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... See more...

Aliases for REL Gene

Aliases for REL Gene

  • REL Proto-Oncogene, NF-KB Subunit 2 3 5
  • V-Rel Avian Reticuloendotheliosis Viral Oncogene Homolog 2 3
  • Proto-Oncogene C-Rel 3 4
  • HIVEN86A 2 3
  • C-Rel 2 3
  • Oncogene REL, Avian Reticuloendotheliosis 3
  • I-Rel 2
  • REL 5

External Ids for REL Gene

Previous GeneCards Identifiers for REL Gene

  • GC02P061237
  • GC02P061067
  • GC02P061083
  • GC02P061020
  • GC02P061108
  • GC02P060851

Summaries for REL Gene

Entrez Gene Summary for REL Gene

  • 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]

CIViC Summary for REL Gene

GeneCards Summary for REL Gene

REL (REL Proto-Oncogene, NF-KB Subunit) is a Protein Coding gene. Diseases associated with REL include B-Cell Lymphoma and Primary Mediastinal B-Cell Lymphoma. Among its related pathways are Immune response IL-23 signaling pathway and Toll-Like receptor Signaling Pathways. Gene Ontology (GO) annotations related to this gene include DNA-binding transcription factor activity and chromatin binding. An important paralog of this gene is RELA.

UniProtKB/Swiss-Prot Summary for REL Gene

  • Proto-oncogene that may play a role in differentiation and lymphopoiesis. NF-kappa-B is a pleiotropic transcription factor which is present in almost all cell types and is involved in many biological processed such as inflammation, immunity, differentiation, cell growth, tumorigenesis and apoptosis. NF-kappa-B is a homo- or heterodimeric complex formed by the Rel-like domain-containing proteins RELA/p65, RELB, NFKB1/p105, NFKB1/p50, REL and NFKB2/p52. The dimers bind at kappa-B sites in the DNA of their target genes and the individual dimers have distinct preferences for different kappa-B sites that they can bind with distinguishable affinity and specificity. Different dimer combinations act as transcriptional activators or repressors, respectively. NF-kappa-B is controlled by various mechanisms of post-translational modification and subcellular compartmentalization as well as by interactions with other cofactors or corepressors. NF-kappa-B complexes are held in the cytoplasm in an inactive state complexed with members of the NF-kappa-B inhibitor (I-kappa-B) family. In a conventional activation pathway, I-kappa-B is phosphorylated by I-kappa-B kinases (IKKs) in response to different activators, subsequently degraded thus liberating the active NF-kappa-B complex which translocates to the nucleus. The NF-kappa-B heterodimer RELA/p65-c-Rel is a transcriptional activator.

Gene Wiki entry for REL Gene

No data available for Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for REL Gene

Genomics for REL Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for REL Gene
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around REL on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for REL

Top Transcription factor binding sites by QIAGEN in the REL gene promoter:
  • AP-1
  • AREB6
  • ATF-2
  • c-Jun
  • C/EBPbeta
  • IRF-1
  • IRF-7A
  • Sp1

Genomic Locations for REL Gene

Latest Assembly
chr2:60,881,521-60,931,612
(GRCh38/hg38)
Size:
50,092 bases
Orientation:
Plus strand

Previous Assembly
chr2:61,108,709-61,158,747
(GRCh37/hg19 by Entrez Gene)
Size:
50,039 bases
Orientation:
Plus strand

chr2:61,108,656-61,158,745
(GRCh37/hg19 by Ensembl)
Size:
50,090 bases
Orientation:
Plus strand

Genomic View for REL Gene

Genes around REL on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
REL Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for REL Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for REL Gene

Proteins for REL Gene

  • Protein details for REL Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q04864-REL_HUMAN
    Recommended name:
    Proto-oncogene c-Rel
    Protein Accession:
    Q04864
    Secondary Accessions:
    • Q17RU2
    • Q2PNZ7
    • Q6LDY0

    Protein attributes for REL Gene

    Size:
    619 amino acids
    Molecular mass:
    68520 Da
    Quaternary structure:
    • Component of the NF-kappa-B p65-c-Rel complex. Component of the NF-kappa-B p50-c-Rel complex. Component of the NF-kappa-B p52-c-Rel complex. Homodimer; component of the NF-kappa-B c-Rel-c-Rel complex (By similarity). Interacts with NKIRAS1. Interacts with NFKBIB (By similarity). Interacts with NFKBIE.

