GeneBe

ITGAV

protein-coding

integrin subunit alpha V, the group of Integrin alpha subunits|CD molecules

Gene summary

The product of this gene belongs to the integrin alpha chain family. Integrins are heterodimeric integral membrane proteins composed of an alpha subunit and a beta subunit that function in cell surface adhesion and signaling. The encoded preproprotein is proteolytically processed to generate light and heavy chains that comprise the alpha V subunit. This subunit associates with beta 1, beta 3, beta 5, beta 6 and beta 8 subunits. The heterodimer consisting of alpha V and beta 3 subunits is also known as the vitronectin receptor. This integrin may regulate angiogenesis and cancer progression. Alternative splicing results in multiple transcript variants. Note that the integrin alpha 5 and integrin alpha V subunits are encoded by distinct genes. [provided by RefSeq, Oct 2015]

Previous symbols:
  • VNRA
  • MSK8
  • VTNR

MANE transcript

NM_002210.5

Inheritance

—

ClinVar variants

P:6U:163B:14

Top phenotype

ITGAV-related disorder

gnomAD constraint

pLI —, LoF o/e 0.3

Max pathogenic AF

—

Genomic locus

chr2:186,590,010-186,680,901

External References & Databases

Ensembl (ENSG00000138448)NCBI Gene (3685)OMIM (193210)HGNC:6150GenCCUniProt (P06756)AlphaFoldClinVar (ITGAV)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~90.9 kb
Loading mutation effect viewer...

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 ITGAV variants in ClinVar

6 Conditions Cataloged
not specifiedTotal: 142
not providedTotal: 11
ITGAV-related disorderTotal: 11
ITGAV deficiencyTotal: 4
Immune dysregulation, neurodevelopmental defects, and colitisTotal: 4
Susceptibility to severe COVID-19Total: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_002210.5. 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.

EffectPLPVUSLBBSum
synonymous
2
clinvar
6
clinvar
4
clinvar
 12
missense
2
clinvar
148
clinvar
4
clinvar
 154
nonsense
1
clinvar
 1
start loss
0
frameshift
0
splice donor/acceptor (+/-2bp)
1
clinvar
3
clinvar
12
clinvar
 16
Total33163104183

Highest pathogenic variant AF is 0.000004105124

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 37 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_002210.5RefSeqNP_002201.230MANE Select
ENST00000261023.8EnsemblENSP00000261023.330MANE Select
NM_001144999.3RefSeqNP_001138471.230Standard
NM_001145000.3RefSeqNP_001138472.228Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / ModelOrganismObserved Phenotype
itgavDanio rerio

Structure: caudal vein plexus

Quality: decreased diameter

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

  • PI3K-Akt signaling pathway - Homo sapiens (human)
  • Cell adhesion molecules (CAMs) - Homo sapiens (human)
  • ECM-receptor interaction - Homo sapiens (human)
  • Focal adhesion - Homo sapiens (human)
  • Dilated cardiomyopathy (DCM) - Homo sapiens (human)

Biological Process

  • angiogenesis
  • vasculogenesis
  • antigen processing and presentation of exogenous peptide antigen via MHC class I, TAP-dependent
  • cell adhesion
  • cell-matrix adhesion

Molecular Function

  • virus receptor activity
  • opsonin binding
  • fibronectin binding
  • protease binding
  • protein kinase C binding

Cellular Component

  • cytosol
  • plasma membrane
  • integral component of plasma membrane
  • focal adhesion
  • integrin complex

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000261023
Coding exons
30
Length
90837
Individuals with no LoFs
125712
Homozygous LoFs
0
Heterozygous LoFs
36
Defined
125748
p
0.000143
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense0.8885055640.8950.00002896825
Missense (PolyPhen)173224.120.771912769
Synonymous0.4411952030.9610.00001052009
Loss of Function5.131962.90.3020.00000325749

Population LoF Frequency

PopulationCAFp-valueStatus
African0.0000730.000062rare
Latino/Admixed American0.000210.00020rare
Ashkenazi Jewish0.0000990.000099rare
East Asian0.0000540.000054rare
Finnish0.0000460.000046rare
European (Non-Finnish)0.000160.00016rare
South Asian0.000130.00013rare
Other0.000490.00049rare

dbNSFP Gene Annotations

Source: dbNSFP

Function
FUNCTION: The alpha-V (ITGAV) integrins are receptors for vitronectin, cytotactin, fibronectin, fibrinogen, laminin, matrix metalloproteinase-2, osteopontin, osteomodulin, prothrombin, thrombospondin and vWF. They recognize the sequence R-G-D in a wide array of ligands. ITGAV:ITGB3 binds to fractalkine (CX3CL1) and may act as its coreceptor in CX3CR1-dependent fractalkine signaling (PubMed:23125415). ITGAV:ITGB3 binds to NRG1 (via EGF domain) and this binding is essential for NRG1-ERBB signaling (PubMed:20682778). ITGAV:ITGB3 binds to FGF1 and this binding is essential for FGF1 signaling (PubMed:18441324). ITGAV:ITGB3 binds to FGF2 and this binding is essential for FGF2 signaling (PubMed:28302677). ITGAV:ITGB3 binds to IGF1 and this binding is essential for IGF1 signaling (PubMed:19578119). ITGAV:ITGB3 binds to IGF2 and this binding is essential for IGF2 signaling (PubMed:28873464). ITGAV:ITGB3 binds to IL1B and this binding is essential for IL1B signaling (PubMed:29030430). ITGAV:ITGB3 binds to PLA2G2A via a site (site 2) which is distinct from the classical ligand-binding site (site 1) and this induces integrin conformational changes and enhanced ligand binding to site 1 (PubMed:18635536, PubMed:25398877). ITGAV:ITGB3 and ITGAV:ITGB6 act as a receptor for fibrillin-1 (FBN1) and mediate R-G-D- dependent cell adhesion to FBN1 (PubMed:12807887, PubMed:17158881). Integrin alpha-V/beta-6 or alpha-V/beta-8 (ITGAV:ITGB6 or ITGAV:ITGB8) mediates R-G-D-dependent release of transforming growth factor beta-1 (TGF-beta-1) from regulatory Latency-associated peptide (LAP), thereby playing a key role in TGF-beta-1 activation (PubMed:15184403, PubMed:22278742, PubMed:28117447). {ECO:0000269|PubMed:12807887, ECO:0000269|PubMed:15184403, ECO:0000269|PubMed:17158881, ECO:0000269|PubMed:18441324, ECO:0000269|PubMed:18635536, ECO:0000269|PubMed:19578119, ECO:0000269|PubMed:20682778, ECO:0000269|PubMed:22278742, ECO:0000269|PubMed:23125415, ECO:0000269|PubMed:25398877, ECO:0000269|PubMed:28117447, ECO:0000269|PubMed:28302677, ECO:0000269|PubMed:28873464, ECO:0000269|PubMed:29030430}.; FUNCTION: (Microbial infection) Integrin ITGAV:ITGB5 and ITGAV:ITGB3 act as receptors for Coxsackievirus A9 and B1. {ECO:0000269|PubMed:15194773, ECO:0000269|PubMed:7519807, ECO:0000269|PubMed:9426447}.; FUNCTION: (Microbial infection) Integrin ITGAV:ITGB6 acts as a receptor for herpes simplex 1/HHV-1. {ECO:0000269|PubMed:24367260}.; FUNCTION: (Microbial infection) Integrin ITGAV:ITGB3 acts as a receptor for West nile virus. {ECO:0000269|PubMed:23658209}.;

Recessive Scores

pRec
0.598

Intolerance Scores

LoFtool
0.178
RVIS EVS
-1.48
RVIS percentile EVS
3.69

Essentials

Essential (CRISPR)
N
Essential (CRISPR2)
E
Essential (gene trap)
H
Indispensability pred.
E
Indispensability score
0.844

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
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