ITGA3

integrin subunit alpha 3, the group of Integrin alpha subunits|CD molecules

Basic information

Region (hg38): 17:50055968-50090481

Previous symbols: [ "MSK18" ]

Links

ENSG00000005884 ∙ NCBI:3675 ∙ OMIM:605025 ∙ HGNC:6139 ∙ Uniprot:P26006 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• pidermolysis bullosa, junctional 7, with interstitial lung disease and nephrotic syndrome (Definitive), mode of inheritance: AR
• pidermolysis bullosa, junctional 7, with interstitial lung disease and nephrotic syndrome (Strong), mode of inheritance: AR
• pidermolysis bullosa, junctional 7, with interstitial lung disease and nephrotic syndrome (Strong), mode of inheritance: AR
• pidermolysis bullosa, junctional 7, with interstitial lung disease and nephrotic syndrome (Strong), mode of inheritance: AR
• pidermolysis bullosa, junctional 7, with interstitial lung disease and nephrotic syndrome (Strong), mode of inheritance: AR
• pidermolysis bullosa, junctional 7, with interstitial lung disease and nephrotic syndrome (Supportive), mode of inheritance: AR
• pidermolysis bullosa, junctional 7, with interstitial lung disease and nephrotic syndrome (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Epidermolysis bullosa, junctional 7, with interstitial lung disease and nephrotic syndrome	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; Pulmonary; Renal	22512483; 25810266

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ITGA3 gene.

• not provided (1 variants)
• Pidermolysis bullosa, junctional 7, with interstitial lung disease and nephrotic syndrome (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ITGA3 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			1	72	7	80
missense		3	87	10	3	103
nonsense		4				4
start loss						0
frameshift	1	1				2
inframe indel						0
splice donor/acceptor (+/-2bp)	1	3	1			5
splice region			2	20		22
non coding			8	68	46	122
Total	2	11	97	150	56

Variants in ITGA3

This is a list of pathogenic ClinVar variants found in the ITGA3 region.

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

Position	Type	Phenotype	Significance	ClinVar
17-50056003-G-A			Likely benign (Mar 26, 2020)
17-50056099-G-C			Benign (Nov 12, 2018)
17-50056292-G-A			Likely benign (Mar 26, 2020)
17-50056445-C-T			Likely benign (Jul 03, 2023)
17-50056463-G-A			Likely benign (Aug 10, 2023)
17-50056476-C-A		Inborn genetic diseases	Uncertain significance (Nov 30, 2022)
17-50056516-G-C			Uncertain significance (Jun 13, 2022)
17-50056523-C-T		Epidermolysis bullosa, junctional 7, with interstitial lung disease and nephrotic syndrome	Likely benign (Oct 28, 2022)
17-50056524-G-A		Inborn genetic diseases	Uncertain significance (Dec 19, 2022)
17-50056545-G-T		ITGA3-related disorder	Uncertain significance (Aug 09, 2023)
17-50056571-G-T			Uncertain significance (Apr 07, 2022)
17-50056581-C-T			Uncertain significance (Jan 09, 2024)
17-50056583-G-C		ITGA3-related disorder	Likely benign (May 19, 2020)
17-50056585-G-A			Uncertain significance (Mar 10, 2022)
17-50056643-C-T			Likely benign (Dec 29, 2021)
17-50056858-T-A			Likely benign (Jan 05, 2021)
17-50056926-C-T			Likely benign (Mar 31, 2020)
17-50063970-G-A			Benign (Nov 12, 2018)
17-50064059-C-T		Epidermolysis bullosa, junctional 7, with interstitial lung disease and nephrotic syndrome	Benign/Likely benign (Jan 01, 2024)
17-50064062-C-T			Likely benign (Jul 20, 2023)
17-50064063-G-A			Benign (Oct 05, 2022)
17-50064092-C-T		Epidermolysis bullosa, junctional 7, with interstitial lung disease and nephrotic syndrome	Benign/Likely benign (Nov 07, 2023)
17-50064095-C-A			Likely benign (Aug 24, 2022)
17-50064095-C-T			Likely benign (Nov 24, 2023)
17-50064096-C-T		Inborn genetic diseases	Uncertain significance (May 31, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ITGA3	protein_coding	protein_coding	ENST00000007722	25	34514

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
3.55e-7	1.00	125691	0	57	125748	0.000227

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.36	469	637	0.737	0.0000387	6825
Missense in Polyphen		140	244.96	0.57153		2710
Synonymous	1.60	236	270	0.876	0.0000166	2191
Loss of Function	4.45	22	58.9	0.374	0.00000322	609

