ITGA1

Summary

ITGA1 (integrin subunit alpha 1, HGNC:6134) is a protein-coding gene on chromosome 5q11.2, encoding Integrin alpha-1 (P56199). Integrin alpha-1/beta-1 is a receptor for laminin and collagen.

This gene encodes the alpha 1 subunit of integrin receptors. This protein heterodimerizes with the beta 1 subunit to form a cell-surface receptor for collagen and laminin. The heterodimeric receptor is involved in cell-cell adhesion and may play a role in inflammation and fibrosis. The alpha 1 subunit contains an inserted (I) von Willebrand factor type I domain which is thought to be involved in collagen binding.

Source: NCBI Gene 3672 — RefSeq curated summary.

At a glance

• GWAS associations: 48
• Clinical variants (ClinVar): 223 total
• Druggable target: yes
• MANE Select transcript: NM_181501

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6134
Approved symbol	ITGA1
Name	integrin subunit alpha 1
Location	5q11.2
Locus type	gene with protein product
Status	Approved
Aliases	VLA1, CD49a
Ensembl gene	ENSG00000213949
Ensembl biotype	protein_coding
OMIM	192968
Entrez	3672

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 4 protein_coding_CDS_not_defined, 2 retained_intron, 1 protein_coding, 1 nonsense_mediated_decay

ENST00000282588, ENST00000504086, ENST00000504669, ENST00000506275, ENST00000509049, ENST00000513737, ENST00000514262, ENST00000650673

RefSeq mRNA: 1 — MANE Select: NM_181501 NM_181501

CCDS: CCDS3955

Canonical transcript exons

ENST00000282588 — 29 exons

Exon	Start	End
ENSE00001006613	52893675	52893840
ENSE00001006619	52905763	52905908
ENSE00001006625	52849365	52849485
ENSE00001006629	52952407	52959209
ENSE00001006632	52897455	52897528
ENSE00001006633	52898239	52898383
ENSE00001006634	52887815	52887965
ENSE00001145956	52861447	52861559
ENSE00002078767	52787916	52788414
ENSE00003468040	52910162	52910419
ENSE00003489988	52939840	52939944
ENSE00003491432	52920332	52920468
ENSE00003495300	52937401	52937514
ENSE00003495397	52918732	52918898
ENSE00003506531	52864763	52864851
ENSE00003509915	52944943	52945035
ENSE00003528725	52908898	52909041
ENSE00003555229	52947345	52947461
ENSE00003561059	52865690	52865817
ENSE00003570527	52915464	52915594
ENSE00003573279	52933894	52933996
ENSE00003573938	52929625	52929701
ENSE00003577244	52939590	52939691
ENSE00003592676	52932047	52932136
ENSE00003595260	52927584	52927664
ENSE00003597605	52864971	52865082
ENSE00003621865	52881873	52882021
ENSE00003643558	52925278	52925487
ENSE00003661946	52922777	52922887

Expression profiles

Bgee: expression breadth ubiquitous, 264 present calls, max score 98.69.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 7.0371 / max 256.4063, expressed in 1017 samples.

FANTOM5 promoters (11 alternative TSS)

Promoter ID	TPM avg	Samples expressed
56387	7.8091	1289
56395	2.9596	740
56394	1.3409	427
56396	1.2748	520
56397	0.5065	241
56393	0.3891	146
56391	0.2536	122
56386	0.2140	122
56390	0.1425	75
56392	0.0881	39

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
calcaneal tendon	UBERON:0003701	98.69	gold quality
adrenal tissue	UBERON:0018303	98.19	gold quality
mucosa of stomach	UBERON:0001199	97.35	gold quality
right coronary artery	UBERON:0001625	97.17	gold quality
stromal cell of endometrium	CL:0002255	97.11	gold quality
colonic epithelium	UBERON:0000397	96.94	gold quality
saphenous vein	UBERON:0007318	96.78	gold quality
lower esophagus muscularis layer	UBERON:0035833	96.50	gold quality
lower esophagus	UBERON:0013473	96.44	gold quality
right lung	UBERON:0002167	96.23	gold quality
popliteal artery	UBERON:0002250	96.14	gold quality
tibial artery	UBERON:0007610	96.14	gold quality
artery	UBERON:0001637	96.07	gold quality
coronary artery	UBERON:0001621	95.83	gold quality
vein	UBERON:0001638	95.78	gold quality
left coronary artery	UBERON:0001626	95.75	gold quality
muscle layer of sigmoid colon	UBERON:0035805	95.73	gold quality
aorta	UBERON:0000947	95.33	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	95.03	gold quality
descending thoracic aorta	UBERON:0002345	94.74	gold quality
thoracic aorta	UBERON:0001515	94.26	gold quality
ascending aorta	UBERON:0001496	94.21	gold quality
decidua	UBERON:0002450	93.89	gold quality
cauda epididymis	UBERON:0004360	93.87	gold quality
spleen	UBERON:0002106	93.53	gold quality
adrenal gland	UBERON:0002369	93.32	gold quality
urethra	UBERON:0000057	93.12	gold quality
left adrenal gland	UBERON:0001234	92.99	gold quality
vena cava	UBERON:0004087	92.89	gold quality
upper lobe of lung	UBERON:0008948	92.76	gold quality

Single-cell (SCXA)

Detected in 18 experiment(s), a significant marker in 16.

Experiment	Marker?	Max mean expression
E-MTAB-11268	yes	2455.54
E-HCAD-23	yes	2068.92
E-CURD-122	yes	457.56
E-HCAD-10	yes	43.94
E-CURD-88	yes	40.03
E-HCAD-31	yes	23.27
E-HCAD-35	yes	21.99
E-MTAB-8410	yes	19.20
E-CURD-119	yes	16.73
E-MTAB-8142	yes	14.88
E-ANND-3	yes	14.49
E-MTAB-5061	yes	11.69
E-MTAB-6678	yes	11.67
E-GEOD-83139	yes	7.61
E-ENAD-27	yes	6.97

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CTNNB1

miRNA regulators (miRDB)

98 targeting ITGA1, 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-3613-3P	100.00	76.36	7965
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-3134	100.00	66.43	777
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-432-3P	100.00	67.86	705
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-3605-5P	99.96	67.12	932
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-8082	99.95	67.27	1170
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-3119	99.92	71.34	2390
HSA-MIR-1305	99.91	71.43	3443
HSA-MIR-329-3P	99.91	66.56	1234
HSA-MIR-362-3P	99.91	66.38	1267
HSA-MIR-3686	99.90	70.53	2432
HSA-MIR-380-3P	99.89	70.18	1978
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-30A-3P	99.87	69.74	2928

Literature-anchored findings (GeneRIF, showing 40)

• results suggest that the inadequate trophoblastic invasion, induced by antiphospholipid antibodies, can be the result of decreased alpha1 integrin and VE-cadherin and increased alpha5 integrin and E-cadherin expression in the trophoblast (PMID:11937138)
• role of VLA1 in migration of multiple sclerosis derived antigen-reactive T-cell migration (PMID:12078857)
• determination of crystal structure in complex with an antibody Fab fragment (PMID:12662928)
• endometrial integrin alpha1 and alpha4 expression is more consistently present in the early luteal phase in stimulated cycles than in natural cycles (PMID:12694973)
• VEGF-A induced alpha1 & alpha2 integrins, promoting lymphatic endothelial tube formation & haptotactic migration. Lineage-specific integrin receptor expression contribute to the distinct dynamics of wound-associated angiogenesis & lymphangiogenesis. (PMID:15132990)
• alpha(1)beta(1) and Col-IV contribute to beta-cell functions known to be important for islet morphogenesis and glucose homeostasis (PMID:15485856)
• Enhanced expression of Integrin alpha1 is associated with liver metastases from gastrointestinal tumours (PMID:15679046)
• analysis of binding between collagen type III and integrins alpha1beta1 and alpha2beta1 (PMID:16043429)
• No statistical difference was observed on the expression of alpha1 integrin subunit expression in endometrium in tubal phimosis or hydrosalpinx (PMID:16412752)
• identified integrin alpha1 as a protein tyrosine phosphatase type IVA-interacting protein for the first time, and verified this physical association with pull-down and co-immunoprecipitation assays (PMID:16472776)
• alpha1beta1 integrin is a type IV collagen receptor in pancreatic cancer cells (PMID:17312461)
• results define a crucial role for alpha1beta1 in controlling the accumulation of epidermal type 1 polarized effector memory T cells in a common human immunopathology and provide the basis for new strategies in psoriasis treatment (PMID:17603494)
• thrombopoietin-induced in vitro differentiation of primary human cord blood mononuclear cells into megakaryocytes, we observed rapid, progressive CpG methylation of ITGA1, but not PELO or ITGA2. (PMID:17669516)
• A significant subset of VLA-1-positive effector T cells from rheumatoid arthritis patients persists in vivo and in vitro during monoclonal antibody therapy and contributes to residual and recurring inflammation. (PMID:17891451)
• are suggestive of the association of ITGA1 with osteoporosis and related risk in postmenopausal women (PMID:17931993)
• Activation of the FAK-src molecular scaffolds and p130Cas-JNK signaling cascades by alpha1-integrins during colon cancer cell invasion. (PMID:17982677)
• Group B streptococci ACP binds alpha(1)beta(1)-integrin via the D1 domain that promotes GBS internalization within epithelial cells. (PMID:18048918)
• Expression of VLA-1 was found significantly higher in lesional dermal blood vessels of psoriatic patients compared with atopic patients. (PMID:18269595)
• progesterone has an impact on alpha(1)-integrin distribution in the endometrium of patients with unexplained infertility (PMID:18377961)
• These results indicate that NSP4 interaction with integrin alpha1 and alpha2 is an important component of enterotoxin function and rotavirus pathogenesis, further distinguishing this viral virulence factor from other microbial enterotoxins. (PMID:18587047)
• distinct amino acids distal to the GFFKR motif of the alpha1 integrin cytoplasmic tail mediate activation of selective downstream signaling pathways and specific endothelial cell functions (PMID:18647959)
• MYCN may limit cell adhesion to the extracellular matrix and promote cell migration by downregulating integrin alpha1 (PMID:18813796)
• alpha(1)beta(1) integrin is of importance not only for the differentiation of mesenchymal cells into myofibroblasts but also for the neovascularization and connective tissue organization (PMID:19397781)
• ERbeta affects integrin expression and clustering and consequently modulates adhesion and migration of breast cancer cells. (PMID:19780039)
• Results show that plumieribetin, a fish lectin from the scorpionfish (Scorpaena plumieri), inhibits alpha1beta1 integrin binding to basement membrane collagen IV. (PMID:19850917)
• Pancreatic beta cell mesenchymal transition and decline in insulin gene expression are induced by elements of the ECM, by b1-integrin ligation, and by signaling via Src, JNK, and ERK. (PMID:20232313)
• Androgens increased INT alpha1 and alpha2 subunits in tubuloepithelial cells and in healthy labial salivary glands. (PMID:20436081)
• Prostate tissue-derived CD133+ cells exhibited a moderate level of expression of alpha1 integrin (PMID:20531279)
• Streptococcus pyogenes M49 plasminogen/plasmin binding facilitates keratinocyte invasion via integrin-integrin-linked kinase (ILK) pathways and protects from macrophage killing (PMID:21521694)
• Integrin alpha2beta1 might play a more crucial role in maintaining the mechanical creep properties of the collagen matrix than does integrin alpha1beta1. (PMID:21647271)
• the C-linker has a role as a spring-like element that allows relaxation of the alphaI domain in the resting state and controlled tension of the alphaI domain during activation, exerted by the beta chain (PMID:21965670)
• There was no evidence for differences in integrin alpha1, alpha4, beta1 and beta3 protein levels between the follicular and mid-luteal staged samples. (PMID:22002573)
• study characterized the collagen binding properties of an activated variant of the alpha1I domain, harboring a gain-of-function mutation E317A; the activated alpha(1)I domain represents a novel conformation of the alphaI domain, mimicking the structural state where the Arg(287)-Glu(317) ion pair has just broken during the integrin activation (PMID:22030389)
• study identified integrin alpha1/beta1 and alpha2/beta1 heterodimer as a new candidate IgA1 receptor in human mesangial cells (PMID:22298882)
• we have identified a new locus candidate, ITGA1, influencing both fasting glucose and BMD, that may begin to explain the genetic contribution to the epidemiological observations linking type 2 diabetes and osteoporosis (PMID:22698912)
• Dynamic structural changes are observed upon collagen and metal ion binding to the integrin alpha1 I domain. (PMID:22847004)
• CagL is a versatile surface protein equipped with at least two motifs to promote binding to integrins, thereby causing aberrant signaling within host cells and facilitating translocation of CagA into host cells. (PMID:22919661)
• Collagen receptors alpha(1)beta(1) and alpha(2)beta(1) integrins are involved in transmigration of peripheral blood eosinophils, but not mononuclear cells through human microvascular endothelial cells monolayer (PMID:23070086)
• Discoidin domain receptors promote alpha1beta1- and alpha2beta1-integrin mediated cell adhesion to collagen by enhancing integrin activation. (PMID:23284937)
• Pro-inflammatory cytokine tumor necrosis factor (TNF)-alpha strongly promotes pericyte proliferation and migration, and concomitantly induces a switch in pericyte integrins, from alpha1 to alpha2 integrin. (PMID:23448258)

