ITGA6

integrin subunit alpha 6, the group of CD molecules|Integrin alpha subunits

Basic information

Region (hg38): 2:172234216-172506459

Links

ENSG00000091409 ∙ ∙ OMIM:147556 ∙ HGNC:6142 ∙ Uniprot:P23229 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• junctional epidermolysis bullosa with pyloric atresia (Limited), mode of inheritance: AD
• junctional epidermolysis bullosa with pyloric atresia (Strong), mode of inheritance: AR
• junctional epidermolysis bullosa with pyloric atresia (Strong), mode of inheritance: AR
• junctional epidermolysis bullosa with pyloric atresia (Strong), mode of inheritance: AR
• junctional epidermolysis bullosa with pyloric atresia (Supportive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Epidermolysis bullosa, junctional 6, with pyloric atresia	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	Dermatologic; Gastrointestinal	9185503; 9158140; 11251584; 20301336

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ITGA6 gene.

• not provided (23 variants)
• Junctional epidermolysis bullosa with pyloric atresia (2 variants)
• Junctional epidermolysis bullosa (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ITGA6 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			4	190	4	198
missense			79	7	5	91
nonsense	8	1	1			10
start loss						0
frameshift	18	1	1			20
inframe indel		1				1
splice donor/acceptor (+/-2bp)		9		1		10
splice region			3	33	5	41
non coding			37	153	63	253
Total	26	12	122	351	72

Highest pathogenic variant AF is 0.0000263

Variants in ITGA6

This is a list of pathogenic ClinVar variants found in the ITGA6 region.

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

Position	Type	Phenotype	Significance	ClinVar
2-172427633-G-A		Junctional epidermolysis bullosa with pyloric atresia	Uncertain significance (Jan 12, 2018)
2-172427651-G-A		Junctional epidermolysis bullosa with pyloric atresia	Benign (May 12, 2021)
2-172427667-C-T		Junctional epidermolysis bullosa with pyloric atresia	Uncertain significance (Jan 13, 2018)
2-172427761-C-A		Junctional epidermolysis bullosa with pyloric atresia	Uncertain significance (Jan 13, 2018)
2-172427775-C-G		Junctional epidermolysis bullosa with pyloric atresia	Benign (Jan 13, 2018)
2-172427794-C-T			Likely benign (Dec 21, 2023)
2-172427797-C-A			Likely benign (May 19, 2023)
2-172427798-G-A		Junctional epidermolysis bullosa with pyloric atresia	Likely benign (Jan 17, 2024)
2-172427800-C-G			Likely benign (Nov 28, 2023)
2-172427803-G-C			Likely benign (Jul 29, 2023)
2-172427807-C-T			Likely benign (Jun 09, 2023)
2-172427809-G-A			Likely benign (Feb 08, 2023)
2-172427812-C-T			Likely benign (Mar 04, 2023)
2-172427818-C-T			Likely benign (Apr 05, 2023)
2-172427827-G-C			Likely benign (Jul 10, 2023)
2-172427828-G-A		Inborn genetic diseases	Uncertain significance (Jun 05, 2024)
2-172427830-G-A			Likely benign (Jun 16, 2023)
2-172427843-C-T		Inborn genetic diseases	Uncertain significance (Sep 22, 2022)
2-172427848-C-T			Likely benign (Jan 21, 2024)
2-172427876-G-T			Pathogenic (Feb 21, 2023)
2-172427890-C-A			Likely benign (Jan 22, 2024)
2-172427890-C-T			Likely benign (Nov 13, 2023)
2-172427896-A-G			Likely benign (Oct 07, 2023)
2-172427905-C-T			Likely benign (Jan 20, 2023)
2-172427907-C-T		Inborn genetic diseases	Uncertain significance (Feb 21, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ITGA6	protein_coding	protein_coding	ENST00000409080	25	79100

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.90e-7	1.00	125685	0	63	125748	0.000251

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.65	463	574	0.807	0.0000318	7108
Missense in Polyphen		121	196.92	0.61445		2445
Synonymous	0.945	202	220	0.919	0.0000131	2088
Loss of Function	4.56	23	61.6	0.373	0.00000360	731

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000628	0.000539
Ashkenazi Jewish	0.0000992	0.0000992
East Asian	0.000282	0.000272
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.000304	0.000290
Middle Eastern	0.000282	0.000272
South Asian	0.000342	0.000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Integrin alpha-6/beta-1 is a receptor for laminin on platelets. Integrin alpha-6/beta-4 is a receptor for laminin in epithelial cells and it plays a critical structural role in the hemidesmosome (By similarity). ITGA6:ITGB4 binds to NRG1 (via EGF domain) and this binding is essential for NRG1-ERBB signaling (PubMed:20682778). ITGA6:ITGB4 binds to IGF1 and this binding is essential for IGF1 signaling (PubMed:22351760). ITGA6:ITGB4 binds to IGF2 and this binding is essential for IGF2 signaling (PubMed:28873464). {ECO:0000250|UniProtKB:Q61739, ECO:0000269|PubMed:20682778, ECO:0000269|PubMed:22351760, ECO:0000269|PubMed:28873464}.
• Disease: DISEASE: Epidermolysis bullosa letalis, with pyloric atresia (EB- PA) [MIM:226730]: An autosomal recessive, frequently lethal, epidermolysis bullosa with variable involvement of skin, nails, mucosa, and with variable effects on the digestive system. It is characterized by mucocutaneous fragility, aplasia cutis congenita, and gastrointestinal atresia, which most commonly affects the pylorus. Pyloric atresia is a primary manifestation rather than a scarring process secondary to epidermolysis bullosa. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: 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);Arrhythmogenic right ventricular cardiomyopathy (ARVC) - Homo sapiens (human);Small cell lung cancer - Homo sapiens (human);Regulation of actin cytoskeleton - Homo sapiens (human);Hypertrophic cardiomyopathy (HCM) - Homo sapiens (human);Toxoplasmosis - Homo sapiens (human);Pathways in cancer - Homo sapiens (human);Hematopoietic cell lineage - Homo sapiens (human);Human papillomavirus infection - Homo sapiens (human);Integrin-mediated Cell Adhesion;Arrhythmogenic Right Ventricular Cardiomyopathy;Alpha 6 Beta 4 signaling pathway;Focal Adhesion;Regulation of Apoptosis by Parathyroid Hormone-related Protein;Focal Adhesion-PI3K-Akt-mTOR-signaling pathway;PI3K-Akt Signaling Pathway;Ebola Virus Pathway on Host;Ebola Virus Pathway on Host;Assembly of collagen fibrils and other multimeric structures;Alpha6Beta4Integrin;Integrin cell surface interactions;Laminin interactions;Collagen formation;Extracellular matrix organization;Integrin;Cell surface interactions at the vascular wall;Hemostasis;a6b1 and a6b4 Integrin signaling;Arf6 trafficking events;Syndecan interactions;Plexin-D1 Signaling;Non-integrin membrane-ECM interactions;Basigin interactions;Type I hemidesmosome assembly;Cell junction organization;Cell-Cell communication;Validated targets of C-MYC transcriptional repression;Beta1 integrin cell surface interactions;Alpha6 beta4 integrin-ligand interactions (Consensus)

Recessive Scores

• pRec: 0.490

Intolerance Scores

• loftool: 0.608
• rvis_EVS: 0.25
• rvis_percentile_EVS: 69.66

Haploinsufficiency Scores

• pHI: 0.618
• hipred: Y
• hipred_score: 0.680
• ghis: 0.476

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.776

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Itga6
• 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); growth/size/body region phenotype; endocrine/exocrine gland phenotype; cellular phenotype; vision/eye phenotype; craniofacial phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); hematopoietic system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); neoplasm; embryo phenotype; respiratory system phenotype; immune system phenotype; renal/urinary system phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); limbs/digits/tail phenotype; digestive/alimentary phenotype

Zebrafish Information Network

• Gene name: itga6a
• Affected structure: whole organism
• Phenotype tag: abnormal
• Phenotype quality: decreased length

Gene ontology

• Biological process: cell-substrate junction assembly;cell-matrix adhesion;integrin-mediated signaling pathway;ectodermal cell differentiation;positive regulation of cell-substrate adhesion;positive regulation of cell-cell adhesion;extracellular matrix organization;positive regulation of cell migration;hemidesmosome assembly;cell-substrate adhesion;cellular response to extracellular stimulus;nail development;positive regulation of phosphorylation;positive regulation of apoptotic process;positive regulation of GTPase activity;skin development;positive regulation of transcription by RNA polymerase II;filopodium assembly;digestive tract development;brown fat cell differentiation;leukocyte migration;cellular response to organic cyclic compound;renal system development;amelogenesis;cell-cell adhesion;negative regulation of extrinsic apoptotic signaling pathway
• Cellular component: basement membrane;plasma membrane;cell-cell adherens junction;focal adhesion;external side of plasma membrane;basal plasma membrane;cell surface;hemidesmosome;filopodium;integrin alpha6-beta4 complex
• Molecular function: protein binding;insulin-like growth factor I binding;neuregulin binding;laminin binding;protein-containing complex binding;cadherin binding;metal ion binding