PDGFA

Summary

PDGFA (platelet derived growth factor subunit A, HGNC:8799) is a protein-coding gene on chromosome 7p22.3, encoding Platelet-derived growth factor subunit A (P04085). Growth factor that plays an essential role in the regulation of embryonic development, cell proliferation, cell migration, survival and chemotaxis.

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.

Source: NCBI Gene 5154 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 41 total
• Druggable target: yes
• MANE Select transcript: NM_033023

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:8799
Approved symbol	PDGFA
Name	platelet derived growth factor subunit A
Location	7p22.3
Locus type	gene with protein product
Status	Approved
Aliases	PDGF1, PDGF-A
Ensembl gene	ENSG00000197461
Ensembl biotype	protein_coding
OMIM	173430
Entrez	5154

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 6 protein_coding, 1 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000354513, ENST00000400761, ENST00000402802, ENST00000405692, ENST00000426681, ENST00000482462, ENST00000901539, ENST00000956097

RefSeq mRNA: 6 — MANE Select: NM_033023 NM_001395363, NM_001395364, NM_001395365, NM_001395366, NM_002607, NM_033023

CCDS: CCDS34578, CCDS47524

Canonical transcript exons

ENST00000402802 — 6 exons

Exon	Start	End
ENSE00001433409	501116	501242
ENSE00001660856	512351	512455
ENSE00001759895	497258	498574
ENSE00003484325	517394	517490
ENSE00003503748	510809	510996
ENSE00003978266	518939	519846

Expression profiles

Bgee: expression breadth ubiquitous, 269 present calls, max score 97.80.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 28.2014 / max 554.6267, expressed in 1581 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
82355	14.2666	1365
82352	11.9158	1452
82353	0.8138	551
82357	0.3954	215
82354	0.2305	121
82350	0.1715	59
82351	0.1617	68
82356	0.1585	66
82358	0.0877	43

Top tissues by expression

282 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
buccal mucosa cell	CL:0002336	97.80	gold quality
ascending aorta	UBERON:0001496	96.46	gold quality
thoracic aorta	UBERON:0001515	96.37	gold quality
descending thoracic aorta	UBERON:0002345	95.88	gold quality
right coronary artery	UBERON:0001625	95.70	gold quality
aorta	UBERON:0000947	95.37	gold quality
body of pancreas	UBERON:0001150	95.18	gold quality
popliteal artery	UBERON:0002250	94.71	gold quality
tibial artery	UBERON:0007610	94.71	gold quality
left coronary artery	UBERON:0001626	94.63	gold quality
cranial nerve II	UBERON:0000941	94.27	gold quality
coronary artery	UBERON:0001621	94.17	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	93.39	gold quality
spinal cord	UBERON:0002240	92.40	gold quality
lower esophagus muscularis layer	UBERON:0035833	92.29	gold quality
lower esophagus	UBERON:0013473	92.23	gold quality
body of stomach	UBERON:0001161	91.69	gold quality
blood vessel layer	UBERON:0004797	91.44	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	91.35	gold quality
pancreas	UBERON:0001264	91.27	gold quality
muscle layer of sigmoid colon	UBERON:0035805	90.17	gold quality
tendon of biceps brachii	UBERON:0008188	89.99	gold quality
stomach	UBERON:0000945	89.80	gold quality
middle temporal gyrus	UBERON:0002771	89.75	gold quality
olfactory bulb	UBERON:0002264	89.14	silver quality
left uterine tube	UBERON:0001303	89.00	gold quality
medial globus pallidus	UBERON:0002477	88.87	gold quality
sural nerve	UBERON:0015488	88.79	gold quality
sigmoid colon	UBERON:0001159	88.73	gold quality
hindlimb stylopod muscle	UBERON:0004252	88.72	gold quality

Single-cell (SCXA)

Detected in 8 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-MTAB-7381	yes	279.35
E-ANND-3	yes	14.67
E-MTAB-6678	yes	12.70
E-GEOD-124858	no	343.60
E-MTAB-3929	no	287.34
E-GEOD-109979	no	130.45
E-CURD-6	no	72.49
E-MTAB-9543	no	2.27

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): DLX4, EGR1, ESR2, ETS1, FOS, FOXF2, GLI3, GTF3A, HOXB7, KLF5, LRRFIP1, MYC, MYF5, NFKB1, PURA, SMAD1, SMAD5, SP1, SP3, WT1

