IL5RA

Chr 3

interleukin 5 receptor subunit alpha

Also known as: CD125, CDw125, HSIL5R3, IL5R

The IL5RA protein is the interleukin-5 specific alpha subunit of a heterodimeric cytokine receptor that regulates eosinophil survival, differentiation, and chemotaxis through JAK-STAT signaling. Mutations cause primary immunodeficiency with eosinophilia and increased susceptibility to infections, following an autosomal recessive inheritance pattern. The gene shows minimal constraint against loss-of-function variants, consistent with viable homozygous loss in patients.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
13
Pubs (1 yr)
80
P/LP submissions
0%
P/LP missense
1.05
LOEUF
Multiple*
Mechanism· predicted
Clinical SummaryIL5RA
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
80 unique Pathogenic / Likely Pathogenic· 86 VUS of 182 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.05LOEUF
pLI 0.000
Z-score 1.36
OE 0.69 (0.461.05)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-0.59Z-score
OE missense 1.11 (1.001.24)
247 obs / 222.1 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.69 (0.461.05)
00.351.4
Missense OE1.11 (1.001.24)
00.61.4
Synonymous OE0.99
01.21.6
LoF obs/exp: 15 / 21.9Missense obs/exp: 247 / 222.1Syn Z: 0.07
DN
0.75top 25%
GOF
0.72top 25%
LOF
0.2091th %ile

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

DNprediction above median
GOFprediction 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

182 submitted variants in ClinVar

Classification Summary

Pathogenic73
Likely Pathogenic7
VUS86
Likely Benign7
Benign2
73
Pathogenic
7
Likely Pathogenic
86
VUS
7
Likely Benign
2
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
73
0
73
Likely Pathogenic
0
0
7
0
7
VUS
0
62
24
0
86
Likely Benign
0
5
1
1
7
Benign
0
0
1
1
2
Total0671062175

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

View in ClinVar →

Protein Context — Lollipop Plot

IL5RA · 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.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →