CXCL3

Chr 4

C-X-C motif chemokine ligand 3

Also known as: CINC-2b, GRO3, GROg, MIP-2b, MIP2B, SCYB3

NCBI Gene: 2921 ENSG00000163734 UniProt: P19876 OMIM: 139111

The protein is a secreted chemokine that functions as a chemoattractant for neutrophils and signals through the CXCR2 receptor to mediate inflammatory responses. This gene is not loss-of-function intolerant (pLI = 0.0003, LOEUF = 1.848), and no well-established Mendelian diseases have been linked to CXCL3 mutations in current genetic databases.

OMIM ResearchSummary from RefSeq, UniProt

This antimicrobial gene encodes a member of the CXC subfamily of chemokines. The encoded protein is a secreted growth factor that signals through the G-protein coupled receptor, CXC receptor 2. This protein plays a role in inflammation and as a chemoattractant for neutrophils. [provided by RefSeq, Sep 2014]

OMIM ResearchGenerating clinical summary…

DNmechanismLOEUF 1.85

Clinical Summary— CXCL3

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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

14 VUS of 18 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?

1.85LOEUF

pLI 0.000

Z-score -0.17

OE 1.08 (0.55–1.85)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.72Z-score

OE missense 1.28 (1.05–1.58)

66 obs / 51.4 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?1.08 (0.55–1.85)

0≤0.351.4

Missense OE?1.28 (1.05–1.58)

0≤0.61.4

Synonymous OE?1.30

0≤1.21.6

LoF obs/exp: 5 / 4.6Missense obs/exp: 66 / 51.4Syn Z: -1.13

This gene — mechanism propensity

0.78top 25%

GOF

0.5759th %ile

LOF

0.2289th %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

18 submitted variants in ClinVar

ClinVar

Classification Summary

VUS14

Likely Benign3

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	14	14
Likely Benign	3	3
Benign	0	0
Total	17	17

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

View in ClinVar →

23 pathogenic / likely-pathogenic (of 27) ClinVar copy-number / structural variants overlap CXCL3 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →