PDGFD

Summary

PDGFD (platelet derived growth factor D, HGNC:30620) is a protein-coding gene on chromosome 11q22.3, encoding Platelet-derived growth factor D (Q9GZP0). 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, seven of which are found in this factor. This gene product only forms homodimers and, therefore, does not dimerize with the other three family members. It differs from alpha and beta members of this family in having an unusual N-terminal domain, the CUB domain. Two splice variants have been identified for this gene.

Source: NCBI Gene 80310 — RefSeq curated summary.

At a glance

• Gene–disease (curated): pulmonary arterial hypertension (Limited, ClinGen)
• GWAS associations: 29
• Clinical variants (ClinVar): 64 total
• MANE Select transcript: NM_025208

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30620
Approved symbol	PDGFD
Name	platelet derived growth factor D
Location	11q22.3
Locus type	gene with protein product
Status	Approved
Aliases	SCDGF-B, MSTP036, IEGF
Ensembl gene	ENSG00000170962
Ensembl biotype	protein_coding
OMIM	609673
Entrez	80310

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 4 protein_coding

ENST00000302251, ENST00000393158, ENST00000529268, ENST00000956141

RefSeq mRNA: 2 — MANE Select: NM_025208 NM_025208, NM_033135

CCDS: CCDS41703, CCDS8326

Canonical transcript exons

ENST00000393158 — 7 exons

Exon	Start	End
ENSE00001138232	103926912	103927126
ENSE00001138241	103943452	103943650
ENSE00001138251	103947662	103947724
ENSE00001138261	103996065	103996245
ENSE00001514313	104000051	104000255
ENSE00002157970	103907189	103909819
ENSE00002168772	104163804	104164147

Expression profiles

Bgee: expression breadth ubiquitous, 252 present calls, max score 98.41.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 6.1165 / max 111.2736, expressed in 1009 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
122059	1.8042	586
122058	1.3313	479
122060	1.1517	467
122061	0.8688	409
122062	0.3988	216
122063	0.3964	227
122057	0.1653	57

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
periodontal ligament	UBERON:0008266	98.41	gold quality
germinal epithelium of ovary	UBERON:0001304	96.90	gold quality
seminal vesicle	UBERON:0000998	96.30	gold quality
adrenal cortex	UBERON:0001235	96.12	gold quality
ventricular zone	UBERON:0003053	96.09	gold quality
left adrenal gland cortex	UBERON:0035825	96.09	gold quality
synovial joint	UBERON:0002217	96.08	gold quality
left adrenal gland	UBERON:0001234	95.88	gold quality
right adrenal gland cortex	UBERON:0035827	95.69	gold quality
descending thoracic aorta	UBERON:0002345	95.63	gold quality
thoracic aorta	UBERON:0001515	95.43	gold quality
right adrenal gland	UBERON:0001233	95.42	gold quality
ascending aorta	UBERON:0001496	95.33	gold quality
adrenal gland	UBERON:0002369	95.04	gold quality
skin of hip	UBERON:0001554	94.10	gold quality
gall bladder	UBERON:0002110	94.02	gold quality
right coronary artery	UBERON:0001625	93.25	gold quality
mammary duct	UBERON:0001765	93.18	gold quality
stromal cell of endometrium	CL:0002255	93.14	gold quality
heart right ventricle	UBERON:0002080	92.94	gold quality
left ovary	UBERON:0002119	92.78	gold quality
tibia	UBERON:0000979	92.63	gold quality
layer of synovial tissue	UBERON:0007616	92.62	gold quality
right ovary	UBERON:0002118	92.24	gold quality
epithelium of mammary gland	UBERON:0003244	92.08	gold quality
parietal pleura	UBERON:0002400	91.89	gold quality
thoracic mammary gland	UBERON:0005200	91.50	gold quality
ovary	UBERON:0000992	91.45	gold quality
mammary gland	UBERON:0001911	91.23	gold quality
left coronary artery	UBERON:0001626	90.96	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	8.91

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ETS1, IRF1, NFKB, SP1

miRNA regulators (miRDB)

110 targeting PDGFD, 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-5011-5P	100.00	83.46	5820
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-4487	99.96	64.58	1252
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-6835-3P	99.93	70.49	2904
HSA-MIR-381-3P	99.93	71.87	2854
HSA-MIR-300	99.92	71.76	2856
HSA-MIR-450B-5P	99.92	71.48	3175
HSA-MIR-145-5P	99.92	71.13	1836
HSA-MIR-5195-3P	99.92	70.92	1877
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-153-5P	99.89	73.86	6317

Literature-anchored findings (GeneRIF, showing 40)

• Platelet-derived growth factor D: tumorigenicity in mice and dysregulated expression in human cancer (PMID:11980634)
• we localized PDGF-D in human kidneys suggesting that PDGF-D may have a role in kidney development. (PMID:12427128)
• PDGF-D plays an important role in the pathogenesis of tubulointerstitial injury through binding of PDGF-Rbeta in both human obstructive nephropathy (PMID:14514732)
• full-length PDGF-D is activated in tissues and is capable of increasing interstitial fluid pressure and macrophage recruitment and the maturation of blood vessels in angiogenic processes. (PMID:15271796)
• PDGF D is activated and processed by urokinase plasminogen activator and they colocalize in human prostate carcinoma. (PMID:15988036)
• Sp1, like Ets-1, induces PDGF-D transcription and mRNA expression; H2O2 stimulates Ets-1, but not Sp1, and activates D3-dependent PDGF-D transcription (PMID:16189269)
• PDGF-D is present in the neointima of the arteriopathy of Chronic allograft nephropathy, where it can engage PDGF-Rbeta to promote mesenchymal cell migration, proliferation, and neointima formation. (PMID:18187181)
• All 3 residues in Sp1 (Thr668, Ser670, and Thr681) are required for Sp1-dependent platelet-derived growth factor-D activation in response to angiotensin II (PMID:18258854)
• PDGF-D promotes epithelial-mesenchymal transitiion and thus could be a novel therapeutic target for the prevention and/or treatment of prostate cancer. (PMID:18403754)
• Compared with control group, levels of PDGF-D and PDGF-B were progressively elevated in blood and urine of IgA nephropathy children. (PMID:18471357)
• 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)
• Association of platelet-derived growth factor-D gene polymorphism with ischemic stroke in a Chinese case-control study (PMID:18600092)
• uPA not only generates active PDGF-DD, but also regulates its spatial distribution, provides novel insights into the biological function of PDGF-DD. (PMID:18997817)
• PDGF-DD, a novel mediator of smooth muscle cell phenotypic modulation, is upregulated in endothelial cells exposed to atherosclerosis-prone flow patterns. (PMID:19028801)
• PDGF-DD serum levels in patients with IgA nephropathy (IgAN) were significantly higher (1.67 +/- 0.45 ng/ml) and in patients with lupus nephritis significantly lower (0.66 +/- 0.86 ng/ml) compared to healthy controls. (PMID:19357108)
• PDGF-D-induced acquisition of the EMT phenotype in PC3 cells is, in part, a result of repression of miR-200. (PMID:19544444)
• LH significantly increased PDGF-D messenger RNA (mRNA) expression but suppressed PDGF-B and PDGF-C mRNA in human granulosa-luteal cells (PMID:19733850)
• human umbilical cord blood tropism toward glioma cells are partially dependent on the PDGF/PGGFR system. (PMID:20406896)
• Study unveiled a novel signaling axis of matriptase/PDGF-D/beta-PDGFR in PCa, providing new insights into functional interplay between serine protease and growth factor signaling networks. (PMID:21098708)
• The results of this study suggested that PDGFD -858A/C variant is probably associated with risk for non-hypertensive intracerebral hemorrhage. (PMID:22289441)
• PDGF-D promotes malignant mesothelioma cell chemotaxis through PDGF-betabeta receptor signaling pathways along a PI3 kinase/PDK1/Akt/Rac1/ROCK axis and relevant to ERK activation (PMID:22415093)
• High PDGFD expression promotes ovarian cancer invasion by regulating matrix metalloproteinases 2 and 9 (PMID:22471482)
• Taken together with our previous finding that matriptase is a proteolytic activator of PDGF D, this study provides a molecular insight into signal amplification of the proteolytic network and PDGF signaling loop during cancer progression. (PMID:22689130)
• Meta-analysis showed that single nucleotide polymorphism rs974819 of PDGFD gene was significantly associated with an increasing risk of coronary heart disease (OR=1.08, 95% CI=1.05 - 1.11) in both Europeans and South Asians including Han Chinese. (PMID:22704460)
• Down-regulation of platelet-derived growth factor-D expression blockades NF-kappaB pathway to inhibit cell proliferation and invasion as well as induce apoptosis in esophageal squamous cell carcinoma. (PMID:23187740)
• Platelet-derived growth factor-D and Rho GTPases regulate recruitment of cancer-associated fibroblasts in cholangiocarcinoma. (PMID:23505219)
• PDGF-D is highly expressed in gemcitabine resistant (GR) liver neoplasm cells. Furthermore, down-regulation of PDGF-D in GR cells led to partial reversal of the EMT phenotype. (PMID:24158561)
• Data suggest that targeting platelet-derived growth factor-D as a strategy for endometrial cancer treatment. (PMID:24646915)
• Compared with matched normal endometrial cases, PDGF-D was up-regulated in endometrial cancer. Expression of PDGF-D protein, found in 78% of the cases, was associated with nonendometrioid histologic type. (PMID:24870786)
• PDGF-DD secreted by gastric cancer derived mesenchymal stem cells is capable of promoting gastric cancer cell progression in vitro and in vivo. (PMID:24938433)
• PDGF-D is highly expressed by ASCs, where it acts as a potent mitogenic factor. (PMID:25332166)
• PDGFD, CDH1 and SLIT2 are upregulated in low grade meningiomas and schwannomas compared with healthy tissue. (PMID:25333347)
• PDGFD-PDGFRbeta signalling is required for human neocortical development and local production of growth factors by radial glia supports the expanded germinal region and progenitor heterogeneity of species with large brains (PMID:25391964)
• PDGF-D expression is associated with miR-106a and Twist1 in HCC patients (PMID:25760076)
• Novel findings reveal a new paradigm in matriptase activation involving PDGF-D-specific signal transduction leading to extracellular acidosis. (PMID:26157007)
• polymorphism of rs7950273 in the PDGFD gene is not associated with ischaemic stroke in the Chinese Han population (PMID:26362023)
• upregulated in kidney fibrosis, may mediate renal scarring, and is dispensable for normal kidney development and physiological functions (PMID:26924050)
• This study suggested that epithelial-mesenchymal transition process can be triggered by the PDGF-D/PDGFRb axis in tongue squamous cell carcinoma, and then involved in the tumor cell invasion via activation of p38/AKT/ERK/ epithelial-mesenchymal transition pathway. (PMID:27507215)
• No specific genotype of rs974819 of Platelet-derived growth factor D demonstrated increased cardiovascular mortality in the total population, however, the male group with genotypes A/A and G/A demonstrated an increased risk that persisted in a multivariate evaluation where adjustments were made for well-known cardiovascular risk factors. (PMID:27585990)
• PDGF-D promotes tumor growth and aggressiveness of colorectal carcinoma. Down-regulation of PDGF-D inactivates Notch1/Twist1 axis, which could reverse epithelial mesenchymal transformation and prevent CRC progression. (PMID:28035069)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	pdgfd	ENSDARG00000077677
mus_musculus	Pdgfd	ENSMUSG00000032006
rattus_norvegicus	Pdgfd	ENSRNOG00000029148

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), PDGFC (ENSG00000145431), CNTNAP4 (ENSG00000152910), CNTNAP3B (ENSG00000154529), CNTNAP5 (ENSG00000155052), CDCP2 (ENSG00000157211), PCOLCE2 (ENSG00000163710), EDIL3 (ENSG00000164176), NETO1 (ENSG00000166342), BMP1 (ENSG00000168487), 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 D — Q9GZP0 (reviewed: Q9GZP0)

Alternative names: Iris-expressed growth factor, Spinal cord-derived growth factor B

All UniProt accessions (2): Q9GZP0, H0YD37

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. Plays an important role in wound healing. Induces macrophage recruitment, increased interstitial pressure, and blood vessel maturation during angiogenesis. Can initiate events that lead to a mesangial proliferative glomerulonephritis, including influx of monocytes and macrophages and production of extracellular matrix.

Subunit / interactions. Homodimer; disulfide-linked. Interacts with PDGFRB homodimers, and with heterodimers formed by PDGFRA and PDGFRB.

Subcellular location. Secreted.

Tissue specificity. Expressed at high levels in the heart, pancreas, adrenal gland and ovary and at low levels in placenta, liver, kidney, prostate, testis, small intestine, spleen and colon. In the kidney, expressed by the visceral epithelial cells of the glomeruli. A widespread expression is also seen in the medial smooth muscle cells of arteries and arterioles, as well as in smooth muscle cells of vasa rectae in the medullary area. Expressed in the adventitial connective tissue surrounding the suprarenal artery. In chronic obstructive nephropathy, a persistent expression is seen in glomerular visceral epithelial cells and vascular smooth muscle cells, as well as de novo expression by periglomerular interstitial cells and by some neointimal cells of atherosclerotic vessels. Expression in normal prostate is seen preferentially in the mesenchyme of the gland while expression is increased and more profuse in prostate carcinoma. Expressed in many ovarian, lung, renal and brain cancer-derived cell lines.

Post-translational modifications. Activated by proteolytic cleavage. 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 Arg-247 or Arg-249 by urokinase plasminogen activator gives rise to the active form.

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

Isoforms (2)

UniProt ID	Names	Canonical?
Q9GZP0-1	1, Long, SCDGF-B-L	yes
Q9GZP0-2	2, Short, SCDGF-B-S

RefSeq proteins (2): NP_079484, NP_149126 (=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 (16 total): disulfide bond 4, chain 2, sequence variant 2, mutagenesis site 2, site 2, signal peptide 1, splice variant 1, domain 1, glycosylation site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9GZP0-F1	73.85	0.42

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 (2): 247–248 (cleavage); 249–250 (cleavage)

Disulfide bonds (4): 306–362, 109–131, 296, 302–360

Glycosylation sites (1): 276

Mutagenesis-validated functional residues (2):

Position	Phenotype
247	abolishes cleavage into active form; when associated with a-249.
249	abolishes cleavage into active form; when associated with a-247.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-186797	Signaling by PDGF

MSigDB gene sets: 261 (showing top): VALK_AML_WITH_FLT3_ITD, GOBP_PLATELET_DERIVED_GROWTH_FACTOR_RECEPTOR_SIGNALING_PATHWAY, WAMUNYOKOLI_OVARIAN_CANCER_LMP_DN, MULLIGHAN_NPM1_SIGNATURE_3_UP, GOBP_MYELOID_LEUKOCYTE_MIGRATION, GOBP_CELL_CHEMOTAXIS, BERTUCCI_MEDULLARY_VS_DUCTAL_BREAST_CANCER_DN, GOBP_RESPONSE_TO_ACID_CHEMICAL, chr11q22, XU_HGF_TARGETS_REPRESSED_BY_AKT1_DN, GOBP_POSITIVE_REGULATION_OF_FIBROBLAST_PROLIFERATION, GOBP_POSITIVE_REGULATION_OF_CELLULAR_EXTRAVASATION, GOBP_POSITIVE_REGULATION_OF_MAPK_CASCADE, GOMF_GROWTH_FACTOR_ACTIVITY, GOBP_MUSCLE_CELL_PROLIFERATION

GO Biological Process (15): positive regulation of cell population proliferation (GO:0008284), positive regulation of cell migration (GO:0030335), cellular response to platelet-derived growth factor stimulus (GO:0036120), platelet-derived growth factor receptor signaling pathway (GO:0048008), positive regulation of fibroblast proliferation (GO:0048146), positive regulation of smooth muscle cell proliferation (GO:0048661), positive regulation of cell division (GO:0051781), positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction (GO:0051897), cellular response to hydrogen peroxide (GO:0070301), positive regulation of ERK1 and ERK2 cascade (GO:0070374), cellular response to amino acid stimulus (GO:0071230), cellular response to transforming growth factor beta stimulus (GO:0071560), positive regulation of smooth muscle cell chemotaxis (GO:0071673), positive regulation of glomerular mesangial cell proliferation (GO:0072126), positive regulation of monocyte extravasation (GO:2000439)

GO Molecular Function (2): platelet-derived growth factor receptor binding (GO:0005161), growth factor activity (GO:0008083)

GO Cellular Component (5): Golgi membrane (GO:0000139), extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), endoplasmic reticulum lumen (GO:0005788), 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
positive regulation of cellular process	2
cellular response to growth factor stimulus	2
positive regulation of cell population proliferation	2
cellular anatomical structure	2
cell population proliferation	1
regulation of cell population proliferation	1
cell migration	1
regulation of cell migration	1
positive regulation of cell motility	1
response to platelet-derived growth factor	1
cell surface receptor protein tyrosine kinase signaling pathway	1
fibroblast proliferation	1
regulation of fibroblast proliferation	1
smooth muscle cell proliferation	1
regulation of smooth muscle cell proliferation	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
cellular response to reactive oxygen species	1
response to hydrogen peroxide	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
response to transforming growth factor beta	1
positive regulation of smooth muscle cell migration	1
positive regulation of chemotaxis	1
smooth muscle cell chemotaxis	1
regulation of smooth muscle cell chemotaxis	1
glomerular mesangial cell proliferation	1
regulation of glomerular mesangial cell proliferation	1
positive regulation of cell proliferation involved in kidney development	1
positive regulation of cellular extravasation	1
monocyte extravasation	1
positive regulation of mononuclear cell migration	1
regulation of monocyte extravasation	1
growth factor receptor binding	1

Protein interactions and networks

STRING

1200 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PDGFD	PDGFRB	P09619	997
PDGFD	PDGFRA	P16234	991
PDGFD	PDGFA	P04085	921
PDGFD	PDGFB	P01127	911
PDGFD	PDGFC	Q9NRA1	855
PDGFD	NCR2	O95944	692
PDGFD	FLT1	P16057	679
PDGFD	KDR	P35968	570
PDGFD	FGFR1	P11362	544
PDGFD	AGT	P01019	497
PDGFD	PTPRC	P08575	497
PDGFD	MIA3	Q5JRA6	489
PDGFD	THBS2	P35442	456
PDGFD	DLL1	O00548	438
PDGFD	ITGAV	P06756	433

IntAct

6 interactions, top by confidence:

A	B	Type	Score
PDGFD	DCTN6	psi-mi:“MI:0914”(association)	0.530
TLK2	IGKV1D-13	psi-mi:“MI:0914”(association)	0.350
HCN1	POTEF	psi-mi:“MI:0914”(association)	0.350

BioGRID (38): POTEE (Affinity Capture-MS), DCTN5 (Affinity Capture-MS), DCTN6 (Affinity Capture-MS), UBR1 (Affinity Capture-MS), DCTN4 (Affinity Capture-MS), ACTR10 (Affinity Capture-MS), NEURL4 (Affinity Capture-MS), DCTN3 (Affinity Capture-MS), SEH1L (Affinity Capture-MS), UBR5 (Affinity Capture-MS), DCTN1 (Affinity Capture-MS), DCTN2 (Affinity Capture-MS), ACTR1B (Affinity Capture-MS), LRP2 (Affinity Capture-MS), ECI2 (Affinity Capture-MS)

ESM2 similar proteins: A0A1D5PUP4, A5YT95, O35757, O62650, O75882, O95980, P07225, P09858, P10669, P17247, P19883, P21214, P21674, P26012, P26013, P27090, P30371, P31514, P31515, P47931, P49767, P50291, P61811, P61812, P97299, P97953, Q07257, Q0VBD0, Q17QD6, Q38L25, Q5RA73, Q6NW40, Q6V9H4, Q6ZQ11, Q863H1, Q86X52, Q8BFR2, Q8CI19, Q8JG54, Q8N475

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, B3EX01, B8JI71, B8VIV4

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	53
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2917 predictions. Top by Δscore:

Variant	Effect	Δscore
11:103926082:AGAC:A	donor_gain	1.0000
11:103927124:CAA:C	acceptor_gain	1.0000
11:103927127:C:CC	acceptor_gain	1.0000
11:103943446:TCTTA:T	donor_loss	1.0000
11:103943447:CTTAC:C	donor_loss	1.0000
11:103943448:TTA:T	donor_loss	1.0000
11:103943449:TAC:T	donor_loss	1.0000
11:103943450:ACCT:A	donor_loss	1.0000
11:103943451:C:A	donor_loss	1.0000
11:103943603:C:CT	acceptor_gain	1.0000
11:103947660:A:AC	donor_gain	1.0000
11:103947661:C:CC	donor_gain	1.0000
11:103947721:CTTC:C	acceptor_gain	1.0000
11:103947722:TTCC:T	acceptor_loss	1.0000
11:103947724:CCTG:C	acceptor_loss	1.0000
11:103947725:C:CA	acceptor_loss	1.0000
11:103947726:T:A	acceptor_loss	1.0000
11:103996063:A:AC	donor_gain	1.0000
11:103996064:C:CC	donor_gain	1.0000
11:103996064:CCAG:C	donor_gain	1.0000
11:103996241:CATAC:C	acceptor_gain	1.0000
11:103996242:ATAC:A	acceptor_gain	1.0000
11:103996243:TAC:T	acceptor_gain	1.0000
11:103996244:AC:A	acceptor_gain	1.0000
11:103996245:CC:C	acceptor_gain	1.0000
11:103996253:C:CT	acceptor_gain	1.0000
11:103996254:A:T	acceptor_gain	1.0000
11:103996256:T:C	acceptor_gain	1.0000
11:104000296:CAAT:C	acceptor_gain	1.0000
11:104000299:T:C	acceptor_gain	1.0000

AlphaMissense

2428 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:103996117:G:A	S153F	1.000
11:103927013:A:G	C296R	0.999
11:103996087:A:G	F163S	0.999
11:103996090:C:T	G162E	0.999
11:103996117:G:T	S153Y	0.999
11:103996118:A:G	S153P	0.999
11:103996123:A:G	F151S	0.999
11:103996240:T:A	D112V	0.999
11:103996241:C:G	D112H	0.999
11:104000054:C:G	C109S	0.999
11:104000054:C:T	C109Y	0.999
11:104000055:A:G	C109R	0.999
11:104000055:A:T	C109S	0.999
11:104000182:A:C	S66R	0.999
11:104000182:A:T	S66R	0.999
11:104000184:T:G	S66R	0.999
11:103909728:C:G	C360S	0.998
11:103909729:A:T	C360S	0.998
11:103926994:C:G	C302S	0.998
11:103926995:A:G	C302R	0.998
11:103926995:A:T	C302S	0.998
11:103927011:G:C	C296W	0.998
11:103927012:C:G	C296S	0.998
11:103927013:A:T	C296S	0.998
11:103927084:C:G	C272S	0.998
11:103927085:A:G	C272R	0.998
11:103927085:A:T	C272S	0.998
11:103996086:G:C	F163L	0.998
11:103996086:G:T	F163L	0.998
11:103996088:A:G	F163L	0.998

dbSNP variants (sampled 300 via entrez): RS1000008990 (11:104008345 C>G), RS1000011354 (11:103953144 A>G), RS1000025581 (11:103999676 C>T), RS1000030728 (11:104106800 G>A), RS1000034938 (11:104128763 G>T), RS1000049584 (11:103948186 G>A,C,T), RS1000063078 (11:104055237 G>A), RS1000071577 (11:103967083 G>C,T), RS1000120663 (11:104024183 G>A,T), RS1000142276 (11:103963777 G>A,T), RS1000165351 (11:104021169 G>T), RS1000166036 (11:104014552 C>T), RS1000174878 (11:104143940 C>T), RS1000179821 (11:103988327 A>G,T), RS1000188185 (11:104048818 C>G)

Disease associations

OMIM: gene MIM:609673 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
pulmonary arterial hypertension	Limited	Autosomal dominant

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
pulmonary arterial hypertension	Limited	AD

Mondo (1): pulmonary arterial hypertension (MONDO:0015924)

Orphanet (0):

HPO phenotypes

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

GWAS associations

29 associations (top):

Study	Trait	p-value
GCST000975_3	LDL cholesterol	3.000000e-06
GCST000999_11	Coronary heart disease	2.000000e-09
GCST001059_15	Neutrophil count	6.000000e-07
GCST002671_10	Toenail selenium levels	2.000000e-06
GCST002875_71	Diisocyanate-induced asthma	2.000000e-06
GCST003116_28	Coronary artery disease	7.000000e-11
GCST003117_16	Myocardial infarction	4.000000e-09
GCST004787_25	Coronary artery disease (myocardial infarction, percutaneous transluminal coronary angioplasty, coronary artery bypass grafting, angina or chromic ischemic heart disease)	2.000000e-11
GCST005924_1	Corticosteroid-induced adrenal suppression (peak cortisol < 500 nmol/L)	4.000000e-10
GCST005927_1	Corticosteroid-induced adrenal suppression (peak cortisol < 350 nmol/L)	4.000000e-09
GCST006248_2	Response to lurasidone in schizophrenia	2.000000e-07
GCST006585_148	Blood protein levels	3.000000e-129
GCST006810_19	Self-reported risk-taking behaviour	2.000000e-08
GCST009391_1720	Metabolite levels	8.000000e-06
GCST010204_129	Low density lipoprotein cholesterol levels	4.000000e-11
GCST010225_25	Cortical surface area (visual PC2)	3.000000e-10
GCST010241_247	Apolipoprotein A1 levels	4.000000e-09
GCST010242_239	HDL cholesterol levels	1.000000e-08
GCST010243_66	Apolipoprotein B levels	4.000000e-08
GCST010245_32	LDL cholesterol levels	1.000000e-09
GCST010397_117	Gut microbiota (bacterial taxa, rank normal transformation method)	4.000000e-07
GCST010479_21	Coronary artery disease	2.000000e-08
GCST010480_9	Coronary artery disease	3.000000e-09
GCST010736_8	Urinary albumin-to-creatinine ratio	4.000000e-07
GCST011364_18	Myocardial infarction	3.000000e-11
GCST011365_42	Myocardial infarction	2.000000e-18
GCST011616_56	Cortical volume	8.000000e-11
GCST90000015_23	Parkinson’s disease motor subtype (tremor to postural instability/gait difficulty score ratio)	8.000000e-06
GCST90017148_1	Brain asymmetrical skew (vertical)	2.000000e-07

EFO canonical traits (14, from GWAS)

EFO ID	Trait name
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0004833	neutrophil count
EFO:0006995	response to diisocyanate
EFO:0009176	adrenal suppression measurement
EFO:0008579	risk-taking behaviour
EFO:0010341	cholesteryl ester 16:0 measurement
EFO:0004771	visual cortical surface area measurement
EFO:0004614	apolipoprotein A 1 measurement
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0004615	apolipoprotein B measurement
EFO:0007874	gut microbiome measurement
EFO:0007778	urinary albumin to creatinine ratio
EFO:0600011	Parkinson’s disease symptom measurement
EFO:0004346	neuroimaging measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D000081029	Pulmonary Arterial Hypertension	C08.381.423.847

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression, affects expression	5
sodium arsenite	decreases expression, increases expression	3
bisphenol A	increases expression, affects methylation, affects cotreatment, increases methylation	2
Doxorubicin	decreases expression, increases expression	2
8-Bromo Cyclic Adenosine Monophosphate	decreases expression, increases expression	2
Aflatoxin B1	decreases expression, decreases methylation	2
bisphenol F	affects cotreatment, affects expression	1
ammonium 2,3,3,3-tetrafluoro-2-(heptafluoropropoxy)-propanoate	affects expression, affects cotreatment	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
trichostatin A	decreases expression, increases expression	1
arsenite	increases methylation	1
mono-(2-ethylhexyl)phthalate	decreases expression	1
butyraldehyde	decreases expression	1
perfluorooctanoic acid	affects cotreatment, affects expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	affects expression, affects cotreatment	1
CGP 52608	affects binding, increases reaction	1
perfluoro-n-nonanoic acid	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	decreases reaction, decreases expression	1
4(2’-aminoethyl)amino-1,8-dimethylimidazo(1,2-a)quinoxaline	decreases expression, decreases reaction	1
abrine	decreases expression	1
perfluorobutanesulfonic acid	affects expression, affects cotreatment	1
asparanin A	decreases expression	1
incobotulinumtoxinA	increases expression	1
Temozolomide	increases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Air Pollutants	increases abundance, decreases expression	1
Arsenic	affects expression	1
Benzo(a)pyrene	increases methylation, affects methylation	1

