ITGA7

Summary

ITGA7 (integrin subunit alpha 7, HGNC:6143) is a protein-coding gene on chromosome 12q13.2, encoding Integrin alpha-7 (Q13683). Integrin alpha-7/beta-1 is the primary laminin receptor on skeletal myoblasts and adult myofibers.

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.

Source: NCBI Gene 3679 — RefSeq curated summary.

At a glance

• Gene–disease (curated): congenital muscular dystrophy due to integrin alpha-7 deficiency (Strong, GenCC) — +1 more curated relationship
• GWAS associations: 2
• Clinical variants (ClinVar): 1,073 total — 27 pathogenic, 22 likely-pathogenic
• Phenotypes (HPO): 71
• MANE Select transcript: NM_002206

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6143
Approved symbol	ITGA7
Name	integrin subunit alpha 7
Location	12q13.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000135424
Ensembl biotype	protein_coding
OMIM	600536
Entrez	3679

Gene structure

Transcript identifiers

Ensembl transcripts: 57 — 38 protein_coding, 9 retained_intron, 9 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000257879, ENST00000347027, ENST00000452168, ENST00000553276, ENST00000553737, ENST00000553804, ENST00000553893, ENST00000554327, ENST00000554359, ENST00000554543, ENST00000554724, ENST00000555687, ENST00000555728, ENST00000555809, ENST00000556273, ENST00000556371, ENST00000557058, ENST00000557257, ENST00000557488, ENST00000557555, ENST00000686981, ENST00000687390, ENST00000688413, ENST00000689678, ENST00000691052, ENST00000691846, ENST00000691973, ENST00000888129, ENST00000888132, ENST00000888133, ENST00000888135, ENST00000888136, ENST00000888137, ENST00000888138, ENST00000888139, ENST00000888141, ENST00000888142, ENST00000888144, ENST00000888145, ENST00000888146, ENST00000888147, ENST00000888148, ENST00000888149, ENST00000888150, ENST00000888151, ENST00000888152, ENST00000888153, ENST00000912204, ENST00000912205, ENST00000945415, ENST00000945416, ENST00000945417, ENST00000945418, ENST00000945419, ENST00000945420, ENST00000945421, ENST00000945422

RefSeq mRNA: 14 — MANE Select: NM_002206 NM_001144996, NM_001144997, NM_001367993, NM_001367994, NM_001374465, NM_001410977, NM_001414029, NM_001414030, NM_001414031, NM_001414032, NM_001414033, NM_001414034, NM_001414035, NM_002206

CCDS: CCDS44914, CCDS55832, CCDS8888, CCDS91703, CCDS91704

Canonical transcript exons

ENST00000257879 — 25 exons

Exon	Start	End
ENSE00000920106	55698383	55698576
ENSE00000920111	55697695	55697822
ENSE00000920112	55697451	55697546
ENSE00000920115	55697216	55697277
ENSE00000920117	55696899	55697068
ENSE00000920118	55696283	55696432
ENSE00000920121	55695522	55695637
ENSE00000920122	55694778	55694970
ENSE00003468249	55688202	55688300
ENSE00003479538	55693141	55693317
ENSE00003485322	55687971	55688096
ENSE00003495424	55694443	55694522
ENSE00003523541	55697938	55698026
ENSE00003558864	55699870	55699989
ENSE00003564484	55688844	55688957
ENSE00003577977	55702872	55702951
ENSE00003596092	55700899	55701154
ENSE00003613380	55694021	55694123
ENSE00003621501	55698710	55698917
ENSE00003634743	55703051	55703178
ENSE00003665810	55692844	55692975
ENSE00003669776	55694615	55694695
ENSE00003681034	55694256	55694330
ENSE00003900554	55684568	55685288
ENSE00003902802	55707477	55707904

Expression profiles

Bgee: expression breadth ubiquitous, 270 present calls, max score 99.32.

FANTOM5 (CAGE): breadth broad, TPM avg 5.8827 / max 289.9253, expressed in 807 samples.

FANTOM5 promoters (12 alternative TSS)

Promoter ID	TPM avg	Samples expressed
131399	4.0982	769
131402	0.7685	123
131405	0.3921	73
131409	0.1713	36
131406	0.1195	37
206736	0.0999	41
131408	0.0845	40
131404	0.0574	32
206737	0.0356	19
131407	0.0251	16

Top tissues by expression

294 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
apex of heart	UBERON:0002098	99.32	gold quality
right coronary artery	UBERON:0001625	99.23	gold quality
descending thoracic aorta	UBERON:0002345	99.18	gold quality
right atrium auricular region	UBERON:0006631	99.16	gold quality
thoracic aorta	UBERON:0001515	99.14	gold quality
ascending aorta	UBERON:0001496	99.13	gold quality
aorta	UBERON:0000947	99.08	gold quality
saphenous vein	UBERON:0007318	99.08	gold quality
popliteal artery	UBERON:0002250	99.07	gold quality
tibial artery	UBERON:0007610	99.07	gold quality
heart left ventricle	UBERON:0002084	99.04	gold quality
cardiac atrium	UBERON:0002081	99.03	gold quality
lower esophagus muscularis layer	UBERON:0035833	99.03	gold quality
cardiac ventricle	UBERON:0002082	98.99	gold quality
lower esophagus	UBERON:0013473	98.99	gold quality
coronary artery	UBERON:0001621	98.98	gold quality
left coronary artery	UBERON:0001626	98.97	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	98.91	gold quality
hindlimb stylopod muscle	UBERON:0004252	98.77	gold quality
adipose tissue of abdominal region	UBERON:0007808	98.70	gold quality
omental fat pad	UBERON:0010414	98.69	gold quality
peripheral nervous system	UBERON:0000010	98.68	gold quality
heart	UBERON:0000948	98.68	gold quality
tibial nerve	UBERON:0001323	98.68	gold quality
subcutaneous adipose tissue	UBERON:0002190	98.68	gold quality
peritoneum	UBERON:0002358	98.64	gold quality
adipose tissue	UBERON:0001013	98.60	gold quality
left uterine tube	UBERON:0001303	98.55	gold quality
gastrocnemius	UBERON:0001388	98.50	gold quality
muscle layer of sigmoid colon	UBERON:0035805	98.49	gold quality

Single-cell (SCXA)

Detected in 8 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-MTAB-7037	yes	54.96
E-GEOD-134144	yes	9.12
E-MTAB-6678	no	1301.37
E-GEOD-130473	no	947.45
E-MTAB-6379	no	282.92
E-MTAB-6386	no	20.65
E-GEOD-81547	no	5.32
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ATF3, EEF1D, ITGB8, MYC, MYOD1, MYOG

miRNA regulators (miRDB)

45 targeting ITGA7, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-6748-5P	100.00	65.81	1057
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-6768-5P	99.92	67.36	1942
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-4271	99.88	68.32	2244
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-3121-3P	99.82	71.96	3630
HSA-MIR-4319	99.76	69.83	2586
HSA-MIR-6745	99.74	65.33	1321
HSA-MIR-6766-5P	99.68	67.70	2325
HSA-MIR-3202	99.66	67.70	2737
HSA-MIR-7156-5P	99.64	68.81	1369
HSA-MIR-4499	99.62	67.29	1470
HSA-MIR-497-3P	99.61	69.71	1990
HSA-MIR-7106-5P	99.53	67.47	3574
HSA-MIR-4672	99.50	71.58	2893
HSA-MIR-6727-3P	99.49	65.92	1333
HSA-MIR-363-5P	99.46	64.51	1015
HSA-MIR-4273	99.45	67.93	1206
HSA-MIR-372-5P	99.41	69.11	2299
HSA-MIR-4722-3P	99.35	65.22	1099
HSA-MIR-7515	99.31	68.22	1795
HSA-MIR-8085	99.28	67.56	2362
HSA-MIR-6731-5P	99.28	67.42	2375
HSA-MIR-4505	99.27	67.81	2678
HSA-MIR-6739-3P	99.22	68.84	1843
HSA-MIR-5787	99.22	67.86	2628

Literature-anchored findings (GeneRIF, showing 38)

• conclude that secondary integrin alpha 7 deficiency is rather common in muscular dystrophy/myopathy of unknown etiology (PMID:12057917)
• FHL2 and FHL3, respectively, are colocalized with alpha(7)beta(1) integrin receptor at the periphery of Z-discs, suggesting a role in mechanical stabilization of muscle cells (PMID:15117962)
• alpha7-expressing fetal myoblasts are capable of differentiation to osteoblast lineage with a coordinated switch in integrin profiles and may represent a mechanism that promotes homing and recruitment of myogenic stem cells for tissue remodeling. (PMID:17054947)
• Integrin alpha7 mutations are associated with prostate cancer, liver cancer, glioblastoma multiforme, and leiomyosarcoma (PMID:17551147)
• analysis of how distinct acidic clusters and hydrophobic residues in the alternative splice domains X1 and X2 of alpha7 integrins define specificity for laminin isoforms (PMID:17618648)
• Alpha7B is a novel marker of the contractile phenotype, and alpha7 expression is essential for human airway smooth muscle cell maturation, which is a laminin-dependent process. (PMID:17641293)
• cleavage is a novel mechanism that regulates alpha7 integrin functions in skeletal muscle, and that the generation of such cleavage sites is another evolutionary mechanism for expanding and modifying protein functions. (PMID:18940796)
• laminin-111 (alpha(1), beta(1), gamma(1)), which is expressed during embryonic development but absent in normal or dystrophic skeletal muscle, increased alpha(7)-integrin expression in mouse and DMD patient myoblasts (PMID:19416897)
• ILK interaction with MCM7 and MCM7 phosphorylation may be a critical event in ITGA7 signaling pathway, leading to tumor suppression. (PMID:20460506)
• This report provides a novel insight into the mechanism, involving interaction with high temperature requirement A2, by which ITGA7 acts as a tumor suppressor. (PMID:20651226)
• Digenic mutational inheritance of the integrin alpha 7 and the myosin heavy chain 7B genes causes congenital myopathy with left ventricular non-compact cardiomyopathy. [ITGA7] (PMID:23800289)
• ITGA7 binds to tissue inhibitor of metalloproteinase 3 (TIMP3) in prostate cancer cells. (PMID:23830872)
• Alpha7beta1D integrin modifies Ca2+ regulatory pathways and offers a means to protect the myocardium from ischemic injury. (PMID:24091324)
• The absence of either alpha7beta1 integrin or alpha6beta1 integrin impairs the ability of Schwann cells to spread and to bind laminin. (PMID:24227711)
• Data suggest that ITGA7 is an epigenetically regulated tumour suppressor gene and a prognostic factor in human malignant pleural mesothelioma. (PMID:26011651)
• Taken together, these results further support the use of a7 integrin as a potential therapy for Duchenne muscular dystrophy (PMID:26076707)
• Data indicate that S100 calcium binding protein P (S100P) increased lung cancer cell migration by binding integrin alpha7. (PMID:26320193)
• As knockdown of Integrin alpha7 (ITGA7) can effectively reduce the stemness of oesophageal squamous cell carcinoma (OSCC) cells, ITGA7 could be a potential therapeutic target in OSCC treatment. (PMID:27924820)
• targeting of ITGA7 by RNAi or blocking mAbs impaired laminin-induced signaling, and it led to a significant delay in tumor engraftment plus a strong reduction in tumor size and invasion. (PMID:28602620)
• we identified forkhead box C1 (FOXC1) as a novel regulator of colorectal cancer metastases. FOXC1 directly binds its target genes integrin alpha7 (ITGA7) and fibroblast growth factor receptor 4 (FGFR4) and activates their expression (PMID:29884889)
• circITGA7 inhibits the proliferation and metastasis of colorectal cancer cells by suppressing the Ras signalling pathway and promoting the transcription of ITGA7. (PMID:29943828)
• Speculate that the postnatal splicing of alpha7A to alpha7B and of beta1A to beta1D integrins is delayed, altering spontaneous descent of the testes in the first months of life. (PMID:30089289)
• Integrin alpha7 expression is increased in asthmatic patients and its inhibition reduces Kras protein abundance in airway smooth muscle cells. (PMID:31289310)
• Overexpression of ITGA7 is associated with breast cancer. (PMID:31325216)
• Overexpression of ITGA7 is associated with non-small-cell lung cancer. (PMID:31418948)
• Integrin alpha 7 correlates with poor clinical outcomes, and it regulates cell proliferation, apoptosis and stemness via PTK2-PI3K-Akt signaling pathway in hepatocellular carcinoma. (PMID:31698037)
• Integrin alpha7 is overexpressed and correlates with higher pathological grade, increased T stage, advanced TNM stage as well as worse survival in clear cell renal cell carcinoma patients: A retrospective study. (PMID:31713264)
• Integrin alpha7 correlates with worse clinical features and prognosis, and its knockdown inhibits cell proliferation and stemness in tongue squamous cell carcinoma. (PMID:31789398)
• Predictive value of integrin alpha7 for acute myeloid leukemia risk and its correlation with prognosis in acute myeloid leukemia patients. (PMID:31855276)
• Downregulating integrin subunit alpha 7 (ITGA7) promotes proliferation, invasion, and migration of papillary thyroid carcinoma cells through regulating epithelial-to-mesenchymal transition. (PMID:31942970)
• Transcriptome profiles of stem-like cells from primary breast cancers allow identification of ITGA7 as a predictive marker of chemotherapy response. (PMID:34253873)
• ITGA7 relates to disease risk, pathological feature, treatment response and survival in Ph(-) acute lymphoblastic leukemia. (PMID:34743543)
• Decrease in ITGA7 Levels Is Associated with an Increase in alpha-Synuclein Levels in an MPTP-Induced Parkinson’s Disease Mouse Model and SH-SY5Y Cells. (PMID:34884422)
• ITGA7, CD133, ALDH1 are inter-correlated, and linked with poor differentiation, lymph node metastasis as well as worse survival in surgical cervical cancer. (PMID:35194895)
• The relationship among integrin alpha 7, CD133 and Nestin as well as their correlation with clinicopathological features and prognosis in astrocytoma patients. (PMID:35430343)
• Integrin alpha7 Mutations Are Associated With Adult-Onset Cardiac Dysfunction in Humans and Mice. (PMID:36444867)
• ITGA7 loss drives the differentiation of adipose-derived mesenchymal stem cells to cancer-associated fibroblasts. (PMID:38174862)
• CircITGA7 regulates malignant phenotypes in bladder cancer cells via targeting miR-330-3p/KLF10 axis. (PMID:38523597)

Cross-species orthologs

10 orthologs

Organism	Symbol	Gene ID
danio_rerio		ENSDARG00000109859
mus_musculus	Itga7	ENSMUSG00000025348
rattus_norvegicus	Itga7	ENSRNOG00000007905
drosophila_melanogaster	if	FBGN0001250
drosophila_melanogaster	mew	FBGN0004456
drosophila_melanogaster	ItgaPS4	FBGN0034005
drosophila_melanogaster	ItgaPS5	FBGN0034880
drosophila_melanogaster	scb	FBGN0286785
caenorhabditis_elegans		WBGENE00002081
caenorhabditis_elegans		WBGENE00003929

Paralogs (17): ITGAL (ENSG00000005844), ITGA3 (ENSG00000005884), ITGA2B (ENSG00000005961), ITGA8 (ENSG00000077943), ITGAE (ENSG00000083457), ITGA6 (ENSG00000091409), ITGA4 (ENSG00000115232), ITGA11 (ENSG00000137809), ITGAV (ENSG00000138448), ITGAX (ENSG00000140678), ITGA10 (ENSG00000143127), ITGA9 (ENSG00000144668), ITGAD (ENSG00000156886), ITGA5 (ENSG00000161638), ITGA2 (ENSG00000164171), ITGAM (ENSG00000169896), ITGA1 (ENSG00000213949)

Protein

Protein identifiers

Integrin alpha-7 — Q13683 (reviewed: Q13683)

All UniProt accessions (12): A0A8I5KSX0, A0A8I5KXI3, A0A8I5QJA5, Q13683, G3V2C6, G3V2I4, G3V2Q6, G3V3L8, H0YJ26, H0YJ98, H0YJS5, J3KNV4

UniProt curated annotations — full annotation on UniProt →

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 a Schwann cell receptor for laminin-2. Acts as a receptor of COMP and mediates its effect on vascular smooth muscle cells (VSMCs) maturation. Required to promote contractile phenotype acquisition in differentiated airway smooth muscle (ASM) cells.

Subunit / interactions. Heterodimer of an alpha and a beta subunit. The alpha subunit is composed of a heavy and a light chain linked by a disulfide bond. Alpha-7 associates with beta-1. Interacts with COMP. Interacts (via C-terminus intracellular tail region) with CIB1; the interaction is stabilized/increased in a calcium- and magnesium-dependent manner.

Subcellular location. Membrane.

Tissue specificity. Isoforms containing segment A are predominantly expressed in skeletal muscle. Isoforms containing segment B are abundantly expressed in skeletal muscle, moderately in cardiac muscle, small intestine, colon, ovary and prostate and weakly in lung and testes. Isoforms containing segment X2D are expressed at low levels in fetal and adult skeletal muscle and in cardiac muscle, but are not detected in myoblasts and myotubes. In muscle fibers isoforms containing segment A and B are expressed at myotendinous and neuromuscular junctions; isoforms containing segment C are expressed at neuromuscular junctions and at extrasynaptic sites. Isoforms containing segments X1 or X2 or, at low levels, X1X2 are expressed in fetal and adult skeletal muscle (myoblasts and myotubes) and cardiac muscle.

Post-translational modifications. ADP-ribosylated on at least two sites of the extracellular domain in skeletal myotubes. A 70 kDa form is created by proteolytic cleavage. Cleavage is elevated during myogenic differentiation and the cleaved form enhances cell adhesion and spreading on laminin.

Disease relevance. 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. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the integrin alpha chain family.

Isoforms (6)

UniProt ID	Names	Canonical?
Q13683-1	Alpha-7X1X2B	yes
Q13683-3	Alpha-7X1B
Q13683-7	Alpha-7X2B
Q13683-9	Alpha-7X2DB
Q13683-10	Alpha-7X1X2A
Q13683-13	2

RefSeq proteins (14): NP_001138468, NP_001138469, NP_001354922, NP_001354923, NP_001361394, NP_001397906, NP_001400958, NP_001400959, NP_001400960, NP_001400961, NP_001400962, NP_001400963, NP_001400964, NP_002197* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000413	Integrin_alpha	Family
IPR013517	FG-GAP	Repeat
IPR013519	Int_alpha_beta-p	Repeat
IPR013649	Integrin_alpha_Ig-like_1	Domain
IPR018184	Integrin_alpha_C_CS	Conserved_site
IPR028994	Integrin_alpha_N	Homologous_superfamily
IPR032695	Integrin_dom_sf	Homologous_superfamily
IPR048285	Integrin_alpha_Ig-like_2	Domain
IPR048286	Integrin_alpha_Ig-like_3	Domain

Pfam: PF01839, PF08441, PF20805, PF20806

UniProt features (65 total): binding site 13, repeat 10, disulfide bond 9, splice variant 6, glycosylation site 5, sequence variant 5, chain 4, region of interest 3, sequence conflict 3, topological domain 2, signal peptide 1, short sequence motif 1, compositionally biased region 1, site 1, transmembrane region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q13683-F1	79.14	0.45

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (1): 647–648 (cleavage; by urokinase)

Ligand- & substrate-binding residues (13): 372; 374; 376; 380; 434; 436; 438; 442; 492; 494; 496; 498 …

Disulfide bonds (9): 94–103, 140–163, 184–197, 539–546, 552–615, 681–687, 781–792, 939–994, 1001–1006

Glycosylation sites (5): 86, 786, 989, 1025, 1045

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-216083	Integrin cell surface interactions
R-HSA-3000157	Laminin interactions
R-HSA-3000178	ECM proteoglycans
R-HSA-1474244	Extracellular matrix organization

MSigDB gene sets: 408 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_COLON_TUMORAL_MACROPHAGE_DN, CHIBA_RESPONSE_TO_TSA_UP, GOBP_REGULATION_OF_CELL_MORPHOGENESIS, GOBP_FORMATION_OF_PRIMARY_GERM_LAYER, GCANCTGNY_MYOD_Q6, GOCC_CELL_SURFACE, SMID_BREAST_CANCER_RELAPSE_IN_LUNG_DN, TGACCTY_ERR1_Q2, MEF2_02, NKX61_01, MODULE_66, GOBP_CELL_CELL_ADHESION, GTGCCTT_MIR506, GOBP_LEUKOCYTE_MIGRATION, NKX62_Q2

GO Biological Process (10): cell-matrix adhesion (GO:0007160), integrin-mediated signaling pathway (GO:0007229), muscle organ development (GO:0007517), regulation of cell shape (GO:0008360), heterotypic cell-cell adhesion (GO:0034113), endodermal cell differentiation (GO:0035987), leukocyte migration (GO:0050900), cell-cell adhesion (GO:0098609), cell adhesion (GO:0007155), cell-substrate adhesion (GO:0031589)

GO Molecular Function (3): signaling receptor activity (GO:0038023), metal ion binding (GO:0046872), protein binding (GO:0005515)

GO Cellular Component (4): plasma membrane (GO:0005886), integrin complex (GO:0008305), cell surface (GO:0009986), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Extracellular matrix organization	3

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cell adhesion	2
cellular anatomical structure	2
cell-substrate adhesion	1
cell surface receptor signaling pathway	1
animal organ development	1
muscle structure development	1
regulation of cell morphogenesis	1
regulation of biological quality	1
cell-cell adhesion	1
endoderm formation	1
cell differentiation	1
immune system process	1
cell migration	1
cellular process	1
molecular transducer activity	1
cation binding	1
binding	1
membrane	1
cell periphery	1
protein complex involved in cell adhesion	1
plasma membrane signaling receptor complex	1

Protein interactions and networks

STRING

1422 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ITGA7	ITGB1	P05556	933
ITGA7	NMRK2	Q9NPI5	760
ITGA7	UTRN	P46939	756
ITGA7	ADAM12	O43184	712
ITGA7	LAMA2	P24043	711
ITGA7	DAG1	Q14118	709
ITGA7	DMD	P11532	703
ITGA7	FN1	P02751	700
ITGA7	MYL6B	P14649	695
ITGA7	NMRK1	Q9NWW6	693
ITGA7	ITGB5	P18084	690
ITGA7	ITGB4	P16144	685
ITGA7	LAMA4	Q16363	682
ITGA7	SGCD	Q92629	654
ITGA7	TIMP3	P35625	608

IntAct

123 interactions, top by confidence:

A	B	Type	Score
TNFSF13B	IPO8	psi-mi:“MI:0914”(association)	0.640
CA10	WDHD1	psi-mi:“MI:0914”(association)	0.640
TRDN	TMEM223	psi-mi:“MI:0914”(association)	0.640
PSG8	PEX7	psi-mi:“MI:0914”(association)	0.530
TSPAN11	IGLL5	psi-mi:“MI:0914”(association)	0.530
DEFA1	MANBA	psi-mi:“MI:0914”(association)	0.530
CD1E	SUSD5	psi-mi:“MI:0914”(association)	0.530
LGALS1	PODXL	psi-mi:“MI:0914”(association)	0.530
CLGN	NPC1	psi-mi:“MI:0914”(association)	0.530
TMED6	SMPD2	psi-mi:“MI:0914”(association)	0.530
DNAJC3	DEDD	psi-mi:“MI:0914”(association)	0.530
FHL2	ITGA7	psi-mi:“MI:0915”(physical association)	0.510
PCNA	ITGA7	psi-mi:“MI:0915”(physical association)	0.370
LGALS8	SLC22A23	psi-mi:“MI:0914”(association)	0.350
BTNL8	TMEM131L	psi-mi:“MI:0914”(association)	0.350
DKKL1	VWA8	psi-mi:“MI:0914”(association)	0.350
SUSD4	CCDC85C	psi-mi:“MI:0914”(association)	0.350
TMPRSS11B		psi-mi:“MI:0914”(association)	0.350
TMED6	UPK3BL1	psi-mi:“MI:0914”(association)	0.350
TAZ	MANBA	psi-mi:“MI:0914”(association)	0.350
PCDH20		psi-mi:“MI:0914”(association)	0.350
SLAMF1	RTCA	psi-mi:“MI:0914”(association)	0.350
ST8SIA4	NRP1	psi-mi:“MI:0914”(association)	0.350
IL17RC	C2CD2L	psi-mi:“MI:0914”(association)	0.350
PCDHGA5	MAP2K7	psi-mi:“MI:0914”(association)	0.350

BioGRID (144): ITGA7 (Affinity Capture-MS), ITGA7 (Affinity Capture-MS), ITGA7 (Affinity Capture-MS), ITGA7 (Affinity Capture-MS), ITGA7 (Affinity Capture-MS), ITGA7 (Affinity Capture-MS), ITGA7 (Affinity Capture-MS), ITGA7 (Affinity Capture-MS), ITGA7 (Affinity Capture-MS), ITGA7 (Affinity Capture-MS), ITGA7 (Affinity Capture-MS), ITGA7 (Affinity Capture-MS), ITGA7 (Affinity Capture-MS), ITGA7 (Affinity Capture-MS), ITGA7 (Affinity Capture-MS)

ESM2 similar proteins: A2ARA8, B0S5N4, B8JK39, F1MMS9, O08665, P05555, P06756, P08514, P08648, P11215, P11688, P13612, P17301, P17852, P18564, P20701, P23229, P24063, P26006, P26007, P26008, P26009, P38570, P43406, P53708, P53710, P53711, P61622, P61625, P80746, Q00651, Q06274, Q13683, Q13797, Q60677, Q61738, Q61739, Q62469, Q62470, Q63258

Diamond homologs: F1MMS9, P05555, P17852, P23229, P26006, P26007, P80108, P80109, Q13683, Q61738, Q61739, Q62470, Q63258, Q8R2H5, A2ARA8, O70362, O75578, P08514, P08648, P11688, P12080, P20701, P26009, P34446, P38570, P53708, Q00651, Q06274, Q13797, Q24247, Q27977, Q60677, Q91687, Q9QUM0, Q9W1M8, P13612, A2AX52, A6H584, A6NMZ7, B8JK39

SIGNOR signaling

5 interactions.

A	Effect	B	Mechanism
ITGA7	“form complex”	“a7/b1 integrin”	binding
MYOD1	“up-regulates quantity by expression”	ITGA7	“transcriptional regulation”
MYOG	“up-regulates quantity by expression”	ITGA7	“transcriptional regulation”
MYC	“down-regulates quantity by repression”	ITGA7	“transcriptional regulation”
EEF1D	“down-regulates quantity by repression”	ITGA7	“transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

1073 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	27
Likely pathogenic	22
Uncertain significance	463
Likely benign	412
Benign	71

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1072319	NM_002206.3(ITGA7):c.517del (p.Arg173fs)	Pathogenic
1394724	NM_002206.3(ITGA7):c.2331_2344del (p.Glu777fs)	Pathogenic
1456806	NM_002206.3(ITGA7):c.187C>T (p.Gln63Ter)	Pathogenic
1949025	NM_002206.3(ITGA7):c.2710del (p.Leu904fs)	Pathogenic
2154907	NM_002206.3(ITGA7):c.2446C>T (p.Gln816Ter)	Pathogenic
2415506	NM_002206.3(ITGA7):c.2670del (p.Gln891fs)	Pathogenic
2424369	NC_000012.11:g.(?56091458)(56093230_?)del	Pathogenic
2753782	NM_002206.3(ITGA7):c.1767del (p.Ile589fs)	Pathogenic
2780776	NM_002206.3(ITGA7):c.2817del (p.Ala940fs)	Pathogenic
2824329	NM_002206.3(ITGA7):c.2276del (p.Gln759fs)	Pathogenic
2873714	NM_002206.3(ITGA7):c.2749dup (p.Glu917fs)	Pathogenic
2891692	NM_002206.3(ITGA7):c.1966del (p.Thr656fs)	Pathogenic
2911826	NM_002206.3(ITGA7):c.1327_1328del (p.Leu443fs)	Pathogenic
2997928	NM_002206.3(ITGA7):c.2491C>T (p.Gln831Ter)	Pathogenic
3242261	NM_002206.3(ITGA7):c.97_98insTG (p.Ala33fs)	Pathogenic
3689579	NM_002206.3(ITGA7):c.1173_1182del (p.Asn392fs)	Pathogenic
3711857	NM_002206.3(ITGA7):c.1559dup (p.Thr521fs)	Pathogenic
470560	NC_000012.12:g.(?55697675)(55698937_?)del	Pathogenic
4714719	NM_002206.3(ITGA7):c.866_869del (p.Asn289fs)	Pathogenic
4726824	NM_002206.3(ITGA7):c.246del (p.Gln83fs)	Pathogenic
537989	NM_002206.3(ITGA7):c.1456C>T (p.Arg486Ter)	Pathogenic
537990	NM_002206.3(ITGA7):c.1072dup (p.Tyr358fs)	Pathogenic
838697	NM_002206.3(ITGA7):c.207G>A (p.Trp69Ter)	Pathogenic
9049	NM_002206.3(ITGA7):c.1506-2A>G	Pathogenic
9050	NM_002206.3(ITGA7):c.2712+2T>C	Pathogenic
9051	NM_002206.3(ITGA7):c.1205del (p.Gly402fs)	Pathogenic
971915	NM_002206.3(ITGA7):c.29G>A (p.Trp10Ter)	Pathogenic
1067219	NM_002206.3(ITGA7):c.334+1G>T	Likely pathogenic
1180774	NM_002206.3(ITGA7):c.94_95dup (p.Ala33fs)	Likely pathogenic
1324588	NM_002206.3(ITGA7):c.1825C>T (p.Gln609Ter)	Likely pathogenic

