RELA

Chr 11

RELA proto-oncogene, NF-kB subunit

Also known as: AIF3BL3, CMCU, NFKB3, p65

NCBI Gene: 5970 ENSG00000173039 UniProt: Q04206

RELA encodes the p65 subunit of NF-κB, a transcription factor that regulates immune responses, inflammation, and cell survival by activating target gene expression when translocated from cytoplasm to nucleus. Heterozygous mutations cause autosomal dominant autoinflammatory disease with Behçet-like features affecting multiple organ systems. The gene is highly constrained against loss-of-function variants (pLI 0.999), reflecting its essential role in immune regulation.

ResearchSummary from RefSeq, OMIM, UniProt

NF-kappa-B is a ubiquitous transcription factor involved in several biological processes. It is held in the cytoplasm in an inactive state by specific inhibitors. Upon degradation of the inhibitor, NF-kappa-B moves to the nucleus and activates transcription of specific genes. NF-kappa-B is composed of NFKB1 or NFKB2 bound to either REL, RELA, or RELB. The most abundant form of NF-kappa-B is NFKB1 complexed with the product of this gene, RELA. Four transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2011]

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtAutoinflammatory disease, familial, Behcet-like 3

Clinical highlights

Gene–disease validity (ClinGen)

Definitive · obsolete immune deficiency and dysregulation due to RELA insufficiency · AD · ClinGen 2023

Active trials

672

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

—

LOEUF

LOF

Mechanism· predicted

Some data sources returned errors (2)

gnomad: Error: gnomAD API error: 400

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD

Constraint data not available from gnomAD.

Background carrier burden — how many people carry a rare variant somewhere in RELA?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 130

666 rare PASS variants

Rare truncating (LoF)

1 in 2,600

51 rare PASS variants

Rare synonymous (reference)

1 in 170

323 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for RELA. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 180	1 in 1,700
South Asian	~43k	1 in 100	1 in 1,800
Remaining (unassigned)	~30k	1 in 130	1 in 520
European (Finnish)	~27k	1 in 240	≈ 1 in 26,000
Admixed American	~22k	1 in 120	1 in 2,600
African / African American	~21k	1 in 84	1 in 930
East Asian	~20k	1 in 180	≈ 1 in 4,800
Ashkenazi Jewish	~13k	1 in 180	≈ 1 in 13,000
Middle Eastern	~2,884	1 in 150	≈ 1 in 1,400

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.