CXCL2

Chr 4

C-X-C motif chemokine ligand 2

Also known as: CINC-2a, GRO2, GROb, MGSA-b, MIP-2a, MIP2, MIP2A, SCYB2

NCBI Gene: 2920 ENSG00000081041 UniProt: P19875 OMIM: 139110

CXCL2 encodes a chemokine that is produced by activated monocytes and neutrophils at sites of inflammation and suppresses hematopoietic progenitor cell proliferation. The gene shows very low constraint against loss-of-function variants, and no definitive Mendelian diseases have been established for CXCL2 mutations in current databases. Given its role in immune regulation and hematopoiesis, pathogenic variants would likely affect inflammatory responses and blood cell development.

OMIM ResearchSummary from RefSeq, UniProt

This antimicrobial gene is part of a chemokine superfamily that encodes secreted proteins involved in immunoregulatory and inflammatory processes. The superfamily is divided into four subfamilies based on the arrangement of the N-terminal cysteine residues of the mature peptide. This chemokine, a member of the CXC subfamily, is expressed at sites of inflammation and may suppress hematopoietic progenitor cell proliferation. [provided by RefSeq, Sep 2014]

OMIM ResearchGenerating clinical summary…

DNmechanismLOEUF 1.95

Clinical Summary— CXCL2

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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

15 VUS of 21 total submissions

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Clinical Trials

3 active or recruiting trials — 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?

1.95LOEUF

pLI 0.000

Z-score -1.38

OE 1.68 (0.90–1.95)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.10Z-score

OE missense 1.04 (0.83–1.31)

53 obs / 51.0 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?1.68 (0.90–1.95)

0≤0.351.4

Missense OE?1.04 (0.83–1.31)

0≤0.61.4

Synonymous OE?1.35

0≤1.21.6

LoF obs/exp: 8 / 4.8Missense obs/exp: 53 / 51.0Syn Z: -1.30

This gene — mechanism propensity

0.77top 25%

GOF

0.5268th %ile

LOF

0.2581th %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

21 submitted variants in ClinVar

ClinVar

Classification Summary

VUS15

Likely Benign4

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	15	15
Likely Benign	4	4
Benign	0	0
Total	19	19

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

View in ClinVar →

23 pathogenic / likely-pathogenic (of 30) ClinVar copy-number / structural variants overlap CXCL2 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →