VASP

Summary

VASP (vasodilator stimulated phosphoprotein, HGNC:12652) is a protein-coding gene on chromosome 19q13.32, encoding Vasodilator-stimulated phosphoprotein (P50552). Ena/VASP proteins are actin-associated proteins involved in a range of processes dependent on cytoskeleton remodeling and cell polarity such as axon guidance, lamellipodial and filopodial dynamics, platelet activation and cell migration.

Vasodilator-stimulated phosphoprotein (VASP) is a member of the Ena-VASP protein family. Ena-VASP family members contain an EHV1 N-terminal domain that binds proteins containing E/DFPPPPXD/E motifs and targets Ena-VASP proteins to focal adhesions. In the mid-region of the protein, family members have a proline-rich domain that binds SH3 and WW domain-containing proteins. Their C-terminal EVH2 domain mediates tetramerization and binds both G and F actin. VASP is associated with filamentous actin formation and likely plays a widespread role in cell adhesion and motility. VASP may also be involved in the intracellular signaling pathways that regulate integrin-extracellular matrix interactions. VASP is regulated by the cyclic nucleotide-dependent kinases PKA and PKG.

Source: NCBI Gene 7408 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 34 total
• Druggable target: yes
• MANE Select transcript: NM_003370

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:12652
Approved symbol	VASP
Name	vasodilator stimulated phosphoprotein
Location	19q13.32
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000125753
Ensembl biotype	protein_coding
OMIM	601703
Entrez	7408

Gene structure

Transcript identifiers

Ensembl transcripts: 29 — 22 protein_coding, 4 retained_intron, 2 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000245932, ENST00000586014, ENST00000586619, ENST00000587444, ENST00000588273, ENST00000588463, ENST00000588482, ENST00000589627, ENST00000590459, ENST00000590603, ENST00000592139, ENST00000705986, ENST00000705987, ENST00000862924, ENST00000862925, ENST00000862926, ENST00000862927, ENST00000862928, ENST00000862929, ENST00000916557, ENST00000916558, ENST00000916559, ENST00000916560, ENST00000916561, ENST00000916562, ENST00000916563, ENST00000916564, ENST00000916565, ENST00000952562

RefSeq mRNA: 1 — MANE Select: NM_003370 NM_003370

CCDS: CCDS33051

Canonical transcript exons

ENST00000245932 — 13 exons

Exon	Start	End
ENSE00000858231	45521322	45521406
ENSE00000858233	45522340	45522581
ENSE00001112676	45526140	45526983
ENSE00001375539	45507479	45507776
ENSE00003490354	45523644	45523695
ENSE00003496624	45524097	45524142
ENSE00003572258	45524570	45524660
ENSE00003577795	45522718	45522818
ENSE00003620729	45525946	45526003
ENSE00003626970	45517929	45518094
ENSE00003672473	45523841	45523877
ENSE00003675557	45522168	45522217
ENSE00003791075	45517663	45517834

Expression profiles

Bgee: expression breadth ubiquitous, 257 present calls, max score 98.76.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 156.0280 / max 5345.2021, expressed in 1828 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
176490	152.7382	1828
176489	2.2219	1022
176494	0.5814	314
176493	0.3232	137
176495	0.1633	45

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
granulocyte	CL:0000094	98.76	gold quality
monocyte	CL:0000576	98.70	gold quality
leukocyte	CL:0000738	98.53	gold quality
mononuclear cell	CL:0000842	98.49	gold quality
mucosa of transverse colon	UBERON:0004991	97.87	gold quality
spleen	UBERON:0002106	97.59	gold quality
saphenous vein	UBERON:0007318	97.59	gold quality
blood	UBERON:0000178	97.53	gold quality
muscle layer of sigmoid colon	UBERON:0035805	97.46	gold quality
transverse colon	UBERON:0001157	97.41	gold quality
lower esophagus	UBERON:0013473	97.38	gold quality
lower esophagus muscularis layer	UBERON:0035833	97.38	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	97.18	gold quality
sigmoid colon	UBERON:0001159	97.02	gold quality
rectum	UBERON:0001052	96.76	gold quality
thoracic aorta	UBERON:0001515	96.72	gold quality
ascending aorta	UBERON:0001496	96.71	gold quality
colon	UBERON:0001155	96.63	gold quality
descending thoracic aorta	UBERON:0002345	96.61	gold quality
left uterine tube	UBERON:0001303	96.60	gold quality
colonic epithelium	UBERON:0000397	96.53	gold quality
large intestine	UBERON:0000059	96.45	gold quality
right coronary artery	UBERON:0001625	96.44	gold quality
aorta	UBERON:0000947	96.39	gold quality
small intestine Peyer’s patch	UBERON:0003454	96.31	gold quality
upper lobe of left lung	UBERON:0008952	96.30	gold quality
popliteal artery	UBERON:0002250	96.21	gold quality
tibial artery	UBERON:0007610	96.21	gold quality
intestine	UBERON:0000160	96.14	gold quality
upper lobe of lung	UBERON:0008948	96.14	gold quality

Single-cell (SCXA)

Detected in 6 experiment(s), a significant marker in 6.

Experiment	Marker?	Max mean expression
E-CURD-112	yes	34.53
E-HCAD-4	yes	28.40
E-HCAD-6	yes	25.29
E-ANND-3	yes	20.03
E-HCAD-10	yes	16.55
E-MTAB-8498	yes	10.60

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): FOXO1, FOXO3, HIF1A, NFKB

miRNA regulators (miRDB)

104 targeting VASP, 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-190A-3P	100.00	80.35	5520
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-4455	100.00	65.48	1587
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-6748-5P	100.00	65.81	1057
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-3667-3P	99.99	67.17	1636
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
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-551B-5P	99.96	71.28	3493
HSA-MIR-3910	99.95	71.13	2227
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-22-3P	99.93	68.13	917
HSA-MIR-106A-5P	99.90	73.94	2683
HSA-MIR-17-5P	99.89	73.83	2665
HSA-MIR-7162-3P	99.89	68.16	1682
HSA-MIR-106B-5P	99.88	74.72	2795
HSA-MIR-20A-5P	99.88	74.76	2769
HSA-MIR-20B-5P	99.88	74.01	2621

Literature-anchored findings (GeneRIF, showing 40)

• Results show that VASP is expressed in a cell-specific and trimester-specific manner in the human placenta, and may be important for blastocyst implantation and placental develpoment. (PMID:11756574)
• Data show that phosphorylation of VASP is dynamically regulated by cellular adhesion to extracellular matrix. (PMID:12087107)
• The C-terminal fragment of VASP (336-380) forms a tetramer in solution via a coiled coil arrangement and is solely responsible for tetramerization of full-length VASP. (PMID:12220179)
• These results suggest that VASP may participate in vasculogenesis and endothelial sprouting during placental vasculogenesis (PMID:12397215)
• The platelet VASP shift is modified during coronary perfusion, and this modification correlates with mononuclear infiltration in the graft. (PMID:12566781)
• Phosphorylation of VASP induced by either cGMP analogs or a nitric oxide donor is inhibited by PKA; PKA plays a predominant role in the cGMP-induced phosphorylation of VASP and platelet inhibition in human platelets. (PMID:12576312)
• laminar shear stress can induce VASP translocation and phosphorylation in HUVECs, leading to actin filaments rearrangement, aligning cells along the flow direction. (PMID:12652017)
• These findings show that vasodilator-stimulated phosphoprotein and diaphanous 1 function cooperatively downstream of Rho to control F-actin assembly and serum response factor activity. (PMID:12805219)
• VASP, an important component of the cellular microfilament system, plays a major role in regulating serum response element-dependent transcription (PMID:14679200)
• M10 carries Mena/VASP from the root to the tip of the filopodia where extension of actin filament takes place (PMID:15158464)
• VASP phosphorylation at serine157 is required for the growth-stimulatory effect of transfected human VASP in rodent SMCs, whereas VASP phosphorylation at serine239 is involved in the growth inhibitory effects of NO on SMCs. (PMID:15178555)
• The basis for the right-handed geometry of VASP TD is a 15-residue repeat in its amino acid sequence, which reveals a characteristic pattern of hydrophobic residues (PMID:15569942)
• VASP is phosphorylated in patients with ischemic cardiovascular diseases and clopidogrel resistance (PMID:15634270)
• Galpha13-induced VASP phosphorylation that involves activation of RhoA and MEKK1, phosphorylation and degradation of IkappaB, release of PKA catalytic subunit from the complex with IkappaB and NF-kappaB, and subsequent phosphorylation of VASP (PMID:16046415)
• Rho kinase and PKC were identified as the major kinases that phosphorylate VASP Ser157 in response to thrombin in human platelets. (PMID:16197368)
• Migfilin has a role in interacting with vasodilator-stimulated phosphoprotein (VASP) and regulates VASP localization to cell-matrix adhesions and migration (PMID:16531412)
• VASP is a new AMP-activated protein kinase substrate (PMID:17082196)
• VASP may play a role in assembling and stabilizing the mitotic spindle of cells, and phosphorylation of the protein is the precondition for it to exert this function. (PMID:17167837)
• RSV resistance in a minority of clones was due to mono-allelic disruption of the cellular gene for VASP. (PMID:17351763)
• VASP phosphorylation may have a role in the individual response to clopidogrel loading dose prior to percutaneous coronary intervention (PMID:17488353)
• Data show that phosphorylation of Ser239 of VASP results in loss of lamellipodial protrusions and cell rounding, and is a powerful means of controlling directed actin polymerization within lamellipodia. (PMID:17684063)
• analysis of the structural basis of profilin-actin complexes during filament elongation by Ena/VASP (PMID:17914456)
• VASP has a role in increased impaired platelet responsiveness in patients with subacute stent thrombosis (PMID:17938817)
• Determination of VASP phosphorylation is superior to conventional platelet aggregometry and angiographic parameters for assessing the risk of stent thrombosis. (PMID:18064332)
• VASP phosphorylation demonstrated concordance across the response range of P2Y(12) receptor blockade following thienopyridine administration. (PMID:18217157)
• Examine prothrombotic status in low responder patients to clopidogrel indentified by VASP analysis. (PMID:18278200)
• Vasoactive gases CO and NO promote cytoskeletal changes through site- and cell type-specific VASP phosphorylation, and in diabetes, blunted responses to these agents may lead to reduced vascular repair and tissue perfusion (PMID:18559661)
• H2O2 in the absence of NO or exogenous haem- containing proteins induces nitration of platelet VASP (PMID:18569864)
• These results indicate that force-mediated adhesion strengthening occurs in endothelial adherens junctions and that dynamic VASP activity is necessary for this process. (PMID:18680720)
• Positive regulation of migration and invasion by vasodilator-stimulated phosphoprotein via Rac1 pathway in human breast cancer cells. (PMID:18813837)
• The antiplatelet effects of cilostazol intake could be evaluated by measuring VASP phosphorylation levels and maximal aggregation rates in platelets by ex vivo treatment with a low concentration of PGE(1). (PMID:18832777)
• VASP associated with nucleophosmin-ALK, and its phosphorylation required ALK activity. (PMID:18845790)
• Data show that both human and Dictyostelium VASP are directly involved in accelerating actin filament elongation by delivering monomeric actin to the growing barbed end. (PMID:18923426)
• Assessment of VASP index in acute coronary syndrome patients identifies low responders to clopidogrel who are at increased risk of recurrent cardiovascular events. (PMID:19059569)
• LPA receptor-induced VASP phosphorylation is a critical mediator of tumor cell migration initiation (PMID:19081821)
• Data demonstrate that profilin-1 downregulation results in a hyper-motile phenotype of MDA-MB-231 breast cancer cells in an Ena/VASP-dependent mechanism. (PMID:19115233)
• Data provide the first demonstration that direct interaction of VASP with CXCR2 is essential for proper CXCR2 function and demonstrate a crucial role for VASP in mediating chemotaxis in leukocytes. (PMID:19435808)
• Results from the VASP-02 (Vasodilator-Stimulated Phosphoprotein-02) randomized study which used guided switching to clopidogrel 150 mg/day after 2 weeks in low responders. (PMID:19463377)
• These results identify tissue-specific VASP as a central protein in the control of the alveolar-capillary barrier properties during acute lung injury. (PMID:19690214)
• VASP phosphorylation at serine239 regulates cytoskeleton remodeling. (PMID:19798690)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	vaspb	ENSDARG00000017105
danio_rerio	vaspa	ENSDARG00000099690
mus_musculus	Vasp	ENSMUSG00000030403
rattus_norvegicus	Vasp	ENSRNOG00000016367
drosophila_melanogaster	ena	FBGN0000578
caenorhabditis_elegans		WBGENE00006770

Paralogs (5): ENAH (ENSG00000154380), SPRED1 (ENSG00000166068), SPRED3 (ENSG00000188766), EVL (ENSG00000196405), SPRED2 (ENSG00000198369)

Protein

Protein identifiers

Vasodilator-stimulated phosphoprotein — P50552 (reviewed: P50552)

All UniProt accessions (9): P50552, A0A024R0V4, A0A994J508, A0A994J7X3, K7EIG8, K7EM16, K7ENL7, K7ENR7, K7EQD0

UniProt curated annotations — full annotation on UniProt →

Function. Ena/VASP proteins are actin-associated proteins involved in a range of processes dependent on cytoskeleton remodeling and cell polarity such as axon guidance, lamellipodial and filopodial dynamics, platelet activation and cell migration. VASP promotes actin filament elongation. It protects the barbed end of growing actin filaments against capping and increases the rate of actin polymerization in the presence of capping protein. VASP stimulates actin filament elongation by promoting the transfer of profilin-bound actin monomers onto the barbed end of growing actin filaments. Plays a role in actin-based mobility of Listeria monocytogenes in host cells. Regulates actin dynamics in platelets and plays an important role in regulating platelet aggregation.

Subunit / interactions. Homotetramer. Interacts with PFN1, PFN2, LPP, ACTN1 and ACTG1. Interacts, via the EVH1 domain, with the Pro-rich regions of ZYX. This interaction is important for targeting to focal adhesions and the formation of actin-rich structures at the apical surface of cells. Interacts, via the EVH1 domain, with the Pro-rich domain of Listeria monocytogenes actA. Interacts with APBB1IP. Interacts, via the Pro-rich domain, with the C-terminal SH3 domain of DNMBP. Interacts weakly with MEFV.

Subcellular location. Cytoplasm. Cytoskeleton. Cell junction. Focal adhesion. Tight junction. Cell projection. Lamellipodium membrane. Filopodium membrane.

Tissue specificity. Highly expressed in platelets.

Post-translational modifications. Major substrate for cAMP-dependent (PKA) and cGMP-dependent protein kinase (PKG) in platelets. The preferred site for PKA is Ser-157, the preferred site for PKG/PRKG1, Ser-239. In ADP-activated platelets, phosphorylation by PKA or PKG on Ser-157 leads to fibrinogen receptor inhibition. Phosphorylation on Thr-278 requires prior phosphorylation on Ser-157 and Ser-239. In response to phorbol ester (PMA) stimulation, phosphorylated by PKC/PRKCA. In response to thrombin, phosphorylated by both PKC and ROCK1. Phosphorylation at Thr-278 by AMPK does not require prior phosphorylation at Ser-157 or Ser-239. Phosphorylation at Ser-157 by PKA is required for localization to the tight junctions in epithelial cells. Phosphorylation modulates F-actin binding, actin filament elongation and platelet activation. Phosphorylation at Ser-322 by AMPK also alters actin filament binding. Carbon monoxide (CO) promotes phosphorylation at Ser-157, while nitric oxide (NO) promotes phosphorylation at Ser-157, but also at Ser-239. Response to NO and CO is blunted in platelets from diabetic patients, and VASP is not phosphorylated efficiently at Ser-157 and Ser-239.

Domain organisation. The EVH2 domain is comprised of 3 regions. Block A is a thymosin-like domain required for G-actin binding. The KLKR motif within this block is essential for the G-actin binding and for actin polymerization. Block B is required for F-actin binding and subcellular location, and Block C for tetramerization. The WH1 domain mediates interaction with XIRP1.

Miscellaneous. VASP phosphorylation is used to monitor the effect of so-called antiplatelet drugs that reduce platelet reactivity and are used to prevent stent thrombosis, strokes and heart attacks in patients at risk for these problems.

Similarity. Belongs to the Ena/VASP family.

RefSeq proteins (1): NP_003361* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000697	WH1/EVH1_dom	Domain
IPR011993	PH-like_dom_sf	Homologous_superfamily
IPR014885	VASP_tetra	Domain
IPR017354	VASP/EVL	Family
IPR038023	VASP_sf	Homologous_superfamily

Pfam: PF00568, PF08776

UniProt features (53 total): modified residue 14, strand 8, region of interest 6, mutagenesis site 6, compositionally biased region 3, helix 3, repeat 2, sequence variant 2, sequence conflict 2, turn 2, initiator methionine 1, chain 1, coiled-coil region 1, short sequence motif 1, domain 1

Structure

Experimental structures (PDB)

11 structures.

PDB	Method	Resolution (Å)
1USE	X-RAY DIFFRACTION	1.3
2PBD	X-RAY DIFFRACTION	1.5
1USD	X-RAY DIFFRACTION	1.7
2PAV	X-RAY DIFFRACTION	1.8
3CHW	X-RAY DIFFRACTION	2.3
9UB1	ELECTRON MICROSCOPY	2.35
8YVL	ELECTRON MICROSCOPY	2.47
9UAX	ELECTRON MICROSCOPY	2.71
8GAT	ELECTRON MICROSCOPY	3
8GAU	ELECTRON MICROSCOPY	3.6
1EGX	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P50552-F1	71.43	0.38

Antibody-complex structures (SAbDab): 3 — 8GAT, 8GAU, 8YVL

Functional residue map

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

Post-translational modifications (14): 2, 39, 46, 157, 239, 278, 283, 284, 305, 314, 316, 322, 323, 325

Mutagenesis-validated functional residues (6):

Position	Phenotype
157	promotes f-actin assembly; when associated with a-239 and a-278. interferes with f-actin assembly; when associated with
239	promotes f-actin assembly; when associated with a-157 and a-278. interferes with f-actin assembly; when associated with
278	promotes f-actin assembly; when associated with a-157 and a-239.
278	interferes with f-actin assembly; when associated with a-157 and a-239.
370	lower stability of tetramerization domain.
370	no change in stability of tetramerization domain.

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-202433	Generation of second messenger molecules
R-HSA-376176	Signaling by ROBO receptors
R-HSA-446353	Cell-extracellular matrix interactions

MSigDB gene sets: 370 (showing top): GSE45365_NK_CELL_VS_CD11B_DC_DN, GSE45365_NK_CELL_VS_BCELL_UP, GOBP_MORPHOGENESIS_OF_AN_EPITHELIUM, AGGAAGC_MIR5163P, AP1_01, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_REGULATION_OF_PROTEIN_POLYMERIZATION, WWTAAGGC_UNKNOWN, GOBP_PROTEIN_HOMOTETRAMERIZATION, SWEET_KRAS_ONCOGENIC_SIGNATURE, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, RORA1_01, LFA1_Q6, ENK_UV_RESPONSE_KERATINOCYTE_UP

GO Biological Process (6): neural tube closure (GO:0001843), axon guidance (GO:0007411), actin polymerization or depolymerization (GO:0008154), positive regulation of actin filament polymerization (GO:0030838), protein homotetramerization (GO:0051289), actin cytoskeleton organization (GO:0030036)

GO Molecular Function (5): actin binding (GO:0003779), profilin binding (GO:0005522), SH3 domain binding (GO:0017124), cadherin binding (GO:0045296), protein binding (GO:0005515)

GO Cellular Component (17): cytosol (GO:0005829), plasma membrane (GO:0005886), bicellular tight junction (GO:0005923), focal adhesion (GO:0005925), actin cytoskeleton (GO:0015629), lamellipodium membrane (GO:0031258), filopodium membrane (GO:0031527), extracellular exosome (GO:0070062), postsynapse (GO:0098794), glutamatergic synapse (GO:0098978), cytoplasm (GO:0005737), cytoskeleton (GO:0005856), membrane (GO:0016020), lamellipodium (GO:0030027), filopodium (GO:0030175), cell projection (GO:0042995), anchoring junction (GO:0070161)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
TCR signaling	1
Axon guidance	1
Cell junction organization	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
cell projection membrane	2
synapse	2
primary neural tube formation	1
tube closure	1
axonogenesis	1
neuron projection guidance	1
actin filament organization	1
actin filament polymerization	1
regulation of actin filament polymerization	1
positive regulation of protein polymerization	1
positive regulation of cytoskeleton organization	1
positive regulation of supramolecular fiber organization	1
protein homooligomerization	1
protein tetramerization	1
cytoskeleton organization	1
actin filament-based process	1
cytoskeletal protein binding	1
protein binding	1
protein domain specific binding	1
cell adhesion molecule binding	1
binding	1
cytoplasm	1
membrane	1
cell periphery	1
apical junction complex	1
tight junction	1
cell-substrate junction	1
cytoskeleton	1
lamellipodium	1
leading edge membrane	1
filopodium	1
extracellular vesicle	1
intracellular anatomical structure	1
intracellular membraneless organelle	1
cell leading edge	1
plasma membrane bounded cell projection	1
actin-based cell projection	1
cell junction	1

Protein interactions and networks

STRING

2514 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
VASP	PFN1	P07737	999
VASP	ZYX	Q15942	999
VASP	VCL	P18206	998
VASP	PFN3	P60673	998
VASP	PFN4	Q8NHR9	998
VASP	RAPH1	Q70E73	997
VASP	APBB1IP	Q7Z5R6	993
VASP	ACTA1	P02568	983
VASP	TLN1	Q9Y490	980
VASP	BAIAP2	Q9UQB8	966
VASP	PXN	P49023	965
VASP	TLN2	Q9Y4G6	965
VASP	HCLS1	P14317	939
VASP	CTTN	Q14247	937
VASP	FAT1	Q14517	934

IntAct

165 interactions, top by confidence:

A	B	Type	Score
VASP	ZYX	psi-mi:“MI:0915”(physical association)	0.800
VASP	CEP43	psi-mi:“MI:0915”(physical association)	0.740
ABI2	VASP	psi-mi:“MI:0915”(physical association)	0.740
CEP43	VASP	psi-mi:“MI:0915”(physical association)	0.740
VASP	ABI2	psi-mi:“MI:0915”(physical association)	0.740
VASP	CEP43	psi-mi:“MI:0914”(association)	0.740
ABI3	VASP	psi-mi:“MI:0915”(physical association)	0.720
VASP	ABI3	psi-mi:“MI:0915”(physical association)	0.720
VASP	TRIM9	psi-mi:“MI:0915”(physical association)	0.670
VASP	XIRP1	psi-mi:“MI:0915”(physical association)	0.650
VASP	XIRP1	psi-mi:“MI:0407”(direct interaction)	0.650
XIRP1	VASP	psi-mi:“MI:0407”(direct interaction)	0.650
XIRP1	VASP	psi-mi:“MI:0403”(colocalization)	0.650
BAIAP2	VASP	psi-mi:“MI:0407”(direct interaction)	0.650
BAIAP2	VASP	psi-mi:“MI:0915”(physical association)	0.650
VASP	BAIAP2	psi-mi:“MI:0407”(direct interaction)	0.650
VASP	BAIAP2	psi-mi:“MI:0915”(physical association)	0.650
AKT1	RPS6KB1	psi-mi:“MI:0914”(association)	0.640
act1	PFN1	psi-mi:“MI:0915”(physical association)	0.610

BioGRID (423): VASP (Two-hybrid), ABI2 (Two-hybrid), FGFR1OP (Two-hybrid), ABI3 (Two-hybrid), VASP (Affinity Capture-RNA), VASP (Affinity Capture-RNA), VASP (Affinity Capture-MS), VASP (Affinity Capture-MS), ENAH (Affinity Capture-MS), GTPBP1 (Affinity Capture-MS), CYFIP2 (Affinity Capture-MS), EVL (Affinity Capture-MS), CIRH1A (Affinity Capture-MS), ABI1 (Affinity Capture-MS), LRP4 (Affinity Capture-MS)

ESM2 similar proteins: A4IG59, A7Z063, A8K0Z3, A8MWX3, B0BN56, B2RYF7, B5DEB9, C4AMC7, D4A702, F1RCE7, O08719, O48713, O75061, P42768, P50551, P50552, P70315, P70429, P70460, Q08BD8, Q0VBD2, Q27974, Q28DN4, Q2TA49, Q32N92, Q5R896, Q5RHY1, Q5U4A3, Q5XG48, Q5ZKA6, Q61733, Q68FU8, Q6VEQ5, Q7JW27, Q7L590, Q80TZ3, Q8BH43, Q8BYZ1, Q8CH02, Q8IWZ8

Diamond homologs: O08719, P50551, P50552, P70429, P70460, Q03173, Q2TA49, Q3C2P8, Q5R896, Q5RDN2, Q5TJ65, Q5Y171, Q64GL0, Q6NYK3, Q7Z698, Q8N8S7, Q8T4F7, Q924S7, Q9UI08, Q2MJR0, Q6P6N5, Q9Z2X5, A2VDU1, O43597, O43610, Q08E39, Q2PFN5, Q3UUD2, Q5R959, Q66JG9, Q7Z699, Q866R9, Q924S8, Q9C004, Q9PTL2, Q9QXV8, Q9WTP2

SIGNOR signaling

20 interactions.

A	Effect	B	Mechanism
PRKG1	unknown	VASP	phosphorylation
PRKACA	unknown	VASP	phosphorylation
PRKAA2	down-regulates	VASP	phosphorylation
RPS6KA1	down-regulates	VASP	phosphorylation
AMPK	down-regulates	VASP	phosphorylation
RPS6K	down-regulates	VASP	phosphorylation
PKA	“up-regulates activity”	VASP	phosphorylation
PRKG1	“down-regulates activity”	VASP	phosphorylation
VASP	up-regulates	Axonal_growth_cone_formation
VASP	up-regulates	Neurite_outgrowth
RAPH1	“up-regulates activity”	VASP	binding
VASP	“up-regulates activity”	ATIC	phosphorylation
TRIM9	“down-regulates quantity”	VASP	ubiquitination
PRKG1	down-regulates	VASP	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 121 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Parasite infection	8	33.0×	2e-08
Leishmania phagocytosis	8	33.0×	2e-08
RHO GTPases Activate WASPs and WAVEs	8	30.2×	2e-08
Fcgamma receptor (FCGR) dependent phagocytosis	8	26.5×	5e-08
Signaling by VEGF	9	23.5×	2e-08
FCGR3A-mediated phagocytosis	9	20.1×	5e-08
Regulation of actin dynamics for phagocytic cup formation	9	19.7×	5e-08
Leishmania infection	10	19.4×	2e-08

GO biological processes:

GO term	Partners	Fold	FDR
actin polymerization or depolymerization	6	44.2×	3e-06
positive regulation of actin filament polymerization	5	15.9×	3e-03
actin filament organization	8	9.1×	1e-03
regulation of cell shape	7	8.3×	4e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	21
Likely benign	1
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

1822 predictions. Top by Δscore:

Variant	Effect	Δscore
19:45517654:C:A	acceptor_gain	1.0000
19:45517830:AGCAG:A	donor_loss	1.0000
19:45517831:GCAG:G	donor_gain	1.0000
19:45517832:CAG:C	donor_loss	1.0000
19:45517833:AGGTG:A	donor_loss	1.0000
19:45517834:GGTG:G	donor_loss	1.0000
19:45517836:T:G	donor_loss	1.0000
19:45518040:G:GT	donor_gain	1.0000
19:45518091:GAAGG:G	donor_loss	1.0000
19:45518092:AAG:A	donor_loss	1.0000
19:45518093:AGG:A	donor_loss	1.0000
19:45518094:GGTC:G	donor_loss	1.0000
19:45518095:G:A	donor_loss	1.0000
19:45518096:T:A	donor_loss	1.0000
19:45522707:A:G	acceptor_gain	1.0000
19:45522819:GTGA:G	donor_loss	1.0000
19:45523639:T:A	acceptor_gain	1.0000
19:45523641:CA:C	acceptor_loss	1.0000
19:45523642:A:AC	acceptor_loss	1.0000
19:45523642:A:AG	acceptor_gain	1.0000
19:45523642:AGAAG:A	acceptor_gain	1.0000
19:45523643:G:GA	acceptor_gain	1.0000
19:45523643:GA:G	acceptor_gain	1.0000
19:45523643:GAA:G	acceptor_gain	1.0000
19:45523643:GAAGG:G	acceptor_gain	1.0000
19:45523691:CCAAT:C	donor_gain	1.0000
19:45523693:AAT:A	donor_gain	1.0000
19:45523694:AT:A	donor_gain	1.0000
19:45523696:G:GG	donor_gain	1.0000
19:45523697:TAA:T	donor_loss	1.0000

AlphaMissense

2439 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:45517724:T:A	W23R	1.000
19:45517724:T:C	W23R	1.000
19:45517725:G:C	W23S	1.000
19:45517726:G:C	W23C	1.000
19:45517726:G:T	W23C	1.000
19:45517764:T:A	V36D	1.000
19:45517986:T:C	F79L	1.000
19:45517987:T:C	F79S	1.000
19:45517987:T:G	F79C	1.000
19:45517988:C:A	F79L	1.000
19:45517988:C:G	F79L	1.000
19:45517995:T:A	W82R	1.000
19:45517995:T:C	W82R	1.000
19:45518019:G:C	G90R	1.000
19:45518020:G:A	G90D	1.000
19:45518023:T:C	L91P	1.000
19:45518028:T:C	F93L	1.000
19:45518030:C:A	F93L	1.000
19:45518030:C:G	F93L	1.000
19:45522797:T:C	M267T	1.000
19:45517703:T:G	Y16D	0.999
19:45517799:C:A	R48S	0.999
19:45517800:G:C	R48P	0.999
19:45517803:T:A	V49D	0.999
19:45517808:G:C	G51R	0.999
19:45517809:G:A	G51D	0.999
19:45517965:T:C	Y72H	0.999
19:45517965:T:G	Y72D	0.999
19:45517986:T:G	F79V	0.999
19:45517989:C:G	H80D	0.999

dbSNP variants (sampled 300 via entrez): RS1000087615 (19:45523248 G>A), RS1000288245 (19:45507526 C>T), RS1000335641 (19:45518436 C>T), RS1000493359 (19:45512552 T>C), RS1000624398 (19:45507575 G>C), RS1000632085 (19:45518905 C>T), RS1000823197 (19:45512206 A>G,T), RS1000913144 (19:45523955 A>T), RS1001171042 (19:45521519 C>A,T), RS1001409545 (19:45526898 A>G,T), RS1001812718 (19:45511274 G>A), RS1001945579 (19:45507481 A>C,G,T), RS1001954448 (19:45524542 C>T), RS1001955144 (19:45512727 G>A), RS1002061281 (19:45517347 C>A)

Disease associations

OMIM: gene MIM:601703 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST007827_3	Alzheimer’s disease or HDL levels (pleiotropy)	1.000000e-97

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004612	high density lipoprotein cholesterol measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4295774 (SINGLE PROTEIN)

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

PharmGKB clinical annotations

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs10995	Efficacy	3	hydrochlorothiazide	Hypertension

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs10995	VASP	3	0.00	1	hydrochlorothiazide

ChEMBL bioactivities

2 potent at pChembl≥5 of 2 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.06	Kd	87.65	nM	CHEMBL5653589
7.06	ED50	87.65	nM	CHEMBL5653589

PubChem BioAssay actives

1 with measured affinity, of 3 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
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149756: Binding affinity to human VASP incubated for 45 mins by Kinobead based pull down assay	kd	0.0877	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression, increases expression, affects cotreatment	5
cyanoginosin LR	affects localization, increases phosphorylation, affects expression, increases response to substance, decreases reaction	5
Resveratrol	affects cotreatment, decreases expression, decreases reaction, increases phosphorylation	5
Valproic Acid	decreases expression, increases expression, affects expression	3
N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide	decreases reaction, increases phosphorylation	2
(5-fluoro-2-methyl-1-(4-pyridyl)methylene-3-(N-benzyl)-indene)-acetamide hydrochloride	increases phosphorylation	2
bisphenol S	decreases expression, increases expression, affects cotreatment	2
Dichlorodiphenyl Dichloroethylene	increases activity, increases phosphorylation, decreases expression	2
Nitroglycerin	decreases reaction, increases phosphorylation	2
Smoke	decreases expression, increases expression	2
Tobacco Smoke Pollution	affects expression, increases expression	2
Tretinoin	increases expression	2
Cyclosporine	decreases expression, increases expression	2
aristolochic acid I	increases expression	1
GSK-J4	decreases expression	1
2,4,6-tribromophenol	decreases expression	1
testosterone enanthate	affects expression	1
triphenyl phosphate	affects expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, affects localization, increases expression	1
silychristin	increases phosphorylation	1
silidianin	increases phosphorylation	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
sodium arsenite	increases expression	1
cobaltous chloride	decreases expression	1
butyraldehyde	increases expression	1
tetrabromobisphenol A	decreases expression	1
sulindac sulfone	increases phosphorylation	1
cupric chloride	increases expression	1
N(6)-benzoyl-cyclic AMP	decreases reaction, increases phosphorylation	1
8-((4-chlorophenyl)thio)cyclic-3’,5’-GMP	increases phosphorylation	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
CHEMBL4118547	Binding	Binding affinity to VASP in human NCI-H23 cells at 1 uM by mass spectrometry based pull down assay	Studies of TAK1-centered polypharmacology with novel covalent TAK1 inhibitors. — Bioorg Med Chem

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B2KU	Abcam HeLa VASP KO	Cancer cell line	Female

Clinical trials (associated diseases)

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