NRAS Gene (Neuroblastoma RAS Viral Oncogene Homolog)
Key oncogene in the RAS/MAPK pathway, frequently mutated in melanoma, leukemia, and thyroid cancer.
Gene Information Card
| Symbol | NRAS |
|---|---|
| Full Name | Neuroblastoma RAS viral oncogene homolog |
| Gene Type | Protein coding |
| Chromosomal Location | 1p13.2 |
| NCBI Gene ID | 4893 ncbi.nlm.nih.gov/gene/4893 |
| Ensembl ID | ENSG00000213281 |
| UniProt ID | P01111 |
| OMIM ID | 164790 |
| HGNC ID | 7989 |
| Aliases | ALPS4, CMNS, NCMS, NRAS1, NS6 |
Description
NRAS (Neuroblastoma RAS viral oncogene homolog) encodes a membrane-bound GTPase that functions as a molecular switch in signal transduction pathways, primarily the RAS/MAPK and PI3K/AKT pathways. It regulates cell proliferation, differentiation, and survival. Somatic mutations, most commonly at codons 12, 13, and 61, result in constitutive activation and are frequently found in various cancers, including melanoma, colorectal cancer, and hematological malignancies.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Melanoma | Activating mutations (e.g., Q61R/K) lead to constitutive RAS signaling, promoting tumor growth and metastasis. | COSMIC, ClinVar |
| Acute Myeloid Leukemia (AML) | NRAS mutations (G12D, G13D, Q61L) are common and contribute to uncontrolled proliferation of myeloid progenitors. | COSMIC, ClinVar |
| Thyroid Carcinoma | NRAS mutations (especially Q61R) are associated with follicular and papillary thyroid cancers, driving tumorigenesis. | COSMIC, ClinVar |
| Colorectal Cancer | NRAS mutations (G12, G13, Q61) are less frequent than KRAS but confer resistance to anti-EGFR therapy. | COSMIC, ClinVar |
| Juvenile Myelomonocytic Leukemia (JMML) | Germline or somatic NRAS mutations cause hyperactive RAS signaling, leading to myeloproliferative disorder. | OMIM, ClinVar |
| Noonan Syndrome | Germline NRAS mutations (e.g., T50I, G60E) cause a RASopathy with developmental abnormalities. | OMIM, ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Bone Marrow | 12.4 | Medium |
| Lymph Node | 10.8 | Medium |
| Spleen | 9.7 | Medium |
| Thyroid | 8.5 | Low |
| Skin | 7.2 | Low |
| Lung | 6.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| A549 (Lung) | 15.3 | High expression |
| MCF7 (Breast) | 12.1 | Medium |
| K562 (Leukemia) | 18.7 | High expression |
| HeLa (Cervical) | 9.8 | Medium |
| HepG2 (Liver) | 7.5 | Low |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| G12D | Missense | 10-15% in melanoma | Constitutive activation, impaired GTP hydrolysis |
| G12V | Missense | 5-10% in AML | Constitutive activation, impaired GTP hydrolysis |
| G13D | Missense | 5% in colorectal cancer | Constitutive activation, altered nucleotide exchange |
| Q61R | Missense | 20-30% in melanoma | Constitutive activation, reduced intrinsic GTPase activity |
| Q61K | Missense | 10% in thyroid cancer | Constitutive activation, reduced intrinsic GTPase activity |
| Q61L | Missense | 5% in AML | Constitutive activation, reduced intrinsic GTPase activity |
Mutation functional classification
Loss of Function (LOF)
Rare; loss-of-function mutations are not well characterized and may lead to reduced RAS signaling, but are not commonly observed in cancer.
Gain of Function (GOF)
Most NRAS mutations are gain-of-function, leading to constitutive activation of RAS signaling, promoting cell proliferation and survival.
Dominant Negative (DN)
Some germline mutations (e.g., T50I) in Noonan syndrome may act as dominant-negative, interfering with normal RAS signaling, but this is less common than gain-of-function.
View complete mutation data：
Gene Ontology (GO)
| • GTPase activity | • GTP binding |
| • GDP binding | • Signal transduction |
| • Ras protein signal transduction | • Cell proliferation |
| • Cell differentiation | • Apoptosis |
Pathways
• MAPK/ERK signaling pathway
• PI3K/AKT signaling pathway
• RAS signaling pathway
• RAF/MAPK cascade
• Regulation of cell cycle
Protein Summary
The NRAS protein is a small GTPase that cycles between an active GTP-bound and inactive GDP-bound state. It is anchored to the plasma membrane via a C-terminal farnesyl group. Upon growth factor stimulation, it activates downstream effectors such as RAF, PI3K, and RALGDS, leading to cell proliferation and survival. Mutations at codons 12, 13, and 61 disrupt its intrinsic GTPase activity, locking it in the active state and driving oncogenesis.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| NRAS Knockout HEK293 Cell Line | EDJ-KQ641 | Human | 4893 | Details Get a Quote |
| NRAS Knockout A-549 Cell Line | EDJ-KQ20472 | Human | 4893 | Details Get a Quote |
| NRAS Knockout HCT 116 Cell Line | EDJ-KQ20474 | Human | 4893 | Details Get a Quote |
| NRAS Knockout HeLa Cell Line | EDJ-KQ20475 | Human | 4893 | Details Get a Quote |
| NRAS (p.Q61R) Point Mutation in HCT 116 Cell Line | EDC03177 | Human | 4893 | Details Get a Quote |
| NRAS (p.E62fs*6) Point Mutation in HCT 116 Cell Line | EDC03124 | Human | 4893 | Details Get a Quote |
| NRAS (p.G12S) Point Mutation in HCT 116 Cell Line | EDC03123 | Human | 4893 | Details Get a Quote |
| NRAS (p.G12C) Point Mutation in HCT 116 Cell Line | EDC03074 | Human | 4893 | Details Get a Quote |
| NRAS (p.G12D) Point Mutation in HCT 116 Cell Line | EDC03073 | Human | 4893 | Details Get a Quote |
| NRAS (p.G13R) Point Mutation in HCT 116 Cell Line | EDC03122 | Human | 4893 | Details Get a Quote |
| NRAS (p.G13D) Point Mutation in HCT 116 Cell Line | EDC03072 | Human | 4893 | Details Get a Quote |
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