RASGRP1
RAS guanyl releasing protein 1
Gene Information Card
| Symbol | RASGRP1 |
|---|---|
| Full Name | RAS guanyl releasing protein 1 |
| Gene Type | protein-coding |
| Chromosomal Location | 15q14 |
| NCBI Gene ID | 10125 ncbi.nlm.nih.gov/gene/10125 |
| Ensembl ID | ENSG00000172575 |
| UniProt ID | O95267 |
| OMIM ID | 603962 |
| HGNC ID | 9878 |
| Aliases | CALDAG-GEFI, RASGRP, VAV3, FLJ00279 |
Description
RASGRP1 (RAS guanyl releasing protein 1) encodes a calcium- and diacylglycerol (DAG)-regulated guanine nucleotide exchange factor (GEF) that activates RAS and other small GTPases. It plays a critical role in T-cell receptor (TCR) signaling, lymphocyte development, and immune homeostasis. Mutations in RASGRP1 are associated with primary immunodeficiency and autoimmune lymphoproliferative syndrome.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Primary immunodeficiency due to RASGRP1 deficiency | Loss-of-function mutations impair RAS activation and TCR signaling, leading to defective T-cell proliferation and immune deficiency. | ClinVar, OMIM |
| Autoimmune lymphoproliferative syndrome (ALPS) | Dysregulated apoptosis due to impaired RASGRP1-mediated signaling results in lymphoproliferation and autoimmunity. | OMIM, PubMed |
| Epstein-Barr virus (EBV) susceptibility | RASGRP1 deficiency impairs T-cell responses to EBV, increasing risk of severe infection and lymphoproliferation. | ClinVar, PubMed |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Lymph node | 12.5 | Medium |
| Spleen | 10.8 | Medium |
| Thymus | 9.2 | Medium |
| Bone marrow | 6.7 | Low |
| Whole blood | 4.3 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Jurkat (T-cell leukemia) | 15.2 | High expression |
| Raji (Burkitt lymphoma) | 8.1 | Moderate expression |
| HEK293 (embryonic kidney) | 2.5 | Low expression |
| HeLa (cervical carcinoma) | 1.8 | Very low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.518G>A (p.Arg173His) | Missense | Rare | Loss of GEF activity; associated with primary immunodeficiency |
| c.742C>T (p.Arg248*) | Nonsense | Rare | Premature truncation; loss of function |
| c.1063_1064del (p.Gln355Valfs*12) | Frameshift | Rare | Loss of function; linked to ALPS |
Mutation functional classification
Loss of Function (LOF)
Most reported mutations (missense, nonsense, frameshift) result in loss of GEF activity, impairing RAS activation and TCR signaling.
Gain of Function (GOF)
Not described in the literature.
Dominant Negative (DN)
Not described in the literature.
View complete mutation data：
Gene Ontology (GO)
| • guanyl-nucleotide exchange factor activity | • calcium ion binding |
| • diacylglycerol binding | • RAS protein signal transduction |
| • intracellular signal transduction | • T cell receptor signaling pathway |
| • positive regulation of GTPase activity |
Pathways
• RAS signaling pathway (Reactome: R-HSA-167044)
• TCR signaling (Reactome: R-HSA-202403)
• MAPK cascade (Reactome: R-HSA-5673001)
Protein Summary
RASGRP1 is a 797-amino acid protein containing a C1 domain (DAG-binding), a Ras exchange motif (REM), a CDC25 homology domain (GEF catalytic), and EF-hand motifs (calcium-binding). It localizes to the plasma membrane upon calcium and DAG stimulation, where it activates RAS and initiates downstream MAPK signaling essential for T-cell activation and proliferation.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| RASGRP1 Knockout HEK293 Cell Line | EDJ-KQ185 | Human | 10125 | Details Get a Quote |
| RASGRP1 Knockout A-549 Cell Line | EDJ-KQ19395 | Human | 10125 | Details Get a Quote |
| RASGRP1 Knockout HeLa Cell Line | EDJ-KQ19396 | Human | 10125 | Details Get a Quote |
| RASGRP1 Knockout HCT 116 Cell Line | EDJ-KQ72265 | Human | 10125 | Details Get a Quote |
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