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    RASA1 RAS p21 protein activator 1 [ Homo sapiens (human) ]

    Gene ID: 5921, updated on 10-Dec-2024

    Summary

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    Official Symbol
    RASA1provided by HGNC
    Official Full Name
    RAS p21 protein activator 1provided by HGNC
    Primary source
    HGNC:HGNC:9871
    See related
    Ensembl:ENSG00000145715 MIM:139150; AllianceGenome:HGNC:9871
    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
    GAP; PKWS; RASA; p120; CMAVM; CM-AVM; CMAVM1; RASGAP; p120GAP; p120RASGAP
    Summary
    The protein encoded by this gene is located in the cytoplasm and is part of the GAP1 family of GTPase-activating proteins. The gene product stimulates the GTPase activity of normal RAS p21 but not its oncogenic counterpart. Acting as a suppressor of RAS function, the protein enhances the weak intrinsic GTPase activity of RAS proteins resulting in the inactive GDP-bound form of RAS, thereby allowing control of cellular proliferation and differentiation. Mutations leading to changes in the binding sites of either protein are associated with basal cell carcinomas. Mutations also have been associated with hereditary capillary malformations (CM) with or without arteriovenous malformations (AVM) and Parkes Weber syndrome. Alternative splicing results in two isoforms where the shorter isoform, lacking the N-terminal hydrophobic region but retaining the same activity, appears to be abundantly expressed in placental but not adult tissues. [provided by RefSeq, May 2012]
    Expression
    Broad expression in placenta (RPKM 37.4), testis (RPKM 12.6) and 24 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See RASA1 in Genome Data Viewer
    Location:
    5q14.3
    Exon count:
    25
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 5 NC_000005.10 (87267883..87391916)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 5 NC_060929.1 (87749006..87873021)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 5 NC_000005.9 (86563700..86687733)

    Chromosome 5 - NC_000005.10Genomic Context describing neighboring genes Neighboring gene MIR4280 host gene Neighboring gene ATAC-STARR-seq lymphoblastoid active region 22750 Neighboring gene uncharacterized LOC101929380 Neighboring gene microRNA 4280 Neighboring gene MPRA-validated peak5332 silencer Neighboring gene ATAC-STARR-seq lymphoblastoid active region 22751 Neighboring gene long intergenic non-protein coding RNA 1949 Neighboring gene Sharpr-MPRA regulatory region 12969 Neighboring gene Sharpr-MPRA regulatory region 46 Neighboring gene H3K27ac hESC enhancer GRCh37_chr5:86563777-86564664 Neighboring gene uncharacterized LOC124901022 Neighboring gene H3K27ac hESC enhancer GRCh37_chr5:86595594-86596094 Neighboring gene H3K27ac hESC enhancer GRCh37_chr5:86596095-86596595 Neighboring gene RNA, 7SL, cytoplasmic 629, pseudogene Neighboring gene RNA, U6 small nuclear 606, pseudogene Neighboring gene uncharacterized LOC644285 Neighboring gene cyclin H Neighboring gene ATAC-STARR-seq lymphoblastoid active region 22753 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 22754 Neighboring gene uncharacterized LOC105379066 Neighboring gene RNA, U6 small nuclear 727, pseudogene Neighboring gene uncharacterized LOC124901222

    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. A novel association between RASA1 mutations and spinal arteriovenous anomalies. Thiex R, et al. AJNR Am J Neuroradiol, 2010 Apr. PMID 20007727, Free PMC Article
    2. RASA1 mosaic mutations in patients with capillary malformation-arteriovenous malformation. Revencu N, et al. J Med Genet, 2020 Jan. PMID 31300548
    3. Constitutional mosaicism in RASA1-related capillary malformation-arteriovenous malformation. Gordo G, et al. Clin Genet, 2019 Apr. PMID 30635911
    4. The RasGAP N-terminal fragment generated by caspase cleavage protects cells in a Ras/PI3K/Akt-dependent manner that does not rely on NFkappa B activation. Yang JY, et al. J Biol Chem, 2002 Apr 26. PMID 11847220
    5. Expanding the clinical and molecular findings in RASA1 capillary malformation-arteriovenous malformation. Wooderchak-Donahue WL, et al. Eur J Hum Genet, 2018 Oct. PMID 29891884, Free PMC Article

    See all (269) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. p120 RasGAP and ZO-2 are essential for Hippo signaling and tumor-suppressor function mediated by p190A RhoGAP.
      Title: p120 RasGAP and ZO-2 are essential for Hippo signaling and tumor-suppressor function mediated by p190A RhoGAP.
    2. Spectrum of lymphatic anomalies in patients with RASA1-related CM-AVM.
      Title: Spectrum of lymphatic anomalies in patients with RASA1-related CM-AVM.
    3. Diverse p120RasGAP interactions with doubly phosphorylated partners EphB4, p190RhoGAP, and Dok1.
      Title: Diverse p120RasGAP interactions with doubly phosphorylated partners EphB4, p190RhoGAP, and Dok1.
    4. Three Cases of Familial Moyamoya Disease with RASA1 Mutations-A Case Report.
      Title: Three Cases of Familial Moyamoya Disease with RASA1 Mutations-A Case Report.
    5. Regulation of IncRNA ZNF667-AS1 in Proliferation and Invasion of Esophageal Squamous Cell Carcinoma Cells via Mediating ceRNA Network.
      Title: Regulation of IncRNA ZNF667-AS1 in Proliferation and Invasion of Esophageal Squamous Cell Carcinoma Cells via Mediating ceRNA Network.
    6. Assessing the association of common genetic variants in EPHB4 and RASA1 with phenotype severity in familial cerebral cavernous malformation.
      Title: Assessing the association of common genetic variants in EPHB4 and RASA1 with phenotype severity in familial cerebral cavernous malformation.
    7. RASA1 phenotype overlaps with hereditary haemorrhagic telangiectasia: two case reports.
      Title: RASA1 phenotype overlaps with hereditary haemorrhagic telangiectasia: two case reports.
    8. Abnormal H3K27 histone methylation of RASA1 gene leads to unexplained recurrent spontaneous abortion by regulating Ras-MAPK pathway in trophoblast cells.
      Title: Abnormal H3K27 histone methylation of RASA1 gene leads to unexplained recurrent spontaneous abortion by regulating Ras-MAPK pathway in trophoblast cells.
    9. The long noncoding RNA MEG3 regulates Ras-MAPK pathway through RASA1 in trophoblast and is associated with unexplained recurrent spontaneous abortion.
      Title: The long noncoding RNA MEG3 regulates Ras-MAPK pathway through RASA1 in trophoblast and is associated with unexplained recurrent spontaneous abortion.
    10. CircMTO1 inhibits ox-LDL-stimulated vascular smooth muscle cell proliferation and migration via regulating the miR-182-5p/RASA1 axis.
      Title: CircMTO1 inhibits ox-LDL-stimulated vascular smooth muscle cell proliferation and migration via regulating the miR-182-5p/RASA1 axis.
    Submit: New GeneRIF Correction See all GeneRIFs (97)

    Phenotypes

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    Review eQTL and phenotype association data in this region using PheGenI

    Associated conditions

    Description Tests
    Basal cell carcinoma, susceptibility to, 1
    MedGen: C2751544 OMIM: 605462 GeneReviews: Not available
    		not available
    Capillary malformation-arteriovenous malformation 1
    MedGen: C4747394 OMIM: 608354 GeneReviews: Capillary Malformation-Arteriovenous Malformation Syndrome
    		not available

    Copy number response

    Description
    Copy number response
    Triplosensitivity

    No evidence available (Last evaluated 2020-04-22)

    ClinGen Genome Curation Page
    Haploinsufficency

    Sufficient evidence for dosage pathogenicity (Last evaluated 2020-04-22)

    ClinGen Genome Curation PagePubMed

    EBI GWAS Catalog

    Description
    Common genetic variation and antidepressant efficacy in major depressive disorder: a meta-analysis of three genome-wide pharmacogenetic studies.
    EBI GWAS Catalog
    Meta-analysis of genome-wide association studies for personality.
    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)

    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

    Clone Names

    • DKFZp434N071

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables GTPase activator activity EXP
    Inferred from Experiment
    more info
    		 PubMed 
    enables GTPase activity TAS
    Traceable Author Statement
    more info
    		  
    enables GTPase binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables phosphotyrosine residue binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables potassium channel inhibitor activity NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables signaling receptor binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in blood vessel morphogenesis IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in ephrin receptor signaling pathway TAS
    Traceable Author Statement
    more info
    		  
    involved_in intracellular signal transduction NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    involved_in mitotic cytokinesis ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in negative regulation of apoptotic process IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in negative regulation of cell adhesion IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in negative regulation of cell-matrix adhesion IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in negative regulation of neuron apoptotic process ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in regulation of RNA metabolic process NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    involved_in regulation of actin filament polymerization IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in regulation of cell shape NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    involved_in signal transduction IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in vasculogenesis ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    Component Evidence Code Pubs
    located_in cytoplasm NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    located_in cytosol TAS
    Traceable Author Statement
    more info
    		  
    located_in plasma membrane IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in ruffle IEA
    Inferred from Electronic Annotation
    more info
    		  

    General protein information

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    Preferred Names
    ras GTPase-activating protein 1
    Names
    RAS p21 protein activator (GTPase activating protein) 1
    p120 RAS GTPase activating protein
    triphosphatase-activating protein

    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_011650.1 RefSeqGene

      Range
      4550..128583
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_002890.3 → NP_002881.1  ras GTPase-activating protein 1 isoform 1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) lacks the alternatively spliced insert found in variant 2, resulting in translation of the longer isoform (1).
      Source sequence(s)
      AB209106, AC126776, M23379
      Consensus CDS
      CCDS34200.1
      UniProtKB/Swiss-Prot
      B2R6W3, B4DTL2, P20936, Q68CU6, Q9UDI1
      UniProtKB/TrEMBL
      E9PGC0
      Related
      ENSP00000274376.6, ENST00000274376.11
      Conserved Domains (6) summary
      cd08400
      Location:591 → 716
      C2_Ras_p21A1; C2 domain present in RAS p21 protein activator 1 (RasA1)
      cd10353
      Location:161 → 264
      SH2_Nterm_RasGAP; N-terminal Src homology 2 (SH2) domain found in Ras GTPase-activating protein 1 (GAP)
      cd10354
      Location:350 → 426
      SH2_Cterm_RasGAP; C-terminal Src homology 2 (SH2) domain found in Ras GTPase-activating protein 1 (GAP)
      cd11788
      Location:281 → 339
      SH3_RasGAP; Src Homology 3 domain of Ras GTPase-Activating Protein 1
      cd05391
      Location:714 → 1045
      RasGAP_p120GAP; Ras-GTPase Activating Domain of p120
      cd13260
      Location:489 → 576
      PH_RASA1; RAS p21 protein activator (GTPase activating protein) 1 Pleckstrin homology (PH) domain

    2. NM_022650.3 → NP_072179.1  ras GTPase-activating protein 1 isoform 2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) includes an alternatively spliced exon in the 5' portion of the transcript, allowing for translation from an alternative initiation codon and resulting in the shorter isoform (2) which is missing the hydrophobic amino terminus found in isoform 1.
      Source sequence(s)
      CF528258, DA863496, M23612
      Consensus CDS
      CCDS47243.1
      UniProtKB/TrEMBL
      E9PGC0
      Related
      ENSP00000411221.2, ENST00000456692.6
      Conserved Domains (6) summary
      cd08400
      Location:414 → 539
      C2_Ras_p21A1; C2 domain present in RAS p21 protein activator 1 (RasA1)
      cd10354
      Location:173 → 249
      SH2_Cterm_RasGAP; C-terminal Src homology 2 (SH2) domain found in Ras GTPase-activating protein 1 (GAP)
      cd11788
      Location:104 → 162
      SH3_RasGAP; Src Homology 3 domain of Ras GTPase-Activating Protein 1
      cd05391
      Location:537 → 868
      RasGAP_p120GAP; Ras-GTPase Activating Domain of p120
      cl15255
      Location:4 → 87
      SH2; Src homology 2 (SH2) domain
      cl17171
      Location:312 → 399
      PH-like; Pleckstrin homology-like domain

    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_000005.10 Reference GRCh38.p14 Primary Assembly

      Range
      87267883..87391916
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060929.1 Alternate T2T-CHM13v2.0

      Range
      87749006..87873021
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    P20936.1 GenPept UniProtKB/Swiss-Prot:P20936

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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