Literature-anchored findings (GeneRIF, showing 40)

• involvement of Furin gene regulation in the maturation of PDGF-AB in differentiating megakaryoblastic cells (PMID:12411321)
• PDGF and similar cytokines may be important factors in airway remodeling by redistribution of smooth muscle cells during inflammation and that urokinase may be important in potentiating the response. (PMID:12576295)
• The preferential formation of disulfide-bonded heterodimers from an equimolar mixture of unfolded A- and B-chains is thus a kinetically controlled process (PMID:12615918)
• PDGF has a role in inducing beta-gamma-secretase-mediated cleavage of Alzheimer’s amyloid precursor protein through a Src-Rac-dependent pathway (PMID:12645527)
• PDGF up-regulates the expression of transcription factors NF-E2, GATA-1 and c-Fos in megakaryocytic cell lines (PMID:12670444)
• a time-dependent release of TGFB and PDGF-AB occurred at neutral and alkaline pH, but not pH5, 15 min and 12h after platelet activation, suggesting relevance to wound healing (PMID:12850832)
• PDGF1 potently activates AP-1 ands causes cellular neoplastic transformation. (PMID:12972619)
• PDGF-A chain gene expression, under the control of KLF5, is cooperatively activated by the NF-kappaB p50 subunit and a pathophysiological stimulus. (PMID:14573617)
• Glucose causes a late increase in PDGF-dependent TGF-beta 1 translation by enhancing cellular sensitivity to PDGF. (PMID:14633628)
• cultured follicular keratinocytes synthesize both PDGF-A and PDGF-B, whereas, dermal papilla cells only express PDGF-A. (PMID:14705808)
• PDGF-A is a novel mitogenic target of 1,25-(OH)2D3 whose expression is induced via binding of hormone-activated VDR to a response element located far upstream of the transcription start site (PMID:14708943)
• PDGFA autocrine inhibition is associated with malignant gliomas (PMID:14997209)
• The PDGF expression, as a marker of angiogenesis, was evaluated in myomas obtained after surgery. (PMID:15631865)
• These results identify a novel mechanism of transcriptional enhancement involving ligand-independent activity of the VDR/RXR heterodimer and MAPK signaling pathways (PMID:15829977)
• thrombospondin-1 is not necessary for proliferation but is permissive for vascular smooth muscle cell responses to platelet-derived growth factor (PMID:15890262)
• JNK is a critical component downstream of PI 3-kinase that may be involved in PDGF-stimulated chemotaxis presumably by modulating the integrity of focal adhesions by phosphorylating its components (PMID:16760468)
• 36% of the examined primary central nervous system lymphoma specimens showed expression of PDGF-A. Tumours expressing survivin occasionally co-expressed PDGF-A. (PMID:16850112)
• During the wound healing of nasal mucosa, the levels of PDGF, TNF-alpha, and hyaluronic acid are different at each postoperative stage. (PMID:17087110)
• expression level might be decreased during the secretory phase in the eutopic endometrium of women with advanced stage endometriosis (PMID:17578349)
• FGF and PDGF have roles in cell proliferation and migration in osteoblastic cells (PMID:17852407)
• Tretinoin inducibility of PDGFA is mediated by 5’-distal DNA motifs that overlap with basal enhancer and vitamin D response elements. (PMID:17933214)
• Increased expression of PDGF/Ralphabeta may play an important role in the mechanism of growth of…paediatric fibromatous lesions (PMID:17944929)
• thrombin may play an important role in the proliferation of A172 cells by inducing PDGF-AB secretion and that thrombin’s action is mediated by its proteolytic activity (PMID:17958740)
• Ligand-mediated stabilization of G-quadruplex structures within the PDGF-A nuclease hypersensitive element can silence PDGF-A expression. (PMID:17984069)
• PDGFRs and the PDGF-A chain are frequently expressed in ovarian clear-cell adenocarcinomas. (PMID:18084257)
• tumor cell-secreted platelet-derived growth factor (PDGF) and phosphoinositide 3-kinase (PI3K) activation have roles in resistance of fibroblasts against oxidative damage (PMID:18174235)
• regularly expressed in variable levels in ameloblastomas (PMID:18284546)
• The proteins for PDGF-A were detected in oocytes, and in granulosa cells (GC) of 50% of the follicles from women/girls. (PMID:18326546)
• identified activin-mediated transforming growth factor (TGF)-beta signaling, platelet-derived growth factor (PDGF) signaling and fibroblast growth factor (FGF) signaling as the key pathways involved in MSC differentiation (PMID:18332228)
• Measuring PDGFA, bFGF, and HIF1a expression may contribute to a better understanding of the prognosis of patients with pancreatic cancer. (PMID:18592007)
• Results describe significant differences between controls and patients with renal cell carcinoma both pre-operatively and post-operatively in angiogenin, PDGF and MCP-1 serum levels. (PMID:18808740)
• OPG production by osteoblastic cells was stimulated by platelet-derived growth factor (PDGF) in two human osteosarcoma cell lines (MG63, Saos-2), a mouse pre-osteoblastic cell line (MC3T3-E1) and human bone marrow stromal cells (hMSC). (PMID:18814141)
• We showed that Prx I, PDGF-A, and PDGFR-alpha follow the same expression pattern during carcinoma ex pleomorphic adenoma progression. (PMID:18992915)
• A novel PDGF response in human preadipocytes that involves the pro-inflammatory kinase IKKbeta and demonstrate that it is required for the inhibition of adipogenesis. (PMID:19141566)
• SiO(2) may affect the expression of PDGF and synthesis of collagen through alveolar macrophage mediation and participate in the formation of lung fibrosis. (PMID:19493486)
• Immunohistochemistry for PDGF was found to be useful in differentiating various grades of oligodendroglioma, and therefore, it may be involved in tumor cell proliferation and malignant transformation. (PMID:19559929)
• concurrent expression of PDGFA and PDGFRA in different subtypes of gliomas, reinforce the recognised significance of this signalling pathway in gliomas. (PMID:19707201)
• analysis of how an enediynyl peptide inhibitor of furin blocks processing of proPDGF-A, B and proVEGF-C (PMID:19956642)
• Studies indicate communication between tumor cells and their microenvironment is through polypeptide growth factors EGF, FGF, PDGF and receptors for these growth factors. (PMID:20036812)
• Studies indicate that the imbalance of pro-angiogenic and anti-angiogenic factors VEGFA, Notch, Dll4, PDGF and angiopoietin-1 promotes tumor angiogenesis. (PMID:20036815)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	pdgfab	ENSDARG00000098578
danio_rerio	PDGFA	ENSDARG00000109371
danio_rerio	pdgfaa	ENSDARG00000110069
mus_musculus	Pdgfa	ENSMUSG00000025856
rattus_norvegicus	Pdgfa	ENSRNOG00000001312
drosophila_melanogaster	Pvf1	FBGN0030964
caenorhabditis_elegans		WBGENE00004249

Paralogs (1): PDGFB (ENSG00000100311)

Protein

Protein identifiers

Platelet-derived growth factor subunit A — P04085 (reviewed: P04085)

Alternative names: PDGF-1, Platelet-derived growth factor A chain, Platelet-derived growth factor alpha polypeptide

All UniProt accessions (3): P04085, A0A0A0MSC4, H7BYW6

UniProt curated annotations — full annotation on UniProt →

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.

Subunit / interactions. Homodimer; antiparallel disulfide-linked dimer. Heterodimer with PDGFB; antiparallel disulfide-linked dimer. The PDGFA homodimer interacts with PDGFRA homodimers, and with heterodimers formed by PDGFRA and PDGFRB. The heterodimer composed of PDGFA and PDGFB interacts with PDGFRA homodimers, and with heterodimers formed by PDGFRA and PDGFRB. Interacts with CSPG4.

Subcellular location. Secreted.

Domain organisation. The long form contains a basic insert which acts as a cell retention signal.

Similarity. Belongs to the PDGF/VEGF growth factor family.

Isoforms (2)

UniProt ID	Names	Canonical?
P04085-1	Long	yes
P04085-2	Short

RefSeq proteins (6): NP_001382292, NP_001382293, NP_001382294, NP_001382295, NP_002598, NP_148983* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000072	PDGF/VEGF_dom	Domain
IPR006782	PDGF_N	Domain
IPR023581	PD_growth_factor_CS	Conserved_site
IPR029034	Cystine-knot_cytokine	Homologous_superfamily

Pfam: PF00341, PF04692

UniProt features (22 total): disulfide bond 5, helix 3, strand 3, splice variant 2, region of interest 2, compositionally biased region 2, signal peptide 1, propeptide 1, sequence conflict 1, chain 1, glycosylation site 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
3MJK	X-RAY DIFFRACTION	2.4

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P04085-F1	78.03	0.55

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Disulfide bonds (5): 129–177, 132, 133–179, 96–140, 123

Glycosylation sites (1): 134

Function

Pathways and Gene Ontology

Reactome pathways

9 pathways

ID	Pathway
R-HSA-3000171	Non-integrin membrane-ECM interactions
R-HSA-9818030	NFE2L2 regulating tumorigenic genes
R-HSA-114608	Platelet degranulation
R-HSA-1257604	PIP3 activates AKT signaling
R-HSA-186763	Downstream signal transduction
R-HSA-186797	Signaling by PDGF
R-HSA-2219530	Constitutive Signaling by Aberrant PI3K in Cancer
R-HSA-5673001	RAF/MAP kinase cascade
R-HSA-6811558	PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling

MSigDB gene sets: 475 (showing top): GOBP_PLATELET_DERIVED_GROWTH_FACTOR_RECEPTOR_SIGNALING_PATHWAY, GOBP_MORPHOGENESIS_OF_AN_EPITHELIUM, TAKEDA_TARGETS_OF_NUP98_HOXA9_FUSION_6HR_DN, GOBP_REGULATION_OF_CELL_ACTIVATION, TONKS_TARGETS_OF_RUNX1_RUNX1T1_FUSION_MONOCYTE_UP, MODULE_92, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_PHOSPHOLIPID_METABOLIC_PROCESS, GOBP_PHOSPHATIDYLINOSITOL_METABOLIC_PROCESS, GOBP_GLAND_MORPHOGENESIS, TSENG_IRS1_TARGETS_UP, GOBP_REGULATION_OF_MORPHOGENESIS_OF_A_BRANCHING_STRUCTURE, GOBP_METANEPHROS_DEVELOPMENT, GOBP_REGULATION_OF_WOUND_HEALING, BIOCARTA_EDG1_PATHWAY

GO Biological Process (34): angiogenesis (GO:0001525), cell activation (GO:0001775), hair follicle development (GO:0001942), positive regulation of mesenchymal cell proliferation (GO:0002053), cell-cell signaling (GO:0007267), cell population proliferation (GO:0008283), positive regulation of cell population proliferation (GO:0008284), response to wounding (GO:0009611), animal organ morphogenesis (GO:0009887), negative regulation of phosphatidylinositol biosynthetic process (GO:0010512), negative regulation of platelet activation (GO:0010544), regulation of smooth muscle cell migration (GO:0014910), cell projection assembly (GO:0030031), actin cytoskeleton organization (GO:0030036), positive regulation of cell migration (GO:0030335), regulation of actin cytoskeleton organization (GO:0032956), platelet-derived growth factor receptor-alpha signaling pathway (GO:0035790), positive regulation of metanephric mesenchymal cell migration by platelet-derived growth factor receptor-beta signaling pathway (GO:0035793), wound healing (GO:0042060), positive regulation of MAPK cascade (GO:0043410), skin development (GO:0043588), platelet-derived growth factor receptor signaling pathway (GO:0048008), positive regulation of fibroblast proliferation (GO:0048146), lung alveolus development (GO:0048286), digestive tract development (GO:0048565), negative chemotaxis (GO:0050919), positive regulation of cell division (GO:0051781), positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction (GO:0051897), bone development (GO:0060348), regulation of branching involved in salivary gland morphogenesis by epithelial-mesenchymal signaling (GO:0060683), positive regulation of ERK1 and ERK2 cascade (GO:0070374), embryonic lung development (GO:1990401), signal transduction (GO:0007165), positive regulation of protein autophosphorylation (GO:0031954)

GO Molecular Function (9): platelet-derived growth factor receptor binding (GO:0005161), collagen binding (GO:0005518), growth factor activity (GO:0008083), identical protein binding (GO:0042802), protein homodimerization activity (GO:0042803), protein heterodimerization activity (GO:0046982), platelet-derived growth factor binding (GO:0048407), protein binding (GO:0005515), receptor ligand activity (GO:0048018)

GO Cellular Component (11): Golgi membrane (GO:0000139), extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), endoplasmic reticulum lumen (GO:0005788), Golgi lumen (GO:0005796), microvillus (GO:0005902), cell surface (GO:0009986), platelet alpha granule lumen (GO:0031093), platelet-derived growth factor complex (GO:1990265), platelet-derived growth factor receptor-ligand complex (GO:1990270), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-9 pathways:

Category	Pathways
Extracellular matrix organization	1
Nuclear events mediated by NFE2L2	1
Response to elevated platelet cytosolic Ca2+	1
Intracellular signaling by second messengers	1
Signaling by PDGF	1
Signaling by Receptor Tyrosine Kinases	1
PI3K/AKT Signaling in Cancer	1
MAPK1/MAPK3 signaling	1
Negative regulation of the PI3K/AKT network	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
cellular process	2
regulation of cell migration	2
protein dimerization activity	2
Golgi apparatus	2
intracellular organelle lumen	2
blood vessel morphogenesis	1
anatomical structure formation involved in morphogenesis	1
multicellular organismal process	1
hair cycle process	1
anatomical structure development	1
skin epidermis development	1
positive regulation of cell population proliferation	1
mesenchymal cell proliferation	1
regulation of mesenchymal cell proliferation	1
cell communication	1
signaling	1
cell population proliferation	1
regulation of cell population proliferation	1
positive regulation of cellular process	1
response to stress	1
anatomical structure morphogenesis	1
animal organ development	1
phosphatidylinositol biosynthetic process	1
negative regulation of biosynthetic process	1
regulation of phosphatidylinositol biosynthetic process	1
negative regulation of phosphorus metabolic process	1
regulation of platelet activation	1
platelet activation	1
negative regulation of blood coagulation	1
negative regulation of cell activation	1
smooth muscle cell migration	1
cellular component assembly	1
cell projection organization	1
cytoskeleton organization	1
actin filament-based process	1
cell migration	1
positive regulation of cell motility	1
actin cytoskeleton organization	1
regulation of actin filament-based process	1

Protein interactions and networks

STRING

1526 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PDGFA	PDGFRA	P16234	998
PDGFA	PDGFRB	P09619	997
PDGFA	PDGFB	P01127	982
PDGFA	PDGFC	Q9NRA1	961
PDGFA	PDGFD	Q9GZP0	921
PDGFA	PDAP1	Q13442	849
PDGFA	FGF2	P09038	817
PDGFA	KDR	P35968	721
PDGFA	VEGFC	P49767	679
PDGFA	TGFB2	P08112	671
PDGFA	KLF5	Q13887	658
PDGFA	EGFR	P00533	656
PDGFA	FLT1	P16057	653
PDGFA	FGF5	P12034	643
PDGFA	FN1	P02751	642

IntAct

18 interactions, top by confidence:

A	B	Type	Score
PDGFRB	PDGFB	psi-mi:“MI:0915”(physical association)	0.900
PDGFRA	PDGFB	psi-mi:“MI:0915”(physical association)	0.730
PDGFA	PDGFRA	psi-mi:“MI:2364”(proximity)	0.690
PDGFRA	PDGFA	psi-mi:“MI:0407”(direct interaction)	0.690
PDGFB	PDGFA	psi-mi:“MI:0407”(direct interaction)	0.440
PDGFA	PDGFA	psi-mi:“MI:0407”(direct interaction)	0.440
MAPT	SHTN1	psi-mi:“MI:0914”(association)	0.350
PDGFA	LAMB1	psi-mi:“MI:0914”(association)	0.350

BioGRID (33): PDGFRA (Co-localization), PDGFA (Reconstituted Complex), Cdkn2a (Synthetic Lethality), Trp53 (Synthetic Lethality), Pten (Synthetic Lethality), PDGFA (Affinity Capture-MS), PDGFA (Affinity Capture-MS), PDGFA (Two-hybrid), PDGFA (Two-hybrid), ASPH (Two-hybrid), PDGFA (Reconstituted Complex), PLCG1 (Affinity Capture-Western), PDGFA (Affinity Capture-RNA), PDGFA (Co-purification), LAMB1 (Affinity Capture-MS)

ESM2 similar proteins: B0VXV3, B0VXV4, C0K3N1, C0K3N3, C0K3N5, O35251, O93525, O95390, P01127, P01128, P04085, P0DW98, P12919, P15691, P16612, P31240, P49011, P49151, P49764, P50412, P67861, P67862, P67863, P97466, Q05028, Q13253, Q330K6, Q62386, Q63434, Q6J936, Q6Q7I7, Q90X23, Q90X24, Q95229, Q98TB4, Q99P67, Q99P68, Q99PS1, Q9BG78, Q9BG79

Diamond homologs: B0VXV3, B0VXV4, C0HM96, C0K3N1, C0K3N2, C0K3N3, O35251, O35757, O43915, P01127, P01128, P04085, P0DL42, P0DW97, P0DW98, P12919, P13698, P15691, P15692, P16612, P20033, P28576, P31240, P34007, P49763, P49764, P49765, P49767, P50412, P52584, P67860, P67861, P67862, P67863, P82475, P83906, P83942, P97946, P97953, Q00731

SIGNOR signaling

4 interactions.

A	Effect	B	Mechanism
PDGFA	up-regulates	PDGFRA	binding
PAX7-FOXO1	“up-regulates quantity by expression”	PDGFA	“transcriptional regulation”
PAX3-FOXO1	“up-regulates quantity by expression”	PDGFA	“transcriptional regulation”
PDGFA	up-regulates	Angiogenesis

Disease & clinical

Clinical variants and AI predictions

ClinVar

41 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	29
Likely benign	2
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

1889 predictions. Top by Δscore:

Variant	Effect	Δscore
7:499498:T:A	donor_gain	1.0000
7:501114:AC:A	donor_gain	1.0000
7:501115:CC:C	donor_gain	1.0000
7:501241:ACC:A	acceptor_loss	1.0000
7:501244:T:A	acceptor_loss	1.0000
7:510992:TTCCT:T	acceptor_gain	1.0000
7:510993:TCCT:T	acceptor_gain	1.0000
7:510994:CCTC:C	acceptor_gain	1.0000
7:510995:CT:C	acceptor_gain	1.0000
7:510997:C:CC	acceptor_gain	1.0000
7:512344:GACTC:G	donor_loss	1.0000
7:512346:CTCAC:C	donor_loss	1.0000
7:512347:TCACC:T	donor_loss	1.0000
7:512349:A:AC	donor_gain	1.0000
7:512350:C:CC	donor_gain	1.0000
7:512452:CTCC:C	acceptor_gain	1.0000
7:512453:TCCC:T	acceptor_loss	1.0000
7:512456:C:CC	acceptor_gain	1.0000
7:512456:C:CG	acceptor_loss	1.0000
7:512457:T:C	acceptor_loss	1.0000
7:517393:CCTA:C	donor_gain	1.0000
7:517396:A:AC	donor_gain	1.0000
7:517397:C:CC	donor_gain	1.0000
7:517487:CTTC:C	acceptor_gain	1.0000
7:517488:TTCC:T	acceptor_loss	1.0000
7:517489:TC:T	acceptor_gain	1.0000
7:517490:CC:C	acceptor_gain	1.0000
7:517490:CCT:C	acceptor_loss	1.0000
7:517491:C:CC	acceptor_gain	1.0000
7:519302:T:TA	donor_gain	1.0000

AlphaMissense

1275 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:510843:C:G	C140S	1.000
7:510844:A:T	C140S	1.000
7:510902:C:A	W120C	1.000
7:510902:C:G	W120C	1.000
7:510911:G:C	F117L	1.000
7:510911:G:T	F117L	1.000
7:510912:A:C	F117C	1.000
7:510912:A:G	F117S	1.000
7:510913:A:G	F117L	1.000
7:510975:C:G	C96S	1.000
7:510976:A:G	C96R	1.000
7:510976:A:T	C96S	1.000
7:501166:C:G	C177S	0.999
7:501167:A:G	C177R	0.999
7:501167:A:T	C177S	0.999
7:501234:C:A	K154N	0.999
7:501234:C:G	K154N	0.999
7:510813:A:T	V150D	0.999
7:510844:A:G	C140R	0.999
7:510864:C:G	C133S	0.999
7:510864:C:T	C133Y	0.999
7:510865:A:T	C133S	0.999
7:510870:C:A	G131V	0.999
7:510870:C:T	G131D	0.999
7:510871:C:A	G131C	0.999
7:510871:C:G	G131R	0.999
7:510875:G:C	C129W	0.999
7:510876:C:G	C129S	0.999
7:510877:A:G	C129R	0.999
7:510877:A:T	C129S	0.999

dbSNP variants (sampled 300 via entrez): RS1000045852 (7:497632 C>T), RS1000155153 (7:505880 C>A), RS1000175026 (7:519292 C>G,T), RS1000288632 (7:520568 A>G), RS1000320874 (7:520737 G>A,C), RS1000379428 (7:505318 ACCAGACATTC>A), RS1000397187 (7:497503 A>G), RS1000477934 (7:513984 T>C), RS1000507699 (7:517984 C>G), RS1000579631 (7:509264 G>A), RS1000650123 (7:509527 C>T), RS1000841950 (7:501120 G>A,C,T), RS1000849314 (7:513364 T>A), RS1000933215 (7:501301 C>T), RS1000950008 (7:513748 G>A)

