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…

Active trials

885

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.18

LOEUF

Mechanism· predicted

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

Background carrier burden — how many people carry a rare variant somewhere in CXCL1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 240

151 rare PASS variants

Rare truncating (LoF)

1 in 10,000

22 rare PASS variants

Rare synonymous (reference)

1 in 240

84 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for CXCL1. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 640	1 in 12,000
South Asian	~43k	1 in 160	1 in 2,400
Remaining (unassigned)	~30k	1 in 380	none seen
European (Finnish)	~27k	1 in 250	≈ 1 in 27,000
Admixed American	~22k	1 in 190	≈ 1 in 11,000
African / African American	~21k	1 in 320	≈ 1 in 21,000
East Asian	~20k	1 in 400	≈ 1 in 9,700
Ashkenazi Jewish	~13k	1 in 540	none seen
Middle Eastern	~2,884	1 in 310	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 4 coding exons well covered in gnomAD exomes and genomes.? see exons ↓