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    REL REL proto-oncogene, NF-kB subunit [ Homo sapiens (human) ]

    Gene ID: 5966, updated on 10-Dec-2024

    Summary

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    Official Symbol
    RELprovided by HGNC
    Official Full Name
    REL proto-oncogene, NF-kB subunitprovided by HGNC
    Primary source
    HGNC:HGNC:9954
    See related
    Ensembl:ENSG00000162924 MIM:164910; AllianceGenome:HGNC:9954
    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
    C-Rel; IMD92; HIVEN86A
    Summary
    This gene encodes a protein that belongs to the Rel homology domain/immunoglobulin-like fold, plexin, transcription factor (RHD/IPT) family. Members of this family regulate genes involved in apoptosis, inflammation, the immune response, and oncogenic processes. This proto-oncogene plays a role in the survival and proliferation of B lymphocytes. Mutation or amplification of this gene is associated with B-cell lymphomas, including Hodgkin's lymphoma. Single nucleotide polymorphisms in this gene are associated with susceptibility to ulcerative colitis and rheumatoid arthritis. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Apr 2014]
    Expression
    Ubiquitous expression in bone marrow (RPKM 13.2), appendix (RPKM 8.6) and 25 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See REL in Genome Data Viewer
    Location:
    2p16.1
    Exon count:
    12
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 2 NC_000002.12 (60881574..60931612)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 2 NC_060926.1 (60887420..60937448)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 2 NC_000002.11 (61108709..61158747)

    Chromosome 2 - NC_000002.12Genomic Context describing neighboring genes Neighboring gene ATAC-STARR-seq lymphoblastoid active region 15819 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 15820 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 15821 Neighboring gene RNA, 7SL, cytoplasmic 632, pseudogene Neighboring gene ATAC-STARR-seq lymphoblastoid active region 15822 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 15823 Neighboring gene REL divergent transcript Neighboring gene ribosomal protein L21 pseudogene 33 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 15824 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 15825 Neighboring gene H3K27ac hESC enhancer GRCh37_chr2:61108452-61109121 Neighboring gene Sharpr-MPRA regulatory region 13586 Neighboring gene RNA, U4 small nuclear 51, pseudogene Neighboring gene ribosomal protein S12 pseudogene 3 Neighboring gene non-POU domain containing, octamer-binding pseudogene 2

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Bibliography

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    Related articles in PubMed

    1. Deletion analysis and alternative splicing define a transactivation inhibitory domain in human oncoprotein REL. Leeman JR, et al. Oncogene, 2008 Dec 4. PMID 18695674, Free PMC Article
    2. Chromosomal and gene amplification in diffuse large B-cell lymphoma. Rao PH, et al. Blood, 1998 Jul 1. PMID 9639522
    3. Gains of REL in primary mediastinal B-cell lymphoma coincide with nuclear accumulation of REL protein. Weniger MA, et al. Genes Chromosomes Cancer, 2007 Apr. PMID 17243160
    4. Protease inhibitors block lipopolysaccharide induction of tissue factor gene expression in human monocytic cells by preventing activation of c-Rel/p65 heterodimers. Mackman N. J Biol Chem, 1994 Oct 21. PMID 7929355
    5. Association of REL Polymorphism with Cow's Milk Proteins Allergy in Pediatric Algerian Population. Rahmoun N, et al. Fetal Pediatr Pathol, 2018 Feb. PMID 29336650

    See all (207) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. REL and BHLHE40 Variants Are Associated with IL-12 and IL-10 Responses and Tuberculosis Risk.
      Title: REL and BHLHE40 Variants Are Associated with IL-12 and IL-10 Responses and Tuberculosis Risk.
    2. METTL3 restrains papillary thyroid cancer progression via m(6)A/c-Rel/IL-8-mediated neutrophil infiltration.
      Title: METTL3 restrains papillary thyroid cancer progression via m(6)A/c-Rel/IL-8-mediated neutrophil infiltration.
    3. NF-kappaB c-Rel Is Dispensable for the Development but Is Required for the Cytotoxic Function of NK Cells.
      Title: NF-κB c-Rel Is Dispensable for the Development but Is Required for the Cytotoxic Function of NK Cells.
    4. Association study between vitiligo and autoimmune-related genes CYP27B1, REL, TNFAIP3, IL2 and IL21.
      Title: Association study between vitiligo and autoimmune-related genes CYP27B1, REL, TNFAIP3, IL2 and IL21.
    5. Pro-survival and anti-inflammatory roles of NF-kappaB c-Rel in the Parkinson's disease models.
      Title: Pro-survival and anti-inflammatory roles of NF-κB c-Rel in the Parkinson's disease models.
    6. Constitutive expression of c-REL in uveal melanoma patients: correlation with clinicopathological parameters and patient outcome.
      Title: Constitutive expression of c-REL in uveal melanoma patients: correlation with clinicopathological parameters and patient outcome.
    7. A Matter of Choice: Inhibition of c-Rel Shifts Neuronal to Oligodendroglial Fate in Human Stem Cells.
      Title: A Matter of Choice: Inhibition of c-Rel Shifts Neuronal to Oligodendroglial Fate in Human Stem Cells.
    8. Human galectin-16 has a pseudo ligand binding site and plays a role in regulating c-Rel-mediated lymphocyte activity.
      Title: Human galectin-16 has a pseudo ligand binding site and plays a role in regulating c-Rel-mediated lymphocyte activity.
    9. The c-Rel-c-Myc axis controls metabolism and proliferation of human T leukemia cells.
      Title: The c-Rel-c-Myc axis controls metabolism and proliferation of human T leukemia cells.
    10. c-Rel is involved in G2/M phase regulation, prevention of polyploidy and, consequently, chromosomal stability in human melanoma cells
      Title: c-Rel is a cell cycle modulator in human melanoma cells.
    Submit: New GeneRIF Correction See all GeneRIFs (83)

    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
    Immunodeficiency 92
    MedGen: C5562039 OMIM: 619652 GeneReviews: Not available
    		not available

    EBI GWAS Catalog

    Description
    A genome-wide association study identifies new psoriasis susceptibility loci and an interaction between HLA-C and ERAP1.
    EBI GWAS Catalog
    A genome-wide association study of Hodgkin's lymphoma identifies new susceptibility loci at 2p16.1 (REL), 8q24.21 and 10p14 (GATA3).
    EBI GWAS Catalog
    A genome-wide scan of Ashkenazi Jewish Crohn's disease suggests novel susceptibility loci.
    EBI GWAS Catalog
    A meta-analysis of Hodgkin lymphoma reveals 19p13.3 TCF3 as a novel susceptibility locus.
    EBI GWAS Catalog
    Genetics of rheumatoid arthritis contributes to biology and drug discovery.
    EBI GWAS Catalog
    Genome-wide association identifies multiple ulcerative colitis susceptibility loci.
    EBI GWAS Catalog
    Genome-wide association study meta-analysis identifies seven new rheumatoid arthritis risk loci.
    EBI GWAS Catalog
    Genome-wide meta-analysis increases to 71 the number of confirmed Crohn's disease susceptibility loci.
    EBI GWAS Catalog
    Genome-wide meta-analysis of psoriatic arthritis identifies susceptibility locus at REL.
    EBI GWAS Catalog
    Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease.
    EBI GWAS Catalog
    Multiple common variants for celiac disease influencing immune gene expression.
    EBI GWAS Catalog
    REL, encoding a member of the NF-kappaB family of transcription factors, is a newly defined risk locus for rheumatoid arthritis.
    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)

    HIV-1 interactions

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    Protein interactions

    Protein Gene Interaction Pubs
    Tat tat HIV-1 Tat specifically associates with c-Rel promoter to downregulate c-Rel expression in T cells PubMed
    tat HIV-1 Tat upregulates c-rel and RelA transcription factor binding to the CD28-responsive element in the IL-8 promoter, leading to super-induction of IL-8 PubMed
    tat HIV-1 Tat interacts with the cooperative rel/AP1 complex, downregulating its transactivation activity and leading to a decrease in IL-2 gene transcription PubMed
    tat The c-rel protein is a strong activator of HIV-1 gene expression suggesting a possible interaction with HIV-1 Tat, however results from co-expression experiments did not detect synergy with Tat activation PubMed
    Vpr vpr Overexpression of REL is induced by HIV-1 Vpr in the transfected 293T 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 DNA-binding transcription activator activity, RNA polymerase II-specific IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables DNA-binding transcription factor activity NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    enables DNA-binding transcription factor activity, RNA polymerase II-specific IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables DNA-binding transcription factor activity, RNA polymerase II-specific ISA
    Inferred from Sequence Alignment
    more info
    		  