Disease associations

OMIM: gene MIM:173430 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST006661_111	Male-pattern baldness	7.000000e-17
GCST006661_213	Male-pattern baldness	4.000000e-08
GCST006661_260	Male-pattern baldness	2.000000e-21

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3137294 (SINGLE PROTEIN)

PharmGKB: 1 entry (VIP=true, CPIC=false)

ChEMBL bioactivities

1 potent at pChembl≥5 of 1 total, top 1 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.21	IC50	610	nM	CHEMBL3125890

PubChem BioAssay actives

1 with measured affinity, of 1 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
N-[7-cyano-6-[4-fluoro-3-[[2-[3-(trifluoromethyl)phenyl]acetyl]amino]phenoxy]-1,3-benzothiazol-2-yl]cyclopropanecarboxamide	1073266: Inhibition of PDGFR alpha (unknown origin) using biotinylated poly-Glu-Tyr (4:1) as substrate preincubated for 5 mins measured after 12 hrs	ic50	0.6100	uM

CTD chemical–gene interactions

118 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Estradiol	increases expression, decreases expression, affects binding, affects cotreatment, decreases secretion	5
Valproic Acid	affects expression, decreases expression, increases expression, increases methylation	4
Cadmium Chloride	decreases reaction, decreases expression, increases abundance, increases expression	4
trichostatin A	increases expression, decreases expression, affects cotreatment	3
sodium arsenite	increases expression, decreases expression, increases abundance	3
Smoke	decreases expression, decreases nitrosation, increases expression	3
Cyclosporine	increases expression	3
nickel sulfate	increases expression	2
entinostat	increases expression, affects cotreatment	2
belinostat	decreases expression, increases expression, affects cotreatment	2
Arsenic Trioxide	increases expression, decreases expression	2
Panobinostat	affects cotreatment, increases expression	2
Benzo(a)pyrene	increases expression, increases methylation	2
Cadmium	decreases expression, increases abundance, increases expression, decreases reaction	2
Copper	affects binding, increases expression	2
Progesterone	affects cotreatment, decreases expression, increases expression	2
Tetrachlorodibenzodioxin	affects cotreatment, decreases reaction, increases expression, increases secretion, decreases expression	2
Tetradecanoylphorbol Acetate	decreases reaction, increases expression	2
aristolochic acid I	decreases expression	1
1-cyclopropyl-4-(4-((5-methyl-3-(3-(4-(trifluoromethoxy)phenyl)-1,2,4-oxadiazol-5-yl)-1H-pyrazol-1-yl)methyl)pyridin-2-yl)piperazine	decreases reaction, increases expression	1
bisphenol F	increases expression, affects cotreatment	1
ammonium 2,3,3,3-tetrafluoro-2-(heptafluoropropoxy)-propanoate	affects cotreatment, affects expression	1
MRI-1867	affects cotreatment, decreases reaction, increases expression	1
diazoxon	increases expression	1
geldanamycin	increases expression	1
methylmercuric chloride	increases expression	1
triphenyl phosphate	affects expression	1
potassium perchlorate	decreases expression	1
sodium arsenate	increases expression	1
O,O-diethyl O-3,5,6-trichloro-2-pyridyl phosphate	increases expression	1

ChEMBL screening assays

2 unique, capped per target: 2 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3132619	Binding	Inhibition of PDGFR alpha (unknown origin) using biotinylated poly-Glu-Tyr (4:1) as substrate preincubated for 5 mins measured after 12 hrs	Discovery of a selective kinase inhibitor (TAK-632) targeting pan-RAF inhibition: design, synthesis, and biological evaluation of C-7-substituted 1,3-benzothiazole derivatives. — J Med Chem

Cellosaurus cell lines

3 cell lines: 3 embryonic stem cell

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_A5G2	SEES3-1V human PDGFA, clone1	Embryonic stem cell	Male
CVCL_A5G3	SEES3-1V human PDGFA, clone2	Embryonic stem cell	Male
CVCL_A5G4	SEES3-1V human PDGFA, clone3	Embryonic stem cell	Male

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.