NFKBIZ

Chr 3

NFKB inhibitor zeta

Also known as: I-kappa-B-zeta, IKBZ, INAP, IkappaB-zeta, MAIL, ikB-zeta, ikappaBzeta

This gene is a member of the ankyrin-repeat family and is induced by lipopolysaccharide (LPS). The C-terminal portion of the encoded product which contains the ankyrin repeats, shares high sequence similarity with the I kappa B family of proteins. The latter are known to play a role in inflammatory responses to LPS by their interaction with NF-B proteins through ankyrin-repeat domains. Studies in mouse indicate that this gene product is one of the nuclear I kappa B proteins and an activator of IL-6 production. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

OMIMResearchGenerating clinical summary…
LOFmechanismLOEUF 0.19
Clinical SummaryNFKBIZ
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Gene-Disease Validity (ClinGen)
hereditary nonpolyposis colon cancer · ADLimited

Limited evidence — not for standalone diagnostic reporting

Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
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ClinVar Variants
80 VUS of 113 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint?
0.19LOEUF
pLI 1.000
Z-score 5.02
OE 0.06 (0.020.19)
Highly constrained

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

Missense Constraint?
1.18Z-score
OE missense 0.83 (0.750.91)
299 obs / 362.3 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?
LoF OE?0.06 (0.020.19)
00.351.4
Missense OE?0.83 (0.750.91)
00.61.4
Synonymous OE?1.13
01.21.6
LoF obs/exp: 2 / 33.2Missense obs/exp: 299 / 362.3Syn Z: -1.23

This gene — mechanism propensity

DN
0.4090th %ile
GOF
0.3391th %ile
LOF
0.72top 10%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.19

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

113 submitted variants in ClinVar

Classification Summary

VUS80
Likely Benign10
80
VUS
10
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
0
0
0
Likely Pathogenic
0
0
0
0
0
VUS
0
80
0
0
80
Likely Benign
0
9
0
1
10
Benign
0
0
0
0
0
Total0890190

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

9 pathogenic / likely-pathogenic (of 13) ClinVar copy-number / structural variants overlap NFKBIZ — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →

Protein Context — Lollipop Plot

NFKBIZ · 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.

Search ClinicalTrials.gov →