HRAS (Harvey rat sarcoma viral oncogene homolog)

1999-02-01   Franz Watzinger , Thomas Lion 

Childrens Cancer Research Institute (CCRI), Kinderspitalgasse 6, A-1090 Vienna, Austria

Identity

HGNC
LOCATION
11p15.5
IMAGE
Atlas Image
LEGEND
Probe(s) - Courtesy Mariano Rocchi, Resources for Molecular Cytogenetics
LOCUSID
ALIAS
C-BAS/HAS,C-H-RAS,C-HA-RAS1,CTLO,H-RASIDX,HAMSV,HRAS1,RASH1,p21ras
FUSION GENES

DNA/RNA

Atlas Image
H-ras splicing variants :
alternative splicing of H-ras precursor mRNA leads to the two transcripts p19 and p21 which differ by the ex- or inclusion of the Intron D Exon (IDX); Exons that encode protein are shown as black boxes, untranslated exons as white boxes; the upstream untranslated exon is indicated as Exon -1

Description

consists of six exons, spread over 6.6kb of genomic DNA

Transcription

alternative RNA splicing reveals two different transcripts (see Fig); if the Intron D Exon (IDX) is skipped exon 4 is directly joined to exon 3

Note

to be quoted is the existence of a pseudogene, c-Ha-ras 2, inactivated, processed pseudogene which is located on Chromosome X.

Proteins

Entity

p21H-ras

Description

regular RAS protein - characterized in the RAS family page

Expression

ubiquitously expressed

Localisation

anchored to the inner surface of the plasma membrane

Function

analogously to other GTP-binding proteins (such as Translation Elongation Factor EFTu or signal transducing G-Proteins) RAS proteins are involved in signal transduction pathways

Homology

ras gene family is part of the ras superfamily including the mammalian RAS, RAL, RAC, RHO, RAP, and RAB gene families and the yeast homologs like SEC4 and YPT1 genes; genes encode small monomeric proteins of low molecular mass (20-30 kDa) which share at least 30% homology with RAS proteins.

Implicated in

Entity name
tumor (frequency of H-RAS mutations); references in Full Bibliography

Bibliography

Pubmed IDLast YearTitleAuthors
21149811990ras oncogenes: their role in neoplasia.Barbacid M et al
25475131989ras oncogenes in human cancer: a review.Bos JL et al
97240791998Variability of Ha-ras (codon 12) proto-oncogene mutations in diverse thyroid cancers.Bouras M et al
80961491993Codon 12 Harvey-ras mutations are rare events in non-melanoma human skin cancer.Campbell C et al
89195451996Ras oncogene mutations in thyroid tumors: polymerase chain reaction-restriction-fragment-length polymorphism analysis from paraffin-embedded tissues.Capella G et al
22081481990ras gene mutations in human prostate cancer.Carter BS et al
83530521993The absence of Harvey ras mutations during development and progression of squamous cell carcinomas of the head and neck.Clark LJ et al
26677641989Expression of the H-ras proto-oncogene is controlled by alternative splicing.Cohen JB et al
16717961991Correlation of mutations of oncogene C-Ha-ras at codon 12 with metastasis and survival of gastric cancer patients.Deng GR et al
36007951987A new oncogene in human thyroid papillary carcinomas and their lymph-nodal metastases.Fusco A et al
19989541991Activated ras alleles in human carcinoma of the prostate are rare.Gumerlock PH et al
90484881996A PCR-RFLP method for the detection of activated H-ras oncogene with a point mutation at codon 12 and 61.Hong SJ et al
92613591997A splicing enhancer in the 3'-terminal c-H-ras exon influences mRNA abundance and transforming activity.Hwang DY et al
75990401995Mutations, expression and genomic instability of the H-ras proto-oncogene in squamous cell carcinomas of the head and neck.Kiaris H et al
91374941997Mutation of ras oncogene in gastric adenocarcinoma: association with histological phenotype.Kim TY et al
90183361997Comparison of ras activation in prostate carcinoma in Japanese and American men.Konishi N et al
60892001984A position 12-activated H-ras oncogene in all HS578T mammary carcinosarcoma cells but not normal mammary cells of the same patient.Kraus MH et al
26482531989High frequency of ras oncogene activation in all stages of human thyroid tumorigenesis.Lemoine NR et al
40847261985Oncogenes and bladder cancer.Malone PR et al
14211671992ras activation in experimental carcinogenesis.Mangues R et al
20497761991K-ras activation in gastric epithelial tumors in Japanese.Miki H et al
21790351990Infrequent point mutations of ras oncogenes in gastric cancers.Nanus DM et al
33077601987Human cancer and cellular oncogenes.Nishimura S et al
97039271998Low-frequency mutation of Ha-ras and Ki-ras oncogenes in transitional cell carcinoma of the bladder.Olderøy G et al
21838721990Low incidence of ras oncogene activation in human squamous cell carcinomas.Rumsby G et al
91796931997Screening of H-ras gene point mutations in 50 cases of bladder carcinoma.Saito S et al
20215411991High frequency mutation in codons 12 and 61 of H-ras oncogene in chewing tobacco-related human oral carcinoma in India.Saranath D et al
97134621998Mutations of ras genes are relatively frequent in Japanese prostate cancers: pointing to genetic differences between populations.Shiraishi T et al
34350511987Oncogene activation in malignant transformation: a study of H-ras in human breast cancer.Spandidos DA et al
32836561988Detection of activated ras oncogenes in human thyroid carcinomas.Suárez HG et al
15018841992Mapping of UV photoproducts within ras proto-oncogenes in UV-irradiated cells: correlation with mutations in human skin cancer.Törmänen VT et al
89601471996ras gene mutations in human endometrial carcinoma.Varras MN et al
21990311990No evidence for point mutations in codons 12, 13, and 61 of the ras gene in a high-incidence area for esophageal and gastric cancers.Victor T et al
31446941988Preferential and novel activation of H-ras in human bladder carcinomas.Visvanathan KV et al

Other Information

Locus ID:

NCBI: 3265
MIM: 190020
HGNC: 5173
Ensembl: ENSG00000174775

Variants:

dbSNP: 3265
ClinVar: 3265
TCGA: ENSG00000174775
COSMIC: HRAS

RNA/Proteins

Gene IDTranscript IDUniprot
ENSG00000174775ENST00000311189P01112
ENSG00000174775ENST00000311189X5D945
ENSG00000174775ENST00000397594P01112
ENSG00000174775ENST00000397596P01112
ENSG00000174775ENST00000397596X5D945
ENSG00000174775ENST00000417302P01112
ENSG00000174775ENST00000451590P01112
ENSG00000174775ENST00000451590X5D945
ENSG00000174775ENST00000493230P01112

Expression (GTEx)

0
50
100
150

Pathways

PathwaySourceExternal ID
MAPK signaling pathwayKEGGko04010
ErbB signaling pathwayKEGGko04012
Autophagy - animalKEGGko04140
mTOR signaling pathwayKEGGko04150
ApoptosisKEGGko04210
Axon guidanceKEGGko04360
VEGF signaling pathwayKEGGko04370
Focal adhesionKEGGko04510
Gap junctionKEGGko04540
Jak-STAT signaling pathwayKEGGko04630
Natural killer cell mediated cytotoxicityKEGGko04650
T cell receptor signaling pathwayKEGGko04660
B cell receptor signaling pathwayKEGGko04662
Fc epsilon RI signaling pathwayKEGGko04664
Long-term potentiationKEGGko04720
Long-term depressionKEGGko04730
Regulation of actin cytoskeletonKEGGko04810
Insulin signaling pathwayKEGGko04910
GnRH signaling pathwayKEGGko04912
MelanogenesisKEGGko04916
Renal cell carcinomaKEGGko05211
Endometrial cancerKEGGko05213
GliomaKEGGko05214
Prostate cancerKEGGko05215
Thyroid cancerKEGGko05216
MelanomaKEGGko05218
Bladder cancerKEGGko05219
Chronic myeloid leukemiaKEGGko05220
Acute myeloid leukemiaKEGGko05221
Non-small cell lung cancerKEGGko05223
MAPK signaling pathwayKEGGhsa04010
ErbB signaling pathwayKEGGhsa04012
Autophagy - animalKEGGhsa04140
mTOR signaling pathwayKEGGhsa04150
ApoptosisKEGGhsa04210
Axon guidanceKEGGhsa04360
VEGF signaling pathwayKEGGhsa04370
Focal adhesionKEGGhsa04510
Gap junctionKEGGhsa04540
Jak-STAT signaling pathwayKEGGhsa04630
Natural killer cell mediated cytotoxicityKEGGhsa04650
T cell receptor signaling pathwayKEGGhsa04660
B cell receptor signaling pathwayKEGGhsa04662
Fc epsilon RI signaling pathwayKEGGhsa04664
Long-term potentiationKEGGhsa04720
Long-term depressionKEGGhsa04730
Regulation of actin cytoskeletonKEGGhsa04810
Insulin signaling pathwayKEGGhsa04910
GnRH signaling pathwayKEGGhsa04912
MelanogenesisKEGGhsa04916
Pathways in cancerKEGGhsa05200
Renal cell carcinomaKEGGhsa05211
Endometrial cancerKEGGhsa05213
GliomaKEGGhsa05214
Prostate cancerKEGGhsa05215
Thyroid cancerKEGGhsa05216
MelanomaKEGGhsa05218
Bladder cancerKEGGhsa05219
Chronic myeloid leukemiaKEGGhsa05220
Acute myeloid leukemiaKEGGhsa05221
Non-small cell lung cancerKEGGhsa05223
Chemokine signaling pathwayKEGGko04062
Chemokine signaling pathwayKEGGhsa04062
Neurotrophin signaling pathwayKEGGko04722
Neurotrophin signaling pathwayKEGGhsa04722
EndocytosisKEGGko04144
EndocytosisKEGGhsa04144
Hepatitis CKEGGko05160
Hepatitis CKEGGhsa05160
Cholinergic synapseKEGGhsa04725
HTLV-I infectionKEGGko05166
HTLV-I infectionKEGGhsa05166
Serotonergic synapseKEGGhsa04726
AlcoholismKEGGhsa05034
AlcoholismKEGGko05034
Viral carcinogenesisKEGGhsa05203
Viral carcinogenesisKEGGko05203
PI3K-Akt signaling pathwayKEGGhsa04151
PI3K-Akt signaling pathwayKEGGko04151
Hepatitis BKEGGhsa05161
Proteoglycans in cancerKEGGhsa05205
Proteoglycans in cancerKEGGko05205
Estrogen signaling pathwayKEGGhsa04915
Estrogen signaling pathwayKEGGko04915
Prolactin signaling pathwayKEGGhsa04917
Prolactin signaling pathwayKEGGko04917
MicroRNAs in cancerKEGGhsa05206
MicroRNAs in cancerKEGGko05206
Ras signaling pathwayKEGGhsa04014
Rap1 signaling pathwayKEGGhsa04015
Rap1 signaling pathwayKEGGko04015
FoxO signaling pathwayKEGGhsa04068
Thyroid hormone signaling pathwayKEGGhsa04919
Oxytocin signaling pathwayKEGGhsa04921
Oxytocin signaling pathwayKEGGko04921
Signaling pathways regulating pluripotency of stem cellsKEGGhsa04550
Signaling pathways regulating pluripotency of stem cellsKEGGko04550
Central carbon metabolism in cancerKEGGhsa05230
Choline metabolism in cancerKEGGhsa05231
Central carbon metabolism in cancerKEGGko05230
Choline metabolism in cancerKEGGko05231
Sphingolipid signaling pathwayKEGGhsa04071
Sphingolipid signaling pathwayKEGGko04071
Neuronal SystemREACTOMER-HSA-112316
Transmission across Chemical SynapsesREACTOMER-HSA-112315
Neurotransmitter Receptor Binding And Downstream Transmission In The Postsynaptic CellREACTOMER-HSA-112314
Activation of NMDA receptor upon glutamate binding and postsynaptic eventsREACTOMER-HSA-442755
Post NMDA receptor activation eventsREACTOMER-HSA-438064
CREB phosphorylation through the activation of RasREACTOMER-HSA-442742
Ras activation uopn Ca2+ infux through NMDA receptorREACTOMER-HSA-442982
DiseaseREACTOMER-HSA-1643685
Diseases of signal transductionREACTOMER-HSA-5663202
Signaling by EGFR in CancerREACTOMER-HSA-1643713
Signaling by Ligand-Responsive EGFR Variants in CancerREACTOMER-HSA-5637815
Constitutive Signaling by Ligand-Responsive EGFR Cancer VariantsREACTOMER-HSA-1236382
Signaling by EGFRvIII in CancerREACTOMER-HSA-5637812
Constitutive Signaling by EGFRvIIIREACTOMER-HSA-5637810
Signaling by FGFR in diseaseREACTOMER-HSA-1226099
Signaling by FGFR1 in diseaseREACTOMER-HSA-5655302
Signaling by FGFR2 in diseaseREACTOMER-HSA-5655253
Signaling by FGFR3 in diseaseREACTOMER-HSA-5655332
Signaling by FGFR4 in diseaseREACTOMER-HSA-5655291
Immune SystemREACTOMER-HSA-168256
Adaptive Immune SystemREACTOMER-HSA-1280218
Signaling by the B Cell Receptor (BCR)REACTOMER-HSA-983705
Downstream signaling events of B Cell Receptor (BCR)REACTOMER-HSA-1168372
Activation of RAS in B cellsREACTOMER-HSA-1169092
Innate Immune SystemREACTOMER-HSA-168249
DAP12 interactionsREACTOMER-HSA-2172127
DAP12 signalingREACTOMER-HSA-2424491
RAF/MAP kinase cascadeREACTOMER-HSA-5673001
RAF activationREACTOMER-HSA-5673000
MAP2K and MAPK activationREACTOMER-HSA-5674135
Negative regulation of MAPK pathwayREACTOMER-HSA-5675221
Regulation of RAS by GAPsREACTOMER-HSA-5658442
Fc epsilon receptor (FCERI) signalingREACTOMER-HSA-2454202
FCERI mediated MAPK activationREACTOMER-HSA-2871796
C-type lectin receptors (CLRs)REACTOMER-HSA-5621481
CD209 (DC-SIGN) signalingREACTOMER-HSA-5621575
Cytokine Signaling in Immune systemREACTOMER-HSA-1280215
Signaling by InterleukinsREACTOMER-HSA-449147
Interleukin-2 signalingREACTOMER-HSA-451927
Interleukin receptor SHC signalingREACTOMER-HSA-912526
Interleukin-3, 5 and GM-CSF signalingREACTOMER-HSA-512988
HemostasisREACTOMER-HSA-109582
Cell surface interactions at the vascular wallREACTOMER-HSA-202733
Tie2 SignalingREACTOMER-HSA-210993
Signal TransductionREACTOMER-HSA-162582
Signaling by EGFRREACTOMER-HSA-177929
GRB2 events in EGFR signalingREACTOMER-HSA-179812
SHC1 events in EGFR signalingREACTOMER-HSA-180336
Signaling by FGFRREACTOMER-HSA-190236
Signaling by FGFR1REACTOMER-HSA-5654736
Downstream signaling of activated FGFR1REACTOMER-HSA-5654687
FRS-mediated FGFR1 signalingREACTOMER-HSA-5654693
SHC-mediated cascade:FGFR1REACTOMER-HSA-5654688
Signaling by FGFR2REACTOMER-HSA-5654738
Downstream signaling of activated FGFR2REACTOMER-HSA-5654696
FRS-mediated FGFR2 signalingREACTOMER-HSA-5654700
SHC-mediated cascade:FGFR2REACTOMER-HSA-5654699
Signaling by FGFR3REACTOMER-HSA-5654741
Downstream signaling of activated FGFR3REACTOMER-HSA-5654708
FRS-mediated FGFR3 signalingREACTOMER-HSA-5654706
SHC-mediated cascade:FGFR3REACTOMER-HSA-5654704
Signaling by FGFR4REACTOMER-HSA-5654743
Downstream signaling of activated FGFR4REACTOMER-HSA-5654716
FRS-mediated FGFR4 signalingREACTOMER-HSA-5654712
