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    RAG2 recombination activating 2 [ Homo sapiens (human) ]

    Gene ID: 5897, updated on 28-Oct-2024

    Summary

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    Official Symbol
    RAG2provided by HGNC
    Official Full Name
    recombination activating 2provided by HGNC
    Primary source
    HGNC:HGNC:9832
    See related
    Ensembl:ENSG00000175097 MIM:179616; AllianceGenome:HGNC:9832
    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
    RAG-2
    Summary
    This gene encodes a protein that is involved in the initiation of V(D)J recombination during B and T cell development. This protein forms a complex with the product of the adjacent recombination activating gene 1, and this complex can form double-strand breaks by cleaving DNA at conserved recombination signal sequences. The recombination activating gene 1 component is thought to contain most of the catalytic activity, while the N-terminal of the recombination activating gene 2 component is thought to form a six-bladed propeller in the active core that serves as a binding scaffold for the tight association of the complex with DNA. A C-terminal plant homeodomain finger-like motif in this protein is necessary for interactions with chromatin components, specifically with histone H3 that is trimethylated at lysine 4. Mutations in this gene cause Omenn syndrome, a form of severe combined immunodeficiency associated with autoimmune-like symptoms. [provided by RefSeq, Jul 2008]
    Expression
    Restricted expression toward thyroid (RPKM 16.6) See more
    Orthologs
    mouse all
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    Genomic context

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    See RAG2 in Genome Data Viewer
    Location:
    11p12
    Exon count:
    2
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 11 NC_000011.10 (36590996..36598236, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 11 NC_060935.1 (36734171..36741410, complement)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 11 NC_000011.9 (36613493..36619786, complement)

    Chromosome 11 - NC_000011.10Genomic Context describing neighboring genes Neighboring gene CDK7 strongly-dependent group 2 enhancer GRCh37_chr11:36522348-36523547 Neighboring gene TNF receptor associated factor 6 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 4633 Neighboring gene recombination activating 1 Neighboring gene NANOG hESC enhancer GRCh37_chr11:36603130-36603633 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 4634 Neighboring gene intraflagellar transport associated protein Neighboring gene uncharacterized LOC107984325 Neighboring gene transforming acidic coiled-coil containing protein 3 pseudogene

    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. From variant of uncertain significance to likely pathogenic in two siblings with atypical RAG2 Deficiency: a case report and review of the literature. Taghizadeh Mortezaei N, et al. BMC Pediatr, 2024 Feb 13. PMID 38350907, Free PMC Article
    2. Spatio-temporal regulation of RAG2 following genotoxic stress. Rodgers W, et al. DNA Repair (Amst), 2015 Mar. PMID 25625798, Free PMC Article
    3. Detection of RAG mutations and prenatal diagnosis in families presenting with either T-B- severe combined immunodeficiency or Omenn's syndrome. Tabori U, et al. Clin Genet, 2004 Apr. PMID 15025726
    4. Effect of CpG methylation on RAG1/RAG2 reactivity: implications of direct and indirect mechanisms for controlling V(D)J cleavage. Nakase H, et al. EMBO Rep, 2003 Aug. PMID 12897800, Free PMC Article
    5. A novel homozygous mutation in recombination activating gene 2 in 2 relatives with different clinical phenotypes: Omenn syndrome and hyper-IgM syndrome. Chou J, et al. J Allergy Clin Immunol, 2012 Dec. PMID 22841008, Free PMC Article

