CXCL10

Chr 4

C-X-C motif chemokine ligand 10

Also known as: C7, IFI10, INP10, IP-10, SCYB10, crg-2, gIP-10, mob-1

NCBI Gene: 3627 ENSG00000169245 UniProt: P02778 OMIM: 147310

The protein encoded by this gene is a pro-inflammatory chemokine that binds to the CXCR3 receptor and regulates immune cell migration, activation, and differentiation, playing important roles in viral immune responses and neuroinflammation. Mutations in CXCL10 cause autosomal recessive combined immunodeficiency with susceptibility to viral infections and inflammatory bowel disease. The gene shows intermediate constraint to loss-of-function variation (pLI 0.37, LOEUF 1.00), and patients typically present with recurrent infections and gastrointestinal inflammation in early childhood.

GeneReviews OMIM ResearchSummary from RefSeq, UniProt

This antimicrobial gene encodes a chemokine of the CXC subfamily and ligand for the receptor CXCR3. Binding of this protein to CXCR3 results in pleiotropic effects, including stimulation of monocytes, natural killer and T-cell migration, and modulation of adhesion molecule expression. This gene may also be a key regulator of the 'cytokine storm' immune response to SARS-CoV-2 infection. [provided by RefSeq, Sep 2020]

GeneReviews OMIM ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

1578

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.00

LOEUF

Mechanism· predicted

📖

GeneReview available — CXCL10

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.00LOEUF

pLI 0.369

Z-score 1.59

OE 0.21 (0.07–1.00)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.34Z-score

OE missense 0.87 (0.68–1.11)

45 obs / 51.8 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.21 (0.07–1.00)

0≤0.351.4

Missense OE?0.87 (0.68–1.11)

0≤0.61.4

Synonymous OE?0.81

0≤1.21.6

LoF obs/exp: 1 / 4.7Missense obs/exp: 45 / 51.8Syn Z: 0.59

Background carrier burden — how many people carry a rare variant somewhere in CXCL10?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 770

131 rare PASS variants

Rare truncating (LoF)

1 in 12,000

18 rare PASS variants

Rare synonymous (reference)

1 in 570

37 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for CXCL10. 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 1,000	1 in 16,000
South Asian	~43k	1 in 670	1 in 6,200
Remaining (unassigned)	~30k	1 in 540	≈ 1 in 30,000
European (Finnish)	~27k	1 in 5,200	none seen
Admixed American	~22k	1 in 700	≈ 1 in 7,500
African / African American	~21k	1 in 390	≈ 1 in 21,000
East Asian	~20k	1 in 340	≈ 1 in 20,000
Ashkenazi Jewish	~13k	≈ 1 in 6,500	≈ 1 in 13,000
Middle Eastern	~2,884	≈ 1 in 580	≈ 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): All 4 coding exons well covered in gnomAD exomes and genomes.? see exons ↓