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This is an N-ras oncogene encoding a membrane protein that shuttles between the Golgi apparatus and the plasma membrane. This shuttling is regulated through palmitoylation and depalmitoylation by the ZDHHC9-GOLGA7 complex. The encoded protein, which has intrinsic GTPase activity, is activated by a guanine nucleotide-exchange factor and inactivated by a GTPase activating protein. Mutations in this gene have been associated with somatic rectal cancer, follicular thyroid cancer, autoimmune lymphoproliferative syndrome, Noonan syndrome, and juvenile myelomonocytic leukemia. [provided by RefSeq, Jun 2011]
Mutations in the RAS family of proteins have frequently been observed across cancer types. The amino acid positions G12, G13 and Q61 account for the overwhelming majority of these mutations. The isoforms, despite their raw similarity, also behave very differently when expressed in non-native tissue types, likely due to differences in the C-terminal hyper-variable regions. Mis-regulation of isoform expression has been shown to be a driving event in cancer, as well as missense mutations at the three hotspots previously mentioned. While highly recurrent in cancer, targeting these RAS mutants has also been very elusive, and has not yet become common practice in the clinic.
NRAS (NRAS Proto-Oncogene, GTPase) is a Protein Coding gene. Diseases associated with NRAS include Ras-Associated Autoimmune Leukoproliferative Disorder and Melanocytic Nevus Syndrome, Congenital. Among its related pathways are Negative regulation of MAPK pathway and NGF Pathway. Gene Ontology (GO) annotations related to this gene include GTP binding. An important paralog of this gene is KRAS.
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0000166 | nucleotide binding | IEA | -- |
GO:0003924 | GTPase activity | IBA,IDA | 30712867 |
GO:0005515 | protein binding | IPI | 18641128 |
GO:0005525 | GTP binding | IBA | 21873635 |
GO:0019003 | GDP binding | IBA | 21873635 |
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0000139 | Golgi membrane | IEA | -- |
GO:0005794 | Golgi apparatus | IDA | 21968647 |
GO:0005886 | plasma membrane | TAS | -- |
GO:0016020 | membrane | HDA | 19946888 |
GO:0070062 | extracellular exosome | HDA | 20458337 |
SuperPathway | Contained pathways | ||
---|---|---|---|
1 | RET signaling |
.92
|
.92
|
2 | Downstream signaling of activated FGFR2 | ||
3 | IL-2 Pathway |
ErbB Family Pathway
.59
ErbB4 Pathway
.59
Prolactin Signaling
.54
Thrombopoietin Pathway
.51
ErbB2-ErbB3 Heterodimers
.49
IL-2 Pathway
.48
|
LPS Stimulated MAPK Signaling
.47
UVC-Induced MAPK Signaling
.44
TREM1 Pathway
.43
HMGB1 Pathway
.36
PI3K Signaling in B-Lymphocyte
.35
IL-4 Pathway
.34
|
4 | Endometrial cancer |
.36
.32
|
|
5 | fMLP Pathway |
CCR3 Pathway in Eosinophils
.44
VEGF and S-1P Signaling
.44
fMLP Pathway
.43
|
CXCR4 Pathway
.39
Alpha-Adrenergic Signaling
.38
Internalin Pathway
.31
|
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0000165 | MAPK cascade | TAS | -- |
GO:0001938 | positive regulation of endothelial cell proliferation | IMP | 23619365 |
GO:0002223 | stimulatory C-type lectin receptor signaling pathway | TAS | -- |
GO:0007165 | signal transduction | IEA | -- |
GO:0007265 | Ras protein signal transduction | TAS | -- |
Name | Status | Disease Links | Group | Role | Mechanism of Action | Clinical Trials |
---|---|---|---|---|---|---|
Trametinib | Approved | Pharma | MEK 1/2 inhibitor, MEK Inhibitors, Kinase Inhibitors, Mitogen-activated protein/extracellular signal-regulated kinase (MEK) inhibitors | 194 | ||
Cetuximab | Approved | Pharma | EGFR Inhibitors, Therapeutic Antibodies, Epidermal growth factor receptor (EGFR) inhibitors | 869 | ||
Dabrafenib | Approved, Investigational | Pharma | BRAF kinase inhibitor, Kinase Inhibitors, Mutant BRAF Kinase | 116 | ||
Fludarabine | Approved | Pharma | DNA synthsis inhibitor | 1533,1533 | ||
Carboplatin | Approved | Pharma | Antitumor agent that forms platinum-DNA adducts., Platinum | 2588 |
Name | Synonyms | Role | CAS Number | PubChem IDs | PubMed IDs |
---|
This gene was present in the common ancestor of animals and fungi.
Organism | Taxonomy | Gene | Similarity | Type | Details |
---|---|---|---|---|---|
Dog (Canis familiaris) |
Mammalia | N-RAS 31 |
|
OneToOne | |
NRAS 30 |
|
||||
Chimpanzee (Pan troglodytes) |
Mammalia | NRAS 30 31 |
|
OneToOne | |
Oppossum (Monodelphis domestica) |
Mammalia | NRAS 31 |
|
OneToMany | |
-- 31 |
|
OneToMany | |||
Cow (Bos Taurus) |
Mammalia | NRAS 30 31 |
|
OneToOne | |
Mouse (Mus musculus) |
Mammalia | Nras 30 17 31 |
|
OneToOne | |
Rat (Rattus norvegicus) |
Mammalia | Nras 30 |
|
||
Platypus (Ornithorhynchus anatinus) |
Mammalia | NRAS 31 |
|
OneToOne | |
Chicken (Gallus gallus) |
Aves | N-RAS 31 |
|
OneToOne | |
NRAS 30 |
|
||||
Lizard (Anolis carolinensis) |
Reptilia | NRAS 31 |
|
OneToOne | |
Tropical Clawed Frog (Silurana tropicalis) |
Amphibia | LOC549517 30 |
|
||
Str.17112 30 |
|
||||
African clawed frog (Xenopus laevis) |
Amphibia | Xl.895 30 |
|
||
Zebrafish (Danio rerio) |
Actinopterygii | nras 30 31 |
|
OneToOne | |
-- 30 |
|
||||
Fruit Fly (Drosophila melanogaster) |
Insecta | Ras85D 31 32 |
|
OneToMany | |
Worm (Caenorhabditis elegans) |
Secernentea | let-60 31 |
|
OneToMany | |
C08F8.7 32 |
|
|
|||
Baker's yeast (Saccharomyces cerevisiae) |
Saccharomycetes | RAS1 31 |
|
ManyToMany | |
RAS2 31 |
|
ManyToMany |
SNP ID | Clinical significance and condition | Chr 01 pos | Variation | AA Info | Type |
---|---|---|---|---|---|
644733 | Uncertain Significance: Rasopathy | 114,708,544(-) | C/T | SYNONYMOUS_VARIANT | |
651614 | Uncertain Significance: Rasopathy | 114,709,699(-) | T/G | MISSENSE_VARIANT | |
658879 | Uncertain Significance: Rasopathy | 114,716,096(-) | T/C | MISSENSE_VARIANT | |
761147 | Likely Benign: not provided | 114,709,575(-) | G/A | SYNONYMOUS_VARIANT | |
762535 | Likely Benign: not provided | 114,716,116(-) | C/G | SYNONYMOUS_VARIANT |
Disorder | Aliases | PubMed IDs |
---|---|---|
ras-associated autoimmune leukoproliferative disorder |
|
|
melanocytic nevus syndrome, congenital |
|
|
noonan syndrome 6 |
|
|
melanosis, neurocutaneous |
|
|
nevus, epidermal |
|