    See all (105) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. From variant of uncertain significance to likely pathogenic in two siblings with atypical RAG2 Deficiency: a case report and review of the literature.
      Title: From variant of uncertain significance to likely pathogenic in two siblings with atypical RAG2 Deficiency: a case report and review of the literature.
    2. Heterogeneity in RAG1 and RAG2 deficiency: 35 cases from a single-centre.
      Title: Heterogeneity in RAG1 and RAG2 deficiency: 35 cases from a single-centre.
    3. A novel loss of function mutation in the PHD domain of the RAG2 gene, affecting zinc-binding affinity.
      Title: A novel loss of function mutation in the PHD domain of the RAG2 gene, affecting zinc-binding affinity.
    4. Hypomorphic RAG deficiency: impact of disease burden on survival and thymic recovery argues for early diagnosis and HSCT.
      Title: Hypomorphic RAG deficiency: impact of disease burden on survival and thymic recovery argues for early diagnosis and HSCT.
    5. Rag2(-/-) accelerates lipofuscin accumulation in the brain: Implications for human stem cell brain transplantation studies.
      Title: Rag2(-/-) accelerates lipofuscin accumulation in the brain: Implications for human stem cell brain transplantation studies.
    6. Partial RAG deficiency in humans induces dysregulated peripheral lymphocyte development and humoral tolerance defect with accumulation of T-bet(+) B cells.
      Title: Partial RAG deficiency in humans induces dysregulated peripheral lymphocyte development and humoral tolerance defect with accumulation of T-bet(+) B cells.
    7. RAG2 abolishes RAG1 aggregation to facilitate V(D)J recombination.
      Title: RAG2 abolishes RAG1 aggregation to facilitate V(D)J recombination.
    8. Survival-Assured Liver Injury Preconditioning (SALIC) Enables Robust Expansion of Human Hepatocytes in Fah(-/-) Rag2(-/-) IL2rg(-/-) Rats.
      Title: Survival-Assured Liver Injury Preconditioning (SALIC) Enables Robust Expansion of Human Hepatocytes in Fah(-/-) Rag2(-/-) IL2rg(-/-) Rats.
    9. Clinical Manifestations, Mutational Analysis, and Immunological Phenotype in Patients with RAG1/2 Mutations: First Cases Series from Mexico and Description of Two Novel Mutations.
      Title: Clinical Manifestations, Mutational Analysis, and Immunological Phenotype in Patients with RAG1/2 Mutations: First Cases Series from Mexico and Description of Two Novel Mutations.
    10. The Interplay Between Chromatin Architecture and Lineage-Specific Transcription Factors and the Regulation of Rag Gene Expression.
      Title: The Interplay Between Chromatin Architecture and Lineage-Specific Transcription Factors and the Regulation of Rag Gene Expression.
    Submit: New GeneRIF Correction See all GeneRIFs (67)

    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
    Combined immunodeficiency with skin granulomas
    MedGen: C2673536 OMIM: 233650 GeneReviews: Not available
    		not available
    Histiocytic medullary reticulosis
    MedGen: C2700553 OMIM: 603554 GeneReviews: Not available
    		not available
    Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-positive
    MedGen: C1832322 OMIM: 601457 GeneReviews: Not available
    		not available

    EBI GWAS Catalog

    Description
    Genetics of rheumatoid arthritis contributes to biology and drug discovery.
    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

    HIV-1 interactions

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    Protein interactions

    Protein Gene Interaction Pubs
    Vif vif HIV-1 Vif downregulates the expression of recombination activating gene 2 (RAG2) in Vif-expression T cells PubMed

    Go to the HIV-1, Human Interaction Database

    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 chromatin binding ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    enables methylated histone binding ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    enables phosphatidylinositol binding ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    enables phosphatidylinositol-3,4,5-trisphosphate binding ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    enables phosphatidylinositol-3,4-bisphosphate binding ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    enables phosphatidylinositol-3,5-bisphosphate binding ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    enables phosphatidylinositol-4,5-bisphosphate binding ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    enables sequence-specific DNA binding IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables zinc ion binding ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    Process Evidence Code Pubs
    involved_in B cell differentiation ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in B cell homeostatic proliferation IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in B cell lineage commitment IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in DN2 thymocyte differentiation IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in T cell differentiation in thymus ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in T cell lineage commitment IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in V(D)J recombination IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in V(D)J recombination ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in chromatin organization IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in defense response to bacterium IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in mature B cell differentiation involved in immune response IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in negative regulation of T cell differentiation in thymus IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in organ growth IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in positive regulation of organ growth IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in pre-B cell allelic exclusion ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    Component Evidence Code Pubs
    part_of DNA recombinase complex IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in nucleoplasm TAS
    Traceable Author Statement
    more info
    		  

