CSF2RA

Chr YAR

colony stimulating factor 2 receptor subunit alpha

Also known as: CD116, CDw116, CSF2R, CSF2RAX, CSF2RAY, CSF2RX, CSF2RY, GM-CSF-R-alpha

The CSF2RA protein is the alpha subunit of the granulocyte-macrophage colony-stimulating factor receptor, which transduces signals for proliferation, differentiation, and functional activation of hematopoietic cells. Mutations cause surfactant metabolism dysfunction, pulmonary, 4 with pseudoautosomal recessive inheritance. The gene is extremely intolerant to loss-of-function variants (pLI near zero), indicating strong selective constraint against protein-truncating mutations.

OMIMResearchSummary from RefSeq, OMIM, UniProt
MultiplemechanismARLOEUF 1.121 OMIM phenotype
Clinical SummaryCSF2RA
🧬
Gene-Disease Validity (ClinGen)
surfactant metabolism dysfunction, pulmonary, 4 · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.12LOEUF
pLI 0.000
Z-score 1.11
OE 0.75 (0.521.12)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-0.84Z-score
OE missense 1.16 (1.041.28)
260 obs / 224.7 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.75 (0.521.12)
00.351.4
Missense OE1.16 (1.041.28)
00.61.4
Synonymous OE1.45
01.21.6
LoF obs/exp: 18 / 23.9Missense obs/exp: 260 / 224.7Syn Z: -3.40
DN
0.75top 25%
GOF
0.74top 25%
LOF
0.2582th %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

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

CSF2RA · protein map & ClinVar variants

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

3D Protein StructureAlphaFold
Clinical Literature
Open Research Assistant →