RELA

RELA proto-oncogene, NF-kB subunit, the group of IPT domain containing|NF-kappa B complex subunits

Basic information

Region (hg38): 11:65653598-65663090

Previous symbols: [ "NFKB3" ]

Links

ENSG00000173039 ∙ NCBI:5970 ∙ OMIM:164014 ∙ HGNC:9955 ∙ Uniprot:Q04206 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• hereditary pediatric Behçet-like disease (Supportive), mode of inheritance: AD
• mucocutaneous ulceration, chronic (Limited), mode of inheritance: AD
• mucocutaneous ulceration, chronic (Strong), mode of inheritance: AD
• combined immunodeficiency due to RELA haploinsufficiency (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Autoinflammatory disease, familial, Behcet-like 3	AD	Allergy/Immunology/Infectious	Individuals can have chronic mucocutaneous ulcerations, and medical management (with a tumor necrosis factor inhibitor) has been described as beneficial	Allergy/Immunology/Infectious	28600438

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the RELA gene.

• not provided (260 variants)
• Inborn genetic diseases (11 variants)
• Mucocutaneous ulceration, chronic (9 variants)
• not specified (2 variants)
• RELA-related condition (1 variants)
• Childhood-onset schizophrenia (1 variants)
• Mucocutaneous ulceration (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the RELA gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			3	74	6	83
missense		1	91	6		98
nonsense	7	3				10
start loss						0
frameshift	4	1	3	1	1	10
inframe indel			4			4
splice donor/acceptor (+/-2bp)						0
splice region			8	6	2	16
non coding		1	3	36	6	46
Total	11	6	104	117	13

Highest pathogenic variant AF is 0.00000657

Variants in RELA

This is a list of pathogenic ClinVar variants found in the RELA region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
11-65654379-T-C			Uncertain significance (Aug 09, 2022)
11-65654381-G-A		RELA-related disorder	Benign (Jan 25, 2024)
11-65654389-T-A			Uncertain significance (Dec 09, 2023)
11-65654390-C-T			Likely benign (Oct 20, 2023)
11-65654401-G-A			Likely benign (Apr 01, 2021)
11-65654408-G-T			Uncertain significance (Nov 01, 2022)
11-65654416-T-C			Uncertain significance (Jan 12, 2024)
11-65654421-G-A			Uncertain significance (Nov 27, 2023)
11-65654422-C-T		not specified	Uncertain significance (Oct 13, 2023)
11-65654425-T-C			Uncertain significance (Nov 18, 2023)
11-65654425-TGGA-T			Uncertain significance (Oct 29, 2023)
11-65654426-G-A			Likely benign (Jan 25, 2023)
11-65654427-G-C		not specified	Uncertain significance (Jun 01, 2023)
11-65654438-T-A			Uncertain significance (Jan 28, 2024)
11-65654447-T-C			Likely benign (Aug 09, 2022)
11-65654452-G-T		not specified	Conflicting classifications of pathogenicity (Jan 22, 2024)
11-65654453-G-A			Likely benign (Dec 07, 2023)
11-65654460-T-C			Uncertain significance (Oct 14, 2023)
11-65654471-C-T			Likely benign (Jan 04, 2024)
11-65654482-G-A			Likely benign (Jun 17, 2023)
11-65654493-G-C			Uncertain significance (Feb 01, 2022)
11-65654495-T-C		RELA-related disorder	Likely benign (Nov 07, 2023)
11-65654497-G-C			Uncertain significance (Jul 16, 2022)
11-65654497-G-T		not specified	Uncertain significance (Jan 26, 2024)
11-65654500-C-CG			Uncertain significance (Jul 14, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
RELA	protein_coding	protein_coding	ENST00000406246	11	9499

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.999	0.000517	125293	0	5	125298	0.0000200

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.45	208	334	0.623	0.0000208	3514
Missense in Polyphen		41	127.77	0.3209		1334
Synonymous	-0.833	145	133	1.09	0.00000774	1176
Loss of Function	4.56	1	26.2	0.0382	0.00000163	261

