RASAL1: A Key Regulator of RAS Signaling in Development and Disease
Comprehensive gene card, expression, mutations, and clinical relevance of RASAL1
Gene Information Card
| Symbol | RASAL1 |
|---|---|
| Full Name | RAS protein activator like 1 |
| Gene Type | protein-coding |
| Chromosomal Location | 12q24.13 |
| NCBI Gene ID | 8437 ncbi.nlm.nih.gov/gene/8437 |
| Ensembl ID | ENSG00000111371 |
| UniProt ID | O95294 |
| OMIM ID | 604183 |
| HGNC ID | 9874 |
| Aliases | RASAL, RASAL1, RAS protein activator like 1 |
Description
RASAL1 (RAS protein activator like 1) encodes a member of the RAS-GAP (GTPase-activating protein) family. The protein contains a C2 domain, a Ras-GAP domain, and a PH domain. It functions as a negative regulator of RAS signaling by accelerating GTP hydrolysis, thereby converting active RAS-GTP to inactive RAS-GDP. RASAL1 is involved in cell proliferation, differentiation, and survival. Dysregulation of RASAL1 is implicated in various cancers and developmental disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Hereditary gingival fibromatosis type 1 | Loss-of-function mutations in RASAL1 lead to increased RAS signaling, promoting fibroblast proliferation and excessive gingival tissue growth. | OMIM #135300; PMID: 21779174 |
| Colorectal cancer | Hypermethylation of the RASAL1 promoter results in reduced expression, contributing to RAS pathway activation and tumor progression. | COSMIC; PMID: 19252504 |
| Hepatocellular carcinoma | RASAL1 downregulation via promoter methylation correlates with poor prognosis and increased RAS activity. | PMID: 21912515 |
| Lung cancer | RASAL1 expression is frequently reduced due to epigenetic silencing, associated with enhanced RAS signaling. | COSMIC; PMID: 22952447 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 5.2 | Low |
| Heart | 3.8 | Low |
| Kidney | 4.1 | Low |
| Liver | 2.9 | Not detected |
| Lung | 6.7 | Medium |
| Pancreas | 1.5 | Not detected |
| Skeletal muscle | 1.2 | Not detected |
| Spleen | 8.3 | Medium |
| Testis | 12.4 | High |
| Thyroid | 7.1 | Medium |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 9.8 | Embryonic kidney cells; moderate expression |
| HeLa | 6.2 | Cervical cancer cells; low expression |
| A549 | 4.5 | Lung carcinoma; reduced expression due to methylation |
| HepG2 | 3.1 | Hepatocellular carcinoma; low expression |
| MCF7 | 7.4 | Breast cancer; moderate expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.205C>T (p.Arg69*) | Nonsense | Rare | Loss of function; truncation of GAP domain |
| c.497G>A (p.Arg166Gln) | Missense | Rare | Loss of function; impaired RAS-GAP activity |
| c.1048C>T (p.Arg350Trp) | Missense | Rare | Loss of function; reduced protein stability |
| c.1261G>A (p.Gly421Arg) | Missense | Rare | Loss of function; disrupted catalytic activity |
Mutation functional classification
Loss of Function (LOF)
Most reported mutations in RASAL1 are loss-of-function, leading to reduced GAP activity and sustained RAS-GTP signaling.
Gain of Function (GOF)
No gain-of-function mutations have been reported for RASAL1.
Dominant Negative (DN)
Dominant-negative effects have not been described for RASAL1 mutations.
View complete mutation data：
Gene Ontology (GO)
| • GTPase activator activity | • RAS GTPase binding |
| • C2 domain binding | • PH domain binding |
| • Cytoplasm | • Plasma membrane |
| • Negative regulation of RAS protein signal transduction | • Cell proliferation |
| • Cell differentiation |
Pathways
• RAS signaling pathway
• MAPK signaling pathway
• Regulation of RAS activity
Protein Summary
RASAL1 is a 780-amino acid protein containing an N-terminal C2 domain, a central PH domain, and a C-terminal Ras-GAP domain. It acts as a GTPase-activating protein for RAS, accelerating the conversion of active RAS-GTP to inactive RAS-GDP. The C2 domain mediates calcium-dependent membrane translocation, while the PH domain contributes to phosphoinositide binding. RASAL1 is widely expressed, with highest levels in testis and spleen. Loss of RASAL1 function, often through epigenetic silencing or mutation, leads to aberrant RAS activation and contributes to tumorigenesis.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| RASAL1 Knockout HEK293 Cell Line | EDJ-KQ1230 | Human | 8437 | Details Get a Quote |
| RASAL1 Knockout HCT 116 Cell Line | EDJ-KQ20574 | Human | 8437 | Details Get a Quote |
| RASAL1 Knockout HeLa Cell Line | EDJ-KQ54909 | Human | 8437 | Details Get a Quote |
| RASAL1 Knockout A-549 Cell Line | EDJ-KQ63396 | Human | 8437 | Details Get a Quote |
