PDGFA
protein-codingplatelet derived growth factor subunit A
Gene summary
This gene encodes a member of the protein family comprised of both platelet-derived growth factors (PDGF) and vascular endothelial growth factors (VEGF). The encoded preproprotein is proteolytically processed to generate platelet-derived growth factor subunit A, which can homodimerize, or alternatively, heterodimerize with the related platelet-derived growth factor subunit B. These proteins bind and activate PDGF receptor tyrosine kinases, which play a role in a wide range of developmental processes. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2015]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~23.0 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to PDGFA variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_033023.5. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 1 | 1 | ||||
| missense | 27 | 2 | 29 | |||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 28 | 2 | 1 | 31 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_148983.1 | 6 | MANE Select | |
| Ensembl | ENSP00000383889.3 | 6 | MANE Select | |
| RefSeq | NP_001382292.1 | 7 | Standard | |
| RefSeq | NP_001382293.1 | 6 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| pdgfaa | Danio rerio | Structure: trabecula communis Quality: cleft abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- PI3K-Akt signaling pathway - Homo sapiens (human)
- Focal adhesion - Homo sapiens (human)
- Choline metabolism in cancer - Homo sapiens (human)
- Melanoma - Homo sapiens (human)
- Jak-STAT signaling pathway - Homo sapiens (human)
Biological Process
- MAPK cascade
- angiogenesis
- cell activation
- hair follicle development
- positive regulation of mesenchymal cell proliferation
Molecular Function
- Ras guanyl-nucleotide exchange factor activity
- platelet-derived growth factor receptor binding
- protein binding
- collagen binding
- growth factor activity
Cellular Component
- Golgi membrane
- extracellular region
- extracellular space
- endoplasmic reticulum lumen
- Golgi lumen
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000354513
- Coding exons
- 6
- Length
- 23039
- Individuals with no LoFs
- 125617
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 3
- Defined
- 125620
- p
- 0.0000119
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.686 | 102 | 123 | 0.826 | 0.00000819 | 1349 |
| Missense (PolyPhen) | 31 | 51.783 | 0.59865 | 476 | ||
| Synonymous | -1.20 | 64 | 52.9 | 1.21 | 0.00000385 | 405 |
| Loss of Function | 2.61 | 1 | 9.82 | 0.102 | 4.17e-7 | 137 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.000029 | 0.000029 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.000054 | 0.000054 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.0000088 | 0.0000088 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Growth factor that plays an essential role in the regulation of embryonic development, cell proliferation, cell migration, survival and chemotaxis. Potent mitogen for cells of mesenchymal origin. Required for normal lung alveolar septum formation during embryogenesis, normal development of the gastrointestinal tract, normal development of Leydig cells and spermatogenesis. Required for normal oligodendrocyte development and normal myelination in the spinal cord and cerebellum. Plays an important role in wound healing. Signaling is modulated by the formation of heterodimers with PDGFB (By similarity). {ECO:0000250}.;
Intolerance Scores
- RVIS EVS
- -0.16
- RVIS percentile EVS
- 41.64
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.539
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |