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RRAS2 RAS related 2 [ Homo sapiens (human) ]

Gene ID: 22800, updated on 27-Nov-2024

Summary

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Official Symbol
RRAS2provided by HGNC
Official Full Name
RAS related 2provided by HGNC
Primary source
HGNC:HGNC:17271
See related
Ensembl:ENSG00000133818 MIM:600098; AllianceGenome:HGNC:17271
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
NS12; TC21
Summary
This gene encodes a member of the R-Ras subfamily of Ras-like small GTPases. The encoded protein associates with the plasma membrane and may function as a signal transducer. This protein may play an important role in activating signal transduction pathways that control cell proliferation. Mutations in this gene are associated with the growth of certain tumors. Pseudogenes of this gene are found on chromosomes 1 and 2. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Apr 2010]
Expression
Ubiquitous expression in small intestine (RPKM 12.4), kidney (RPKM 11.9) and 25 other tissues See more
Orthologs
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Genomic context

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See RRAS2 in Genome Data Viewer
Location:
11p15.2
Exon count:
11
Annotation release Status Assembly Chr Location
RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 11 NC_000011.10 (14277920..14364506, complement)
RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 11 NC_060935.1 (14373520..14459786, complement)
RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 11 NC_000011.9 (14299466..14386052, complement)

Chromosome 11 - NC_000011.10Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC124902637 Neighboring gene NANOG hESC enhancer GRCh37_chr11:13987555-13988073 Neighboring gene spondin 1 Neighboring gene NANOG hESC enhancer GRCh37_chr11:14043232-14043739 Neighboring gene NANOG hESC enhancer GRCh37_chr11:14165203-14165715 Neighboring gene RNA, 5S ribosomal pseudogene 332 Neighboring gene Sharpr-MPRA regulatory region 134 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr11:14252080-14252666 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 4468 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr11:14280438-14280962 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr11:14280963-14281486 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 4469 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 4470 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 4471 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr11:14362237-14362911 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr11:14373862-14374748 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr11:14374749-14375635 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 4472 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 3170 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 3171 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 3172 Neighboring gene NANOG hESC enhancer GRCh37_chr11:14385715-14386272 Neighboring gene Sharpr-MPRA regulatory region 2156 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr11:14428638-14429316 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr11:14443710-14444362 Neighboring gene 60S ribosomal protein L13a-like Neighboring gene RNA, U7 small nuclear 49 pseudogene Neighboring gene COPI coat complex subunit beta 1

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: 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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Related articles in PubMed

  1. RRAS2 knockdown suppresses osteosarcoma progression by inactivating the MEK/ERK signaling pathway. Wang K, et al. Anticancer Drugs, 2019 Oct. PMID 31517733
  2. Characterization of Three Somatic Mutations in the 3'UTR of RRAS2 and Their Inverse Correlation with Lymphocytosis in Chronic Lymphocytic Leukemia. Lacuna M, et al. Cells, 2023 Nov 22. PMID 38067115, Free PMC Article
  3. The RRAS2 pathogenic variant (c.67G>T; p. Gly23Cys) produces Noonan syndrome with embryonal rhabdomyosarcoma. Zeng L, et al. Mol Genet Genomic Med, 2024 Jan. PMID 37942564, Free PMC Article
  4. A human oncogene of the RAS superfamily unmasked by expression cDNA cloning. Chan AM, et al. Proc Natl Acad Sci U S A, 1994 Aug 2. PMID 8052619, Free PMC Article
  5. Germline-Activating RRAS2 Mutations Cause Noonan Syndrome. Niihori T, et al. Am J Hum Genet, 2019 Jun 6. PMID 31130285, Free PMC Article

