RASGRP3
RAS guanyl releasing protein 3
Gene Information Card
| Symbol | RASGRP3 |
|---|---|
| Full Name | RAS guanyl releasing protein 3 |
| Gene Type | protein-coding |
| Chromosomal Location | 2p22.3 |
| NCBI Gene ID | 25780 ncbi.nlm.nih.gov/gene/25780 |
| Ensembl ID | ENSG00000152689 |
| UniProt ID | Q8IV61 |
| OMIM ID | 609531 |
| HGNC ID | 14545 |
| Aliases | GRP3, KIAA0846, RASGRP3 |
Description
RASGRP3 encodes a member of the Ras guanine nucleotide exchange factor (RasGEF) family. The protein contains a Ras exchange motif, a CDC25 homology domain, and two EF-hand calcium-binding domains, as well as a diacylglycerol (DAG)-binding C1 domain. It activates Ras and other small GTPases in response to increased intracellular calcium and DAG, playing a role in lymphocyte development, T-cell receptor signaling, and neuronal differentiation.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Melanoma | RASGRP3 overexpression leads to increased RAS-MAPK signaling, promoting tumor growth and metastasis | COSMIC, PMID: 23542255 |
| B-cell acute lymphoblastic leukemia (B-ALL) | Somatic mutations and copy number alterations in RASGRP3 contribute to aberrant RAS activation | ClinVar, PMID: 28481359 |
| Immunodeficiency with hyper-IgM | Loss-of-function mutations impair T-cell receptor signaling and B-cell class switching | OMIM, PMID: 24665091 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.3 | Medium |
| Lymph node | 8.7 | Low |
| Spleen | 6.5 | Low |
| Skin | 4.2 | Low |
| Testis | 3.1 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 15.2 | Moderate expression |
| Jurkat T cells | 22.8 | High expression |
| A375 melanoma | 18.5 | High expression |
| K562 | 5.6 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.742C>T (p.Arg248Trp) | Missense | 0.02% (COSMIC) | Potential gain-of-function in melanoma |
| c.1135G>A (p.Glu379Lys) | Missense | 0.01% (ClinVar) | Uncertain significance |
| c.1681_1682del (p.Gln561fs) | Frameshift | <0.01% | Loss-of-function in immunodeficiency |
Mutation functional classification
Loss of Function (LOF)
Frameshift and nonsense mutations in the CDC25 domain impair RasGEF activity, leading to reduced T-cell activation and immunodeficiency.
Gain of Function (GOF)
Missense mutations in the C1 domain (e.g., Arg248Trp) enhance DAG binding and constitutive RAS activation, contributing to oncogenesis.
Dominant Negative (DN)
No well-characterized dominant-negative mutations reported for RASGRP3.
View complete mutation data：
Gene Ontology (GO)
Pathways
• RAS signaling pathway (Reactome: R-HSA-167044)
• MAPK cascade (Reactome: R-HSA-5673001)
• T-cell receptor signaling (KEGG: hsa04660)
• B-cell receptor signaling (KEGG: hsa04662)
Protein Summary
RASGRP3 is a 609-amino-acid protein (UniProt Q8IV61) that functions as a calcium- and diacylglycerol-regulated guanine nucleotide exchange factor for Ras. It is predominantly expressed in the brain and lymphoid tissues. The protein contains a C1 domain for DAG binding, two EF-hand motifs for calcium sensing, and a catalytic CDC25 homology domain. RASGRP3 is critical for lymphocyte activation and has been implicated in melanoma and B-cell leukemia.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| RASGRP3 Knockout HEK293 Cell Line | EDJ-KQ747 | Human | 25780 | Details Get a Quote |
| RASGRP3 Knockout A-549 Cell Line | EDJ-KQ19400 | Human | 25780 | Details Get a Quote |
| RASGRP3 Knockout HeLa Cell Line | EDJ-KQ19401 | Human | 25780 | Details Get a Quote |
| RASGRP3 Knockout HCT 116 Cell Line | EDJ-KQ72762 | Human | 25780 | Details Get a Quote |
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