VTN

Summary

VTN (vitronectin, HGNC:12724) is a protein-coding gene on chromosome 17q11.2, encoding Vitronectin (P04004). Vitronectin is a cell adhesion and spreading factor found in serum and tissues.

The protein encoded by this gene functions in part as an adhesive glycoprotein. Differential expression of this protein can promote either cell adhesion or migration as it links cells to the extracellular matrix through a variety of ligands. These ligands include integrins, plasminogen activator inhibitor-1, and urokinase plasminogen activator receptor. This secreted protein can be present in the plasma as a monomer or dimer and forms a multimer in the extracellular matrix of several tissues. This protein also inhibits the membrane-damaging effect of the terminal cytolytic complement pathway and binds to several serpin serine protease inhibitors. This protein can also promote extracellular matrix degradation and thus plays a role in tumorigenesis. It is involved in a variety of other biological processes such as the regulation of the coagulation pathway, wound healing, and tissue remodeling. The heparin-binding domain of this protein give it anti-microbial properties. It is also a lipid binding protein that forms a principal component of high density lipoprotein.

Source: NCBI Gene 7448 — RefSeq curated summary.

At a glance

• Gene–disease (curated): atypical hemolytic-uremic syndrome (Limited, GenCC)
• GWAS associations: 6
• Clinical variants (ClinVar): 106 total
• Druggable target: yes
• MANE Select transcript: NM_000638

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:12724
Approved symbol	VTN
Name	vitronectin
Location	17q11.2
Locus type	gene with protein product
Status	Approved
Aliases	VN
Ensembl gene	ENSG00000109072
Ensembl biotype	protein_coding
OMIM	193190
Entrez	7448

Gene structure

Transcript identifiers

Ensembl transcripts: 14 — 13 protein_coding, 1 retained_intron

ENST00000226218, ENST00000539746, ENST00000542029, ENST00000886528, ENST00000886529, ENST00000886530, ENST00000886531, ENST00000886532, ENST00000886533, ENST00000886534, ENST00000886535, ENST00000886536, ENST00000886537, ENST00000954238

RefSeq mRNA: 1 — MANE Select: NM_000638 NM_000638

CCDS: CCDS11229

Canonical transcript exons

ENST00000226218 — 8 exons

Exon	Start	End
ENSE00001177290	28367284	28367481
ENSE00001177296	28370140	28370307
ENSE00003468231	28369507	28369851
ENSE00003522630	28368872	28369028
ENSE00003552924	28369289	28369428
ENSE00003559675	28367715	28368059
ENSE00003669747	28369927	28370046
ENSE00003672972	28368521	28368673

Expression profiles

Bgee: expression breadth ubiquitous, 132 present calls, max score 99.89.

FANTOM5 (CAGE): breadth broad, TPM avg 25.3644 / max 8987.4336, expressed in 463 samples.

FANTOM5 promoters (14 alternative TSS)

Promoter ID	TPM avg	Samples expressed
165011	17.7470	264
165010	5.4020	379
165009	1.8013	114
165002	0.0687	12
164999	0.0576	12
165008	0.0482	11
165000	0.0395	6
165003	0.0357	8
164998	0.0354	7
165007	0.0340	9

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right lobe of liver	UBERON:0001114	99.89	gold quality
liver	UBERON:0002107	99.85	gold quality
right adrenal gland	UBERON:0001233	98.16	gold quality
right adrenal gland cortex	UBERON:0035827	97.89	gold quality
left adrenal gland	UBERON:0001234	97.32	gold quality
left adrenal gland cortex	UBERON:0035825	97.01	gold quality
adrenal gland	UBERON:0002369	94.85	gold quality
gall bladder	UBERON:0002110	93.85	gold quality
heart left ventricle	UBERON:0002084	91.61	gold quality
apex of heart	UBERON:0002098	90.88	gold quality
placenta	UBERON:0001987	90.79	gold quality
heart	UBERON:0000948	85.07	gold quality
right hemisphere of cerebellum	UBERON:0014890	83.42	gold quality
cerebellar hemisphere	UBERON:0002245	82.99	gold quality
cerebellar cortex	UBERON:0002129	82.82	gold quality
cerebellum	UBERON:0002037	82.68	gold quality
islet of Langerhans	UBERON:0000006	81.98	gold quality
pancreas	UBERON:0001264	81.15	gold quality
body of pancreas	UBERON:0001150	80.99	gold quality
adrenal tissue	UBERON:0018303	80.81	gold quality
right atrium auricular region	UBERON:0006631	79.95	gold quality
duodenum	UBERON:0002114	74.09	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	73.82	gold quality
omental fat pad	UBERON:0010414	73.61	gold quality
right frontal lobe	UBERON:0002810	73.37	gold quality
right coronary artery	UBERON:0001625	72.70	gold quality
left coronary artery	UBERON:0001626	72.14	gold quality
primary visual cortex	UBERON:0002436	71.85	gold quality
nucleus accumbens	UBERON:0001882	71.25	gold quality
putamen	UBERON:0001874	71.13	gold quality

Single-cell (SCXA)

Detected in 12 experiment(s), a significant marker in 11.

Experiment	Marker?	Max mean expression
E-CURD-98	yes	5802.60
E-MTAB-7407	yes	4871.68
E-MTAB-9388	yes	3917.97
E-HCAD-9	yes	3190.67
E-MTAB-11121	yes	1444.82
E-ANND-5	yes	727.62
E-GEOD-134144	yes	528.19
E-GEOD-81383	yes	265.34
E-MTAB-6701	yes	68.22
E-MTAB-10553	yes	35.11
E-MTAB-5061	no	4.33
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): FOXA1, FOXM1, HNF4A, NR2F1, TCF3

Literature-anchored findings (GeneRIF, showing 40)

• studies reveal that vitronectin associates with fibrin during coagulation, and may thereby modulate hemostasis and inflammation (PMID:11744726)
• uPA-dependent VSMC adhesion is a function of selective Vn phosphorylation by the ectoprotein kinase CK2 (PMID:11756447)
• Mapped the fibrin binding sites in vitronectin (PMID:11785953)
• Plasminogen activator inhibitor type 1 promotes the self-association of vitronectin into complexes (PMID:11796716)
• Snake venom disintegrin, saxatilin, inhibits interaction of human umbilical vein cells to immobilized vitronectin and adhesion of smooth muscle cells to vitronectin as well as vitronectin-induced migration of the SMC cells. (PMID:11864711)
• the rSMB domain of vitronectin is distinct from the crossed pattern present in most small disulfide bond-rich proteins (PMID:12019263)
• demonstrated that the avidity of heparin binding to vitronectin is governed by both the conformational state of the monomer and multimerization of the molecule (PMID:12071840)
• Adhesion of hairy cells to vitronectin inhibits interferon-alpha-induced apoptosis. (PMID:12091360)
• REVIEW: studies defining the binding sites of vitronectin and PAI-1 and binding affinities in the formation of larger PAI-1/VTN complexes. (PMID:12437099)
• strong vitronectin accumulation in extracellular matrix around some breast cancer cell clusters and in the subendothelial area of some blood vessels (PMID:12757937)
• importance of IGFBPs in modulating IGF-I binding to VN and that this binding has functional consequences in cells. (PMID:12810534)
• Plasma vitronectin level potentially represents a pathogenic factor for atherogenesis and thrombus formation in patients with coronary artery disease. (PMID:12913402)
• Results indicate that multimeric vitronectin in encapsulating peritoneal sclerosis (EPS)ascites plays a potential role in peritoneal fibrogenesis in EPS. (PMID:14586734)
• Turnover of soluble vitronectin requires ligation of vitronectin’s basic domain and that this binding event can work in trans to regulate vitronectin degradation. (PMID:14681059)
• VN-potentiated platelet-clot interaction requires VN in the clot and multimeric VN bound to the platelet surface; self-assembly of VTN may provide a physiologically relevant contribution to platelet aggregation on a blood clot. (PMID:15069014)
• Results describe the three-dimensional structure of an N-terminal fragment comprising the first 51 amino acids from human plasma vitronectin. (PMID:15123712)
• Human mesenchymal stem cells cultured on purified vitronectin produce a mineralized matrix, and express osteopontin, osteocalcin, collagen I, and alkaline phosphatase. (PMID:15123885)
• IGF-II:VN and IGF-I:IGFBP-5:VN complexes may be useful in situations where enhanced keratinocyte cell migration and proliferation is required, such as in wound healing and skin regeneration. (PMID:15140223)
• Structural model provides an indication of the disposition of the central domain and C-terminal heparin-binding domains of vitronectin with respect to the N-terminal somatomedin B domain. (PMID:15641781)
• Through promoting Met-Integrin association, HGF-FN and HGF-VN complexes coordinated and enhanced endothelial cell migration through activation of the PI-3 kinase pathway involving a Ras-dependent mechanism (PMID:15717924)
• Vittronectin can enhance epidermal growth factor and basic fibroblast growth factor ) to enhance keratinocyte cell division. (PMID:15777802)
• examination of the mechanism by which granzyme B cleaves vitronectin (PMID:15843372)
• Complexation wiwth serpin peptidase inibitor (PAI-1), with a sedimentation coefficient of 6.5 S, is the key intermediate for the assembly of higher order complexes. (PMID:15905170)
• IGROV1 cells were shown to adhere rapidly on the HUVECs monolayer; adhesion was inhibited by anti-alphav integrin and anti-Vn blocking antibodies, but not by anti-beta1 integrin antibodies (PMID:15914035)
• Binding of vitronectin to outer membrane protein Haemophilus influenzae type b surface fibrils (Hsf) inhibits complement-mediated bactericidal activity and prevents complement-induced cell lysis. (PMID:16785539)
• Osteogenesis on vitronectin correlated with enhanced focal adhesion formation, the activation of focal adhesion kinase (FAK) and paxillin, and the diminished activation of extracellular signal-regulated kinase (ERK). (PMID:16815299)
• PLAUR and the somatomedin B region of VTN direct the localization of UPA to focal adhesions in microvessel endothelial cells. (PMID:17344041)
• Solution structure of recombinant somatomedin B domain from VN produced in Pichia pastoris is reported. (PMID:17766387)
• vitronectin without the somatomedin B domain exhibits residual plasminogen activator inhibitor-1-binding activity (PMID:18174166)
• Vitronectin and growth factor complexes way have roles in wound healing (PMID:18200066)
• MMP-2 enhanced peritoneal adhesion of ovarian cancer cells through cleavage of ECM proteins fibronectin (FN) and vitronectin (Vn) into small fragments (PMID:18340378)
• A composite role of vitronectin and urokinase in the modulation of cell morphology upon expression of the urokinase receptor. (PMID:18362146)
• reports the crystal structures of uPAR in complex with both urokinase (uPA) and vitronectin and reveal that uPA occupies the central cavity of the receptor, whereas vitronectin binds at the outer side of the receptor (PMID:18376415)
• vitronectin and integrin beta(3) contribute to the initiation of TLR2 responses (PMID:18516040)
• analysis of a site on PAI-1 that binds to vitronectin outside of the somatomedin B domain (PMID:18658131)
• ability of ovarian carcinoma cells to bind to peritoneal mesothelium in vitro and strongly suggest that vitronectin and its receptors contribute to this crucial event. (PMID:18781095)
• pneumococci exploit the vitronectin-alphavbeta3-integrin complex as a cellular receptor for invasion and this integrin-mediated internalization requires the cooperation between the host signalling molecules ILK, PI3K and Akt. (PMID:19118218)
• support the beneficial effect of VN on oligodendrocytic differentiation of human embryonic stem cells (PMID:19162023)
• These results support a model for PAI-1 binding to vitronectin in which the interaction surface extends beyond the region of PAI-1 occupied by the SMB domain. (PMID:19193026)
• A vitronectin M381T polymorphism increases risk of hemangioblastoma in patients with VHL gene defect (PMID:19288063)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	vtnb	ENSDARG00000053831
danio_rerio	vtna	ENSDARG00000055388
mus_musculus	Vtn	ENSMUSG00000017344
rattus_norvegicus	Vtn	ENSRNOG00000010031

Paralogs (1): PRG4 (ENSG00000116690)

Protein

Protein identifiers

Vitronectin — P04004 (reviewed: P04004)

Alternative names: S-protein, Serum-spreading factor, V75

All UniProt accessions (3): P04004, D9ZGG2, F5GX75

UniProt curated annotations — full annotation on UniProt →

Function. Vitronectin is a cell adhesion and spreading factor found in serum and tissues. Vitronectin interact with glycosaminoglycans and proteoglycans. Is recognized by certain members of the integrin family and serves as a cell-to-substrate adhesion molecule. Inhibitor of the membrane-damaging effect of the terminal cytolytic complement pathway. Somatomedin-B is a growth hormone-dependent serum factor with protease-inhibiting activity.

Subunit / interactions. Exists in two forms: a single chain 75 kDa form (V75) and a clipped form composed of two chains (65 kDa and 10 kDa) (V65+V10) which are held together by a disulfide bond. Interacts with SERPINE1/PAI1, insulin and C1QBP. (Microbial infection) Interacts (via hemopexin repeat 2) with P.falciparum (isolate CDC / Honduras) SERA5 P47 (via C-terminus); may form heterotetramers of two VTN and SERA5 P47 heterodimers; the interaction may protect merozoites from phagocytosis by host monocytes; VTN glycosylation appears to be dispensable for the interaction.

Subcellular location. Secreted. Extracellular space Parasitophorous vacuole.

Tissue specificity. Expressed in the retina pigment epithelium (at protein level). Expressed in plasma (at protein level). Expressed in serum (at protein level).

Post-translational modifications. Sulfated on tyrosine residues. N- and O-glycosylated. Phosphorylation on Thr-69 and Thr-76 favors cell adhesion and spreading. It has been suggested that the active SMB domain may be permitted considerable disulfide bond heterogeneity or variability, thus two alternate disulfide patterns based on 3D structures are described with 1 disulfide bond conserved in both. Phosphorylation sites are present in the extracellular medium.

Domain organisation. The SMB domain mediates interaction with SERPINE1/PAI1. The heparin-binding domain mediates interaction with insulin.

RefSeq proteins (1): NP_000629* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000585	Hemopexin-like_dom	Domain
IPR001212	Somatomedin_B_dom	Domain
IPR018486	Hemopexin_CS	Conserved_site
IPR018487	Hemopexin-like_repeat	Repeat
IPR020436	SMB_chordata	Domain
IPR036024	Somatomedin_B-like_dom_sf	Homologous_superfamily
IPR036375	Hemopexin-like_dom_sf	Homologous_superfamily
IPR051298	Heme_transport/Cell_adhesion	Family

Pfam: PF00045, PF01033

UniProt features (80 total): strand 20, modified residue 11, disulfide bond 8, helix 6, mutagenesis site 4, turn 4, repeat 4, chain 3, region of interest 3, compositionally biased region 3, glycosylation site 3, sequence variant 3, sequence conflict 3, signal peptide 1, short sequence motif 1, site 1, peptide 1, domain 1

Structure

Experimental structures (PDB)

9 structures.

PDB	Method	Resolution (Å)
7RJ9	X-RAY DIFFRACTION	1.7
6O5E	X-RAY DIFFRACTION	1.9
1OC0	X-RAY DIFFRACTION	2.28
3BT2	X-RAY DIFFRACTION	2.5
3BT1	X-RAY DIFFRACTION	2.8
4K24	X-RAY DIFFRACTION	4.5
1S4G	SOLUTION NMR
1SSU	SOLUTION NMR
2JQ8	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P04004-F1	67.62	0.31

Antibody-complex structures (SAbDab): 2 — 3BT2, 4K24

Functional residue map

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

Catalytic / active sites (1): 398–399 (cleavage)

Post-translational modifications (11): 69, 75, 76, 78, 130, 137, 282, 312, 397, 417, 420

Disulfide bonds (8): 24–40, 24–28, 28–58, 38–51, 38–40, 44–50, 51–58, 293–430

Glycosylation sites (3): 86, 169, 242

Mutagenesis-validated functional residues (4):

Position	Phenotype
69	abolishes phosphorylation by ck2 and inhibits adhesion and spreading; when associated with a-76.
69	abolishes phosphorylation by ck2 and enhances adhesion and spreading; when associated with e-76.
76	abolishes phosphorylation by ck2 and inhibits adhesion and spreading; when associated with a-69.
76	abolishes phosphorylation by ck2 and enhances adhesion and spreading; when associated with e-69.

Function

Pathways and Gene Ontology

Reactome pathways

7 pathways

ID	Pathway
R-HSA-2129379	Molecules associated with elastic fibres
R-HSA-216083	Integrin cell surface interactions
R-HSA-3000170	Syndecan interactions
R-HSA-3000178	ECM proteoglycans
R-HSA-977606	Regulation of Complement cascade
R-HSA-9920588	Dengue virus activates/modulates innate and adaptive immune responses
R-HSA-9925563	Developmental Lineage of Pancreatic Ductal Cells

MSigDB gene sets: 309 (showing top): RNGTGGGC_UNKNOWN, GOBP_HEPATICOBILIARY_SYSTEM_DEVELOPMENT, GOBP_REGULATION_OF_CELLULAR_RESPONSE_TO_GROWTH_FACTOR_STIMULUS, GOBP_NEGATIVE_REGULATION_OF_PROTEOLYSIS, REACTOME_INNATE_IMMUNE_SYSTEM, CHIBA_RESPONSE_TO_TSA_UP, GOBP_VASCULAR_ENDOTHELIAL_GROWTH_FACTOR_SIGNALING_PATHWAY, HNF3ALPHA_Q6, GOBP_POSITIVE_REGULATION_OF_ENDOCYTOSIS, GOBP_REGULATION_OF_WOUND_HEALING, GOBP_REGULATION_OF_COAGULATION, GOBP_FORMATION_OF_PRIMARY_GERM_LAYER, GNF2_GSTM1, GNF2_HPN, GOBP_POSITIVE_REGULATION_OF_COAGULATION

GO Biological Process (25): immune response (GO:0006955), cell adhesion (GO:0007155), cell-matrix adhesion (GO:0007160), integrin-mediated signaling pathway (GO:0007229), positive regulation of cell-substrate adhesion (GO:0010811), positive regulation of smooth muscle cell migration (GO:0014911), cell migration (GO:0016477), regulation of cell adhesion (GO:0030155), negative regulation of blood coagulation (GO:0030195), extracellular matrix organization (GO:0030198), positive regulation of vascular endothelial growth factor receptor signaling pathway (GO:0030949), cell adhesion mediated by integrin (GO:0033627), endodermal cell differentiation (GO:0035987), negative regulation of proteolysis (GO:0045861), positive regulation of receptor-mediated endocytosis (GO:0048260), oligodendrocyte differentiation (GO:0048709), protein polymerization (GO:0051258), negative regulation of fibrinolysis (GO:0051918), smooth muscle cell-matrix adhesion (GO:0061302), positive regulation of wound healing (GO:0090303), liver regeneration (GO:0097421), positive regulation of vascular endothelial growth factor signaling pathway (GO:1900748), positive regulation of integrin-mediated signaling pathway (GO:2001046), vesicle-mediated transport (GO:0016192), cell differentiation (GO:0030154)

GO Molecular Function (9): scavenger receptor activity (GO:0005044), integrin binding (GO:0005178), extracellular matrix structural constituent (GO:0005201), collagen binding (GO:0005518), heparin binding (GO:0008201), polysaccharide binding (GO:0030247), identical protein binding (GO:0042802), extracellular matrix binding (GO:0050840), protein binding (GO:0005515)

GO Cellular Component (13): extracellular region (GO:0005576), basement membrane (GO:0005604), obsolete extracellular space (GO:0005615), endoplasmic reticulum (GO:0005783), Golgi lumen (GO:0005796), symbiont-containing vacuole (GO:0020003), extracellular matrix (GO:0031012), rough endoplasmic reticulum lumen (GO:0048237), extracellular exosome (GO:0070062), alphav-beta3 integrin-vitronectin complex (GO:0071062), blood microparticle (GO:0072562), protein complex involved in cell-matrix adhesion (GO:0098637), peptidase inhibitor complex (GO:1904090)

Reactome top-level categories

Rollup of top-6 pathways:

Category	Pathways
Extracellular matrix organization	2
Elastic fibre formation	1
Non-integrin membrane-ECM interactions	1
Complement cascade	1
Dengue Virus-Host Interactions	1
Developmental Cell Lineages of the Exocrine Pancreas	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
cell-substrate adhesion	2
cell adhesion	2
protein-containing complex binding	2
extracellular matrix	2
binding	2
immune system process	1
response to stimulus	1
cellular process	1
cell surface receptor signaling pathway	1
regulation of cell-substrate adhesion	1
positive regulation of cell adhesion	1
smooth muscle cell migration	1
regulation of smooth muscle cell migration	1
positive regulation of cell migration	1
cell motility	1
regulation of cellular process	1
blood coagulation	1
regulation of blood coagulation	1
negative regulation of coagulation	1
negative regulation of wound healing	1
negative regulation of hemostasis	1
extracellular structure organization	1
external encapsulating structure organization	1
positive regulation of signal transduction	1
regulation of vascular endothelial growth factor receptor signaling pathway	1
vascular endothelial growth factor receptor signaling pathway	1
endoderm formation	1
cell differentiation	1
proteolysis	1
regulation of proteolysis	1
negative regulation of protein metabolic process	1
receptor-mediated endocytosis	1
positive regulation of endocytosis	1
regulation of receptor-mediated endocytosis	1
central nervous system development	1
glial cell differentiation	1
protein-containing complex assembly	1
positive regulation of blood coagulation	1
positive regulation of response to external stimulus	1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

159 interactions, top by confidence:

A	B	Type	Score
VTN	C1QBP	psi-mi:“MI:0915”(physical association)	0.770
C1QBP	VTN	psi-mi:“MI:0914”(association)	0.770
C1QBP	VTN	psi-mi:“MI:0915”(physical association)	0.770
L3MBTL2	E2F6	psi-mi:“MI:0914”(association)	0.730
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
GOPC	VTN	psi-mi:“MI:0915”(physical association)	0.670
VTN	GOPC	psi-mi:“MI:0915”(physical association)	0.670
CFTR	HAX1	psi-mi:“MI:0914”(association)	0.610
lph	VTN	psi-mi:“MI:0915”(physical association)	0.600
lph	VTN	psi-mi:“MI:0407”(direct interaction)	0.600
	VTN	psi-mi:“MI:0407”(direct interaction)	0.600
	VTN	psi-mi:“MI:0915”(physical association)	0.600
VTN	lph	psi-mi:“MI:0915”(physical association)	0.600

BioGRID (223): GOPC (Two-hybrid), VTN (Affinity Capture-MS), VTN (Affinity Capture-MS), VTN (Two-hybrid), UACA (Affinity Capture-MS), TRIOBP (Affinity Capture-MS), GLI4 (Affinity Capture-MS), RAI14 (Affinity Capture-MS), OTUD4 (Affinity Capture-MS), C21orf2 (Affinity Capture-MS), ZNF483 (Affinity Capture-MS), GPRIN1 (Affinity Capture-MS), ZNF696 (Affinity Capture-MS), MPRIP (Affinity Capture-MS), RNF14 (Affinity Capture-MS)

ESM2 similar proteins: A2BD09, A2BDP1, A4IFM1, A4IIA2, A6ND36, B1AL88, E7F4V6, E9PY61, F1N4M2, L7VG99, O14525, O75949, O95156, O95157, O95158, P04004, P21743, P22458, P51693, P56722, Q03157, Q14C87, Q14DG7, Q28145, Q3UN70, Q5EGE1, Q5SWY7, Q5XHC5, Q61137, Q61199, Q68BL7, Q6L8S8, Q6P6V6, Q6S5C2, Q6UWH4, Q6ZVN8, Q766D5, Q76HP2, Q76HP3, Q76KP1

Diamond homologs: A0A0N9E2K8, D0EM77, G5EBU3, O04529, O54732, O55761, O75900, O88272, O88676, O93470, P04004, P22458, P22757, P41245, P48819, P50280, P51511, P53690, P55032, Q02853, Q10739, Q196W5, Q2TBM7, Q499S5, Q5XF51, Q8K3F2, Q8N119, Q90YC2, Q99542, Q9NRE1, O13065, O18767, O18927, O23507, O35548, O44836, O55123, O60882, O62806, O70138

SIGNOR signaling

8 interactions.

A	Effect	B	Mechanism
FGG	“down-regulates activity”	VTN	binding
VTN	“up-regulates activity”	“A8/b1 integrin”	binding
CSNK2A1	“up-regulates activity”	VTN	phosphorylation
PRKCA	“up-regulates quantity by stabilization”	VTN	phosphorylation
PRKCB	“up-regulates quantity by stabilization”	VTN	phosphorylation
PRKCG	“up-regulates quantity by stabilization”	VTN	phosphorylation
PRKACA	unknown	VTN	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 95 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
Regulation of clotting cascade	5	20.8×	1e-03

GO biological processes:

GO term	Partners	Fold	FDR
blood coagulation	5	11.3×	1e-02

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	79
Likely benign	16
Benign	8

Top pathogenic / likely-pathogenic (0)

SpliceAI

1239 predictions. Top by Δscore:

Variant	Effect	Δscore
17:28367404:A:AC	donor_gain	1.0000
17:28367405:C:CC	donor_gain	1.0000
17:28367477:CTTGT:C	acceptor_gain	1.0000
17:28367482:C:CC	acceptor_gain	1.0000
17:28367709:TCCTA:T	donor_loss	1.0000
17:28367710:CCTA:C	donor_loss	1.0000
17:28367711:CTA:C	donor_loss	1.0000
17:28367712:TA:T	donor_loss	1.0000
17:28367712:TAC:T	donor_loss	1.0000
17:28367713:ACC:A	donor_loss	1.0000
17:28367716:T:TA	donor_gain	1.0000
17:28368056:CCAG:C	acceptor_gain	1.0000
17:28368057:CAG:C	acceptor_gain	1.0000
17:28368057:CAGC:C	acceptor_gain	1.0000
17:28368516:CATA:C	donor_loss	1.0000
17:28368519:AC:A	donor_loss	1.0000
17:28368870:AC:A	donor_gain	1.0000
17:28368871:CC:C	donor_gain	1.0000
17:28368893:C:CA	donor_gain	1.0000
17:28368906:G:C	donor_gain	1.0000
17:28368934:T:TA	donor_gain	1.0000
17:28369024:CTACC:C	acceptor_gain	1.0000
17:28369285:GCACC:G	donor_loss	1.0000
17:28369288:C:G	donor_loss	1.0000
17:28369306:T:TA	donor_gain	1.0000
17:28369307:C:A	donor_gain	1.0000
17:28369308:C:A	donor_gain	1.0000
17:28369424:CTGCC:C	acceptor_gain	1.0000
17:28369425:TGCC:T	acceptor_gain	1.0000
17:28369426:GCC:G	acceptor_gain	1.0000

AlphaMissense

3144 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:28369992:C:G	C40S	0.996
17:28369993:A:T	C40S	0.996
17:28369293:A:G	F222S	0.995
17:28369980:C:G	C44S	0.995
17:28369981:A:T	C44S	0.995
17:28369938:C:G	C58S	0.994
17:28369939:A:T	C58S	0.994
17:28369979:G:C	C44W	0.994
17:28370040:C:G	C24S	0.994
17:28370041:A:T	C24S	0.994
17:28369336:C:G	A208P	0.993
17:28369959:C:G	C51S	0.993
17:28369960:A:T	C51S	0.993
17:28370016:A:C	F32C	0.993
17:28370040:C:T	C24Y	0.993
17:28369515:G:T	A174D	0.992
17:28369980:C:T	C44Y	0.992
17:28369981:A:G	C44R	0.992
17:28370015:G:C	F32L	0.992
17:28370015:G:T	F32L	0.992
17:28370017:A:G	F32L	0.992
17:28369360:A:G	W200R	0.991
17:28369360:A:T	W200R	0.991
17:28369549:C:G	A163P	0.991
17:28368932:C:G	A256P	0.990
17:28369019:A:C	Y227D	0.990
17:28369316:G:C	N214K	0.990
17:28369316:G:T	N214K	0.990
17:28369332:G:T	A209D	0.990
17:28369509:C:G	R176P	0.990

dbSNP variants (sampled 300 via entrez): RS1002456899 (17:28371700 C>T), RS1004386282 (17:28371746 G>T), RS1006705877 (17:28367717 C>G,T), RS1009074725 (17:28368761 A>G), RS1010856225 (17:28366930 C>T), RS1011440385 (17:28367950 G>A,C), RS1011525841 (17:28369242 C>T), RS1011726388 (17:28367803 C>A,G,T), RS1012223491 (17:28369965 C>T), RS1012592076 (17:28368326 G>T), RS1012667049 (17:28369734 T>C,G), RS1013648330 (17:28371672 C>A), RS1015661580 (17:28371749 T>G), RS1016889455 (17:28368357 C>T), RS1017660406 (17:28368773 T>C)

Disease associations

OMIM: gene MIM:193190 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
atypical hemolytic-uremic syndrome	Limited	Autosomal dominant

Mondo (1): atypical hemolytic-uremic syndrome (MONDO:0016244)

Orphanet (0):

HPO phenotypes

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

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST002546_2	Osteoprotegerin levels	1.000000e-09
GCST003219_13	Advanced age-related macular degeneration	1.000000e-08
GCST006612_19	LDL cholesterol	1.000000e-13
GCST006979_810	Heel bone mineral density	2.000000e-15
GCST010204_209	Low density lipoprotein cholesterol levels	3.000000e-15
GCST011347_53	Low density lipoprotein cholesterol levels	1.000000e-10

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:1001492	atrophic macular degeneration
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0009270	heel bone mineral density

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D065766	Atypical Hemolytic Uremic Syndrome	C12.050.351.968.419.936.463.500; C12.200.777.419.936.463.500; C12.950.419.936.463.500; C15.378.050.141.610.500; C15.378.140.855.925.500.500; C15.378.243.937.925.500.500

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL1075314 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	increases expression, decreases reaction, increases abundance, affects cotreatment, affects expression (+1 more)	4
Benzo(a)pyrene	affects methylation, decreases expression, decreases methylation, increases mutagenesis	3
Copper	affects binding, decreases reaction, decreases stability	3
Nickel	affects binding, decreases reaction, decreases stability	3
Cyclosporine	decreases expression	3
Cadmium	increases expression, affects binding	2
Cobalt	decreases reaction, decreases stability	2
Valproic Acid	affects expression, decreases expression	2
Zinc	affects binding, decreases expression	2
bisphenol F	affects cotreatment, increases expression	1
sotorasib	affects cotreatment, increases expression	1
ginger extract	decreases reaction, increases abundance, increases expression, decreases expression	1
methyleugenol	decreases expression	1
glycidyl methacrylate	decreases expression	1
ascorbate-2-phosphate	increases expression, affects binding, affects cotreatment	1
terbufos	increases methylation	1
pyrazolo(3,4-d)pyrimidine	affects expression	1
afimoxifene	decreases expression, decreases reaction	1
sulforaphane	decreases expression	1
sodium arsenite	decreases expression	1
perfluorooctanoic acid	increases expression	1
2,3-dimethoxy-1,4-naphthoquinone	decreases expression	1
perfluorooctane sulfonic acid	decreases expression	1
CGP 52608	affects binding, increases reaction	1
corosolic acid	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
Chir 99021	affects binding, affects cotreatment, increases expression	1
Grape Seed Proanthocyanidins	affects cotreatment, increases expression	1
XAV939	affects binding, affects cotreatment, increases expression	1
LDN 193189	affects cotreatment, increases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1120569	Binding	Inhibition of vitronectin	Emerging targets in osteoporosis disease modification. — J Med Chem

Cellosaurus cell lines

8 cell lines: 7 transformed cell line, 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_E0T1	Ubigene HeLa VTN KO	Cancer cell line	Female
CVCL_E4HU	CHO SSF3KVN1	Transformed cell line	Female
CVCL_E4HV	CHO SSF3KVN7	Transformed cell line	Female
CVCL_E4HW	CHO SSF3VN8	Transformed cell line	Female
CVCL_E4HX	CHO SSF3VN9	Transformed cell line	Female
CVCL_E4HY	CHO SSF3VN17	Transformed cell line	Female
CVCL_E4HZ	CHO SSF3VN9Luc	Transformed cell line	Female
CVCL_E4I0	CHO SSF3VN9hmGluR1b	Transformed cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT02574403	PHASE4	COMPLETED	Study Assessing an Algorithm-based Strategy of Eculizumab Discontinuation in Children and Adults With aHUS
NCT07308574	PHASE4	RECRUITING	Post-Marketing Clinical Study of Ravulizumab in Participants With Clinical aHUS
NCT02949128	PHASE3	COMPLETED	Study of ALXN1210 in Complement Inhibitor Treatment-Naïve Adult and Adolescent Participants With Atypical Hemolytic Uremic Syndrome (aHUS)
NCT03131219	PHASE3	COMPLETED	Study of Ravulizumab in Children and Adolescents With Atypical Hemolytic Uremic Syndrome (aHUS)
NCT03205995	PHASE3	TERMINATED	Safety and Efficacy Study of OMS721 in Patients With Atypical Hemolytic Uremic Syndrome
NCT04861259	PHASE3	ACTIVE_NOT_RECRUITING	A Study Evaluating the Efficacy, Safety, Pharmacokinetics and Pharmacodynamics of Crovalimab in Adult and Adolescent Participants With Atypical Hemolytic Uremic Syndrome (aHUS)
NCT04889430	PHASE3	COMPLETED	Efficacy and Safety of Iptacopan (LNP023) in Adult Patients With Atypical Hemolytic Uremic Syndrome Naive to Complement Inhibitor Therapy
NCT04958265	PHASE3	ACTIVE_NOT_RECRUITING	A Study Evaluating the Efficacy, Safety, Pharmacokinetics and Pharmacodynamics of Crovalimab in Pediatric Participants With Atypical Hemolytic Uremic Syndrome (aHUS)
NCT05795140	PHASE3	RECRUITING	Evaluate Long-term Safety, Tolerability and Efficacy of Iptacopan in Study Participants With aHUS
NCT05935215	PHASE3	RECRUITING	Efficacy and Safety of Switching From Anti-C5 Antibody Treatment to Iptacopan Treatment in Study Participants With Atypical Hemolytic Uremic Syndrome (aHUS)
NCT00838513	PHASE2	COMPLETED	Open Label Controlled Trial of Eculizumab in Adult Patients With Plasma Therapy-sensitive Atypical Hemolytic Uremic Syndrome (aHUS)
NCT00844428	PHASE2	COMPLETED	Open Label Controlled Trial of Eculizumab in Adolescent Patients With Plasma Therapy-Sensitive aHUS
NCT00844545	PHASE2	COMPLETED	Open Label Controlled Trial of Eculizumab in Adult Patients With Plasma Therapy-Resistant aHUS
NCT00844844	PHASE2	COMPLETED	Open Label Controlled Trial of Eculizumab in Adolescent Patients With Plasma Therapy-Resistant aHUS
NCT01193348	PHASE2	COMPLETED	An Open-Label, Multi-Center Clinical Trial of Eculizumab in Pediatric Patients With Atypical Hemolytic-Uremic Syndrome
NCT01194973	PHASE2	COMPLETED	An Open-label, Multi-center Clinical Trial of Eculizumab in Adult Patients With Atypical Hemolytic-uremic Syndrome
NCT01757431	PHASE2	COMPLETED	The Safety and Efficacy of Eculizumab in Japanese Patients With Atypical Hemolytic Uremic Syndrome (aHUS)
NCT02464891	PHASE2	TERMINATED	Complement Inhibition in aHUS Dialysis Patients
NCT03303313	PHASE2	WITHDRAWN	A Study of an Investigational Drug, Cemdisiran (ALN-CC5), in Patients With Atypical Hemolytic Uremic Syndrome
NCT03518203	PHASE2	COMPLETED	Eculizumab to Treat Thrombotic Microangiopathy/Atypical Hemolytic Uremic Syndrome -Associated Multiple Organ Dysfunction Syndrome in Hematopoietic Stem Cell Transplant Recipients
NCT03999840	PHASE2	WITHDRAWN	Eculizumab to Cemdisiran Switch in aHUS
NCT04725812	PHASE2	TERMINATED	Complement Regulation to Undo Systemic Harm in Preeclampsia
NCT01522170	Not specified	TERMINATED	aHUS Observational Long Term Follow-Up
NCT01522183	Not specified	RECRUITING	Atypical Hemolytic-Uremic Syndrome (aHUS) Registry
NCT01755429	Not specified	COMPLETED	To Characterize the Safety and Tolerability of Eculizumab in Two Japanese aHUS Patients
NCT01770951	Not specified	COMPLETED	A Retrospective, Observational, Non-interventional Trial to Assess Eculizumab Treatment Effect in Patients With Atypical Hemolytic Uremic Syndrome (aHUS)
NCT01793168	Not specified	RECRUITING	Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford
NCT02614898	Not specified	TERMINATED	Evaluation of Potential Predictors of Disease Progression in Participants With Atypical Hemolytic Uremic Syndrome (aHUS) Including Genetics, Biomarkers, and Treatment
NCT02626663	Not specified	WITHDRAWN	The Role of Microparticles as a Biomarker
NCT03574506	Not specified	UNKNOWN	Eculizumab Use in the Postpartum Period for the Treatment of Pregnancy Associated aHUS: A Case Series
NCT03605511	Not specified	UNKNOWN	TTP and aHUS in Complicated Pregnancies
NCT04749810	Not specified	COMPLETED	Observational Study of Elizaria® in aHUS Patients
NCT05405777	Not specified	COMPLETED	A Retrospective Study to Evaluate the Clinical Outcome According to Treatment in aHUS Patients in South Korea
NCT05805202	Not specified	RECRUITING	Functional Implications of Rare Gene Mutations in aHUS Open the Door to Personalized Therapy
NCT05996731	Not specified	RECRUITING	Developing a Pipeline to Employ RNA-Seq as a Complementary Diagnostic Tool in Rare Diseases
NCT06065852	Not specified	RECRUITING	National Registry of Rare Kidney Diseases
NCT06099236	Not specified	ACTIVE_NOT_RECRUITING	A Prospective, Non-interventional, Observational Study of Presentation, Treatment Patterns and Outcomes in Atypical Hemolytic Uremic Syndrome Patients
NCT06312644	Not specified	RECRUITING	Study of Ultomiris® (Ravulizumab) Safety in Pregnancy
NCT07218536	Not specified	RECRUITING	The Burden of Atypical Hemolytic Uremic Syndrome and The Clinical Characteristics of Patients in Egyptian Hospitals A Multicenter, Observational, Retrospective Cohort Study in Egypt
NCT07399730	Not specified	NOT_YET_RECRUITING	Ravulizumab Outcomes in Polish Patients With aHUS