HRAS HRas proto-oncogene, GTPase [Homo sapiens (human)] - Gene

Summary

Official Symbol: HRASprovided by HGNC
Official Full Name: HRas proto-oncogene, GTPaseprovided by HGNC
Primary source: HGNC:HGNC:5173
See related: Ensembl:ENSG00000174775 MIM:190020; AllianceGenome:HGNC:5173
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: CTLO; HAMSV; HRAS1; RASH1; p21ras; C-H-RAS; H-RASIDX; C-BAS/HAS; C-HA-RAS1
Summary: 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. Mutations in this gene cause Costello syndrome, a disease characterized by increased growth at the prenatal stage, growth deficiency at the postnatal stage, predisposition to tumor formation, cognitive disability, skin and musculoskeletal abnormalities, distinctive facial appearance and cardiovascular abnormalities. Defects in this gene are implicated in a variety of cancers, including bladder cancer, follicular thyroid cancer, and oral squamous cell carcinoma. Multiple transcript variants, which encode different isoforms, have been identified for this gene. [provided by RefSeq, Jul 2008]
Expression: Ubiquitous expression in skin (RPKM 24.4), brain (RPKM 14.8) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 11p15.5

Exon count:: 7

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	11	NC_000011.10 (532242..535576, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	11	NC_060935.1 (579238..582554, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	11	NC_000011.9 (532242..535576, complement)

Chromosome 11 - NC_000011.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Overexpression of wild-type HRAS drives non-alcoholic steatohepatitis to hepatocellular carcinoma in mice.
Title: Overexpression of wild-type HRAS drives non-alcoholic steatohepatitis to hepatocellular carcinoma in mice.
Unraveling the Genetic Web: H-Ras Expression and Mutation in Oral Squamous Cell Carcinoma-A Systematic Review.
Title: Unraveling the Genetic Web: H-Ras Expression and Mutation in Oral Squamous Cell Carcinoma-A Systematic Review.
ITPR1-AS1 promotes small cell lung cancer metastasis by facilitating P21[HRAS] splicing and stabilizing DDX3X to activate the cRaf-MEK-ERK cascade.
Title: ITPR1-AS1 promotes small cell lung cancer metastasis by facilitating P21(HRAS) splicing and stabilizing DDX3X to activate the cRaf-MEK-ERK cascade.
Cytosolic EpCAM cooperates with H-Ras to regulate epithelial to mesenchymal transition through ZEB1.
Title: Cytosolic EpCAM cooperates with H-Ras to regulate epithelial to mesenchymal transition through ZEB1.
Mutant HRas Signaling and Rationale for Use of Farnesyltransferase Inhibitors in Head and Neck Squamous Cell Carcinoma.
Title: Mutant HRas Signaling and Rationale for Use of Farnesyltransferase Inhibitors in Head and Neck Squamous Cell Carcinoma.
RAS gene mutations and histomorphometric measurements in oral squamous cell carcinoma.
Title: RAS gene mutations and histomorphometric measurements in oral squamous cell carcinoma.
A very mild phenotype in six individuals of a three-generation family with the novel HRAS variant c.176C > G p.(Ala59Gly): Emergence of a new HRAS-related RASopathy distinct from Costello syndrome.
Title: A very mild phenotype in six individuals of a three-generation family with the novel HRAS variant c.176C > G p.(Ala59Gly): Emergence of a new HRAS-related RASopathy distinct from Costello syndrome.
A Subset of Salivary Intercalated Duct Lesions Harbors Recurrent CTNNB1 and HRAS Mutations: A Molecular Link to Basal Cell Adenoma and Epithelial-Myoepithelial Carcinoma?
Title: A Subset of Salivary Intercalated Duct Lesions Harbors Recurrent CTNNB1 and HRAS Mutations: A Molecular Link to Basal Cell Adenoma and Epithelial-Myoepithelial Carcinoma?
Crystal Structure of an i-Motif from the HRAS Oncogene Promoter.
Title: Crystal Structure of an i-Motif from the HRAS Oncogene Promoter.
Mutated HRAS Activates YAP1-AXL Signaling to Drive Metastasis of Head and Neck Cancer.
Title: Mutated HRAS Activates YAP1-AXL Signaling to Drive Metastasis of Head and Neck Cancer.

Submit: New GeneRIF Correction See all GeneRIFs (514)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Costello syndrome MedGen: C0587248 OMIM: 218040 GeneReviews: HRAS-Related Costello Syndrome	Compare labs
Epidermal nevus MedGen: C0334082 OMIM: 162900 GeneReviews: PIK3CA-Related Overgrowth Spectrum	Compare labs
Large congenital melanocytic nevus MedGen: C1842036 OMIM: 137550 GeneReviews: Not available	Compare labs
Linear nevus sebaceous syndrome MedGen: C4552097 OMIM: 163200 GeneReviews: Not available	Compare labs
Malignant tumor of urinary bladder MedGen: C0005684 OMIM: 109800 GeneReviews: Not available	Compare labs
Thyroid cancer, nonmedullary, 2 MedGen: C4225426 OMIM: 188470 GeneReviews: Not available	Compare labs

Copy number response

Description
Copy number response Haploinsufficency No evidence available (Last evaluated 2024-07-15) ClinGen Genome Curation Page Triplosensitivity No evidence available (Last evaluated 2024-07-15) ClinGen Genome Curation Page

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Protein interactions

Protein	Gene	Interaction	Pubs
Envelope surface glycoprotein gp160, precursor	env	Pretreatment of cells with HIV-1 gp160 results in marked inhibition of tyrosine phosphorylation of p59(fyn), PLC-gamma1, ras activation, and TNF-alpha secretion in anti-CD3 mAb activated CD4+ T cells	PubMed
	env	HIV-1 gp160 alone or CD4/gp160 cross-linking induces tyrosine phosphorylation of intracellular substrates p59fyn, zap 70, and p95vav and also leads to ras activation	PubMed
Nef	nef	HIV-1 Nef activates signal transduction pathways from Ras to mitogen-activated protein kinase cascades leading to induction of HIV-1 from latency	PubMed
	nef	In HIV-1 Nef-expressing cells, phorbol 12-myristate 13-acetate treatment results in a 100-fold increase in NFAT-directed gene expression, indicating that Nef and the Ras/MAPK pathway synergistically activate NFAT activity	PubMed
Tat	tat	Knocking down oxidase Nox4 completely suppresses Tat-dependent Ras and ERK activation downstream of Rac1 and RhoA and blocks Tat-dependent proliferation	PubMed
	tat	HIV-1 Tat activates Ras activity and induces ERK phosphorylation through its arginine-glycine-aspartic (RGD) region in endothelial cells; Tat-induced Ras activation is mediated by tyrosine phosphorylation of Shc and recruitment of Grb2	PubMed

Go to the HIV-1, Human Interaction Database

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

PMC33481P1 (e-PCR)
- UniSTS:273164

GDB:177542 (e-PCR)
- UniSTS:154921

GDB:177543 (e-PCR)
- UniSTS:154922

HRAS (e-PCR), detects polymorphism
- UniSTS:266552

SHGC-146715 (e-PCR)
- UniSTS:172666

SHGC-146716 (e-PCR)
- UniSTS:172667

PMC152554P1 (e-PCR)
- UniSTS:271231

PMC152554P2 (e-PCR)
- UniSTS:271232

SHGC-58456 (e-PCR)
- UniSTS:94344

GDB:187026 (e-PCR)
- UniSTS:155536

G29883 (e-PCR)
- UniSTS:64957

HRAS (e-PCR), detects polymorphism
- UniSTS:64703

RH75826 (e-PCR)
- UniSTS:90048

GDB:177373 (e-PCR)
- UniSTS:154870

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables G protein activity	IEA Inferred from Electronic Annotation more info
enables GDP binding	IBA Inferred from Biological aspect of Ancestor more info
enables GDP binding	IMP Inferred from Mutant Phenotype more info	PubMed
enables GTP binding	IBA Inferred from Biological aspect of Ancestor more info
enables GTP binding	IDA Inferred from Direct Assay more info	PubMed
enables GTP binding	IMP Inferred from Mutant Phenotype more info	PubMed
enables GTPase activity	IBA Inferred from Biological aspect of Ancestor more info
enables GTPase activity	IDA Inferred from Direct Assay more info	PubMed
enables GTPase activity	IMP Inferred from Mutant Phenotype more info	PubMed
enables GTPase activity	TAS Traceable Author Statement more info
enables phospholipase C activator activity	IDA Inferred from Direct Assay more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein-membrane adaptor activity	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
involved_in MAPK cascade	TAS Traceable Author Statement more info
involved_in Ras protein signal transduction	IBA Inferred from Biological aspect of Ancestor more info
involved_in Ras protein signal transduction	IDA Inferred from Direct Assay more info	PubMed
involved_in Schwann cell development	IEA Inferred from Electronic Annotation more info
involved_in T cell receptor signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in T-helper 1 type immune response	IEA Inferred from Electronic Annotation more info
involved_in adipose tissue development	IEA Inferred from Electronic Annotation more info
involved_in animal organ morphogenesis	TAS Traceable Author Statement more info	PubMed
involved_in cell surface receptor signaling pathway	TAS Traceable Author Statement more info	PubMed
involved_in cellular response to gamma radiation	IDA Inferred from Direct Assay more info	PubMed
involved_in cellular senescence	IBA Inferred from Biological aspect of Ancestor more info
involved_in cellular senescence	IDA Inferred from Direct Assay more info	PubMed
involved_in chemotaxis	TAS Traceable Author Statement more info	PubMed
involved_in defense response to protozoan	IEA Inferred from Electronic Annotation more info
involved_in endocytosis	IEA Inferred from Electronic Annotation more info
involved_in fibroblast proliferation	IEA Inferred from Electronic Annotation more info
involved_in insulin receptor signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in intrinsic apoptotic signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in myelination	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of GTPase activity	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of cell population proliferation	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of gene expression	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of neuron apoptotic process	IEA Inferred from Electronic Annotation more info
involved_in neuron apoptotic process	IEA Inferred from Electronic Annotation more info
involved_in oncogene-induced cell senescence	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of ERK1 and ERK2 cascade	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of GTPase activity	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of JNK cascade	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of MAP kinase activity	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of MAPK cascade	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of cell migration	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of cell population proliferation	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of epithelial cell proliferation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of fibroblast proliferation	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of miRNA metabolic process	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of protein phosphorylation	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of protein targeting to membrane	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of ruffle assembly	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of transcription by RNA polymerase II	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of type II interferon production	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of wound healing	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of actin cytoskeleton organization	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of regulation of cell cycle	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of cell population proliferation	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of long-term neuronal synaptic plasticity	IEA Inferred from Electronic Annotation more info
involved_in regulation of neurotransmitter receptor localization to postsynaptic specialization membrane	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of neurotransmitter receptor localization to postsynaptic specialization membrane	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of transcription by RNA polymerase II	IDA Inferred from Direct Assay more info	PubMed
involved_in signal transduction	NAS Non-traceable Author Statement more info	PubMed

Component	Evidence Code	Pubs
part_of GTPase complex	IPI Inferred from Physical Interaction more info	PubMed
located_in Golgi apparatus	IDA Inferred from Direct Assay more info	PubMed
located_in Golgi membrane	TAS Traceable Author Statement more info
located_in cytoplasm	TAS Traceable Author Statement more info	PubMed
located_in cytosol	IDA Inferred from Direct Assay more info
located_in cytosol	TAS Traceable Author Statement more info
located_in endoplasmic reticulum membrane	TAS Traceable Author Statement more info
is_active_in glutamatergic synapse	IDA Inferred from Direct Assay more info	PubMed
is_active_in glutamatergic synapse	IMP Inferred from Mutant Phenotype more info	PubMed
located_in nucleoplasm	IDA Inferred from Direct Assay more info
located_in perinuclear region of cytoplasm	IEA Inferred from Electronic Annotation more info
is_active_in plasma membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in plasma membrane	IDA Inferred from Direct Assay more info	PubMed
located_in plasma membrane	TAS Traceable Author Statement more info

General protein information

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Preferred Names: GTPase HRas

Names: GTP- and GDP-binding peptide B; Ha-Ras1 proto-oncoprotein; Harvey rat sarcoma viral oncogene homolog; Harvey rat sarcoma viral oncoprotein; Ras family small GTP binding protein H-Ras; c-has/bas p21 protein; p19 H-RasIDX protein; transformation gene: oncogene HAMSV; transforming protein p21; v-Ha-ras Harvey rat sarcoma viral oncogene homolog

NP_001123914.1

EC 3.6.5.2

NP_001304983.1

EC 3.6.5.2

NP_005334.1

EC 3.6.5.2

NP_789765.1

EC 3.6.5.2

XP_054224585.1

EC 3.6.5.2

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_007666.1 RefSeqGene

Range

4975..8309

Download

GenBank, FASTA, Sequence Viewer (Graphics), LRG_506

mRNA and Protein(s)

NM_001130442.3 → NP_001123914.1 GTPase HRas isoform 1

See identical proteins and their annotated locations for NP_001123914.1

Status: REVIEWED

Description

Transcript Variant: This variant (3) differs in the 3' UTR, compared to variant 1. Both variants 1 and 3 encode the same isoform (1).

Source sequence(s)

AC137894, BM808879, BQ574535, BQ674260

Consensus CDS

CCDS7698.1

UniProtKB/Swiss-Prot

B5BUA0, P01112, Q14080, Q6FHV9, Q9BR65, Q9UCE2

UniProtKB/TrEMBL

X5D945

Related

ENSP00000407586.1, ENST00000451590.5

Conserved Domains (1) summary

cd04138
Location:3 → 164

H_N_K_Ras_like; Ras GTPase family containing H-Ras,N-Ras and K-Ras4A/4B
NM_001318054.2 → NP_001304983.1 GTPase HRas isoform 3

Status: REVIEWED

Description

Transcript Variant: This variant (4) includes an alternate exon resulting in a different 5' UTR and the use of a downstream translation start site compared to variant 1. The encoded isoform (3) has a shorter N-terminus compared to isoform 1.

Source sequence(s)

AC137894, BC006499, BM808879

UniProtKB/Swiss-Prot

P01112

Conserved Domains (1) summary

cl38936
Location:67 → 85

P-loop_NTPase; P-loop containing Nucleoside Triphosphate Hydrolases
NM_005343.4 → NP_005334.1 GTPase HRas isoform 1

See identical proteins and their annotated locations for NP_005334.1

Status: REVIEWED

Description

Transcript Variant: This variant (1) encodes the longer isoform (1). Both variants 1 and 3 encode the same isoform (1).

Source sequence(s)

AC137894, BC006499, BM801600, BM808879

Consensus CDS

CCDS7698.1

UniProtKB/Swiss-Prot

B5BUA0, P01112, Q14080, Q6FHV9, Q9BR65, Q9UCE2

UniProtKB/TrEMBL

X5D945

Related

ENSP00000309845.7, ENST00000311189.8

Conserved Domains (1) summary

cd04138
Location:3 → 164

H_N_K_Ras_like; Ras GTPase family containing H-Ras,N-Ras and K-Ras4A/4B
NM_176795.5 → NP_789765.1 GTPase HRas isoform 2

See identical proteins and their annotated locations for NP_789765.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) includes an alternate exon resulting in a frameshift and an early stop codon compared to variant 1. The encoded isoform (2) has a shorter and distinct C-terminus compared to isoform 1.

Source sequence(s)

AC137894, BM808879, BQ574535, BQ674260

Consensus CDS

CCDS7699.1

UniProtKB/TrEMBL

A0A804HJ06

Related

ENSP00000388246.1, ENST00000417302.7

Conserved Domains (1) summary

cd04138
Location:3 → 150

H_N_K_Ras_like; Ras GTPase family containing H-Ras,N-Ras and K-Ras4A/4B