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

Gene ID: 5921, updated on 2-Nov-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
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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 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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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
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)

Genotypes

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

    See identical proteins and their annotated locations for NP_002881.1

    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

    See identical proteins and their annotated locations for NP_072179.1

    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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