NFKB1

Chr 4AD

nuclear factor kappa B subunit 1

Also known as: CVID12, EBP-1, KBF1, NF-kB, NF-kB1, NF-kappa-B1, NF-kappaB, NF-kappabeta

This gene encodes a 105 kD protein which can undergo cotranslational processing by the 26S proteasome to produce a 50 kD protein. The 105 kD protein is a Rel protein-specific transcription inhibitor and the 50 kD protein is a DNA binding subunit of the NF-kappa-B (NFKB) protein complex. NFKB is a transcription regulator that is activated by various intra- and extra-cellular stimuli such as cytokines, oxidant-free radicals, ultraviolet irradiation, and bacterial or viral products. Activated NFKB translocates into the nucleus and stimulates the expression of genes involved in a wide variety of biological functions. Inappropriate activation of NFKB has been associated with a number of inflammatory diseases while persistent inhibition of NFKB leads to inappropriate immune cell development or delayed cell growth. NFKB is a critical regulator of the immediate-early response to viral infection. Alternative splicing results in multiple transcript variants encoding different isoforms, at least one of which is proteolytically processed. [provided by RefSeq, Aug 2020]

OMIMResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Immunodeficiency, common variable, 12MIM #616576
AD

Clinical highlights

Gene-disease validity (ClinGen)
immunodeficiency, common variable, 12 · ADDefinitivesufficient evidence for diagnostic panels
Interpreting a novel variant
This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.
0
Active trials
Pubs (1 yr)
P/LP submissions
P/LP missense
0.14
LOEUF· LoF intol.
LOF
Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Dual constrained — LoF & missense intolerant
LoF Constraint?
0.14LOEUF
pLI 1.000
Z-score 5.98
OE 0.04 (0.020.14)
Highly constrained

Among the most LoF-intolerant genes (~top 3%)

Missense Constraint?
3.19Z-score
OE missense 0.62 (0.560.67)
337 obs / 547.2 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios?
LoF OE?0.04 (0.020.14)
00.351.4
Missense OE?0.62 (0.560.67)
00.61.4
Synonymous OE?1.00
01.21.6
LoF obs/exp: 2 / 45.6Missense obs/exp: 337 / 547.2Syn Z: -0.05

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

NFKB1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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