PDGFC

Summary

PDGFC (platelet derived growth factor C, HGNC:8801) is a protein-coding gene on chromosome 4q32.1, encoding Platelet-derived growth factor C (Q9NRA1). Growth factor that plays an essential role in the regulation of embryonic development, cell proliferation, cell migration, survival and chemotaxis.

The protein encoded by this gene is a member of the platelet-derived growth factor family. The four members of this family are mitogenic factors for cells of mesenchymal origin and are characterized by a core motif of eight cysteines. This gene product appears to form only homodimers. It differs from the platelet-derived growth factor alpha and beta polypeptides in having an unusual N-terminal domain, the CUB domain. Alternatively spliced transcript variants have been found for this gene.

Source: NCBI Gene 56034 — RefSeq curated summary.

At a glance

• GWAS associations: 39
• Clinical variants (ClinVar): 54 total
• MANE Select transcript: NM_016205

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:8801
Approved symbol	PDGFC
Name	platelet derived growth factor C
Location	4q32.1
Locus type	gene with protein product
Status	Approved
Aliases	SCDGF, fallotein
Ensembl gene	ENSG00000145431
Ensembl biotype	protein_coding
OMIM	608452
Entrez	56034

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 5 protein_coding_CDS_not_defined, 3 protein_coding, 2 nonsense_mediated_decay

ENST00000274071, ENST00000422544, ENST00000502773, ENST00000504672, ENST00000506880, ENST00000510982, ENST00000511985, ENST00000512711, ENST00000513664, ENST00000954544

RefSeq mRNA: 1 — MANE Select: NM_016205 NM_016205

CCDS: CCDS3795

Canonical transcript exons

ENST00000502773 — 6 exons

Exon	Start	End
ENSE00001228035	156970786	156971799
ENSE00002056160	156760454	156763206
ENSE00003476743	156810837	156811017
ENSE00003611938	156772686	156772893
ENSE00003616663	156767773	156767990
ENSE00003649341	156850221	156850416

Expression profiles

Bgee: expression breadth ubiquitous, 282 present calls, max score 99.06.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 27.9060 / max 630.3934, expressed in 1527 samples.

FANTOM5 promoters (18 alternative TSS)

Promoter ID	TPM avg	Samples expressed
54566	17.4813	1475
54564	1.9132	593
54561	1.1620	548
54560	1.0138	409
54563	0.8896	323
54571	0.8524	410
54570	0.7997	396
54557	0.6849	426
54568	0.5681	319
54559	0.5632	293

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
parotid gland	UBERON:0001831	99.06	gold quality
germinal epithelium of ovary	UBERON:0001304	98.77	gold quality
tibia	UBERON:0000979	97.66	gold quality
parietal pleura	UBERON:0002400	96.94	gold quality
blood vessel layer	UBERON:0004797	96.84	gold quality
periodontal ligament	UBERON:0008266	96.71	gold quality
skin of hip	UBERON:0001554	96.61	gold quality
pleura	UBERON:0000977	96.57	gold quality
nephron tubule	UBERON:0001231	96.56	gold quality
metanephric glomerulus	UBERON:0004736	96.45	gold quality
seminal vesicle	UBERON:0000998	96.44	gold quality
stromal cell of endometrium	CL:0002255	96.43	gold quality
renal glomerulus	UBERON:0000074	96.34	gold quality
pigmented layer of retina	UBERON:0001782	96.25	gold quality
visceral pleura	UBERON:0002401	96.04	gold quality
synovial joint	UBERON:0002217	95.12	gold quality
cauda epididymis	UBERON:0004360	94.45	gold quality
caput epididymis	UBERON:0004358	94.28	gold quality
mammary duct	UBERON:0001765	94.19	gold quality
endothelial cell	CL:0000115	93.94	gold quality
epithelium of mammary gland	UBERON:0003244	93.79	gold quality
adult organism	UBERON:0007023	93.76	gold quality
upper leg skin	UBERON:0004262	93.48	gold quality
layer of synovial tissue	UBERON:0007616	93.27	gold quality
gluteal muscle	UBERON:0002000	92.86	gold quality
thoracic mammary gland	UBERON:0005200	92.76	gold quality
descending thoracic aorta	UBERON:0002345	92.75	gold quality
mammary gland	UBERON:0001911	92.74	gold quality
cartilage tissue	UBERON:0002418	92.57	gold quality
mucosa of urinary bladder	UBERON:0001259	92.52	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-HCAD-10	yes	36.16
E-ANND-3	yes	9.23
E-MTAB-10290	no	256.47

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): EGR1, SP1

miRNA regulators (miRDB)

87 targeting PDGFC, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-1236-3P	99.94	68.04	1695
HSA-MIR-4778-3P	99.93	70.40	1818
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-3671	99.90	73.04	3897
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-106B-5P	99.88	74.72	2795
HSA-MIR-20A-5P	99.88	74.76	2769
HSA-MIR-629-3P	99.85	67.99	1875
HSA-MIR-4503	99.85	71.45	1869
HSA-MIR-6715A-3P	99.83	68.05	1473
HSA-MIR-3121-3P	99.82	71.96	3630
HSA-MIR-944	99.82	70.85	3042
HSA-MIR-374C-5P	99.80	72.06	2910

Literature-anchored findings (GeneRIF, showing 40)

• PDGFC was identified as target of EWS/ETS transcriptionalderegulation specific to EWS/FLI-1 chimeras in the Ewing Family Tumors suggesting that it may be a significant mediator of EWS/FLI driven oncogenesis. (PMID:11313995)
• Dominant negative PDGF-C inhibits growth of Ewing family tumor cell lines. (PMID:12032822)
• determination of PDGFC expression levels in medulloblastoma tumor cell lines (PMID:12176024)
• PDGF-C has a higher structural homology to the vascular endothelial growth factor than to PDGF-B (PMID:12598536)
• PDGF-C is constitutively expressed in the human kidney and is upregulated in podocytes and interstitial cells after injury/activation of these cells. (PMID:12707385)
• In adult human tissues, PDGF-C was largely in smooth muscle. It binds & activate alpha PDGFR, & activates beta PDGFR when it is co-expressed with alpha PDGFR through heterodimer formation. PDGF C is likely to play a role in platelet biology. (PMID:15061151)
• Plays a role in tissue remodeling. (PMID:15389578)
• PDGF-C transgenic mice represent a unique model for the study of hepatic fibrosis progressing to tumorigenesis (PMID:15728360)
• determine the molecular mechanism of tPA-mediated activation of PDGF-C dimer (PMID:15911618)
• Expression of PDGF-C in leiomyomata was significantly higher (approximately 2.4-fold) than in the adjacent normal myometrium. (PMID:17482170)
• PDGF-C and PDGF-D, like PDGF-A and PDGF-B, play important roles in atherosclerosis by stimulating MMP activity and influencing monocyte migration (PMID:18573494)
• A novel splice variant of human PDGF-C (PDGF-Cb), which encodes an N-terminally truncated protein, lacking the signal peptide and CUB domain, is reported. (PMID:18588873)
• The PDGF-C regulatory region SNP rs28999109 decreases promoter transcriptional activity and is associated with cleft lip with or without cleft palate (CL/P) (PMID:19092777)
• some tumors may overcome inhibition of VEGF-mediated angiogenesis through upregulation of PDGF-C (PMID:19111878)
• Upregulation of PDGFC expression may contribute to the clonal expansion of fibroid-derived smooth muscle cells in the development of uterine fibroids. (PMID:19553600)
• Data suggest that five novel genes, LUM, PDE3B, PDGF-C, NRG1 and PKD2, have great potential for predicting the efficacy of cisplatin-based chemotherapy against OSCC. (PMID:19569180)
• PDGFC mRNA expression were down-regulated in biopsies containing infiltrated lymphocytes or thyroiditis. (PMID:19968886)
• Data suggest that the variant rs1425486 genotype could differentially affect targeting by miR-425 in ovarian cancer cells leading to higher PDGFC expression. (PMID:21118967)
• Melanoma cell-derived platelet-derived growth factor (PDGF)-AA and PDGF-CC were identified as major mediators that signal through PDGFR-alpha and thus induce HAS2-mediated HA synthesis in fibroblasts (PMID:21993555)
• Platelet-derived growth factor-C (PDGF-C) activation by serine proteases. (PMID:22035541)
