CXCL16

Chr 17

C-X-C motif chemokine ligand 16

Also known as: CXCLG16, SR-PSOX, SRPSOX

NCBI Gene: 58191ENSG00000161921UniProt: Q9H2A7

Enables chemokine activity. Involved in several processes, including positive regulation of cell growth; response to tumor necrosis factor; and response to type II interferon. Located in extracellular space. Biomarker of COVID-19 and systemic scleroderma. [provided by Alliance of Genome Resources, Jul 2025]

66
ClinVar variants
22
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— CXCL16
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
22 Pathogenic / Likely Pathogenic· 35 VUS of 66 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
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.
1.34LOEUF
pLI 0.000
Z-score 0.77
OE 0.75 (0.44–1.34)
Tolerant

Highly tolerant — LoF variants common in population

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.
0.35Z-score
OE missense 0.92 (0.80–1.06)
140 obs / 152.0 exp
Tolerant

Mild missense constraint

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.0.75 (0.44–1.34)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.92 (0.80–1.06)
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.0.84
0≤1.21.6
LoF obs/exp: 8 / 10.7Missense obs/exp: 140 / 152.0Syn Z: 0.98

ClinVar Variant Classifications

66 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic21
Likely Pathogenic1
VUS35
Likely Benign7
Benign2
21
Pathogenic
1
Likely Pathogenic
35
VUS
7
Likely Benign
2
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
21
0
21
Likely Pathogenic
0
0
1
0
1
VUS
0
16
19
0
35
Likely Benign
0
6
1
0
7
Benign
0
1
1
0
2
Total02343066

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

View in ClinVar →

Protein Context — Lollipop Plot

CXCL16 · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Activation of Piezo1 contributes to matrix stiffness-induced angiogenesis in hepatocellular carcinoma.
Li M et al.·Cancer Commun (Lond)
2022
Genomic and drug target evaluation of 90 cardiovascular proteins in 30,931 individuals.
Folkersen L et al.·Nat Metab
2020
Alistipes finegoldii augments the efficacy of immunotherapy against solid tumors.
Wu ZY et al.·Cancer Cell
2025
Single-cell dissection of cellular components and interactions shaping the tumor immune phenotypes in ovarian cancer.
Hornburg M et al.·Cancer Cell
2021
Targeting CXCL16 and STAT1 augments immune checkpoint blockade therapy in triple-negative breast cancer.
Palakurthi B et al.·Nat Commun
2023
Role of the CXCR6/CXCL16 axis in autoimmune diseases.
Bao N et al.·Int Immunopharmacol
2023Review
Stromal oncostatin M cytokine promotes breast cancer progression by reprogramming the tumor microenvironment.
Araujo AM et al.·J Clin Invest
2022
Chemokines and atherosclerosis.
Sheikine Y et al.·Ann Med
2004Review
Polyfunctional, Proinflammatory, Tissue-Resident Memory Phenotype and Function of Synovial Interleukin-17A+CD8+ T Cells in Psoriatic Arthritis.
Steel KJA et al.·Arthritis Rheumatol
2020Functional
CXCR6 is required for antitumor efficacy of intratumoral CD8(+) T cell.
Wang B et al.·J Immunother Cancer
2021
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
KANK4 Regulates CXCL16 Glycosylation Through TMEM260 to Modulate Microglial Activation in Sepsis-associated Encephalopathy.
Peng M et al.·Inflammation
2026
Targeting CXCL16-expressing macrophages with a biomimetic nanocarrier system attenuates cartilage degeneration in osteoarthritis.
Yang Q et al.·J Control Release
2026
Triple targeting of STING, TGF-β, and PD-L1 boosts CXCL16-CXCR6 signaling for potent antitumor response.
Yi M et al.·Nat Commun
2026🔓 Open Access
Multiomics analysis reveals that senescent CXCL16+ macrophages promote lung adenocarcinoma progression through TGF-β signalling.
Zhang ZH et al.·J Transl Med
2026🔓 Open Access
Altered Expression of CXCL16/CXCR6 and Its Correlation with Decidual Macrophage Polarization in Preeclampsia.
Huang S et al.·Int J Womens Health
2025🔓 Open Access
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