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00127	0.00127
Ashkenazi Jewish	0.00	0.00
East Asian	0.000331	0.000326
Finnish	0.0000467	0.0000462
European (Non-Finnish)	0.000153	0.000149
Middle Eastern	0.000331	0.000326
South Asian	0.000131	0.000131
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Integrin alpha-3/beta-1 is a receptor for fibronectin, laminin, collagen, epiligrin, thrombospondin and CSPG4. Integrin alpha-3/beta-1 provides a docking site for FAP (seprase) at invadopodia plasma membranes in a collagen-dependent manner and hence may participate in the adhesion, formation of invadopodia and matrix degradation processes, promoting cell invasion. Alpha- 3/beta-1 may mediate with LGALS3 the stimulation by CSPG4 of endothelial cells migration. {ECO:0000269|PubMed:10455171, ECO:0000269|PubMed:15181153}.
• Disease: DISEASE: Interstitial lung disease, nephrotic syndrome, and epidermolysis bullosa, congenital (ILNEB) [MIM:614748]: A multiorgan disorder characterized by congenital nephrotic syndrome, interstitial lung disease, and epidermolysis bullosa. The respiratory and renal features predominate, and lung involvement accounts for the lethal course of the disease. {ECO:0000269|PubMed:22512483, ECO:0000269|PubMed:27717396}. 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);Small cell lung cancer - Homo sapiens (human);Regulation of actin cytoskeleton - Homo sapiens (human);Hypertrophic cardiomyopathy (HCM) - 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;Primary Focal Segmental Glomerulosclerosis FSGS;Focal Adhesion;Focal Adhesion-PI3K-Akt-mTOR-signaling pathway;PI3K-Akt Signaling Pathway;Ebola Virus Pathway on Host;Ebola Virus Pathway on Host;Signal Transduction;Integrin cell surface interactions;Laminin interactions;Extracellular matrix organization;Integrin;EGFR1;Cell surface interactions at the vascular wall;Hemostasis;Validated transcriptional targets of TAp63 isoforms;Arf6 trafficking events;Plexin-D1 Signaling;Basigin interactions;MET activates PTK2 signaling;MET promotes cell motility;Signaling by MET;Signaling by Receptor Tyrosine Kinases;IL23-mediated signaling events;Validated transcriptional targets of deltaNp63 isoforms;Beta1 integrin cell surface interactions;Reelin signaling pathway;Urokinase-type plasminogen activator (uPA) and uPAR-mediated signaling (Consensus)

Recessive Scores

• pRec: 0.572

Intolerance Scores

• loftool: 0.713
• rvis_EVS: -0.88
• rvis_percentile_EVS: 10.56

Haploinsufficiency Scores

• pHI: 0.187
• hipred: Y
• hipred_score: 0.683
• ghis: 0.545

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.804

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Itga3
• Phenotype: endocrine/exocrine gland 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; cellular phenotype; homeostasis/metabolism phenotype; immune system phenotype; respiratory system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); embryo phenotype; neoplasm; 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); 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); vision/eye phenotype; limbs/digits/tail 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); digestive/alimentary phenotype; renal/urinary system phenotype

Zebrafish Information Network

• Gene name: itga3b
• Affected structure: melanocyte
• Phenotype tag: abnormal
• Phenotype quality: irregular spatial pattern

Gene ontology

• Biological process: neuron migration;cell-matrix adhesion;integrin-mediated signaling pathway;heart development;memory;positive regulation of gene expression;positive regulation of epithelial cell migration;positive regulation of cell-substrate adhesion;positive regulation of neuron projection development;regulation of transforming growth factor beta receptor signaling pathway;regulation of Wnt signaling pathway;extracellular matrix organization;lung development;regulation of BMP signaling pathway;negative regulation of cell projection organization;response to gonadotropin;negative regulation of Rho protein signal transduction;exploration behavior;response to drug;skin development;mesodermal cell differentiation;leukocyte migration;maternal process involved in female pregnancy;nephron development;dendritic spine maintenance;renal filtration;positive regulation of protein localization to plasma membrane
• Cellular component: plasma membrane;focal adhesion;integrin complex;external side of plasma membrane;cell surface;basolateral plasma membrane;filopodium membrane;integrin alpha3-beta1 complex;receptor complex;perinuclear region of cytoplasm;excitatory synapse;extracellular exosome;invadopodium membrane;cell periphery;synaptic membrane;growth cone filopodium
• Molecular function: fibronectin binding;protease binding;integrin binding;protein binding;collagen binding;protein domain specific binding;laminin binding;metal ion binding;protein heterodimerization activity