ITGA8

integrin subunit alpha 8, the group of Integrin alpha subunits

Basic information

Region (hg38): 10:15513954-15719922

Links

ENSG00000077943 ∙ NCBI:8516 ∙ OMIM:604063 ∙ HGNC:6144 ∙ Uniprot:P53708 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• renal hypodysplasia/aplasia 1 (Strong), mode of inheritance: AR
• renal hypodysplasia/aplasia 1 (Strong), mode of inheritance: AR
• bilateral renal agenesis (Supportive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Renal hypodysplasia/aplasia 1	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	Renal	24439109

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ITGA8 gene.

• not provided (1 variants)
• Renal hypodysplasia/aplasia 1 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ITGA8 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	44	11	56
missense			107	9	6	122
nonsense		2				2
start loss						0
frameshift	2	1				3
inframe indel						0
splice donor/acceptor (+/-2bp)		3				3
splice region			2	8	1	11
non coding			2	15	82	99
Total	2	6	110	68	99

Variants in ITGA8

This is a list of pathogenic ClinVar variants found in the ITGA8 region.

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

Position	Type	Phenotype	Significance	ClinVar
10-15517161-T-C			Likely benign (Nov 01, 2022)
10-15517179-A-T		Inborn genetic diseases	Uncertain significance (Nov 16, 2021)
10-15517200-G-T			Benign (Jun 03, 2023)
10-15519283-A-G			Likely benign (Apr 07, 2018)
10-15519310-A-G			Likely benign (Apr 17, 2023)
10-15519316-C-T		Inborn genetic diseases	Conflicting classifications of pathogenicity (Oct 13, 2023)
10-15519317-G-A			Likely benign (Jul 26, 2018)
10-15519382-T-C		Inborn genetic diseases	Uncertain significance (Apr 07, 2023)
10-15519384-G-A		Inborn genetic diseases	Uncertain significance (Dec 27, 2022)
10-15531043-TACTC-T			Uncertain significance (Jul 16, 2021)
10-15531048-A-G		Renal hypodysplasia/aplasia 1	Pathogenic/Likely pathogenic (Jul 31, 2021)
10-15531051-A-G		Renal hypodysplasia/aplasia 1	Benign (Jan 30, 2024)
10-15531055-T-C		Renal hypodysplasia/aplasia 1	Benign/Likely benign (Jan 26, 2024)
10-15531057-C-T		Inborn genetic diseases	Uncertain significance (Feb 07, 2023)
10-15531106-C-T		Inborn genetic diseases	Uncertain significance (Jan 17, 2024)
10-15531111-A-G		Inborn genetic diseases	Uncertain significance (Sep 21, 2023)
10-15531206-T-C			Benign (Jun 20, 2021)
10-15531338-G-C			Benign (Nov 12, 2018)
10-15531367-G-A			Benign (Jun 20, 2021)
10-15531371-C-G			Benign (Jun 20, 2021)
10-15531399-T-C			Benign (Jun 20, 2021)
10-15531415-T-C			Benign (Jun 20, 2021)
10-15548145-G-A			Benign (Jun 20, 2021)
10-15548353-A-G			Benign (Jun 20, 2021)
10-15548373-G-T			Benign (Nov 12, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ITGA8	protein_coding	protein_coding	ENST00000378076	30	206177

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
6.08e-13	1.00	125672	0	76	125748	0.000302

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.272	593	575	1.03	0.0000296	6939
Missense in Polyphen		230	232.16	0.99072		2779
Synonymous	-0.996	234	215	1.09	0.0000124	2012
Loss of Function	3.74	31	63.0	0.492	0.00000329	742

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000719	0.000658
Ashkenazi Jewish	0.000201	0.000198
East Asian	0.000655	0.000653
Finnish	0.0000924	0.0000924
European (Non-Finnish)	0.000221	0.000220
Middle Eastern	0.000655	0.000653
South Asian	0.000558	0.000555
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Integrin alpha-8/beta-1 functions in the genesis of kidney and probably of other organs by regulating the recruitment of mesenchymal cells into epithelial structures. It recognizes the sequence R-G-D in a wide array of ligands including TNC, FN1, SPP1 TGFB1, TGFB3 and VTN. NPNT is probably its functional ligand in kidney genesis. Neuronal receptor for TNC it mediates cell-cell interactions and regulates neurite outgrowth of sensory and motor neurons. {ECO:0000269|PubMed:12415008, ECO:0000269|PubMed:15721307}.
• 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);Human papillomavirus infection - Homo sapiens (human);Integrin-mediated Cell Adhesion;Arrhythmogenic Right Ventricular Cardiomyopathy;Focal Adhesion;Focal Adhesion-PI3K-Akt-mTOR-signaling pathway;PI3K-Akt Signaling Pathway;Integrin cell surface interactions;Extracellular matrix organization;Molecules associated with elastic fibres;Elastic fibre formation;Integrin;Arf6 trafficking events;Plexin-D1 Signaling;ECM proteoglycans;Beta1 integrin cell surface interactions (Consensus)

Recessive Scores

• pRec: 0.190

Intolerance Scores

• rvis_EVS: -0.79
• rvis_percentile_EVS: 12.63

Haploinsufficiency Scores

• pHI: 0.193
• hipred: Y
• hipred_score: 0.737
• ghis: 0.605

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.877

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Itga8
• Phenotype: homeostasis/metabolism phenotype; cellular 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); hearing/vestibular/ear phenotype; renal/urinary system phenotype; skeleton phenotype; respiratory system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); 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)

Zebrafish Information Network

• Gene name: itga8
• Affected structure: neuromast hair cell
• Phenotype tag: abnormal
• Phenotype quality: decreased process quality

Gene ontology

• Biological process: metanephros development;kidney development;cell-matrix adhesion;integrin-mediated signaling pathway;brain development;memory;cell projection organization;extracellular matrix organization;positive regulation of transforming growth factor beta receptor signaling pathway;substrate adhesion-dependent cell spreading;inner ear morphogenesis;establishment of protein localization;mesodermal cell differentiation;smooth muscle tissue development;cell-cell adhesion;positive regulation of transcription from RNA polymerase II promoter involved in smooth muscle cell differentiation
• Cellular component: endoplasmic reticulum;plasma membrane;focal adhesion;integrin complex;cell surface;postsynaptic density;dendritic spine membrane;integrin alpha8-beta1 complex;perikaryon;apical part of cell
• Molecular function: metal ion binding