VILL

Summary

VILL (villin like, HGNC:30906) is a protein-coding gene on chromosome 3p22.2, encoding Villin-like protein (O15195). Possible tumor suppressor.

The protein encoded by this gene belongs to the villin/gelsolin family. It contains 6 gelsolin-like repeats and a headpiece domain. It may play a role in actin-bundling.

Source: NCBI Gene 50853 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 159 total
• MANE Select transcript: NM_015873

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30906
Approved symbol	VILL
Name	villin like
Location	3p22.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000136059
Ensembl biotype	protein_coding
OMIM	619666
Entrez	50853

Gene structure

Transcript identifiers

Ensembl transcripts: 31 — 25 protein_coding, 5 retained_intron, 1 nonsense_mediated_decay

ENST00000283713, ENST00000383759, ENST00000412008, ENST00000460040, ENST00000463080, ENST00000465644, ENST00000484717, ENST00000486616, ENST00000488209, ENST00000492491, ENST00000886992, ENST00000886993, ENST00000886994, ENST00000886995, ENST00000886996, ENST00000886997, ENST00000886998, ENST00000886999, ENST00000887000, ENST00000887001, ENST00000887002, ENST00000887003, ENST00000887004, ENST00000887005, ENST00000887006, ENST00000887007, ENST00000887008, ENST00000887009, ENST00000887010, ENST00000887011, ENST00000964665

RefSeq mRNA: 5 — MANE Select: NM_015873 NM_001370264, NM_001370265, NM_001385038, NM_001385039, NM_015873

CCDS: CCDS2670

Canonical transcript exons

ENST00000383759 — 20 exons

Exon	Start	End
ENSE00000923149	38006181	38006252
ENSE00001298643	38006449	38006700
ENSE00001307788	38004255	38004399
ENSE00001498517	37994261	37994466
ENSE00001498518	37993898	37993972
ENSE00001524723	38006942	38007185
ENSE00002028374	37993587	37993732
ENSE00003462749	37999339	37999439
ENSE00003473006	37998266	37998364
ENSE00003494243	38005792	38005974
ENSE00003540344	37998090	37998168
ENSE00003551372	37995739	37995847
ENSE00003552313	38001456	38001593
ENSE00003553818	38001702	38001860
ENSE00003582178	37998912	37999050
ENSE00003634499	38002396	38002575
ENSE00003666748	37997483	37997685
ENSE00003686788	38003168	38003313
ENSE00003786425	37997077	37997187
ENSE00003916426	37990786	37990829

Expression profiles

Bgee: expression breadth ubiquitous, 191 present calls, max score 96.94.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 5.8832 / max 202.7946, expressed in 1394 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
36088	4.6019	1333
36089	0.6204	73
36087	0.3798	86
36084	0.2236	47
36086	0.0289	16
36083	0.0146	8
36085	0.0141	6

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
mucosa of transverse colon	UBERON:0004991	96.94	gold quality
ileal mucosa	UBERON:0000331	94.94	gold quality
duodenum	UBERON:0002114	92.79	gold quality
rectum	UBERON:0001052	92.03	gold quality
transverse colon	UBERON:0001157	91.49	gold quality
small intestine Peyer’s patch	UBERON:0003454	91.42	gold quality
body of stomach	UBERON:0001161	90.93	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	90.85	gold quality
jejunal mucosa	UBERON:0000399	90.65	gold quality
small intestine	UBERON:0002108	90.32	gold quality
granulocyte	CL:0000094	90.13	gold quality
colonic mucosa	UBERON:0000317	89.68	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	89.67	gold quality
stomach	UBERON:0000945	89.24	gold quality
nasal cavity epithelium	UBERON:0005384	88.86	silver quality
epithelium of bronchus	UBERON:0002031	88.81	gold quality
mucosa of sigmoid colon	UBERON:0004993	88.39	gold quality
bronchial epithelial cell	CL:0002328	88.37	gold quality
bronchus	UBERON:0002185	88.14	gold quality
lower esophagus mucosa	UBERON:0035834	87.94	gold quality
gall bladder	UBERON:0002110	87.15	gold quality
intestine	UBERON:0000160	87.00	gold quality
mucosa of stomach	UBERON:0001199	86.72	gold quality
large intestine	UBERON:0000059	86.07	gold quality
colon	UBERON:0001155	86.06	gold quality
caudate nucleus	UBERON:0001873	86.03	gold quality
putamen	UBERON:0001874	84.63	gold quality
nucleus accumbens	UBERON:0001882	83.72	gold quality
nasal cavity mucosa	UBERON:0001826	83.39	gold quality
fundus of stomach	UBERON:0001160	83.08	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	9.22

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

7 targeting VILL, 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-3605-5P	99.96	67.12	932
HSA-MIR-4688	99.48	64.68	828
HSA-MIR-6743-5P	99.48	63.60	721
HSA-MIR-6829-5P	98.86	65.12	1480
HSA-MIR-615-5P	98.10	63.76	591
HSA-MIR-6734-5P	95.70	65.56	950
HSA-MIR-6789-5P	94.05	66.19	285

Literature-anchored findings (GeneRIF, showing 3)

• phospholipase C-gamma1 interaction with villin regulates epithelial cell migration (PMID:16921170)
• Brm is required for villin expression, a definitive marker of intestinal metaplasia and differentiation (PMID:18006815)
• Predicting the effect of a point mutation on a protein fold: the villin and advillin headpieces and their Pro62Ala mutants. (PMID:18022635)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	vill	ENSDARG00000001909
mus_musculus	Vill	ENSMUSG00000038775
rattus_norvegicus	Vill	ENSRNOG00000011446
drosophila_melanogaster	Gel	FBGN0010225
caenorhabditis_elegans		WBGENE00010593

Paralogs (7): SCIN (ENSG00000006747), CAPG (ENSG00000042493), VIL1 (ENSG00000127831), AVIL (ENSG00000135407), GSN (ENSG00000148180), FLII (ENSG00000177731), SVIL (ENSG00000197321)

Protein

Protein identifiers

Villin-like protein — O15195 (reviewed: O15195)

All UniProt accessions (4): O15195, D6R9H2, E9PFV5, H7BZ43

UniProt curated annotations — full annotation on UniProt →

Function. Possible tumor suppressor.

Tissue specificity. Ubiquitously expressed in 16 tissues examined.

Similarity. Belongs to the villin/gelsolin family.

Isoforms (2)

UniProt ID	Names	Canonical?
O15195-1	1	yes
O15195-2	2

RefSeq proteins (5): NP_001357193, NP_001357194, NP_001371967, NP_001371968, NP_056957* (*=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 (15 total): repeat 6, sequence variant 3, chain 1, splice variant 1, sequence conflict 1, domain 1, region of interest 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O15195-F1	82.48	0.54

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 0 (showing top):

GO Biological Process (5): actin polymerization or depolymerization (GO:0008154), actin filament severing (GO:0051014), barbed-end actin filament capping (GO:0051016), cytoskeleton organization (GO:0007010), actin filament capping (GO:0051693)

GO Molecular Function (4): structural constituent of cytoskeleton (GO:0005200), phosphatidylinositol-4,5-bisphosphate binding (GO:0005546), actin filament binding (GO:0051015), actin binding (GO:0003779)

GO Cellular Component (2): cytoplasm (GO:0005737), actin cytoskeleton (GO:0015629)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cytoskeleton	2
actin filament organization	1
actin filament-based process	1
actin filament capping	1
organelle organization	1
negative regulation of actin filament depolymerization	1
negative regulation of actin filament polymerization	1
structural molecule activity	1
cytoskeleton organization	1
phosphatidylinositol phosphate binding	1
phosphatidylinositol bisphosphate binding	1
actin binding	1
protein-containing complex binding	1
cytoskeletal protein binding	1
intracellular anatomical structure	1
cellular anatomical structure	1

Protein interactions and networks

STRING

556 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
VILL	SLC22A14	Q9Y267	527
VILL	CTDSPL	O15194	435
VILL	DLEC1	Q9Y238	388
VILL	SVIL	O95425	375
VILL	PLCD1	P51178	358
VILL	EXTL1	Q92935	348
VILL	KIF14	Q15058	343
VILL	DMTN	Q08495	342
VILL	PRR7	Q8TB68	338
VILL	EPM2AIP1	Q7L775	335
VILL	MIF4GD	A9UHW6	329
VILL	STARD9	Q9P2P6	325
VILL	TWF2	Q6IBS0	324
VILL	CHPT1	Q8WUD6	315
VILL	ABLIM1	O14639	315

IntAct

6 interactions, top by confidence:

A	B	Type	Score
ASAP2	VILL	psi-mi:“MI:0915”(physical association)	0.400
VILL	EIF3J	psi-mi:“MI:0915”(physical association)	0.400
M		psi-mi:“MI:0914”(association)	0.350
TBC1D14	TRAPPC13	psi-mi:“MI:0914”(association)	0.350
ZNF418	ZNF195	psi-mi:“MI:0914”(association)	0.350

BioGRID (8): HSPA8 (Affinity Capture-MS), TIMM13 (Affinity Capture-MS), HSPA6 (Affinity Capture-MS), EIF3J (Proximity Label-MS), VILL (Affinity Capture-MS), VILL (Affinity Capture-MS), VILL (Affinity Capture-MS), VILL (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

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	119
Likely benign	14
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

3590 predictions. Top by Δscore:

Variant	Effect	Δscore
3:37988239:G:GG	donor_gain	1.0000
3:37994467:G:GG	donor_gain	1.0000
3:37997065:T:TA	acceptor_gain	1.0000
3:37997066:G:A	acceptor_gain	1.0000
3:37997071:T:TA	acceptor_gain	1.0000
3:37997212:G:GT	donor_gain	1.0000
3:37997481:AG:A	acceptor_gain	1.0000
3:37997482:GG:G	acceptor_gain	1.0000
3:37997681:TACCA:T	donor_gain	1.0000
3:37997682:ACCA:A	donor_gain	1.0000
3:37997684:CA:C	donor_gain	1.0000
3:37997685:AGT:A	donor_loss	1.0000
3:37997686:GT:G	donor_loss	1.0000
3:37997686:GTGA:G	donor_gain	1.0000
3:37998908:CCA:C	acceptor_loss	1.0000
3:37998910:A:AG	acceptor_gain	1.0000
3:37998910:A:C	acceptor_loss	1.0000
3:37998910:AG:A	acceptor_gain	1.0000
3:37998910:AGG:A	acceptor_gain	1.0000
3:37998911:G:GA	acceptor_gain	1.0000
3:37998911:GG:G	acceptor_gain	1.0000
3:37998911:GGG:G	acceptor_gain	1.0000
3:37998911:GGGC:G	acceptor_gain	1.0000
3:37998911:GGGCT:G	acceptor_gain	1.0000
3:37999028:G:GT	donor_gain	1.0000
3:37999029:A:T	donor_gain	1.0000
3:37999034:G:GT	donor_gain	1.0000
3:37999038:C:G	donor_gain	1.0000
3:37999046:GAGGG:G	donor_gain	1.0000
3:37999048:GGG:G	donor_gain	1.0000

AlphaMissense

5651 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:38006996:T:C	F838L	0.986
3:38006998:C:A	F838L	0.986
3:38006998:C:G	F838L	0.986
3:38006963:T:C	F827L	0.976
3:38006965:C:A	F827L	0.976
3:38006965:C:G	F827L	0.976
3:37997149:T:A	W175R	0.973
3:37997149:T:C	W175R	0.973
3:38006997:T:C	F838S	0.960
3:38002564:T:A	W550R	0.959
3:38002564:T:C	W550R	0.959
3:38005801:T:A	W654R	0.957
3:38005801:T:C	W654R	0.957
3:38006964:T:C	F827S	0.957
3:38006989:G:C	K835N	0.955
3:38006989:G:T	K835N	0.955
3:38001588:T:A	W439R	0.954
3:38001588:T:C	W439R	0.954
3:38005945:T:C	F702L	0.953
3:38005947:C:A	F702L	0.953
3:38005947:C:G	F702L	0.953
3:37997089:T:A	W155R	0.952
3:37997089:T:C	W155R	0.952
3:38007034:A:C	K850N	0.952
3:38007034:A:T	K850N	0.952
3:37997116:T:C	F164L	0.951
3:37997118:C:A	F164L	0.951
3:37997118:C:G	F164L	0.951
3:37994314:G:C	W63C	0.946
3:37994314:G:T	W63C	0.946

dbSNP variants (sampled 300 via entrez): RS1000138794 (3:37995397 C>T), RS1000224253 (3:38004628 G>A,T), RS1000355847 (3:37998886 A>C,G), RS1000487286 (3:37992145 C>A), RS1000810317 (3:37998634 T>A), RS1000911337 (3:38003412 G>A), RS1001351402 (3:37986285 G>A), RS1001593158 (3:38005594 G>A), RS1001646324 (3:37992180 C>T), RS1001667941 (3:37998661 GCTCT>G,GCT), RS1001764507 (3:37999708 T>G), RS1001782974 (3:37991958 T>C,G), RS1001789774 (3:37986856 C>T), RS1002045452 (3:38005313 C>T), RS1002218488 (3:37987475 G>A)

Disease associations

OMIM: gene MIM:619666 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

26 total (human), top 26 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
perfluorooctane sulfonic acid	decreases expression, increases expression	2
aristolochic acid I	increases expression	1
GSK-J4	decreases expression	1
propionaldehyde	increases expression	1
bisphenol A	affects cotreatment, increases methylation	1
glycidyl methacrylate	decreases expression	1
arsenite	increases methylation	1
methylparaben	increases expression	1
butyraldehyde	increases expression	1
perfluorooctanoic acid	decreases expression	1
butylparaben	increases expression	1
perfluoro-n-nonanoic acid	decreases expression	1
perfluorohexanesulfonic acid	decreases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Cisplatin	increases expression	1
Estradiol	affects cotreatment, decreases expression	1
Selenium	increases expression	1
Silicon Dioxide	decreases expression	1
Smoke	decreases expression	1
Tobacco Smoke Pollution	affects expression	1
Tretinoin	increases expression	1
Urethane	decreases expression	1
Valproic Acid	increases methylation	1
Okadaic Acid	increases expression	1
Copper Sulfate	decreases expression	1

Clinical trials (associated diseases)

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