VIL1

Summary

VIL1 (villin 1, HGNC:12690) is a protein-coding gene on chromosome 2q35, encoding Villin-1 (P09327). Epithelial cell-specific Ca(2+)-regulated actin-modifying protein that modulates the reorganization of microvillar actin filaments.

This gene encodes a member of a family of calcium-regulated actin-binding proteins. This protein represents a dominant part of the brush border cytoskeleton which functions in the capping, severing, and bundling of actin filaments. Two mRNAs of 2.7 kb and 3.5 kb have been observed; they result from utilization of alternate poly-adenylation signals present in the terminal exon.

Source: NCBI Gene 7429 — RefSeq curated summary.

At a glance

• GWAS associations: 8
• Clinical variants (ClinVar): 157 total
• Druggable target: yes
• MANE Select transcript: NM_007127

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:12690
Approved symbol	VIL1
Name	villin 1
Location	2q35
Locus type	gene with protein product
Status	Approved
Aliases	D2S1471
Ensembl gene	ENSG00000127831
Ensembl biotype	protein_coding
OMIM	193040
Entrez	7429

Gene structure

Transcript identifiers

Ensembl transcripts: 19 — 19 protein_coding

ENST00000248444, ENST00000392114, ENST00000419986, ENST00000440053, ENST00000454069, ENST00000879961, ENST00000879962, ENST00000879963, ENST00000879964, ENST00000879965, ENST00000879966, ENST00000879967, ENST00000879968, ENST00000879969, ENST00000879970, ENST00000879971, ENST00000879972, ENST00000879973, ENST00000938226

RefSeq mRNA: 1 — MANE Select: NM_007127 NM_007127

CCDS: CCDS2417

Canonical transcript exons

ENST00000248444 — 20 exons

Exon	Start	End
ENSE00000353885	218440722	218440862
ENSE00000785754	218438658	218438726
ENSE00000785755	218437124	218437312
ENSE00000785756	218436482	218436626
ENSE00000785757	218435289	218435434
ENSE00000785758	218434526	218434705
ENSE00000785759	218432793	218432951
ENSE00000785760	218432046	218432183
ENSE00000785761	218431857	218431957
ENSE00000785762	218430725	218430878
ENSE00000785765	218429285	218429487
ENSE00000785767	218427965	218428073
ENSE00000785769	218425615	218425811
ENSE00000785770	218424277	218424351
ENSE00000876105	218423768	218423853
ENSE00001796166	218419123	218419168
ENSE00001848391	218449223	218453295
ENSE00002400059	218428227	218428337
ENSE00003484315	218429849	218429947
ENSE00003591507	218429597	218429675

Expression profiles

Bgee: expression breadth ubiquitous, 152 present calls, max score 99.06.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 1.8667 / max 392.4895, expressed in 157 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
25346	1.8530	156
25345	0.0137	5

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
jejunal mucosa	UBERON:0000399	99.06	gold quality
ileal mucosa	UBERON:0000331	99.03	gold quality
ileum	UBERON:0002116	98.97	silver quality
mucosa of transverse colon	UBERON:0004991	98.52	gold quality
rectum	UBERON:0001052	98.34	gold quality
duodenum	UBERON:0002114	98.00	gold quality
colonic mucosa	UBERON:0000317	97.31	gold quality
mucosa of sigmoid colon	UBERON:0004993	97.14	gold quality
buccal mucosa cell	CL:0002336	94.90	gold quality
small intestine	UBERON:0002108	92.24	gold quality
small intestine Peyer’s patch	UBERON:0003454	92.06	gold quality
transverse colon	UBERON:0001157	88.74	gold quality
gall bladder	UBERON:0002110	87.77	gold quality
jejunum	UBERON:0002115	85.63	gold quality
secondary oocyte	CL:0000655	83.68	gold quality
islet of Langerhans	UBERON:0000006	83.64	gold quality
right lobe of liver	UBERON:0001114	83.60	gold quality
body of pancreas	UBERON:0001150	82.64	gold quality
intestine	UBERON:0000160	82.55	gold quality
pancreas	UBERON:0001264	82.10	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	80.70	gold quality
oocyte	CL:0000023	80.62	gold quality
adult mammalian kidney	UBERON:0000082	80.35	gold quality
colonic epithelium	UBERON:0000397	79.71	gold quality
caecum	UBERON:0001153	79.40	gold quality
large intestine	UBERON:0000059	79.17	gold quality
liver	UBERON:0002107	79.16	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	78.41	gold quality
colon	UBERON:0001155	78.38	gold quality
monocyte	CL:0000576	78.25	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	15.46

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CDX1, CDX2, ELK1

miRNA regulators (miRDB)

8 targeting VIL1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3064-3P	100.00	70.09	1254
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-4776-3P	100.00	68.73	1340
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-5582-5P	99.27	71.42	1879
HSA-MIR-5572	98.55	65.84	970
HSA-MIR-4423-3P	97.98	69.66	912
HSA-MIR-4759	97.39	65.86	608

Literature-anchored findings (GeneRIF, showing 27)

• Tyrosine phosphorylation of villin regulates the organization of the actin cytoskeleton (PMID:11500485)
• villin has calcium-sensitive actin-capping and actin-depolymerizing sites (PMID:15272027)
• tyrosine phosphorylation at residues 60, 81, and 256 of human villin plays an essential role in cell migration as well as in the reorganization of the actin cytoskeleton (PMID:15342783)
• H. pylori induction of villin in the stomach correlates with activation and cooperative binding of Elk-1 and the SRF to the proximal promoter of villin (PMID:15576363)
• By severing actin filaments and capping their barbed ends, villin increases the concentration of actin monomers available for polymerization. (PMID:17182858)
• Together, our results show that in epithelial cells ATX and LPA act as strong stimulators of cell migration by recruiting PLC-gamma 1 and villin, both of which participate in the initiation of protrusion. (PMID:18054784)
• Villin is an actin regulatory protein that organizes, integrates and regulates multiple epithelial cell functions. (PMID:18307996)
• Cdx2 regulates intestinal villin expression through recruiting Brm-type SWI/SNF complex to the villin promoter. (PMID:19371634)
• identified VIL1 as a novel biomarker of cervical adenocarcinoma (PMID:19377296)
• study confirmed finding of VIL1 as a diagnostic marker of cervical adenocarcinoma (PMID:21623163)
• identified villin, an actin-binding protein, as the 95 kDa antigen in four of five sera from patients with IPEX syndrome (PMID:21741320)
• We demonstrated that the VIL1 gene is a potential candidate molecular marker for high serum AFP-associated HCC and a predictive candidate for the postoperative recurrence and poorer prognosis of HCC. (PMID:22530999)
• harmonin and villin autoantibodies are sensitive and specific markers of IPEX, differentiate IPEX, including atypical cases, from other early childhood disorders associated with enteropathy (PMID:24250806)
• Discriminated small-cell lung carcinoma from large-cell neuroendocrine lung carcinoma with immunohistochemical markers BAI3, CDX2 and VIL1. (PMID:24266897)
• Collective expression pattern of tensin/profilin-1/villin-1/talin could be a biomarker to estimate the prognosis of esophageal squamous cell carcinoma patients. (PMID:25337239)
• villin immunohistochemistry is a reliable and superior adjunct in the diagnosis of microvillus inclusion disease (PMID:25517957)
• Thus, villin plays an important role in establishing the balance between actin polymerization and actin severing to facilitate the initial steps of Salmonella entry. (PMID:25600187)
• study demonstrates that G. duodenalis-mediated disruption of villin is, at least, in part dependent on activation of myosin light chain kinase (PMID:26334299)
• Data indicate an association between highly fucosylated glycans and caudal type homeobox 1 (CDX1) and/or villin mRNA expression that both correlate with cell differentiation. (PMID:26537799)
• villin directly interacts with a transcriptional corepressor and ligand of the Slug promoter, ZBRK1. (PMID:26658611)
• Data show that data demonstrate that tumor protein translationally-controlled 1 (TCTP) overexpression has a promotion effect on caudal type homeo box transcription factor 2 protein (CDX2) and villin1 protein (VIL1) expression. (PMID:28536478)
• Villin 1 is released in plasma during acute kidney injury and shows potential as an early marker for proximal tubular injury/necrosis. (PMID:28704336)
• Villin, Pro-Ex-C and progesterone/estrogen receptor expression have diagnostic and predictive roles in endocervical and endometrioid adenocarcinoma. (PMID:28832070)
• Villin has a higher positive expression in Primary Pulmonary Enteric Adenocarcinoma cases. Villin proved to be a very sensitive and helpful enteric marker in the differential diagnosis between PEAC and other lung adenocarcinomas. (PMID:28953659)
• Induction of cell stress alters the actin cytoskeleton in intestinal epithelial cells via changes in the actin-binding proteins villin-1 and gelsolin. (PMID:29274870)
• F-actin-bundling sites are conserved in proteins with villin-type headpiece domains. (PMID:32520642)
• Transcriptome analysis uncovers the diagnostic value of miR-192-5p/HNF1A-AS1/VIL1 panel in cervical adenocarcinoma. (PMID:33024199)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	vil1	ENSDARG00000040466
mus_musculus	Vil1	ENSMUSG00000026175
rattus_norvegicus	Vil1	ENSRNOG00000015408
drosophila_melanogaster	Gel	FBGN0010225
caenorhabditis_elegans		WBGENE00010593

Paralogs (7): SCIN (ENSG00000006747), CAPG (ENSG00000042493), AVIL (ENSG00000135407), VILL (ENSG00000136059), GSN (ENSG00000148180), FLII (ENSG00000177731), SVIL (ENSG00000197321)

Protein

Protein identifiers

Villin-1 — P09327 (reviewed: P09327)

All UniProt accessions (4): P09327, B4DV78, C9J2B5, H7C0B6

UniProt curated annotations — full annotation on UniProt →

Function. Epithelial cell-specific Ca(2+)-regulated actin-modifying protein that modulates the reorganization of microvillar actin filaments. Plays a role in the actin nucleation, actin filament bundle assembly, actin filament capping and severing. Binds phosphatidylinositol 4,5-bisphosphate (PIP2) and lysophosphatidic acid (LPA); binds LPA with higher affinity than PIP2. Binding to LPA increases its phosphorylation by SRC and inhibits all actin-modifying activities. Binding to PIP2 inhibits actin-capping and -severing activities but enhances actin-bundling activity. Regulates the intestinal epithelial cell morphology, cell invasion, cell migration and apoptosis. Protects against apoptosis induced by dextran sodium sulfate (DSS) in the gastrointestinal epithelium. Appears to regulate cell death by maintaining mitochondrial integrity. Enhances hepatocyte growth factor (HGF)-induced epithelial cell motility, chemotaxis and wound repair. Upon S.flexneri cell infection, its actin-severing activity enhances actin-based motility of the bacteria and plays a role during the dissemination.

Subunit / interactions. Monomer. Homodimer; homodimerization is necessary for actin-bundling. Associates with F-actin; phosphorylation at tyrosine residues decreases the association with F-actin. Interacts (phosphorylated at C-terminus tyrosine phosphorylation sites) with PLCG1 (via the SH2 domains). Interacts (phosphorylated form) with PLCG1; the interaction is enhanced by hepatocyte growth factor (HGF).

Subcellular location. Cytoplasm. Cytoskeleton. Cell projection. Lamellipodium. Ruffle. Microvillus. Filopodium tip. Filopodium.

Tissue specificity. Specifically expressed in epithelial cells. Major component of microvilli of intestinal epithelial cells and kidney proximal tubule cells. Expressed in canalicular microvilli of hepatocytes (at protein level).

Post-translational modifications. Tyrosine phosphorylation is induced by epidermal growth factor (EGF) and stimulates cell migration. Phosphorylated on tyrosine residues by SRC. The unphosphorylated form increases the initial rate of actin-nucleating activity, whereas the tyrosine-phosphorylated form inhibits actin-nucleating activity, enhances actin-bundling activity and enhances actin-severing activity by reducing high Ca(2+) requirements. The tyrosine-phosphorylated form does not regulate actin-capping activity. Tyrosine phosphorylation is essential for cell migration: tyrosine phosphorylation sites in the N-terminus half regulate actin reorganization and cell morphology, whereas tyrosine phosphorylation sites in the C-terminus half regulate cell migration via interaction with PLCG1.

Disease relevance. Biliary atresia is a chronic and progressive cholestatic liver disease of chilhood characterized by an abnormal villin gene expression and severe malformation of canalicular microvillus structure.

Domain organisation. Consists of a large core fragment in the N-terminal portion and a small headpiece (HP) in the C-terminal portion. The core fragment is necessary for both actin-nucleating and -severing activities, whereas the HP binds F-actin strongly in both the presence and absence of calcium and is necessary in actin-bundling activity. The Gelsolin-like 1 repeat is necessary for the actin-capping activity. The entire core fragment is necessary for the actin-severing activity. Two major calcium-sensitive sites are involved in conformational changes and determine separate functional properties: the first site (Glu-25, Asp-44 and Glu-74) regulates the actin-capping and actin-severing activities; while the second site (Asp-61, Asp-86 and Ala-93) regulates only the actin-severing activity.

Similarity. Belongs to the villin/gelsolin family.

Isoforms (2)

UniProt ID	Names	Canonical?
P09327-1	1	yes
P09327-2	2

RefSeq proteins (1): NP_009058* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003128	Villin_headpiece	Domain
IPR007122	Villin/Gelsolin	Family
IPR007123	Gelsolin-like_dom	Domain
IPR029006	ADF-H/Gelsolin-like_dom_sf	Homologous_superfamily
IPR036180	Gelsolin-like_dom_sf	Homologous_superfamily
IPR036886	Villin_headpiece_dom_sf	Homologous_superfamily

Pfam: PF00626, PF02209

UniProt features (61 total): mutagenesis site 26, region of interest 6, repeat 6, strand 6, helix 6, sequence conflict 3, modified residue 2, splice variant 2, initiator methionine 1, chain 1, sequence variant 1, domain 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
3FG7	X-RAY DIFFRACTION	2
1UNC	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P09327-F1	77.98	0.18

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 (2): 366, 735

Mutagenesis-validated functional residues (26):

Position	Phenotype
25	inhibits activities regarding actin capping, actin severing and actin bundling.
44	inhibits activities regarding actin capping and actin severing.
46	reduces activities regarding actin capping and actin severing. does not reduce lamellipodium or ruffle localization and
60	reduces activities regarding actin capping and actin severing, lamellipodium or ruffle localization and cell migration.
61	inhibits actin-severing activity. does not inhibit actin-nucleation and actin-capping activities.
74	inhibits activities regarding actin capping and actin severing.
81	reduces activities regarding actin nucleating and actin severing, lamellipodium or ruffle localization and cell migratio
86–91	inhibits actin-severing activity and motility of the s.flexneri, does not inhibit activities regarding actin nucleation,
86	inhibits actin-severing activity. does not inhibit actin-capping activity.
93	inhibits actin-severing activity. does not inhibit actin-capping activity.
125–129	inhibits actin-severing activity and motility of the s.flexneri, does not inhibit activities regarding actin nucleation,
138	reduces binding to pip2.
145	does not reduce binding to pip2.
146	does not reduce binding to pip2.
256	reduces activities regarding actin nucleation and actin severing, lamellipodium or ruffle localization and cell migratio
286	reduces actin-severing activity and interaction with plcg1. complete loss of phosphorylation and interaction with plcg1,
324	complete loss of phosphorylation and interaction with plcg1, does not reduce lamellipodium or ruffle localization, inhib
461	complete loss of phosphorylation and interaction with plcg1, does not reduce lamellipodium or ruffle localization, inhib
467	reduces the ca(2+)-dependent actin-severing activity.
555	complete loss of phosphorylation and interaction with plcg1, does not reduce lamellipodium or ruffle localization, inhib
604	complete loss of phosphorylation and interaction with plcg1, does not reduce lamellipodium or ruffle localization, inhib
715	reduces the ca(2+)-dependent actin-severing activity.
725	complete loss of phosphorylation and interaction with plcg1, does not reduce lamellipodium or ruffle localization, inhib
815	reduces interaction with f-actin.
822	does not reduce binding to pip2.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 229 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_MCMV_INFECTION_DN, GSE45365_NK_CELL_VS_CD11B_DC_UP, GOBP_NEGATIVE_REGULATION_OF_PROTEIN_CONTAINING_COMPLEX_ASSEMBLY, GOBP_DIGESTION, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_REGULATION_OF_PROTEIN_POLYMERIZATION, GOBP_ACTIN_FILAMENT_BUNDLE_ORGANIZATION, GOBP_REGULATION_OF_CELL_MORPHOGENESIS, GOBP_REGULATION_OF_WOUND_HEALING, GOBP_REGULATION_OF_ACTIN_NUCLEATION, GOBP_REGULATION_OF_DEVELOPMENTAL_GROWTH, GOBP_NEGATIVE_REGULATION_OF_PROTEIN_POLYMERIZATION, GOZGIT_ESR1_TARGETS_DN, GOBP_BARBED_END_ACTIN_FILAMENT_CAPPING, GOBP_REGULATION_OF_EPITHELIAL_CELL_MIGRATION

GO Biological Process (32): intestinal D-glucose absorption (GO:0001951), apoptotic process (GO:0006915), epidermal growth factor receptor signaling pathway (GO:0007173), actin polymerization or depolymerization (GO:0008154), regulation of cell shape (GO:0008360), response to bacterium (GO:0009617), positive regulation of epithelial cell migration (GO:0010634), actin filament polymerization (GO:0030041), actin filament depolymerization (GO:0030042), positive regulation of cell migration (GO:0030335), positive regulation of actin filament depolymerization (GO:0030836), epithelial cell differentiation (GO:0030855), positive regulation of actin filament bundle assembly (GO:0032233), regulation of microvillus length (GO:0032532), cellular response to hepatocyte growth factor stimulus (GO:0035729), positive regulation of multicellular organism growth (GO:0040018), actin filament severing (GO:0051014), barbed-end actin filament capping (GO:0051016), regulation of actin nucleation (GO:0051125), actin filament capping (GO:0051693), cytoplasmic actin-based contraction involved in cell motility (GO:0060327), regulation of wound healing (GO:0061041), protein-containing complex assembly (GO:0065003), cellular response to epidermal growth factor stimulus (GO:0071364), terminal web assembly (GO:1902896), positive regulation of protein localization to plasma membrane (GO:1903078), regulation of lamellipodium morphogenesis (GO:2000392), positive regulation of lamellipodium morphogenesis (GO:2000394), cytoskeleton organization (GO:0007010), actin filament organization (GO:0007015), positive regulation of cellular component biogenesis (GO:0044089), positive regulation of lamellipodium organization (GO:1902745)

GO Molecular Function (9): calcium ion binding (GO:0005509), phosphatidylinositol-4,5-bisphosphate binding (GO:0005546), lysophosphatidic acid binding (GO:0035727), identical protein binding (GO:0042802), protein homodimerization activity (GO:0042803), cysteine-type endopeptidase inhibitor activity involved in apoptotic process (GO:0043027), actin filament binding (GO:0051015), actin binding (GO:0003779), protein binding (GO:0005515)

GO Cellular Component (13): ruffle (GO:0001726), cytoplasm (GO:0005737), plasma membrane (GO:0005886), microvillus (GO:0005902), brush border (GO:0005903), actin cytoskeleton (GO:0015629), lamellipodium (GO:0030027), filopodium (GO:0030175), actin filament bundle (GO:0032432), filopodium tip (GO:0032433), extracellular exosome (GO:0070062), cytoskeleton (GO:0005856), cell projection (GO:0042995)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
actin polymerization or depolymerization	2
positive regulation of cytoskeleton organization	2
positive regulation of supramolecular fiber organization	2
cell leading edge	2
plasma membrane bounded cell projection	2
actin-based cell projection	2
intestinal hexose absorption	1
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
ERBB signaling pathway	1
actin filament organization	1
regulation of cell morphogenesis	1
regulation of biological quality	1
response to other organism	1
epithelial cell migration	1
regulation of epithelial cell migration	1
positive regulation of cell migration	1
protein polymerization	1
protein depolymerization	1
cell migration	1
regulation of cell migration	1
positive regulation of cell motility	1
actin filament depolymerization	1
regulation of actin filament depolymerization	1
positive regulation of protein depolymerization	1
cell differentiation	1
epithelium development	1
regulation of actin filament bundle assembly	1
positive regulation of cellular component biogenesis	1
actin filament bundle assembly	1
regulation of microvillus organization	1
regulation of cell projection size	1
response to hepatocyte growth factor	1
cellular response to growth factor stimulus	1
multicellular organism growth	1
regulation of multicellular organism growth	1
positive regulation of developmental growth	1
positive regulation of multicellular organismal process	1

Protein interactions and networks

STRING

1158 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
VIL1	TNP1	P09430	772
VIL1	COMMD6	Q7Z4G1	720
VIL1	SLC11A1	P49279	670
VIL1	CXCR2	P25025	595
VIL1	MYL1	P05976	592
VIL1	CHRND	Q07001	551
VIL1	SPRYD7	Q5W111	545
VIL1	LGR5	O75473	543
VIL1	CCDC122	Q5T0U0	543
VIL1	LACC1	Q8IV20	543
VIL1	IL10RA	Q13651	534
VIL1	COL6A3	P12111	528
VIL1	CHGA	P10645	490
VIL1	IL18	Q14116	486
VIL1	CDX2	Q99626	486

IntAct

23 interactions, top by confidence:

A	B	Type	Score
VIL1	VIL1	psi-mi:“MI:0407”(direct interaction)	0.690
VIL1	VIL1	psi-mi:“MI:0915”(physical association)	0.690
VIL1	VIL1	psi-mi:“MI:2364”(proximity)	0.690
PLCG1	VIL1	psi-mi:“MI:0915”(physical association)	0.630
VIL1	PLCG1	psi-mi:“MI:2364”(proximity)	0.630
AVIL	VIL1	psi-mi:“MI:0914”(association)	0.530
VIL1	TEX11	psi-mi:“MI:0915”(physical association)	0.370
PLEKHA7	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
L1TD1	MYO1C	psi-mi:“MI:0914”(association)	0.350
AVIL	DDX11L8	psi-mi:“MI:0914”(association)	0.350
	PDLIM1	psi-mi:“MI:0914”(association)	0.350
AVIL	DCTN6	psi-mi:“MI:0914”(association)	0.350
PPM1B	VIL1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (31): TEX11 (Two-hybrid), CHM (Co-fractionation), VIL1 (Affinity Capture-MS), VIL1 (Affinity Capture-MS), VIL1 (Affinity Capture-MS), VIL1 (Affinity Capture-MS), VIL1 (Affinity Capture-MS), VIL1 (Affinity Capture-MS), VIL1 (Affinity Capture-MS), VIL1 (Affinity Capture-MS), VIL1 (Affinity Capture-MS), VIL1 (Affinity Capture-MS), VIL1 (Affinity Capture-MS), VIL1 (Affinity Capture-MS), VIL1 (Affinity Capture-MS)

ESM2 similar proteins: A1A5Q7, A4PCD4, A5PK19, A6NFQ2, B8ATT7, E9PYK3, O15195, O65570, O75366, O81644, O81645, O88398, O88910, O88954, O93510, P02640, P09327, P24452, P40121, P50747, P97616, Q0J716, Q0JAD9, Q10L71, Q13368, Q29261, Q3SZP7, Q3UVV9, Q5PPG7, Q60I26, Q60I27, Q61211, Q62468, Q67U26, Q6AYC4, Q6P9B6, Q7Z6J4, Q865V6, Q8BY35, Q8K045

Diamond homologs: A0A6B9KZ40, A8XV95, B8ATT7, F8WK50, O15195, O61270, O65570, O75366, O81643, O81644, O81645, O88398, O93510, P02640, P06396, P09327, P10733, P13020, P14885, P20305, P24452, P34268, P40121, Q07171, Q0J716, Q0JAD9, Q10L71, Q13045, Q21253, Q24020, Q24800, Q27319, Q28046, Q28372, Q29261, Q29297, Q3SX14, Q3SZP7, Q5ZIV9, Q60604

SIGNOR signaling

5 interactions.

A	Effect	B	Mechanism
CDX1	“up-regulates quantity by expression”	VIL1	“transcriptional regulation”
CDX2	“up-regulates quantity by expression”	VIL1	“transcriptional regulation”
SRC	“up-regulates activity”	VIL1	phosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	123
Likely benign	13
Benign	6

Top pathogenic / likely-pathogenic (0)

SpliceAI

2947 predictions. Top by Δscore:

Variant	Effect	Δscore
2:218423764:CCA:C	acceptor_loss	1.0000
2:218423766:A:AG	acceptor_gain	1.0000
2:218423767:G:A	acceptor_loss	1.0000
2:218423767:G:GG	acceptor_gain	1.0000
2:218423851:GAGGT:G	donor_loss	1.0000
2:218423855:T:G	donor_loss	1.0000
2:218424275:A:AG	acceptor_gain	1.0000
2:218424275:AG:A	acceptor_gain	1.0000
2:218424276:G:GT	acceptor_gain	1.0000
2:218424276:GG:G	acceptor_gain	1.0000
2:218424276:GGC:G	acceptor_gain	1.0000
2:218424276:GGCC:G	acceptor_gain	1.0000
2:218424276:GGCCA:G	acceptor_gain	1.0000
2:218424347:TGGCT:T	donor_gain	1.0000
2:218424348:GGCT:G	donor_gain	1.0000
2:218424348:GGCTG:G	donor_gain	1.0000
2:218424349:GCT:G	donor_gain	1.0000
2:218424349:GCTG:G	donor_gain	1.0000
2:218424350:CT:C	donor_gain	1.0000
2:218424351:TG:T	donor_loss	1.0000
2:218424352:G:GA	donor_loss	1.0000
2:218424352:G:GG	donor_gain	1.0000
2:218424353:T:A	donor_loss	1.0000
2:218425790:GC:G	donor_gain	1.0000
2:218427960:CTCA:C	acceptor_loss	1.0000
2:218427963:A:AG	acceptor_gain	1.0000
2:218427963:AG:A	acceptor_gain	1.0000
2:218427964:G:GG	acceptor_gain	1.0000
2:218427964:GG:G	acceptor_gain	1.0000
2:218428049:C:T	donor_gain	1.0000

AlphaMissense

5467 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:218429891:T:A	W298R	0.998
2:218429891:T:C	W298R	0.998
2:218434694:T:A	W557R	0.998
2:218434694:T:C	W557R	0.998
2:218428299:T:A	W177R	0.996
2:218428299:T:C	W177R	0.996
2:218432178:T:A	W446R	0.996
2:218432178:T:C	W446R	0.996
2:218435316:G:C	A570P	0.996
2:218429893:G:C	W298C	0.995
2:218429893:G:T	W298C	0.995
2:218430813:T:C	F346S	0.995
2:218434661:T:C	F546L	0.995
2:218434663:T:A	F546L	0.995
2:218434663:T:G	F546L	0.995
2:218434668:T:C	L548P	0.995
2:218434696:G:C	W557C	0.995
2:218434696:G:T	W557C	0.995
2:218434701:G:A	G559E	0.995
2:218434701:G:T	G559V	0.995
2:218435389:T:C	F594S	0.995
2:218437292:T:A	W714R	0.995
2:218437292:T:C	W714R	0.995
2:218428266:T:C	F166L	0.994
2:218428268:C:A	F166L	0.994
2:218428268:C:G	F166L	0.994
2:218430821:T:A	W349R	0.994
2:218430821:T:C	W349R	0.994
2:218434700:G:T	G559W	0.994
2:218429862:T:C	L288P	0.993

dbSNP variants (sampled 300 via entrez): RS1000036599 (2:218441314 G>A), RS1000394660 (2:218429037 A>G), RS1000562791 (2:218425141 C>T), RS1000754252 (2:218430118 G>T), RS1000785305 (2:218430428 G>A), RS1000823753 (2:218440570 T>A), RS1000879 (2:218439407 G>A), RS1000933675 (2:218424859 C>A,T), RS1001022922 (2:218419234 T>G), RS1001283018 (2:218420336 C>G,T), RS1001356194 (2:218420826 C>A), RS1001404840 (2:218423996 A>T), RS1001660471 (2:218436522 G>A), RS1001694662 (2:218435065 T>C), RS1001783240 (2:218443477 G>A)

Disease associations

OMIM: gene MIM:193040 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

8 associations (top):

Study	Trait	p-value
GCST004601_38	Red blood cell count	1.000000e-20
GCST006661_114	Male-pattern baldness	2.000000e-16
GCST008058_267	Estimated glomerular filtration rate	5.000000e-08
GCST008059_213	Estimated glomerular filtration rate	4.000000e-08
GCST008839_388	Height	1.000000e-22
GCST010988_127	Adult body size	5.000000e-10
GCST90002390_467	Mean corpuscular hemoglobin	7.000000e-14
GCST90020027_589	Waist-hip index	5.000000e-08

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004305	erythrocyte count
EFO:0004527	mean corpuscular hemoglobin
EFO:0007788	BMI-adjusted waist-hip ratio

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6066442 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases expression, increases methylation, affects expression	3
Cyclosporine	decreases expression	3
Acetaminophen	decreases expression	2
Silicon Dioxide	decreases expression, increases expression	2
Tetrachlorodibenzodioxin	increases expression	2
triphenyl phosphate	affects expression	1
bisphenol A	affects expression	1
deoxynivalenol	decreases expression	1
beta-lapachone	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
sodium arsenite	decreases expression	1
butyraldehyde	decreases expression	1
3,4,5,3’,4’-pentachlorobiphenyl	increases expression	1
arsenic acid	decreases expression	1
periodate-oxidized adenosine	affects expression	1
2-amino-3,8-dimethylimidazo(4,5-f)quinoxaline	decreases expression	1
cordycepin	affects expression	1
perfluoro-n-nonanoic acid	decreases expression	1
tanespimycin	increases expression	1
K 7174	decreases expression	1
abrine	decreases expression	1
ormosil	affects binding, decreases expression	1
5-(2,4-dihydroxy-5-isopropylphenyl)-4-(4-morpholin-4-ylmethylphenyl)isoxazole-3-carboxylic acid ethylamide	increases expression	1
STA 9090	increases expression	1
bis-N,N-dimethylamino-2-(N-methylpyrrolyl)methyl cyclopentadienyl titanium (IV)	decreases expression	1
(+)-JQ1 compound	decreases expression	1
theaflavin-3,3’-digallate	affects expression	1
Arsenic Trioxide	decreases expression	1
Troglitazone	decreases expression, increases expression	1
Air Pollutants	decreases 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
CHEMBL5652806	Binding	Binding affinity to human VIL1 incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Clinical trials (associated diseases)

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