IL9R

Chr Y

interleukin 9 receptor

Also known as: CD129, IL-9R

The IL9R protein is a cytokine receptor that specifically binds interleukin-9 and plays an important role in immune responses against parasites. Mutations in IL9R cause X-linked severe combined immunodeficiency with hypereosinophilia, characterized by recurrent infections, eosinophilia, and immune dysfunction typically presenting in infancy. The gene shows X-linked inheritance and is located in the pseudoautosomal region, making it present on both X and Y chromosomes.

OMIMResearchSummary from RefSeq, UniProt
MultiplemechanismLOEUF 1.87
Clinical SummaryIL9R
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.87LOEUF
pLI 0.000
Z-score -1.77
OE 1.43 (1.051.87)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-2.27Z-score
OE missense 1.39 (1.281.51)
374 obs / 269.1 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE1.43 (1.051.87)
00.351.4
Missense OE1.39 (1.281.51)
00.61.4
Synonymous OE1.29
01.21.6
LoF obs/exp: 28 / 19.6Missense obs/exp: 374 / 269.1Syn Z: -2.40
DN
0.6259th %ile
GOF
0.74top 25%
LOF
0.4332th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median
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

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

IL9R · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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