CXCL16

Chr 17

C-X-C motif chemokine ligand 16

Also known as: CXCLG16, SR-PSOX, SRPSOX

NCBI Gene: 58191 ENSG00000161921 UniProt: Q9H2A7 OMIM: 605398

The CXCL16 protein functions as a chemokine that induces chemotactic responses and calcium mobilization, and also acts as a scavenger receptor on macrophages that binds oxidized low-density lipoprotein. This gene is extremely tolerant to loss-of-function variants in the general population (very low constraint), and no established Mendelian diseases have been definitively linked to CXCL16 mutations in current medical literature.

OMIM ResearchSummary from RefSeq, UniProt

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]

OMIM ResearchGenerating clinical summary…

DNmechanismLOEUF 1.34

Clinical Summary— CXCL16

⚡

Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

📋

ClinVar Variants

24 VUS of 42 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

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?

0.35Z-score

OE missense 0.92 (0.80–1.06)

140 obs / 152.0 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.75 (0.44–1.34)

0≤0.351.4

Missense OE?0.92 (0.80–1.06)

0≤0.61.4

Synonymous OE?0.84

0≤1.21.6

LoF obs/exp: 8 / 10.7Missense obs/exp: 140 / 152.0Syn Z: 0.98

This gene — mechanism propensity

0.75top 25%

GOF

0.6053th %ile

LOF

0.1994th %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

42 submitted variants in ClinVar

ClinVar

Classification Summary

VUS24

Likely Benign6

Benign2

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Non-coding	Total
Pathogenic	0	0	0
Likely Pathogenic	0	0	0
VUS	16	8	24
Likely Benign	6	0	6
Benign	1	1	2
Total	23	9	32

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

View in ClinVar →

23 pathogenic / likely-pathogenic (of 36) ClinVar copy-number / structural variants overlap CXCL16 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →