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

Summary

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

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_000002.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: 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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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

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

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

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

SHGC-80607 (e-PCR)
- UniSTS:102178

RH70902 (e-PCR)
- UniSTS:71477

D16S325 (e-PCR)
- UniSTS:147089

SHGC-35444 (e-PCR)
- UniSTS:5840

Rel (e-PCR), detects polymorphism
- UniSTS:144337

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)

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
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

NC_000002.12 Reference GRCh38.p14 Primary Assembly

Range

60881574..60931612

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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

UniProtKB/TrEMBL

A0A8V8TMU9, A0A8V8TPL7

Related

ENSP00000514191.1, ENST00000699191.1
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)