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    RRAS2 RAS related 2 [ Homo sapiens (human) ]

    Gene ID: 22800, updated on 4-Jan-2025

    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
    mouse all
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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: Tissue-specific circular RNA induction during human fetal development
    • Description: 35 human fetal samples from 6 tissues (3 - 7 replicates per tissue) collected between 10 and 20 weeks gestational time were sequenced using Illumina TruSeq Stranded Total RNA
    • BioProject: PRJNA270632
    • Publication: PMID 26076956
    • Analysis date: Mon Apr 2 22:54:59 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
    		Compare labs

    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

      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

      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

      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

      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

      UniProtKB/TrEMBL
      E9PK85

    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

    Gene LinkOut

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