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000324	0.0000324
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.0000487	0.0000463
European (Non-Finnish)	0.0000277	0.0000265
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: NF-kappa-B is a pleiotropic transcription factor present in almost all cell types and is the endpoint of a series of signal transduction events that are initiated by a vast array of stimuli related to many biological processes 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 heterodimeric RELA- NFKB1 complex appears to be most abundant one. 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. The NF-kappa-B heterodimeric RELA-NFKB1 and RELA-REL complexes, for instance, function as transcriptional activators. 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 inhibitory effect of I-kappa-B on NF-kappa-B through retention in the cytoplasm is exerted primarily through the interaction with RELA. RELA shows a weak DNA-binding site which could contribute directly to DNA binding in the NF-kappa-B complex. Beside its activity as a direct transcriptional activator, it is also able to modulate promoters accessibility to transcription factors and thereby indirectly regulate gene expression. Associates with chromatin at the NF-kappa-B promoter region via association with DDX1. Essential for cytokine gene expression in T-cells (PubMed:15790681). The NF-kappa-B homodimeric RELA-RELA complex appears to be involved in invasin- mediated activation of IL-8 expression. {ECO:0000269|PubMed:10928981, ECO:0000269|PubMed:12748188, ECO:0000269|PubMed:15790681, ECO:0000269|PubMed:17000776, ECO:0000269|PubMed:17620405, ECO:0000269|PubMed:19058135, ECO:0000269|PubMed:19103749, ECO:0000269|PubMed:20547752}.
• Disease: DISEASE: Note=A chromosomal aberration involving C11orf95 is found in more than two-thirds of supratentorial ependymomas. Translocation with C11orf95 produces a C11orf95-RELA fusion protein. C11orf95-RELA translocations are potent oncogenes that probably transform neural stem cells by driving an aberrant NF- kappa-B transcription program (PubMed:24553141). {ECO:0000269|PubMed:24553141}.
• Pathway: PI3K-Akt signaling pathway - Homo sapiens (human);Chronic myeloid leukemia - Homo sapiens (human);Relaxin signaling pathway - Homo sapiens (human);Adipocytokine signaling pathway - Homo sapiens (human);T cell receptor signaling pathway - Homo sapiens (human);B cell receptor signaling pathway - Homo sapiens (human);Kaposi,s sarcoma-associated herpesvirus infection - Homo sapiens (human);Pertussis - Homo sapiens (human);Salmonella infection - Homo sapiens (human);Legionellosis - Homo sapiens (human);Neurotrophin signaling pathway - Homo sapiens (human);Insulin resistance - Homo sapiens (human);Non-alcoholic fatty liver disease (NAFLD) - Homo sapiens (human);AGE-RAGE signaling pathway in diabetic complications - Homo sapiens (human);HIF-1 signaling pathway - Homo sapiens (human);Small cell lung cancer - Homo sapiens (human);Influenza A - Homo sapiens (human);Acute myeloid leukemia - Homo sapiens (human);Inflammatory bowel disease (IBD) - Homo sapiens (human);TNF signaling pathway - Homo sapiens (human);Chemokine signaling pathway - Homo sapiens (human);HTLV-I infection - Homo sapiens (human);Amoebiasis - Homo sapiens (human);Mitophagy - animal - Homo sapiens (human);Cytosolic DNA-sensing pathway - Homo sapiens (human);Epithelial cell signaling in Helicobacter pylori infection - Homo sapiens (human);Prostate cancer - Homo sapiens (human);Longevity regulating pathway - Homo