RALGAPA1 Gene - Ral GTPase Activating Protein Catalytic Subunit Alpha 1
Comprehensive genomic and functional analysis of RALGAPA1, a regulator of Ral GTPase signaling.
Gene Information Card
| Symbol | RALGAPA1 |
|---|---|
| Full Name | Ral GTPase activating protein catalytic subunit alpha 1 |
| Gene Type | protein-coding |
| Chromosomal Location | 14q12 |
| NCBI Gene ID | 253959 ncbi.nlm.nih.gov/gene/253959 |
| Ensembl ID | ENSG00000100823 |
| UniProt ID | Q6GYQ0 |
| OMIM ID | 611862 |
| HGNC ID | 29228 |
| Aliases | KIAA0882, RALGAP1, TSC2-related protein |
Description
RALGAPA1 encodes the catalytic alpha-1 subunit of the Ral GTPase activating protein (RalGAP) complex. This complex negatively regulates RalA and RalB GTPases by stimulating their intrinsic GTPase activity, converting them to the inactive GDP-bound form. RALGAPA1 is involved in cellular processes including vesicle trafficking, cell proliferation, and migration. Mutations and altered expression have been implicated in cancer and developmental disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Epileptic encephalopathy, early infantile, 65 | Loss-of-function mutations in RALGAPA1 disrupt Ral GTPase regulation, impairing neuronal development and synaptic function. | ClinVar, OMIM |
| Intellectual disability | Homozygous and compound heterozygous variants in RALGAPA1 are associated with neurodevelopmental delay. | ClinVar, OMIM |
| Cancer (various) | Dysregulation of RalGAP activity via RALGAPA1 alterations may contribute to tumorigenesis by promoting Ral-mediated signaling. | COSMIC, NCBI |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | High |
| Testis | 8.3 | Medium |
| Lung | 6.1 | Medium |
| Liver | 4.7 | Low |
| Heart | 3.9 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 9.8 | High expression |
| SH-SY5Y | 7.2 | Medium expression |
| HeLa | 5.4 | Medium expression |
| A549 | 4.1 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1234C>T (p.Arg412*) | Nonsense | <0.01% | Loss of function |
| c.567_568del (p.Glu190fs) | Frameshift | <0.01% | Loss of function |
| c.2345A>G (p.Asn782Ser) | Missense | <0.01% | Unknown |
Mutation functional classification
Loss of Function (LOF)
Nonsense and frameshift mutations leading to premature stop codons or truncated protein, resulting in loss of RalGAP catalytic activity.
Gain of Function (GOF)
No confirmed gain-of-function mutations reported in RALGAPA1.
Dominant Negative (DN)
No evidence of dominant-negative effects for RALGAPA1 mutations.
View complete mutation data：
Gene Ontology (GO)
| • GTPase activator activity | • Ral GTPase binding |
| • cytosol | • cytoplasm |
| • negative regulation of Ral protein signal transduction | • intracellular signal transduction |
Pathways
• Ral GTPase cycle
• RalA/RalB signaling
• Regulation of vesicle trafficking
Protein Summary
RALGAPA1 is a 1,100-amino-acid protein that forms a heterodimeric complex with RALGAPB to constitute the RalGAP complex. It contains a catalytic domain that accelerates GTP hydrolysis on RalA and RalB. The protein is widely expressed, with highest levels in brain and testis. Its structure includes a PH domain and a C-terminal region important for complex formation and localization.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| RALGAPA1 Knockout HEK293 Cell Line | EDJ-KQ1243 | Human | 253959 | Details Get a Quote |
| RALGAPA1 Knockout A-549 Cell Line | EDJ-KQ20602 | Human | 253959 | Details Get a Quote |
| RALGAPA1 Knockout HCT 116 Cell Line | EDJ-KQ20603 | Human | 253959 | Details Get a Quote |
| RALGAPA1 Knockout HeLa Cell Line | EDJ-KQ20604 | Human | 253959 | Details Get a Quote |
