RAP1GAP2: RAP1 GTPase Activating Protein 2
A regulator of RAP1 signaling with roles in platelet function and potential links to cancer and developmental disorders.
Gene Information Card
| Symbol | RAP1GAP2 |
|---|---|
| Full Name | RAP1 GTPase Activating Protein 2 |
| Gene Type | protein-coding |
| Chromosomal Location | 17p13.3 |
| NCBI Gene ID | 23108 ncbi.nlm.nih.gov/gene/23108 |
| Ensembl ID | ENSG00000132359 |
| UniProt ID | Q5JWF2 |
| OMIM ID | 609365 |
| HGNC ID | 29163 |
| Aliases | RAP1GAP2, RAP1GAP, RAP1GAP2_v1, RAP1GAP2_v2 |
Description
RAP1GAP2 encodes a GTPase-activating protein (GAP) that specifically inactivates RAP1 by stimulating its intrinsic GTPase activity, converting RAP1 from the active GTP-bound form to the inactive GDP-bound form. RAP1GAP2 is highly expressed in platelets and megakaryocytes, where it negatively regulates RAP1 signaling to control integrin activation and platelet aggregation. The gene is also expressed in brain and other tissues, and its dysregulation has been implicated in cancer progression and developmental disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Platelet-type bleeding disorder | Loss-of-function mutations in RAP1GAP2 impair RAP1 inactivation, leading to enhanced platelet activation and altered hemostasis. | ClinVar, OMIM |
| Colorectal cancer | RAP1GAP2 promoter hypermethylation and reduced expression are associated with tumor progression and poor prognosis. | COSMIC, NCBI |
| Breast cancer | Altered RAP1GAP2 expression correlates with metastatic potential and RAP1 signaling dysregulation. | COSMIC, NCBI |
| Intellectual disability | Rare copy number variants and missense mutations in RAP1GAP2 have been reported in patients with neurodevelopmental phenotypes. | ClinVar, OMIM |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Platelets | High (nTPM not available for platelets in GTEx) | High |
| Brain - cerebellum | 12.5 | Medium |
| Brain - cortex | 8.3 | Medium |
| Testis | 6.1 | Low |
| Lung | 3.2 | Low |
| Spleen | 2.8 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 5.4 | Moderate expression |
| K562 | 3.1 | Low expression |
| MCF7 | 2.0 | Low expression |
| HepG2 | 1.5 | Very low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.205C>T (p.Arg69Cys) | Missense | <0.01% | Reduced GAP activity, altered RAP1 regulation |
| c.487G>A (p.Gly163Arg) | Missense | <0.01% | Unknown functional effect, reported in ClinVar |
| c.1234_1235del (p.Lys412Glufs*3) | Frameshift | <0.01% | Loss of function, associated with bleeding disorder |
| c.1567C>T (p.Arg523*) | Nonsense | <0.01% | Premature truncation, loss of function |
Mutation functional classification
Loss of Function (LOF)
Frameshift and nonsense mutations (e.g., p.Lys412Glufs*3, p.Arg523*) lead to truncated or absent protein, impairing RAP1 inactivation and causing platelet dysfunction.
Gain of Function (GOF)
No confirmed gain-of-function mutations reported in RAP1GAP2.
Dominant Negative (DN)
Missense mutations (e.g., p.Arg69Cys) may act in a dominant-negative manner by forming inactive dimers or competing with wild-type protein, but evidence is limited.
View complete mutation data：
Gene Ontology (GO)
| • GTPase activator activity | • RAP1 GTPase activator activity |
| • negative regulation of RAP1 GTPase activity | • signal transduction |
| • platelet activation | • integrin activation |
| • cytoplasm | • cytosol |
Pathways
• RAP1 signaling pathway (Reactome: R-HSA-392517)
• Platelet activation
• signaling and aggregation (Reactome: R-HSA-76002)
• GPVI-mediated activation cascade (Reactome: R-HSA-114604)
Protein Summary
RAP1GAP2 is a 1003-amino acid protein containing a conserved GAP domain that specifically targets RAP1. It is predominantly expressed in platelets and megakaryocytes, where it localizes to the cytoplasm and regulates integrin activation by controlling RAP1-GTP levels. The protein also contains a C-terminal coiled-coil region that mediates homodimerization and interaction with other signaling molecules. Alternative splicing generates isoforms with distinct expression patterns and functions.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| RAP1GAP2 Knockout HEK293 Cell Line | EDJ-KQ7832 | Human | 23108 | Details Get a Quote |
| RAP1GAP2 Knockout A-549 Cell Line | EDJ-KQ33372 | Human | 23108 | Details Get a Quote |
| RAP1GAP2 Knockout HCT 116 Cell Line | EDJ-KQ33373 | Human | 23108 | Details Get a Quote |
| RAP1GAP2 Knockout HeLa Cell Line | EDJ-KQ33374 | Human | 23108 | Details Get a Quote |