SpliceAI

4970 predictions. Top by Δscore:

Variant	Effect	Δscore
12:55688097:C:CC	acceptor_gain	1.0000
12:55688201:CCA:C	donor_gain	1.0000
12:55688296:TACTC:T	acceptor_gain	1.0000
12:55688298:CTC:C	acceptor_gain	1.0000
12:55688300:CCT:C	acceptor_loss	1.0000
12:55688301:C:CC	acceptor_gain	1.0000
12:55688840:TCAC:T	donor_loss	1.0000
12:55688841:CACCT:C	donor_loss	1.0000
12:55688842:ACCT:A	donor_gain	1.0000
12:55688843:CCTC:C	donor_gain	1.0000
12:55688845:T:TA	donor_gain	1.0000
12:55688954:AGTCC:A	acceptor_loss	1.0000
12:55688956:TCC:T	acceptor_loss	1.0000
12:55688957:CCT:C	acceptor_loss	1.0000
12:55688958:CTAGG:C	acceptor_loss	1.0000
12:55688959:T:A	acceptor_loss	1.0000
12:55692752:TGC:T	donor_gain	1.0000
12:55692788:T:TA	donor_gain	1.0000
12:55693236:T:TA	donor_gain	1.0000
12:55693237:C:A	donor_gain	1.0000
12:55694254:AC:A	donor_gain	1.0000
12:55694255:CC:C	donor_gain	1.0000
12:55694441:A:AC	donor_gain	1.0000
12:55694442:C:CC	donor_gain	1.0000
12:55694442:CGTGG:C	donor_gain	1.0000
12:55694464:T:TA	donor_gain	1.0000
12:55694529:C:CT	acceptor_gain	1.0000
12:55694530:A:T	acceptor_gain	1.0000
12:55694649:CA:C	donor_gain	1.0000
12:55694691:TTCTC:T	acceptor_gain	1.0000

AlphaMissense

7383 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:55693260:A:G	W909R	0.998
12:55693260:A:T	W909R	0.998
12:55695597:C:G	C687S	0.997
12:55695598:A:T	C687S	0.997
12:55695630:A:C	F676C	0.997
12:55701082:A:G	C163R	0.997
12:55688862:C:A	W1024C	0.996
12:55688862:C:G	W1024C	0.996
12:55693316:A:T	V890D	0.996
12:55695590:G:C	S689R	0.996
12:55695590:G:T	S689R	0.996
12:55695592:T:G	S689R	0.996
12:55695615:C:G	C681S	0.996
12:55695616:A:T	C681S	0.996
12:55697734:A:G	L501P	0.996
12:55700899:C:G	G224R	0.996
12:55700979:C:T	C197Y	0.996
12:55701080:G:C	C163W	0.996
12:55701081:C:G	C163S	0.996
12:55701082:A:T	C163S	0.996
12:55693258:C:A	W909C	0.995
12:55693258:C:G	W909C	0.995
12:55694895:G:C	N737K	0.995
12:55694895:G:T	N737K	0.995
12:55700899:C:A	G224C	0.995
12:55700978:G:C	C197W	0.995
12:55700980:A:G	C197R	0.995
12:55701018:C:T	C184Y	0.995
12:55694649:C:G	C792S	0.994
12:55694650:A:T	C792S	0.994

dbSNP variants (sampled 300 via entrez): RS1000133549 (12:55704167 G>A), RS1000187510 (12:55717855 G>A), RS1000287928 (12:55710704 A>G,T), RS1000334552 (12:55689675 T>A,G), RS1000614175 (12:55687681 G>C), RS1000625992 (12:55700054 A>T), RS1000704895 (12:55702385 G>A), RS1000780644 (12:55709654 T>C), RS1000806891 (12:55689299 A>G), RS1000898878 (12:55684419 T>C), RS1001011850 (12:55716436 C>T), RS1001032535 (12:55712865 G>T), RS1001378070 (12:55684306 C>T), RS1001513326 (12:55712030 T>C), RS1001543128 (12:55705967 C>T)

Disease associations

OMIM: gene MIM:600536 | disease phenotypes: MIM:613204

GenCC curated gene-disease

Disease	Classification	Inheritance
congenital muscular dystrophy due to integrin alpha-7 deficiency	Strong	Autosomal recessive
congenital fiber-type disproportion myopathy	Supportive	Autosomal dominant

Mondo (2): congenital muscular dystrophy due to integrin alpha-7 deficiency (MONDO:0013177), congenital fiber-type disproportion myopathy (MONDO:0009711)

Orphanet (1): Congenital muscular dystrophy with integrin alpha-7 deficiency (Orphanet:34520)

HPO phenotypes

71 total (30 of 71 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000218	High palate
HP:0000276	Long face
HP:0000347	Micrognathia
HP:0000473	Torticollis
HP:0000602	Ophthalmoplegia
HP:0000678	Dental crowding
HP:0000767	Pectus excavatum
HP:0001249	Intellectual disability
HP:0001252	Hypotonia
HP:0001270	Motor delay
HP:0001284	Areflexia
HP:0001315	Reduced tendon reflexes
HP:0001324	Muscle weakness
HP:0001371	Flexion contracture
HP:0001374	Congenital hip dislocation
HP:0001508	Failure to thrive
HP:0001558	Decreased fetal movement
HP:0001561	Polyhydramnios
HP:0001609	Hoarse voice
HP:0001627	Abnormal heart morphology
HP:0001648	Cor pulmonale
HP:0001761	Pes cavus
HP:0001762	Talipes equinovarus
HP:0001824	Weight loss
HP:0002015	Dysphagia
HP:0002058	Myopathic facies
HP:0002086	Abnormality of the respiratory system
HP:0002205	Recurrent respiratory infections
HP:0002315	Headache

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST003264_851	Post bronchodilator FEV1/FVC ratio	1.000000e-06
GCST010002_217	Refractive error	6.000000e-174

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004713	FEV/FVC ratio

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C567709	Muscular Dystrophy, Congenital, Due To Integrin Alpha-7 Deficiency (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: catalytic receptor — Integrins

CTD chemical–gene interactions

45 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects cotreatment, decreases expression, increases abundance, increases expression	3
Valproic Acid	decreases methylation, increases expression	3
Arsenic	affects expression, affects cotreatment, decreases expression, increases abundance, increases expression	2
Dexamethasone	increases expression, affects cotreatment	2
Nickel	decreases expression	2
Cyclosporine	decreases expression	2
FR900359	decreases phosphorylation	1
propionaldehyde	increases expression	1
bisphenol A	decreases expression	1
sodium arsenate	decreases expression	1
2,5,2’,5’-tetrachlorobiphenyl	decreases expression	1
trichostatin A	decreases expression	1
beta-lapachone	decreases expression	1
butyraldehyde	increases expression	1
4-hydroxy-2-nonenal	decreases expression	1
nickel sulfate	decreases expression	1
pentanal	increases expression	1
seocalcitol	increases expression	1
abrine	increases expression	1
bisphenol S	increases expression	1
bisphenol AF	increases expression	1
2,3,5-trichloro-6-phenyl-(1,4)benzoquinone	increases expression	1
Sevoflurane	increases expression, increases reaction, decreases expression	1
Sunitinib	decreases expression	1
Aldehydes	increases expression	1
Arsenates	affects cotreatment, increases expression	1
Atrazine	affects cotreatment, increases expression	1
Benzo(a)pyrene	affects methylation, decreases methylation	1
Cadmium	increases abundance, increases expression	1
Calcitriol	increases expression	1

Cellosaurus cell lines

5 cell lines: 5 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_D7SN	Ubigene A-549 ITGA7 KO	Cancer cell line	Male
CVCL_ST33	HAP1 ITGA7 (-) 1	Cancer cell line	Male
CVCL_ST34	HAP1 ITGA7 (-) 2	Cancer cell line	Male
CVCL_ST35	HAP1 ITGA7 (-) 3	Cancer cell line	Male
CVCL_ST36	HAP1 ITGA7 (-) 4	Cancer cell line	Male

Clinical trials (associated diseases)

3 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT01403402	Not specified	RECRUITING	Congenital Muscle Disease Study of Patient and Family Reported Medical Information
NCT00272883	Not specified	RECRUITING	Molecular and Genetic Studies of Congenital Myopathies
NCT06791369	Not specified	NOT_YET_RECRUITING	The Prevalence of RYR1-related Disease