CXCL8
protein-codingC-X-C motif chemokine ligand 8, the group of Interleukins|Chemokine ligands
Gene summary
The protein encoded by this gene is a member of the CXC chemokine family and is a major mediator of the inflammatory response. The encoded protein is commonly referred to as interleukin-8 (IL-8). IL-8 is secreted by mononuclear macrophages, neutrophils, eosinophils, T lymphocytes, epithelial cells, and fibroblasts. It functions as a chemotactic factor by guiding the neutrophils to the site of infection. Bacterial and viral products rapidly induce IL-8 expression. IL-8 also participates with other cytokines in the proinflammatory signaling cascade and plays a role in systemic inflammatory response syndrome (SIRS). This gene is believed to play a role in the pathogenesis of the lower respiratory tract infection bronchiolitis, a common respiratory tract disease caused by the respiratory syncytial virus (RSV). The overproduction of this proinflammatory protein is thought to cause the lung inflammation associated with csytic fibrosis. This proinflammatory protein is also suspected of playing a role in coronary artery disease and endothelial dysfunction. This protein is also secreted by tumor cells and promotes tumor migration, invasion, angiogenesis and metastasis. This chemokine is also a potent angiogenic factor. The binding of IL-8 to one of its receptors (IL-8RB/CXCR2) increases the permeability of blood vessels and increasing levels of IL-8 are positively correlated with increased severity of multiple disease outcomes (eg, sepsis). This gene and other members of the CXC chemokine gene family form a gene cluster in a region of chromosome 4q. [provided by RefSeq, May 2020]
- IL8
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~3.2 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 CXCL8 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_000584.4. 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 | 1 | 1 | ||||
| missense | 4 | 4 | ||||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 5 | 2 | 0 | 7 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_000575.1 | 4 | MANE Select | |
| Ensembl | ENSP00000306512.3 | 4 | MANE Select | |
| RefSeq | NP_001341769.1 | 3 | Standard | |
| Ensembl | ENSP00000385908.1 | 3 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| cxcl8b.1 | Danio rerio | Structure: intersegmental vessel Quality: morphology abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Kaposi,s sarcoma-associated herpesvirus infection - Homo sapiens (human)
- Pertussis - Homo sapiens (human)
- Salmonella infection - Homo sapiens (human)
- Legionellosis - Homo sapiens (human)
- Non-alcoholic fatty liver disease (NAFLD) - Homo sapiens (human)
Biological Process
- angiogenesis
- response to molecule of bacterial origin
- chemotaxis
- inflammatory response
- immune response
Molecular Function
- interleukin-8 receptor binding
- protein binding
- chemokine activity
Cellular Component
- extracellular region
- extracellular space
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000307407
- Coding exons
- 4
- Length
- 3211
- Individuals with no LoFs
- 125329
- Homozygous LoFs
- 3
- Heterozygous LoFs
- 394
- Defined
- 125726
- p
- 0.00158
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.516 | 59 | 48.8 | 1.21 | 0.00000221 | 637 |
| Missense (PolyPhen) | 24 | 15.702 | 1.5285 | 214 | ||
| Synonymous | -0.455 | 20 | 17.6 | 1.14 | 8.36e-7 | 187 |
| Loss of Function | -0.229 | 5 | 4.48 | 1.12 | 1.87e-7 | 63 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.00047 | 0.00046 | rare |
| Ashkenazi Jewish | 0.0036 | 0.0036 | notable |
| East Asian | 0.00027 | 0.00027 | rare |
| Finnish | 0.0069 | 0.0069 | notable |
| European (Non-Finnish) | 0.0012 | 0.0012 | notable |
| South Asian | 0.0015 | 0.0014 | notable |
| Other | 0.0020 | 0.0020 | notable |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: IL-8 is a chemotactic factor that attracts neutrophils, basophils, and T-cells, but not monocytes. It is also involved in neutrophil activation. It is released from several cell types in response to an inflammatory stimulus. IL-8(6-77) has a 5-10-fold higher activity on neutrophil activation, IL-8(5-77) has increased activity on neutrophil activation and IL-8(7-77) has a higher affinity to receptors CXCR1 and CXCR2 as compared to IL-8(1-77), respectively. {ECO:0000269|PubMed:11978786, ECO:0000269|PubMed:2145175, ECO:0000269|PubMed:2212672}.;
Recessive Scores
- pRec
- 0.908
Intolerance Scores
- RVIS EVS
- -0.21
- RVIS percentile EVS
- 38.28
Essentials
- Essential (gene trap)
- N