PDGFRA

platelet derived growth factor receptor alpha, the group of CD molecules|Receptor tyrosine kinases|I-set domain containing

Basic information

Region (hg38): 4:54229279-54298245

Links

ENSG00000134853 ∙ NCBI:5156 ∙ OMIM:173490 ∙ HGNC:8803 ∙ Uniprot:P16234 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• polyps, multiple and recurrent inflammatory fibroid, gastrointestinal (Moderate), mode of inheritance: AD
• gastrointestinal stromal tumor (Strong), mode of inheritance: AD
• gastrointestinal stromal tumor (Definitive), mode of inheritance: AD
• congenital heart disease (Limited), mode of inheritance: AD
• isolated cleft palate (Limited), mode of inheritance: Unknown
• polyps, multiple and recurrent inflammatory fibroid, gastrointestinal (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Gastrointestinal stromal tumor; GIST-plus syndrome	AD	Oncologic	Individuals with Gastrointestinal stromal tumor may be at high risk for the development of gastrointestinal stromal tumor, and surveillance and/or awareness of cancer risk may allow early diagnosis and treatment of tumors, which may reduce morbidity and mortality; Individuals with GIST-plus syndrome may be at risk of multiple mesenchymal tumors of the gastrointestinal tract, and surveillance and/or awareness of cancer risk may allow early diagnosis and treatment of tumors, which may reduce morbidity and mortality	Craniofacial; Dental; Dermatologic; Musculoskeletal; Oncologic	14699510; 17087943; 17566086; 25975287; 29486293

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PDGFRA gene.

• Gastrointestinal stromal tumor (2513 variants)
• Hereditary cancer-predisposing syndrome (1066 variants)
• not provided (184 variants)
• Idiopathic hypereosinophilic syndrome (141 variants)
• Polyps, multiple and recurrent inflammatory fibroid, gastrointestinal (109 variants)
• not specified (45 variants)
• PDGFRA-related condition (20 variants)
• Ovarian cancer (11 variants)
• Inborn genetic diseases (9 variants)
• Myeloproliferative neoplasm, unclassifiable (4 variants)
• Gastrointestinal stromal tumor;Idiopathic hypereosinophilic syndrome (4 variants)
• Polyps, multiple and recurrent inflammatory fibroid, gastrointestinal;Idiopathic hypereosinophilic syndrome (3 variants)
• Isolated cleft palate (3 variants)
• Squamous cell lung carcinoma (2 variants)
• Idiopathic hypereosinophilic syndrome;Gastrointestinal stromal tumor (2 variants)
• Carcinoma of colon (1 variants)
• Idiopathic hypereosinophilic syndrome;Polyps, multiple and recurrent inflammatory fibroid, gastrointestinal (1 variants)
• Hereditary cancer (1 variants)
• Melanoma (1 variants)
• Lung sarcomatoid carcinoma (1 variants)
• Hypereosinophilic syndrome, idiopathic, resistant to imatinib (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PDGFRA gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			12	664	9	685
missense		1	1374	18	2	1395
nonsense			22			22
start loss			1			1
frameshift			26			26
inframe indel			10			10
splice donor/acceptor (+/-2bp)			11	1		12
splice region			81	93	3	177
non coding			63	300	74	437
Total	0	1	1519	983	85

Variants in PDGFRA

This is a list of pathogenic ClinVar variants found in the PDGFRA region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
4-54229321-CAG-C		Gastrointestinal stromal tumor • Idiopathic hypereosinophilic syndrome	Benign (Jul 06, 2018)
4-54229427-G-T		Gastrointestinal stromal tumor • Idiopathic hypereosinophilic syndrome	Uncertain significance (Jan 13, 2018)
4-54229515-G-GA			Benign (Aug 30, 2019)
4-54229547-T-G			Likely benign (Apr 01, 2020)
4-54229560-A-AT			Likely benign (Nov 30, 2020)
4-54234484-G-A		PDGFRA-related disorder	Uncertain significance (Aug 28, 2023)
4-54240088-A-G		PDGFRA-related disorder	Likely benign (Jul 14, 2023)
4-54240094-C-T		PDGFRA-related disorder	Likely benign (Feb 14, 2024)
4-54258424-A-G			Benign (Jan 10, 2019)
4-54258600-A-G			Benign (Jun 23, 2018)
4-54258765-A-T		Hereditary cancer-predisposing syndrome	Uncertain significance (Mar 29, 2021)
4-54258769-A-G		Gastrointestinal stromal tumor	Uncertain significance (Jul 09, 2023)
4-54258769-A-T		Gastrointestinal stromal tumor	Uncertain significance (Mar 26, 2023)
4-54258770-T-G		Gastrointestinal stromal tumor	Uncertain significance (Apr 02, 2020)
4-54258772-G-A		Gastrointestinal stromal tumor	Uncertain significance (Dec 14, 2021)
4-54258773-G-A		Gastrointestinal stromal tumor • Hereditary cancer-predisposing syndrome	Uncertain significance (Sep 08, 2023)
4-54258773-G-C		Hereditary cancer-predisposing syndrome	Uncertain significance (Mar 03, 2024)
4-54258774-G-T		Gastrointestinal stromal tumor	Likely benign (May 24, 2022)
4-54258776-C-G		Hereditary cancer-predisposing syndrome • Gastrointestinal stromal tumor	Uncertain significance (Feb 19, 2022)
4-54258777-T-A		Hereditary cancer-predisposing syndrome	Likely benign (Aug 30, 2023)
4-54258777-T-C		Gastrointestinal stromal tumor	Likely benign (Oct 29, 2021)
4-54258778-T-G		Gastrointestinal stromal tumor	Uncertain significance (May 17, 2022)
4-54258779-C-A		Gastrointestinal stromal tumor	Uncertain significance (Jul 06, 2023)
4-54258779-C-G		Gastrointestinal stromal tumor • Hereditary cancer-predisposing syndrome	Uncertain significance (Feb 28, 2024)
4-54258779-C-T		Gastrointestinal stromal tumor • Hereditary cancer-predisposing syndrome	Uncertain significance (Dec 21, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PDGFRA	protein_coding	protein_coding	ENST00000257290	22	69151

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	0.00000217	125721	0	12	125733	0.0000477

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.94	458	591	0.775	0.0000332	7162
Missense in Polyphen		116	241.41	0.48051		3039
Synonymous	-0.103	229	227	1.01	0.0000139	2072
Loss of Function	6.31	4	54.1	0.0740	0.00000283	689

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000206	0.000206
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000440	0.0000440
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Tyrosine-protein kinase that acts as a cell-surface receptor for PDGFA, PDGFB and PDGFC and plays an essential role in the regulation of embryonic development, cell proliferation, survival and chemotaxis. Depending on the context, promotes or inhibits cell proliferation and cell migration. Plays an important role in the differentiation of bone marrow-derived mesenchymal stem cells. Required for normal skeleton development and cephalic closure during embryonic development. Required for normal development of the mucosa lining the gastrointestinal tract, and for recruitment of mesenchymal cells and normal development of intestinal villi. Plays a role in cell migration and chemotaxis in wound healing. Plays a role in platelet activation, secretion of agonists from platelet granules, and in thrombin-induced platelet aggregation. Binding of its cognate ligands - homodimeric PDGFA, homodimeric PDGFB, heterodimers formed by PDGFA and PDGFB or homodimeric PDGFC -leads to the activation of several signaling cascades; the response depends on the nature of the bound ligand and is modulated by the formation of heterodimers between PDGFRA and PDGFRB. Phosphorylates PIK3R1, PLCG1, and PTPN11. Activation of PLCG1 leads to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate, mobilization of cytosolic Ca(2+) and the activation of protein kinase C. Phosphorylates PIK3R1, the regulatory subunit of phosphatidylinositol 3-kinase, and thereby mediates activation of the AKT1 signaling pathway. Mediates activation of HRAS and of the MAP kinases MAPK1/ERK2 and/or MAPK3/ERK1. Promotes activation of STAT family members STAT1, STAT3 and STAT5A and/or STAT5B. Receptor signaling is down-regulated by protein phosphatases that dephosphorylate the receptor and its down-stream effectors, and by rapid internalization of the activated receptor. {ECO:0000269|PubMed:10734113, ECO:0000269|PubMed:10947961, ECO:0000269|PubMed:11297552, ECO:0000269|PubMed:12522257, ECO:0000269|PubMed:1646396, ECO:0000269|PubMed:1709159, ECO:0000269|PubMed:17141222, ECO:0000269|PubMed:20972453, ECO:0000269|PubMed:21224473, ECO:0000269|PubMed:21596750, ECO:0000269|PubMed:2554309, ECO:0000269|PubMed:8188664, ECO:0000269|PubMed:8760137, ECO:0000269|PubMed:8943348}.
• Disease: DISEASE: Note=A chromosomal aberration involving PDGFRA is found in some cases of hypereosinophilic syndrome. Interstitial chromosomal deletion del(4)(q12q12) causes the fusion of FIP1L1 and PDGFRA (FIP1L1-PDGFRA). Mutations that cause overexpression and/or constitutive activation of PDGFRA may be a cause of hypereosinophilic syndrome. {ECO:0000269|PubMed:12808148}.; DISEASE: Gastrointestinal stromal tumor (GIST) [MIM:606764]: Common mesenchymal neoplasms arising in the gastrointestinal tract, most often in the stomach. They are histologically, immunohistochemically, and genetically different from typical leiomyomas, leiomyosarcomas, and schwannomas. Most GISTs are composed of a fairly uniform population of spindle-shaped cells. Some tumors are dominated by epithelioid cells or contain a mixture of spindle and epithelioid morphologies. Primary GISTs in the gastrointestinal tract commonly metastasize in the omentum and mesenteries, often as multiple nodules. However, primary tumors may also occur outside of the gastrointestinal tract, in other intra-abdominal locations, especially in the omentum and mesentery. {ECO:0000269|PubMed:12522257, ECO:0000269|PubMed:15928335}. Note=The gene represented in this entry may be involved in disease pathogenesis. Mutations causing PDGFRA constitutive activation have been found in gastrointestinal stromal tumors lacking KIT mutations (PubMed:12522257). {ECO:0000269|PubMed:12522257}.
• Pathway: PI3K-Akt signaling pathway - Homo sapiens (human);Focal adhesion - Homo sapiens (human);Central carbon metabolism in cancer - Homo sapiens (human);Choline metabolism in cancer - Homo sapiens (human);Melanoma - Homo sapiens (human);Jak-STAT signaling pathway - Homo sapiens (human);Endocytosis - Homo sapiens (human);Gap junction - Homo sapiens (human);HTLV-I infection - Homo sapiens (human);Regulation of actin cytoskeleton - Homo sapiens (human);Glioma - Homo sapiens (human);Prostate cancer - Homo sapiens (human);Calcium signaling pathway - Homo sapiens (human);Rap1 signaling pathway - Homo sapiens (human);Ras signaling pathway - Homo sapiens (human);MAPK signaling pathway - Homo sapiens (human);Phospholipase D signaling pathway - Homo sapiens (human);MicroRNAs in cancer - Homo sapiens (human);Pathways in cancer - Homo sapiens (human);Cytokine-cytokine receptor interaction - Homo sapiens (human);Vemurafenib Pathway, Pharmacodynamics;update your name in edit mode;Signaling Pathways in Glioblastoma;Allograft Rejection;Cardiac Progenitor Differentiation;Focal Adhesion;Osteoblast Signaling;Photodynamic therapy-induced AP-1 survival signaling.;Imatinib and Chronic Myeloid Leukemia;ESC Pluripotency Pathways;Focal Adhesion-PI3K-Akt-mTOR-signaling pathway;Protein alkylation leading to liver fibrosis;Pathways in clear cell renal cell carcinoma;PI3K-Akt Signaling Pathway;Ras Signaling;Regulation of Actin Cytoskeleton;Disease;Signal Transduction;role of pi3k subunit p85 in regulation of actin organization and cell migration;phospholipids as signalling intermediaries;rac1 cell motility signaling pathway;Signaling by PDGF;ATF-2 transcription factor network;pdgf signaling pathway;IL-7 signaling;PDGF receptor signaling network;RAF/MAP kinase cascade;MAPK1/MAPK3 signaling;MAPK family signaling cascades;PIP3 activates AKT signaling;JAK STAT pathway and regulation;PDGF;EPO signaling;Downstream signal transduction;PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling;Negative regulation of the PI3K/AKT network;Constitutive Signaling by Aberrant PI3K in Cancer;PI3K/AKT Signaling in Cancer;Signaling by Receptor Tyrosine Kinases;VEGF;Intracellular signaling by second messengers;Diseases of signal transduction;PDGFR-alpha signaling pathway (Consensus)

Recessive Scores

• pRec: 0.117

Intolerance Scores

• loftool: 0.125
• rvis_EVS: -0.64
• rvis_percentile_EVS: 16.76

Haploinsufficiency Scores

• pHI: 0.964
• hipred: Y
• hipred_score: 0.853
• ghis: 0.563

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: H
• gene_indispensability_pred: E
• gene_indispensability_score: 0.990

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Pdgfra
• Phenotype: endocrine/exocrine gland phenotype; growth/size/body region phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); homeostasis/metabolism phenotype; cellular phenotype; craniofacial phenotype; digestive/alimentary phenotype; muscle phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); limbs/digits/tail phenotype; neoplasm; hematopoietic system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); reproductive system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); normal phenotype; respiratory system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); embryo phenotype; renal/urinary system phenotype; skeleton phenotype; immune system phenotype

Zebrafish Information Network

• Gene name: pdgfra
• Affected structure: hematopoietic multipotent progenitor cell
• Phenotype tag: abnormal
• Phenotype quality: decreased amount

Gene ontology

• Biological process: MAPK cascade;luteinization;in utero embryonic development;cell activation;hematopoietic progenitor cell differentiation;transmembrane receptor protein tyrosine kinase signaling pathway;positive regulation of cytosolic calcium ion concentration;estrogen metabolic process;positive regulation of cell population proliferation;negative regulation of platelet activation;positive regulation of phospholipase C activity;positive regulation of phosphatidylinositol 3-kinase signaling;viral process;peptidyl-tyrosine phosphorylation;signal transduction involved in regulation of gene expression;extracellular matrix organization;lung development;adrenal gland development;positive regulation of cell migration;male genitalia development;Leydig cell differentiation;cellular response to reactive oxygen species;platelet-derived growth factor receptor-alpha signaling pathway;positive regulation of cell proliferation by VEGF-activated platelet derived growth factor receptor signaling pathway;wound healing;odontogenesis of dentin-containing tooth;positive regulation of MAPK cascade;positive regulation of phosphatidylinositol 3-kinase activity;protein autophosphorylation;phosphatidylinositol phosphorylation;platelet-derived growth factor receptor signaling pathway;phosphatidylinositol-mediated signaling;positive regulation of fibroblast proliferation;embryonic digestive tract morphogenesis;embryonic cranial skeleton morphogenesis;embryonic skeletal system morphogenesis;regulation of chemotaxis;positive regulation of protein kinase B signaling;cardiac myofibril assembly;roof of mouth development;face morphogenesis;cell chemotaxis;retina vasculature development in camera-type eye;positive regulation of ERK1 and ERK2 cascade;platelet aggregation;cellular response to amino acid stimulus;metanephric glomerular capillary formation;regulation of actin cytoskeleton reorganization;regulation of mesenchymal stem cell differentiation
• Cellular component: nucleus;cytoplasm;Golgi apparatus;plasma membrane;integral component of plasma membrane;microvillus;cilium;external side of plasma membrane;membrane;cell junction;intrinsic component of plasma membrane;protein-containing complex;receptor complex
• Molecular function: protein kinase activity;transmembrane receptor protein tyrosine kinase activity;platelet-derived growth factor alpha-receptor activity;vascular endothelial growth factor-activated receptor activity;Ras guanyl-nucleotide exchange factor activity;platelet-derived growth factor receptor binding;protein binding;ATP binding;vascular endothelial growth factor binding;protein homodimerization activity;protein-containing complex binding;phosphatidylinositol-4,5-bisphosphate 3-kinase activity;platelet-derived growth factor binding