    Alternative splice isoforms for REL Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for REL Gene

Post-translational modifications for REL Gene

  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Other Protein References for REL Gene

Antibodies for research

  • Abcam antibodies for REL

No data available for DME Specific Peptides for REL Gene

Domains & Families for REL Gene

Gene Families for REL Gene

HGNC:
Human Protein Atlas (HPA):
  • Cancer-related genes
  • Predicted intracellular proteins
  • Transcription factors

Protein Domains for REL Gene

InterPro:
Blocks:
  • Cell surface receptor IPT/TIG
  • NF-kappa-B/Rel/dorsal family
  • Rel homology

Suggested Antigen Peptide Sequences for REL Gene

GenScript: Design optimal peptide antigens:
  • Proto-oncogene c-Rel (REL_HUMAN)
genes like me logo Genes that share domains with REL: view

No data available for Graphical View of Domain Structure and UniProtKB/Swiss-Prot for REL Gene

Function for REL Gene

Molecular function for REL Gene

UniProtKB/Swiss-Prot Function:
Proto-oncogene that may play a role in differentiation and lymphopoiesis. NF-kappa-B is a pleiotropic transcription factor which is present in almost all cell types and is involved in many biological processed such as inflammation, immunity, differentiation, cell growth, tumorigenesis and apoptosis. NF-kappa-B is a homo- or heterodimeric complex formed by the Rel-like domain-containing proteins RELA/p65, RELB, NFKB1/p105, NFKB1/p50, REL and NFKB2/p52. The dimers bind at kappa-B sites in the DNA of their target genes and the individual dimers have distinct preferences for different kappa-B sites that they can bind with distinguishable affinity and specificity. Different dimer combinations act as transcriptional activators or repressors, respectively. NF-kappa-B is controlled by various mechanisms of post-translational modification and subcellular compartmentalization as well as by interactions with other cofactors or corepressors. NF-kappa-B complexes are held in the cytoplasm in an inactive state complexed with members of the NF-kappa-B inhibitor (I-kappa-B) family. In a conventional activation pathway, I-kappa-B is phosphorylated by I-kappa-B kinases (IKKs) in response to different activators, subsequently degraded thus liberating the active NF-kappa-B complex which translocates to the nucleus. The NF-kappa-B heterodimer RELA/p65-c-Rel is a transcriptional activator.
GENATLAS Biochemistry:
avian reticuloendotheliosis viral (v-rel) oncogene homolog,involved in lymphomagenesis (diffuse large B cell lymphoma)

Phenotypes From GWAS Catalog for REL Gene

Gene Ontology (GO) - Molecular Function for REL Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000978 RNA polymerase II proximal promoter sequence-specific DNA binding IDA 1406630
GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific ISA --
GO:0001228 DNA-binding transcription activator activity, RNA polymerase II-specific IDA 1406630
GO:0003677 DNA binding IEA --
GO:0003700 DNA-binding transcription factor activity IEA,NAS 8423996
genes like me logo Genes that share ontologies with REL: view
genes like me logo Genes that share phenotypes with REL: view

Animal Models for REL Gene

MGI Knock Outs for REL:
  • Rel Rel<tm1Hcl>
  • Rel Rel<tm1Grd>
  • Rel Rel<tm1Brv>
  • Rel Rel<tm1b(EUCOMM)Wtsi>

miRNA for REL Gene

miRTarBase miRNAs that target REL

Transcription Factor Targets for REL Gene

Selected GeneGlobe predicted Target genes for REL

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for REL

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology and HOMER Transcription for REL Gene

Localization for REL Gene

Subcellular locations from UniProtKB/Swiss-Prot for REL Gene

Nucleus.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for REL gene
Compartment Confidence
nucleus 5
cytosol 4
plasma membrane 3
extracellular 3
cytoskeleton 2
mitochondrion 2
endoplasmic reticulum 2
endosome 2
lysosome 2
golgi apparatus 2
peroxisome 1

Gene Ontology (GO) - Cellular Components for REL Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000785 chromatin ISA --
GO:0005634 nucleus IMP 22065573
GO:0005654 nucleoplasm TAS --
GO:0005667 transcription factor complex IEA --
GO:0005737 cytoplasm IEA --
genes like me logo Genes that share ontologies with REL: view

No data available for Subcellular locations from the Human Protein Atlas (HPA) for REL Gene

Pathways & Interactions for REL Gene

PathCards logo

SuperPathways for REL Gene

SuperPathway Contained pathways
1 Toll-Like receptor Signaling Pathways
.42
.33
2 Immune response NFAT in immune response
.56
.56
.52
.52
3 Bacterial infections in CF airways
.78
.78
.46
4 Development A3 receptor signaling
.65
.65
.53
5 Development IGF-1 receptor signaling
.48
.48
.38
genes like me logo Genes that share pathways with REL: view

Pathways by source for REL Gene

46 GeneGo (Thomson Reuters) pathways for REL Gene
  • Apoptosis and survival Anti-apoptotic TNFs/NF-kB/Bcl-2 pathway
  • Apoptosis and survival Anti-apoptotic TNFs/NF-kB/IAP pathway
  • Apoptosis and survival TNFR1 signaling pathway
  • Bacterial infections in CF airways
  • Cytokine production by Th17 cells in CF
3 Qiagen pathways for REL Gene
  • Activation of NF-KappaB by PKR
  • NF-KappaB Family Pathway
  • PKR Pathway
1 Cell Signaling Technology pathway for REL Gene

SIGNOR curated interactions for REL Gene

Activates:
Is activated by:

Gene Ontology (GO) - Biological Process for REL Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006355 regulation of transcription, DNA-templated IEA --
GO:0006357 regulation of transcription by RNA polymerase II IBA 21873635
GO:0006954 inflammatory response IBA 21873635
GO:0007249 I-kappaB kinase/NF-kappaB signaling IEA,IBA 21873635
GO:0010629 negative regulation of gene expression IDA 22065573
genes like me logo Genes that share ontologies with REL: view

Drugs & Compounds for REL Gene

(17) Drugs for REL Gene - From: ApexBio and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Triptolide Investigational Pharma IL-2/MMP-3/MMP7/MMP19 inhibitor 8
JSH-23 Pharma NF-κB inhibitor 0
QNZ (EVP4593) Pharma Potent NF-κB inhibitor 0

(7) Additional Compounds for REL Gene - From: Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs

(3) ApexBio Compounds for REL Gene

Compound Action Cas Number
JSH-23 NF-κB inhibitor 749886-87-1
QNZ (EVP4593) Potent NF-κB inhibitor 545380-34-5
Triptolide IL-2/MMP-3/MMP7/MMP19 inhibitor 38748-32-2
genes like me logo Genes that share compounds with REL: view

Drug products for research

Transcripts for REL Gene

mRNA/cDNA for REL Gene

2 REFSEQ mRNAs :
11 NCBI additional mRNA sequence :
3 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for REL

Alternative Splicing Database (ASD) splice patterns (SP) for REL Gene

No ASD Table

Relevant External Links for REL Gene

GeneLoc Exon Structure for
REL

Expression for REL Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for REL Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for REL Gene

This gene is overexpressed in Whole Blood (x4.4).

Protein differential expression in normal tissues from HIPED for REL Gene

This gene is overexpressed in Peripheral blood mononuclear cells (18.6) and Monocytes (11.4).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for REL Gene



Protein tissue co-expression partners for REL Gene

- Elite partner

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for REL

SOURCE GeneReport for Unigene cluster for REL Gene:

Hs.631886

Evidence on tissue expression from TISSUES for REL Gene

  • Intestine(4.6)
  • Spleen(3.4)
  • Blood(3.2)
  • Lung(3.1)
  • Nervous system(3.1)
  • Skin(2.9)
  • Heart(2.9)
  • Lymph node(2.9)
  • Kidney(2.8)
  • Muscle(2.8)
  • Liver(2.8)
  • Bone marrow(2.8)
  • Pancreas(2.5)
  • Eye(2)
  • Stomach(2)
genes like me logo Genes that share expression patterns with REL: view

Primer products for research

No data available for mRNA Expression by UniProt/SwissProt and Phenotype-based relationships between genes and organs from Gene ORGANizer for REL Gene

Orthologs for REL Gene

This gene was present in the common ancestor of animals.

Orthologs for REL Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia REL 29 30
  • 99.66 (n)
OneToOne
Dog
(Canis familiaris)
Mammalia REL 29 30
  • 89.69 (n)
OneToOne
Cow
(Bos Taurus)
Mammalia REL 29 30
  • 89.46 (n)
OneToOne
Mouse
(Mus musculus)
Mammalia Rel 29 16 30
  • 82.22 (n)
OneToOne
Rat
(Rattus norvegicus)
Mammalia Rel 29
  • 78.27 (n)
Oppossum
(Monodelphis domestica)
Mammalia REL 30
  • 66 (a)
OneToOne
Platypus
(Ornithorhynchus anatinus)
Mammalia REL 30
  • 63 (a)
OneToOne
Chicken
(Gallus gallus)
Aves REL 29 30
  • 62.79 (n)
OneToOne
Lizard
(Anolis carolinensis)
Reptilia REL 30
  • 49 (a)
OneToOne
African clawed frog
(Xenopus laevis)
Amphibia rel-A 29
Zebrafish
(Danio rerio)
Actinopterygii rel 30
  • 43 (a)
OneToOne
Fruit Fly
(Drosophila melanogaster)
Insecta Rel 31
  • 37 (a)
dl 30 31
  • 16 (a)
ManyToMany
Dif 30 31
  • 15 (a)
ManyToMany
Sea Vase
(Ciona intestinalis)
Ascidiacea Cin.770 29
Species where no ortholog for REL was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • Alpha proteobacteria (Wolbachia pipientis)
  • Amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • Baker's yeast (Saccharomyces cerevisiae)
  • Barley (Hordeum vulgare)
  • Beta proteobacteria (Neisseria meningitidis)
  • Bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • Common water flea (Daphnia pulex)
  • Corn (Zea mays)
  • E. coli (Escherichia coli)
  • Filamentous fungi (Aspergillus nidulans)
  • Firmicute Bacteria (Streptococcus pneumoniae)
  • Fission Yeast (Schizosaccharomyces pombe)
  • Green Algae (Chlamydomonas reinhardtii)
  • Honey Bee (Apis mellifera)
  • K. Lactis Yeast (Kluyveromyces lactis)
  • Loblloly Pine (Pinus taeda)
  • Malaria Parasite (Plasmodium falciparum)
  • Medicago Trunc (Medicago Truncatula)
  • Moss (Physcomitrella patens)
  • Orangutan (Pongo pygmaeus)
  • Pig (Sus scrofa)
  • Rainbow Trout (Oncorhynchus mykiss)
  • Rice (Oryza sativa)
  • Rice Blast Fungus (Magnaporthe grisea)
  • Schistosome Parasite (Schistosoma mansoni)
  • Sea Anemone (Nematostella vectensis)
  • Sea Squirt (Ciona savignyi)
  • Sea Urchin (Strongylocentrotus purpuratus)
  • Sorghum (Sorghum bicolor)
  • Soybean (Glycine max)
  • Stem Rust Fungus (Puccinia graminis)
  • Sugarcane (Saccharum officinarum)
  • Thale Cress (Arabidopsis thaliana)
  • Tomato (Lycopersicon esculentum)
  • Toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • Tropical Clawed Frog (Silurana tropicalis)
  • Wheat (Triticum aestivum)
  • Worm (Caenorhabditis elegans)

Evolution for REL Gene

ENSEMBL:
Gene Tree for REL (if available)
TreeFam:
Gene Tree for REL (if available)
Aminode:
Evolutionary constrained regions (ECRs) for REL: view image
Alliance of Genome Resources:
Additional Orthologs for REL

