Gene:
NRAS
neuroblastoma RAS viral (v-ras) oncogene homolog
PharmGKB contains no prescribing info for this . Contact us to report known genotype-based dosing guidelines, or if you are interested in developing guidelines.
Annotated Labels
- Annotation of FDA Label for cetuximab and EGFR,HRAS,KRAS,NRAS
- Annotation of FDA Label for dabrafenib and BRAF,HRAS,KRAS,NRAS
- Annotation of FDA Label for vemurafenib and BRAF,NRAS
1. Annotation of FDA Label for cetuximab and EGFR,HRAS,KRAS,NRAS
Summary
Cetuximab is used in alone or in combination therapy to treat head and neck cancer and to treat K-Ras wild-type, EGFR-expressing metastatic colorectal cancer.
There's more of this label. Read more.
2. Annotation of FDA Label for dabrafenib and BRAF,HRAS,KRAS,NRAS
Summary
The drug label for dabrafenib (TAFINLAR) states that it is indicated for use in patients with unresectable or metastatic melanoma with a BRAF V600E mutation, or in combination with trametinib for patients with the V600K mutation, as detected by an FDA-approved test; the drug is not indicated for treatment of patients with wild-type BRAF melanoma. The label also notes that the drug may promote growth and development of malignancies with activation of RAS.
There's more of this label. Read more.
3. Annotation of FDA Label for vemurafenib and BRAF,NRAS
Summary
Vemurafenib is a kinase inhibitor used to treat patients with unresectable or metastatic melanoma ONLY in cases where the BRAF V600E mutation is found by an FDA-approved test. In vitro evidence points to BRAF wild-type cells proliferation with exposure to BRAF inhibitors. Therefore, testing is required. Additionally, the label notes progression of pre-existing chronic myelomonocytic leukemia with NRAS mutation in postmarketing experience.
There's more of this label. Read more.
PharmGKB contains no Clinical Variants that meet the highest level of criteria.
To see more Clinical Variants with lower levels of criteria, click the button at the bottom of the table.
Disclaimer: The PharmGKB's clinical annotations reflect expert consensus based on clinical evidence and peer-reviewed literature available at the time they are written and are intended only to assist clinicians in decision-making and to identify questions for further research. New evidence may have emerged since the time an annotation was submitted to the PharmGKB. The annotations are limited in scope and are not applicable to interventions or diseases that are not specifically identified.
The annotations do not account for individual variations among patients, and cannot be considered inclusive of all proper methods of care or exclusive of other treatments. It remains the responsibility of the health-care provider to determine the best course of treatment for a patient. Adherence to any guideline is voluntary, with the ultimate determination regarding its application to be made solely by the clinician and the patient. PharmGKB assumes no responsibility for any injury or damage to persons or property arising out of or related to any use of the PharmGKB clinical annotations, or for any errors or omissions.
The table below contains information about pharmacogenomic variants on PharmGKB. Please follow the link in the "Variant" column for more information about a particular variant. Each link in the "Variant" column leads to the corresponding PharmGKB Variant Page. The Variant Page contains summary data, including PharmGKB manually curated information about variant-drug pairs based on individual PubMed publications. The PMIDs for these PubMed publications can be found on the Variant Page.
The tags in the first column of the table indicate what type of information can be found on the corresponding Variant Page on the appropriate tab.
Links in the "Drugs" column lead to PharmGKB Drug Pages.
List of all variant annotations for NRAS
|
Variant?
(147) |
Alternate Names ? | Chemicals ? |
Alleles
?
(+ chr strand) |
Function ? |
Amino Acid?
Translation |
|
|---|---|---|---|---|---|---|
| rs1065634 | NC_000001.10:g.115259768T>C, NC_000001.11:g.114717147T>C, NG_007572.1:g.4748A>G, NM_001007553.2:c.*1022A>G, NM_001130523.2:c.*1022A>G, NM_001242891.1:c.*1022A>G, NM_001242892.1:c.*1022A>G, NM_001242893.1:c.*1022A>G, NM_002524.4:c.-507A>G, NM_007158.5:c.*1022A>G, XM_005271178.1:c.*1022A>G, rs3167734, rs57399409 |
T > C
|
SNP |
Overview
| Alternate Names: | None |
|---|---|
| Alternate Symbols: | N-ras |
| PharmGKB Accession Id: | PA31768 |
Details
| Cytogenetic Location: | chr1 : p13.2 - p13.2 |
|---|---|
| GP mRNA Boundary†: | chr1 : 115247085 - 115259515 |
| GP Gene Boundary†: | chr1 : 115244085 - 115269515 |
| Strand: | minus |
Visualization
UCSC has a Genome Browser that you can use to view PharmGKB annotations for this gene in context with many other sources of information.
View on UCSC BrowserThe NRAS gene is an important pharmacogene for cancer PGx.
KRAS codes for one of the three RAS family proteins which are key players in the RAS-RAF-MEK-ERK signaling pathway (reviewed in [Article:24985059])
Oncogenic NRAS mutations occur in several cancer types, notably melanoma, acute myelogenous leukemia (AML), hepatocellular carcinoma and less commonly, colon adenocarcinoma, thyroid carcinoma, NSCLC and uterine cancer [Article:24895460] [Article:21829508]. There are currently no therapies directed at NRAS itself.
Although NRAS mutations are not as frequent as KRAS in colorectal cancer, there is still evidence that they may influence response to treatment [Article:26438111].
NRAS mutations occur in 1-6% of colorectal cancers [Article:21829508]PMID: 21305640. Several studies have shown that patients with NRAS-mutated tumors are less likely to respond to cetuximab or panitumumab, but this may not have an effect on PFS or overall survival [Article:21729679]PMID: 20619739.
The ASCO guidelines for use of anti-EGFR antibodies in colorectal cancer were updated in 2015 to include the recommendation for testing of NRAS exons 2 (codons 12 and 13), 3 (codons 59 and 61), and 4 (codons 117 and 146) in addition to KRAS tests [Article:26438111].
NRAS mutations also are important in acquired resistance to BRAF inhibitors. In melanoma patients receiving vemurafenib or dabrafenib after initial positive response, many patients develop resistance about 15% of them do not achieve tumor regression at all. Approximately 8-23% of BRAF inhibitor resistant patients have NRAS mutations (reviewed in [Article:25344914]).
rs numbers for important variants
| rs number | protein change | mRNA change |
|---|---|---|
| rs121913250 | p.Gly12Cys (G12C) | c.34G>T |
| rs121913250 | p.Gly12Arg (G12R) | c.34G>C |
| rs121913250 | p.Gly12Ser (G12S) | c.34G>A |
| rs121913237 | p.Gly12Asp (G12D) | c.35G>A |
| rs121434595 | p.Gly13Arg (G13R) | c.37G>C |
| rs121434596 | p.Gly13Asp (G13D) | c.38G>A |
| rs121913254 | p.Gln61Lys (Q61K) | c.181C>A |
| rs11554290 | p.Gln61Arg (Q61R) | c.182A>G |
| Citation |
M. Whirl-Carrillo, E.M. McDonagh, J. M. Hebert, L. Gong, K. Sangkuhl, C.F. Thorn, R.B. Altman and T.E. Klein.
"Pharmacogenomics Knowledge for Personalized Medicine"
Clinical Pharmacology & Therapeutics (2012) 92(4): 414-417.
Full text
|
|---|---|
| History |
Submitted by Caroline F Thorn |
| Key Publications |
|
| Drugs |
Drug (4)
|
| Diseases | |
| Pathways |
PharmGKB Curated Pathways
Pathways created internally by PharmGKB based primarily on literature evidence.
-
Bisphosphonate Pathway, Pharmacodynamics
Representation of genes involved in bisphosphonates' effects in osteoclasts.
-
EGFR Inhibitor Pathway, Pharmacodynamics
Model non-tissue specific cancer cell displaying genes that may be involved in the treatment using epidermal growth factor receptor specific tyrosine kinase inhibitors or monoclonal antibodies.
-
Sorafenib Pharmacodynamics
Mechanism of action of sorafenib
-
VEGF Signaling Pathway
Model endothelial cell displaying genes of the VEGF signalling pathway and the sites at which bevacizumab, sorafenib, sunitinib, brivanib and cilengitide are known to act.
-
Vemurafenib Pathway, Pharmacodynamics
Simplified diagram of mechanism of action of vemurafenib and downstream signaling effects.
Curated Information ?
| Evidence | Drug |
|---|---|
| carboplatin | |
| cetuximab | |
| cisplatin | |
| dabrafenib | |
| gemcitabine | |
| panitumumab | |
| vemurafenib |
Curated Information ?
| Evidence | Disease |
|---|---|
| Carcinoma, Non-Small-Cell Lung | |
| Colorectal Neoplasms | |
| Melanoma | |
| overall survival |
Publications related to NRAS: 21
LinkOuts
- RefSeq DNA:
- NG_007572
- NT_032977
- UniProtKB:
- RASN_HUMAN (P01111)
- Q5U091_HUMAN (Q5U091)
- Ensembl:
- ENSG00000213281
- GenAtlas:
- NRAS
- GeneCard:
- NRAS