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

Gene ID: 5966, updated on 2-Nov-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
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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

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. 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)

Genotypes

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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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
    A0A8V8TPL7

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

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.

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