IKBKB

Chr 8ADAR

inhibitor of nuclear factor kappa B kinase subunit beta

Also known as: IKK-2, IKK-beta, IKK2, IKKB, IMD15, IMD15A, IMD15B, NFKBIKB

NCBI Gene: 3551 ENSG00000104365 UniProt: O14920 OMIM: 603258

The protein encoded by this gene phosphorylates the inhibitor in the inhibitor/NF-kappa-B complex, causing dissociation of the inhibitor and activation of NF-kappa-B. The encoded protein itself is found in a complex of proteins. Several transcript variants, some protein-coding and some not, have been found for this gene. [provided by RefSeq, Sep 2011]

GeneReviews OMIM Research

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Immunodeficiency 15AMIM #618204

Immunodeficiency 15BMIM #615592

Clinical highlights

Gene–disease validity (ClinGen)

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.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.29

LOEUF· LoF intol.

Multiple*

Mechanism· predicted

📖

GeneReview available — IKBKB

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.29LOEUF

pLI 0.992

Z-score 5.68

OE 0.17 (0.10–0.29)

Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?

2.59Z-score

OE missense 0.65 (0.59–0.72)

285 obs / 437.3 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.17 (0.10–0.29)

0≤0.351.4

Missense OE?0.65 (0.59–0.72)

0≤0.61.4

Synonymous OE?0.80

0≤1.21.6

LoF obs/exp: 9 / 54.1Missense obs/exp: 285 / 437.3Syn Z: 2.04

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

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 63

849 rare PASS variants

Rare truncating (LoF)

1 in 810

91 rare PASS variants

Rare synonymous (reference)

1 in 120

380 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for IKBKB. 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 100	1 in 2,100
South Asian	~43k	1 in 46	1 in 3,700
Remaining (unassigned)	~30k	1 in 67	1 in 3,000
European (Finnish)	~27k	1 in 160	1 in 1,700
Admixed American	~22k	1 in 80	≈ 1 in 11,000
African / African American	~21k	1 in 73	1 in 670
East Asian	~20k	1 in 84	1 in 970
Ashkenazi Jewish	~13k	1 in 330	≈ 1 in 6,500
Middle Eastern	~2,884	1 in 58	≈ 1 in 630

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.