ITGA7

integrin subunit alpha 7, the group of Integrin alpha subunits

Basic information

Region (hg38): 12:55684567-55716404

Links

ENSG00000135424 ∙ NCBI:3679 ∙ OMIM:600536 ∙ HGNC:6143 ∙ Uniprot:Q13683 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• congenital merosin-deficient muscular dystrophy 1A (Definitive), mode of inheritance: AR
• congenital fiber-type disproportion myopathy (Supportive), mode of inheritance: AD
• congenital muscular dystrophy due to integrin alpha-7 deficiency (Supportive), mode of inheritance: AR
• congenital muscular dystrophy due to integrin alpha-7 deficiency (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Muscular dystrophy, congenital, due to integrin alpha-7 deficiency	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	Musculoskeletal; Neurologic	9590299; 19260934

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ITGA7 gene.

• Congenital muscular dystrophy due to integrin alpha-7 deficiency (777 variants)
• not provided (181 variants)
• not specified (70 variants)
• Inborn genetic diseases (56 variants)
• ITGA7-related condition (2 variants)
• Congenital Muscular Dystrophy, ITGA7-related (2 variants)
• Abnormal brain morphology (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ITGA7 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			6	168	9	183
missense			395	10	5	410
nonsense	9	10	1			20
start loss			1			1
frameshift	7	8	2			17
inframe indel			2			2
splice donor/acceptor (+/-2bp)		6				6
splice region			23	38	6	67
non coding			7	112	44	163
Total	16	24	414	290	58

Highest pathogenic variant AF is 0.0000657

Variants in ITGA7

This is a list of pathogenic ClinVar variants found in the ITGA7 region.

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

Position	Type	Phenotype	Significance	ClinVar
12-55684886-GA-G		Congenital Muscular Dystrophy, ITGA7-related	Uncertain significance (Jun 14, 2016)
12-55685063-C-T		Congenital muscular dystrophy due to integrin alpha-7 deficiency • not specified	Uncertain significance (Sep 26, 2023)
12-55685067-G-A		Congenital muscular dystrophy due to integrin alpha-7 deficiency	Likely benign (Jul 03, 2023)
12-55685067-G-C		Congenital muscular dystrophy due to integrin alpha-7 deficiency	Likely benign (Jan 23, 2020)
12-55685076-T-C		Congenital muscular dystrophy due to integrin alpha-7 deficiency	Likely benign (Jul 16, 2023)
12-55685078-G-C		Congenital muscular dystrophy due to integrin alpha-7 deficiency	Uncertain significance (Apr 06, 2022)
12-55685084-C-T		Congenital muscular dystrophy due to integrin alpha-7 deficiency	Uncertain significance (Aug 23, 2022)
12-55685085-A-G		Congenital muscular dystrophy due to integrin alpha-7 deficiency	Likely benign (Aug 09, 2022)
12-55685087-C-T		Congenital muscular dystrophy due to integrin alpha-7 deficiency	Uncertain significance (Sep 22, 2022)
12-55685088-G-A		not specified • Congenital muscular dystrophy due to integrin alpha-7 deficiency	Benign/Likely benign (Feb 01, 2024)
12-55685099-C-G		Congenital muscular dystrophy due to integrin alpha-7 deficiency • not specified	Uncertain significance (Oct 18, 2022)
12-55685099-C-T		Congenital muscular dystrophy due to integrin alpha-7 deficiency • not specified	Uncertain significance (Aug 10, 2023)
12-55685100-G-A		Congenital muscular dystrophy due to integrin alpha-7 deficiency	Likely benign (Nov 22, 2023)
12-55685108-C-T		Congenital muscular dystrophy due to integrin alpha-7 deficiency	Uncertain significance (Aug 10, 2022)
12-55685109-G-A		Congenital muscular dystrophy due to integrin alpha-7 deficiency	Likely benign (Dec 06, 2023)
12-55685117-C-T		Congenital muscular dystrophy due to integrin alpha-7 deficiency	Uncertain significance (Jan 28, 2022)
12-55685119-A-G		Congenital muscular dystrophy due to integrin alpha-7 deficiency	Uncertain significance (Feb 14, 2020)
12-55685123-T-C		Congenital muscular dystrophy due to integrin alpha-7 deficiency	Uncertain significance (Jul 17, 2022)
12-55685123-T-G		Congenital muscular dystrophy due to integrin alpha-7 deficiency	Uncertain significance (May 26, 2021)
12-55685124-G-A		Congenital muscular dystrophy due to integrin alpha-7 deficiency	Likely benign (Oct 13, 2022)
12-55685124-G-C		Congenital muscular dystrophy due to integrin alpha-7 deficiency	Likely benign (Jun 04, 2022)
12-55685130-T-G		Congenital muscular dystrophy due to integrin alpha-7 deficiency	Likely benign (Nov 28, 2023)
12-55685136-C-T		Congenital muscular dystrophy due to integrin alpha-7 deficiency	Likely benign (Jun 01, 2023)
12-55685137-G-A		Congenital muscular dystrophy due to integrin alpha-7 deficiency	Uncertain significance (Aug 31, 2022)
12-55685137-G-C		Congenital muscular dystrophy due to integrin alpha-7 deficiency	Uncertain significance (Sep 07, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ITGA7	protein_coding	protein_coding	ENST00000553804	25	31476

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
4.27e-17	0.994	125534	0	214	125748	0.000851

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.359	637	663	0.961	0.0000415	7337
Missense in Polyphen		206	224.83	0.91625		2491
Synonymous	0.273	275	281	0.979	0.0000173	2383
Loss of Function	2.83	36	59.5	0.605	0.00000349	618

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00123	0.00123
Ashkenazi Jewish	0.0000993	0.0000992
East Asian	0.00120	0.00120
Finnish	0.000421	0.000416
European (Non-Finnish)	0.00106	0.00105
Middle Eastern	0.00120	0.00120
South Asian	0.000785	0.000784
Other	0.00147	0.00147

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Integrin alpha-7/beta-1 is the primary laminin receptor on skeletal myoblasts and adult myofibers. During myogenic differentiation, it may induce changes in the shape and mobility of myoblasts, and facilitate their localization at laminin-rich sites of secondary fiber formation. It is involved in the maintenance of the myofibers cytoarchitecture as well as for their anchorage, viability and functional integrity. Isoform Alpha-7X2B and isoform Alpha-7X1B promote myoblast migration on laminin 1 and laminin 2/4, but isoform Alpha-7X1B is less active on laminin 1 (In vitro). Acts as Schwann cell receptor for laminin-2. Acts as a receptor of COMP and mediates its effect on vascular smooth muscle cells (VSMCs) maturation (By similarity). Required to promote contractile phenotype acquisition in differentiated airway smooth muscle (ASM) cells. {ECO:0000250, ECO:0000269|PubMed:10694445, ECO:0000269|PubMed:17641293, ECO:0000269|PubMed:9307969}.
• Disease: DISEASE: Muscular dystrophy congenital due to integrin alpha-7 deficiency (MDCI) [MIM:613204]: A form of congenital muscular dystrophy. Patients present at birth, or within the first few months of life, with hypotonia, muscle weakness and often with joint contractures. {ECO:0000269|PubMed:9590299}. 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;Focal Adhesion;Focal Adhesion-PI3K-Akt-mTOR-signaling pathway;PI3K-Akt Signaling Pathway;Integrin cell surface interactions;Laminin interactions;Extracellular matrix organization;Integrin;Arf6 trafficking events;Plexin-D1 Signaling;ECM proteoglycans;Beta1 integrin cell surface interactions (Consensus)

Recessive Scores

• pRec: 0.366

Intolerance Scores

• loftool: 0.935
• rvis_EVS: 0.17
• rvis_percentile_EVS: 65.35

Haploinsufficiency Scores

• pHI: 0.268
• hipred: Y
• hipred_score: 0.635
• ghis: 0.479

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.751

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Itga7
• Phenotype: growth/size/body region phenotype; cellular phenotype; homeostasis/metabolism phenotype; muscle 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); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); skeleton 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)

Zebrafish Information Network

• Gene name: itga7
• Affected structure: skeletal muscle cell
• Phenotype tag: abnormal
• Phenotype quality: retracted

Gene ontology

• Biological process: cell-matrix adhesion;integrin-mediated signaling pathway;muscle organ development;regulation of cell shape;extracellular matrix organization;heterotypic cell-cell adhesion;endodermal cell differentiation
• Cellular component: plasma membrane;integrin complex;cell surface
• Molecular function: protein binding;metal ion binding