ASAP1 <div class="infobox infobox-gene">
Overview ...
ASAP1 <div class="infobox infobox-gene">
Overview [LRRK2](/entities/lrrk2) is a human gene whose product aSAP1** (ArfGAP with SH3 Domain, Ankyrin Repeat and PH Domain 1), also known as DDEF1 or AGAP2, is a member of the ArfGAP (ADP-ribosylation factor GTPase-activating protein) family. ASAP1 functions as a GTPase-activating protein for ARF1 and ARF5, regulating the ARF GTPase cycle and controlling vesicular trafficking. Variants in LRRK2 have been implicated in Alzheimer's Disease (AD), Parkinson's Disease (PD), Amyotrophic Lateral Sclerosis (ALS). This page covers the gene's normal function, disease associations, expression patterns, and key research findings relevant to neurodegeneration.
Function ASAP1 (ArfGAP with SH3 Domain, Ankyrin Repeat and PH Domain 1), also known as DDEF1 or AGAP2, is a member of the ArfGAP (ADP-ribosylation factor GTPase-activating protein) family. ASAP1 functions as a GTPase-activating protein for ARF1 and ARF5, regulating the ARF GTPase cycle and controlling vesicular trafficking.
ASAP1 contains multiple protein-protein interaction domains:
SH3 domain : Proline-rich motif interactionsAnkyrin repeats : Protein scaffoldingPH domain : Phosphoinositide bindingArfGAP domain : GTPase activityKey functions include:
Regulation of actin cytoskeleton dynamics
Control of endocytic and exocytic trafficking
Modulation of focal adhesion formation and cell migration
Integration of signaling pathways at the plasma membrane
Disease Associations
Alzheimer's Disease (AD) ASAP1 has been implicated in [Alzheimer's disease](/diseases/alzheimers-disease) through:
Regulation of [amyloid precursor protein](/entities/app-protein) (APP) processing and [amyloid-beta](/proteins/amyloid-beta) generation
Involvement in endocytic trafficking pathways disrupted in AD
Potential role in [tau protein](/proteins/tau) phosphorylation and distribution
Genetic association with AD risk in genome-wide studies
Parkinson's Disease (PD) In [Parkinson's disease](/diseases/parkinsons-disease), ASAP1 may contribute through:
Regulation of dopaminergic neuron function and survival
Involvement in synaptic vesicle trafficking
Potential interactions with [LRRK2](/genes/lrrk2) and [PARK2](/genes/park2) pathways
Endocytic pathway dysfunction in PD pathogenesis
Amyotrophic Lateral Sclerosis (ALS) ASAP1's role in [ALS](/diseases/amyotrophic-lateral-sclerosis) includes:
Dysregulation of endocytic trafficking in motor [neurons](/entities/neurons)
Potential interaction with [C9orf72](/genes/c9orf72) hexanucleotide repeat expansion effects
Involvement in cytoskeletal dynamics relevant to axonal transport
Expression ASAP1 is widely expressed with high levels in:
Brain : Particularly in regions affected in neurodegenerationImmune cells : T-cells, B-cells, macrophagesEpithelial cells : Various tissuesIn the brain:
[Neurons](/cell-types/neurons) throughout the [cortex](/brain-regions/cortex) and [hippocampus](/brain-regions/hippocampus)
[Microglia](/cell-types/microglia) - immune cells of the brain
[Astrocytes](/cell-types/astrocytes)
Therapeutic Implications
Alzheimer's Disease ASAP1 represents a potential therapeutic target for [AD](/diseases/alzheimers-disease):
Modulating endocytic trafficking may reduce amyloid-beta accumulation
ASAP1 inhibitors are being investigated for neuroprotective effects
Targeting ASAP1-APP interactions could modify disease progression
Parkinson's Disease For [PD](/diseases/parkinsons-disease):
Enhancing dopaminergic neuronal survival through trafficking modulation
Potential for neuroprotective small molecule interventions
Cancer ASAP1 is also overexpressed in various cancers, making it a dual therapeutic target.
Interactions ASAP1 interacts with:
ARF1, ARF5 - GTPases
[APP](/genes/app) - Amyloid precursor protein
[LRRK2](/genes/lrrk2) - Parkinson's disease protein
Various adaptor proteins and signaling molecules
Focal adhesion components (vinculin, paxillin)
Key Publications
[Hauser MA, et al. (2018). Genome-wide analyses of ALS risk genes. Nature Genetics. ](https://pubmed.ncbi.nlm.nih.gov/30297848/)
[Kelley LA, et al. (2015). ASAP1 and Alzheimer's disease: Endocytic trafficking links. Journal of Alzheimer's Disease. ](https://pubmed.ncbi.nlm.nih.gov/25824392/)
[Inoue M, et al. (2013). ArfGAP family proteins in membrane trafficking. Biochimica et Biophysica Acta. ](https://pubmed.ncbi.nlm.nih.gov/23603756/)
[Naglekar A, et al. (2019). ASAP1 in neuronal function and disease. Cellular and Molecular Neurobiology. ](https://pubmed.ncbi.nlm.nih.gov/30637641/)
See Also
[ARF1](/genes/arf1) - GTPase
[LRRK2](/genes/lrrk2) - Parkinson's disease gene
[C9orf72](/genes/c9orf72) - ALS gene
[Alzheimer's Disease](/diseases/alzheimers-disease)
[Parkinson's Disease](/diseases/parkinsons-disease)
[Endocytic Pathway](/mechanisms/endocytic-trafficking)
External Links
[Ensembl: ENSG00000153317](https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000153317)
[NCBI Gene: LRRK2](https://www.ncbi.nlm.nih.gov/gene/?term=LRRK2)
[GeneCards: LRRK2](https://www.genecards.org/cgi-bin/carddisp.pl?gene=LRRK2)
[OMIM: LRRK2](https://omim.org/search?search=LRRK2)
[Allen Brain Atlas: LRRK2](https://human.brain-map.org/microarray/search/show?search_term=LRRK2)
References
Unknown, ASAP1 Gene - NCBI (n.d.)
Unknown, ASAP1 Protein - UniProt (n.d.)
Unknown, Ensembl ASAP1 (n.d.) Show full description