CXCL9

Chr 4

C-X-C motif chemokine ligand 9

Also known as: CMK, Humig, MIG, SCYB9, crg-10

NCBI Gene: 4283 ENSG00000138755 UniProt: Q07325 OMIM: 601704

The encoded protein is a chemokine that functions as a chemoattractant for activated T cells and binds to the CXCR3 receptor, playing a role in immune and inflammatory responses. Mutations in this gene are associated with neurological disorders, though this gene shows low constraint to loss-of-function variation (pLI = 0.003, LOEUF = 1.69). A GeneReviews entry is available for detailed clinical information about associated conditions and inheritance patterns.

GeneReviews OMIM ResearchSummary from RefSeq, UniProt

DNmechanismLOEUF 1.69

Clinical Summary— CXCL9

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

23 unique Pathogenic / Likely Pathogenic· 26 VUS of 55 total submissions

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Clinical Trials

10 active or recruiting trials — potential therapeutic options may be available

Explore recent and relevant literature in Research Assistant →

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GeneReview available — CXCL9

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

1.69LOEUF

pLI 0.003

Z-score 0.40

OE 0.81 (0.39–1.69)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint

-0.03Z-score

OE missense 1.01 (0.83–1.24)

66 obs / 65.3 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios

LoF OE0.81 (0.39–1.69)

0≤0.351.4

Missense OE1.01 (0.83–1.24)

0≤0.61.4

Synonymous OE1.20

0≤1.21.6

LoF obs/exp: 4 / 5.0Missense obs/exp: 66 / 65.3Syn Z: -0.72

0.77top 25%

GOF

0.3094th %ile

LOF

0.2873th %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

55 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic23

VUS26

Likely Benign2

Benign1

Pathogenic

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	23	0	23
Likely Pathogenic	0	0	0	0
VUS	19	7	0	26
Likely Benign	1	1	0	2
Benign	0	0	1	1
Total	20	31	1	52

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

CXCL9 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

External Resources

Links to major genomics databases and tools

Franklin by Genoox

AI-powered variant curation and clinical analysis

DECIPHER

Genomic variants and phenotypes in rare disease patients

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GeneReview available — CXCL9

Authoritative clinical overview · NCBI Bookshelf · Recommended first read

Open GeneReview ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

MetforminAging

Pilot Study on Evaluating the Geroprotective Effect of Metformin

RECRUITING

NCT06459310Phase PHASE2Xuanwu Hospital, BeijingStarted 2024-06-30

Metformin Hydrochloride tabletPlacebo

Kidney TransplantRejection

Detection of Circulating Kidney DNA in Kidney Transplant Patients Facing an Episode of Graft Rejection

RECRUITING

NCT06351488Assistance Publique - Hôpitaux de ParisStarted 2024-08-21

Glioma

The Role of B7-H4 in Tumor Vaccine

RECRUITING

NCT06156150Huashan HospitalStarted 2023-11-26

tumor vaccine

Breast NeoplasmTriple Negative Breast Cancer (TNBC)HRD

PHOENIX DDR/Anti-PD-L1 Trial: A Pre-surgical Window of Opportunity and Post-surgical Adjuvant Biomarker Study of DNA Damage Response Inhibition With or Without Anti-PD-L1 Immunotherapy in Patients With Neoadjuvant Treatment Resistant Residual Triple Negative Breast Cancer

RECRUITING

NCT03740893Phase PHASE2Institute of Cancer Research, United KingdomStarted 2019-10-15

AZD6738OlaparibDurvalumab

Central Centrifugal Cicatricial AlopeciaFrontal Fibrosing Alopecia

Deucravacitinib in the Treatment of Cicatricial Alopecias

NOT YET RECRUITING

NCT07508488Phase PHASE2Icahn School of Medicine at Mount SinaiStarted 2026-04

Deucravacitinib

COVID-19Influenza

Clinical Study on the Immune Response Characteristics of Novel Coronavirus and Influenza Virus Infection

RECRUITING

NCT06667063Zhongnan HospitalStarted 2024-09-19