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

Summary

Official Symbol: NRASprovided by HGNC
Official Full Name: NRAS proto-oncogene, GTPaseprovided by HGNC
Primary source: HGNC:HGNC:7989
See related: Ensembl:ENSG00000213281 MIM:164790; AllianceGenome:HGNC:7989
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: NS6; CMNS; KRAS; NCMS; ALPS4; N-ras; NRAS1
Summary: 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]
Expression: Ubiquitous expression in bone marrow (RPKM 23.0), colon (RPKM 17.3) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 1p13.2

Exon count:: 7

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	1	NC_000001.11 (114704469..114716771, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	1	NC_060925.1 (114715929..114728216, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	1	NC_000001.10 (115247090..115259392, complement)

Chromosome 1 - NC_000001.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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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?

Loss of Heterozygosity and Mutations in the RAS-ERK Pathway Genes in Tumor Cells of Various Loci in Multiple Myeloma.
Title: Loss of Heterozygosity and Mutations in the RAS-ERK Pathway Genes in Tumor Cells of Various Loci in Multiple Myeloma.
The prominent pervasive oncogenic role and tissue specific permissiveness of RAS gene mutations.
Title: The prominent pervasive oncogenic role and tissue specific permissiveness of RAS gene mutations.
eIF4F controls ERK MAPK signaling in melanomas with BRAF and NRAS mutations.
Title: eIF4F controls ERK MAPK signaling in melanomas with BRAF and NRAS mutations.
Organ involvement in adults with BPDCN is associated with sun exposure history, TET2 and RAS mutations, and survival.
Title: Organ involvement in adults with BPDCN is associated with sun exposure history, TET2 and RAS mutations, and survival.
Titration of RAS alters senescent state and influences tumour initiation.
Title: Titration of RAS alters senescent state and influences tumour initiation.
Mutational cooperativity of RUNX1::RUNX1T1 isoform 9a and oncogenic NRAS in zebrafish myeloid leukaemia.
Title: Mutational cooperativity of RUNX1::RUNX1T1 isoform 9a and oncogenic NRAS in zebrafish myeloid leukaemia.
NRAS[Q61R] mutation drives elevated angiopoietin-2 expression in human endothelial cells and a genetic mouse model.
Title: NRAS(Q61R) mutation drives elevated angiopoietin-2 expression in human endothelial cells and a genetic mouse model.
Variation in KRAS/NRAS/BRAF-Mutation Status by Age, Sex, and Race/Ethnicity Among a Large Cohort of Patients with Metastatic Colorectal Cancer (mCRC).
Title: Variation in KRAS/NRAS/BRAF-Mutation Status by Age, Sex, and Race/Ethnicity Among a Large Cohort of Patients with Metastatic Colorectal Cancer (mCRC).
Amplification of Mutant NRAS in Melanocytic Tumors With Features of Spitz Tumors.
Title: Amplification of Mutant NRAS in Melanocytic Tumors With Features of Spitz Tumors.
Mechanism of co-operation of mutant IL-7Ralpha and mutant NRAS in acute lymphoblastic leukemia: role of MYC.
Title: Mechanism of co-operation of mutant IL-7Rα and mutant NRAS in acute lymphoblastic leukemia: role of MYC.

Submit: New GeneRIF Correction See all GeneRIFs (516)

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
Autoimmune lymphoproliferative syndrome type 4 MedGen: C2674723 OMIM: 614470 GeneReviews: Not available	not available
Cetuximab response MedGen: CN077967 GeneReviews: Not available	not available
Colorectal cancer MedGen: C0346629 OMIM: 114500 GeneReviews: Lynch Syndrome	not available
Epidermal nevus MedGen: C0334082 OMIM: 162900 GeneReviews: PIK3CA-Related Overgrowth Spectrum	not available
Large congenital melanocytic nevus MedGen: C1842036 OMIM: 137550 GeneReviews: Not available	not available
Linear nevus sebaceous syndrome MedGen: C4552097 OMIM: 163200 GeneReviews: Not available	not available
Neurocutaneous melanocytosis MedGen: C0544862 OMIM: 249400 GeneReviews: Not available	not available
Noonan syndrome 6 MedGen: C2750732 OMIM: 613224 GeneReviews: Noonan Syndrome	not available
Panitumumab response MedGen: CN077999 GeneReviews: Not available	not available
Thyroid cancer, nonmedullary, 2 MedGen: C4225426 OMIM: 188470 GeneReviews: Not available	not available

EBI GWAS Catalog

Description
Common genetic variants on 1p13.2 associate with risk of autism. EBI GWAS Catalog EBI GWAS CatalogPubMed

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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Replication interactions

Interaction	Pubs
HIV-1 infection (VSV-G pseudotyped) of CEMT4 T cells downregulates plasma membrane expression of NRAS	PubMed
Knockdown of neuroblastoma RAS viral (v-ras) oncogene homolog (NRAS) by shRNA library screening inhibits HIV-1 replication in cultured Jurkat T-cells	PubMed

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-induced relocalization of LCK is correlated with N-Ras activation at recycling endosome/TGN compartments	PubMed
Tat	tat	HIV-1 Tat activates PRKCQ (PKC-theta) kinase activity, which leads to RELA (NFkB), NRAS, RAF1, MAP2K1 (MEK1), MAP2K2 (MEK2), MAPK3 (ERK1), and MAPK1 (ERK2) activation, in Jurkat T cells that stably express Tat	PubMed
	tat	Treatment with Tat activates the Ras pathway in human brain micro vascular endothelial cells (HBMECs), an effect that is markedly attenuated by caveolin-1 silencing	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

PMC28413P1 (e-PCR)
- UniSTS:272411

GDB:177539 (e-PCR)
- UniSTS:154918

SHGC-32741 (e-PCR)
- UniSTS:67373

RH64875 (e-PCR)
- UniSTS:90936

G20630 (e-PCR)
- UniSTS:11324

WI-21546 (e-PCR)
- UniSTS:29257

GDB:178391 (e-PCR)
- UniSTS:155001

WI-17660 (e-PCR)
- UniSTS:18053

D1S3316 (e-PCR)
- UniSTS:42652

RH17093 (e-PCR)
- UniSTS:84912

RH64700 (e-PCR)
- UniSTS:62961

GDB:177368 (e-PCR)
- UniSTS:154866

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 GTP binding	IBA Inferred from Biological aspect of Ancestor more info
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	TAS Traceable Author Statement more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein-containing complex binding	IDA Inferred from Direct Assay more info	PubMed

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 myoblast differentiation	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of endothelial cell proliferation	IMP Inferred from Mutant Phenotype more info	PubMed

Component	Evidence Code	Pubs
located_in Golgi apparatus	IDA Inferred from Direct Assay more info	PubMed
located_in Golgi membrane	TAS Traceable Author Statement more info
located_in cytosol	TAS Traceable Author Statement more info
located_in endoplasmic reticulum membrane	TAS Traceable Author Statement more info
located_in extracellular exosome	HDA more info	PubMed
located_in membrane	HDA more info	PubMed
is_active_in plasma membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in plasma membrane	TAS Traceable Author Statement more info
located_in tertiary granule membrane	TAS Traceable Author Statement more info

General protein information

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Preferred Names: GTPase NRas

Names: N-ras protein part 4; neuroblastoma RAS viral (v-ras) oncogene homolog; neuroblastoma RAS viral oncogene homolog; proto-oncogene GTPase; transforming protein N-Ras; v-ras neuroblastoma RAS viral oncogene homolog

NP_002515.1

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.