HRAS
In databases:
● Entrez (http://www.ncbi.nlm.nih.gov/sites/gquery): 3265 or HRAS
● Ensembl (http://www.ensembl.org/index.html): ENSG00000174775
● GeneCards (http://www.genecards.org/): HRAS
● HGNC (http://www.genenames.org/): 5173 or HRAS
Gene locus :
11p15.5
Protein name:
v-Ha-ras Harvey
Protein Size:
189 amino acids; about 21 kDa
Function:
The protein encoded by this gene belongs to the Ras oncogene family, whose members are related to the transforming genes of mammalian sarcoma retroviruses. The products encoded by these genes function in signal transduction pathways. These proteins can bind GTP and GDP, and they have intrinsic GTPase activity. This protein undergoes a continuous cycle of de- and re-palmitoylation, which regulates its rapid exchange between the plasma membrane and the Golgi apparatus.
Cancer-related alterations:
Somatic HRAS mutations have been observed in tumors of salivary glands (about 15% of cases), urinary tract, upper aerodigestive tract, cervix. In most cases, mutations are substitution “missenses”. Mutation hot spots are related to amino acids 12, 13 and 61
HRAS mutations may cause Costello syndrome, a disease characterized by increased growth at the prenatal stage, growth deficiency at the postnatal stage, predisposition to tumor formation, mental retardation, skin and musculoskeletal abnormalities, distinctive facial appearance and cardiovascular abnormalities. Costello syndrome is also characterized by tumor predisposition. Defects in HRAS are the cause of congenital myopathy with excess of muscle spindles (CMEMS), which is a variant of Costello syndrome.
Hurthle cell thyroid carcinoma, which accounts for approximately 3% of all thyroid cancers, is associated to HRAS genetic alterations. Although Hurthle cell thyroid carcinoma are classified as variants of follicular neoplasms, they are more often multifocal and somewhat more aggressive and are less likely to take up iodine than are other follicular neoplasms.
HRAS-associated bladder cancer often presents with multiple tumors appearing at different times and at different sites in the bladder.
Oral squamous cell carcinoma (OSCC) has been associated with HRAS alterations.
References (open access):
Costello Syndrome. Gripp KW, Lin AE. In: Pagon RA, Bird TD, Dolan CR, Stephens K, editors. SourceGeneReviews [Internet]. Seattle (WA): University of Washington, Seattle; 1993-.2006 Aug 29 [updated 2009 May 19].
Oncogenic RAS induces accelerated transition through G2/M and promotes defects in the G2 DNA damage and mitotic spindle checkpoints. Knauf JA, Ouyang B, Knudsen ES, Fukasawa K, Babcock G, Fagin JA. J Biol Chem. 2006 Feb 17;281(7):3800-9.
Genetic pathways and mutation profiles of human cancers: site- and exposure-specific patterns. Lea IA , Jackson MA, Li X, Bailey S, Peddada SD
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