VIL1

protein-coding

villin 1, the group of Gelsolin/villins

Gene summary

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. [provided by RefSeq, Jul 2008]

Previous symbols:

MANE transcript

NM_007127.3

Inheritance

—

ClinVar variants

U:129B:15

Top phenotype

VIL1-related disorder

gnomAD constraint

pLI —, LoF o/e 0.63

Max pathogenic AF

—

Genomic locus

chr2:218,419,121-218,453,295

External References & Databases

Ensembl (ENSG00000127831)

Transcript & Mutation Effects

hg38 • Region Span ~34.2 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to VIL1 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 125

VIL1-related disorderTotal: 14

not providedTotal: 7

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_007127.3. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			1 clinvar	4 clinvar	1 clinvar	6
missense			125 clinvar	5 clinvar	5 clinvar	135
nonsense						0
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	129	9	6	144

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 38 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_007127.3	RefSeq	NP_009058.2	19	MANE Select
ENST00000248444.10	Ensembl	ENSP00000248444.5	19	MANE Select
ENST00000392114.6	Ensembl	ENSP00000375962.2	12	Standard
ENST00000392114.7	Ensembl	ENSP00000375962.2	12	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Regulation of Actin Cytoskeleton
IL2

Biological Process

intestinal D-glucose absorption
apoptotic process
epidermal growth factor receptor signaling pathway
regulation of cell shape
response to bacterium

Molecular Function

calcium ion binding
protein binding
phosphatidylinositol-4,5-bisphosphate binding
lysophosphatidic acid binding
identical protein binding

Cellular Component

ruffle
cytoplasm
plasma membrane
microvillus
brush border

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000248444
Coding exons: 19
Length: 34204
Individuals with no LoFs: 125638
Homozygous LoFs: 0
Heterozygous LoFs: 109
Defined: 125747
p: 0.000434

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.901	436	492	0.886	0.0000285	5439
Missense (PolyPhen)		128	153.08	0.83618		1767
Synonymous	0.346	197	203	0.969	0.0000129	1597
Loss of Function	2.32	29	45.9	0.631	0.00000231	489

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0013	0.0013	notable
Latino/Admixed American	0.00044	0.00043	rare
Ashkenazi Jewish	0.00010	0.000099	rare
East Asian	0.00027	0.00022	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.00035	0.00035	rare
South Asian	0.00073	0.00072	rare
Other	0.00082	0.00081	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: 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. {ECO:0000269|PubMed:11500485, ECO:0000269|PubMed:14594952, ECO:0000269|PubMed:15084600, ECO:0000269|PubMed:15272027, ECO:0000269|PubMed:15342783, ECO:0000269|PubMed:16921170, ECO:0000269|PubMed:17182858, ECO:0000269|PubMed:17229814, ECO:0000269|PubMed:17606613, ECO:0000269|PubMed:18054784, ECO:0000269|PubMed:18198174, ECO:0000269|PubMed:19808673, ECO:0000269|PubMed:3087992}.;
Disease: DISEASE: Note=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.;

Recessive Scores

pRec: 0.358

Intolerance Scores

LoFtool: 0.796
RVIS EVS: 0.21
RVIS percentile EVS: 67.54

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.924

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium