Combined Immunodeficiency

Gene: RELB

Green List (high evidence)

RELB (RELB proto-oncogene, NF-kB subunit)
EnsemblGeneIds (GRCh38): ENSG00000104856
EnsemblGeneIds (GRCh37): ENSG00000104856
OMIM: 604758, Gene2Phenotype
RELB is in 2 panels

3 reviews

Chirag Patel (Genetic Health Queensland)

Green List (high evidence)

2 unrelated adults with childhood onset severe and recurrent viral, bacterial, and fungal diseases, and combined T- and B-cell immunodeficiency and autoantibodies neutralizing type I interferons (IFNs). WES identified biallelic loss-of-function variants in RELB gene. P1 had a homozygous variant (p.Q72Tfs*152) which segregated with the parents and healthy siblings. P2 had a maternally inherited variant (p.E145K) and a de novo variant (p.P364L), with parental linkage confirmed by a microsatellite panel analysis.

There was a resulting deficiency of functional RelB which impaired the induction of NFKB2 mRNA and NF-κB2 protein by lymphotoxin in the fibroblasts of the patients. These defects were rescued by transduction with wild-type RELB complementary DNA (cDNA). By contrast, the response of RelB-deficient fibroblasts to Tumor Necrosis Factor (TNF) or IL-1β via the canonical NF-κB pathway remained intact. Both patients had low proportions of naïve CD4+ and CD8+ T cells and of memory B cells. Their naïve B cells could not differentiate into immunoglobulin G (IgG)- or immunoglobulin A (IgA)-secreting cells in response to CD40L/IL-21, and the development of IL-17A/F-producing T cells was strongly impaired in vitro. Both patients produced neutralizing autoantibodies against type I interferons (IFNs), even after hematopoietic stem cell transplantation, attesting to a persistent dysfunction of thymic epithelial cells in T cell selection and central tolerance to some autoantigens.
Created: 3 Oct 2024, 9:01 p.m. | Last Modified: 3 Oct 2024, 9:01 p.m.
Panel Version: 1.73

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
T-cell and B cell immunodeficiency; Immunodeficiency 53, OMIM #617585,

Publications

Peter McNaughton (Queensland Children's Hospital)

I don't know

3 related patients (unrelated to kindred reported in PMID: 26385063) with predominately severe autoimmune manifestations involving the liver, gut, lung, and skin, as well as repeated infection, and the range of patient ages (4–18 years). Homozygous mutation in RelB (P364L), RelB protein by Western blotting revealed markedly reduced levels compared to control, but not a complete absence of RelB as observed in RelB null cases. Functional studies demonstrating dysregulation of the NFκB main pathway with marked skewing towards pro-inflammation.
? Green given now multiple kindreds
Created: 24 Nov 2023, 1:58 a.m. | Last Modified: 24 Nov 2023, 1:58 a.m.
Panel Version: 1.51

Phenotypes
Complex autoimmunity

Publications

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

I don't know

Single family reported, functional data.
Sources: Expert list
Created: 3 Apr 2020, 3:42 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Immunodeficiency 53, MIM# 617585; T cells: normal number, poor diversity, poor function; recurrent infections

Publications

Details

Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • Expert list
Phenotypes
  • Immunodeficiency 53, MIM# 617585
  • T cells: normal number, poor diversity, poor function
  • recurrent infections
OMIM
604758
Clinvar variants
Variants in RELB
Penetrance
None
Publications
Panels with this gene

History Filter Activity

5 Oct 2024, Gel status: 3

Set publications

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Publications for gene: RELB were set to 7834753; 26385063

3 Oct 2024, Gel status: 3

Entity classified by Genomics England curator

Chirag Patel (Genetic Health Queensland)

Gene: relb has been classified as Green List (High Evidence).

3 Apr 2020, Gel status: 2

Entity classified by Genomics England curator

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Gene: relb has been classified as Amber List (Moderate Evidence).

3 Apr 2020, Gel status: 2

Entity classified by Genomics England curator

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Gene: relb has been classified as Amber List (Moderate Evidence).

3 Apr 2020, Gel status: 1

Created, Added New Source, Set mode of inheritance, Set publications, Set Phenotypes

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

gene: RELB was added gene: RELB was added to Combined Immunodeficiency. Sources: Expert list Mode of inheritance for gene: RELB was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: RELB were set to 7834753; 26385063 Phenotypes for gene: RELB were set to Immunodeficiency 53, MIM# 617585; T cells: normal number, poor diversity, poor function; recurrent infections Review for gene: RELB was set to AMBER