Familial Meniere Disease

Gene: NFKB1

Red List (low evidence)

NFKB1 (nuclear factor kappa B subunit 1)
EnsemblGeneIds (GRCh38): ENSG00000109320
EnsemblGeneIds (GRCh37): ENSG00000109320
OMIM: 164011, Gene2Phenotype
NFKB1 is in 3 panels

2 reviews

Eleanor Williams (Genomics England Curator)

Comment when marking as ready: Involvement of NFKB1 found in sporadic Meniere disease. No further evidence of association with Meniere disease in OMIM, Gene2Phenotype or PubMed searches.
Created: 21 Mar 2018, 2:02 p.m.
Comment on list classification: In Frejo et al 2017 (PMID:29326686) an immune genotype array with 420 bilateral MD patients (NOT familial) identified an association with bilateral MD at 6p21.33 (leading signal rs4947296). In vitro studies suggest that the carriers of the risk genotype may develop an NF-κB-mediated inflammatory response in MD. Cabrera et al 2014 (PMID:25397881) found by genotyping array two potential regulatory variants in the NFKB1 gene (rs3774937 and rs4648011) were associated with a faster hearing loss progression in patients with unilateral sensorineural hearing loss in MD patients (716 patients).
Created: 21 Mar 2018, 2:01 p.m.

Jose Antonio Lopez-Escamez (Center for Genomic GENyO)

Green List (high evidence)

This gene is not associated with familial MD, but it is related with inflammation in the carriers of rs4749296.
We conducted a case-control study in two phases using an immune genotyping array in a total of 420 patients with bilateral MD and 1,630 controls. We have identified the first locus, at 6p21.33, suggesting an association with bilateral MD [meta-analysis leading signal rs4947296, OR = 2.089 (1.661-2.627); p = 1.39 × 10-09]. Gene expression profiles of homozygous genotype-selected peripheral blood mononuclear cells (PBMCs) demonstrated that this region is a trans-expression quantitative trait locus (eQTL) in PBMCs. Signaling analysis predicted several tumor necrosis factor-related pathways, the TWEAK/Fn14 pathway being the top candidate (p = 2.42 × 10-11). This pathway is involved in the modulation of inflammation in several human AD, including multiple sclerosis, systemic lupus erythematosus, or rheumatoid arthritis. In vitro studies with genotype-selected lymphoblastoid cells from patients with MD suggest that this trans-eQTL may regulate cellular proliferation in lymphoid cells through the TWEAK/Fn14 pathway by increasing the translation of NF-κB. Taken together; these findings suggest that the carriers of the risk genotype may develop an NF-κB-mediated inflammatory response in MD.
Created: 20 Feb 2018, 5:59 p.m.

Mode of inheritance
Other

Phenotypes
Bilateral Meniere disease; autoimmune MD

Publications

Details

Sources
  • Expert Review Red
  • Literature
Phenotypes
  • Bilateral Meniere disease
  • autoimmune Meniere disease
OMIM
164011
Clinvar variants
Variants in NFKB1
Penetrance
None
Publications
Panels with this gene

History Filter Activity

27 Mar 2018, Gel status: 1

Panel promoted to version 1.0

Eleanor Williams (Genomics England Curator)

External reviews collated. Internal clinical input. Ready for version 1.

21 Mar 2018, Gel status: 1

Gene classified by Genomics England curator

Eleanor Williams (Genomics England Curator)

This gene has been classified as Red List (Low Evidence).

21 Mar 2018, Gel status: 1

Gene classified by Genomics England curator

Eleanor Williams (Genomics England Curator)

This gene has been classified as Red List (Low Evidence).

21 Mar 2018, Gel status: 1

Set publications

Eleanor Williams (Genomics England Curator)

Publications for NFKB1 were set to 28787010; 29326686; 25397881

21 Mar 2018, Gel status: 1

Set publications

Eleanor Williams (Genomics England Curator)

Publications for NFKB1 were set to 28787010; 29326686

21 Mar 2018, Gel status: 1

Set publications

Eleanor Williams (Genomics England Curator)

Publications for NFKB1 were set to 28787010

21 Mar 2018, Gel status: 1

Set Phenotypes

Eleanor Williams (Genomics England Curator)

Phenotypes for NFKB1 were set to Bilateral Meniere disease; autoimmune Meniere disease

17 Jan 2018, Gel status: 1

Added New Source

Eleanor Williams (Genomics England Curator)

NFKB1 was added to Familial Meniere Disease panel. Sources: Literature

17 Jan 2018, Gel status: 1

Created

Eleanor Williams (Genomics England Curator)

NFKB1 was created by Eleanor Williams