• Single nucleotide polymorphisms in the PDGF-C gene are linked to the development of oral clefts. (PMID:23029525)
• Results indicate that the alpha-SMA inducing effect of M2 macrophages is in part mediated by secretion of PGDF-CC. (PMID:23182716)
• PDGF-C is both angiogenic and a neuronal survival factor, and it is an important component of neurovascular crosstalk. [Review] (PMID:23714575)
• High PDGF-C expression induces progressive fibrosis, chronic inflammation, neoangiogenesis and sinusoidal congestion resulting in hepatocellular carcinoma. (PMID:23929039)
• The results indicate that PDGF-C upregulation and calpain-3 downregulation are involved in the aggressiveness of malignant melanoma and suggest that modulators of these proteins (PMID:24126726)
• Data indicate uPA (plau) and PAI1 (Serpine1) were up-regulated in human PDGF-C Tg mice, suggesting that uPA could be compensating for the loss of tissue-type plasminogen activator (tPA) activity in PDGF-C Tg; tpa KO mice. (PMID:24269585)
• Platelet-derived growth factor-C (PDGF-C) induces anti-apoptotic effects on macrophages through Akt and Bad phosphorylation. (PMID:24421315)
• Concomitant upregulation of PDGF-C with VEGF in Glioblastoma tumor cells. (PMID:24612214)
• PDGF-C up-regulation was mediated by the human embryonic lethal abnormal vision-like protein HuR, which stabilizes the PDGF-C transcript by binding to two predicted AU-rich elements (AREs) in the 3’-untranslated region (3’-UTR). (PMID:25383675)
• We conclude that PDGF-CC-induced blood-spinal cord barrier dysfunction can contribute to timing of amyotrophic lateral sclerosis onset (PMID:26687981)
• High glucose-mediated induction of PDGF-C via ChREBP in mesangial cells contributes to the development of glomerular mesangial expansion in diabetes. (PMID:27033449)
• There are four platelet-derived growth factor (PDGF) genes (PDGFA, PDGFB, PDGFC and PDGFD) that reside on chromosomes 7, 22, 4 and 11. (PMID:28267575)
• Numerous studies have shown that PDGF-C and PDGF-D are critical regulators of the cardiovascular system as angiogenic and survival factors. PDGF-C and PDGFD are widely expressed in many different types of cells with pleotropic effects. [review] (PMID:28965749)
• PDGF-C and PDGF-D are relatively new members of the PDGF family and are potent angiogenic and survival factors. Recent studies have demonstrated their important roles in different types of eye diseases. [review] (PMID:29079201)
• Protein expression of tumour and/or stromal cell PDGFRalpha, PDGFRbeta and PDGF-CC was evaluated in primary tumours (N = 489), synchronous lymph node metastases (N = 135) and asynchronous recurrences (N = 39) using immunohistochemistry in a prospectively maintained cohort of primary breast cancer patients (PMID:29380207)
• paracrine crosstalk between cancer cells expressing platelet-derived growth factor (PDGF)-CC and cancer-associated fibroblasts expressing the cognate receptors in human basal-like mammary carcinomas, was identified. (PMID:29529015)
• High PDGFC expression is associated with glioblastoma. (PMID:31482267)
• The authors found PDGF-C to be highly expressed in breast carcinoma cell lines. I (PMID:31542979)
• Platelet-Derived Growth Factor C in Alcoholics. (PMID:31897468)
• Cancer-associated fibroblast secretion of PDGFC promotes gastrointestinal stromal tumor growth and metastasis. (PMID:33603171)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	pdgfc	ENSDARG00000077588
mus_musculus	Pdgfc	ENSMUSG00000028019
rattus_norvegicus	Pdgfc	ENSRNOG00000010695

Paralogs (35): NRXN3 (ENSG00000021645), TLL1 (ENSG00000038295), CP (ENSG00000047457), DCBLD2 (ENSG00000057019), HEPH (ENSG00000089472), TLL2 (ENSG00000095587), NRP1 (ENSG00000099250), PCOLCE (ENSG00000106333), CNTNAP3 (ENSG00000106714), CUBN (ENSG00000107611), CNTNAP1 (ENSG00000108797), NRXN2 (ENSG00000110076), MEP1A (ENSG00000112818), NRP2 (ENSG00000118257), CUZD1 (ENSG00000138161), MFGE8 (ENSG00000140545), MEP1B (ENSG00000141434), CNTNAP4 (ENSG00000152910), CNTNAP3B (ENSG00000154529), CNTNAP5 (ENSG00000155052), CDCP2 (ENSG00000157211), PCOLCE2 (ENSG00000163710), EDIL3 (ENSG00000164176), NETO1 (ENSG00000166342), BMP1 (ENSG00000168487), PDGFD (ENSG00000170962), NETO2 (ENSG00000171208), CNTNAP2 (ENSG00000174469), NRXN1 (ENSG00000179915), HEPHL1 (ENSG00000181333), F8 (ENSG00000185010), ASTL (ENSG00000188886), F5 (ENSG00000198734), MFRP (ENSG00000235718), CNTNAP3C (ENSG00000283378)

Protein

Protein identifiers

Platelet-derived growth factor C — Q9NRA1 (reviewed: Q9NRA1)

Alternative names: Fallotein, Spinal cord-derived growth factor, VEGF-E

All UniProt accessions (3): Q9NRA1, H0Y9N2, J3KN71

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 and chemoattractant for cells of mesenchymal origin. Required for normal skeleton formation during embryonic development, especially for normal development of the craniofacial skeleton and for normal development of the palate. Required for normal skin morphogenesis during embryonic development. Plays an important role in wound healing, where it appears to be involved in three stages: inflammation, proliferation and remodeling. Plays an important role in angiogenesis and blood vessel development. Involved in fibrotic processes, in which transformation of interstitial fibroblasts into myofibroblasts plus collagen deposition occurs. The CUB domain has mitogenic activity in coronary artery smooth muscle cells, suggesting a role beyond the maintenance of the latency of the PDGF domain. In the nucleus, PDGFC seems to have additional function.

Subunit / interactions. Homodimer; disulfide-linked. Interacts with PDGFRA homodimers, and with heterodimers formed by PDGFRA and PDGFRB. Interacts (via CUB domain) with PLAT (via kringle domain).

Subcellular location. Cytoplasm. Cytosol. Secreted. Nucleus. Cytoplasmic granule. Cell membrane.

Tissue specificity. Expressed in the fallopian tube, vascular smooth muscle cells in kidney, breast and colon and in visceral smooth muscle of the gastrointestinal tract. Highly expressed in retinal pigment epithelia. Expressed in medulloblastoma. In the kidney, constitutively expressed in parietal epithelial cells of Bowman’s capsule, tubular epithelial cells and in arterial endothelial cells (at protein level). Highly expressed in the platelets, prostate, testis and uterus. Higher expression is observed in uterine leiomyomata. Weaker expression in the spleen, thymus, heart, pancreas, liver, ovary cells and small intestine, and negligible expression in the colon and peripheral blood leukocytes.

Post-translational modifications. Proteolytic removal of the N-terminal CUB domain releasing the core domain is necessary for unmasking the receptor-binding epitopes of the core domain. Cleavage after basic residues in the hinge region (region connecting the CUB and growth factor domains) gives rise to the receptor-binding form. Cleaved by PLAT and PLG. Sumoylated with SUMO1. N-glycosylated.

Induction. Up-regulated by EWS-FLI1 chimeric transcription factor in tumor derived cells. Up-regulated in podocytes and interstitial cells after injury/activation of these cells. FGF2 activates PDGFC transcription via EGR1. Up-regulated by TGFB1 in concert with FGF2.

Miscellaneous. A lower molecular weight form (around 43 kDa) is present in patients with papillary thyroid carcinoma.

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

Isoforms (4)

UniProt ID	Names	Canonical?
Q9NRA1-1	1	yes
Q9NRA1-2	2
Q9NRA1-3	3
Q9NRA1-4	4

RefSeq proteins (1): NP_057289* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000072	PDGF/VEGF_dom	Domain
IPR000859	CUB_dom	Domain
IPR029034	Cystine-knot_cytokine	Homologous_superfamily
IPR035914	Sperma_CUB_dom_sf	Homologous_superfamily

Pfam: PF00341, PF00431

UniProt features (25 total): disulfide bond 6, splice variant 4, mutagenesis site 4, site 3, chain 2, sequence conflict 2, glycosylation site 2, signal peptide 1, domain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NRA1-F1	76.30	0.44

Functional residue map

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

Catalytic / active sites (3): 225–226 (cleavage); 231–232 (cleavage); 234–235 (cleavage)

Disulfide bonds (6): 250–294, 274, 280–335, 286, 287–337, 104–124

Glycosylation sites (2): 25, 55

Mutagenesis-validated functional residues (4):

Position	Phenotype
124	loss of mitogenic activity of cub domain in coronary artery smooth muscle cells.
231	essential for cleavage by plat.
232	not essential for cleavage by plat.
234	not essential for cleavage by plat.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-186797	Signaling by PDGF

MSigDB gene sets: 302 (showing top): GOBP_PLATELET_DERIVED_GROWTH_FACTOR_RECEPTOR_SIGNALING_PATHWAY, WAMUNYOKOLI_OVARIAN_CANCER_LMP_DN, chr4q32, GOBP_SKELETAL_SYSTEM_DEVELOPMENT, GOBP_RESPONSE_TO_ACID_CHEMICAL, GOBP_POSITIVE_REGULATION_OF_FIBROBLAST_PROLIFERATION, DITTMER_PTHLH_TARGETS_UP, GOBP_POSITIVE_REGULATION_OF_MAPK_CASCADE, GOCC_CELL_SURFACE, MCBRYAN_PUBERTAL_TGFB1_TARGETS_UP, GOMF_GROWTH_FACTOR_ACTIVITY, RACCACAR_AML_Q6, GOBP_CELLULAR_RESPONSE_TO_ACID_CHEMICAL, CHANDRAN_METASTASIS_DN, CEBPB_01

GO Biological Process (14): central nervous system development (GO:0007417), positive regulation of cell population proliferation (GO:0008284), animal organ morphogenesis (GO:0009887), positive regulation of cell migration (GO:0030335), platelet-derived growth factor receptor signaling pathway (GO:0048008), fibroblast proliferation (GO:0048144), positive regulation of fibroblast proliferation (GO:0048146), digestive tract development (GO:0048565), positive regulation of cell division (GO:0051781), positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction (GO:0051897), bone development (GO:0060348), positive regulation of ERK1 and ERK2 cascade (GO:0070374), cellular response to amino acid stimulus (GO:0071230), positive regulation of cold-induced thermogenesis (GO:0120162)

GO Molecular Function (4): platelet-derived growth factor receptor binding (GO:0005161), growth factor activity (GO:0008083), protein homodimerization activity (GO:0042803), protein binding (GO:0005515)

GO Cellular Component (11): Golgi membrane (GO:0000139), extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), nucleus (GO:0005634), endoplasmic reticulum lumen (GO:0005788), cytosol (GO:0005829), plasma membrane (GO:0005886), cell surface (GO:0009986), extracellular exosome (GO:0070062), cytoplasm (GO:0005737), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Signaling by Receptor Tyrosine Kinases	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
cell population proliferation	2
positive regulation of cellular process	2
animal organ development	2
nervous system development	1
system development	1
regulation of cell population proliferation	1
anatomical structure morphogenesis	1
cell migration	1
regulation of cell migration	1
positive regulation of cell motility	1
cell surface receptor protein tyrosine kinase signaling pathway	1
positive regulation of cell population proliferation	1
fibroblast proliferation	1
regulation of fibroblast proliferation	1
tube development	1
digestive system development	1
cell division	1
regulation of cell division	1
phosphatidylinositol 3-kinase/protein kinase B signal transduction	1
regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	1
positive regulation of intracellular signal transduction	1
skeletal system development	1
positive regulation of MAPK cascade	1
ERK1 and ERK2 cascade	1
regulation of ERK1 and ERK2 cascade	1
response to amino acid	1
cellular response to acid chemical	1
positive regulation of multicellular organismal process	1
cold-induced thermogenesis	1
regulation of cold-induced thermogenesis	1
growth factor receptor binding	1
receptor ligand activity	1
identical protein binding	1
protein dimerization activity	1
binding	1
Golgi apparatus	1
bounding membrane of organelle	1
intracellular membrane-bounded organelle	1
endoplasmic reticulum	1

Protein interactions and networks

STRING

1184 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PDGFC	PDGFRA	P16234	998
PDGFC	KDR	P35968	994
PDGFC	PDGFRB	P09619	985
PDGFC	FLT4	P35916	977
PDGFC	FLT1	P16057	972
PDGFC	PDGFB	P01127	968
PDGFC	PDGFA	P04085	961
PDGFC	PGF	P49763	876
PDGFC	VEGFC	P49767	864
PDGFC	PDGFD	Q9GZP0	855
PDGFC	VEGFB	P49765	811
PDGFC	NRP1	O14786	792
PDGFC	NTRK1	P04629	696
PDGFC	FIP1L1	Q6UN15	640
PDGFC	SNX15	Q9NRS6	637

IntAct

12 interactions, top by confidence:

A	B	Type	Score
PDGFRA	PDGFB	psi-mi:“MI:0915”(physical association)	0.730
PDGFC	PDGFRA	psi-mi:“MI:0407”(direct interaction)	0.660
PDGFC	PDGFC	psi-mi:“MI:0407”(direct interaction)	0.440
CREB3	OGT	psi-mi:“MI:0914”(association)	0.350
PDGFRA	MYO1B	psi-mi:“MI:0914”(association)	0.350
SCGB2A1	RAP1BL	psi-mi:“MI:0914”(association)	0.350
ADAMTS13	C2CD4B	psi-mi:“MI:0914”(association)	0.350
RLN1	RTL8C	psi-mi:“MI:0914”(association)	0.350
L3MBTL4	PSMA7	psi-mi:“MI:0914”(association)	0.350
EEA1	PDLIM1	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (16): PDGFC (Affinity Capture-MS), PDGFC (Affinity Capture-MS), PDGFC (Affinity Capture-MS), PDGFC (Proximity Label-MS), PDGFC (Reconstituted Complex), PDGFC (Affinity Capture-Western), PDGFC (Affinity Capture-MS), PDGFC (Affinity Capture-MS), PDGFC (Affinity Capture-MS), PDGFC (Affinity Capture-MS), PDGFC (Affinity Capture-MS), PDGFC (Proximity Label-MS), PDGFC (Biochemical Activity), PDGFC (Biochemical Activity), PDGFC (Biochemical Activity)

ESM2 similar proteins: A0A1D5PUP4, A5YT95, A8WCC4, O35757, O62650, O75882, O95633, O95980, P07224, P07225, P10669, P19883, P21674, P26012, P26013, P31514, P31515, P47931, P49767, P50291, P97953, Q0VBD0, Q17QD6, Q2VWQ2, Q5RA73, Q6PFE7, Q8BFR2, Q8CI19, Q8IYR6, Q8N475, Q90844, Q91590, Q925I7, Q92832, Q99J86, Q99PW7, Q9EQC7, Q9EQT1, Q9EQX6, Q9GZP0

Diamond homologs: A8WCC4, F1RWC3, O35276, O35375, O43897, O57382, O57460, O60462, O60494, O70244, P13497, P25723, P98063, P98070, Q20176, Q5RA73, Q62381, Q6V9H4, Q7Z407, Q7Z408, Q80T79, Q8CI19, Q8JI28, Q8QFX6, Q925I7, Q9DER7, Q9EQT1, Q9EQX6, Q9GZP0, Q9I946, Q9JLB4, Q9NRA1, Q9TU53, Q9VC47, Q9W332, Q9WVM6, Q9Y6L7, A8Q2D1, B3EX01, B8VIV4

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
EGR1	“up-regulates quantity by expression”	PDGFC	“transcriptional regulation”
SP1	“up-regulates quantity by expression”	PDGFC	“transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	30
Likely benign	4
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

3324 predictions. Top by Δscore:

Variant	Effect	Δscore
4:156767988:CCA:C	acceptor_gain	1.0000
4:156767989:CACTA:C	acceptor_gain	1.0000
4:156767991:C:CC	acceptor_gain	1.0000
4:156770559:A:C	donor_gain	1.0000
4:156772890:ATTG:A	acceptor_gain	1.0000
4:156772891:TTG:T	acceptor_gain	1.0000
4:156772894:C:CC	acceptor_gain	1.0000
4:156807693:A:C	donor_gain	1.0000
4:156810829:GTACT:G	donor_loss	1.0000
4:156810830:TACTT:T	donor_loss	1.0000
4:156810831:ACTT:A	donor_loss	1.0000
4:156810832:CTTAC:C	donor_loss	1.0000
4:156810833:TTA:T	donor_loss	1.0000
4:156810834:TACT:T	donor_loss	1.0000
4:156810835:A:AC	donor_gain	1.0000
4:156810835:ACTGG:A	donor_gain	1.0000
4:156810836:C:CG	donor_gain	1.0000
4:156810836:CTG:C	donor_gain	1.0000
4:156810836:CTGG:C	donor_gain	1.0000
4:156810836:CTGGC:C	donor_gain	1.0000
4:156811013:CATAC:C	acceptor_gain	1.0000
4:156811015:TAC:T	acceptor_gain	1.0000
4:156811016:ACCT:A	acceptor_loss	1.0000
4:156811017:CCTG:C	acceptor_loss	1.0000
4:156811018:CTGCA:C	acceptor_loss	1.0000
4:156811019:T:C	acceptor_loss	1.0000
4:156834824:TCATA:T	donor_gain	1.0000
4:156850219:A:AC	donor_gain	1.0000
4:156850220:C:CC	donor_gain	1.0000
4:156850220:CTTG:C	donor_gain	1.0000

AlphaMissense

2264 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:156810865:A:G	F156S	0.999
4:156810895:G:A	S146F	0.999
4:156810901:A:G	F144S	0.999
4:156850225:A:G	C104R	0.999
4:156850355:G:C	S60R	0.999
4:156850355:G:T	S60R	0.999
4:156850357:T:G	S60R	0.999
4:156810864:G:C	F156L	0.998
4:156810864:G:T	F156L	0.998
4:156810866:A:G	F156L	0.998
4:156810868:C:T	G155E	0.998
4:156810869:C:A	G155W	0.998
4:156810895:G:T	S146Y	0.998
4:156810907:A:T	I142K	0.998
4:156810961:C:G	C124S	0.998
4:156810962:A:G	C124R	0.998
4:156810962:A:T	C124S	0.998
4:156811006:A:T	V109E	0.998
4:156811012:T:A	D107V	0.998
4:156811013:C:G	D107H	0.998
4:156850224:C:G	C104S	0.998
4:156850224:C:T	C104Y	0.998
4:156850225:A:T	C104S	0.998
4:156850272:A:G	L88P	0.998
4:156850305:A:G	L77S	0.998
4:156850312:A:G	W75R	0.998
4:156850312:A:T	W75R	0.998
4:156850346:A:C	F63L	0.998
4:156850346:A:T	F63L	0.998
4:156850348:A:G	F63L	0.998

dbSNP variants (sampled 300 via entrez): RS1000007635 (4:156824421 CATAT>C,CAT,CATATAT), RS1000016347 (4:156863733 C>T), RS1000019028 (4:156897586 T>C), RS1000049319 (4:156936738 T>C,G), RS1000050092 (4:156897323 A>C,G,T), RS1000066297 (4:156776126 GA>G,GAA), RS10000702 (4:156771179 G>A,T), RS1000075747 (4:156902603 T>A), RS1000095501 (4:156851762 T>G), RS1000113038 (4:156794630 A>T), RS1000133802 (4:156816604 C>A,T), RS1000138429 (4:156891195 G>A,T), RS1000148167 (4:156941943 A>C,G), RS1000170729 (4:156811769 T>C), RS1000179876 (4:156837071 A>G)

Disease associations

OMIM: gene MIM:608452 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

39 associations (top):

