CXCL6

Chr 4

C-X-C motif chemokine ligand 6

Also known as: CKA-3, GCP-2, GCP2, SCYB6

NCBI Gene: 6372 ENSG00000124875 UniProt: P80162 OMIM: 138965

CXCL6 encodes a CXC chemokine that attracts neutrophils through CXCR1 and CXCR2 receptors and has antibacterial activity against gram-positive and gram-negative bacteria. The gene is not highly constrained against loss-of-function variants, and no Mendelian diseases have been definitively associated with CXCL6 mutations in current databases. This chemokine is part of a gene cluster on chromosome 4q involved in innate immune responses.

OMIM ResearchSummary from RefSeq, UniProt

The protein encoded by this gene is a member CXC chemokine family. The encoded protein is a chemotactic for neutrophil granulocytes and has antibacterial action against gram-negative and gram-positive bacteria. This gene and other members of the CXC chemokine gene family form a gene cluster in a region of chromosome 4q. [provided by RefSeq, Jun 2020]

OMIM ResearchGenerating clinical summary…

DNmechanismLOEUF 1.97

Clinical Summary— CXCL6

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Population Constraint (gnomAD)

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

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ClinVar Variants

21 VUS of 23 total submissions

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Clinical Trials

1 active or recruiting trial — potential therapeutic options may be available

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?

1.97LOEUF

pLI 0.000

Z-score -2.30

OE 2.15 (1.10–1.97)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.68Z-score

OE missense 1.24 (1.03–1.49)

81 obs / 65.5 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?2.15 (1.10–1.97)

0≤0.351.4

Missense OE?1.24 (1.03–1.49)

0≤0.61.4

Synonymous OE?1.23

0≤1.21.6

LoF obs/exp: 10 / 4.6Missense obs/exp: 81 / 65.5Syn Z: -1.03

This gene — mechanism propensity

0.74top 25%

GOF

0.6248th %ile

LOF

0.2484th %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

23 submitted variants in ClinVar

ClinVar

Classification Summary

VUS21

Benign1

VUS

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Total
Pathogenic	0	0	0
Likely Pathogenic	0	0	0
VUS	0	21	21
Likely Benign	0	0	0
Benign	1	0	1
Total	1	21	22

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

View in ClinVar →

24 pathogenic / likely-pathogenic (of 27) ClinVar copy-number / structural variants overlap CXCL6 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →