study of Bin1 — Bridging Integrator 1 has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.
Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.