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    RIN2 Ras and Rab interactor 2 [ Homo sapiens (human) ]

    Gene ID: 54453, updated on 10-Dec-2024

    Summary

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    Official Symbol
    RIN2provided by HGNC
    Official Full Name
    Ras and Rab interactor 2provided by HGNC
    Primary source
    HGNC:HGNC:18750
    See related
    Ensembl:ENSG00000132669 MIM:610222; AllianceGenome:HGNC:18750
    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
    MACS; RASSF4
    Summary
    The RAB5 protein is a small GTPase involved in membrane trafficking in the early endocytic pathway. The protein encoded by this gene binds the GTP-bound form of the RAB5 protein preferentially over the GDP-bound form, and functions as a guanine nucleotide exchange factor for RAB5. The encoded protein is found primarily as a tetramer in the cytoplasm and does not bind other members of the RAB family. Mutations in this gene cause macrocephaly alopecia cutis laxa and scoliosis (MACS) syndrome, an elastic tissue disorder, as well as the related connective tissue disorder, RIN2 syndrome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jun 2011]
    Expression
    Ubiquitous expression in lung (RPKM 8.3), endometrium (RPKM 7.8) and 25 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See RIN2 in Genome Data Viewer
    Location:
    20p11.23
    Exon count:
    24
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 20 NC_000020.11 (19757599..20002456)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 20 NC_060944.1 (19809879..20056735)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 20 NC_000020.10 (19738902..19983100)

    Chromosome 20 - NC_000020.11Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC101929547 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr20:19188093-19188651 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 12705 Neighboring gene uncharacterized LOC124904879 Neighboring gene SLC24A3 antisense RNA 1 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 17596 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 17597 Neighboring gene solute carrier family 24 member 3 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 17598 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 17599 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 17600 Neighboring gene MED14-independent group 3 enhancer GRCh37_chr20:19477291-19478490 Neighboring gene ReSE screen-validated silencer GRCh37_chr20:19496927-19497144 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr20:19563919-19564420 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr20:19600691-19601604 Neighboring gene NANOG-H3K27ac hESC enhancer GRCh37_chr20:19658252-19659230 Neighboring gene H3K27ac hESC enhancer GRCh37_chr20:19659231-19660207 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr20:19691947-19692447 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr20:19739291-19739865 Neighboring gene Sharpr-MPRA regulatory region 11499 Neighboring gene cutaneous T cell lymphoma-associated antigen 1 pseudogene Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 12706 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr20:19819023-19819524 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr20:19866384-19866884 Neighboring gene ribosomal protein L12 pseudogene 12 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 17601 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 17602 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr20:19938653-19939384 Neighboring gene OCT4-NANOG-H3K4me1 hESC enhancer GRCh37_chr20:19939385-19940116 Neighboring gene H3K27ac hESC enhancer GRCh37_chr20:19960987-19961488 Neighboring gene H3K27ac hESC enhancer GRCh37_chr20:19961489-19961988 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr20:19973649-19974520 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 12707 Neighboring gene H3K27ac hESC enhancer GRCh37_chr20:19998307-19998807 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 12708 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 17603 Neighboring gene MED14-independent group 3 enhancer GRCh37_chr20:19999269-20000468 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 17604 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 17605 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 12709 Neighboring gene N-alpha-acetyltransferase 20, NatB catalytic subunit Neighboring gene crooked neck pre-mRNA splicing factor 1 Neighboring gene cilia and flagella associated protein 61

    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. The RIN2 syndrome: a new autosomal recessive connective tissue disorder caused by deficiency of Ras and Rab interactor 2 (RIN2). Syx D, et al. Hum Genet, 2010 Jul. PMID 20424861
    2. RIN2 deficiency results in macrocephaly, alopecia, cutis laxa, and scoliosis: MACS syndrome. Basel-Vanagaite L, et al. Am J Hum Genet, 2009 Aug. PMID 19631308, Free PMC Article
    3. Newly described clinical features in two siblings with MACS syndrome and a novel mutation in RIN2. Aslanger AD, et al. Am J Med Genet A, 2014 Feb. PMID 24449201
    4. RIN2 syndrome: Expanding the clinical phenotype. Rosato S, et al. Am J Med Genet A, 2016 Sep. PMID 27277385
    5. Leukoencephalopathy in RIN2 syndrome: Novel mutation and expansion of clinical spectrum. Kameli R, et al. Eur J Med Genet, 2020 Jan. PMID 30769224

    See all (36) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. NAA20 recruits Rin2 and promotes triple-negative breast cancer progression by regulating Rab5A-mediated activation of EGFR signaling.
      Title: NAA20 recruits Rin2 and promotes triple-negative breast cancer progression by regulating Rab5A-mediated activation of EGFR signaling.
    2. Rare adult pilocytic astrocytoma of the septum pellucidum with novel RIN2::BRAF fusion.
      Title: Rare adult pilocytic astrocytoma of the septum pellucidum with novel RIN2::BRAF fusion.
    3. The endosomal RIN2/Rab5C machinery prevents VEGFR2 degradation to control gene expression and tip cell identity during angiogenesis.
      Title: The endosomal RIN2/Rab5C machinery prevents VEGFR2 degradation to control gene expression and tip cell identity during angiogenesis.
    4. Leukoencephalopathy in RIN2 syndrome: Novel mutation and expansion of clinical spectrum.
      Title: Leukoencephalopathy in RIN2 syndrome: Novel mutation and expansion of clinical spectrum.
    5. Rab5 as a novel regulator of calpain2 activity and focal adhesion proteolysis leading to cell migration
      Title: Calpain2 mediates Rab5-driven focal adhesion disassembly and cell migration.
    6. we describe a 10th patient, the first patient of Caucasian origin and the oldest reported patient so far, who harbors the previously identified homozygous RIN2 mutation c.1878dupC (p. (Ile627Hisfs*7)). Besides the hallmark features, this patient also presents problems not previously associated with RIN2 syndrome, including cervical vertebral fusion, mild hearing loss, and colonic fibrosis.
      Title: RIN2 syndrome: Expanding the clinical phenotype.
    7. We describe the fourth family with RIN2 syndrome in two siblings with a novel homozygous mutation in the RIN2 gene and exhibiting additional clinical features that may also contribute to further delineation of the phenotypic spectrum.
      Title: Newly described clinical features in two siblings with MACS syndrome and a novel mutation in RIN2.
    8. These findings confirm that RIN2 defects are associated with a distinct genodermatosis and underscore the involvement of RIN2 and its associated pathways in the pathogenesis of connective tissue disorders.
      Title: The RIN2 syndrome: a new autosomal recessive connective tissue disorder caused by deficiency of Ras and Rab interactor 2 (RIN2).
    9. RIN2 deficiency results in macrocephaly, alopecia, cutis laxa, and scoliosis: MACS syndrome.
      Title: RIN2 deficiency results in macrocephaly, alopecia, cutis laxa, and scoliosis: MACS syndrome.
    Submit: New GeneRIF Correction

    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
    RIN2 syndrome
    MedGen: C2751321 OMIM: 613075 GeneReviews: Not available
    		Compare labs

    EBI GWAS Catalog

    Description
    A genome-wide meta-analysis identifies novel loci associated with schizophrenia and bipolar disorder.
    EBI GWAS Catalog
    Genome-wide association study of bipolar disorder accounting for effect of body mass index identifies a new risk allele in TCF7L2.
    EBI GWAS Catalog
    Novel genetic loci identified for the pathophysiology of childhood obesity in the Hispanic population.
    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

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables GTPase activator activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables GTPase regulator activity NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    enables guanyl-nucleotide exchange factor activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables guanyl-nucleotide exchange factor activity NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    enables small GTPase binding IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    Process Evidence Code Pubs
    involved_in endocytosis IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in positive regulation of endothelial cell migration IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in positive regulation of endothelial cell-matrix adhesion via fibronectin IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in positive regulation of vasculogenesis IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in small GTPase-mediated signal transduction NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    Component Evidence Code Pubs
    is_active_in cytosol IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in cytosol TAS
    Traceable Author Statement
    more info
    		  
    is_active_in endocytic vesicle IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  

    General protein information

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    Preferred Names
    ras and Rab interactor 2
    Names
    RAB5 interacting protein 2
    RAS association (RalGDS/AF-6) domain containing protein JC265
    RAS association domain family 4
    RAS inhibitor JC265
    RAS interaction/interference protein 2

    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_016310.3 RefSeqGene

      Range
      5661..249859
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001242581.2 → NP_001229510.1  ras and Rab interactor 2 isoform 1

      See identical proteins and their annotated locations for NP_001229510.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1).
      Source sequence(s)
      AI695804, AK094884, AL136924, BM973182
      UniProtKB/TrEMBL
      B3KT35
      Conserved Domains (3) summary
      smart00167
      Location:697 → 815
      VPS9; Domain present in VPS9
      cd01776
      Location:839 → 925
      Rin1_RA; Ubiquitin domain of RIN1 RAS effector
      cd10394
      Location:135 → 234
      SH2_RIN2; Src homology 2 (SH2) domain found in Ras and Rab interactor 2 (RIN2)-like proteins

    2. NM_001378238.1 → NP_001365167.1  ras and Rab interactor 2 isoform 3

      Status: REVIEWED

      Source sequence(s)
      AL049538, AL121761, AL132821
      Conserved Domains (2) summary
      smart00167
      Location:442 → 560
      VPS9; Domain present in VPS9
      cd16131
      Location:581 → 671
      RA_Rin2; Ras-associating (RA) domain found in Ras and Rab interactor 2 (Rin2)

    3. NM_018993.4 → NP_061866.1  ras and Rab interactor 2 isoform 2

      See identical proteins and their annotated locations for NP_061866.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) lacks a portion of the 5' UTR and 5' coding region, and uses a downstream in-frame start codon, compared to variant 1. The encoded isoform (2) is shorter at the N-terminus, compared to isoform 1.
      Source sequence(s)
      AL049538, AL121761, AL132821
      Consensus CDS
      CCDS93018.1
      UniProtKB/Swiss-Prot
      Q00425, Q5TFT8, Q8WYP3, Q9BQL3, Q9H071
      UniProtKB/TrEMBL
      B3KT35
      Related
      ENSP00000255006.7, ENST00000255006.12
      Conserved Domains (3) summary
      smart00167
      Location:648 → 766
      VPS9; Domain present in VPS9
      cd10394
      Location:86 → 185
      SH2_RIN2; Src homology 2 (SH2) domain found in Ras and Rab interactor 2 (RIN2)-like proteins
      cd16131
      Location:787 → 877
      RA_Rin2; Ras-associating (RA) domain found in Ras and Rab interactor 2 (Rin2)

    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_000020.11 Reference GRCh38.p14 Primary Assembly

      Range
      19757599..20002456
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_047440212.1 → XP_047296168.1  ras and Rab interactor 2 isoform X2

      UniProtKB/TrEMBL
      B3KT35

    2. XM_047440213.1 → XP_047296169.1  ras and Rab interactor 2 isoform X2

      UniProtKB/TrEMBL
      B3KT35

    3. XM_017027888.2 → XP_016883377.1  ras and Rab interactor 2 isoform X2

      UniProtKB/TrEMBL
      B3KT35
      Conserved Domains (3) summary
      smart00167
      Location:697 → 815
      VPS9; Domain present in VPS9
      cd01776
      Location:839 → 925
      Rin1_RA; Ubiquitin domain of RIN1 RAS effector
      cd10394
      Location:135 → 234
      SH2_RIN2; Src homology 2 (SH2) domain found in Ras and Rab interactor 2 (RIN2)-like proteins

    4. XM_017027887.2 → XP_016883376.1  ras and Rab interactor 2 isoform X2

      UniProtKB/TrEMBL
      B3KT35
      Conserved Domains (3) summary
      smart00167
      Location:697 → 815
      VPS9; Domain present in VPS9
      cd01776
      Location:839 → 925
      Rin1_RA; Ubiquitin domain of RIN1 RAS effector
      cd10394
      Location:135 → 234
      SH2_RIN2; Src homology 2 (SH2) domain found in Ras and Rab interactor 2 (RIN2)-like proteins

    5. XM_047440211.1 → XP_047296167.1  ras and Rab interactor 2 isoform X2

      UniProtKB/TrEMBL
      B3KT35

    6. XM_047440215.1 → XP_047296171.1  ras and Rab interactor 2 isoform X4

      UniProtKB/Swiss-Prot
      Q00425, Q5TFT8, Q8WYP3, Q9BQL3, Q9H071
      UniProtKB/TrEMBL
      B3KT35

    7. XM_047440210.1 → XP_047296166.1  ras and Rab interactor 2 isoform X2

      UniProtKB/TrEMBL
      B3KT35

    8. XM_047440209.1 → XP_047296165.1  ras and Rab interactor 2 isoform X2

      UniProtKB/TrEMBL
      B3KT35

    9. XM_047440214.1 → XP_047296170.1  ras and Rab interactor 2 isoform X4

      UniProtKB/Swiss-Prot
      Q00425, Q5TFT8, Q8WYP3, Q9BQL3, Q9H071
      UniProtKB/TrEMBL
      B3KT35

    10. XM_017027890.2 → XP_016883379.1  ras and Rab interactor 2 isoform X4

      UniProtKB/Swiss-Prot
      Q00425, Q5TFT8, Q8WYP3, Q9BQL3, Q9H071
      UniProtKB/TrEMBL
      B3KT35
      Related
      ENSP00000498085.1, ENST00000648440.1
      Conserved Domains (3) summary
      smart00167
      Location:648 → 766
      VPS9; Domain present in VPS9
      cd10394
      Location:86 → 185
      SH2_RIN2; Src homology 2 (SH2) domain found in Ras and Rab interactor 2 (RIN2)-like proteins
      cd16131
      Location:787 → 877
      RA_Rin2; Ras-associating (RA) domain found in Ras and Rab interactor 2 (Rin2)

    11. XM_011529255.3 → XP_011527557.3  ras and Rab interactor 2 isoform X1

      UniProtKB/TrEMBL
      B3KT35

    12. XM_006723577.2 → XP_006723640.1  ras and Rab interactor 2 isoform X4

      See identical proteins and their annotated locations for XP_006723640.1

      UniProtKB/Swiss-Prot
      Q00425, Q5TFT8, Q8WYP3, Q9BQL3, Q9H071
      UniProtKB/TrEMBL
      B3KT35
      Conserved Domains (3) summary
      smart00167
      Location:648 → 766
      VPS9; Domain present in VPS9
      cd10394
      Location:86 → 185
      SH2_RIN2; Src homology 2 (SH2) domain found in Ras and Rab interactor 2 (RIN2)-like proteins
      cd16131
      Location:787 → 877
      RA_Rin2; Ras-associating (RA) domain found in Ras and Rab interactor 2 (Rin2)

    13. XM_017027893.2 → XP_016883382.2  ras and Rab interactor 2 isoform X7

    14. XM_017027889.2 → XP_016883378.1  ras and Rab interactor 2 isoform X3

      UniProtKB/TrEMBL
      B3KT35

    15. XM_047440216.1 → XP_047296172.1  ras and Rab interactor 2 isoform X5

      UniProtKB/TrEMBL
      B3KT35

    16. XM_017027892.2 → XP_016883381.1  ras and Rab interactor 2 isoform X6

      UniProtKB/TrEMBL
      B3KT35
      Conserved Domains (3) summary
      smart00167
      Location:595 → 713
      VPS9; Domain present in VPS9
      cd01776
      Location:737 → 823
      Rin1_RA; Ubiquitin domain of RIN1 RAS effector
      cd10394
      Location:33 → 132
      SH2_RIN2; Src homology 2 (SH2) domain found in Ras and Rab interactor 2 (RIN2)-like proteins

    17. XM_011529259.3 → XP_011527561.1  ras and Rab interactor 2 isoform X6

      UniProtKB/TrEMBL
      B3KT35
      Related
      ENST00000484638.1
      Conserved Domains (3) summary
      smart00167
      Location:595 → 713
      VPS9; Domain present in VPS9
      cd01776
      Location:737 → 823
      Rin1_RA; Ubiquitin domain of RIN1 RAS effector
      cd10394
      Location:33 → 132
      SH2_RIN2; Src homology 2 (SH2) domain found in Ras and Rab interactor 2 (RIN2)-like proteins

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060944.1 Alternate T2T-CHM13v2.0

      Range
      19809879..20056735
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054323534.1 → XP_054179509.1  ras and Rab interactor 2 isoform X2

      UniProtKB/TrEMBL
      B3KT35

    2. XM_054323536.1 → XP_054179511.1  ras and Rab interactor 2 isoform X2

      UniProtKB/TrEMBL
      B3KT35

    3. XM_054323539.1 → XP_054179514.1  ras and Rab interactor 2 isoform X4

      UniProtKB/Swiss-Prot
      Q00425, Q5TFT8, Q8WYP3, Q9BQL3, Q9H071
      UniProtKB/TrEMBL
      B3KT35

    4. XM_054323535.1 → XP_054179510.1  ras and Rab interactor 2 isoform X2

      UniProtKB/TrEMBL
      B3KT35

    5. XM_054323533.1 → XP_054179508.1  ras and Rab interactor 2 isoform X2

      UniProtKB/TrEMBL
      B3KT35

    6. XM_054323538.1 → XP_054179513.1  ras and Rab interactor 2 isoform X4

      UniProtKB/Swiss-Prot
      Q00425, Q5TFT8, Q8WYP3, Q9BQL3, Q9H071
      UniProtKB/TrEMBL
      B3KT35

    7. XM_054323540.1 → XP_054179515.1  ras and Rab interactor 2 isoform X4

      UniProtKB/Swiss-Prot
      Q00425, Q5TFT8, Q8WYP3, Q9BQL3, Q9H071
      UniProtKB/TrEMBL
      B3KT35

    8. XM_054323543.1 → XP_054179518.1  ras and Rab interactor 2 isoform X9

    9. XM_054323532.1 → XP_054179507.1  ras and Rab interactor 2 isoform X8

      UniProtKB/TrEMBL
      B3KT35

    10. XM_054323537.1 → XP_054179512.1  ras and Rab interactor 2 isoform X3

      UniProtKB/TrEMBL
      B3KT35

    11. XM_054323541.1 → XP_054179516.1  ras and Rab interactor 2 isoform X5

      UniProtKB/TrEMBL
      B3KT35

    12. XM_054323542.1 → XP_054179517.1  ras and Rab interactor 2 isoform X6

      UniProtKB/TrEMBL
      B3KT35

    Suppressed Reference Sequence(s)

    The following Reference Sequences have been suppressed. Explain

    1. NM_001378236.1: Suppressed sequence

      Description
      NM_001378236.1: This RefSeq was removed because it is redundant with another RefSeq.
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q8WYP3.1 GenPept UniProtKB/Swiss-Prot:Q8WYP3

    Gene LinkOut

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

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