CXCL8

protein-coding

C-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]

Previous symbols:
  • IL8

MANE transcript

NM_000584.4

Inheritance

—

ClinVar variants

U:5B:2

Top phenotype

CXCL8-related disorder

gnomAD constraint

pLI —, LoF o/e 1.12

Max pathogenic AF

—

Genomic locus

chr4:73,740,519-73,743,716

External References & Databases

Transcript & Mutation Effects

hg38 • Region Span ~3.2 kb
Loading mutation effect viewer...

GenCC 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

3 Conditions Cataloged
not specifiedTotal: 3
not providedTotal: 2
CXCL8-related disorderTotal: 1

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.

EffectPLPVUSLBBSum
synonymous
1
clinvar
1
missense
4
clinvar
4
nonsense
1
clinvar
1
start loss
0
frameshift
0
splice donor/acceptor (+/-2bp)
1
clinvar
1
Total005207
Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 8 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_000584.4RefSeqNP_000575.14MANE Select
ENST00000307407.8EnsemblENSP00000306512.34MANE Select
NM_001354840.3RefSeqNP_001341769.13Standard
ENST00000401931.1EnsemblENSP00000385908.13Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / ModelOrganismObserved Phenotype
cxcl8b.1Danio 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: gnomAD

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-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense-0.5165948.81.210.00000221637
Missense (PolyPhen)2415.7021.5285214
Synonymous-0.4552017.61.148.36e-7187
Loss of Function-0.22954.481.121.87e-763

Population LoF Frequency

PopulationCAFp-valueStatus
African00.0absent
Latino/Admixed American0.000470.00046rare
Ashkenazi Jewish0.00360.0036notable
East Asian0.000270.00027rare
Finnish0.00690.0069notable
European (Non-Finnish)0.00120.0012notable
South Asian0.00150.0014notable
Other0.00200.0020notable

dbNSFP Gene Annotations

Source: dbNSFP

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
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