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…

Active trials

126

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.85

LOEUF

Mechanism· predicted

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

Background carrier burden — how many people carry a rare variant somewhere in CXCL3?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 370

158 rare PASS variants

Rare truncating (LoF)

1 in 10,000

24 rare PASS variants

Rare synonymous (reference)

1 in 350

65 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for CXCL3. 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 360	1 in 13,000
South Asian	~43k	1 in 800	1 in 3,500
Remaining (unassigned)	~30k	1 in 420	≈ 1 in 7,400
European (Finnish)	~27k	1 in 910	≈ 1 in 20,000
Admixed American	~22k	1 in 440	≈ 1 in 5,600
African / African American	~21k	1 in 370	1 in 3,200
East Asian	~20k	1 in 210	1 in 2,500
Ashkenazi Jewish	~13k	≈ 1 in 3,000	none seen
Middle Eastern	~2,884	1 in 350	≈ 1 in 2,900

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): 3 of 4 coding exons well covered in gnomAD exomes; exon 1 marginal. Genomes: all 4.? see exons ↓