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    ARHGEF3 Rho guanine nucleotide exchange factor 3 [ Homo sapiens (human) ]

    Gene ID: 50650, updated on 2-Nov-2024

    Summary

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    Official Symbol
    ARHGEF3provided by HGNC
    Official Full Name
    Rho guanine nucleotide exchange factor 3provided by HGNC
    Primary source
    HGNC:HGNC:683
    See related
    Ensembl:ENSG00000163947 MIM:612115; AllianceGenome:HGNC:683
    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
    GEF3; STA3; XPLN
    Summary
    Rho-like GTPases are involved in a variety of cellular processes, and they are activated by binding GTP and inactivated by conversion of GTP to GDP by their intrinsic GTPase activity. Guanine nucleotide exchange factors (GEFs) accelerate the GTPase activity of Rho GTPases by catalyzing their release of bound GDP. This gene encodes a guanine nucleotide exchange factor, which specifically activates two members of the Rho GTPase family: RHOA and RHOB, both of which have a role in bone cell biology. It has been identified that genetic variation in this gene plays a role in the determination of bone mineral density (BMD), indicating the implication of this gene in postmenopausal osteoporosis. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]
    Expression
    Ubiquitous expression in endometrium (RPKM 17.9), adrenal (RPKM 16.7) and 24 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See ARHGEF3 in Genome Data Viewer
    Location:
    3p14.3
    Exon count:
    22
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 3 NC_000003.12 (56727420..57079268, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 3 NC_060927.1 (56767765..57119568, complement)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 3 NC_000003.11 (56761448..57113296, complement)

    Chromosome 3 - NC_000003.12Genomic Context describing neighboring genes Neighboring gene ELKS/RAB6-interacting/CAST family member 2 Neighboring gene NANOG hESC enhancer GRCh37_chr3:56469501-56470002 Neighboring gene uncharacterized LOC105377099 Neighboring gene Sharpr-MPRA regulatory region 10072 Neighboring gene H3K27ac hESC enhancer GRCh37_chr3:56590646-56591318 Neighboring gene H3K27ac hESC enhancer GRCh37_chr3:56591319-56591990 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr3:56716124-56717068 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 14471 Neighboring gene coiled-coil domain containing 66 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr3:56796980-56797857 Neighboring gene transcription activation suppressor Neighboring gene ATAC-STARR-seq lymphoblastoid active region 19982 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 19983 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 14472 Neighboring gene Sharpr-MPRA regulatory region 9253 Neighboring gene P300/CBP strongly-dependent group 1 enhancer GRCh37_chr3:56886037-56887236 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 14473 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 14474 Neighboring gene Sharpr-MPRA regulatory region 9226 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr3:56949810-56950362 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr3:56950363-56950913 Neighboring gene ARHGEF3 antisense RNA 1 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr3:57040522-57041053 Neighboring gene Sharpr-MPRA regulatory region 6639 Neighboring gene H3K27ac hESC enhancer GRCh37_chr3:57049075-57049840 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr3:57086410-57086910 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr3:57086911-57087411 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr3:57097817-57098598 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 19985 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 14476 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 14477 Neighboring gene BRD4-independent group 4 enhancer GRCh37_chr3:57131244-57132443 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr3:57144939-57145652 Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancers GRCh37_chr3:57162623-57163448 and GRCh37_chr3:57163449-57164275 Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr3:57164276-57165101 Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr3:57165102-57165928 Neighboring gene uncharacterized LOC105377101 Neighboring gene spermatogenesis associated 12 Neighboring gene interleukin 17 receptor D Neighboring gene ribosomal protein L19 pseudogene 2

    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. Identification of a role for the ARHGEF3 gene in postmenopausal osteoporosis. Mullin BH, et al. Am J Hum Genet, 2008 Jun. PMID 18499081, Free PMC Article
    2. ARHGEF3 Associated with Invasion, Metastasis, and Proliferation in Human Osteosarcoma. Gong J, et al. Biomed Res Int, 2021. PMID 34350290, Free PMC Article
    3. Redefining the specificity of phosphoinositide-binding by human PH domain-containing proteins. Singh N, et al. Nat Commun, 2021 Jul 15. PMID 34267198, Free PMC Article
    4. Further genetic evidence suggesting a role for the RhoGTPase-RhoGEF pathway in osteoporosis. Mullin BH, et al. Bone, 2009 Aug. PMID 19427924
    5. ARHGEF3 controls HDACi-induced differentiation via RhoA-dependent pathways in acute myeloid leukemias. D'Amato L, et al. Epigenetics, 2015. PMID 25494542, Free PMC Article

    See all (49) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. ARHGEF3 regulates the stability of ACLY to promote the proliferation of lung cancer.
      Title: ARHGEF3 regulates the stability of ACLY to promote the proliferation of lung cancer.
    2. ARHGEF3 Associated with Invasion, Metastasis, and Proliferation in Human Osteosarcoma.
      Title: ARHGEF3 Associated with Invasion, Metastasis, and Proliferation in Human Osteosarcoma.
    3. Redefining the specificity of phosphoinositide-binding by human PH domain-containing proteins.
      Title: Redefining the specificity of phosphoinositide-binding by human PH domain-containing proteins.
    4. Genetic variants in RET, ARHGEF3 and CTNNAL1, and relevant interaction networks, contribute to the risk of Hirschsprung disease.
      Title: Genetic variants in RET, ARHGEF3 and CTNNAL1, and relevant interaction networks, contribute to the risk of Hirschsprung disease.
    5. The predicted expression of the ARHGEF3 gene in fibroblasts (effect, -0.48; P = 9.8 x 10-04) was associated with Major Depression.
      Title: DNA Methylation Signatures of Depressive Symptoms in Middle-aged and Elderly Persons: Meta-analysis of Multiethnic Epigenome-wide Studies.
    6. This is the first study describing the involvement of XPLN in the regulation of the mTORC2-SPARC axis, and these findings may help uncover regulatory mechanisms mediated by XPLN in idiopathic pulmonary fibrosis
      Title: XPLN is modulated by HDAC inhibitors and negatively regulates SPARC expression by targeting mTORC2 in human lung fibroblasts.
    7. Our findings suggest that increased expression of ARHGEF3 plays a critical oncogenic role in nasopharyngeal carcinoma pathogenesis
      Title: The putative tumor activator ARHGEF3 promotes nasopharyngeal carcinoma cell pathogenesis by inhibiting cellular apoptosis.
    8. Data suggest that modulation of ARHGEF3 gene expression in humans with a promoter-localized SNP plays a role in human megakaryocytes and human platelet function-a finding resulting from the biological follow-up of human genetic studies. Arhgef3 KO mice partially recapitulate the human phenotype.
      Title: SNP in human ARHGEF3 promoter is associated with DNase hypersensitivity, transcript level and platelet function, and Arhgef3 KO mice have increased mean platelet volume.
    9. ARHGEF3 has a crucial role in myeloid differentiation.
      Title: ARHGEF3 controls HDACi-induced differentiation via RhoA-dependent pathways in acute myeloid leukemias.
    10. ARHGEF3 and RHOA are potential regulators of a number of genes in bone cells, with influences on ACTA2 evident in both osteoblast-like and osteoclast-like cells.
      Title: Influence of ARHGEF3 and RHOA knockdown on ACTA2 and other genes in osteoblasts and osteoclasts.
    Submit: New GeneRIF Correction See all GeneRIFs (17)

    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
    A genome- and phenome-wide association study to identify genetic variants influencing platelet count and volume and their pleiotropic effects.
    EBI GWAS Catalog
    A genome-wide association study identifies three loci associated with mean platelet volume.
    EBI GWAS Catalog
    A genome-wide meta-analysis identifies 22 loci associated with eight hematological parameters in the HaemGen consortium.
    EBI GWAS Catalog
    Genome-wide association study of rheumatoid arthritis in Koreans: population-specific loci as well as overlap with European susceptibility loci.
    EBI GWAS Catalog
    GWAS of blood cell traits identifies novel associated loci and epistatic interactions in Caucasian and African-American children.
    EBI GWAS Catalog
    New gene functions in megakaryopoiesis and platelet formation.
    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 Variation Viewer (GRCh37.p13)

    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

    • FLJ98126, MGC118905, DKFZp434F2429

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables guanyl-nucleotide exchange factor activity TAS
    Traceable Author Statement
    more info
    		  
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in Rho protein signal transduction TAS
    Traceable Author Statement
    more info
    		 PubMed 
    involved_in positive regulation of Rho protein signal transduction IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in regulation of small GTPase mediated signal transduction TAS
    Traceable Author Statement
    more info
    		  
    Component Evidence Code Pubs
    located_in cytosol TAS
    Traceable Author Statement
    more info
    		  

    General protein information

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    Preferred Names
    rho guanine nucleotide exchange factor 3
    Names
    59.8 kDA protein
    Rho guanine nucleotide exchange factor (GEF) 3
    RhoGEF protein
    exchange factor found in platelets and leukemic and neuronal tissues, XPLN

    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.

    mRNA and Protein(s)

    1. NM_001128615.2 → NP_001122087.1  rho guanine nucleotide exchange factor 3 isoform 1

      See identical proteins and their annotated locations for NP_001122087.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) encodes the longest isoform (1).
      Source sequence(s)
      AF433662, AL136832, DC334772
      Consensus CDS
      CCDS46854.1
      UniProtKB/TrEMBL
      B7Z6B2
      Related
      ENSP00000341071.4, ENST00000338458.8
      Conserved Domains (2) summary
      cd10572
      Location:348 → 480
      PH_RhoGEF3_XPLN; Rho guanine nucleotide exchange factor 3 Pleckstrin homology (PH) domain
      pfam00621
      Location:158 → 334
      RhoGEF; RhoGEF domain

    2. NM_001128616.2 → NP_001122088.1  rho guanine nucleotide exchange factor 3 isoform 2

      See identical proteins and their annotated locations for NP_001122088.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) lacks several 5' exons but has an alternate 5' exon, as compared to variant 1. The resulting isoform (2) has a distinct and shorter N-terminus, as compared to isoform 1. Isoforms 2 and 4 are the same length but have different N-termini.
      Source sequence(s)
      AB209661, AL136832, DC334437
      Consensus CDS
      CCDS46855.1
      UniProtKB/TrEMBL
      B7Z1T0
      Related
      ENSP00000410922.2, ENST00000413728.6
      Conserved Domains (2) summary
      cd10572
      Location:322 → 454
      PH_RhoGEF3_XPLN; Rho guanine nucleotide exchange factor 3 Pleckstrin homology (PH) domain
      pfam00621
      Location:132 → 308
      RhoGEF; RhoGEF domain

    3. NM_001289698.2 → NP_001276627.1  rho guanine nucleotide exchange factor 3 isoform 4

      See identical proteins and their annotated locations for NP_001276627.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (4) lacks several 5' exons but has an alternate 5' exon, as compared to variant 1. The resulting isoform (4) has a distinct and shorter N-terminus, as compared to isoform 1. Isoforms 2 and 4 are the same length but have different N-termini.
      Source sequence(s)
      AF433662, AK300045, AL136832
      Consensus CDS
      CCDS74948.1
      UniProtKB/TrEMBL
      B7Z6B2, E9PG37
      Related
      ENSP00000420420.1, ENST00000496106.5
      Conserved Domains (2) summary
      cd10572
      Location:322 → 454
      PH_RhoGEF3_XPLN; Rho guanine nucleotide exchange factor 3 Pleckstrin homology (PH) domain
      pfam00621
      Location:132 → 308
      RhoGEF; RhoGEF domain

    4. NM_001377407.1 → NP_001364336.1  rho guanine nucleotide exchange factor 3 isoform 1

      Status: REVIEWED

      Source sequence(s)
      AC097358, AC099327, AC099559, AC099781
      Consensus CDS
      CCDS46854.1
      UniProtKB/TrEMBL
      B7Z6B2
      Conserved Domains (2) summary
      cd10572
      Location:348 → 480
      PH_RhoGEF3_XPLN; Rho guanine nucleotide exchange factor 3 Pleckstrin homology (PH) domain
      pfam00621
      Location:158 → 334
      RhoGEF; RhoGEF domain

    5. NM_001377408.1 → NP_001364337.1  rho guanine nucleotide exchange factor 3 isoform 5

      Status: REVIEWED

      Source sequence(s)
      AC097358, AC099327, AC099559, AC099781
      UniProtKB/TrEMBL
      B7Z6B2
      Conserved Domains (2) summary
      cd10572
      Location:328 → 460
      PH_RhoGEF3_XPLN; Rho guanine nucleotide exchange factor 3 Pleckstrin homology (PH) domain
      pfam00621
      Location:138 → 314
      RhoGEF; RhoGEF domain

    6. NM_001377409.1 → NP_001364338.1  rho guanine nucleotide exchange factor 3 isoform 5

      Status: REVIEWED

      Source sequence(s)
      AC097358, AC099327, AC099559, AC099781
      UniProtKB/TrEMBL
      B7Z6B2
      Conserved Domains (2) summary
      cd10572
      Location:328 → 460
      PH_RhoGEF3_XPLN; Rho guanine nucleotide exchange factor 3 Pleckstrin homology (PH) domain
      pfam00621
      Location:138 → 314
      RhoGEF; RhoGEF domain

    7. NM_001377410.1 → NP_001364339.1  rho guanine nucleotide exchange factor 3 isoform 5

      Status: REVIEWED

      Source sequence(s)
      AC097358, AC099327, AC099559, AC099781
      UniProtKB/TrEMBL
      B7Z6B2
      Conserved Domains (2) summary
      cd10572
      Location:328 → 460
      PH_RhoGEF3_XPLN; Rho guanine nucleotide exchange factor 3 Pleckstrin homology (PH) domain
      pfam00621
      Location:138 → 314
      RhoGEF; RhoGEF domain

    8. NM_001377411.1 → NP_001364340.1  rho guanine nucleotide exchange factor 3 isoform 6

      Status: REVIEWED

      Source sequence(s)
      AC097358, AC099327, AC099559, AC099781
      UniProtKB/TrEMBL
      B7Z6B2
      Conserved Domains (2) summary
      cd10572
      Location:317 → 449
      PH_RhoGEF3_XPLN; Rho guanine nucleotide exchange factor 3 Pleckstrin homology (PH) domain
      pfam00621
      Location:127 → 303
      RhoGEF; RhoGEF domain

    9. NM_001377412.1 → NP_001364341.1  rho guanine nucleotide exchange factor 3 isoform 6

      Status: REVIEWED

      Source sequence(s)
      AC097358, AC099327, AC099559, AC099781
      UniProtKB/TrEMBL
      B7Z6B2
      Conserved Domains (2) summary
      cd10572
      Location:317 → 449
      PH_RhoGEF3_XPLN; Rho guanine nucleotide exchange factor 3 Pleckstrin homology (PH) domain
      pfam00621
      Location:127 → 303
      RhoGEF; RhoGEF domain

    10. NM_001377413.1 → NP_001364342.1  rho guanine nucleotide exchange factor 3 isoform 7

      Status: REVIEWED

      Source sequence(s)
      AC099781
      Conserved Domains (2) summary
      pfam00621
      Location:132 → 308
      RhoGEF; RhoGEF domain
      cl17171
      Location:322 → 403
      PH-like; Pleckstrin homology-like domain

    11. NM_001377414.1 → NP_001364343.1  rho guanine nucleotide exchange factor 3 isoform 8

      Status: REVIEWED

      Source sequence(s)
      AC099559, AC099781
      Conserved Domains (2) summary
      pfam00621
      Location:126 → 302
      RhoGEF; RhoGEF domain
      cl17171
      Location:316 → 397
      PH-like; Pleckstrin homology-like domain

    12. NM_001377415.1 → NP_001364344.1  rho guanine nucleotide exchange factor 3 isoform 9

      Status: REVIEWED

      Source sequence(s)
      AC099559, AC099781
      Consensus CDS
      CCDS93293.1
      UniProtKB/TrEMBL
      C9J586
      Related
      ENSP00000417986.1, ENST00000495373.5
      Conserved Domains (2) summary
      pfam00621
      Location:126 → 302
      RhoGEF; RhoGEF domain
      cl17171
      Location:316 → 410
      PH-like; Pleckstrin homology-like domain