See all (97) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. Unmutated RRAS2 emerges as a key oncogene in post-partum-associated triple negative breast cancer.
    Title: Unmutated RRAS2 emerges as a key oncogene in post-partum-associated triple negative breast cancer.
  2. Characterization of Three Somatic Mutations in the 3'UTR of RRAS2 and Their Inverse Correlation with Lymphocytosis in Chronic Lymphocytic Leukemia.
    Title: Characterization of Three Somatic Mutations in the 3'UTR of RRAS2 and Their Inverse Correlation with Lymphocytosis in Chronic Lymphocytic Leukemia.
  3. The RRAS2 pathogenic variant (c.67G>T; p. Gly23Cys) produces Noonan syndrome with embryonal rhabdomyosarcoma.
    Title: The RRAS2 pathogenic variant (c.67G>T; p. Gly23Cys) produces Noonan syndrome with embryonal rhabdomyosarcoma.
  4. MicroRNA-23b Plays a Tumor-Suppressive Role in Cutaneous Squamous Cell Carcinoma and Targets Ras-Related Protein RRAS2.
    Title: MicroRNA-23b Plays a Tumor-Suppressive Role in Cutaneous Squamous Cell Carcinoma and Targets Ras-Related Protein RRAS2.
  5. Characterization of mutant versions of the R-RAS2/TC21 GTPase found in tumors.
    Title: Characterization of mutant versions of the R-RAS2/TC21 GTPase found in tumors.
  6. R-Ras subfamily proteins elicit distinct physiologic effects and phosphoproteome alterations in neurofibromin-null MPNST cells.
    Title: R-Ras subfamily proteins elicit distinct physiologic effects and phosphoproteome alterations in neurofibromin-null MPNST cells.
  7. RRAS2 knockdown suppresses osteosarcoma progression by inactivating the MEK/ERK signaling pathway.
    Title: RRAS2 knockdown suppresses osteosarcoma progression by inactivating the MEK/ERK signaling pathway.
  8. Germline-Activating RRAS2 Mutations Cause Noonan Syndrome.
    Title: Germline-Activating RRAS2 Mutations Cause Noonan Syndrome.
  9. Activating Mutations of RRAS2 Cause Noonan Syndrome.
    Title: Activating Mutations of RRAS2 Are a Rare Cause of Noonan Syndrome.
  10. Equilibrium dissociation constants were determined for the binding of HRAS, KRAS, NRAS and RRAS2 to the RAS binding (RB) domain of binding proteins.
    Title: The RAS-Effector Interface: Isoform-Specific Differences in the Effector Binding Regions.
Submit: New GeneRIF Correction See all GeneRIFs (19)

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
Noonan syndrome 12
MedGen: C5231432 OMIM: 618624 GeneReviews: Noonan Syndrome
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EBI GWAS Catalog

Description
A genome-wide association study in the genetic analysis of idiopathic thrombophilia project suggests sex-specific regulation of mitochondrial DNA levels.
EBI GWAS Catalog
Genome-wide association study of the rate of cognitive decline in Alzheimer's disease.
EBI GWAS Catalog
Genome-wide association study of vitamin D levels in children: replication in the Western Australian Pregnancy Cohort (Raine) study.
EBI GWAS Catalog

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
Knockdown of related RAS viral (r-ras) oncogene homolog 2 (RRAS2) by shRNA library screening inhibits HIV-1 replication in cultured Jurkat T-cells PubMed

Go to the HIV-1, Human Interaction Database

Pathways from PubChem

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Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Gene Ontology Provided by GOA

Function Evidence Code Pubs
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 membrane scission GTPase motor activity IEA
Inferred from Electronic Annotation
more info
  
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
Process Evidence Code Pubs
involved_in Ras protein signal transduction IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in Schwann cell migration IEA
Inferred from Electronic Annotation
more info
  
involved_in osteoblast differentiation HDA PubMed 
involved_in positive regulation of Schwann cell migration IEA
Inferred from Electronic Annotation
more info
  
Component Evidence Code Pubs
located_in Golgi membrane IEA
Inferred from Electronic Annotation
more info
  
located_in endoplasmic reticulum NAS
Non-traceable Author Statement
more info
 PubMed 
located_in extracellular exosome HDA PubMed 
located_in focal adhesion HDA PubMed 
located_in membrane HDA PubMed 
is_active_in plasma membrane IBA
Inferred from Biological aspect of Ancestor
more info
  
is_active_in plasma membrane IDA
Inferred from Direct Assay
more info
 PubMed 

General protein information

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Preferred Names
ras-related protein R-Ras2
Names
ras-like protein TC21
related RAS viral (r-ras) oncogene homolog 2
teratocarcinoma oncogene
NP_001096139.1
NP_001170785.1
NP_001170786.1
NP_036382.2
XP_016872852.1
XP_047282523.1
XP_047282524.1
XP_054224023.1
XP_054224024.1
XP_054224025.1

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

  1. NG_017058.1 RefSeqGene

    Range
    10324..91585
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_001102669.2 → NP_001096139.1  ras-related protein R-Ras2 isoform b

    See identical proteins and their annotated locations for NP_001096139.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) differs in the 5' UTR and 5' coding region, compared to variant 1. The resulting isoform (b) is shorter at the N-terminus compared to isoform a. Both variants 2 and 4 encode the same isoform (b).
    Source sequence(s)
    AA873016, AC011084, AK309683, BG428983, BQ020351, BQ023701
    Consensus CDS
    CCDS44544.1
    UniProtKB/Swiss-Prot
    P62070
    Related
    ENSP00000434104.1, ENST00000526063.5
    Conserved Domains (1) summary
    cl38936
    Location:1 → 99
    P-loop_NTPase; P-loop containing Nucleoside Triphosphate Hydrolases

  2. NM_001177314.2 → NP_001170785.1  ras-related protein R-Ras2 isoform c

    See identical proteins and their annotated locations for NP_001170785.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3) differs in the 5' UTR and 5' coding region and initiates translation at an alternate start codon, compared to variant 1. The resulting isoform (b) is shorter and has a distinct N-terminus compared to isoform a.
    Source sequence(s)
    AA873016, AK300103, BQ020351, BQ023701
    Consensus CDS
    CCDS53603.1
    UniProtKB/TrEMBL
    E9PK85
    Related
    ENSP00000437547.1, ENST00000537760.5
    Conserved Domains (1) summary
    cl38936
    Location:2 → 141
    P-loop_NTPase; P-loop containing Nucleoside Triphosphate Hydrolases

  3. NM_001177315.1 → NP_001170786.1  ras-related protein R-Ras2 isoform b

    See identical proteins and their annotated locations for NP_001170786.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (4) differs in the 5' UTR and 5' coding region, compared to variant 1. The resulting isoform (b) is shorter at the N-terminus compared to isoform a. Both variants 2 and 4 encode the same isoform (b).
    Source sequence(s)
    AA873016, AK309550, BQ020351, BQ023701
    Consensus CDS
    CCDS44544.1
    UniProtKB/Swiss-Prot
    P62070
    Related
    ENSP00000431954.1, ENST00000532814.5
    Conserved Domains (1) summary
    cl38936
    Location:1 → 99
    P-loop_NTPase; P-loop containing Nucleoside Triphosphate Hydrolases

  4. NM_012250.6 → NP_036382.2  ras-related protein R-Ras2 isoform a

    See identical proteins and their annotated locations for NP_036382.2

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (a).
    Source sequence(s)
    AA873016, AK309683, AK313976, BQ020351, BQ023701
    Consensus CDS
    CCDS7814.1
    UniProtKB/Swiss-Prot
    B2R9Z3, B7Z5Z2, B7Z6C4, B7Z7H6, P17082, P62070
    Related
    ENSP00000256196.4, ENST00000256196.9
    Conserved Domains (1) summary
    cd04145
    Location:13 → 176
    M_R_Ras_like; R-Ras2/TC21, M-Ras/R-Ras3

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000011.10 Reference GRCh38.p14 Primary Assembly

    Range
    14277920..14364506 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_047426567.1 → XP_047282523.1  ras-related protein R-Ras2 isoform X2

    Related
    ENSP00000403282.2, ENST00000414023.6

  2. XM_017017363.2 → XP_016872852.1  ras-related protein R-Ras2 isoform X1

    UniProtKB/TrEMBL
    E9PK85

  3. XM_047426568.1 → XP_047282524.1  ras-related protein R-Ras2 isoform X2

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060935.1 Alternate T2T-CHM13v2.0

    Range
    14373520..14459786 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054368049.1 → XP_054224024.1  ras-related protein R-Ras2 isoform X2

  2. XM_054368048.1 → XP_054224023.1  ras-related protein R-Ras2 isoform X1

  3. XM_054368050.1 → XP_054224025.1  ras-related protein R-Ras2 isoform X2

Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
P62070.1 GenPept UniProtKB/Swiss-Prot:P62070

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