Paralogs for REL Gene

Paralogs for REL Gene

(3) SIMAP similar genes for REL Gene using alignment to 2 proteins:

  • REL_HUMAN
  • Q17RU2_HUMAN
genes like me logo Genes that share paralogs with REL: view

Variants for REL Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for REL Gene

SNP ID Clinical significance and condition Chr 02 pos Variation AA Info Type
871169 Pathogenic: not provided 60,921,756(+) C/A
NM_001291746.2(REL):c.992-7C>A
INTRON
rs140572082 Benign: not provided 60,921,972(+) A/G
NM_001291746.2(REL):c.1201A>G (p.Thr401Ala)
MISSENSE
rs34661029 Benign: not provided 60,921,853(+) C/G
NM_001291746.2(REL):c.1082C>G (p.Pro361Arg)
MISSENSE
rs6729789 Benign: not provided 60,894,435(+) A/G
NM_001291746.2(REL):c.192A>G (p.Thr64=)
SYNONYMOUS
rs751888284 Likely Benign: not provided 60,922,427(+) T/G
NM_001291746.2(REL):c.1656T>G (p.Thr552=)
SYNONYMOUS

dbSNP identifiers (rs#s) for variants without ClinVar clinical significance for REL Gene

All consequence types are included: molecular consequences (e.g. missense, synonymous), and location-based (e.g. intron, upstream).

Structural Variations from Database of Genomic Variants (DGV) for REL Gene

Variant ID Type Subtype PubMed ID
dgv6908n54 CNV gain 21841781
nsv1127728 CNV deletion 24896259
nsv1134866 CNV deletion 24896259
nsv2749 CNV insertion 18451855
nsv524802 CNV loss 19592680
nsv834215 CNV loss 17160897
nsv953131 CNV duplication 24416366

Variation tolerance for REL Gene

Residual Variation Intolerance Score: 28% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 1.84; 34.60% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for REL Gene

Human Gene Mutation Database (HGMD)
REL
SNPedia medical, phenotypic, and genealogical associations of SNPs for
REL
Leiden Open Variation Database (LOVD)
REL

SNP Genotyping and Copy Number Assays for research

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for REL Gene

Disorders for REL Gene

MalaCards: The human disease database

(23) MalaCards diseases for REL Gene - From: COP and GCD

Disorder Aliases PubMed IDs
b-cell lymphoma
  • b-cell lymphocytic neoplasm
primary mediastinal b-cell lymphoma
  • large cell lymphoma of the mediastinum
lymphoma
  • lymphoid cancer
colitis
ulcerative colitis
  • left-sided ulcerative colitis
- elite association - COSMIC cancer census association via MalaCards
Search REL in MalaCards View complete list of genes associated with diseases

Additional Disease Information for REL

Human Genome Epidemiology Navigator
(HuGE)
Atlas
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
Open Targets Platform
Open Targets Platform
genes like me logo Genes that share disorders with REL: view

No data available for UniProtKB/Swiss-Prot and Genatlas for REL Gene

Publications for REL Gene

  1. Activation of multiple NF-kappa B/Rel DNA-binding complexes by tumor necrosis factor. (PMID: 8152812) Beg AA … Baldwin AS (Oncogene 1994) 3 4 22
  2. Genome-wide meta-analysis of psoriatic arthritis identifies susceptibility locus at REL. (PMID: 22170493) Ellinghaus E … Franke A (The Journal of investigative dermatology 2012) 3 40
  3. Genome-wide association identifies multiple ulcerative colitis susceptibility loci. (PMID: 20228799) McGovern DP … Seielstad M (Nature genetics 2010) 3 40
  4. Variation at the NFATC2 locus increases the risk of thiazolidinedione-induced edema in the Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) study. (PMID: 20628086) Bailey SD … DREAM investigators (Diabetes care 2010) 3 40
  5. Genome-wide association study meta-analysis identifies seven new rheumatoid arthritis risk loci. (PMID: 20453842) Stahl EA … Plenge RM (Nature genetics 2010) 3 40

Products for REL Gene

  • Addgene plasmids for REL

Sources for REL Gene