Study	Trait	p-value
GCST000492_2	Speech perception in dyslexia	5.000000e-08
GCST001526_9	Fasting blood insulin (BMI interaction)	5.000000e-09
GCST002563_6	Hypospadias	1.000000e-09
GCST003901_20	Cognitive decline (age-related)	6.000000e-06
GCST004093_28	Prostate-specific antigen levels	2.000000e-09
GCST004232_86	HDL cholesterol levels	1.000000e-08
GCST004603_225	Platelet count	1.000000e-09
GCST004607_230	Plateletcrit	5.000000e-12
GCST005185_9	Fasting blood insulin	6.000000e-07
GCST005231_32	Major depressive disorder	6.000000e-06
GCST006288_317	Heel bone mineral density	1.000000e-07
GCST006288_530	Heel bone mineral density	2.000000e-10
GCST006611_123	HDL cholesterol	1.000000e-08
GCST006624_122	Systolic blood pressure	2.000000e-17
GCST006666_14	Lipid traits (pleiotropy) (HIPO component 1)	2.000000e-08
GCST006979_758	Heel bone mineral density	9.000000e-14
GCST006979_759	Heel bone mineral density	4.000000e-26
GCST007267_3	Systolic blood pressure	3.000000e-13
GCST007269_279	Pulse pressure	5.000000e-09
GCST009356_2	Nonsyndromic cleft palate	2.000000e-08
GCST009357_15	Nonsyndromic cleft lip	1.000000e-06
GCST009379_268	Type 2 diabetes	2.000000e-08
GCST009615_7	Triglyceride levels x loop diuretics use interaction	2.000000e-06
GCST010242_210	HDL cholesterol levels	6.000000e-09
GCST010244_151	Triglyceride levels	1.000000e-11
GCST010701_116	Cortical surface area (MOSTest)	3.000000e-11
GCST010702_177	Subcortical volume (MOSTest)	2.000000e-34
GCST010703_336	Brain morphology (MOSTest)	3.000000e-10
GCST012049_3	High density lipoprotein cholesterol levels	4.000000e-07
GCST012137_1	Motor coordination	8.000000e-06

EFO canonical traits (19, from GWAS)

EFO ID	Trait name
EFO:0004336	speech perception
EFO:0004340	body mass index
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0004309	platelet count
EFO:0007985	platelet crit
EFO:0009270	heel bone mineral density
EFO:0006335	systolic blood pressure
EFO:0004530	triglyceride measurement
EFO:0004574	total cholesterol measurement
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0005763	pulse pressure measurement
EFO:0003959	cleft lip
EFO:0004346	neuroimaging measurement
EFO:0010749	motor function measurement
EFO:0004980	appendicular lean mass
EFO:0004348	hematocrit
EFO:0004509	hemoglobin measurement
EFO:0007986	reticulocyte count
EFO:0005091	monocyte count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression, decreases methylation	9
Benzo(a)pyrene	decreases expression, increases methylation	5
trichostatin A	affects cotreatment, increases expression	3
Air Pollutants	decreases expression, increases abundance	3
bisphenol A	decreases methylation, decreases expression, affects cotreatment	2
potassium chromate(VI)	affects cotreatment, decreases expression	2
mercuric bromide	increases expression, affects cotreatment	2
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	decreases reaction, increases expression, affects cotreatment	2
(+)-JQ1 compound	decreases expression, decreases reaction, increases expression	2
Panobinostat	affects cotreatment, increases expression	2
Arsenic	affects expression, affects cotreatment, decreases expression, increases abundance	2
Copper	affects binding, decreases expression, increases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Tobacco Smoke Pollution	decreases expression	2
Particulate Matter	decreases expression, increases abundance	2
aristolochic acid I	decreases expression	1
ammonium 2,3,3,3-tetrafluoro-2-(heptafluoropropoxy)-propanoate	affects cotreatment, affects expression	1
triphenyl phosphate	affects expression	1
arsenite	increases methylation	1
sulforaphane	increases expression	1
sodium arsenite	increases abundance, affects cotreatment, decreases expression	1
cobaltous chloride	decreases expression	1
perfluorooctanoic acid	affects expression, affects cotreatment	1
manganese chloride	affects cotreatment, decreases expression, increases abundance	1
S-(1,2-dichlorovinyl)cysteine	decreases expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
octa-2,4,6-trienoic acid	increases expression	1
di-n-butylphosphoric acid	affects expression	1
chromium hexavalent ion	decreases expression	1
perfluorooctane sulfonic acid	affects expression, affects cotreatment	1

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B2A9	Abcam HeLa PDGFC KO	Cancer cell line	Female
CVCL_E2GI	HAP1 PDGFC (-) 1	Cancer cell line	Male
CVCL_E2GJ	HAP1 PDGFC (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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