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NRAS
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NRAS G12C
GeneNRAS
Variantmissense
Amino Acid ChangeG12C
Transcript ID (GRCh37/hg19)ENST00000369535
Codon12
Exon2
Germline/Somatic?Somatic
Pertinent Negative In
Tumor TypePrimary Site
See All Pertinent Negatives

Interpretations

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Tier 1
NRAS
Variants
NRAS G12A
NRAS G12V
NRAS G12D
NRAS G12C
NRAS G12S
NRAS G12R
NRAS G13D
NRAS G13C
NRAS G13S
NRAS G13R
NRAS G13A
NRAS G13V
NRAS Q61H
NRAS Q61L
NRAS Q61K
NRAS Q61R
NRAS codon(s) 12, 13, 61, 146 any
Primary Sites
Colon
Rectum
Tumor Types
Adenocarcinoma
Interpretation

NRAS mutations occur in approximately 1--6% of colorectal cancers. 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.

Last updated: 2019-04-05 15:39:05 UTC
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Tier 1
NRAS
Variants
NRAS G12A
NRAS G12V
NRAS G12D
NRAS G12C
NRAS G12S
NRAS G12R
NRAS G13D
NRAS G13C
NRAS G13S
NRAS G13R
NRAS G13A
NRAS G13V
NRAS Q61H
NRAS Q61L
NRAS Q61K
NRAS Q61R
NRAS codon(s) 12, 13, 61, 146 any
Primary Sites
Skin
Tumor Types
Melanoma
Interpretation

Somatic mutations in NRAS have been found in approximately 13-25% of all malignant melanomas. The result of these mutations is constitutive activation of NRAS signaling pathways. NRAS mutations are found in all melanoma subtypes, but may be slightly more common in melanomas derived from chronic sun-damaged (CSD) skin . Currently, there are no direct anti-NRAS therapies available.

Last updated: 2020-07-24 14:53:31 UTC
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Tier 1
NRAS
Variants
NRAS G12A
NRAS G12V
NRAS G12D
NRAS G12C
NRAS G12S
NRAS G12R
NRAS G13D
NRAS G13C
NRAS G13S
NRAS G13R
NRAS G13A
NRAS G13V
NRAS codon(s) 12, 13, 61, 146 any
Primary Sites
Thyroid
Tumor Types
Follicular Carcinoma
Papillary Carcinoma
Interpretation

RAS mutations (HRAS, NRAS and KRAS) are found in all epithelial thyroid malignancies. The frequency of HRAS mutations in thyroid carcinomas is 4%. RAS mutations are identified in 10-20% of papillary carcinomas, 40-50% of follicular carcinomas and 20-40% of poorly differentiated and anaplastic carcinomas .

Last updated: 2020-07-24 14:53:44 UTC
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Tier 1
NRAS
Variants
NRAS G12A
NRAS G12V
NRAS G12D
NRAS G12C
NRAS G12S
NRAS G12R
NRAS G13D
NRAS G13C
NRAS G13S
NRAS G13R
NRAS G13A
NRAS G13V
NRAS Q61H
NRAS Q61L
NRAS Q61K
NRAS Q61R
NRAS codon(s) 12, 13, 61, 146 any
Primary Sites
Thyroid
Tumor Types
Interpretation

RAS mutations have also been identified in benign Follicular Adenomas(FA); however, it is unclear whether RAS positive FA have a higher chance of progression to cancer. The prevalence of this mutation in benign thyroid nodules is between 20 and 40%. The low overall prevalence of RAS mutations in thyroid cancers and the relatively high mutation rate in benign nodules makes ras mutation analysis unsuitable as a standalone test to predict malignancy in indeterminate thyroid nodules.

Last updated: 2015-12-09 20:21:38 UTC
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Tier 2
NRAS
Variants
NRAS G12A
NRAS G12V
NRAS G12D
NRAS G12C
NRAS G12S
NRAS G12R
NRAS G13D
NRAS G13C
NRAS G13S
NRAS G13R
NRAS G13A
NRAS G13V
NRAS Q61H
NRAS Q61L
NRAS Q61K
NRAS Q61R
NRAS codon(s) 12, 13, 61, 146 any
NRAS T58I
Primary Sites
Lung
Tumor Types
Adenocarcinoma
Non-Small Cell Lung Carcinoma
Interpretation

NRAS is a member of the RAS family of oncogenes and activating mutations of NRAS have been reported in about 1% of NSCLCs and are mostly exclusive of other known driver mutations. The Q61 codon is most frequently affected. In preclinical studies, cell lines harboring NRAS mutation(s) showed variable sensitivities to pathway inhibitors.

Last updated: 2019-01-22 18:51:07 UTC
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Tier 2
NRAS
Variants
NRAS G12A
NRAS G12V
NRAS G12D
NRAS G12C
NRAS G12S
NRAS G12R
NRAS G13D
NRAS G13C
NRAS G13S
NRAS G13R
NRAS G13A
NRAS G13V
NRAS Q61H
NRAS Q61L
NRAS Q61K
NRAS Q61R
NRAS codon(s) 12, 13, 61, 146 any
Primary Sites
Bladder
Tumor Types
Urothelial Carcinoma
Interpretation

NRAS is a member of the RAS family of oncogenes and activating mutations of NRAS have been reported in a wide variety of tumors including occasional cases of bladder cancer. This finding may influence targeted therapy options.

Last updated: 2017-01-20 03:27:37 UTC
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Tier 2
NRAS
Variants
NRAS G12A
NRAS G12V
NRAS G12D
NRAS G12C
NRAS G12S
NRAS G12R
NRAS G13D
NRAS G13C
NRAS G13S
NRAS G13R
NRAS G13A
NRAS G13V
NRAS Q61H
NRAS Q61L
NRAS Q61K
NRAS Q61R
Primary Sites
Kidney
Tumor Types
Urothelial Carcinoma
Interpretation

NRAS gene belongs to the family of RAS genes. It encodes a G protein that is important in the transmission of growth-promoting signals from the cell surface receptors to the nucleus through RAS-RAF- mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase (PI3K)-AKT cell signaling pathways. NRAS mutations are identified in multiple cancer types and tend in concentrate in codons 12, 13, and 61. NRAS mutations are rare in urothelial carcinomas of both the upper and lower urinary tract and are found in about 1% of cases. Currently, there are no direct anti-NRAS therapies available. The clinicopathologic significance of NRAS mutations in urothelial carcinoma remains to be further elucidated.

Last updated: 2018-05-24 20:15:40 UTC
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When using PMKB, please cite: Huang et al., JAMIA 2017


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