CXCL11

Chr 4

C-X-C motif chemokine ligand 11

Also known as: H174, I-TAC, IP-9, IP9, SCYB11, SCYB9B, b-R1

NCBI Gene: 6373 ENSG00000169248 UniProt: O14625 OMIM: 604852

The protein encoded by this gene is a chemokine that recruits activated T-cells through binding to the CXCR3 receptor and plays a role in central nervous system immune responses. Currently, no Mendelian diseases have been definitively associated with mutations in CXCL11 in pediatric populations. The gene shows tolerance to loss-of-function variants (pLI 0.31, LOEUF 1.14), suggesting haploinsufficiency is unlikely to cause severe developmental phenotypes.

OMIM ResearchSummary from RefSeq, UniProt

Chemokines are a group of small (approximately 8 to 14 kD), mostly basic, structurally related molecules that regulate cell trafficking of various types of leukocytes through interactions with a subset of 7-transmembrane, G protein-coupled receptors. Chemokines also play fundamental roles in the development, homeostasis, and function of the immune system, and they have effects on cells of the central nervous system as well as on endothelial cells involved in angiogenesis or angiostasis. Chemokines are divided into 2 major subfamilies, CXC and CC. This antimicrobial gene is a CXC member of the chemokine superfamily. Its encoded protein induces a chemotactic response in activated T-cells and is the dominant ligand for CXC receptor-3. The gene encoding this protein contains 4 exons and at least three polyadenylation signals which might reflect cell-specific regulation of expression. IFN-gamma is a potent inducer of transcription of this gene. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2014]

OMIM ResearchGenerating clinical summary…

DNmechanismLOEUF 1.14

Clinical Summary— CXCL11

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Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.24) despite low pLI — interpret in context.

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ClinVar Variants

15 VUS of 21 total submissions

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?

1.14LOEUF

pLI 0.314

Z-score 1.43

OE 0.24 (0.09–1.14)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.32Z-score

OE missense 0.87 (0.69–1.12)

45 obs / 51.5 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.24 (0.09–1.14)

0≤0.351.4

Missense OE?0.87 (0.69–1.12)

0≤0.61.4

Synonymous OE?1.03

0≤1.21.6

LoF obs/exp: 1 / 4.1Missense obs/exp: 45 / 51.5Syn Z: -0.10

This gene — mechanism propensity

0.7230th %ile

GOF

0.4282th %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 Benign1

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	1	1
Benign	0	0
Total	16	16

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 CXCL11 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →