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    RASAL1 RAS protein activator like 1 [ Homo sapiens (human) ]

    Gene ID: 8437, updated on 3-Apr-2024

    Summary

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    Official Symbol
    RASAL1provided by HGNC
    Official Full Name
    RAS protein activator like 1provided by HGNC
    Primary source
    HGNC:HGNC:9873
    See related
    Ensembl:ENSG00000111344 MIM:604118; AllianceGenome:HGNC:9873
    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
    RASAL
    Summary
    The protein encoded by this gene is member of the GAP1 family of GTPase-activating proteins. These proteins stimulate 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. This particular family member contains domains which are characteristic of the GAP1 subfamily of RasGAP proteins but, in contrast to the other GAP1 family members, this protein is strongly and selectively expressed in endocrine tissues. Alternatively spliced transcript variants that encode different isoforms have been described [provided by RefSeq, Jul 2010]
    Expression
    Broad expression in brain (RPKM 6.0), lymph node (RPKM 5.1) and 18 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    Location:
    12q24.13
    Exon count:
    25
    Annotation release Status Assembly Chr Location
    RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 12 NC_000012.12 (113099278..113136756, complement)
    RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 12 NC_060936.1 (113075920..113113399, complement)
    105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 12 NC_000012.11 (113537083..113574044, complement)

    Chromosome 12 - NC_000012.12Genomic Context describing neighboring genes Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr12:113495773-113496561 Neighboring gene ribosomal protein S15a pseudogene 32 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:113503073-113503631 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:113504873-113505373 Neighboring gene deltex E3 ubiquitin ligase 1 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7059 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7060 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 4889 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 4890 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:113535297-113535838 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7061 Neighboring gene MPRA-validated peak1969 silencer Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 4891 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:113592609-113593108 Neighboring gene MPRA-validated peak1971 silencer Neighboring gene cilia and flagella associated protein 73 Neighboring gene microRNA 7106 Neighboring gene DEAD-box helicase 54 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7062 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7063 Neighboring gene H3K27ac hESC enhancer GRCh37_chr12:113623217-113623866 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr12:113623867-113624517 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:113624518-113625167 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:113629297-113629950 Neighboring gene RBPJ interacting and tubulin associated 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. Domain topology of human Rasal. Cuellar J, et al. Biol Chem, 2017 Dec 20. PMID 28885980
    2. Prognostic implications of RASAL1 expression in oesophagogastric adenocarcinoma. Knief J, et al. J Clin Pathol, 2017 Mar. PMID 28011578
    3. Hypoxia-induced endothelial-mesenchymal transition is associated with RASAL1 promoter hypermethylation in human coronary endothelial cells. Xu X, et al. FEBS Lett, 2016 Apr. PMID 27012941
    4. RASAL1 attenuates gastric carcinogenesis in nude mice by blocking RAS/ERK signaling. Chen H, et al. Asian Pac J Cancer Prev, 2015. PMID 25735335
    5. Germline alterations in RASAL1 in Cowden syndrome patients presenting with follicular thyroid cancer and in individuals with apparently sporadic epithelial thyroid cancer. Ngeow J, et al. J Clin Endocrinol Metab, 2014 Jul. PMID 24712574, Free PMC Article

    See all (32) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Domain topology of human Rasal
      Title: Domain topology of human Rasal.
    2. HIF1alpha and transforming growth factor (TGF)/SMAD signalling pathways synergistically regulate hypoxia-induced endothelial-to-mesenchymal transition through both DNMT3a-mediated hypermethylation of RASAL1 promoter and direct SNAIL induction.
      Title: Hypoxia-induced endothelial-mesenchymal transition is associated with RASAL1 promoter hypermethylation in human coronary endothelial cells.
    3. RASAL1 role in in sorafenib-resistance of liver cancer cells
      Title: Long non-coding RNA TUC338 is functionally involved in sorafenib-sensitized hepatocarcinoma cells by targeting RASAL1.
    4. our study showed significantly longer overall survival times for oesophagogastric adenocarcinoma patients without RASAL1 expression
      Title: Prognostic implications of RASAL1 expression in oesophagogastric adenocarcinoma.
    5. DNA methylation, TGFbeta1 and RASAL1 appear to have an interacting relationship.
      Title: Hypoxia-Induced Changes in DNA Methylation Alter RASAL1 and TGFβ1 Expression in Human Trabecular Meshwork Cells.
    6. Report a new subtype of high-grade mandibular osteosarcoma with RASAL1/MDM2 amplification.
      Title: A new subtype of high-grade mandibular osteosarcoma with RASAL1/MDM2 amplification.
    7. These findings suggest that Ebp1 suppressed thyroid cancer cell lines by upregulating RASRAL expression.
      Title: EBP1 suppresses growth, migration, and invasion of thyroid cancer cells through upregulating RASAL expression.
    8. large chromosome 12 rearrangement, spanning MDM2 and RASAL1, is the first recurrent molecular abnormality to be reported in juvenile ossifying fibroma
      Title: Chromosome 12 long arm rearrangement covering MDM2 and RASAL1 is associated with aggressive craniofacial juvenile ossifying fibroma and extracranial psammomatoid fibro-osseous lesions.
    9. Loss of RASAL1 expression is associated with gastric carcinogenesis.
      Title: RASAL1 attenuates gastric carcinogenesis in nude mice by blocking RAS/ERK signaling.
    10. Transcriptional suppression of RASAL1 through aberrant promoter methylation contributes to endothelial-mesenchymal transition and ultimately to progression of cardiac fibrosis.
      Title: Epigenetic balance of aberrant Rasal1 promoter methylation and hydroxymethylation regulates cardiac fibrosis.
    Submit: New GeneRIF Correction See all GeneRIFs (22)

    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

    EBI GWAS Catalog

    Description
    Genome-wide association for abdominal subcutaneous and visceral adipose reveals a novel locus for visceral fat in women.
    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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    Homology

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables GTPase activator activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables metal ion binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables phospholipid binding TAS
    Traceable Author Statement
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in cell differentiation IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in cellular response to calcium ion IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in intracellular signal transduction IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in negative regulation of Ras protein signal transduction IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in positive regulation of dendrite extension IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in signal transduction TAS
    Traceable Author Statement
    more info
    		 PubMed 
    Component Evidence Code Pubs
    located_in cytosol IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in cytosol TAS
    Traceable Author Statement
    more info
    		  
    colocalizes_with plasma membrane IDA
    Inferred from Direct Assay
    more info
    		 PubMed 

    General protein information

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    Preferred Names
    rasGAP-activating-like protein 1
    Names
    GAP1 like protein
    ras GTPase-activating-like 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_047089.1 RefSeqGene

      Range
      5479..41962
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001193520.2 → NP_001180449.1  rasGAP-activating-like protein 1 isoform 1

      See identical proteins and their annotated locations for NP_001180449.1

      Status: REVIEWED

      Source sequence(s)
      AC089999
      Consensus CDS
      CCDS55889.1
      UniProtKB/TrEMBL
      B4DG06
      Related
      ENSP00000450244.1, ENST00000546530.5
      Conserved Domains (4) summary
      cd05135
      Location:263 → 550
      RasGAP_RASAL; Ras-GTPase Activating Domain of RASAL1 and similar proteins
      pfam00779
      Location:683 → 710
      BTK; BTK motif
      cl14603
      Location:134 → 255
      C2; C2 domain
      cl17171
      Location:554 → 691
      PH-like; Pleckstrin homology-like domain

    2. NM_001193521.3 → NP_001180450.1  rasGAP-activating-like protein 1 isoform 3

      Status: REVIEWED

      Source sequence(s)
      AC089999
      Consensus CDS
      CCDS55888.1
      UniProtKB/TrEMBL
      B4DG06
      Related
      ENSP00000395920.3, ENST00000446861.7
      Conserved Domains (5) summary
      cd05135
      Location:263 → 549
      RasGAP_RASAL; Ras-GTPase Activating Domain of RASAL1 and similar proteins
      smart00323
      Location:243 → 604
      RasGAP; GTPase-activator protein for Ras-like GTPases
      pfam00779
      Location:653 → 680
      BTK; BTK motif
      cl14603
      Location:134 → 255
      C2; C2 domain
      cl17171
      Location:552 → 661
      PH-like; Pleckstrin homology-like domain

    3. NM_001301202.2 → NP_001288131.1  rasGAP-activating-like protein 1 isoform 4

      Status: REVIEWED

      Source sequence(s)
      AC089999
      Consensus CDS
      CCDS73529.1
      UniProtKB/TrEMBL
      B4DG06
      Related
      ENSP00000448510.1, ENST00000548055.2
      Conserved Domains (4) summary
      cd05135
      Location:263 → 549
      RasGAP_RASAL; Ras-GTPase Activating Domain of RASAL1 and similar proteins
      pfam00779
      Location:682 → 709
      BTK; BTK motif
      cl14603
      Location:134 → 255
      C2; C2 domain
      cl17171
      Location:553 → 690
      PH-like; Pleckstrin homology-like domain

    4. NM_001394081.1 → NP_001381010.1  rasGAP-activating-like protein 1 isoform 1

      Status: REVIEWED

      Source sequence(s)
      AC089999
      Consensus CDS
      CCDS55889.1
      UniProtKB/TrEMBL
      B4DG06
      Conserved Domains (4) summary
      cd05135
      Location:263 → 550
      RasGAP_RASAL; Ras-GTPase Activating Domain of RASAL1 and similar proteins
      pfam00779
      Location:683 → 710
      BTK; BTK motif
      cl14603
      Location:134 → 255
      C2; C2 domain
      cl17171
      Location:554 → 691
      PH-like; Pleckstrin homology-like domain

    5. NM_001394082.1 → NP_001381011.1  rasGAP-activating-like protein 1 isoform 4

      Status: REVIEWED

      Source sequence(s)
      AC089999
      Consensus CDS
      CCDS73529.1
      UniProtKB/TrEMBL
      B4DG06
      Conserved Domains (4) summary
      cd05135
      Location:263 → 549
      RasGAP_RASAL; Ras-GTPase Activating Domain of RASAL1 and similar proteins
      pfam00779
      Location:682 → 709
      BTK; BTK motif
      cl14603
      Location:134 → 255
      C2; C2 domain
      cl17171
      Location:553 → 690
      PH-like; Pleckstrin homology-like domain

    6. NM_001394083.1 → NP_001381012.1  rasGAP-activating-like protein 1 isoform 4

      Status: REVIEWED

      Source sequence(s)
      AC089999
      Consensus CDS
      CCDS73529.1
      UniProtKB/TrEMBL
      B4DG06
      Conserved Domains (4) summary
      cd05135
      Location:263 → 549
      RasGAP_RASAL; Ras-GTPase Activating Domain of RASAL1 and similar proteins
      pfam00779
      Location:682 → 709
      BTK; BTK motif
      cl14603
      Location:134 → 255
      C2; C2 domain
      cl17171
      Location:553 → 690
      PH-like; Pleckstrin homology-like domain

    7. NM_001394084.1 → NP_001381013.1  rasGAP-activating-like protein 1 isoform 4

      Status: REVIEWED

      Source sequence(s)
      AC089999
      Consensus CDS
      CCDS73529.1
      UniProtKB/TrEMBL
      B4DG06
      Conserved Domains (4) summary
      cd05135
      Location:263 → 549
      RasGAP_RASAL; Ras-GTPase Activating Domain of RASAL1 and similar proteins
      pfam00779
      Location:682 → 709
      BTK; BTK motif
      cl14603
      Location:134 → 255
      C2; C2 domain
      cl17171
      Location:553 → 690
      PH-like; Pleckstrin homology-like domain

    8. NM_001394085.1 → NP_001381014.1  rasGAP-activating-like protein 1 isoform 2

      Status: REVIEWED

      Source sequence(s)
      AC089999
      Consensus CDS
      CCDS9165.1
      UniProtKB/Swiss-Prot
      B7ZKM4, C9JFK5, F8VQX1, O95294, Q52M03, Q59H24, Q96CC7
      UniProtKB/TrEMBL
      B4DG06
      Conserved Domains (4) summary
      cd05135
      Location:263 → 549
      RasGAP_RASAL; Ras-GTPase Activating Domain of RASAL1 and similar proteins
      pfam00779
      Location:681 → 708
      BTK; BTK motif
      cl14603
      Location:134 → 255
      C2; C2 domain
      cl17171
      Location:552 → 689
      PH-like; Pleckstrin homology-like domain

    9. NM_001394086.1 → NP_001381015.1  rasGAP-activating-like protein 1 isoform 5

      Status: REVIEWED

      Source sequence(s)
      AC089999
      UniProtKB/TrEMBL
      B4DG06
      Conserved Domains (3) summary
      cd05135
      Location:263 → 549
      RasGAP_RASAL; Ras-GTPase Activating Domain of RASAL1 and similar proteins
      cl14603
      Location:134 → 255
      C2; C2 domain
      cl17171
      Location:553 → 662
      PH-like; Pleckstrin homology-like domain

    10. NM_001394087.1 → NP_001381016.1  rasGAP-activating-like protein 1 isoform 6

      Status: REVIEWED

      Source sequence(s)
      AC089999
      UniProtKB/TrEMBL
      B4DG06
      Conserved Domains (3) summary
      cd05135
      Location:199 → 486
      RasGAP_RASAL; Ras-GTPase Activating Domain of RASAL1 and similar proteins
      cl14603
      Location:80 → 191
      C2; C2 domain
      cl17171
      Location:490 → 627
      PH-like; Pleckstrin homology-like domain

    11. NM_001394088.1 → NP_001381017.1  rasGAP-activating-like protein 1 isoform 7

      Status: REVIEWED

      Source sequence(s)
      AC089999
      Conserved Domains (3) summary
      cd05135
      Location:142 → 428
      RasGAP_RASAL; Ras-GTPase Activating Domain of RASAL1 and similar proteins
      cl14603
      Location:7 → 134
      C2; C2 domain
      cl17171
      Location:432 → 569
      PH-like; Pleckstrin homology-like domain

    12. NM_001394089.1 → NP_001381018.1  rasGAP-activating-like protein 1 isoform 8

      Status: REVIEWED

      Source sequence(s)
      AC089999
      Conserved Domains (2) summary
      cd05135
      Location:41 → 327
      RasGAP_RASAL; Ras-GTPase Activating Domain of RASAL1 and similar proteins
      cl17171
      Location:331 → 468
      PH-like; Pleckstrin homology-like domain

    13. NM_004658.3 → NP_004649.2  rasGAP-activating-like protein 1 isoform 2

      See identical proteins and their annotated locations for NP_004649.2

      Status: REVIEWED

      Source sequence(s)
      AC089999
      Consensus CDS
      CCDS9165.1
      UniProtKB/Swiss-Prot
      B7ZKM4, C9JFK5, F8VQX1, O95294, Q52M03, Q59H24, Q96CC7
      UniProtKB/TrEMBL
      B4DG06
      Related
      ENSP00000261729.5, ENST00000261729.9
      Conserved Domains (4) summary
      cd05135
      Location:263 → 549
      RasGAP_RASAL; Ras-GTPase Activating Domain of RASAL1 and similar proteins
      pfam00779
      Location:681 → 708
      BTK; BTK motif
      cl14603
      Location:134 → 255
      C2; C2 domain
      cl17171
      Location:552 → 689
      PH-like; Pleckstrin homology-like domain

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

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

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000012.12 Reference GRCh38.p14 Primary Assembly

      Range
      113099278..113136756 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_047429676.1 → XP_047285632.1  rasGAP-activating-like protein 1 isoform X1

    2. XM_005253950.5 → XP_005254007.1  rasGAP-activating-like protein 1 isoform X1

      See identical proteins and their annotated locations for XP_005254007.1

      UniProtKB/TrEMBL
      B4DG06
      Conserved Domains (4) summary
      cd05135
      Location:263 → 550
      RasGAP_RASAL; Ras-GTPase Activating Domain of RASAL1 and similar proteins
      pfam00779
      Location:683 → 710
      BTK; BTK motif
      cl14603
      Location:134 → 255
      C2; C2 domain
      cl17171
      Location:554 → 691
      PH-like; Pleckstrin homology-like domain

    3. XM_006719641.4 → XP_006719704.1  rasGAP-activating-like protein 1 isoform X1

      See identical proteins and their annotated locations for XP_006719704.1

      UniProtKB/TrEMBL
      B4DG06
      Conserved Domains (4) summary
      cd05135
      Location:263 → 550
      RasGAP_RASAL; Ras-GTPase Activating Domain of RASAL1 and similar proteins
      pfam00779
      Location:683 → 710
      BTK; BTK motif
      cl14603
      Location:134 → 255
      C2; C2 domain
      cl17171
      Location:554 → 691
      PH-like; Pleckstrin homology-like domain

    4. XM_006719642.4 → XP_006719705.1  rasGAP-activating-like protein 1 isoform X2

      UniProtKB/TrEMBL
      B4DG06
      Conserved Domains (6) summary
      cd05135
      Location:263 → 550
      RasGAP_RASAL; Ras-GTPase Activating Domain of RASAL1 and similar proteins
      smart00323
      Location:243 → 605
      RasGAP; GTPase-activator protein for Ras-like GTPases
      pfam00169
      Location:567 → 673
      PH; PH domain
      pfam00779
      Location:682 → 709
      BTK; BTK motif
      cl14603
      Location:134 → 255
      C2; C2 domain
      cl17171
      Location:553 → 690
      PH-like; Pleckstrin homology-like domain

    5. XM_047429677.1 → XP_047285633.1  rasGAP-activating-like protein 1 isoform X3

    6. XM_011538854.3 → XP_011537156.1  rasGAP-activating-like protein 1 isoform X6

      Conserved Domains (4) summary
      pfam00169
      Location:209 → 315
      PH; PH domain
      pfam00779
      Location:324 → 351
      BTK; BTK motif
      cl02569
      Location:1 → 191
      RasGAP; Ras GTPase Activating Domain
      cl17171
      Location:195 → 332
      PH-like; Pleckstrin homology-like domain

    7. XM_047429679.1 → XP_047285635.1  rasGAP-activating-like protein 1 isoform X5

    8. XM_047429678.1 → XP_047285634.1  rasGAP-activating-like protein 1 isoform X4

    RNA

    1. XR_007063139.1 RNA Sequence

      Related
      ENST00000418411.6

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060936.1 Alternate T2T-CHM13v2.0

      Range
      113075920..113113399 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054373491.1 → XP_054229466.1  rasGAP-activating-like protein 1 isoform X1

    2. XM_054373489.1 → XP_054229464.1  rasGAP-activating-like protein 1 isoform X1

    3. XM_054373490.1 → XP_054229465.1  rasGAP-activating-like protein 1 isoform X1

    4. XM_054373492.1 → XP_054229467.1  rasGAP-activating-like protein 1 isoform X2

    5. XM_054373493.1 → XP_054229468.1  rasGAP-activating-like protein 1 isoform X3

    6. XM_054373496.1 → XP_054229471.1  rasGAP-activating-like protein 1 isoform X6

    7. XM_054373495.1 → XP_054229470.1  rasGAP-activating-like protein 1 isoform X5

    8. XM_054373494.1 → XP_054229469.1  rasGAP-activating-like protein 1 isoform X4

    RNA

    1. XR_008488702.1 RNA Sequence

    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    O95294.3 GenPept UniProtKB/Swiss-Prot:O95294

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