CXCL1

Chr 4

C-X-C motif chemokine ligand 1

Also known as: FSP, GRO1, GROa, MGSA, MGSA-a, NAP-3, SCYB1

NCBI Gene: 2919 ENSG00000163739 UniProt: P09341 OMIM: 155730

CXCL1 encodes a secreted chemokine that functions as a chemoattractant for neutrophils and signals through the G-protein coupled receptor CXCR2 to mediate inflammatory responses. The gene shows low constraint to loss-of-function variants (pLI 0.12, LOEUF 1.18), and no Mendelian diseases have been definitively linked to CXCL1 mutations in current databases. While aberrant expression is associated with tumor progression and inflammation, pathogenic germline variants causing pediatric neurological disorders have not been established.

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. Aberrant expression of this protein is associated with the growth and progression of certain tumors. A naturally occurring processed form of this protein has increased chemotactic activity. Alternate splicing results in coding and non-coding variants of this gene. A pseudogene of this gene is found on chromosome 4. [provided by RefSeq, Sep 2014]

OMIM ResearchGenerating clinical summary…

DNmechanismLOEUF 1.18

Clinical Summary— CXCL1

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Population Constraint (gnomAD)

Low constraint (pLI 0.12) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

20 VUS of 28 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?

1.18LOEUF

pLI 0.118

Z-score 1.33

OE 0.38 (0.15–1.18)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.02Z-score

OE missense 0.99 (0.81–1.23)

61 obs / 61.3 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.38 (0.15–1.18)

0≤0.351.4

Missense OE?0.99 (0.81–1.23)

0≤0.61.4

Synonymous OE?1.65

0≤1.21.6

LoF obs/exp: 2 / 5.3Missense obs/exp: 61 / 61.3Syn Z: -2.67

This gene — mechanism propensity

0.74top 25%

GOF

0.5170th %ile

LOF

0.2776th %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

28 submitted variants in ClinVar

ClinVar

Classification Summary

VUS20

Likely Benign4

Benign1

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Total
Pathogenic	0	0
Likely Pathogenic	0	0
VUS	20	20
Likely Benign	4	4
Benign	1	1
Total	25	25

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 CXCL1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →