ITGB6

integrin subunit beta 6, the group of Integrin beta subunits

Basic information

Region (hg38): 2:160099667-160271888

Links

ENSG00000115221NCBI:3694OMIM:147558HGNC:6161Uniprot:P18564AlphaFoldGenCCjaxSfariGnomADPubmedClinVar

Phenotypes

GenCC

Source: genCC

  • amelogenesis imperfecta type 1 (Supportive), mode of inheritance: AD
  • amelogenesis imperfecta, type 3A (Supportive), mode of inheritance: AD
  • amelogenesis imperfecta type 1H (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Amelogenesis imperfecta, type IHARGeneralGenetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testingDental24305999; 24319098

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ITGB6 gene.

  • Inborn_genetic_diseases (106 variants)
  • not_provided (39 variants)
  • Amelogenesis_imperfecta_type_1H (12 variants)
  • ITGB6-related_disorder (11 variants)
  • Prostate_cancer (1 variants)
  • Adolescent_alopeciam_dentogingival_abnormalitites_and_intellectual_disability (1 variants)
  • not_specified (1 variants)
  • Microcephaly (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ITGB6 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000000888.5. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

EffectPLPVUSLBBSum
synonymous
17
clinvar
9
clinvar
26
missense
3
clinvar
2
clinvar
110
clinvar
7
clinvar
3
clinvar
125
nonsense
2
clinvar
1
clinvar
3
start loss
0
frameshift
1
clinvar
1
splice donor/acceptor (+/-2bp)
0
Total 5 3 111 24 12

Highest pathogenic variant AF is 0.0000369412

Loading clinvar variants...

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
ITGB6protein_codingprotein_codingENST00000283249 15172223
pLI Probability
LOF Intolerant
pRec Probability
LOF Recessive
Individuals with
no LOFs
Individuals with
Homozygous LOFs
Individuals with
Heterozygous LOFs
Defined p
1.63e-220.0026412564301051257480.000418
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense-0.6944784371.090.00002355192
Missense in Polyphen197186.431.05672202
Synonymous-0.1891721691.020.00001041489
Loss of Function0.3943537.60.9310.00000188466

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.0006800.000680
Ashkenazi Jewish0.0005960.000595
East Asian0.0005450.000544
Finnish0.00004700.0000462
European (Non-Finnish)0.0005390.000528
Middle Eastern0.0005450.000544
South Asian0.0002680.000261
Other0.0001630.000163

dbNSFP

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.;
Pathway
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);Regulation of actin cytoskeleton - Homo sapiens (human);Hypertrophic cardiomyopathy (HCM) - Homo sapiens (human);Human papillomavirus infection - Homo sapiens (human);Integrin-mediated Cell Adhesion;Arrhythmogenic Right Ventricular Cardiomyopathy;miRNA targets in ECM and membrane receptors;Focal Adhesion;Focal Adhesion-PI3K-Akt-mTOR-signaling pathway;PI3K-Akt Signaling Pathway;TGF-beta Receptor Signaling;Integrin cell surface interactions;Extracellular matrix organization;Molecules associated with elastic fibres;Elastic fibre formation;Integrin;ECM proteoglycans;Beta5 beta6 beta7 and beta8 integrin cell surface interactions (Consensus)

Recessive Scores

pRec
0.259

Intolerance Scores

loftool
0.223
rvis_EVS
-0.59
rvis_percentile_EVS
18.23

Haploinsufficiency Scores

pHI
0.498
hipred
Y
hipred_score
0.602
ghis
0.432

Essentials

essential_gene_CRISPR
N
essential_gene_CRISPR2
N
essential_gene_gene_trap
N
gene_indispensability_pred
E
gene_indispensability_score
0.666

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium

Mouse Genome Informatics

Gene name
Itgb6
Phenotype
homeostasis/metabolism phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); immune system phenotype; hematopoietic system phenotype; respiratory system phenotype;

Gene ontology

Biological process
inflammatory response;cell adhesion;cell-matrix adhesion;integrin-mediated signaling pathway;cell migration;extracellular matrix organization;cell adhesion mediated by integrin;transforming growth factor-beta secretion;viral entry into host cell;regulation of transforming growth factor beta activation
Cellular component
nucleoplasm;centrosome;plasma membrane;focal adhesion;integrin complex;external side of plasma membrane;cell surface;cell junction;integrin alphav-beta6 complex;receptor complex
Molecular function
virus receptor activity;integrin binding;protein binding;signaling receptor activity