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
| 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: 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
| 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.
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:
| Tissue | QTL | q-value | Slope | Lead variant |
|---|---|---|---|---|
| Whole Blood | sqtl | 1.4e-143 | -1.15 | 19:45523712:T:A |
| Adipose Subcutaneous | sqtl | 4.1e-52 | -1.01 | 19:45523712:T:A |
| Artery Tibial | sqtl | 2.3e-45 | -1.05 | 19:45523712:T:A |
| Esophagus Muscularis | sqtl | 8.8e-44 | -1.14 | 19:45523712:T:A |
| Colon Transverse | sqtl | 8.6e-41 | -1.04 | 19:45523712:T:A |
| Lung | sqtl | 3.3e-40 | -0.97 | 19:45532204:A:T |
| Breast Mammary Tissue | sqtl | 3.7e-32 | +1.02 | 19:45523712:T:A |
| Adipose Visceral Omentum | sqtl | 1.3e-30 | -0.91 | 19:45523712:T:A |
| Colon Sigmoid | sqtl | 5.9e-30 | -1.15 | 19:45523712:T:A |
| Skin Sun Exposed Lower leg | sqtl | 3.5e-29 | -0.79 | 19:45523712:T:A |
| Nerve Tibial | sqtl | 5.2e-28 | +0.81 | 19:45531253:A:G |
| Skin Not Sun Exposed Suprapubic | sqtl | 2.1e-27 | +0.81 | 19:45527621:T:C |
| Cells EBV-transformed lymphocytes | sqtl | 6.8e-27 | -1.20 | 19:45523712:T:A |
| Artery Aorta | sqtl | 4.9e-26 | -1.01 | 19:45523712:T:A |
| Cells Cultured fibroblasts | sqtl | 8.0e-25 | -0.70 | 19:45532204:A:T |
| Esophagus Gastroesophageal Junction | sqtl | 6.8e-22 | -1.06 | 19:45523712:T:A |
| Esophagus Mucosa | sqtl | 8.9e-19 | -0.79 | 19:45531253:A:G |
| Thyroid | sqtl | 4.0e-18 | +0.75 | 19:45527153:A:G |
| Spleen | sqtl | 7.8e-16 | -1.08 | 19:45523712:T:A |
| Small Intestine Terminal Ileum | sqtl | 5.5e-11 | -1.12 | 19:45523712:T:A |
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
showing 100 of 283 tissues 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 |
| left coronary artery | UBERON:0001626 | 95.94 | gold quality |
| gall bladder | UBERON:0002110 | 95.85 | gold quality |
| body of stomach | UBERON:0001161 | 95.83 | gold quality |
| coronary artery | UBERON:0001621 | 95.80 | gold quality |
| body of uterus | UBERON:0009853 | 95.77 | gold quality |
| small intestine | UBERON:0002108 | 95.76 | gold quality |
| lymph node | UBERON:0000029 | 95.65 | gold quality |
| omental fat pad | UBERON:0010414 | 95.41 | gold quality |
| peritoneum | UBERON:0002358 | 95.39 | gold quality |
| mucosa of sigmoid colon | UBERON:0004993 | 95.18 | gold quality |
| mucosa of stomach | UBERON:0001199 | 95.17 | gold quality |
| stomach | UBERON:0000945 | 95.16 | gold quality |
| fundus of stomach | UBERON:0001160 | 95.08 | gold quality |
| lower esophagus mucosa | UBERON:0035834 | 94.96 | gold quality |
| colonic mucosa | UBERON:0000317 | 94.84 | gold quality |
| esophagus | UBERON:0001043 | 94.70 | gold quality |
| apex of heart | UBERON:0002098 | 94.61 | gold quality |
| pylorus | UBERON:0001166 | 94.52 | gold quality |
| adipose tissue of abdominal region | UBERON:0007808 | 94.52 | gold quality |
| metanephros cortex | UBERON:0010533 | 94.51 | gold quality |
| right lung | UBERON:0002167 | 94.31 | gold quality |
| pericardium | UBERON:0002407 | 94.19 | gold quality |
| pancreatic ductal cell | CL:0002079 | 94.11 | gold quality |
| superior surface of tongue | UBERON:0007371 | 94.02 | gold quality |
| vena cava | UBERON:0004087 | 93.71 | gold quality |
| bone marrow | UBERON:0002371 | 93.47 | gold quality |
| olfactory segment of nasal mucosa | UBERON:0005386 | 93.40 | gold quality |
| caecum | UBERON:0001153 | 93.39 | gold quality |
| cardia of stomach | UBERON:0001162 | 93.14 | gold quality |
| ectocervix | UBERON:0012249 | 93.14 | gold quality |
| stromal cell of endometrium | CL:0002255 | 93.09 | gold quality |
| superficial temporal artery | UBERON:0001614 | 93.05 | silver quality |
| smooth muscle tissue | UBERON:0001135 | 93.04 | gold quality |
| myometrium | UBERON:0001296 | 92.94 | gold quality |
| nipple | UBERON:0002030 | 92.60 | gold quality |
| bone marrow cell | CL:0002092 | 92.58 | gold quality |
| duodenum | UBERON:0002114 | 92.56 | gold quality |
| right atrium auricular region | UBERON:0006631 | 92.54 | gold quality |
| lower lobe of lung | UBERON:0008949 | 92.54 | gold quality |
| endocervix | UBERON:0000458 | 92.45 | gold quality |
| esophagus mucosa | UBERON:0002469 | 92.42 | gold quality |
| vermiform appendix | UBERON:0001154 | 92.25 | gold quality |
| tonsil | UBERON:0002372 | 92.20 | gold quality |
| minor salivary gland | UBERON:0001830 | 92.10 | gold quality |
| skin of leg | UBERON:0001511 | 91.98 | gold quality |
| heart left ventricle | UBERON:0002084 | 91.96 | gold quality |
| skin of abdomen | UBERON:0001416 | 91.95 | gold quality |
| cardiac ventricle | UBERON:0002082 | 91.86 | gold quality |
| trachea | UBERON:0003126 | 91.84 | gold quality |
| pharyngeal mucosa | UBERON:0000355 | 91.74 | gold quality |
| right lobe of thyroid gland | UBERON:0001119 | 91.71 | gold quality |
| cardiac atrium | UBERON:0002081 | 91.68 | gold quality |
| subcutaneous adipose tissue | UBERON:0002190 | 91.64 | gold quality |
| heart | UBERON:0000948 | 91.60 | gold quality |
| lung | UBERON:0002048 | 91.48 | gold quality |
| islet of Langerhans | UBERON:0000006 | 91.46 | gold quality |
| left lobe of thyroid gland | UBERON:0001120 | 91.28 | gold quality |
| left adrenal gland | UBERON:0001234 | 91.26 | gold quality |
| left adrenal gland cortex | UBERON:0035825 | 91.23 | gold quality |
| adrenal cortex | UBERON:0001235 | 91.07 | gold quality |
| right adrenal gland | UBERON:0001233 | 91.02 | gold quality |
| adrenal gland | UBERON:0002369 | 90.95 | gold quality |
| right adrenal gland cortex | UBERON:0035827 | 90.90 | gold quality |
| mouth mucosa | UBERON:0003729 | 90.73 | gold quality |
| right ovary | UBERON:0002118 | 90.56 | gold quality |
| urinary bladder | UBERON:0001255 | 90.44 | gold quality |
| tongue | UBERON:0001723 | 90.13 | gold quality |
| zone of skin | UBERON:0000014 | 90.10 | gold quality |
| cauda epididymis | UBERON:0004360 | 89.99 | gold quality |
| tibial nerve | UBERON:0001323 | 89.98 | 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 |
HPA expression
RNA tissue specificity: Low tissue specificity
showing 60 of 80 HPA tissues / cells by nTPM:
| Tissue / cell | Axis | nTPM | Protein (IHC) |
|---|---|---|---|
| Bone marrow | tissue | 169.9 | high |
| Tonsil | tissue | 109.3 | high |
| Spleen | tissue | 107.0 | high |
| Urinary bladder | tissue | 104.0 | high |
| Appendix | tissue | 102.4 | high |
| Smooth muscle | tissue | 102.1 | medium |
| Colon | tissue | 100.3 | high |
| Stomach 1 | tissue | 87.7 | high |
| Lymph node | tissue | 86.5 | high |
| Rectum | tissue | 78.8 | high |
| Small intestine | tissue | 71.3 | high |
| Duodenum | tissue | 70.6 | high |
| Seminal vesicle | tissue | 68.2 | medium |
| Lung | tissue | 68.2 | high |
| Adipose tissue | tissue | 61.2 | low |
| Placenta | tissue | 60.6 | high |
| Gallbladder | tissue | 58.6 | high |
| Thymus | tissue | 49.6 | |
| Esophagus | tissue | 48.3 | medium |
| Prostate | tissue | 47.1 | high |
| Endometrium 1 | tissue | 45.1 | high |
| Skin 1 | tissue | 41.1 | high |
| Vagina | tissue | 38.9 | medium |
| Liver | tissue | 35.3 | high |
| Cervix | tissue | 33.9 | high |
| Heart muscle | tissue | 31.5 | not detected |
| Epididymis | tissue | 31.0 | medium |
| Choroid plexus | tissue | 28.0 | |
| Fallopian tube | tissue | 27.6 | high |
| Breast | tissue | 26.9 | high |
| Spinal cord | tissue | 25.2 | |
| Adrenal gland | tissue | 24.8 | medium |
| Parathyroid gland | tissue | 23.6 | medium |
| Salivary gland | tissue | 23.5 | medium |
| Ovary | tissue | 22.5 | medium |
| Locus coeruleus | tissue | 22.3 | |
| Pancreas | tissue | 22.1 | high |
| Substantia nigra | tissue | 21.4 | |
| Hippocampus | tissue | 20.7 | low |
| Tongue | tissue | 20.1 | |
| Medulla oblongata | tissue | 20.1 | |
| Thyroid gland | tissue | 19.8 | medium |
| Superior colliculi | tissue | 19.7 | |
| Kidney | tissue | 19.2 | medium |
| Pons | tissue | 18.5 | |
| Midbrain | tissue | 18.3 | |
| Thalamus | tissue | 18.1 | |
| Hypothalamus | tissue | 17.9 | |
| Pituitary gland | tissue | 17.4 | |
| Periaqueductal gray | tissue | 16.5 | |
| Corpus callosum | tissue | 15.9 | |
| Nucleus accumbens | tissue | 15.4 | |
| Hippocampal formation | tissue | 15.0 | |
| Septum | tissue | 13.9 | |
| Postcentral gyrus | tissue | 13.1 | |
| Amygdala | tissue | 12.4 | |
| Putamen | tissue | 12.0 | |
| Cerebral cortex | tissue | 11.9 | medium |
| Ventral forebrain | tissue | 11.9 | |
| Somatosensory cortex | tissue | 11.9 |
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:
| 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 |
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 / exp | o/e | Constrained |
|---|---|---|---|
| 19:45,507,772–45,521,325 | 127 / 170.7 | 0.74 | no |
| 19:45,521,326–45,522,756 | 226 / 196.0 | 1.15 | no |
| 19:45,522,757–45,522,809 | 9 / 26.9 | 0.33 | yes (p 5.5e-04) |
| 19:45,522,810–45,526,174 | 126 / 134.8 | 0.94 | no |
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)
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 physiology | 1 |
| abnormal platelet activation | 1 |
| increased megakaryocyte cell number | 1 |
| increased platelet aggregation | 1 |
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.
| Organism | UniProt | Identity | Method |
|---|---|---|---|
| Pongo abelii | Q5RDN2 | 99.5% | Diamond |
| Xenopus laevis | Q64GL0 | 89.0% | Diamond |
| Canis lupus familiaris | P50551 | 86.2% | Diamond |
| Bos taurus | Q2TA49 | 86.2% | Diamond |
| Xenopus tropicalis | Q5Y171 | 75.5% | Diamond |
| Dictyostelium discoideum | Q5TJ65 | 38.4% | 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).
| Symbol | Type | Entrez |
|---|---|---|
| OPA3-RTN2 | protein-coding | 144667540 |
| PPM1N | protein-coding | 147699 |
| RTN2 | protein-coding | 6253 |
| TRU-TCA1-1 | tRNA | 7234 |
| OPA3 | protein-coding | 80207 |
| GPR4 | protein-coding | 2828 |
| EML2 | protein-coding | 24139 |
| MIR330 | ncRNA | 442902 |
| EML2-AS1 | ncRNA | 100287177 |
| FOSB | protein-coding | 2354 |
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)
| 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 (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:
| PDB | Title | Method | Resolution (Å) |
|---|---|---|---|
| 1USE | human VASP tetramerisation domain | X-RAY DIFFRACTION | 1.3 |
| 2PBD | Ternary complex of profilin-actin with the poly-PRO-GAB domain of VASP* | X-RAY DIFFRACTION | 1.5 |
| 1USD | human VASP tetramerisation domain L352M | X-RAY DIFFRACTION | 1.7 |
| 2PAV | Ternary complex of Profilin-Actin with the Last Poly-Pro of Human VASP | X-RAY DIFFRACTION | 1.8 |
| 3CHW | Complex of Dictyostelium discoideum Actin with Profilin and the Last Poly-Pro of Human … | X-RAY DIFFRACTION | 2.3 |
| 9UB1 | The structure of Myanmar_N2 and M6B12_Fab complex | ELECTRON MICROSCOPY | 2.35 |
| 8YVL | Neuraminidase of A/California/04/2009 HIN1 in complex with CAV-F34 Fab | ELECTRON MICROSCOPY | 2.47 |
| 9UAX | The structure of Myanmar_N2 and AS4C_Fab complex | ELECTRON MICROSCOPY | 2.71 |
| 8GAT | Structure of human NDS.1 Fab and 1G01 Fab in complex with influenza virus neuraminidase … | ELECTRON MICROSCOPY | 3 |
| 8GAU | Structure of human NDS.1 Fab and 1G01 Fab in complex with influenza virus neuraminidase … | ELECTRON MICROSCOPY | 3.6 |
| 1EGX | SOLUTION STRUCTURE OF THE ENA-VASP HOMOLOGY 1 (EVH1) DOMAIN OF HUMAN … | SOLUTION NMR |
Predicted structure (AlphaFold)
| Model | pLDDT | Fraction very-high |
|---|---|---|
| AF-P50552-F1 | 71.43 | 0.38 |
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)
| Type | Positions |
|---|---|
| N-acetylserine | 2 |
| Phosphotyrosine | 39 |
| Phosphoserine | 46, 157, 239, 305, 314, 322, 323, 325 |
| Phosphothreonine | 278, 284, 316 |
| N6-acetyllysine | 283 |
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 a-239 and e-278. |
| 239 | promotes f-actin assembly; when associated with a-157 and a-278. interferes with f-actin assembly; when associated with a-157 and e-278. |
| 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
1 curated (TAS) of 11; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).
11 pathways:
| ID | Pathway | Evidence |
|---|---|---|
| R-HSA-446353 | Cell-extracellular matrix interactions | curated |
| R-HSA-1280218 | Adaptive Immune System | — |
| R-HSA-422475 | Axon guidance | — |
| R-HSA-446728 | Cell junction organization | — |
| R-HSA-1500931 | Cell-Cell communication | — |
| R-HSA-1266738 | Developmental Biology | — |
| R-HSA-202433 | Generation of second messenger molecules | electronic |
| R-HSA-168256 | Immune System | — |
| R-HSA-9675108 | Nervous system development | — |
| R-HSA-376176 | Signaling by ROBO receptors | electronic |
| R-HSA-202403 | TCR 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:
| Category | Pathways |
|---|---|
| TCR signaling | 1 |
| Axon guidance | 1 |
| Cell junction organization | 1 |
| Immune System | 1 |
| Adaptive Immune System | 1 |
| Nervous system development | 1 |
| Cell-Cell communication | 1 |
| Developmental Biology | 1 |
GO top-level categories
36 GO namespaces:
| Category | Terms |
|---|---|
| cellular anatomical structure | 4 |
| protein binding | 2 |
| 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 |
| cytoskeletal 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 |
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 term | NS | Evidence |
|---|---|---|
| positive regulation of actin filament polymerization | BP | direct assay |
| cell junction | CC | direct assay |
| extracellular exosome | CC | high-throughput assay |
| focal adhesion | CC | direct assay |
| plasma membrane | CC | direct assay |
| cadherin binding | MF | high-throughput assay |
| profilin binding | MF | physical interaction |
Protein interactions and networks
STRING
showing 15 of 2,016 interactions by confidence (×1000):
| Protein A | Protein B | Partner UniProt | Score |
|---|---|---|---|
| VASP | ZYX | Q15942 | 943 |
| VASP | PFN4 | Q8NHR9 | 931 |
| VASP | PFN3 | P60673 | 929 |
| VASP | VCL | P18206 | 915 |
| VASP | PFN1 | P07737 | 915 |
| VASP | TLN1 | Q9Y490 | 904 |
| VASP | RAPH1 | Q70E73 | 902 |
| VASP | TLN2 | Q9Y4G6 | 883 |
| VASP | PXN | P49023 | 870 |
| VASP | APBB1IP | Q7Z5R6 | 792 |
| VASP | CFL1 | P23528 | 786 |
| VASP | CFL2 | Q9Y281 | 785 |
| VASP | GPKOW | Q92917 | 773 |
| VASP | CDC42 | P21181 | 766 |
| VASP | WIPF1 | O43516 | 736 |
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:
| Partner | Interaction type | MIscore | Records |
|---|---|---|---|
| ZYX | physical association | 0.800 | 3 |
| ABI2 | physical association | 0.740 | 5 |
| CEP43 | association | 0.740 | 4 |
| ABI3 | physical association | 0.720 | 9 |
| TRIM9 | physical association | 0.670 | 4 |
| BAIAP2 | direct interaction | 0.650 | 6 |
| XIRP1 | physical association | 0.650 | 5 |
| PSORS1C2 | physical association | 0.600 | 4 |
| ABI1 | physical association | 0.560 | 3 |
| SCGB2A2 | physical association | 0.560 | 3 |
| HSPA8 | physical association | 0.560 | 1 |
| PFN1 | physical association | 0.560 | 1 |
| RPS6KA1 | physical association | 0.540 | 4 |
| GTPBP1 | association | 0.530 | 3 |
| EVL | association | 0.530 | 1 |
| NR4A1 | physical association | 0.520 | 2 |
| NSMAF | physical association | 0.500 | 2 |
| MYO10 | direct interaction | 0.490 | 3 |
| DMRTB1 | physical association | 0.490 | 2 |
| FRS3 | physical association | 0.490 | 2 |
| SAT1 | physical association | 0.490 | 2 |
| ACTG1 | proximity | 0.480 | 1 |
| FAF2 | direct interaction | 0.440 | 2 |
| AEBP1 | direct interaction | 0.440 | 1 |
| MAGED1 | direct interaction | 0.440 | 1 |
| MRPL43 | direct interaction | 0.440 | 1 |
| PPP2CA | dephosphorylation reaction | 0.440 | 1 |
| PRKACA | phosphorylation reaction | 0.440 | 1 |
| PRKG1 | phosphorylation reaction | 0.440 | 1 |
| SHROOM3 | direct interaction | 0.440 | 1 |
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:
| 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 |
Protein complexes (CORUM) (3)
Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).
3 complexes by size:
| Complex | Subunits | Members |
|---|---|---|
| ★ PRKCD-VASP complex | 2 | PRKCD, VASP |
| APBB1IP-VASP complex | 2 | APBB1IP, VASP |
| CXCR2-VASP complex, CXCL8-stimulated | 2 | CXCR2, 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:
| Pathway | Partners | Fold | FDR |
|---|---|---|---|
| Parasite infection | 7 | 78.1× | 4e-10 |
| Leishmania phagocytosis | 7 | 78.1× | 4e-10 |
| Fcgamma receptor (FCGR) dependent phagocytosis | 7 | 62.9× | 8e-10 |
| RHO GTPases Activate WASPs and WAVEs | 6 | 61.4× | 2e-08 |
| Signaling by VEGF | 6 | 42.5× | 2e-07 |
| FCGR3A-mediated phagocytosis | 7 | 42.3× | 1e-08 |
| Leishmania infection | 8 | 42.1× | 8e-10 |
| Parasitic Infection Pathways | 8 | 42.1× | 8e-10 |
GO biological processes:
| GO term | Partners | Fold | FDR |
|---|---|---|---|
| actin filament organization | 6 | 16.6× | 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):
| Classification | Count (floor) |
|---|---|
| Pathogenic | 0 |
| Likely pathogenic | 0 |
| Uncertain significance | 21 |
| Likely benign | 1 |
| Benign | 1 |
SpliceAI
Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 27 predictions of 948):
| Position(s) | Effect | Δscore | Sites |
|---|---|---|---|
| 19:45517654 | acceptor_gain | 1.0000 | |
| 19:45517835–45517836 | donor_loss | 1.0000 | 2 |
| 19:45518095–45518096 | donor_loss | 1.0000 | 5 |
| 19:45522707 | acceptor_gain | 1.0000 | |
| 19:45523639 | acceptor_gain | 1.0000 | |
| 19:45523696–45523697 | donor_loss | 1.0000 | 5 |
| 19:45524095 | acceptor_loss | 1.0000 | 3 |
| 19:45524143–45524144 | donor_loss | 1.0000 | 4 |
| 19:45524560 | acceptor_gain | 1.0000 | |
| 19:45524661–45524662 | donor_loss | 1.0000 | 4 |
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:
| Residue | Likely-pathogenic substitutions | Mean am_pathogenicity | Max am_pathogenicity |
|---|---|---|---|
| M267 | 9 | 0.987 | 1.000 |
| M264 | 9 | 0.936 | 0.996 |
| F79 | 8 | 0.996 | 1.000 |
| H80 | 8 | 0.993 | 0.999 |
| F93 | 8 | 0.990 | 1.000 |
| F102 | 8 | 0.983 | 0.999 |
| D84 | 8 | 0.958 | 0.987 |
| D18 | 8 | 0.838 | 0.977 |
| M106 | 8 | 0.815 | 0.989 |
| W23 | 7 | 0.999 | 1.000 |
| W82 | 7 | 0.997 | 1.000 |
| W89 | 7 | 0.991 | 0.998 |
| Q81 | 7 | 0.988 | 0.999 |
| E266 | 7 | 0.986 | 0.997 |
| M14 | 7 | 0.985 | 0.996 |
| F47 | 7 | 0.983 | 0.996 |
| E3 | 7 | 0.972 | 0.991 |
| W310 | 7 | 0.961 | 0.993 |
| N63 | 7 | 0.952 | 0.998 |
| S34 | 7 | 0.945 | 0.998 |
HPA cancer prognostics
RNA cancer specificity: Low cancer specificity
Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.
1 prognostic cancer types:
| Cancer | Prognostic | p-value |
|---|---|---|
| Liver Hepatocellular Carcinoma (TCGA) | unfavorable | 1.48e-06 |
Disease associations
OMIM: gene MIM:601703 | disease phenotypes:
GWAS associations
1 associations:
| Study | Trait | p-value |
|---|---|---|
| GCST007827_3 | Alzheimer’s disease or HDL levels (pleiotropy) | 1e-97 |
EFO canonical traits (from GWAS)
1 canonical traits:
| 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 (CPIC guideline: no)
PharmGKB clinical annotations
1 annotations by evidence level (1 strongest → 4):
| Variant | Association | 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 |
PharmGKB variant annotations
Per-publication pharmacogenomic findings for this gene (significant associations).
1 published findings:
| Variant | Drug(s) | Category | Finding | PMID |
|---|---|---|---|---|
| rs10995 | hydrochlorothiazide | Efficacy | Genotypes 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.
| Ligand | Measure | Value |
|---|---|---|
| CHEMBL5653589 | KD | 1440 nM |
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 expression, increases response to substance, decreases reaction, affects localization, increases phosphorylation | 5 |
| Resveratrol | decreases reaction, increases phosphorylation, affects cotreatment, decreases expression | 5 |
| Valproic Acid | affects expression, decreases expression, increases 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 | increases expression, affects cotreatment, decreases expression | 2 |
| Dichlorodiphenyl Dichloroethylene | decreases expression, increases activity, increases phosphorylation | 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 |
| Particulate Matter | affects cotreatment, increases abundance, increases expression, affects 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 |
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)
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.
Related Atlas pages
- Disease cohort memberships (association, not causation — diseases whose associated-gene cohort lists this gene; a subset are also under Associated diseases): Alzheimer disease