CSF2RB

Chr 22AR

colony stimulating factor 2 receptor subunit beta

Also known as: CD131, CDw131, IL3RB, IL5RB, SMDP5, betaGMR

NCBI Gene: 1439 ENSG00000100368 UniProt: P32927 OMIM: 138981

The protein functions as the common beta chain of high-affinity receptors for interleukin-3, interleukin-5, and granulocyte-macrophage colony-stimulating factor, controlling hematopoietic cell production and differentiation through JAK-STAT signaling pathways. Mutations cause autosomal recessive surfactant metabolism dysfunction, pulmonary type 5, presenting as pulmonary alveolar proteinosis. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.44), indicating some intolerance to complete protein loss.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

The protein encoded by this gene is the common beta chain of the high affinity receptor for IL-3, IL-5 and CSF. Defects in this gene have been reported to be associated with protein alveolar proteinosis (PAP). [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

MultiplemechanismARLOEUF 0.441 OMIM phenotype

Clinical Summary— CSF2RB

🧬

Gene-Disease Validity (ClinGen)

surfactant metabolism dysfunction, pulmonary, 5 · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡

Population Constraint (gnomAD)

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

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.44LOEUF

pLI 0.176

Z-score 4.00

OE 0.24 (0.14–0.44)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

0.13Z-score

OE missense 0.98 (0.92–1.06)

518 obs / 526.3 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.24 (0.14–0.44)

0≤0.351.4

Missense OE?0.98 (0.92–1.06)

0≤0.61.4

Synonymous OE?1.15

0≤1.21.6

LoF obs/exp: 8 / 32.7Missense obs/exp: 518 / 526.3Syn Z: -1.81

This gene — mechanism propensity

0.7326th %ile

GOF

0.75top 25%

LOF

0.3162th %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.