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B2AA	Abcam HeLa PDGFD KO	Cancer cell line	Female
CVCL_D7WP	Ubigene A-549 PDGFD KO	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00058929	PHASE4	COMPLETED	A Transition Study From Flolan® to Remodulin® in Patients With Pulmonary Arterial Hypertension
NCT00303459	PHASE4	COMPLETED	Effects of the Combination of Bosentan and Sildenafil Versus Sildenafil Monotherapy on Pulmonary Arterial Hypertension (PAH)
NCT00323297	PHASE4	COMPLETED	Assess the Efficacy and Safety of Sildenafil When Added to Bosentan in the Treatment of Pulmonary Arterial Hypertension
NCT00367770	PHASE4	COMPLETED	BREATHE 5-OL: Tracleer (Bosentan) in Patients With Pulmonary Arterial Hypertension Related to Eisenmenger Physiology
NCT00403650	PHASE4	COMPLETED	Inhaled Iloprost for Sarcoidosis-associated Pulmonary Hypertension
NCT00430716	PHASE4	TERMINATED	To Assess The Efficacy and Safety Of Oral Sildenafil in the Treatment of Pulmonary Arterial Hypertension.
NCT00433329	PHASE4	COMPLETED	Combination Therapy in Pulmonary Arterial Hypertension
NCT00439946	PHASE4	TERMINATED	Safety, Efficacy, and Treatment Satisfaction Switching From Flolan to Remodulin Using the Crono Five Ambulatory Pump in Patients With PAH
NCT00483626	PHASE4	UNKNOWN	Hemodynamic Response After Six Months of Sildenafil
NCT00494533	PHASE4	TERMINATED	Study of Intravenous Remodulin in Patients in India With Pulmonary Arterial Hypertension
NCT00617305	PHASE4	COMPLETED	Study of Add-on Ambrisentan Therapy to Background Phosphodiesterase Type-5 Inhibitor (PDE5i) Therapy in Pulmonary Arterial Hypertension (ATHENA-1)
NCT00625079	PHASE4	WITHDRAWN	Pulmonary Hypertension Secondary to Idiopathic Pulmonary Fibrosis And Treatment With Sildenafil
NCT00625469	PHASE4	WITHDRAWN	Pulmonary Arterial Hypertension Secondary to Idiopathic Pulmonary Fibrosis and Treatment With Bosentan
NCT00705588	PHASE4	UNKNOWN	Long Acting Phosphodiesterase 5 Inhibitors as Add-on Therapy for Patients With Pulmonary Hypertension Treated With Prostanoids.
NCT00741819	PHASE4	COMPLETED	Safety Evaluation of Inhaled Treprostinil Administration Following Transition From Inhaled Ventavis in Pulmonary Arterial Hypertension (PAH) Subjects
NCT01042158	PHASE4	COMPLETED	A Clinical Trial of Ambrisentan and Tadalafil in Pulmonary Arterial Hypertension Associated With Systemic Sclerosis
NCT01105091	PHASE4	COMPLETED	Epoprostenol for Injection in Pulmonary Arterial Hypertension
NCT01105117	PHASE4	COMPLETED	Epoprostenol for Injection in Pulmonary Arterial Hypertension - Extension of AC-066A401
NCT01268553	PHASE4	COMPLETED	Transition From Injectable Prostacyclin Medication to Inhaled Prostacyclin Medication
NCT01302444	PHASE4	TERMINATED	Treprostinil Combined With Tadalafil for Pulmonary Hypertension
NCT01330108	PHASE4	COMPLETED	Safely Change From Bosentan to Ambrisentan in Pulmonary Hypertension
NCT01433328	PHASE4	TERMINATED	Lidocaine Subcutaneous Infusion for Control of Treprostinil Related Site Pain
NCT01508780	PHASE4	WITHDRAWN	Combined Use of Angiography, Optical Coherence Tomography and Intravascular Ultrasound in Evaluation of Pulmonary Vascular Structure and Function in Patients With Pulmonary Arterial Hypertension Treated With Oral Bosentan
NCT01615627	PHASE4	WITHDRAWN	Hypotonic Treprostinil Subcutaneous Infusion for Control of Treprostinil Related Site Pain
NCT01642407	PHASE4	COMPLETED	Safety And Efficacy Of Sildenafil In Children With Pulmonary Arterial Hypertension
NCT01649739	PHASE4	UNKNOWN	Vardenafil as add-on Therapy for Patients With Pulmonary Hypertension Treated With Inhaled Iloprost
NCT02060487	PHASE4	TERMINATED	Effects of Oral Sildenafil on Mortality in Adults With PAH
NCT02253394	PHASE4	TERMINATED	The Combination Ambrisentan Plus Spironolactone in Pulmonary Arterial Hypertension Study
NCT02284737	PHASE4	TERMINATED	A Study to Investigate the Efficacy of PADN to Improved Functional Capacity and Hemodynamics in Patients With PAH
NCT02310672	PHASE4	COMPLETED	REPAIR: Right vEntricular Remodeling in Pulmonary ArterIal hypeRtension
NCT02847260	PHASE4	COMPLETED	Safety and Tolerability of Rapid Dose Titration of Subcutaneous Remodulin® Therapy in PAH Subjects (RAPID)
NCT02882126	PHASE4	WITHDRAWN	An Open Label Extension Study to Evaluate the Safety of Continued Therapy of Subcutanous Remodulin® in Pulmonary Arterial Hypertension
NCT02885012	PHASE4	TERMINATED	Crossover Study From Macitentan or Bosentan Over to Ambrisentan
NCT02891850	PHASE4	COMPLETED	Riociguat rEplacing PDE-5i Therapy evaLuated Against Continued PDE-5i thErapy
NCT02893995	PHASE4	WITHDRAWN	Safety, Tolerability, Pharmacokinetics and Efficacy of Two Different Rates of Subcutanous Remodulin® Dose Titration in Pulmonary Arterial Hypertension
NCT02968901	PHASE4	TERMINATED	Clinical Study Evaluating the Effects of First-line Oral cOmbination theraPy of maciTentan and tadalafIl in Patients With Newly Diagnosed pulMonary Arterial Hypertension (OPTIMA)
NCT03055221	PHASE4	COMPLETED	TRUST-2: Safety and Efficacy of Intravenous Remodulin® in Patients in India With Pulmonary Arterial Hypertension (PAH)
NCT03078907	PHASE4	COMPLETED	Effect of Selexipag on Daily Life Physical Activity of Patients With Pulmonary Arterial Hypertension.
NCT03236818	PHASE4	UNKNOWN	Goal Oriented Strategy to Preserve Ejection Fraction Trial
NCT03344159	PHASE4	COMPLETED	Spironolactone Therapy in Chronic Stable Right HF Trial