sapiens (human);Chagas disease (American trypanosomiasis) - Homo sapiens (human);Toll-like receptor signaling pathway - Homo sapiens (human);NOD-like receptor signaling pathway - Homo sapiens (human);cAMP signaling pathway - Homo sapiens (human);Fluid shear stress and atherosclerosis - Homo sapiens (human);C-type lectin receptor signaling pathway - Homo sapiens (human);Tuberculosis - Homo sapiens (human);Th17 cell differentiation - Homo sapiens (human);Th1 and Th2 cell differentiation - Homo sapiens (human);Ras signaling pathway - Homo sapiens (human);MAPK signaling pathway - Homo sapiens (human);Leishmaniasis - Homo sapiens (human);IL-17 signaling pathway - Homo sapiens (human);Toxoplasmosis - Homo sapiens (human);Sphingolipid signaling pathway - Homo sapiens (human);Shigellosis - Homo sapiens (human);Prolactin signaling pathway - Homo sapiens (human);Pathways in cancer - Homo sapiens (human);Viral carcinogenesis - Homo sapiens (human);Transcriptional misregulation in cancer - Homo sapiens (human);Hepatitis C - Homo sapiens (human);Hepatitis B - Homo sapiens (human);Measles - Homo sapiens (human);Osteoclast differentiation - Homo sapiens (human);Apoptosis - Homo sapiens (human);NF-kappa B signaling pathway - Homo sapiens (human);Cellular senescence - Homo sapiens (human);Epstein-Barr virus infection - Homo sapiens (human);Pancreatic cancer - Homo sapiens (human);RIG-I-like receptor signaling pathway - Homo sapiens (human);Cocaine addiction - Homo sapiens (human);EGFR Inhibitor Pathway, Pharmacodynamics;Human papillomavirus infection - Homo sapiens (human);Herpes simplex infection - Homo sapiens (human);Tacrolimus/Cyclosporine Pathway, Pharmacodynamics;Androgen receptor signaling pathway;Nucleotide-binding Oligomerization Domain (NOD) pathway;Osteopontin Signaling;Regulation of toll-like receptor signaling pathway;Selenium Micronutrient Network;Vitamin B12 Metabolism;Folate Metabolism;IL-1 signaling pathway;RANKL-RANK (Receptor activator of NFKB (ligand)) Signaling Pathway;Leptin signaling pathway;TNF related weak inducer of apoptosis (TWEAK) Signaling Pathway;Prolactin Signaling Pathway;IL17 signaling pathway;Thymic Stromal LymphoPoietin (TSLP) Signaling Pathway;B Cell Receptor Signaling Pathway;AGE-RAGE pathway;Interleukin-11 Signaling Pathway;Corticotropin-releasing hormone signaling pathway;Oncostatin M Signaling Pathway;Brain-Derived Neurotrophic Factor (BDNF) signaling pathway;Apoptosis;Aryl Hydrocarbon Receptor;EBV LMP1 signaling;Structural Pathway of Interleukin 1 (IL-1);Selenium Metabolism and Selenoproteins;NLR Proteins;Rac1-Pak1-p38-MMP-2 pathway;Initiation of transcription and translation elongation at the HIV-1 LTR;Photodynamic therapy-induced NF-kB survival signaling;Apoptotic Signaling Pathway;MAPK Signaling Pathway;Toll-like Receptor Signaling;RIG-I-like Receptor Signaling;IL-4 Signaling Pathway;VEGFA-VEGFR2 Signaling Pathway;ApoE and miR-146 in inflammation and atherosclerosis;Chemokine signaling pathway;NO-cGMP-PKG mediated Neuroprotection;PI3K-AKT-mTOR - VitD3 Signalling;PI3K-Akt Signaling Pathway;Ras Signaling;T-Cell antigen Receptor (TCR) Signaling Pathway;Toll-like Receptor Signaling Pathway;RAGE;TLR NFkB;TWEAK;Toll Like Receptor 7/8 (TLR7/8) Cascade;Notch;double stranded rna induced gene expression;Signal Transduction;Signaling by Interleukins;p75NTR signals via NF-kB;mechanism of gene regulation by peroxisome proliferators via ppara;human cytomegalovirus and map kinase pathways;influence of ras and rho proteins on g1 to s transition;role of egf receptor transactivation by gpcrs in cardiac hypertrophy;chaperones modulate interferon signaling pathway;trefoil factors initiate mucosal healing;erythropoietin mediated neuroprotection through nf-kb;tnfr2 signaling pathway;akt signaling pathway;cd40l signaling pathway;corticosteroids and cardioprotection;acetylation and deacetylation of rela in nucleus;cadmium induces dna synthesis and proliferation in macrophages;the information processing pathway at the ifn beta enhancer;hiv-1 nef: negative effector of fas and tnf;signal transduction through il1r;the 41bb-dependent immune response;nf-kb signaling pathway;nfkb activation by nontypeable hemophilus influenzae;t cell receptor signaling pathway;keratinocyte differentiation;toll-like receptor pathway;Prolactin;Cytokine Signaling in Immune system;Toll Like Receptor 9 (TLR9) Cascade;MyD88 cascade initiated on plasma membrane;Toll Like Receptor 10 (TLR10) Cascade;Toll Like Receptor 3 (TLR3) Cascade;Toll Like Receptor 5 (TLR5) Cascade;B cell receptor signaling;ZBP1(DAI) mediated induction of type I IFNs;Toll-Like Receptors Cascades;Senescence-Associated Secretory Phenotype (SASP);Cellular Senescence;Downstream TCR signaling;TCR signaling;Cellular responses to stress;TRAF6 mediated NF-kB activation;DDX58/IFIH1-mediated induction of interferon-alpha/beta;Activation of NF-kappaB in B cells;DEx/H-box helicases activate type I IFN and inflammatory cytokines production ;Signaling by the B Cell Receptor (BCR);Interleukin-1 signaling;CLEC7A (Dectin-1) signaling;PKMTs methylate histone lysines;CD209 (DC-SIGN) signaling;C-type lectin receptors (CLRs);Chromatin modifying enzymes;Fc epsilon receptor (FCERI) signaling;TCR;Oncostatin_M;Innate Immune System;Immune System;Ghrelin;Adaptive Immune System;p73 transcription factor network;KitReceptor;inactivation of gsk3 by akt causes accumulation of b-catenin in alveolar macrophages;Downstream signaling events of B Cell Receptor (BCR);BCR;IL-1 NFkB;CRH;ceramide signaling pathway;IL1;RIP-mediated NFkB activation via ZBP1;Cellular responses to external stimuli;TAK1 activates NFkB by phosphorylation and activation of IKKs complex;atm signaling pathway;BDNF;EGFR1;TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation;Glucocorticoid receptor regulatory network;fmlp induced chemokine gene expression in hmc-1 cells;MyD88 dependent cascade initiated on endosome;BCR signaling pathway;bone remodeling;IL2;IL11;NF-kB is activated and signals survival;Death Receptor Signalling;Chromatin organization;Regulated proteolysis of p75NTR;p75 NTR receptor-mediated signalling;Gastrin;Angiopoietin receptor Tie2-mediated signaling;FCERI mediated NF-kB activation;TNFalpha;Cytosolic sensors of pathogen-associated DNA ;TRIF(TICAM1)-mediated TLR4 signaling ;MyD88-independent TLR4 cascade ;Toll Like Receptor 4 (TLR4) Cascade;TNF;Canonical NF-kappaB pathway;MyD88:Mal cascade initiated on plasma membrane;Toll Like Receptor TLR1:TLR2 Cascade;Toll Like Receptor TLR6:TLR2 Cascade;Toll Like Receptor 2 (TLR2) Cascade;Osteopontin-mediated events;IL23-mediated signaling events;HIV-1 Nef: Negative effector of Fas and TNF-alpha;CD40/CD40L signaling;LPA receptor mediated events;TNF receptor signaling pathway ;Fc-epsilon receptor I signaling in mast cells;IL2 signaling events mediated by PI3K;Interleukin-1 processing;IL1-mediated signaling events;Signaling events mediated by HDAC Class I;Ceramide signaling pathway;IL12-mediated signaling events;Atypical NF-kappaB pathway;Interleukin-1 family signaling;CD4 T cell receptor signaling-NFkB cascade;TSLP;CD4 T cell receptor signaling (Consensus)

Recessive Scores

• pRec: 0.754

Intolerance Scores

• loftool: 0.248
• rvis_EVS: -0.69
• rvis_percentile_EVS: 15.12

Haploinsufficiency Scores

• pHI: 0.997
• hipred: Y
• hipred_score: 0.771
• ghis: 0.620

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 1.00

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Rela
• Phenotype: integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); growth/size/body region phenotype; endocrine/exocrine gland phenotype; muscle phenotype; cellular phenotype; homeostasis/metabolism phenotype; immune system phenotype; skeleton phenotype; embryo phenotype; respiratory system phenotype; liver/biliary system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); normal phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); hematopoietic system phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); limbs/digits/tail phenotype; digestive/alimentary phenotype; vision/eye phenotype

Zebrafish Information Network

• Gene name: rela
• Affected structure: whole organism
• Phenotype tag: abnormal
• Phenotype quality: viability

Gene ontology

• Biological process: negative regulation of transcription by RNA polymerase II;liver development;hair follicle development;stimulatory C-type lectin receptor signaling pathway;acetaldehyde metabolic process;chromatin organization;regulation of transcription, DNA-templated;inflammatory response;cellular defense response;I-kappaB kinase/NF-kappaB signaling;aging;positive regulation of cell population proliferation;animal organ morphogenesis;response to organic substance;response to UV-B;positive regulation of Schwann cell differentiation;viral process;cytokine-mediated signaling pathway;membrane protein intracellular domain proteolysis;positive regulation of chondrocyte differentiation;positive regulation of type I interferon production;response to muramyl dipeptide;response to progesterone;response to insulin;tumor necrosis factor-mediated signaling pathway;negative regulation of protein sumoylation;response to cobalamin;response to cytokine;cellular response to hepatocyte growth factor stimulus;cellular response to vascular endothelial growth factor stimulus;response to muscle stretch;NIK/NF-kappaB signaling;Fc-epsilon receptor signaling pathway;negative regulation of protein catabolic process;negative regulation of apoptotic process;positive regulation of I-kappaB kinase/NF-kappaB signaling;response to amino acid;response to morphine;regulation of DNA-templated transcription in response to stress;positive regulation of interleukin-12 biosynthetic process;negative regulation of transcription, DNA-templated;positive regulation of transcription, DNA-templated;positive regulation of transcription by RNA polymerase II;negative regulation of insulin receptor signaling pathway;regulation of inflammatory response;T cell receptor signaling pathway;positive regulation of T cell receptor signaling pathway;positive regulation of NF-kappaB transcription factor activity;response to cAMP;defense response to virus;pri-miRNA transcription by RNA polymerase II;cellular response to hydrogen peroxide;nucleotide-binding oligomerization domain containing 2 signaling pathway;interleukin-1-mediated signaling pathway;response to interleukin-1;cellular response to lipopolysaccharide;cellular response to lipoteichoic acid;cellular response to peptidoglycan;cellular response to nicotine;cellular response to interleukin-1;cellular response to interleukin-6;cellular response to tumor necrosis factor;postsynapse to nucleus signaling pathway;regulation of NIK/NF-kappaB signaling;negative regulation of NIK/NF-kappaB signaling;positive regulation of NIK/NF-kappaB signaling;positive regulation of transcription from RNA polymerase II promoter involved in cellular response to chemical stimulus;negative regulation of pri-miRNA transcription by RNA polymerase II;positive regulation of pri-miRNA transcription by RNA polymerase II;cellular response to angiotensin;positive regulation of leukocyte adhesion to vascular endothelial cell;positive regulation of miRNA metabolic process;negative regulation of extrinsic apoptotic signaling pathway
• Cellular component: nuclear chromatin;nucleus;nucleoplasm;transcription factor complex;nucleolus;cytoplasm;cytosol;NF-kappaB p50/p65 complex;glutamatergic synapse
• Molecular function: RNA polymerase II regulatory region sequence-specific DNA binding;RNA polymerase II proximal promoter sequence-specific DNA binding;RNA polymerase II distal enhancer sequence-specific DNA binding;DNA-binding transcription factor activity, RNA polymerase II-specific;DNA-binding transcription repressor activity, RNA polymerase II-specific;DNA-binding transcription activator activity, RNA polymerase II-specific;DNA binding;chromatin binding;DNA-binding transcription factor activity;protein binding;transcription factor binding;protein kinase binding;chromatin DNA binding;ubiquitin protein ligase binding;activating transcription factor binding;phosphate ion binding;identical protein binding;protein homodimerization activity;actinin binding;histone deacetylase binding;transcription regulatory region DNA binding;protein-containing complex binding;protein heterodimerization activity;protein N-terminus binding;NF-kappaB binding;repressing transcription factor binding;ankyrin repeat binding