    enables RNA polymerase II cis-regulatory region sequence-specific DNA binding IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables RNA polymerase II cis-regulatory region sequence-specific DNA binding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in canonical NF-kappaB signal transduction IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in inflammatory response IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in innate immune response IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in negative regulation of gene expression IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in negative regulation of interferon-beta production IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in non-canonical NF-kappaB signal transduction IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in positive regulation of canonical NF-kappaB signal transduction IEP
    Inferred from Expression Pattern
    more info
    		 PubMed 
    involved_in positive regulation of transcription by RNA polymerase II IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in positive regulation of transcription by RNA polymerase II IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in positive regulation of transcription by RNA polymerase II NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    involved_in response to cytokine IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    Component Evidence Code Pubs
    part_of NF-kappaB complex NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    located_in chromatin ISA
    Inferred from Sequence Alignment
    more info
    		  
    is_active_in cytoplasm IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in cytosol TAS
    Traceable Author Statement
    more info
    		  
    located_in nucleoplasm TAS
    Traceable Author Statement
    more info
    		  
    is_active_in nucleus IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in nucleus IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 

    General protein information

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    Preferred Names
    proto-oncogene c-Rel
    Names
    oncogene REL, avian reticuloendotheliosis
    v-rel avian reticuloendotheliosis viral oncogene homolog

    NCBI Reference Sequences (RefSeq)

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    NEW Try the new Transcript table

    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_001291746.2 → NP_001278675.1  proto-oncogene c-Rel isoform 2

      See identical proteins and their annotated locations for NP_001278675.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) lacks an in-frame exon in the central coding region compared to variant 1. The encoded isoform (2) is shorter than isoform 1.
      Source sequence(s)
      AC010733, BC143885, BG036646, HY123671
      Consensus CDS
      CCDS74515.1
      UniProtKB/TrEMBL
      B4E1P2
      Related
      ENSP00000377989.4, ENST00000394479.4
      Conserved Domains (2) summary
      cd07933
      Location:8 → 179
      RHD-n_c-Rel; N-terminal sub-domain of the Rel homology domain (RHD) of c-Rel
      pfam16179
      Location:187 → 282
      RHD_dimer; Rel homology dimerisation domain

    2. NM_002908.4 → NP_002899.1  proto-oncogene c-Rel isoform 1

      See identical proteins and their annotated locations for NP_002899.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1).
      Source sequence(s)
      AC010733, BG036646, HY123671, X75042
      Consensus CDS
      CCDS1864.1
      UniProtKB/Swiss-Prot
      Q04864, Q17RU2, Q2PNZ7, Q6LDY0
      UniProtKB/TrEMBL
      B4E1P2
      Related
      ENSP00000295025.7, ENST00000295025.12
      Conserved Domains (2) summary
      cd07933
      Location:8 → 179
      RHD-n_c-Rel; N-terminal sub-domain of the Rel homology domain (RHD) of c-Rel
      pfam16179
      Location:187 → 282
      RHD_dimer; Rel homology dimerization 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_000002.12 Reference GRCh38.p14 Primary Assembly

      Range
      60881574..60931612
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_017004627.3 → XP_016860116.1  proto-oncogene c-Rel isoform X1

      UniProtKB/TrEMBL
      A0A8V8TMU9, A0A8V8TPL7
      Related
      ENSP00000514191.1, ENST00000699191.1

    2. XM_011533010.4 → XP_011531312.1  proto-oncogene c-Rel isoform X2

      UniProtKB/TrEMBL
      B4E1P2
      Conserved Domains (2) summary
      pfam16179
      Location:89 → 184
      RHD_dimer; Rel homology dimerization domain
      cl08275
      Location:2 → 81
      RHD-n; N-terminal sub-domain of the Rel homology domain (RHD)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060926.1 Alternate T2T-CHM13v2.0

      Range
      60887420..60937448
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054343267.1 → XP_054199242.1  proto-oncogene c-Rel isoform X1

      UniProtKB/TrEMBL
      A0A8V8TMU9, A0A8V8TPL7

    2. XM_054343268.1 → XP_054199243.1  proto-oncogene c-Rel isoform X2

      UniProtKB/TrEMBL
      B4E1P2
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q04864.1 GenPept UniProtKB/Swiss-Prot:Q04864

    Gene LinkOut

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

    Chemical Information
    Molecular Biology Databases
    Research Materials
    Tools