IL9

Chr 5

interleukin 9

Also known as: HP40, IL-9, P40

NCBI Gene: 3578ENSG00000145839UniProt: P15248

The protein encoded by this gene is a cytokine that acts as a regulator of a variety of hematopoietic cells. This cytokine stimulates cell proliferation and prevents apoptosis. It functions through the interleukin 9 receptor (IL9R), which activates different signal transducer and activator (STAT) proteins and thus connects this cytokine to various biological processes. The gene encoding this cytokine has been identified as a candidate gene for asthma. Genetic studies on a mouse model of asthma demonstrated that this cytokine is a determining factor in the pathogenesis of bronchial hyperresponsiveness. [provided by RefSeq, Jul 2008]

41
ClinVar variants
13
Pathogenic / LP
0.00
pLI score
4
Active trials
Clinical Summary— IL9
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
13 Pathogenic / Likely Pathogenic· 24 VUS of 41 total submissions
💊
Clinical Trials
4 active or recruiting trials — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
1.92LOEUF
pLI 0.000
Z-score -0.90
OE 1.41 (0.79–1.92)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.25Z-score
OE missense 0.92 (0.76–1.12)
70 obs / 76.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.1.41 (0.79–1.92)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.92 (0.76–1.12)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.05
0≤1.21.6
LoF obs/exp: 8 / 5.7Missense obs/exp: 70 / 76.2Syn Z: -0.22

ClinVar Variant Classifications

41 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic12
Likely Pathogenic1
VUS24
Likely Benign4
12
Pathogenic
1
Likely Pathogenic
24
VUS
4
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
12
0
12
Likely Pathogenic
0
0
1
0
1
VUS
0
20
4
0
24
Likely Benign
0
1
2
1
4
Benign
0
0
0
0
0
Total02119141

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

View in ClinVar →

Protein Context — Lollipop Plot

IL9 · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
INTERLEUKIN 9; IL9
MIM #146931 · *
📖
GeneReview available — IL9
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Alopecia Areata: Current Treatments and New Directions.
Dahabreh D et al.·Am J Clin Dermatol
2023Review
Type 2 immunity in the skin and lungs.
Akdis CA et al.·Allergy
2020Review
A human model of asthma exacerbation reveals transcriptional programs and cell circuits specific to allergic asthma.
Alladina J et al.·Sci Immunol
2023Functional
Tear biomarkers in dry eye disease: Progress in the last decade.
Kumar NR et al.·Indian J Ophthalmol
2023Review
PPAR-γ regulates the effector function of human T helper 9 cells by promoting glycolysis.
Bertschi NL et al.·Nat Commun
2023
TL1A is an epithelial alarmin that cooperates with IL-33 for initiation of allergic airway inflammation.
Schmitt P et al.·J Exp Med
2024
Positive feedback loop PU.1-IL9 in Th9 promotes rheumatoid arthritis development.
Tu J et al.·Ann Rheum Dis
2024
Precision management of acute kidney injury in the intensive care unit: current state of the art.
Stanski NL et al.·Intensive Care Med
2023Review
The impact of type 2 immunity and allergic diseases in atherosclerosis.
Fernández-Gallego N et al.·Allergy
2022Review
IL-9 signaling redirects CAR T cell fate toward CD8(+) memory and CD4(+) cycling states, enhancing antitumor efficacy.
Castelli S et al.·Immunity
2026
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
X-linked Severe Combined Immunodeficiency (XSCID)

Lentiviral Gene Transfer for Treatment of Children Older Than Two Years of Age With X-Linked Severe Combined Immunodeficiency (XSCID)

RECRUITING
NCT01306019Phase PHASE1, PHASE2National Institute of Allergy and Infectious Diseases (NIAID)Started 2012-09-25
Ex vivo culture and transduction of the patient's autologous CD34+ HSC with lentivirus vector VSV-G pseudotyped CL20- 4i-EF1alpha-hgammac-OPT vectorBusulfanPalifermin
DysferlinopathyMiyoshi MyopathyLGMDR2

Clinical, Immunological, Morphological and Genetic Characteristics of Patients With Dysferlinopathy (LGMD R2) in the RF

ENROLLING BY INVITATION
NCT04824040Artgen BiotechStarted 2020-01-15
Healthy AdultsHigh AltitudeIsolation, Social

Human Milk Oligosaccharides (HMOs) and Gut Microbiota, Immune System in Antarctica

ENROLLING BY INVITATION
NCT06133530Phase NAIU University of Applied SciencesStarted 2023-09-24
Human milk oligosaccharidesMaltose
Porphyria, Acute Intermittent

Clinical Research on Acute Intermittent Porphyria and the Use of Carbohydrate-Rich Diet as a Treatment

RECRUITING
NCT06273644Phase NANordlandssykehuset HFStarted 2024-01-27
Carbohydrates

External Resources

Links to major genomics databases and tools