RELB

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

Basic information

Region (hg38): 19:45001461-45038192

Links

ENSG00000104856 ∙ NCBI:5971 ∙ OMIM:604758 ∙ HGNC:9956 ∙ Uniprot:Q01201 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• immunodeficiency 53 (Limited), mode of inheritance: Unknown
• immunodeficiency 53 (Limited), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Immunodeficiency 53	AR	Allergy/Immunology/Infectious	Individuals have been described with recurrent respiratory and other infections, and awareness may allow preventative measures and early and aggressive treatment of infections; HSCT has been described	Allergy/Immunology/Infectious	26385063; 28552761

ClinVar

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

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the RELB 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			2	117	7	126
missense			161	3		164
nonsense		1	2			3
start loss			1			1
frameshift			2			2
inframe indel			2			2
splice donor/acceptor (+/-2bp)		1				1
splice region			8	12	1	21
non coding			2	38	4	44
Total	0	2	172	158	11

Variants in RELB

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

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

Position	Type	Phenotype	Significance	ClinVar
19-45001580-A-G			Uncertain significance (Jun 03, 2021)
19-45001593-G-A			Uncertain significance (Aug 30, 2022)
19-45001600-C-T			Likely benign (Mar 23, 2023)
19-45001605-G-A			Uncertain significance (Mar 07, 2022)
19-45001607-C-A		not specified	Uncertain significance (Apr 09, 2024)
19-45001617-C-T			Uncertain significance (Jun 08, 2022)
19-45001619-A-C			Uncertain significance (Aug 23, 2022)
19-45001625-C-T			Uncertain significance (Jul 12, 2022)
19-45001626-G-C		not specified	Uncertain significance (Mar 01, 2023)
19-45001627-G-C			Likely benign (Dec 18, 2023)
19-45001634-C-G			Uncertain significance (Jun 29, 2021)
19-45001635-C-G			Uncertain significance (Jan 11, 2024)
19-45001636-G-C			Likely benign (Aug 16, 2023)
19-45001656-C-T		not specified	Uncertain significance (Dec 31, 2023)
19-45001659-C-G			Uncertain significance (Nov 08, 2022)
19-45001662-C-T			Uncertain significance (Oct 11, 2023)
19-45001666-G-A			Likely benign (Jun 06, 2023)
19-45001668-C-G			Uncertain significance (Nov 03, 2023)
19-45001684-A-C			Uncertain significance (Dec 22, 2021)
19-45001685-G-A		RELB-related disorder	Uncertain significance (Jan 16, 2024)
19-45002949-G-A			Uncertain significance (Dec 01, 2022)
19-45002949-G-T			Uncertain significance (Apr 01, 2023)
19-45002950-G-A			Benign (Jan 08, 2024)
19-45002952-C-T			Uncertain significance (Mar 27, 2023)
19-45002953-C-T			Likely benign (Aug 07, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
RELB	protein_coding	protein_coding	ENST00000221452	12	36765

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.994	0.00600	124361	0	2	124363	0.00000804

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.28	240	362	0.663	0.0000252	3654
Missense in Polyphen		58	125	0.464		1270
Synonymous	-0.0838	169	168	1.01	0.0000131	1232
Loss of Function	4.16	2	24.0	0.0832	0.00000126	273

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000189	0.0000177
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 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. NF-kappa-B heterodimeric RelB-p50 and RelB-p52 complexes are transcriptional activators. RELB neither associates with DNA nor with RELA/p65 or REL. Stimulates promoter activity in the presence of NFKB2/p49. As a member of the NUPR1/RELB/IER3 survival pathway, may provide pancreatic ductal adenocarcinoma with remarkable resistance to cell stress, such as starvation or gemcitabine treatment. Regulates the circadian clock by repressing the transcriptional activator activity of the CLOCK-ARNTL/BMAL1 heterodimer in a CRY1/CRY2 independent manner. Increased repression of the heterodimer is seen in the presence of NFKB2/p52. Is required for both T and B lymphocyte maturation and function (PubMed:26385063). {ECO:0000269|PubMed:1732739, ECO:0000269|PubMed:22565310, ECO:0000269|PubMed:26385063, ECO:0000269|PubMed:7925301, ECO:0000269|PubMed:8441398}.
• Disease: DISEASE: Immunodeficiency 53 (IMD53) [MIM:617585]: An autosomal recessive primary immunodeficiency apparent from early infancy and resulting in recurrent infections, severe autoimmune skin disease rheumatoid arthritis, and failure to thrive. Immunologic workup shows increased CD4+/CD8+ ratio, impaired T-cell proliferative response to multiple antigen, T-cell developmental and functional defects, and impaired ability to produce specific immunoglobulins. {ECO:0000269|PubMed:26385063}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: HTLV-I infection - Homo sapiens (human);C-type lectin receptor signaling pathway - Homo sapiens (human);MAPK signaling pathway - Homo sapiens (human);Osteoclast differentiation - Homo sapiens (human);NF-kappa B signaling pathway - Homo sapiens (human);Epstein-Barr virus infection - Homo sapiens (human);Tacrolimus/Cyclosporine Pathway, Pharmacodynamics;RANKL-RANK (Receptor activator of NFKB (ligand)) Signaling Pathway;TNF related weak inducer of apoptosis (TWEAK) Signaling Pathway;Thymic Stromal LymphoPoietin (TSLP) Signaling Pathway;Photodynamic therapy-induced NF-kB survival signaling;MAPK Signaling Pathway;Toll-like Receptor Signaling;EDA Signalling in Hair Follicle Development;Protein alkylation leading to liver fibrosis;NIK-->noncanonical NF-kB signaling;TNFR2 non-canonical NF-kB pathway;Cytokine Signaling in Immune system;Dectin-1 mediated noncanonical NF-kB signaling;CLEC7A (Dectin-1) signaling;CD209 (DC-SIGN) signaling;C-type lectin receptors (CLRs);Innate Immune System;Immune System;TNFalpha;Alternative NF-kappaB pathway;IL12-mediated signaling events;TSLP (Consensus)

Recessive Scores

• pRec: 0.487

Intolerance Scores

• loftool: 0.0582
• rvis_EVS: -1
• rvis_percentile_EVS: 8.32

Haploinsufficiency Scores

• pHI: 0.658
• hipred: Y
• hipred_score: 0.701
• ghis: 0.599

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.839

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Relb
• Phenotype: limbs/digits/tail phenotype; digestive/alimentary phenotype; renal/urinary system phenotype; immune system phenotype; respiratory system phenotype; liver/biliary system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); reproductive 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); 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); hematopoietic system 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); growth/size/body region phenotype; muscle phenotype; cellular phenotype; homeostasis/metabolism phenotype; endocrine/exocrine gland phenotype

Gene ontology

• Biological process: negative regulation of transcription by RNA polymerase II;stimulatory C-type lectin receptor signaling pathway;inflammatory response;I-kappaB kinase/NF-kappaB signaling;antigen processing and presentation;lymphocyte differentiation;negative regulation of interferon-beta production;circadian regulation of gene expression;response to cytokine;NIK/NF-kappaB signaling;myeloid dendritic cell differentiation;T-helper 1 cell differentiation;positive regulation of transcription by RNA polymerase II;cellular response to osmotic stress
• Cellular component: nucleus;nucleoplasm;centrosome;cytosol;transcriptional repressor complex;protein-containing complex
• Molecular function: RNA polymerase II regulatory region sequence-specific DNA binding;RNA polymerase II distal enhancer sequence-specific DNA binding;DNA-binding transcription factor activity, RNA polymerase II-specific;chromatin binding;DNA-binding transcription factor activity;transcription corepressor activity;protein binding;protein kinase binding;identical protein binding