SHC-mediated cascade:FGFR4REACTOMER-HSA-5654719
Signaling by Insulin receptorREACTOMER-HSA-74752
Insulin receptor signalling cascadeREACTOMER-HSA-74751
IRS-mediated signallingREACTOMER-HSA-112399
SOS-mediated signallingREACTOMER-HSA-112412
Signalling by NGFREACTOMER-HSA-166520
NGF signalling via TRKA from the plasma membraneREACTOMER-HSA-187037
Signalling to ERKsREACTOMER-HSA-187687
Signalling to RASREACTOMER-HSA-167044
p38MAPK eventsREACTOMER-HSA-171007
Signalling to p38 via RIT and RINREACTOMER-HSA-187706
Prolonged ERK activation eventsREACTOMER-HSA-169893
Frs2-mediated activationREACTOMER-HSA-170968
ARMS-mediated activationREACTOMER-HSA-170984
Signaling by PDGFREACTOMER-HSA-186797
Downstream signal transductionREACTOMER-HSA-186763
Signaling by VEGFREACTOMER-HSA-194138
VEGFA-VEGFR2 PathwayREACTOMER-HSA-4420097
VEGFR2 mediated cell proliferationREACTOMER-HSA-5218921
Signaling by SCF-KITREACTOMER-HSA-1433557
Signaling by ERBB2REACTOMER-HSA-1227986
SHC1 events in ERBB2 signalingREACTOMER-HSA-1250196
GRB2 events in ERBB2 signalingREACTOMER-HSA-1963640
Signaling by ERBB4REACTOMER-HSA-1236394
SHC1 events in ERBB4 signalingREACTOMER-HSA-1250347
MAPK family signaling cascadesREACTOMER-HSA-5683057
MAPK1/MAPK3 signalingREACTOMER-HSA-5684996
Signaling by GPCRREACTOMER-HSA-372790
Gastrin-CREB signalling pathway via PKC and MAPKREACTOMER-HSA-881907
EGFR Transactivation by GastrinREACTOMER-HSA-2179392
Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R)REACTOMER-HSA-2404192
IGF1R signaling cascadeREACTOMER-HSA-2428924
SHC-related events triggered by IGF1RREACTOMER-HSA-2428933
IRS-related events triggered by IGF1RREACTOMER-HSA-2428928
Signaling by LeptinREACTOMER-HSA-2586552
Developmental BiologyREACTOMER-HSA-1266738
Axon guidanceREACTOMER-HSA-422475
NCAM signaling for neurite out-growthREACTOMER-HSA-375165
EPH-Ephrin signalingREACTOMER-HSA-2682334
EPHB-mediated forward signalingREACTOMER-HSA-3928662
Phospholipase D signaling pathwayKEGGko04072
Phospholipase D signaling pathwayKEGGhsa04072
AGE-RAGE signaling pathway in diabetic complicationsKEGGko04933
AGE-RAGE signaling pathway in diabetic complicationsKEGGhsa04933
Longevity regulating pathwayKEGGhsa04211
Longevity regulating pathway - multiple speciesKEGGko04213
Longevity regulating pathway - multiple speciesKEGGhsa04213
Signaling by PTK6REACTOMER-HSA-8848021
PTK6 Regulates RHO GTPases, RAS GTPase and MAP kinasesREACTOMER-HSA-8849471
Signaling by FGFR3 point mutants in cancerREACTOMER-HSA-8853338
Signaling by FGFR3 fusions in cancerREACTOMER-HSA-8853334
EGFR tyrosine kinase inhibitor resistanceKEGGko01521
Endocrine resistanceKEGGko01522
EGFR tyrosine kinase inhibitor resistanceKEGGhsa01521
Endocrine resistanceKEGGhsa01522
RET signalingREACTOMER-HSA-8853659
Breast cancerKEGGko05224
Breast cancerKEGGhsa05224
Oncogenic MAPK signalingREACTOMER-HSA-6802957
Signaling by RAS mutantsREACTOMER-HSA-6802949
Signaling by high-kinase activity BRAF mutantsREACTOMER-HSA-6802948
Signaling by moderate kinase activity BRAF mutantsREACTOMER-HSA-6802946
Paradoxical activation of RAF signaling by kinase inactive BRAFREACTOMER-HSA-6802955
Signaling by BRAF and RAF fusionsREACTOMER-HSA-6802952
RAS signaling downstream of NF1 loss-of-function variantsREACTOMER-HSA-6802953
Signaling by METREACTOMER-HSA-6806834
MET activates RAS signalingREACTOMER-HSA-8851805
Apelin signaling pathwayKEGGhsa04371
Mitophagy - animalKEGGko04137
Mitophagy - animalKEGGhsa04137

Protein levels (Protein atlas)

Not detected
Low
Medium
High

PharmGKB

Entity IDNameTypeEvidenceAssociationPKPDPMIDs
PA165946873vemurafenibChemicalLabelAnnotationassociated
PA166114911dabrafenibChemicalLabelAnnotationassociated
PA166115364trametinibChemicalLabelAnnotationassociated
PA24928ARAFGenePathwayassociated
PA25408BRAFGenePathwayassociated28362716
PA26880CRKGenePathwayassociated20124951
PA28127FGFR1GenePathwayassociated28362716
PA28180FLT1GenePathwayassociated28362716
PA28181FLT3GenePathwayassociated28362716
PA28183FLT4GenePathwayassociated28362716
PA30086KDRGenePathwayassociated28362716
PA30128KITGenePathwayassociated28362716
PA30592MAP3K1GenePathwayassociated
PA33148PDGFRBGenePathwayassociated28362716
PA34183RAF1GenePathwayassociated20124951, 28362716
PA34335RETGenePathwayassociated28362716
PA446108Colorectal NeoplasmsDiseaseMultilinkAnnotationassociated26237292
PA7360EGFRGenePathwayassociated

References

Pubmed IDYearTitleCitations
225892702012A comprehensive survey of Ras mutations in cancer.455
191600182009Rho signaling, ROCK and mDia1, in transformation, metastasis and invasion.212
161703162005Germline mutations in HRAS proto-oncogene cause Costello syndrome.173
155971052005The role of RAS oncogene in survival of patients with lung cancer: a systematic review of the literature with meta-analysis.169
194872992009Mutational profile of advanced primary and metastatic radioactive iodine-refractory thyroid cancers reveals distinct pathogenetic roles for BRAF, PIK3CA, and AKT1.151
218418252012ROS-generating NADPH oxidase NOX4 is a critical mediator in oncogenic H-Ras-induced DNA damage and subsequent senescence.102
221790432011The GDI-like solubilizing factor PDEδ sustains the spatial organization and signalling of Ras family proteins.100
184541582008Membrane-dependent signal integration by the Ras activator Son of sevenless.88
210722042010FGFR3, HRAS, KRAS, NRAS and PIK3CA mutations in bladder cancer and their potential as biomarkers for surveillance and therapy.79
165983132006Incidence and prognostic impact of c-Kit, FLT3, and Ras gene mutations in core binding factor acute myeloid leukemia (CBF-AML).78

Citation

Franz Watzinger ; Thomas Lion

HRAS (Harvey rat sarcoma viral oncogene homolog)

Atlas Genet Cytogenet Oncol Haematol. 1999-02-01

Online version: http://atlasgeneticsoncology.org/gene/108/hras-(harvey-rat-sarcoma-viral-oncogene-homolog)