ITGB6

integrin subunit beta 6, the group of Integrin beta subunits

Basic information

Region (hg38): 2:160099667-160271888

Links

ENSG00000115221 ∙ NCBI:3694 ∙ OMIM:147558 ∙ HGNC:6161 ∙ Uniprot:P18564 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

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

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Amelogenesis imperfecta, type IH	AR	General	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	Dental	24305999; 24319098

ClinVar

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

• Amelogenesis imperfecta type 1H (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.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				18	10	28
missense		1	50	5	3	59
nonsense	1		1			2
start loss						0
frameshift			1			1
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region		1		3	3	7
non coding					23	23
Total	1	1	52	23	36

Highest pathogenic variant AF is 0.00000657

Variants in ITGB6

This is a list of pathogenic ClinVar variants found in the ITGB6 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
2-160101634-T-C			Benign (Jun 19, 2021)
2-160101832-T-C			Benign (Dec 31, 2019)
2-160101834-C-T		Inborn genetic diseases	Uncertain significance (Apr 24, 2024)
2-160101838-GA-G		not specified • Amelogenesis imperfecta type 1H	Benign (Aug 19, 2021)
2-160101838-GAA-G		not specified	Benign (Jun 09, 2021)
2-160101948-A-T			Benign (Jun 19, 2021)
2-160101949-A-T			Benign (Jun 19, 2021)
2-160101974-A-G			Benign (Jun 20, 2021)
2-160107546-G-T			Benign (Jun 19, 2021)
2-160107548-A-G			Benign (Jun 19, 2021)
2-160107589-C-A			Benign (Jun 20, 2021)
2-160107701-C-T		Inborn genetic diseases	Uncertain significance (May 03, 2023)
2-160107702-G-T			Likely benign (May 18, 2018)
2-160107712-A-G			Likely benign (Feb 26, 2018)
2-160107777-C-G			Uncertain significance (Nov 05, 2019)
2-160107834-G-T		Inborn genetic diseases	Uncertain significance (Feb 23, 2023)
2-160107946-G-A			Benign (Nov 12, 2018)
2-160111767-A-G			Benign (Nov 12, 2018)
2-160111876-G-A			Benign (Jun 19, 2021)
2-160112097-T-G		Inborn genetic diseases	Uncertain significance (Feb 05, 2024)
2-160112101-T-A		Inborn genetic diseases	Uncertain significance (Mar 06, 2023)
2-160112117-A-G			Benign (Jun 09, 2021)
2-160112232-CA-C			Benign (Nov 12, 2018)
2-160112327-G-T			Benign (Jun 19, 2021)
2-160123802-C-A		Inborn genetic diseases	Uncertain significance (Sep 12, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ITGB6	protein_coding	protein_coding	ENST00000283249	15	172223

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.63e-22	0.00264	125643	0	105	125748	0.000418

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.694	478	437	1.09	0.0000235	5192
Missense in Polyphen		197	186.43	1.0567		2202
Synonymous	-0.189	172	169	1.02	0.0000104	1489
Loss of Function	0.394	35	37.6	0.931	0.00000188	466

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000680	0.000680
Ashkenazi Jewish	0.000596	0.000595
East Asian	0.000545	0.000544
Finnish	0.0000470	0.0000462
European (Non-Finnish)	0.000539	0.000528
Middle Eastern	0.000545	0.000544
South Asian	0.000268	0.000261
Other	0.000163	0.000163

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

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

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