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VASP

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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
  • Regional missense constraint (gnomAD): 1 of 4 regions constrained (≈5% of expected missense variation)
  • GTEx eGene: eQTL in 16 tissues, sQTL in 31 (q < 0.05)
  • Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 0.75 (unconstrained)
  • MANE Select transcript: NM_003370
  • Interaction hub: 2,016 STRING partners (top 7% of genes corpus-wide)

Identifiers

Gene identifiers

FieldValue
HGNC IDHGNC:12652
Approved symbolVASP
Namevasodilator stimulated phosphoprotein
Location19q13.32
Locus typegene with protein product
StatusApproved
Ensembl geneENSG00000125753
Ensembl biotypeprotein_coding
OMIM601703
Entrez7408

Gene structure

Transcript identifiers

Ensembl transcripts: 40 — 23 protein_coding, 12 nonsense_mediated_decay, 4 retained_intron, 1 protein_coding_CDS_not_defined

MANE Select: ENST00000245932

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 1, TSL 2: 6, TSL 3: 2, TSL 5: 2

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, ENST00001007049, ENST00001007050, ENST00001007051, ENST00001007052, ENST00001007053, ENST00001009636, ENST00001085135, ENST00001085136, ENST00001085137, ENST00001085138, ENST00001135582

RefSeq mRNA: 1 — MANE Select: NM_003370 NM_003370

CCDS: CCDS33051

Canonical transcript exons

ENST00000245932 — 13 exons

ExonStartEnd
ENSE000008582314552132245521406
ENSE000008582334552234045522581
ENSE000011126764552614045526983
ENSE000013755394550747945507776
ENSE000034903544552364445523695
ENSE000034966244552409745524142
ENSE000035722584552457045524660
ENSE000035777954552271845522818
ENSE000036207294552594645526003
ENSE000036269704551792945518094
ENSE000036724734552384145523877
ENSE000036755574552216845522217
ENSE000037910754551766345517834

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.

Highest expression (Bgee): granulocyte, monocyte, leukocyte, mononuclear cell, mucosa of transverse colon.

Genetic regulation across tissues (GTEx eQTL / sQTL)

VASP is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 16 tissues and its splicing (sQTL) in 31 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 47 significant tissue × QTL associations:

TissueQTLq-valueSlopeLead variant
Whole Bloodsqtl1.4e-143-1.1519:45523712:T:A
Adipose Subcutaneoussqtl4.1e-52-1.0119:45523712:T:A
Artery Tibialsqtl2.3e-45-1.0519:45523712:T:A
Esophagus Muscularissqtl8.8e-44-1.1419:45523712:T:A
Colon Transversesqtl8.6e-41-1.0419:45523712:T:A
Lungsqtl3.3e-40-0.9719:45532204:A:T
Breast Mammary Tissuesqtl3.7e-32+1.0219:45523712:T:A
Adipose Visceral Omentumsqtl1.3e-30-0.9119:45523712:T:A
Colon Sigmoidsqtl5.9e-30-1.1519:45523712:T:A
Skin Sun Exposed Lower legsqtl3.5e-29-0.7919:45523712:T:A
Nerve Tibialsqtl5.2e-28+0.8119:45531253:A:G
Skin Not Sun Exposed Suprapubicsqtl2.1e-27+0.8119:45527621:T:C
Cells EBV-transformed lymphocytessqtl6.8e-27-1.2019:45523712:T:A
Artery Aortasqtl4.9e-26-1.0119:45523712:T:A
Cells Cultured fibroblastssqtl8.0e-25-0.7019:45532204:A:T
Esophagus Gastroesophageal Junctionsqtl6.8e-22-1.0619:45523712:T:A
Esophagus Mucosasqtl8.9e-19-0.7919:45531253:A:G
Thyroidsqtl4.0e-18+0.7519:45527153:A:G
Spleensqtl7.8e-16-1.0819:45523712:T:A
Small Intestine Terminal Ileumsqtl5.5e-11-1.1219:45523712:T:A

FANTOM5 promoters

5 alternative TSS:

Promoter IDTPM avgSamples expressed
176490152.73821828
1764892.22191022
1764940.5814314
1764930.3232137
1764950.163345

Top tissues by expression

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

TissueAnatomy IDExpression scoreQuality
granulocyteCL:000009498.76gold quality
monocyteCL:000057698.70gold quality
leukocyteCL:000073898.53gold quality
mononuclear cellCL:000084298.49gold quality
mucosa of transverse colonUBERON:000499197.87gold quality
spleenUBERON:000210697.59gold quality
saphenous veinUBERON:000731897.59gold quality
bloodUBERON:000017897.53gold quality
muscle layer of sigmoid colonUBERON:003580597.46gold quality
transverse colonUBERON:000115797.41gold quality
lower esophagusUBERON:001347397.38gold quality
lower esophagus muscularis layerUBERON:003583397.38gold quality
esophagogastric junction muscularis propriaUBERON:003584197.18gold quality
sigmoid colonUBERON:000115997.02gold quality
rectumUBERON:000105296.76gold quality
thoracic aortaUBERON:000151596.72gold quality
ascending aortaUBERON:000149696.71gold quality
colonUBERON:000115596.63gold quality
descending thoracic aortaUBERON:000234596.61gold quality
left uterine tubeUBERON:000130396.60gold quality
colonic epitheliumUBERON:000039796.53gold quality
large intestineUBERON:000005996.45gold quality
right coronary arteryUBERON:000162596.44gold quality
aortaUBERON:000094796.39gold quality
small intestine Peyer’s patchUBERON:000345496.31gold quality
upper lobe of left lungUBERON:000895296.30gold quality
popliteal arteryUBERON:000225096.21gold quality
tibial arteryUBERON:000761096.21gold quality
intestineUBERON:000016096.14gold quality
upper lobe of lungUBERON:000894896.14gold quality
left coronary arteryUBERON:000162695.94gold quality
gall bladderUBERON:000211095.85gold quality
body of stomachUBERON:000116195.83gold quality
coronary arteryUBERON:000162195.80gold quality
body of uterusUBERON:000985395.77gold quality
small intestineUBERON:000210895.76gold quality
lymph nodeUBERON:000002995.65gold quality
omental fat padUBERON:001041495.41gold quality
peritoneumUBERON:000235895.39gold quality
mucosa of sigmoid colonUBERON:000499395.18gold quality
mucosa of stomachUBERON:000119995.17gold quality
stomachUBERON:000094595.16gold quality
fundus of stomachUBERON:000116095.08gold quality
lower esophagus mucosaUBERON:003583494.96gold quality
colonic mucosaUBERON:000031794.84gold quality
esophagusUBERON:000104394.70gold quality
apex of heartUBERON:000209894.61gold quality
pylorusUBERON:000116694.52gold quality
adipose tissue of abdominal regionUBERON:000780894.52gold quality
metanephros cortexUBERON:001053394.51gold quality
right lungUBERON:000216794.31gold quality
pericardiumUBERON:000240794.19gold quality
pancreatic ductal cellCL:000207994.11gold quality
superior surface of tongueUBERON:000737194.02gold quality
vena cavaUBERON:000408793.71gold quality
bone marrowUBERON:000237193.47gold quality
olfactory segment of nasal mucosaUBERON:000538693.40gold quality
caecumUBERON:000115393.39gold quality
cardia of stomachUBERON:000116293.14gold quality
ectocervixUBERON:001224993.14gold quality
stromal cell of endometriumCL:000225593.09gold quality
superficial temporal arteryUBERON:000161493.05silver quality
smooth muscle tissueUBERON:000113593.04gold quality
myometriumUBERON:000129692.94gold quality
nippleUBERON:000203092.60gold quality
bone marrow cellCL:000209292.58gold quality
duodenumUBERON:000211492.56gold quality
right atrium auricular regionUBERON:000663192.54gold quality
lower lobe of lungUBERON:000894992.54gold quality
endocervixUBERON:000045892.45gold quality
esophagus mucosaUBERON:000246992.42gold quality
vermiform appendixUBERON:000115492.25gold quality
tonsilUBERON:000237292.20gold quality
minor salivary glandUBERON:000183092.10gold quality
skin of legUBERON:000151191.98gold quality
heart left ventricleUBERON:000208491.96gold quality
skin of abdomenUBERON:000141691.95gold quality
cardiac ventricleUBERON:000208291.86gold quality
tracheaUBERON:000312691.84gold quality
pharyngeal mucosaUBERON:000035591.74gold quality
right lobe of thyroid glandUBERON:000111991.71gold quality
cardiac atriumUBERON:000208191.68gold quality
subcutaneous adipose tissueUBERON:000219091.64gold quality
heartUBERON:000094891.60gold quality
lungUBERON:000204891.48gold quality
islet of LangerhansUBERON:000000691.46gold quality
left lobe of thyroid glandUBERON:000112091.28gold quality
left adrenal glandUBERON:000123491.26gold quality
left adrenal gland cortexUBERON:003582591.23gold quality
adrenal cortexUBERON:000123591.07gold quality
right adrenal glandUBERON:000123391.02gold quality
adrenal glandUBERON:000236990.95gold quality
right adrenal gland cortexUBERON:003582790.90gold quality
mouth mucosaUBERON:000372990.73gold quality
right ovaryUBERON:000211890.56gold quality
urinary bladderUBERON:000125590.44gold quality
tongueUBERON:000172390.13gold quality
zone of skinUBERON:000001490.10gold quality
cauda epididymisUBERON:000436089.99gold quality
tibial nerveUBERON:000132389.98gold quality

Single-cell (SCXA)

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

ExperimentMarker?Max mean expression
E-CURD-112yes34.53
E-HCAD-4yes28.40
E-HCAD-6yes25.29
E-ANND-3yes20.03
E-HCAD-10yes16.55
E-MTAB-8498yes10.60

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 80 HPA tissues / cells by nTPM:

Tissue / cellAxisnTPMProtein (IHC)
Bone marrowtissue169.9high
Tonsiltissue109.3high
Spleentissue107.0high
Urinary bladdertissue104.0high
Appendixtissue102.4high
Smooth muscletissue102.1medium
Colontissue100.3high
Stomach 1tissue87.7high
Lymph nodetissue86.5high
Rectumtissue78.8high
Small intestinetissue71.3high
Duodenumtissue70.6high
Seminal vesicletissue68.2medium
Lungtissue68.2high
Adipose tissuetissue61.2low
Placentatissue60.6high
Gallbladdertissue58.6high
Thymustissue49.6
Esophagustissue48.3medium
Prostatetissue47.1high
Endometrium 1tissue45.1high
Skin 1tissue41.1high
Vaginatissue38.9medium
Livertissue35.3high
Cervixtissue33.9high
Heart muscletissue31.5not detected
Epididymistissue31.0medium
Choroid plexustissue28.0
Fallopian tubetissue27.6high
Breasttissue26.9high
Spinal cordtissue25.2
Adrenal glandtissue24.8medium
Parathyroid glandtissue23.6medium
Salivary glandtissue23.5medium
Ovarytissue22.5medium
Locus coeruleustissue22.3
Pancreastissue22.1high
Substantia nigratissue21.4
Hippocampustissue20.7low
Tonguetissue20.1
Medulla oblongatatissue20.1
Thyroid glandtissue19.8medium
Superior colliculitissue19.7
Kidneytissue19.2medium
Ponstissue18.5
Midbraintissue18.3
Thalamustissue18.1
Hypothalamustissue17.9
Pituitary glandtissue17.4
Periaqueductal graytissue16.5
Corpus callosumtissue15.9
Nucleus accumbenstissue15.4
Hippocampal formationtissue15.0
Septumtissue13.9
Postcentral gyrustissue13.1
Amygdalatissue12.4
Putamentissue12.0
Cerebral cortextissue11.9medium
Ventral forebraintissue11.9
Somatosensory cortextissue11.9

Brain sub-regions (HPA Brain Atlas): detected in 192; highest nTPM — Blood vessel (81.2), Anterior thalamic nucleus, ventral (38.2), Lateral vestibular nucleus (33.8), Peritrigeminal nucleus (31.9), Ventrolateral tegmental area, A5 NE cell group (31.9).

Regulation

Is transcription factor: no

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

miRNA regulators (miRDB)

Targeting VASP by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 104 miRNAs:

miRNAMax scoreAvg scoremiRNA target_count
HSA-MIR-5011-5P100.0083.465820
HSA-MIR-190A-3P100.0080.355520
HSA-MIR-1277-5P100.0073.955056
HSA-MIR-4455100.0065.481587
HSA-MIR-340-5P100.0072.504437
HSA-MIR-6748-5P100.0065.811057
HSA-MIR-5196-5P100.0067.982761
HSA-MIR-3163100.0077.238605
HSA-MIR-4481100.0066.421669
HSA-MIR-3613-3P100.0076.367965
HSA-MIR-3667-3P99.9967.171636
HSA-MIR-548AJ-3P99.9673.385345
HSA-MIR-548X-3P99.9673.385345
HSA-MIR-548AA99.9670.643753
HSA-MIR-548AP-3P99.9670.643753
HSA-MIR-548T-3P99.9670.643753
HSA-MIR-551B-5P99.9671.283493
HSA-MIR-391099.9571.132227
HSA-MIR-548J-3P99.9472.614881
HSA-MIR-548AE-3P99.9372.664867
HSA-MIR-548AH-3P99.9372.544872
HSA-MIR-548AM-3P99.9372.544872
HSA-MIR-548AQ-3P99.9372.664867
HSA-MIR-22-3P99.9368.13917
HSA-MIR-106A-5P99.9073.942683
HSA-MIR-17-5P99.8973.832665
HSA-MIR-7162-3P99.8968.161682
HSA-MIR-106B-5P99.8874.722795
HSA-MIR-20A-5P99.8874.762769
HSA-MIR-20B-5P99.8874.012621

Functional genomics

gnomAD constraint: pLI 0.000133, LOEUF 0.746, missense Z 0.0961 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000245932 splits into 4 regions with different missense tolerance; 1 is missense-constrained (≈5% of the expected missense variation). Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. gnomAD

Region (GRCh38)Missense obs / expo/eConstrained
19:45,507,772–45,521,325127 / 170.70.74no
19:45,521,326–45,522,756226 / 196.01.15no
19:45,522,757–45,522,8099 / 26.90.33yes (p 5.5e-04)
19:45,522,810–45,526,174126 / 134.80.94no

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

OrganismSymbolGene ID
danio_reriovaspbENSDARG00000017105
danio_reriovaspaENSDARG00000099690
mus_musculusVaspENSMUSG00000030403
rattus_norvegicusVaspENSRNOG00000016367
drosophila_melanogasterenaFBGN0000578
caenorhabditis_elegansWBGENE00006770

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

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:109268) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 4 distinct phenotype terms.

Mouse phenotype (MP)Records
abnormal platelet physiology1
abnormal platelet activation1
increased megakaryocyte cell number1
increased platelet aggregation1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

OrganismUniProtIdentityMethod
Pongo abeliiQ5RDN299.5%Diamond
Xenopus laevisQ64GL089.0%Diamond
Canis lupus familiarisP5055186.2%Diamond
Bos taurusQ2TA4986.2%Diamond
Xenopus tropicalisQ5Y17175.5%Diamond
Dictyostelium discoideumQ5TJ6538.4%Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

SymbolTypeEntrez
OPA3-RTN2protein-coding144667540
PPM1Nprotein-coding147699
RTN2protein-coding6253
TRU-TCA1-1tRNA7234
OPA3protein-coding80207
GPR4protein-coding2828
EML2protein-coding24139
MIR330ncRNA442902
EML2-AS1ncRNA100287177
FOSBprotein-coding2354

Protein

Protein identifiers

Vasodilator-stimulated phosphoprotein — P50552 (reviewed: P50552)

All UniProt accessions (10): A0A024R0V4, A0A0S2Z4H6, A0A994J508, A0A994J7X3, K7EIG8, K7EM16, K7ENL7, K7ENR7, K7EQD0, P50552

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)

IDNameType
IPR000697WH1/EVH1_domDomain
IPR011993PH-like_dom_sfHomologous_superfamily
IPR014885VASP_tetraDomain
IPR017354VASP/EVLFamily
IPR038023VASP_sfHomologous_superfamily

Pfam: PF00568, PF08776

UniProt features (54 total): modified residue 14, strand 8, region of interest 6, mutagenesis site 6, helix 4, compositionally biased region 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 by resolution:

PDBTitleMethodResolution (Å)
1USEhuman VASP tetramerisation domainX-RAY DIFFRACTION1.3
2PBDTernary complex of profilin-actin with the poly-PRO-GAB domain of VASP*X-RAY DIFFRACTION1.5
1USDhuman VASP tetramerisation domain L352MX-RAY DIFFRACTION1.7
2PAVTernary complex of Profilin-Actin with the Last Poly-Pro of Human VASPX-RAY DIFFRACTION1.8
3CHWComplex of Dictyostelium discoideum Actin with Profilin and the Last Poly-Pro of Human …X-RAY DIFFRACTION2.3
9UB1The structure of Myanmar_N2 and M6B12_Fab complexELECTRON MICROSCOPY2.35
8YVLNeuraminidase of A/California/04/2009 HIN1 in complex with CAV-F34 FabELECTRON MICROSCOPY2.47
9UAXThe structure of Myanmar_N2 and AS4C_Fab complexELECTRON MICROSCOPY2.71
8GATStructure of human NDS.1 Fab and 1G01 Fab in complex with influenza virus neuraminidase …ELECTRON MICROSCOPY3
8GAUStructure of human NDS.1 Fab and 1G01 Fab in complex with influenza virus neuraminidase …ELECTRON MICROSCOPY3.6
1EGXSOLUTION STRUCTURE OF THE ENA-VASP HOMOLOGY 1 (EVH1) DOMAIN OF HUMAN …SOLUTION NMR

Predicted structure (AlphaFold)

ModelpLDDTFraction very-high
AF-P50552-F171.430.38

Antibody-complex structures (SAbDab)

3 antibodies co-crystallized with this protein: 8GAT, 8GAU, 8YVL

Human Protein Atlas

Protein class: Predicted intracellular proteins, Plasma proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): cell junctions; focal adhesion sites; plasma membrane

Antibody reliability (HPA): IH enhanced · IF supported

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)

TypePositions
N-acetylserine2
Phosphotyrosine39
Phosphoserine46, 157, 239, 305, 314, 322, 323, 325
Phosphothreonine278, 284, 316
N6-acetyllysine283

Mutagenesis-validated functional residues (6)

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

Function

Pathways and Gene Ontology

Reactome pathways

1 curated (TAS) of 11; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

11 pathways:

IDPathwayEvidence
R-HSA-446353Cell-extracellular matrix interactionscurated
R-HSA-1280218Adaptive Immune System—
R-HSA-422475Axon guidance—
R-HSA-446728Cell junction organization—
R-HSA-1500931Cell-Cell communication—
R-HSA-1266738Developmental Biology—
R-HSA-202433Generation of second messenger moleculeselectronic
R-HSA-168256Immune System—
R-HSA-9675108Nervous system development—
R-HSA-376176Signaling by ROBO receptorselectronic
R-HSA-202403TCR signaling—

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 (5): 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)

GO Molecular Function (6): actin binding (GO:0003779), profilin binding (GO:0005522), SH3 domain binding (GO:0017124), identical protein binding (GO:0042802), cadherin binding (GO:0045296), protein binding (GO:0005515)

GO Cellular Component (15): cytosol (GO:0005829), plasma membrane (GO:0005886), bicellular tight junction (GO:0005923), focal adhesion (GO:0005925), actin cytoskeleton (GO:0015629), cell junction (GO:0030054), 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), lamellipodium (GO:0030027), filopodium (GO:0030175)

Reactome top-level categories

8 top-level categories:

CategoryPathways
TCR signaling1
Axon guidance1
Cell junction organization1
Immune System1
Adaptive Immune System1
Nervous system development1
Cell-Cell communication1
Developmental Biology1

GO top-level categories

36 GO namespaces:

CategoryTerms
cellular anatomical structure4
protein binding2
cell projection membrane2
synapse2
primary neural tube formation1
tube closure1
axonogenesis1
neuron projection guidance1
actin filament organization1
actin filament polymerization1
regulation of actin filament polymerization1
positive regulation of protein polymerization1
positive regulation of cytoskeleton organization1
positive regulation of supramolecular fiber organization1
protein homooligomerization1
protein tetramerization1
cytoskeletal protein binding1
protein domain specific binding1
cell adhesion molecule binding1
binding1
cytoplasm1
membrane1
cell periphery1
apical junction complex1
tight junction1
cell-substrate junction1
cytoskeleton1
lamellipodium1
leading edge membrane1
filopodium1
extracellular vesicle1
intracellular anatomical structure1
intracellular membraneless organelle1
cell leading edge1
plasma membrane bounded cell projection1
actin-based cell projection1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 7 of 26 annotations. The rest are phylogenetic / computational / electronic (IEA).

7 experimentally-supported GO terms:

GO termNSEvidence
positive regulation of actin filament polymerizationBPdirect assay
cell junctionCCdirect assay
extracellular exosomeCChigh-throughput assay
focal adhesionCCdirect assay
plasma membraneCCdirect assay
cadherin bindingMFhigh-throughput assay
profilin bindingMFphysical interaction

Protein interactions and networks

STRING

showing 15 of 2,016 interactions by confidence (×1000):

Protein AProtein BPartner UniProtScore
VASPZYXQ15942943
VASPPFN4Q8NHR9931
VASPPFN3P60673929
VASPVCLP18206915
VASPPFN1P07737915
VASPTLN1Q9Y490904
VASPRAPH1Q70E73902
VASPTLN2Q9Y4G6883
VASPPXNP49023870
VASPAPBB1IPQ7Z5R6792
VASPCFL1P23528786
VASPCFL2Q9Y281785
VASPGPKOWQ92917773
VASPCDC42P21181766
VASPWIPF1O43516736

IntAct

Human interaction partners of VASP in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

showing 30 of 46 partners by confidence:

PartnerInteraction typeMIscoreRecords
ZYXphysical association0.8003
ABI2physical association0.7405
CEP43association0.7404
ABI3physical association0.7209
TRIM9physical association0.6704
BAIAP2direct interaction0.6506
XIRP1physical association0.6505
PSORS1C2physical association0.6004
ABI1physical association0.5603
SCGB2A2physical association0.5603
HSPA8physical association0.5601
PFN1physical association0.5601
RPS6KA1physical association0.5404
GTPBP1association0.5303
EVLassociation0.5301
NR4A1physical association0.5202
NSMAFphysical association0.5002
MYO10direct interaction0.4903
DMRTB1physical association0.4902
FRS3physical association0.4902
SAT1physical association0.4902
ACTG1proximity0.4801
FAF2direct interaction0.4402
AEBP1direct interaction0.4401
MAGED1direct interaction0.4401
MRPL43direct interaction0.4401
PPP2CAdephosphorylation reaction0.4401
PRKACAphosphorylation reaction0.4401
PRKG1phosphorylation reaction0.4401
SHROOM3direct interaction0.4401

BioGRID (426 interactions; top human partners by supporting records): ENAH (Affinity Capture-MS; 10 records), EVL (Affinity Capture-MS; 9 records), ZYX (Affinity Capture-MS; 8 records), PFN2 (Affinity Capture-MS; 6 records), PFN1 (Two-hybrid; 5 records), ABI1 (Affinity Capture-MS; 4 records), ACTB (Proximity Label-MS; 4 records), FGFR1OP (Two-hybrid; 4 records), CIRH1A (Affinity Capture-MS; 3 records), CTU1 (Affinity Capture-MS; 3 records), GPHN (Affinity Capture-Western; 3 records), GTPBP1 (Affinity Capture-MS; 3 records), TACC3 (Affinity Capture-MS; 3 records), TEAD4 (Affinity Capture-MS; 3 records), TES (Affinity Capture-MS; 3 records)

SIGNOR signaling

showing 14 of 20 signaling interactions:

AEffectBMechanism
PRKG1unknownVASPphosphorylation
PRKACAunknownVASPphosphorylation
PRKAA2down-regulatesVASPphosphorylation
RPS6KA1down-regulatesVASPphosphorylation
AMPKdown-regulatesVASPphosphorylation
RPS6Kdown-regulatesVASPphosphorylation
PKA“up-regulates activity”VASPphosphorylation
PRKG1“down-regulates activity”VASPphosphorylation
VASPup-regulatesAxonal_growth_cone_formation
VASPup-regulatesNeurite_outgrowth
RAPH1“up-regulates activity”VASPbinding
VASP“up-regulates activity”ATICphosphorylation
TRIM9“down-regulates quantity”VASPubiquitination
PRKG1down-regulatesVASPphosphorylation

Protein complexes (CORUM) (3)

Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).

3 complexes by size:

ComplexSubunitsMembers
★ PRKCD-VASP complex2PRKCD, VASP
APBB1IP-VASP complex2APBB1IP, VASP
CXCR2-VASP complex, CXCL8-stimulated2CXCR2, VASP

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 46 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:

PathwayPartnersFoldFDR
Parasite infection778.1×4e-10
Leishmania phagocytosis778.1×4e-10
Fcgamma receptor (FCGR) dependent phagocytosis762.9×8e-10
RHO GTPases Activate WASPs and WAVEs661.4×2e-08
Signaling by VEGF642.5×2e-07
FCGR3A-mediated phagocytosis742.3×1e-08
Leishmania infection842.1×8e-10
Parasitic Infection Pathways842.1×8e-10

GO biological processes:

GO termPartnersFoldFDR
actin filament organization616.6×2e-04

Disease & clinical

Genetic variants

Variant evidence for VASP: 34 ClinVar records (0 pathogenic / likely pathogenic); 1 PharmGKB clinical annotation; 1 GWAS association.

ClinVar

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

ClassificationCount (floor)
Pathogenic0
Likely pathogenic0
Uncertain significance21
Likely benign1
Benign1

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 27 predictions of 948):

Position(s)EffectΔscoreSites
19:45517654acceptor_gain1.0000
19:45517835–45517836donor_loss1.00002
19:45518095–45518096donor_loss1.00005
19:45522707acceptor_gain1.0000
19:45523639acceptor_gain1.0000
19:45523696–45523697donor_loss1.00005
19:45524095acceptor_loss1.00003
19:45524143–45524144donor_loss1.00004
19:45524560acceptor_gain1.0000
19:45524661–45524662donor_loss1.00004

AlphaMissense

820 missense substitutions predicted likely pathogenic (of 2,439 scored), across 196 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

ResidueLikely-pathogenic substitutionsMean am_pathogenicityMax am_pathogenicity
M26790.9871.000
M26490.9360.996
F7980.9961.000
H8080.9930.999
F9380.9901.000
F10280.9830.999
D8480.9580.987
D1880.8380.977
M10680.8150.989
W2370.9991.000
W8270.9971.000
W8970.9910.998
Q8170.9880.999
E26670.9860.997
M1470.9850.996
F4770.9830.996
E370.9720.991
W31070.9610.993
N6370.9520.998
S3470.9450.998

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

1 prognostic cancer types:

CancerPrognosticp-value
Liver Hepatocellular Carcinoma (TCGA)unfavorable1.48e-06

Disease associations

OMIM: gene MIM:601703 | disease phenotypes:

GWAS associations

1 associations:

StudyTraitp-value
GCST007827_3Alzheimer’s disease or HDL levels (pleiotropy)1e-97

EFO canonical traits (from GWAS)

1 canonical traits:

EFO IDTrait name
EFO:0004612high density lipoprotein cholesterol measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4295774 (SINGLE PROTEIN)

PharmGKB: 1 entry (CPIC guideline: no)

PharmGKB clinical annotations

1 annotations by evidence level (1 strongest → 4):

VariantAssociationLevelDrugsPhenotypes
rs10995Efficacy3hydrochlorothiazideHypertension

PharmGKB variants

1 variants:

VariantGenesLevelScore#Clin annotsDrugs
rs10995VASP30.001hydrochlorothiazide

PharmGKB variant annotations

Per-publication pharmacogenomic findings for this gene (significant associations).

1 published findings:

VariantDrug(s)CategoryFindingPMID
rs10995hydrochlorothiazideEfficacyGenotypes AG + GG are associated with increased response to hydrochlorothiazide in people with Hypertension as compared to genotype AA.PMID:28115488

Binding affinities (BindingDB)

1 measured of 1 human assays (1 total across all organisms); most potent 1 below. Values come from heterogeneous assays and are not directly comparable.

LigandMeasureValue
CHEMBL5653589KD1440 nM

ChEMBL bioactivities

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

pChemblTypeValueUnitMolecule
7.06Kd87.65nMCHEMBL5653589
7.06ED5087.65nMCHEMBL5653589

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.

CompoundAssayTypeValueUnit
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide2149756: Binding affinity to human VASP incubated for 45 mins by Kinobead based pull down assaykd0.0877uM

CTD chemical–gene interactions

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

ChemicalActions (top 5)PubMed papers
bisphenol Adecreases expression, increases expression, affects cotreatment5
cyanoginosin LRaffects expression, increases response to substance, decreases reaction, affects localization, increases phosphorylation5
Resveratroldecreases reaction, increases phosphorylation, affects cotreatment, decreases expression5
Valproic Acidaffects expression, decreases expression, increases expression3
N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamidedecreases reaction, increases phosphorylation2
(5-fluoro-2-methyl-1-(4-pyridyl)methylene-3-(N-benzyl)-indene)-acetamide hydrochlorideincreases phosphorylation2
bisphenol Sincreases expression, affects cotreatment, decreases expression2
Dichlorodiphenyl Dichloroethylenedecreases expression, increases activity, increases phosphorylation2
Nitroglycerindecreases reaction, increases phosphorylation2
Smokedecreases expression, increases expression2
Tobacco Smoke Pollutionaffects expression, increases expression2
Tretinoinincreases expression2
Cyclosporinedecreases expression, increases expression2
Particulate Matteraffects cotreatment, increases abundance, increases expression, affects expression2
aristolochic acid Iincreases expression1
GSK-J4decreases expression1
2,4,6-tribromophenoldecreases expression1
testosterone enanthateaffects expression1
triphenyl phosphateaffects expression1
pyrogallol 1,3-dimethyl etheraffects cotreatment, affects localization, increases expression1
silychristinincreases phosphorylation1
silidianinincreases phosphorylation1
tris(1,3-dichloro-2-propyl)phosphateincreases expression1
sodium arseniteincreases expression1
cobaltous chloridedecreases expression1
butyraldehydeincreases expression1
tetrabromobisphenol Adecreases expression1
sulindac sulfoneincreases phosphorylation1
cupric chlorideincreases expression1
N(6)-benzoyl-cyclic AMPdecreases reaction, increases phosphorylation1

ChEMBL screening assays

2 unique, capped per target: 2 binding

Representative assays (with source publication via chembl_document):

Assay IDTypeDescriptionSource paper
CHEMBL4118547BindingBinding affinity to VASP in human NCI-H23 cells at 1 uM by mass spectrometry based pull down assayStudies 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):

CellosaurusNameCategorySex
CVCL_B2KUAbcam HeLa VASP KOCancer cell lineFemale

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for VASP across ~30M SureChEMBL compounds — explore on Sugi Predict.

  • Disease cohort memberships (association, not causation — diseases whose associated-gene cohort lists this gene; a subset are also under Associated diseases): Alzheimer disease