PDGFRA
Chr 4Isolated casesSomaticplatelet derived growth factor receptor alpha
Also known as: CD140A, PDGFR-2, PDGFR2
The protein functions as a cell surface tyrosine kinase receptor for platelet-derived growth factors and is essential for embryonic development, gastrointestinal tract development, and mesenchymal cell differentiation. Mutations cause gastrointestinal stromal tumors (GIST), GIST-plus syndrome, and idiopathic hypereosinophilic syndrome through constitutive activation of downstream signaling pathways including PI3K/AKT, MAPK, and STAT cascades. These conditions typically occur as isolated cases or result from somatic mutations.
Primary Disease Associations & Inheritance
Definitive — sufficient evidence for diagnostic panels
2 total gene-disease associations curated
Some data sources returned errors (1)
ensembl: TimeoutError: The operation was aborted due to timeout
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly LoF-intolerant (top ~10% of genes)
Mild missense constraint
This gene has evidence for multiple mechanisms of pathogenicity (loss-of-function and gain-of-function). The Badonyi & Marsh model scores gain-of-function highest among its predictions, but genomic evidence (constraint, ClinVar variant spectrum, and literature) most strongly supports loss-of-function (haploinsufficiency). Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
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. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.
ClinVar Variant Classifications
900 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 0 | 0 | 2 | 0 | 2 |
Likely Pathogenic | 0 | 0 | 0 | 0 | 0 |
VUS | 28 | 429 | 37 | 9 | 503 |
Likely Benign | 1 | 6 | 131 | 193 | 331 |
Benign | 1 | 0 | 3 | 0 | 4 |
Conflicting | — | 3 | |||
| Total | 30 | 435 | 173 | 202 | 843 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
PDGFRA · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
Adapting Treatment to the Tumor Molecular Alterations for Patients With Advanced Solid Tumors: MyOwnSpecificTreatment
RECRUITINGCanadian Profiling and Targeted Agent Utilization Trial (CAPTUR)
RECRUITINGDevelopment of a Multimodal AI System for GIST Management
NOT YET RECRUITINGExternal Resources
Links to major genomics databases and tools