ITGA4

integrin subunit alpha 4, the group of CD molecules|Integrin alpha subunits

Basic information

Region (hg38): 2:181457201-181538940

Previous symbols: [ "CD49D" ]

Links

ENSG00000115232 ∙ NCBI:3676 ∙ OMIM:192975 ∙ HGNC:6140 ∙ Uniprot:P13612 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ITGA4 gene.

• not provided (61 variants)
• Retinitis pigmentosa (39 variants)
• Inborn genetic diseases (29 variants)
• Retinitis pigmentosa 26 (6 variants)
• Retinitis Pigmentosa, Recessive (6 variants)
• Retinal dystrophy (2 variants)
• not specified (1 variants)
• Isolated macular dystrophy (1 variants)
• Cone-rod dystrophy (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ITGA4 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				3	3	6
missense			24	3	1	28
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region				1	2	3
non coding		4	47	25	10	86
Total	0	4	71	31	14

Variants in ITGA4

This is a list of pathogenic ClinVar variants found in the ITGA4 region.

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

Position	Type	Phenotype	Significance	ClinVar
2-181457699-C-A			Likely benign (Jul 01, 2022)
2-181457703-C-T		not specified	Likely benign (Feb 02, 2024)
2-181457736-G-A		not specified	Uncertain significance (Feb 02, 2024)
2-181457736-G-T		not specified	Uncertain significance (Jun 06, 2023)
2-181457778-C-G		not specified	Uncertain significance (Jan 19, 2024)
2-181457797-A-G		not specified	Uncertain significance (Jan 16, 2024)
2-181458218-G-A		not specified	Uncertain significance (Feb 09, 2022)
2-181458296-A-G		not specified	Uncertain significance (Aug 17, 2022)
2-181474963-G-A		not specified	Uncertain significance (Jun 07, 2023)
2-181475034-T-C		not specified	Uncertain significance (Sep 27, 2021)
2-181475194-A-G		not specified	Likely benign (Apr 05, 2023)
2-181475278-G-A			Likely benign (Jul 19, 2018)
2-181480276-A-C			Benign (Apr 16, 2018)
2-181481638-T-C			Likely benign (Aug 20, 2018)
2-181482345-T-C			Benign (Oct 02, 2020)
2-181485875-A-G			Benign (Jul 23, 2018)
2-181485906-C-G		not specified	Uncertain significance (Sep 20, 2023)
2-181485913-C-T		ITGA4-related disorder	Likely benign (Apr 08, 2019)
2-181493336-G-A		not specified	Uncertain significance (Feb 26, 2024)
2-181493375-A-G		not specified	Uncertain significance (Nov 17, 2023)
2-181494819-A-G			Benign (Jul 23, 2018)
2-181495363-T-A		ITGA4-related disorder	Likely benign (Jun 05, 2019)
2-181495846-A-C		not specified	Likely benign (Dec 19, 2022)
2-181495898-T-C		not specified	Uncertain significance (Dec 28, 2022)
2-181498640-A-C		not specified	Uncertain significance (Jan 04, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ITGA4	protein_coding	protein_coding	ENST00000397033	28	78986

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.000101	1.00	124756	0	44	124800	0.000176

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.64	437	545	0.802	0.0000267	6780
Missense in Polyphen		105	201.13	0.52205		2552
Synonymous	-0.0562	199	198	1.01	0.0000104	1901
Loss of Function	4.73	18	56.3	0.320	0.00000259	741

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000636	0.000563
Ashkenazi Jewish	0.00	0.00
East Asian	0.000280	0.000278
Finnish	0.000142	0.000139
European (Non-Finnish)	0.000107	0.000106
Middle Eastern	0.000280	0.000278
South Asian	0.000295	0.000294
Other	0.000166	0.000165

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Integrins alpha-4/beta-1 (VLA-4) and alpha-4/beta-7 are receptors for fibronectin. They recognize one or more domains within the alternatively spliced CS-1 and CS-5 regions of fibronectin. They are also receptors for VCAM1. Integrin alpha- 4/beta-1 recognizes the sequence Q-I-D-S in VCAM1. Integrin alpha- 4/beta-7 is also a receptor for MADCAM1. It recognizes the sequence L-D-T in MADCAM1. On activated endothelial cells integrin VLA-4 triggers homotypic aggregation for most VLA-4-positive leukocyte cell lines. It may also participate in cytolytic T-cell interactions with target cells. ITGA4:ITGB1 binds to fractalkine (CX3CL1) and may act as its coreceptor in CX3CR1-dependent fractalkine signaling (PubMed:23125415). ITGA4:ITGB1 binds to PLA2G2A via a site (site 2) which is distinct from the classical ligand-binding site (site 1) and this induces integrin conformational changes and enhanced ligand binding to site 1 (PubMed:18635536, PubMed:25398877). {ECO:0000269|PubMed:18635536, ECO:0000269|PubMed:19064666, ECO:0000269|PubMed:23125415, ECO:0000269|PubMed:25398877}.
• 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);Regulation of actin cytoskeleton - Homo sapiens (human);Hypertrophic cardiomyopathy (HCM) - Homo sapiens (human);Leishmaniasis - Homo sapiens (human);Hematopoietic cell lineage - Homo sapiens (human);Intestinal immune network for IgA production - Homo sapiens (human);Human papillomavirus infection - Homo sapiens (human);Leukocyte transendothelial migration - Homo sapiens (human);Integrin-mediated Cell Adhesion;Arrhythmogenic Right Ventricular Cardiomyopathy;Focal Adhesion;Focal Adhesion-PI3K-Akt-mTOR-signaling pathway;Transcriptional regulation by RUNX3;PI3K-Akt Signaling Pathway;Ebola Virus Pathway on Host;Ebola Virus Pathway on Host;RUNX3 Regulates Immune Response and Cell Migration;Gene expression (Transcription);Transcriptional regulation by RUNX3;Generic Transcription Pathway;Integrin cell surface interactions;RNA Polymerase II Transcription;Extracellular matrix organization;Immune System;Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell;Adaptive Immune System;Integrin;Cell surface interactions at the vascular wall;Hemostasis;VEGFR3 signaling in lymphatic endothelium;Arf6 trafficking events;Plexin-D1 Signaling;a4b7 Integrin signaling;Beta5 beta6 beta7 and beta8 integrin cell surface interactions;Beta1 integrin cell surface interactions;Alpha4 beta1 integrin signaling events (Consensus)

Recessive Scores

• pRec: 0.476

Intolerance Scores

• loftool: 0.697
• rvis_EVS: -0.62
• rvis_percentile_EVS: 17.4

Haploinsufficiency Scores

• pHI: 0.375
• hipred: Y
• hipred_score: 0.747
• ghis: 0.592

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.788

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Itga4
• Phenotype: cellular 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); 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); hematopoietic system phenotype; embryo phenotype; immune system phenotype

Gene ontology

• Biological process: cell-matrix adhesion involved in ameboidal cell migration;leukocyte cell-cell adhesion;cell-matrix adhesion;integrin-mediated signaling pathway;B cell differentiation;extracellular matrix organization;heterotypic cell-cell adhesion;substrate adhesion-dependent cell spreading;endodermal cell differentiation;receptor clustering;regulation of immune response;leukocyte migration;leukocyte tethering or rolling;diapedesis;axonogenesis involved in innervation;cellular response to cytokine stimulus;negative regulation of protein homodimerization activity;positive regulation of leukocyte tethering or rolling;positive regulation of vascular endothelial cell proliferation;neuron projection extension;clathrin-dependent extracellular exosome endocytosis;positive regulation of endothelial cell apoptotic process;positive regulation of T cell migration
• Cellular component: plasma membrane;focal adhesion;cell surface;membrane;growth cone;integrin alpha4-beta7 complex;neuronal cell body;extracellular exosome
• Molecular function: fibronectin binding;protein binding;coreceptor activity;C-X3-C chemokine binding;metal ion binding;cell adhesion molecule binding;protein antigen binding