NFKBIL1

Chr 6

NFKB inhibitor like 1

Also known as: IKBL, NFKBIL

NCBI Gene: 4795ENSG00000204498UniProt: Q9UBC1

This gene encodes a divergent member of the I-kappa-B family of proteins. Its function has not been determined. The gene lies within the major histocompatibility complex (MHC) class I region on chromosome 6. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2009]

Primary Disease Associations & Inheritance

UniProtRheumatoid arthritis
62
ClinVar variants
7
Pathogenic / LP
0.03
pLI score
0
Active trials
Clinical Summary— NFKBIL1
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.31) despite low pLI — interpret in context.
📋
ClinVar Variants
7 Pathogenic / Likely Pathogenic· 50 VUS of 62 total submissions
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.58LOEUF
pLI 0.026
Z-score 3.05
OE 0.31 (0.17–0.58)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
2.29Z-score
OE missense 0.57 (0.49–0.66)
127 obs / 223.2 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.31 (0.17–0.58)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.57 (0.49–0.66)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.68
0≤1.21.6
LoF obs/exp: 7 / 22.7Missense obs/exp: 127 / 223.2Syn Z: 2.27

ClinVar Variant Classifications

62 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic4
Likely Pathogenic3
VUS50
Likely Benign2
Benign3
4
Pathogenic
3
Likely Pathogenic
50
VUS
2
Likely Benign
3
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
4
0
4
Likely Pathogenic
0
0
3
0
3
VUS
0
47
3
0
50
Likely Benign
0
2
0
0
2
Benign
0
2
0
1
3
Total05110162

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

View in ClinVar →

Protein Context — Lollipop Plot

NFKBIL1 · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype

OMIM

No OMIM entries found.

Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Biomarkers of disease progression in people with psoriasis: a scoping review.
Ramessur R et al.·Br J Dermatol
2022Review
Validation and functional follow-up of cervical cancer risk variants at the HLA locus.
Eisenblätter R et al.·HLA
2024Natural history
A novel link of HLA locus to the regulation of immunity and infection: NFKBIL1 regulates alternative splicing of human immune-related genes and influenza virus M gene.
An J et al.·J Autoimmun
2013
Multiple allelic associations from genes involved in energy metabolism were identified in celiac disease.
Bhagavatula S et al.·J Biosci
2021Meta-analysis
HLA-DPB1 and NFKBIL1 may confer the susceptibility to chronic thromboembolic pulmonary hypertension in the absence of deep vein thrombosis.
Kominami S et al.·J Hum Genet
2009
Genetic variation on the BAT1-NFKBIL1-LTA region of major histocompatibility complex class III associates with periodontitis.
Kallio KA et al.·Infect Immun
2014
Salivary biomarkers in association with periodontal parameters and the periodontitis risk haplotype.
Liukkonen J et al.·Innate Immun
2018
[Association study between exon 4 NFKBIL1 polymorphism and multiple sclerosis].
Owecki MK et al.·Pol Merkur Lekarski
2010
The haplotype block, NFKBIL1-ATP6V1G2-BAT1-MICB-MICA, within the class III-class I boundary region of the human major histocompatibility complex may control susceptibility to hepatitis C virus-associated dilated cardiomyopathy.
Shichi D et al.·Tissue Antigens
2005
TaqMan assays for genotyping of single nucleotide polymorphisms present at a disease susceptibility locus on chromosome 6.
Koch W et al.·Clin Chem Lab Med
2005
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools