PDGFRA Gene Complete Identifier and Functional Mapping Reference
Provide a comprehensive cross-database identifier and functional mapping reference for human PDGFRA — a definitive lookup resource covering: ### Section 1: Gene identifiers For human gene PDGFRA, list ALL gene-level database identifiers. Required: - HGNC ID and approved symbol - Ensembl gene ID (ENSG...) - NCBI Entrez Gene ID - OMIM gene/locus ID - Genomic location: chromosome, start position, end position, strand (GRCh38) ### Section 2: Transcript identifiers For human gene PDGFRA, list ALL transcript-level identifiers. Required: - Ensembl transcripts: ALL ENST IDs with biotype. Total count. - RefSeq transcripts: ALL NM_ mRNA accessions. Mark which is MANE Select. - CCDS IDs. - For the CANONICAL/MANE SELECT transcript: ALL exon IDs (ENSE) with genomic coordinates and total exon count. ### Section 3: Protein identifiers For human gene PDGFRA protein product(s), list ALL protein-level identifiers. Required: - UniProt accessions: ALL entries (reviewed and unreviewed). Mark the canonical reviewed entry. - RefSeq protein: ALL NP_ accessions. - Protein domains and families: list ALL annotated domains/families with identifiers, including name, type (domain/family/superfamily), and ID. - Antibody availability: known antibody resources for the protein. ### Section 4: Structure For human gene PDGFRA protein, list ALL structural data. Required: - Experimental structures: ALL PDB IDs. For each: experimental method (X-ray/NMR/Cryo-EM) and resolution. Total count. - Predicted structures: AlphaFold model ID and confidence metrics (pLDDT). ### Section 5: Cross-species orthologs For human gene PDGFRA, list orthologous genes in key model organisms. Organisms: - Mouse (Mus musculus): gene ID, symbol - Rat (Rattus norvegicus): gene ID, symbol - Zebrafish (Danio rerio): gene ID, symbol - Fruit fly (Drosophila melanogaster): gene ID, symbol - Worm (C. elegans): gene ID, symbol - Yeast (S. cerevisiae): gene ID, symbol ### Section 6: Clinical variants & AI predictions For human gene PDGFRA, summarize clinical variants and AI predictions. Clinical variant annotations (ClinVar): - Total variant count (approximate is fine) - Breakdown by classification: Pathogenic, Likely Pathogenic, VUS, Likely Benign, Benign - TOP 30 pathogenic/likely pathogenic variants with: variant ID, HGVS notation, associated condition AI-based variant effect predictions: - Splice effect predictions: total count + TOP 30 with delta scores if known - Missense pathogenicity from AlphaMissense — total count + TOP 30 likely-pathogenic with am_pathogenicity scores. ### Section 7: Pathways & Gene Ontology For human gene PDGFRA, list biological pathways and Gene Ontology annotations. Pathway membership: - ALL biological pathways this gene participates in, with pathway IDs and names - Total pathway count Gene Ontology: - Biological Process: count and TOP 20 terms with GO IDs - Molecular Function: count and TOP 20 terms with GO IDs - Cellular Component: count and TOP 20 terms with GO IDs ### Section 8: Protein interactions & networks For human gene PDGFRA protein, summarize protein interactions and networks. Protein-protein interactions (STRING, IntAct, BioGRID, etc.): - Total interaction count (approximate) - TOP 30 highest-confidence interacting proteins with scores/evidence Protein similarity: - Structural/embedding similarity (e.g. Foldseek, ESM): TOP 20 similar proteins with scores - Sequence homology: TOP 20 homologous proteins with identity/similarity ### Section 9: Transcription factor regulatory data For human gene PDGFRA, summarize transcription factor regulatory data. If PDGFRA is a transcription factor: - Downstream targets: total count + TOP 30 with regulation type (activates/represses) and evidence - DNA binding motifs from JASPAR — all known motif IDs and motif family classification. Regardless: - Upstream regulators: TFs that regulate PDGFRA — names with evidence type (ChIP-seq / predicted / experimentally validated) If PDGFRA is not a transcription factor, say so briefly and skip the downstream/motif sections. ### Section 10: Drug & pharmacology data For human gene PDGFRA protein as a drug target, summarize pharmacology data. If PDGFRA is a known drug target: - Targeting molecules: total count in ChEMBL/DrugBank + TOP 30 by development phase (molecule ID, name, mechanism, highest phase) - Clinical trials: TOP 20 involving drugs targeting this gene — trial ID, phase, status, intervention - Pharmacogenomics: known drug-gene interactions affecting drug response + dosing guidelines if any If PDGFRA is not currently a drug target, say so briefly. ### Section 11: Expression profiles For human gene PDGFRA, summarize expression profiles. Tissue expression (GTEx, HPA, Bgee, etc.): - TOP 30 tissues with expression scores/levels (direction, units if known) - Note tissue-specific or tissue-enriched patterns Cell type expression (Tabula Sapiens, HCA, etc.): - TOP 30 cell types with expression scores - Note cell-type-specific patterns Single-cell expression: notable datasets or cell populations of interest for this gene. ### Section 12: Disease associations For human gene PDGFRA, summarize disease associations. Mendelian / monogenic disease: - Diseases caused by mutations in PDGFRA: disease name, disease ID (OMIM/Orphanet/Mondo), inheritance pattern, evidence level - Include all directly linked conditions Phenotype associations: - Clinical phenotypes associated with the gene (HPO terms where known) - TOP 30 phenotype terms with HPO IDs Complex-disease / GWAS: - Traits and diseases significantly associated via GWAS: trait name, variant, effect size, study where known - TOP 30 GWAS associations
Executive summary
PDGFRA (platelet-derived growth factor receptor alpha, HGNC:8803) is a receptor tyrosine kinase on chromosome 4 that drives proliferation, migration, and survival signaling in mesenchymal and stromal cells, making it a major oncology target. The 1,089-amino-acid protein (122.67 kDa) signals through 13 Reactome pathways — including PDGF signaling, PI3K/AKT, and RAF/MAP kinase cascades — and interacts with ~5,185 partners, with highest-confidence binding to PDGF ligands (PDGFA, PDGFB, PDGFC, PDGFD) and key effectors PIK3CA, PTPN11, and PTEN. It is expressed in 289/296 tissue conditions (Bgee), with strongest enrichment in connective tissue, synovial joint, pleura, and reproductive stroma, consistent with its canonical role as a fibroblast/mesenchymal marker. Clinically, activating mutations cause gastrointestinal stromal tumors (GIST) and inflammatory fibroid polyps (autosomal dominant, definitive evidence), and the gene is a VIP pharmacogene in PharmGKB with 7 approved tyrosine kinase inhibitors in clinical use, including imatinib, sorafenib, and ponatinib, targeting ~184 documented compounds overall.
Gene identifiers
| Identifier | Value |
|---|---|
| HGNC ID | HGNC:8803 |
| Approved symbol | PDGFRA |
| Ensembl gene ID | ENSG00000134853 |
| NCBI Entrez Gene ID | 5156 |
| OMIM gene/locus ID | 173490 |
| Chromosome | 4 |
| Start position (GRCh38) | 54,229,130 |
| End position (GRCh38) | 54,298,246 |
| Strand | + |
Transcript identifiers
Ensembl transcripts (23 total)
| Transcript ID | Biotype |
|---|---|
| ENST00000257290 | protein_coding |
| ENST00000461294 | retained_intron |
| ENST00000503856 | protein_coding |
| ENST00000504461 | protein_coding |
| ENST00000507536 | retained_intron |
| ENST00000508170 | protein_coding |
| ENST00000509092 | retained_intron |
| ENST00000509490 | nonsense_mediated_decay |
| ENST00000512143 | protein_coding |
| ENST00000512522 | protein_coding |
| ENST00000870889 | protein_coding |
| ENST00000870890 | protein_coding |
| ENST00000958745 | protein_coding |
| ENST00000958746 | protein_coding |
| ENST00000958747 | protein_coding |
| ENST00000958748 | protein_coding |
| ENST00000958749 | protein_coding |
| ENST00000958750 | protein_coding |
| ENST00000958751 | protein_coding |
| ENST00000958752 | protein_coding |
| ENST00000958753 | protein_coding |
| ENST00000958754 | protein_coding |
| ENST00000958755 | protein_coding |
RefSeq mRNA transcripts (human, chromosome 4)
| Accession | MANE Select |
|---|---|
| NM_006206 | ✓ |
| NM_001347827 | |
| NM_001347828 | |
| NM_001347829 | |
| NM_001347830 |
CCDS
| ID |
|---|
| CCDS3495 |
Canonical transcript exons (ENST00000257290 / NM_006206)
Total exons: 23
| Exon ID | Start | End | Length |
|---|---|---|---|
| ENSE00002028061 | 54229293 | 54229415 | 123 |
| ENSE00003482129 | 54258757 | 54258817 | 61 |
| ENSE00003566972 | 54267289 | 54267460 | 172 |
| ENSE00003547009 | 54267552 | 54267741 | 190 |
| ENSE00003674470 | 54270633 | 54270748 | 116 |
| ENSE00003626526 | 54272394 | 54272520 | 127 |
| ENSE00003584929 | 54273537 | 54273730 | 194 |
| ENSE00003548932 | 54274531 | 54274625 | 95 |
| ENSE00003571737 | 54274841 | 54274973 | 133 |
| ENSE00003673604 | 54277388 | 54277492 | 105 |
| ENSE00003529069 | 54277896 | 54278006 | 111 |
| ENSE00003464046 | 54278362 | 54278515 | 154 |
| ENSE00003647873 | 54280316 | 54280482 | 167 |
| ENSE00003580939 | 54264919 | 54265049 | 131 |
| ENSE00003634368 | 54263667 | 54263927 | 261 |
| ENSE00003785223 | 54261095 | 54261412 | 318 |
| ENSE00003483772 | 54285371 | 54285486 | 116 |
| ENSE00003570052 | 54285841 | 54285963 | 123 |
| ENSE00003586981 | 54288799 | 54288898 | 100 |
| ENSE00003462897 | 54289009 | 54289114 | 106 |
| ENSE00003681641 | 54287430 | 54287541 | 112 |
| ENSE00003471835 | 54290313 | 54290554 | 242 |
| ENSE00001226318 | 54295125 | 54298245 | 3121 |
Protein identifiers
UniProt accessions
- P16234 (REVIEWED - canonical) - Platelet-derived growth factor receptor alpha (1089 aa, 122.67 kDa)
- D6RDX0 (unreviewed)
- D6RG11 (unreviewed)
- D6RIG5 (unreviewed)
- D6RJH0 (unreviewed)
RefSeq protein (NP_)
- NP_006197 (MANE select)
- NP_001334758
Protein domains and families
InterPro (15 entries)
| ID | Name | Type |
|---|---|---|
| IPR000719 | Protein kinase domain | Domain |
| IPR001245 | Serine/Threonine/Tyrosine kinase catalytic domain | Domain |
| IPR001824 | Tyrosine kinase receptor 3 conserved site | Conserved_site |
| IPR003598 | Immunoglobulin subtype 2 | Domain |
| IPR003599 | Immunoglobulin subtype | Domain |
| IPR007110 | Immunoglobulin-like domain | Domain |
| IPR008266 | Tyrosine kinase active site | Active_site |
| IPR011009 | Kinase-like domain superfamily | Homologous_superfamily |
| IPR013098 | Immunoglobulin I-set | Domain |
| IPR013783 | Immunoglobulin-like fold superfamily | Homologous_superfamily |
| IPR017441 | Protein kinase ATP binding site | Binding_site |
| IPR020635 | Tyrosine kinase catalytic domain | Domain |
| IPR027290 | PDGFRA | Family |
| IPR036179 | Immunoglobulin-like domain superfamily | Homologous_superfamily |
| IPR050122 | Receptor tyrosine kinase (RTK) | Family |
Pfam domains
- PF07679
- PF07714
- PF25305
SMART domains
- SM00219, SM00220, SM00408, SM00409
Superfamily (SUPFAM)
- SSF48726, SSF56112
CDD (Conserved Domain Database)
- CD05105, CD05859, CD05861
Antibody availability
No direct links in biobtree antibody database. However, PDGFRA is widely available from commercial antibody vendors (Cell Signaling Technology, Abcam, R&D Systems, Santa Cruz Biotechnology, etc.) with multiple monoclonal and polyclonal antibodies targeting various epitopes.
Structure
Experimental Structures (PDB)
Total: 15 structures
| PDB ID | Method | Resolution (Å) |
|---|---|---|
| 5GRN | X-ray diffraction | 1.77 |
| 5K5X | X-ray diffraction | 2.168 |
| 6A32 | X-ray diffraction | 1.87 |
| 6JOI | X-ray diffraction | 3.1 |
| 6JOJ | X-ray diffraction | 2.6 |
| 6JOK | X-ray diffraction | 3.8 |
| 6JOL | X-ray diffraction | 1.9 |
| 8PQH | X-ray diffraction | 2.5 |
| 8PQI | X-ray diffraction | 2.6 |
| 8PQJ | X-ray diffraction | 1.82 |
| 8PQK | X-ray diffraction | 2.0 |
| 9GZH | X-ray diffraction | 2.2 |
| 1GQ5 | X-ray diffraction | 2.2 |
| 7LBF | Cryo-EM | 2.8 |
| 7RAM | Cryo-EM | 3.43 |
Breakdown: 13 X-ray, 2 Cryo-EM
Predicted Structures
AlphaFold Model: P16234
Confidence (pLDDT): 72.91
High-confidence regions (pLDDT > 90): 25% of structure
Cross-species orthologs
| Organism | Gene ID | Symbol |
|---|---|---|
| Mouse (Mus musculus) | 18595 | Pdgfra |
| Rat (Rattus norvegicus) | 25267 | Pdgfra |
| Zebrafish (Danio rerio) | 386856 | pdgfra |
| Fruit fly (Drosophila melanogaster) | none | none |
| Worm (C. elegans) | none | none |
| Yeast (S. cerevisiae) | none | none |
Based on the biobtree data I’ve collected, here’s the comprehensive summary:
Clinical variants & AI predictions
ClinVar Overview
| Classification | Count | Notes |
|---|---|---|
| Total variants | ~3,760 | Germline variants annotated |
| Pathogenic | 4 | Mostly deletions/insertions |
| Likely Pathogenic | 1 | Y555C mutation |
| Uncertain Significance | ~2,000+ | Majority of variants |
| Likely Benign | ~1,000+ | Common synonymous/intronic |
| Benign | ~100+ | Well-characterized neutral variants |
| Conflicting Classifications | ~50+ | Multiple submitter disagreement |
Top Pathogenic/Likely Pathogenic ClinVar Variants
| Variant ID | HGVS Notation | Classification | Associated Condition/Notes |
|---|---|---|---|
| 13545 | NM_006206.6(PDGFRA):c.2533_2544del (p.His845_Asn848del) | Pathogenic | In-frame deletion in kinase domain |
| 13547 | NM_006206.6(PDGFRA):c.1681_1682insAGAGGG (p.Arg560_Val561insGluArg) | Pathogenic | Insertion near kinase domain |
| 13548 | NM_006206.6(PDGFRA):c.1679_1693del (p.Arg560_Ser564del) | Pathogenic | Deletion in kinase domain |
| 13549 | NM_006206.6(PDGFRA):c.1696_1713del (p.Ser566_Glu571del) | Pathogenic | Kinase domain deletion |
| 13552 | NM_006206.6(PDGFRA):c.1664A>G (p.Tyr555Cys) | Likely Pathogenic | Kinase domain missense |
AlphaMissense Predictions
Total likely-pathogenic missense predictions: ~1,500+ (from 7,179 total missense variants)
Top 30 Likely-Pathogenic Variants with AlphaMissense Scores:
| Position | Variant | am_pathogenicity | Effect |
|---|---|---|---|
| 49 | C49S | 0.999 | Stop codon/Ser |
| 49 | C49R | 0.998 | Cys>Arg |
| 49 | C49Y | 0.997 | Cys>Tyr |
| 47 | L47P | 0.996 | Leu>Pro |
| 49 | C49F | 0.995 | Cys>Phe |
| 49 | C49G | 0.987 | Cys>Gly |
| 45 | F45C | 0.981 | Phe>Cys |
| 45 | F45S | 0.983 | Phe>Ser |
| 47 | L47R | 0.978 | Leu>Arg |
| 47 | L47Q | 0.971 | Leu>Gln |
| 45 | F45L | 0.963 | Phe>Leu |
| 28 | P28H | 0.969 | Pro>His |
| 32 | P32R | 0.788 | Pro>Arg |
| 28 | P28R | 0.943 | Pro>Arg |
| 28 | P28S | 0.928 | Pro>Ser |
| 43 | S43P | 0.894 | Ser>Pro |
| 30 | I30N | 0.909 | Ile>Asn |
| 28 | P28T | 0.887 | Pro>Thr |
| 30 | I30T | 0.883 | Ile>Thr |
| 30 | I30S | 0.881 | Ile>Ser |
| 45 | F45Y | 0.675 | Phe>Tyr |
| 32 | P32S | 0.681 | Pro>Ser |
| 46 | S46P | 0.739 | Ser>Pro |
| 39 | V39G | 0.729 | Val>Gly |
| 32 | P32Q | 0.728 | Pro>Gln |
| 28 | P28L | 0.781 | Pro>Leu |
| 32 | P32L | 0.648 | Pro>Leu |
| 45 | F45V | 0.629 | Phe>Val |
| 31 | L31P | 0.666 | Leu>Pro |
| 45 | F45I | 0.597 | Phe>Ile |
SpliceAI Predictions
Total splice-altering variants: ~4,137 predictions
Prediction Types:
- Donor loss events: ~1,200+
- Donor gain events: ~1,500+
- Acceptor loss events: ~600+
- Acceptor gain events: ~800+
High-confidence predictions (scores >0.8) include variants at splice junction positions with strong effects on canonical splice site sequences. Notable examples: 4:54229416 (donor loss, 0.98), 4:54229417 (donor loss, 0.98), 4:54229412 (donor gain, 0.98).
Pathways & Gene Ontology
Reactome Pathways
| Pathway ID | Pathway Name |
|---|---|
| R-HSA-186797 | Signaling by PDGF |
| R-HSA-1257604 | PIP3 activates AKT signaling |
| R-HSA-186763 | Downstream signal transduction |
| R-HSA-5673001 | RAF/MAP kinase cascade |
| R-HSA-6811558 | PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling |
| R-HSA-9673767 | Signaling by PDGFRA transmembrane, juxtamembrane and kinase domain mutants |
| R-HSA-9673770 | Signaling by PDGFRA extracellular domain mutants |
| R-HSA-2219530 | Constitutive Signaling by Aberrant PI3K in Cancer |
| R-HSA-9674396 | Imatinib-resistant PDGFR mutants |
| R-HSA-9674401 | Sunitinib-resistant PDGFR mutants |
| R-HSA-9674403 | Regorafenib-resistant PDGFR mutants |
| R-HSA-9674404 | Sorafenib-resistant PDGFR mutants |
| R-HSA-9674428 | PDGFR mutants bind TKIs |
Total: 13 Reactome pathways
MSigDB Gene Sets
PDGFRA is a member of 100+ gene sets in MSigDB (Molecular Signatures Database), including collections from GO, KEGG, BioCarta, transcription factor targets, cancer modules, and miRNA targets.
Gene Ontology Annotations
Total GO terms: 70 (43 Biological Process, 11 Molecular Function, 16 Cellular Component)
Biological Process (43 terms, top 20)
| GO ID | Term |
|---|---|
| GO:0001553 | luteinization |
| GO:0001701 | in utero embryonic development |
| GO:0001775 | cell activation |
| GO:0002244 | hematopoietic progenitor cell differentiation |
| GO:0007169 | cell surface receptor protein tyrosine kinase signaling pathway |
| GO:0008210 | estrogen metabolic process |
| GO:0008284 | positive regulation of cell population proliferation |
| GO:0010544 | negative regulation of platelet activation |
| GO:0016477 | cell migration |
| GO:0018108 | peptidyl-tyrosine phosphorylation |
| GO:0023019 | signal transduction involved in regulation of gene expression |
| GO:0030198 | extracellular matrix organization |
| GO:0030324 | lung development |
| GO:0030325 | adrenal gland development |
| GO:0030335 | positive regulation of cell migration |
| GO:0030539 | male genitalia development |
| GO:0032956 | regulation of actin cytoskeleton organization |
| GO:0033327 | Leydig cell differentiation |
| GO:0034614 | cellular response to reactive oxygen species |
| GO:0035790 | platelet-derived growth factor receptor-alpha signaling pathway |
Molecular Function (11 terms)
| GO ID | Term |
|---|---|
| GO:0004672 | protein kinase activity |
| GO:0004714 | transmembrane receptor protein tyrosine kinase activity |
| GO:0005018 | platelet-derived growth factor alpha-receptor activity |
| GO:0005021 | vascular endothelial growth factor receptor activity |
| GO:0005161 | platelet-derived growth factor receptor binding |
| GO:0005524 | ATP binding |
| GO:0038085 | vascular endothelial growth factor binding |
| GO:0042803 | protein homodimerization activity |
| GO:0044877 | protein-containing complex binding |
| GO:0048407 | platelet-derived growth factor binding |
| GO:0160185 | phospholipase C activator activity |
Cellular Component (16 terms)
| GO ID | Term |
|---|---|
| GO:0005634 | nucleus |
| GO:0005654 | nucleoplasm |
| GO:0005737 | cytoplasm |
| GO:0005789 | endoplasmic reticulum membrane |
| GO:0005794 | Golgi apparatus |
| GO:0005829 | cytosol |
| GO:0005886 | plasma membrane |
| GO:0005902 | microvillus |
| GO:0005929 | cilium |
| GO:0009897 | external side of plasma membrane |
| GO:0016020 | membrane |
| GO:0016604 | nuclear body |
| GO:0030054 | cell junction |
| GO:0032991 | protein-containing complex |
| GO:0043235 | receptor complex |
| GO:1990270 | platelet-derived growth factor receptor-ligand complex |
Protein interactions & networks
Protein-protein interactions
Total interaction count (approximate): ~5,185 interactions
- STRING: 4,664 interactions
- BioGRID: 432 interactions
- IntAct: 89 interactions
TOP 30 highest-confidence interacting proteins (STRING, scores 0-1000):
| Rank | Protein | UniProt | Score | Description |
|---|---|---|---|---|
| 1 | PDGFA | P04085 | 998 | Platelet-derived growth factor subunit A |
| 2 | PDGFC | Q9NRA1 | 998 | Platelet-derived growth factor C |
| 3 | PDGFB | P01127 | 996 | Platelet-derived growth factor subunit B |
| 4 | PDGFD | Q9GZP0 | 991 | Platelet-derived growth factor D |
| 5 | FIP1 | Q6UN15 | 981 | Pre-mRNA 3’-end-processing factor FIP1 |
| 6 | FGF2 | P09038 | 941 | Fibroblast growth factor 2 |
| 7 | PTPN11 | Q06124 | 889 | Tyrosine-protein phosphatase non-receptor type 11 |
| 8 | EGF | P01133 | 877 | Pro-epidermal growth factor |
| 9 | PIK3CA | P42336 | 867 | PI3K catalytic subunit alpha isoform |
| 10 | KITLG | P21583 | 809 | Kit ligand |
| 11 | OLIG2 | Q13516 | 809 | Oligodendrocyte transcription factor 2 |
| 12 | ANO1 | Q5XXA6 | 804 | Anoctamin-1 |
| 13 | NF1 | P21359 | 803 | Neurofibromin |
| 14 | PIK3R1 | P27986 | 796 | PI3K regulatory subunit alpha |
| 15 | PTEN | P60484 | 796 | Phosphatase PTEN |
| 16 | KRAS | P01116 | 783 | GTPase KRas |
| 17 | SDHB | Q99643 | 776 | Succinate dehydrogenase cytochrome b560 |
| 18 | TGFB1 | P01137 | 761 | Transforming growth factor beta-1 |
| 19 | FGF13 | Q92913 | 760 | Fibroblast growth factor 13 |
| 20 | CSPG4 | Q6UVK1 | 751 | Chondroitin sulfate proteoglycan 4 |
| 21 | CXCL12 | P48061 | 749 | Stromal cell-derived factor 1 |
| 22 | SDHB | P21912 | 746 | Succinate dehydrogenase iron-sulfur subunit |
| 23 | CTNNB1 | P35222 | 745 | Catenin beta-1 |
| 24 | NES | P48681 | 739 | Nestin |
| 25 | SDHD | O14521 | 735 | Succinate dehydrogenase cytochrome b small subunit |
| 26 | CD34 | P28906 | 731 | Hematopoietic progenitor cell antigen CD34 |
| 27 | IDH1 | O75874 | 727 | Isocitrate dehydrogenase [NADP] cytoplasmic |
| 28 | ENG | P17813 | 725 | Endoglin |
| 29 | PECAM1 | P16284 | 723 | Platelet endothelial cell adhesion molecule |
| 30 | GFAP | P14136 | 722 | Glial fibrillary acidic protein |
Key IntAct interactions (high confidence, 0.68-0.77 score):
- PDGFRA ↔ PDGFB (0.73 - direct interaction)
- PDGFRA ↔ PDGFA (0.69 - direct interaction)
- PDGFRA ↔ PDGFC (0.66 - direct interaction)
- PDGFRA ↔ PDGFRB (0.77 - physical association)
- PDGFRA ↔ EGFR (0.68 - physical association)
- PDGFRA ↔ CRK (0.67 - association)
Protein similarity
TOP 20 structural/embedding similarity (ESM2, scores 0-1.0):
| Rank | Protein | UniProt | Top Score | Avg Score |
|---|---|---|---|---|
| 1 | - | O08747 | 1.0000 | 0.9906 |
| 2 | - | O60674 | 1.0000 | 0.9903 |
| 3 | - | P43481 | 1.0000 | 0.9955 |
| 4 | - | Q00495 | 1.0000 | 0.9939 |
| 5 | - | Q14982 | 1.0000 | 0.9899 |
| 6 | - | Q28317 | 1.0000 | 0.9954 |
| 7 | - | P09581 | 1.0000 | 0.9939 |
| 8 | - | P60029 | 1.0000 | 0.9901 |
| 9 | - | A7MB46 | 0.9999 | 0.9876 |
| 10 | - | B3NBB6 | 0.9998 | 0.9896 |
| 11 | - | B4HVU2 | 0.9999 | 0.9895 |
| 12 | - | B4PD96 | 0.9998 | 0.9888 |
| 13 | - | B4QMF4 | 0.9999 | 0.9892 |
| 14 | - | C5IAW9 | 0.9999 | 0.9906 |
| 15 | - | G3V9H8 | 0.9997 | 0.9898 |
| 16 | - | O15146 | 0.9997 | 0.9914 |
| 17 | - | O19064 | 0.9999 | 0.9904 |
| 18 | - | O57261 | 0.9999 | 0.9870 |
| 19 | - | O95185 | 0.9999 | 0.9907 |
| 20 | - | O97799 | 0.9998 | 0.9957 |
TOP 20 sequence homology (DIAMOND BLAST, % identity & bitscore):
| Rank | Protein | UniProt | Identity % | Bitscore |
|---|---|---|---|---|
| 1 | - | P35917 | 95.90 | 2650 |
| 2 | - | P35918 | 95.20 | 2582 |
| 3 | - | P35969 | 92.60 | 2469 |
| 4 | - | P53767 | 92.60 | 2469 |
| 5 | - | P35916 | 86.80 | 2385 |
| 6 | - | P35968 | 85.80 | 2335 |
| 7 | - | P17948 | 82.40 | 2236 |
| 8 | - | P20786 | 96.00 | 2051 |
| 9 | - | P26618 | 96.00 | 2050 |
| 10 | - | P05622 | 96.60 | 2091 |
| 11 | - | Q05030 | 96.60 | 2091 |
| 12 | - | P26619 | 75.60 | 1588 |
| 13 | - | P09619 | 90.40 | 1933 |
| 14 | - | Q03142 | 95.50 | 1519 |
| 15 | - | P22455 | 89.80 | 1431 |
| 16 | - | P07949 | 85.30 | 1949 |
| 17 | - | P07333 | 83.50 | 1565 |
| 18 | - | P10721 | 97.80 | 1840 |
| 19 | - | P13369 | 99.10 | 1827 |
| 20 | - | Q00342 | 85.90 | 1738 |
Transcription factor regulatory data
PDGFRA is not a transcription factor — it encodes a receptor tyrosine kinase (platelet-derived growth factor receptor alpha) involved in cell signaling, not direct transcriptional regulation. Therefore, downstream targets and DNA binding motif sections do not apply.
Upstream regulators
PDGFRA is regulated by 26 transcription factors (from CollecTRI):
| TF Name | Regulation | Confidence | Evidence Source |
|---|---|---|---|
| ATF4 | Activation | High | ExTRI, GEREDB, NTNU Curated |
| E2F1 | Activation | High | Curated |
| GATA6 | Activation | High | Curated |
| GLI1 | Activation | High | Curated |
| CREB1 | Repression | High | Curated |
| PAX3 | Repression | High | Curated |
| POU5F1 | Repression | High | Curated |
| CEBPD | Unknown | High | Curated |
| FOS | Unknown | High | Curated |
| NFKB | Unknown | High | Curated |
| PAX1 | Unknown | High | Curated |
| SP1 | Unknown | High | ExTRI |
| SP3 | Unknown | High | Curated |
| YY1 | Unknown | High | Curated |
| ZNF148 | Unknown | High | Curated |
| ZNF354C | Unknown | High | Curated |
| CEBPG | Unknown | High | Curated |
| ASCL1 | Activation | Low | GEREDB, ExTRI |
| FOXO1 | Repression | Low | Predicted |
| GLI2 | Activation | — | Predicted |
| HOXC6 | Activation | — | Predicted |
| MIXL1 | Activation | — | Predicted |
| CEBPB | Unknown | — | Predicted |
| GATA4 | Unknown | — | Predicted |
| PPARG | Repression | — | Predicted |
| SOX10 | Unknown | — | Predicted |
Evidence classification: High confidence entries represent experimentally validated/curated regulatory interactions; Low confidence and unmarked entries represent predicted interactions from computational methods.
Drug & pharmacology data
PDGFRA is a well-established drug target with 184+ inhibitor molecules in ChEMBL and 894 xref entries indicating additional binding compounds.
Targeting Molecules: Top Approved Drugs (Phase 4)
| ChEMBL ID | Drug Name | Mechanism | Phase |
|---|---|---|---|
| CHEMBL1642 | IMATINIB MESYLATE | BCR-ABL & PDGFRA tyrosine kinase inhibitor | 4 |
| CHEMBL1336 | SORAFENIB | Multi-kinase inhibitor (PDGFRA, PDGFRB, VEGFR, c-KIT, RAF) | 4 |
| CHEMBL1289926 | AXITINIB | VEGFR, PDGFRA, c-KIT inhibitor | 4 |
| CHEMBL1289601 | LENVATINIB | Multi-target inhibitor (PDGFRA, FGFR, VEGFR, RET) | 4 |
| CHEMBL1289494 | TIVOZANIB | VEGFR1-3, PDGFRA, c-KIT inhibitor | 4 |
| CHEMBL1287853 | FEDRATINIB | JAK/FLT3 inhibitor (activity on PDGFRA) | 4 |
| CHEMBL1171837 | PONATINIB | BCR-ABL & pan-kinase inhibitor (including PDGFRA) | 4 |
Phase 3 / Phase 2 Investigational Agents (30+ additional compounds):
- CHEMBL101253: Vatalanib (Phase 3)
- CHEMBL1230609: Foretinib (Phase 2)
- CHEMBL124660: Tandutinib (Phase 2)
- CHEMBL119385: Neflamapimod (Phase 2)
- CHEMBL1738757: Rebastinib (Phase 2)
- CHEMBL103667: Doramapimod (Phase 2)
- CHEMBL1721885: SU-014813 (Phase 2)
- Plus 150+ Phase 0-1 experimental compounds
Total Coverage: ~184 PDGFRA-directed molecules quantified in ChEMBL
Clinical Trials: Top Representative Trials
Notable trials with approved PDGFRA inhibitors:
| Trial ID | Title | Phase | Status | Intervention |
|---|---|---|---|---|
| NCT00471497 | Imatinib vs. Nilotinib in Ph+ CML | 3 | Completed | Imatinib; Nilotinib (TKI) |
| NCT00481247 | Dasatinib vs Imatinib in CML-CP | 3 | Completed | Imatinib; Dasatinib |
| NCT00574873 | Bosutinib vs Imatinib in CML | 3 | Completed | Imatinib; Bosutinib |
| NCT00760877 | Nilotinib vs Imatinib in CML-CP | 3 | Completed | Imatinib; Nilotinib |
| NCT00785785 | Nilotinib vs Imatinib in GIST | 3 | Completed | Imatinib; Nilotinib |
| NCT00116935 | Imatinib Duration in GIST | 3 | Completed | Imatinib monotherapy (12 vs 36 mo) |
| NCT01460693 | Imatinib vs Dasatinib in CML | 3 | Completed | Imatinib; Dasatinib |
| NCT01511289 | Radotinib vs Imatinib in CML-CP | 3 | Completed | Imatinib; Radotinib |
| NCT02130557 | Bosutinib vs Imatinib in CML | 3 | Completed | Imatinib; Bosutinib |
| NCT03589326 | Ponatinib vs Imatinib in Ph+ ALL | 3 | Active/Recruiting | Imatinib; Ponatinib |
| NCT02413736 | Imatinib Adjuvant in GIST | 3 | Active | Imatinib (3 vs 5 years) |
| NCT04971226 | Asciminib vs TKIs in CML-CP | 3 | Active | Imatinib; Asciminib; other TKIs |
| NCT04394416 | Imatinib for COVID-19 (exploratory) | 3 | Completed | Imatinib |
Indications with PDGFRA inhibitor trials:
- Chronic Myeloid Leukemia (CML) — primary indication
- Gastrointestinal Stromal Tumors (GIST) — imatinib/sunitinib standard
- Acute Lymphoblastic Leukemia Ph+ (ALL)
- Hypereosinophilic Syndrome
- Pulmonary Arterial Hypertension (exploratory)
Pharmacogenomics
Gene Status: PDGFRA is a VIP (Very Important Pharmacogene) in PharmGKB with documented variant annotations (PA33147).
Known Drug-Gene Interactions:
- PDGFRA mutations/rearrangements drive imatinib resistance in CML and GIST; specific mutations (e.g., D842V) confer resistance
- Relevant conditions: PDGFRA rearrangements associated with myeloid neoplasms (MONDO:0015689, MONDO:0015688) affecting treatment response
- Pharmacogenomic implications:
- Patients with PDGFRA mutations may require dose escalation or switch to next-generation inhibitors (e.g., ponatinib for resistant mutations)
- No formal CPIC guidelines published; clinical decisions guided by mutation analysis and kinase domain sequencing
Dosing: Imatinib dosing (standard) is 400 mg daily for CML; escalation to 600–800 mg considered for suboptimal response or resistance. Dose adjustments may be needed for severe hepatic/renal impairment.
Summary: PDGFRA is a highly validated oncology drug target with 7 approved tyrosine kinase inhibitors in clinical use (imatinib, sorafenib, axitinib, lenvatinib, tivozanib, fedratinib, ponatinib) and 177+ compounds in development, with strong evidence in CML, GIST, and hematologic malignancies.
Expression profiles
Tissue Expression (Bgee)
PDGFRA shows ubiquitous expression across 289/296 tissue conditions (gold quality: 285/289).
| Rank | Tissue | Expression Score | Quality |
|---|---|---|---|
| 1 | Tibia | 99.38 | Gold |
| 2 | Decidua | 99.29 | Gold |
| 3 | Synovial joint | 99.19 | Gold |
| 4 | Pericardium | 99.04 | Gold |
| 5 | Lower lobe of lung | 98.85 | Gold |
| 6 | Pylorus | 98.75 | Gold |
| 7 | Stromal cell of endometrium | 98.74 | Gold |
| 8 | Parietal pleura | 98.67 | Gold |
| 9 | Caput epididymis | 98.58 | Gold |
| 10 | Left ovary | 98.56 | Gold |
| 11 | Pleura | 98.43 | Gold |
| 12 | Cauda epididymis | 98.42 | Gold |
| 13 | Right ovary | 98.29 | Gold |
| 14 | Layer of synovial tissue | 98.11 | Gold |
| 15 | Visceral pleura | 98.06 | Gold |
| 16 | Germinal epithelium of ovary | 97.97 | Gold |
| 17 | Urethra | 97.96 | Gold |
| 18 | Mucosa of urinary bladder | 97.96 | Gold |
| 19 | Ovary | 97.96 | Gold |
| 20 | Mammary duct | 97.90 | Gold |
| 21 | Skin of hip | 97.84 | Gold |
| 22 | Superficial temporal artery | 97.82 | Gold |
| 23 | Calcaneal tendon | 97.81 | Gold |
| 24 | Tendon of biceps brachii | 97.78 | Gold |
| 25 | Epithelium of mammary gland | 97.69 | Gold |
| 26 | Heart right ventricle | 97.56 | Gold |
| 27 | Cardia of stomach | 97.54 | Gold |
| 28 | Corpus epididymis | 97.47 | Gold |
| 29 | Jejunal mucosa | 97.30 | Gold |
| 30 | Tendon | 97.28 | Gold |
Average expression score: 87.97 (across all 296 conditions)
Tissue-enriched patterns: Strong expression in connective tissues (tendons, pleura, synovial tissue), reproductive organs (ovary, mammary), and mesenchymal compartments. Notable high expression in bone (tibia) and joint tissues, consistent with PDGFRA’s role in fibroblast and mesenchymal cell development.
Single-Cell Expression (SCXA)
- Total experiments: 19 marker experiments
- Cell clusters: 2,728 clusters across datasets
- Expression range:
- Maximum mean: 6,405.27 (TPM/UMI equivalent)
- Average mean: 201.58
Notable datasets: Single Cell Expression Atlas integrates major single-cell studies including tissue-specific scRNA-seq cohorts. PDGFRA is highly expressed as a marker gene across multiple cell clusters, primarily in fibroblasts, myofibroblasts, pericytes, and mesenchymal progenitor populations.
Cell Type-Specific Patterns
Cell-type enrichment inferred from tissue and single-cell data:
- Fibroblasts and myofibroblasts (connective tissue across all organs)
- Pericytes and vascular smooth muscle cells (reflected in artery, tendon, pleura expression)
- Mesenchymal stromal cells (bone, decidua, endometrial stroma)
- Reproductive tissue stroma (high ovarian and mammary expression)
PDGFRA is a canonical marker of fibroblast/mesenchymal differentiation and serves as a receptor for PDGF ligands in stromal compartments across tissues.
Disease associations
Mendelian/Monogenic Diseases
OMIM-linked diseases (via GENCC):
| Disease Name | OMIM ID | Inheritance Pattern | Evidence Level | Submitter |
|---|---|---|---|---|
| Polyps, multiple and recurrent inflammatory fibroid, gastrointestinal | 175510 | Autosomal dominant | Definitive | G2P |
| Polyps, multiple and recurrent inflammatory fibroid, gastrointestinal | 175510 | Autosomal dominant | Strong | Genomics England PanelApp |
| Polyps, multiple and recurrent inflammatory fibroid, gastrointestinal | 175510 | Autosomal dominant | Moderate | Ambry Genetics |
| Gastrointestinal stromal tumor | 606764 | Autosomal dominant | Strong | Labcorp Genetics (formerly Invitae) |
| Isolated cleft palate | 119540 | Unknown | Limited | Labcorp Genetics (formerly Invitae) |
Mondo disease ontology IDs (via ClinVar):
- MONDO:0011719 – Gastrointestinal stromal tumor
- MONDO:0008285 – Polyps, multiple and recurrent inflammatory fibroid, gastrointestinal
- MONDO:0007336 – Isolated cleft palate
- MONDO:0015356 – Hereditary neoplastic syndrome
- MONDO:0011895 – Idiopathic hypereosinophilic syndrome
- MONDO:0019452 – Myeloproliferative neoplasm, unclassifiable
- MONDO:0008170 – Ovarian cancer
- MONDO:0002032 – Colon carcinoma
- MONDO:0005097 – Squamous cell lung carcinoma
- MONDO:0006279 – Lung sarcomatoid carcinoma
Orphanet rare disease IDs (via ClinVar):
- ORD:44890 – Gastrointestinal stromal tumor (7 genes, 18 phenotypes)
- ORD:3260 – Idiopathic hypereosinophilic syndrome (78 phenotypes)
- ORD:140162 – Inherited cancer-predisposing syndrome
- ORD:86830 – Chronic myeloproliferative disease, unclassifiable (1 gene)
- ORD:213500 – Rare ovarian cancer
- ORD:2014 – Cleft palate
Phenotype Associations (HPO Terms)
Top 30 clinical phenotypes associated with PDGFRA (55 total):
- HP:0000006 – Autosomal dominant inheritance
- HP:0000175 – Cleft palate
- HP:0000202 – Orofacial cleft
- HP:0000220 – Velopharyngeal insufficiency
- HP:0000327 – Hypoplasia of the maxilla
- HP:0000403 – Recurrent otitis media
- HP:0000405 – Conductive hearing impairment
- HP:0000689 – Dental malocclusion
- HP:0000707 – Abnormality of the nervous system
- HP:0000750 – Delayed speech and language development
- HP:0000988 – Skin rash
- HP:0000989 – Pruritus
- HP:0001392 – Abnormality of the liver
- HP:0001442 – Typified by somatic mosaicism
- HP:0001611 – Hypernasal speech
- HP:0001723 – Restrictive cardiomyopathy
- HP:0001744 – Splenomegaly
- HP:0001880 – Increased total eosinophil count
- HP:0001903 – Anemia
- HP:0002015 – Dysphagia
- HP:0002017 – Nausea and vomiting
- HP:0002019 – Constipation
- HP:0002033 – Poor suck
- HP:0002113 – Pulmonary infiltrates
- HP:0002239 – Gastrointestinal hemorrhage
- HP:0002240 – Hepatomegaly
- HP:0002576 – Intussusception
- HP:0003326 – Myalgia
- HP:0004395 – Malnutrition
- HP:0004936 – Venous thrombosis
Additional notable phenotypes (31-55):
- HP:0005214 – Intestinal obstruction
- HP:0005547 – Myeloproliferative disorder
- HP:0006292 – Abnormality of dental eruption
- HP:0006342 – Peg-shaped maxillary lateral incisors
- HP:0006685 – Endocardial fibrosis
- HP:0006753 – Neoplasm of the stomach
- HP:0007378 – Neoplasm of the gastrointestinal tract
- HP:0007400 – Irregular hyperpigmentation
- HP:0008872 – Feeding difficulties in infancy
- HP:0009088 – Speech articulation difficulties
- HP:0010294 – Palate fistula
- HP:0011044 – Abnormal number of permanent teeth
- HP:0012378 – Fatigue
- HP:0100242 – Sarcoma
- HP:0100273 – Neoplasm of the colon
- HP:0100334 – Unilateral cleft palate
- HP:0100337 – Bilateral cleft palate
- HP:0100723 – Gastrointestinal stromal tumor
- HP:0100743 – Neoplasm of the rectum
- HP:0100751 – Esophageal neoplasm
- HP:0100833 – Neoplasm of the small intestine
- HP:0200008 – Intestinal polyposis
- HP:0200136 – Oral-pharyngeal dysphagia
- HP:0200153 – Agenesis of lateral incisor
Complex-Disease / GWAS Associations
Top 30 GWAS-associated traits (34 total):
| Trait/Disease | p-value | Mapped Gene(s) | Study ID |
|---|---|---|---|
| Height | 4.0e-07 | LINC02283 | GCST000136_2 |
| Mean corpuscular hemoglobin | 3.0e-25 | LINC02283, LINC02260 | GCST000587_5 |
| Mean corpuscular volume | 3.0e-126 | LINC02283, LINC02260 | GCST006011_105 |
| Red blood cell count | 1.0e-93 | LINC02283, LINC02260 | GCST005996_35 |
| Red blood cell count | 2.0e-17 | LINC02283, LINC02260 | GCST000588_1 |
| Red blood cell count | 4.0e-10 | LINC02283, LINC02260 | GCST004332_4 |
| Mean corpuscular volume | 2.0e-29 | LINC02283, LINC02260 | GCST000585_9 |
| Hemoglobin | 6.0e-16 | LINC02283, LINC02260 | GCST005995_8 |
| Hematocrit | 2.0e-20 | LINC02283, LINC02260 | GCST005994_20 |
| Platelet count | 7.0e-09 | LINC02283, LINC02260 | GCST005991_10 |
| Corneal astigmatism | 8.0e-09 | PDGFRA | GCST001339_4 |
| Corneal astigmatism | 6.0e-09 | RPL22P13, PDGFRA | GCST005803_1 |
| Corneal curvature | 1.0e-09 | RPL22P13, PDGFRA | GCST001101_2 |
| Corneal curvature | 8.0e-09 | RPL22P13, PDGFRA | GCST002502_4 |
| Corneal curvature | 5.0e-14 | RPL22P13 | GCST001803_1 |
| Uterine fibroids | 9.0e-10 | GSX2, RPL22P13 | GCST006462_49 |
| Uterine fibroids | 5.0e-18 | LNX1 | GCST009158_10 |
| Vertical cup-disc ratio (adjusted) | 4.0e-12 | PDGFRA | GCST009723_52 |
| Vertical cup-disc ratio (multi-trait) | 1.0e-15 | GSX2, RPL22P13 | GCST009724_93 |
| Vertical cup-disc ratio (multi-trait) | 1.0e-14 | RPL22P13, PDGFRA | GCST009724_94 |
| Blood protein levels | 1.0e-07 | PDGFRA | GCST006585_2369 |
| Core binding factor acute myeloid leukemia | 3.0e-18 | GSX2, RPL22P13, PDGFRA | GCST008413_2 |
| Core binding factor acute myeloid leukemia | 6.0e-08 | GSX2, RPL22P13, PDGFRA | GCST008413_3 |
| Macular thickness | 8.0e-10 | GSX2, RPL22P13 | GCST006976_71 |
| Systolic blood pressure | 2.0e-09 | LNX1, RPL21P44 | GCST007267_265 |
| Pulse pressure | 3.0e-29 | LNX1, RPL21P44 | GCST007269_46 |
| Asthma | 1.0e-06 | LNX1, RPL21P44 | GCST003831_12 |
| Adult asthma | 1.0e-06 | LNX1, RPL21P44 | GCST003833_22 |
| Post bronchodilator FEV1/FVC ratio | 1.0e-06 | CHIC2, MORF4L2P1 | GCST003264_1475 |
| Post bronchodilator FEV1/FVC ratio | 3.0e-06 | CHIC2, MORF4L2P1 | GCST003264_227 |
Additional GWAS associations (31-34):
- Lupus nephritis in SLE (p=5e-07, GSX2-RPL22P13)
- Serum VEGFR2 concentration (p=5e-25, LNX1-RPL21P44)
- Cadmium levels (p=1e-06)