    General protein information

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    Preferred Names
    V(D)J recombination-activating protein 2
    Names
    recombination activating gene 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_007573.1 RefSeqGene

      Range
      4958..11294
      Download
      GenBank, FASTA, Sequence Viewer (Graphics), LRG_99

    mRNA and Protein(s)

    1. NM_000536.4 → NP_000527.2  V(D)J recombination-activating protein 2

      See identical proteins and their annotated locations for NP_000527.2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the shortest transcript. Variants 1, 3 and 4 encode the same protein.
      Source sequence(s)
      AK292664, AW058148, BC022397, DB146077
      Consensus CDS
      CCDS7903.1
      UniProtKB/Swiss-Prot
      A8K9E9, P55895, Q8TBL4
      Related
      ENSP00000308620.4, ENST00000311485.8
      Conserved Domains (2) summary
      pfam03089
      Location:51 → 388
      RAG2; Recombination activating protein 2
      pfam13341
      Location:414 → 491
      RAG2_PHD; RAG2 PHD domain

    2. NM_001243785.2 → NP_001230714.1  V(D)J recombination-activating protein 2

      See identical proteins and their annotated locations for NP_001230714.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) includes an alternate exon in the 5' UTR compared to variant 1. Variants 1, 3 and 4 encode the same protein.
      Source sequence(s)
      AK292664, AW058148, BC022397, DB124002
      Consensus CDS
      CCDS7903.1
      UniProtKB/Swiss-Prot
      A8K9E9, P55895, Q8TBL4
      Related
      ENSP00000436895.2, ENST00000527033.6
      Conserved Domains (2) summary
      pfam03089
      Location:51 → 388
      RAG2; Recombination activating protein 2
      pfam13341
      Location:414 → 491
      RAG2_PHD; RAG2 PHD domain

    3. NM_001243786.2 → NP_001230715.1  V(D)J recombination-activating protein 2

      See identical proteins and their annotated locations for NP_001230715.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (4) includes an alternate exon in the 5' UTR compared to variant 1. Variants 1, 3 and 4 encode the same protein.
      Source sequence(s)
      AC139427, AK292664, AW058148, BC022397, DB143931
      Consensus CDS
      CCDS7903.1
      UniProtKB/Swiss-Prot
      A8K9E9, P55895, Q8TBL4
      Related
      ENSP00000432174.2, ENST00000532616.2
      Conserved Domains (2) summary
      pfam03089
      Location:51 → 388
      RAG2; Recombination activating protein 2
      pfam13341
      Location:414 → 491
      RAG2_PHD; RAG2 PHD 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_000011.10 Reference GRCh38.p14 Primary Assembly

      Range
      36590996..36598236 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_047427385.1 → XP_047283341.1  V(D)J recombination-activating protein 2 isoform X1

      UniProtKB/Swiss-Prot
      A8K9E9, P55895, Q8TBL4

    2. XM_047427386.1 → XP_047283342.1  V(D)J recombination-activating protein 2 isoform X1

      UniProtKB/Swiss-Prot
      A8K9E9, P55895, Q8TBL4

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060935.1 Alternate T2T-CHM13v2.0

      Range
      36734171..36741410 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054369591.1 → XP_054225566.1  V(D)J recombination-activating protein 2 isoform X1

      UniProtKB/Swiss-Prot
      A8K9E9, P55895, Q8TBL4

    Suppressed Reference Sequence(s)

    The following Reference Sequences have been suppressed. Explain

    1. NR_033666.1: Suppressed sequence

      Description
      NR_033666.1: This RefSeq was temporarily suppressed because currently there is not sufficient data to support this transcript.
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    P55895.1 GenPept UniProtKB/Swiss-Prot:P55895

    Gene LinkOut

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

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