ITGA7

protein-coding

integrin subunit alpha 7, the group of Integrin alpha subunits

Gene summary

The protein encoded by this gene belongs to the integrin alpha chain family. Integrins are heterodimeric integral membrane proteins composed of an alpha chain and a beta chain. They mediate a wide spectrum of cell-cell and cell-matrix interactions, and thus play a role in cell migration, morphologic development, differentiation, and metastasis. This protein functions as a receptor for the basement membrane protein laminin-1. It is mainly expressed in skeletal and cardiac muscles and may be involved in differentiation and migration processes during myogenesis. Defects in this gene are associated with congenital myopathy. Alternatively spliced transcript variants encoding different isoforms have been noted for this gene. [provided by RefSeq, Feb 2009]

MANE transcript

NM_002206.3

Inheritance

AR, AD

ClinVar variants

P:70U:473B:280

Top phenotype

Muscular dystrophy, congenital, due to integrin alpha-7 deficiency

gnomAD constraint

pLI —, LoF o/e 0.6

Max pathogenic AF

—

Genomic locus

chr12:55,684,568-55,716,404

External References & Databases

Ensembl (ENSG00000135424)

Transcript & Mutation Effects

hg38 • Region Span ~31.8 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

congenital muscular dystrophy due to integrin alpha-7 deficiencyMODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0013177

Submitter: G2P

congenital fiber-type disproportion myopathySUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0009711

Submitter: Orphanet

congenital muscular dystrophy due to integrin alpha-7 deficiencySUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0013177

Submitter: Orphanet

congenital muscular dystrophy due to integrin alpha-7 deficiencySTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0013177

Submitter: Labcorp Genetics (formerly Invitae)

congenital muscular dystrophy due to integrin alpha-7 deficiencySTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0013177

Submitter: PanelApp Australia

Clinical Genomic Database (CGD)

Muscular dystrophy, congenital, due to integrin alpha-7 deficiencyAR

Manifestation: Musculoskeletal; Neurologic

Intervention: General

Rationale: 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

Refs: 9590299; 19260934

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to ITGA7 variants in ClinVar

5 Conditions Cataloged

Congenital muscular dystrophy due to integrin alpha-7 deficiencyTotal: 938

not specifiedTotal: 248

not providedTotal: 199

ITGA7-related disorderTotal: 40

Abnormal brain morphologyTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_002206.3. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			8 clinvar	247 clinvar	5 clinvar	260
missense		1 clinvar	456 clinvar	26 clinvar	2 clinvar	485
nonsense	8 clinvar	15 clinvar	1 clinvar			24
start loss			1 clinvar			1
frameshift	17 clinvar	15 clinvar	1 clinvar			33
splice donor/acceptor (+/-2bp)	2 clinvar	12 clinvar	6 clinvar			20
Total	27	43	473	273	7	823

Highest pathogenic variant AF is 0.000095412164

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 80 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_002206.3	RefSeq	NP_002197.2	25	MANE Select
ENST00000257879.11	Ensembl	ENSP00000257879.7	25	MANE Select
NM_001144996.2	RefSeq	NP_001138468.1	25	Standard
NM_001144997.2	RefSeq	NP_001138469.1	25	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
itga7	Danio rerio	Structure: skeletal muscle cell Quality: retracted abnormal

Gene / Model

Organism

Observed Phenotype

itga7

Danio rerio

Structure: skeletal muscle cell

Quality: retracted

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

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)

Biological Process

cell-matrix adhesion
integrin-mediated signaling pathway
muscle organ development
regulation of cell shape
extracellular matrix organization

Molecular Function

protein binding
metal ion binding

Cellular Component

plasma membrane
integrin complex
cell surface

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000553804
Coding exons: 25
Length: 31476
Individuals with no LoFs: 125534
Homozygous LoFs: 0
Heterozygous LoFs: 214
Defined: 125748
p: 0.000851

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.359	637	663	0.961	0.0000415	7337
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00068	0.00068	rare
Latino/Admixed American	0.00055	0.00055	rare
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0.0012	0.0012	notable
Finnish	0.00042	0.00042	rare
European (Non-Finnish)	0.0011	0.0010	notable
South Asian	0.00079	0.00078	rare
Other	0.0015	0.0015	notable

dbNSFP Gene Annotations

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.;

Recessive Scores

pRec: 0.366

Intolerance Scores

LoFtool: 0.935
RVIS EVS: 0.17
RVIS percentile EVS: 65.35

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.751

Gene Damage Prediction

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