CXCL5

Chr 4

C-X-C motif chemokine ligand 5

Also known as: ENA-78, SCYB5

NCBI Gene: 6374 ENSG00000163735 UniProt: P42830 OMIM: 600324

Encodes epithelial neutrophil-activating peptide 78 (ENA-78), a chemokine that recruits and activates neutrophils through binding to CXCR2 receptor and promotes angiogenesis and tissue remodeling. No pediatric neurologic diseases have been associated with mutations in this gene based on the available data. This gene shows very low constraint against loss-of-function variants (pLI near 0, LOEUF 1.9), indicating tolerance to protein-truncating mutations.

OMIM ResearchSummary from RefSeq, UniProt

This gene encodes a protein that is a member of the CXC subfamily of chemokines. Chemokines, which recruit and activate leukocytes, are classified by function (inflammatory or homeostatic) or by structure. This protein is proposed to bind the G-protein coupled receptor chemokine (C-X-C motif) receptor 2 to recruit neutrophils, to promote angiogenesis and to remodel connective tissues. This protein is thought to play a role in cancer cell proliferation, migration, and invasion. [provided by RefSeq, May 2013]

OMIM ResearchGenerating clinical summary…

DNmechanismLOEUF 1.91

Clinical Summary— CXCL5

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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

24 VUS of 27 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?

1.91LOEUF

pLI 0.000

Z-score -0.78

OE 1.37 (0.74–1.91)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.12Z-score

OE missense 1.04 (0.85–1.28)

65 obs / 62.2 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?1.37 (0.74–1.91)

0≤0.351.4

Missense OE?1.04 (0.85–1.28)

0≤0.61.4

Synonymous OE?1.15

0≤1.21.6

LoF obs/exp: 7 / 5.1Missense obs/exp: 65 / 62.2Syn Z: -0.62

This gene — mechanism propensity

0.78top 25%

GOF

0.5954th %ile

LOF

0.2191th %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

27 submitted variants in ClinVar

ClinVar

Classification Summary

VUS24

Likely Benign2

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Total
Pathogenic	0	0
Likely Pathogenic	0	0
VUS	24	24
Likely Benign	2	2
Benign	0	0
Total	26	26

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

View in ClinVar →

23 pathogenic / likely-pathogenic (of 26) ClinVar copy-number / structural variants overlap CXCL5 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →