NFKBIL1
protein-codingNFKB inhibitor like 1
Gene summary
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]
- NFKBIL
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~12.0 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to NFKBIL1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_005007.4. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 3 | 3 | ||||
| missense | 52 | 2 | 1 | 55 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 55 | 2 | 1 | 58 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_004998.3 | 4 | MANE Select | |
| Ensembl | ENSP00000365318.4 | 4 | MANE Select | |
| RefSeq | NP_001138433.1 | 4 | Standard | |
| RefSeq | NP_001138434.1 | 3 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- I-kappaB kinase/NF-kappaB signaling
- negative regulation of lipopolysaccharide-mediated signaling pathway
- negative regulation of NF-kappaB transcription factor activity
- negative regulation of tumor necrosis factor production
- negative regulation of toll-like receptor signaling pathway
Molecular Function
- protein binding
Cellular Component
- nucleus
- cytosol
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000376148
- Coding exons
- 4
- Length
- 11960
- Individuals with no LoFs
- 125663
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 20
- Defined
- 125683
- p
- 0.0000796
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 2.29 | 127 | 223 | 0.569 | 0.0000139 | 2383 |
| Missense (PolyPhen) | 41 | 89.692 | 0.45712 | 1015 | ||
| Synonymous | 2.27 | 57 | 83.3 | 0.684 | 0.00000429 | 799 |
| Loss of Function | 3.05 | 7 | 22.7 | 0.309 | 0.00000176 | 169 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00013 | 0.00012 | rare |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0.000046 | 0.000046 | rare |
| European (Non-Finnish) | 0.00011 | 0.00011 | rare |
| South Asian | 0.000099 | 0.000098 | rare |
| Other | 0.00033 | 0.00033 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Involved in the regulation of innate immune response. Acts as negative regulator of Toll-like receptor and interferon- regulatory factor (IRF) signaling pathways. Contributes to the negative regulation of transcriptional activation of NF-kappa-B target genes in response to endogenous proinflammatory stimuli. {ECO:0000269|PubMed:20829348}.;
Intolerance Scores
- LoFtool
- 0.950
- RVIS EVS
- 0.04
- RVIS percentile EVS
- 56.64
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.918
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |