GeneBe

ITGB6

protein-coding

integrin subunit beta 6, the group of Integrin beta subunits

Gene summary

This gene encodes a protein that is a member of the integrin superfamily. Members of this family are adhesion receptors that function in signaling from the extracellular matrix to the cell. Integrins are heterodimeric integral membrane proteins composed of an alpha chain and a beta chain. The encoded protein forms a dimer with an alpha v chain and this heterodimer can bind to ligands like fibronectin and transforming growth factor beta 1. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Sep 2013]

MANE transcript

NM_000888.5

Inheritance

AR, AD

ClinVar variants

P:14U:145B:36

Top phenotype

Amelogenesis imperfecta, type IH

gnomAD constraint

pLI —, LoF o/e 0.93

Max pathogenic AF

—

Genomic locus

chr2:160,099,667-160,271,888

External References & Databases

Ensembl (ENSG00000115221)NCBI Gene (3694)OMIM (147558)HGNC:6161GenCCUniProt (P18564)AlphaFoldClinVar (ITGB6)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~172.2 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

amelogenesis imperfecta type 1HSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0014540

Submitter: Labcorp Genetics (formerly Invitae)

amelogenesis imperfecta type 1HSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0014540

Submitter: PanelApp Australia

amelogenesis imperfecta, type 3ASUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0007538

Submitter: Orphanet

amelogenesis imperfecta type 1SUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0015047

Submitter: Orphanet

Clinical Genomic Database (CGD)

Amelogenesis imperfecta, type IHAR

Manifestation: Dental

Intervention: General

Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing

Refs: 24305999; 24319098Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to ITGB6 variants in ClinVar

9 Conditions Cataloged
Inborn genetic diseasesTotal: 127
not providedTotal: 48
Amelogenesis imperfecta type 1HTotal: 16
ITGB6-related disorderTotal: 15
Amelogenesis imperfectaTotal: 4
not specifiedTotal: 4
Prostate cancerTotal: 1
Adolescent alopeciam dentogingival abnormalitites and intellectual disabilityTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_000888.5. 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
18
clinvar
8
clinvar
 28
missense
4
clinvar
1
clinvar
138
clinvar
8
clinvar
2
clinvar
 153
nonsense
3
clinvar
2
clinvar
2
clinvar
 7
start loss
0
frameshift
1
clinvar
1
clinvar
2
clinvar
 4
splice donor/acceptor (+/-2bp)
2
clinvar
1
clinvar
 3
Total861452610195

Highest pathogenic variant AF is 0.000036941212

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 44 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_000888.5RefSeqNP_000879.215MANE Select
ENST00000283249.7EnsemblENSP00000283249.215MANE Select
NM_001282353.2RefSeqNP_001269282.115Standard
NM_001282354.2RefSeqNP_001269283.113Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

  • PI3K-Akt signaling pathway - Homo sapiens (human)
  • ECM-receptor interaction - Homo sapiens (human)
  • Focal adhesion - Homo sapiens (human)
  • Dilated cardiomyopathy (DCM) - Homo sapiens (human)
  • Arrhythmogenic right ventricular cardiomyopathy (ARVC) - Homo sapiens (human)

Biological Process

  • inflammatory response
  • cell adhesion
  • cell-matrix adhesion
  • integrin-mediated signaling pathway
  • cell migration

Molecular Function

  • virus receptor activity
  • integrin binding
  • protein binding
  • signaling receptor activity

Cellular Component

  • nucleoplasm
  • centrosome
  • plasma membrane
  • focal adhesion
  • integrin complex

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000283249
Coding exons
15
Length
172223
Individuals with no LoFs
125643
Homozygous LoFs
0
Heterozygous LoFs
105
Defined
125748
p
0.000418
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense-0.6944784371.090.00002355192
Missense (PolyPhen)197186.431.05672202
Synonymous-0.1891721691.020.00001041489
Loss of Function0.3943537.60.9310.00000188466

Population LoF Frequency

PopulationCAFp-valueStatus
African0.000250.00025rare
Latino/Admixed American0.000430.00043rare
Ashkenazi Jewish0.000600.00060rare
East Asian0.000550.00054rare
Finnish0.0000470.000046rare
European (Non-Finnish)0.000540.00053rare
South Asian0.000270.00026rare
Other0.000160.00016rare

dbNSFP Gene Annotations

Source: dbNSFP

Function
FUNCTION: Integrin alpha-V:beta-6 (ITGAV:ITGB6) is a receptor for fibronectin and cytotactin (PubMed:17545607, PubMed:17158881). It recognizes the sequence R-G-D in its ligands (PubMed:17545607, PubMed:17158881). Internalisation of integrin alpha-V/beta-6 via clathrin-mediated endocytosis promotes carcinoma cell invasion (PubMed:17545607, PubMed:17158881). ITGAV:ITGB6 acts as a receptor for fibrillin-1 (FBN1) and mediates R-G-D-dependent cell adhesion to FBN1 (PubMed:17158881). Integrin alpha-V:beta-6 (ITGAV:ITGB6) 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:15184403, ECO:0000269|PubMed:17158881, ECO:0000269|PubMed:17545607, ECO:0000269|PubMed:22278742, ECO:0000269|PubMed:28117447}.; FUNCTION: (Microbial infection) Integrin ITGAV:ITGB6 acts as a receptor for Herpes simplex virus-1/HHV-1 (PubMed:24367260). {ECO:0000269|PubMed:24367260}.;
Disease
DISEASE: Amelogenesis imperfecta 1H (AI1H) [MIM:616221]: A disorder characterized by defective enamel formation, resulting in hypoplastic and hypomineralized tooth enamel that may be rough, pitted, and/or discolored. {ECO:0000269|PubMed:24305999, ECO:0000269|PubMed:24319098}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec
0.259

Intolerance Scores

LoFtool
0.223
RVIS EVS
-0.59
RVIS percentile EVS
18.23

Essentials

Essential (CRISPR)
N
Essential (CRISPR2)
N
Essential (gene trap)
N
Indispensability pred.
E
Indispensability score
0.666

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
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