    13. NM_019555.3 → NP_062455.1  rho guanine nucleotide exchange factor 3 isoform 3

      See identical proteins and their annotated locations for NP_062455.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) lacks several 5' exons but has an alternate 5' exon, as compared to variant 1. The resulting isoform (3) has a distinct and shorter N-terminus, as compared to isoform 1.
      Source sequence(s)
      AL136832, DA401228
      Consensus CDS
      CCDS2878.1
      UniProtKB/Swiss-Prot
      A8K5U7, Q4FZB6, Q4QQI5, Q4QQQ0, Q59F00, Q6NUN3, Q7Z4U2, Q7Z5T2, Q9H7T4, Q9NR81
      UniProtKB/TrEMBL
      B7Z1T0
      Related
      ENSP00000296315.3, ENST00000296315.8
      Conserved Domains (2) summary
      cd10572
      Location:316 → 448
      PH_RhoGEF3_XPLN; Rho guanine nucleotide exchange factor 3 Pleckstrin homology (PH) domain
      pfam00621
      Location:126 → 302
      RhoGEF; RhoGEF 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_000003.12 Reference GRCh38.p14 Primary Assembly

      Range
      56727420..57079268 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_017006503.2 → XP_016861992.1  rho guanine nucleotide exchange factor 3 isoform X4

    2. XM_047448224.1 → XP_047304180.1  rho guanine nucleotide exchange factor 3 isoform X1

    3. XM_047448226.1 → XP_047304182.1  rho guanine nucleotide exchange factor 3 isoform X4

    4. XM_047448223.1 → XP_047304179.1  rho guanine nucleotide exchange factor 3 isoform X1

    5. XM_047448222.1 → XP_047304178.1  rho guanine nucleotide exchange factor 3 isoform X1

    6. XM_011533764.2 → XP_011532066.1  rho guanine nucleotide exchange factor 3 isoform X2

      See identical proteins and their annotated locations for XP_011532066.1

      UniProtKB/TrEMBL
      B7Z6B2
      Conserved Domains (2) summary
      cd10572
      Location:334 → 466
      PH_RhoGEF3_XPLN; Rho guanine nucleotide exchange factor 3 Pleckstrin homology (PH) domain
      pfam00621
      Location:144 → 320
      RhoGEF; RhoGEF domain

    7. XM_047448225.1 → XP_047304181.1  rho guanine nucleotide exchange factor 3 isoform X3

    8. XM_047448227.1 → XP_047304183.1  rho guanine nucleotide exchange factor 3 isoform X5

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060927.1 Alternate T2T-CHM13v2.0

      Range
      56767765..57119568 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054346678.1 → XP_054202653.1  rho guanine nucleotide exchange factor 3 isoform X4

    2. XM_054346674.1 → XP_054202649.1  rho guanine nucleotide exchange factor 3 isoform X1

      UniProtKB/TrEMBL
      B7Z7T8

    3. XM_054346677.1 → XP_054202652.1  rho guanine nucleotide exchange factor 3 isoform X4

    4. XM_054346673.1 → XP_054202648.1  rho guanine nucleotide exchange factor 3 isoform X1

      UniProtKB/TrEMBL
      B7Z7T8

    5. XM_054346675.1 → XP_054202650.1  rho guanine nucleotide exchange factor 3 isoform X1

      UniProtKB/TrEMBL
      B7Z7T8

    6. XM_054346672.1 → XP_054202647.1  rho guanine nucleotide exchange factor 3 isoform X1

      UniProtKB/TrEMBL
      B7Z7T8

    7. XM_054346676.1 → XP_054202651.1  rho guanine nucleotide exchange factor 3 isoform X2

    8. XM_054346679.1 → XP_054202654.1  rho guanine nucleotide exchange factor 3 isoform X5

    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q9NR81.1 GenPept UniProtKB/Swiss-Prot:Q9NR81

    Gene LinkOut

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