AGAP1 (ArfGAP With GTPase Domain, Ankyrin Repeat And PH Domain 1)
A GTPase-activating protein involved in vesicle trafficking and neuronal function.
Gene Information Card
| Symbol | AGAP1 |
|---|---|
| Full Name | ArfGAP With GTPase Domain, Ankyrin Repeat And PH Domain 1 |
| Gene Type | Protein-coding |
| Chromosomal Location | 2q37.2 |
| NCBI Gene ID | 116987 ncbi.nlm.nih.gov/gene/116987 |
| Ensembl ID | ENSG00000157978 |
| UniProt ID | Q9UPQ3 |
| OMIM ID | 608651 |
| HGNC ID | 16922 |
| Aliases | AGAP-1, CENTG2, GGAP1, KIAA1099 |
Description
AGAP1 encodes a member of the AGAP family of GTPase-activating proteins (GAPs) that specifically regulate ADP-ribosylation factor (Arf) and Rho family GTPases. The protein contains an N-terminal GTPase domain, a pleckstrin homology (PH) domain, an ArfGAP domain, and ankyrin repeats. It plays a role in clathrin-dependent vesicle trafficking, neurite outgrowth, and cytoskeletal organization. AGAP1 is widely expressed, with highest levels in the brain.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Intellectual disability | AGAP1 variants may disrupt vesicle trafficking in neurons, impairing synaptic function. | ClinVar, OMIM |
| Autism spectrum disorder | De novo missense and loss-of-function variants identified in ASD cohorts. | ClinVar, NCBI |
| Schizophrenia | Rare copy number variants and SNPs associated with increased risk. | NCBI, OMIM |
| Cancer (various) | Altered expression and somatic mutations reported in breast, lung, and colorectal cancers. | COSMIC, NCBI |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain (cerebral cortex) | 15.2 | High |
| Testis | 8.7 | Medium |
| Thyroid | 6.1 | Medium |
| Adrenal gland | 5.4 | Medium |
| Liver | 2.3 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 12.5 | Neuronal model |
| HEK293 (embryonic kidney) | 8.9 | Common cell line |
| HeLa (cervical carcinoma) | 6.3 | Epithelial |
| MCF7 (breast cancer) | 4.1 | Hormone-responsive |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.214C>T (p.Arg72Trp) | Missense | 0.001% | Reduced GAP activity; associated with neurodevelopmental delay |
| c.1024_1025del (p.Leu342fs) | Frameshift | <0.001% | Loss of function; reported in autism |
| c.1567G>A (p.Gly523Arg) | Missense | 0.002% | Impaired protein stability; linked to schizophrenia |
| c.2450A>G (p.Asn817Ser) | Missense | 0.005% | Somatic mutation in colorectal cancer |
Mutation functional classification
Loss of Function (LOF)
Frameshift and nonsense mutations that truncate the protein or disrupt the GAP domain lead to loss of ArfGAP activity.
Gain of Function (GOF)
Not well characterized; some missense mutations may alter substrate specificity.
Dominant Negative (DN)
Missense mutations in the GTPase domain may interfere with wild-type protein function.
View complete mutation data：
Gene Ontology (GO)
| • GTPase activator activity | • Arf GTPase activator activity |
| • GTP binding | • clathrin-coated vesicle |
| • cytoplasm | • Golgi apparatus |
| • neuronal cell body | • vesicle-mediated transport |
| • regulation of GTPase activity | • actin cytoskeleton organization |
Pathways
• Arf6 signaling pathway
• Clathrin-mediated endocytosis
• Vesicle trafficking
• Rho GTPase cycle
Protein Summary
AGAP1 is a multidomain protein that integrates GTPase signaling with vesicle trafficking. Its N-terminal GTPase domain binds GTP, while the PH domain mediates membrane localization. The ArfGAP domain inactivates Arf GTPases, and the ankyrin repeats facilitate protein-protein interactions. AGAP1 is essential for neurite extension and synaptic vesicle recycling, and its dysregulation is implicated in neurodevelopmental disorders and cancer.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| AGAP1 Knockout HEK293 Cell Line | EDJ-KQ3453 | Human | 116987 | Details Get a Quote |
| AGAP1 Knockout A-549 Cell Line | EDJ-KQ25192 | Human | 116987 | Details Get a Quote |
| AGAP1 Knockout HCT 116 Cell Line | EDJ-KQ25193 | Human | 116987 | Details Get a Quote |
| AGAP1 Knockout HeLa Cell Line | EDJ-KQ25194 | Human | 116987 | Details Get a Quote |
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