CXCL8

Chr 4

C-X-C motif chemokine ligand 8

Also known as: GCP-1, GCP1, IL8, LECT, LUCT, LYNAP, MDNCF, MONAP

The CXCL8 protein (interleukin-8) is a chemokine that attracts and activates neutrophils and other immune cells to sites of infection and inflammation. Mutations in CXCL8 cause autosomal recessive severe congenital neutropenia, characterized by recurrent bacterial infections due to impaired neutrophil chemotaxis and immune dysfunction. This gene shows low constraint against loss-of-function variants (pLI 0.0003, LOEUF 1.86), consistent with its recessive inheritance pattern.

OMIMResearchSummary from RefSeq, UniProt
DNmechanismLOEUF 1.86
Clinical SummaryCXCL8
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
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Clinical Trials
12 active or recruiting trials — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.86LOEUF
pLI 0.000
Z-score -0.23
OE 1.12 (0.561.86)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-0.52Z-score
OE missense 1.21 (0.981.50)
59 obs / 48.8 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE1.12 (0.561.86)
00.351.4
Missense OE1.21 (0.981.50)
00.61.4
Synonymous OE1.14
01.21.6
LoF obs/exp: 5 / 4.5Missense obs/exp: 59 / 48.8Syn Z: -0.46
DN
0.78top 25%
GOF
0.4678th %ile
LOF
0.2387th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

CXCL8 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

Cystic Fibrosis-related DiabetesCystic Fibrosis

Metformin for People With CFRD on CFTR Modulator Therapy to Improve Ion Channel Function

RECRUITING
NCT04530383Phase PHASE2University of Kansas Medical CenterStarted 2022-02-14
Metformin Hydrochloride
Porphyria, Acute Intermittent

Clinical Research on Acute Intermittent Porphyria and the Use of Carbohydrate-Rich Diet as a Treatment

RECRUITING
NCT06273644Phase NANordlandssykehuset HFStarted 2024-01-27
Carbohydrates
Metastatic Colorectal CancerMetastatic Cancer to Liver

FAPI Molecular Imaging for Diagnosis of the CMS4 Unfavorable Colorectal Cancer Subtype

NOT YET RECRUITING
NCT06191120Phase NAUMC UtrechtStarted 2024-04
[18F]-ALF-FAPI-74 PET/CT scan
Congenital Adrenal Hyperplasia (CAH)

Fertility And Sexual Function In CAH: CALLIOPE

RECRUITING
NCT07099456University of Roma La SapienzaStarted 2024-11-01
COPD (Chronic Obstructive Pulmonary Disease)

Effect of High-intensity Interval Training on the Lung in Patients With COPD Referred for Lung Volume Reduction Surgery: The PREGENERATE Trial

ENROLLING BY INVITATION
NCT07343375Phase NARigshospitalet, DenmarkStarted 2026-04
High Intensity interval training (HIIT)
Multiple Myeloma (MM)

Moving Foward With Myeloma (MFM)

NOT YET RECRUITING
NCT07236502Phase NAMedical College of WisconsinStarted 2026-01-30
Immediate interventionWaitlist
Aging

Evaluation of the Efficacy of Calcium a -Ketoglutarate(AKG-Ca) in Improving Human Aging

ACTIVE NOT RECRUITING
NCT07114536Phase NAShenzhen Hygieia Biotech Co., LtdStarted 2025-08-20
Calcium-a-ketoglutaratePlacebo(starch)
Prostate CancerProstate Inflammation

Characterization of Microbiological and Genetic Features in Prostate Cancer and Their Association with Disease Stage

ENROLLING BY INVITATION
NCT06505356Phase NAEdgaras BurzinskisStarted 2024-09-01
Prostate biopsy
Obstructive Sleep Apnea

Dexamethasone Treatment for OSA in Children

ACTIVE NOT RECRUITING
NCT05638087Phase PHASE3The Hospital for Sick ChildrenStarted 2022-10-26
DexamethasonePlacebo Control
Breast Cancer Early Stage Breast Cancer (Stage 1-3)Prehabilitation

Multimodal Prehabilitation Program That Combines Physical Exercise, Psychological Intervention and Nutritional Support to Improve the Response to Neoadjuvant Chemoterhapy in Early Breast Cancer Patients

RECRUITING
NCT07107594Phase NAHospital Clinic of BarcelonaStarted 2025-01-14
Multimodal prehabilitation
Arrhythmogenic Right Ventricular Dysplasia

Blockade of the Renin-angiotensin-aldosterone System in Patients With ARVD

RECRUITING
NCT03593317Phase PHASE2Hospices Civils de LyonStarted 2024-12-20
SpironolactonePlacebo
Concussion, BrainMild Traumatic Brain Injury

Risk Stratification in Children With Concussion

RECRUITING
NCT05825027Duke UniversityStarted 2023-05-23
Clinical Literature
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