Cross-species orthologs

10 orthologs

Organism	Symbol	Gene ID
danio_rerio	itga1	ENSDARG00000074316
mus_musculus	Itga1	ENSMUSG00000042284
rattus_norvegicus	Itga1	ENSRNOG00000053550
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), ITGA7 (ENSG00000135424), ITGA11 (ENSG00000137809), ITGAV (ENSG00000138448), ITGAX (ENSG00000140678), ITGA10 (ENSG00000143127), ITGA9 (ENSG00000144668), ITGAD (ENSG00000156886), ITGA5 (ENSG00000161638), ITGA2 (ENSG00000164171), ITGAM (ENSG00000169896)

Protein

Protein identifiers

Integrin alpha-1 — P56199 (reviewed: P56199)

Alternative names: CD49 antigen-like family member A, Laminin and collagen receptor, VLA-1

All UniProt accessions (2): A0A494C0F7, P56199

UniProt curated annotations — full annotation on UniProt →

Function. Integrin alpha-1/beta-1 is a receptor for laminin and collagen. It recognizes the proline-hydroxylated sequence G-F-P-G-E-R in collagen. Involved in anchorage-dependent, negative regulation of EGF-stimulated cell growth.

Subunit / interactions. Heterodimer of an alpha and a beta subunit. Alpha-1 associates with beta-1. Interacts with RAB21. Interacts (via cytoplasmic domain) with PTPN2; activates PTPN2 phosphatase activity towards EGFR and negatively regulates EGF signaling.

Subcellular location. Membrane.

Domain organisation. The integrin I-domain (insert) is a VWFA domain. Integrins with I-domains do not undergo protease cleavage.

Similarity. Belongs to the integrin alpha chain family.

RefSeq proteins (1): NP_852478* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000413	Integrin_alpha	Family
IPR002035	VWF_A	Domain
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
IPR036465	vWFA_dom_sf	Homologous_superfamily
IPR048285	Integrin_alpha_Ig-like_2	Domain
IPR048286	Integrin_alpha_Ig-like_3	Domain

Pfam: PF00092, PF01839, PF08441, PF20805, PF20806

UniProt features (85 total): glycosylation site 26, binding site 12, helix 12, repeat 7, disulfide bond 7, strand 5, sequence variant 4, sequence conflict 3, topological domain 2, turn 2, signal peptide 1, chain 1, short sequence motif 1, transmembrane region 1, domain 1

Structure

Experimental structures (PDB)

7 structures.

PDB	Method	Resolution (Å)
5HGJ	X-RAY DIFFRACTION	1.4
1PT6	X-RAY DIFFRACTION	1.87
4A0Q	X-RAY DIFFRACTION	1.9
1QC5	X-RAY DIFFRACTION	2
1QCY	X-RAY DIFFRACTION	2.3
2L8S	SOLUTION NMR
2M32	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P56199-F1	83.68	0.42

Functional residue map

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

Ligand- & substrate-binding residues (12): 498; 500; 502; 506; 580; 582; 584; 588; 642; 644; 646; 650

Disulfide bonds (7): 82–92, 688–697, 703–756, 808–814, 878–886, 1030–1062, 1065–1072

Glycosylation sites (26): 74, 100, 105, 112, 217, 317, 341, 402, 418, 460, 532, 699, 748, 780, 840, 883, 908, 915, 939, 966 …

Function

Pathways and Gene Ontology

Reactome pathways

14 pathways

ID	Pathway
R-HSA-216083	Integrin cell surface interactions
R-HSA-3000157	Laminin interactions
R-HSA-416700	Other semaphorin interactions
R-HSA-445355	Smooth Muscle Contraction
R-HSA-447041	CHL1 interactions
R-HSA-75892	Platelet Adhesion to exposed collagen
R-HSA-109582	Hemostasis
R-HSA-1266738	Developmental Biology
R-HSA-1474244	Extracellular matrix organization
R-HSA-373755	Semaphorin interactions
R-HSA-373760	L1CAM interactions
R-HSA-397014	Muscle contraction
R-HSA-422475	Axon guidance
R-HSA-9675108	Nervous system development

MSigDB gene sets: 317 (showing top): RRAGTTGT_UNKNOWN, GOBP_REGULATION_OF_ERBB_SIGNALING_PATHWAY, GOBP_MYELOID_LEUKOCYTE_MIGRATION, GOBP_CIRCULATORY_SYSTEM_PROCESS, GOBP_CELL_CHEMOTAXIS, GOCC_SECRETORY_GRANULE, GOBP_NEGATIVE_REGULATION_OF_ERBB_SIGNALING_PATHWAY, REACTOME_OTHER_SEMAPHORIN_INTERACTIONS, PID_PRL_SIGNALING_EVENTS_PATHWAY, HALMOS_CEBPA_TARGETS_UP, GAUSSMANN_MLL_AF4_FUSION_TARGETS_C_UP, GOBP_POSITIVE_REGULATION_OF_MAPK_CASCADE, IVANOVA_HEMATOPOIESIS_LATE_PROGENITOR, GOCC_CELL_SURFACE, GOBP_NEUROGENESIS

GO Biological Process (13): cell-matrix adhesion (GO:0007160), integrin-mediated signaling pathway (GO:0007229), negative regulation of cell population proliferation (GO:0008285), neutrophil chemotaxis (GO:0030593), negative regulation of epidermal growth factor receptor signaling pathway (GO:0042059), vasodilation (GO:0042311), positive regulation of MAPK cascade (GO:0043410), positive regulation of neuron apoptotic process (GO:0043525), cellular extravasation (GO:0045123), neuron projection morphogenesis (GO:0048812), cell-cell adhesion (GO:0098609), cell adhesion (GO:0007155), cell chemotaxis (GO:0060326)

GO Molecular Function (8): signaling receptor binding (GO:0005102), collagen binding (GO:0005518), phosphatase activator activity (GO:0019211), protein phosphatase binding (GO:0019903), signaling receptor activity (GO:0038023), metal ion binding (GO:0046872), collagen binding involved in cell-matrix adhesion (GO:0098639), protein binding (GO:0005515)

GO Cellular Component (11): acrosomal vesicle (GO:0001669), plasma membrane (GO:0005886), focal adhesion (GO:0005925), integrin complex (GO:0008305), external side of plasma membrane (GO:0009897), cell surface (GO:0009986), membrane (GO:0016020), integrin alpha1-beta1 complex (GO:0034665), perikaryon (GO:0043204), basal part of cell (GO:0045178), extracellular exosome (GO:0070062)

Reactome top-level categories

Rollup of top-8 pathways:

Category	Pathways
Extracellular matrix organization	2
Axon guidance	2
Semaphorin interactions	1
Muscle contraction	1
L1CAM interactions	1
Hemostasis	1
Nervous system development	1
Developmental Biology	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
cell-substrate adhesion	1
cell surface receptor signaling pathway	1
cell population proliferation	1
regulation of cell population proliferation	1
negative regulation of cellular process	1
granulocyte chemotaxis	1
neutrophil migration	1
epidermal growth factor receptor signaling pathway	1
regulation of epidermal growth factor receptor signaling pathway	1
negative regulation of ERBB signaling pathway	1
blood vessel diameter maintenance	1
MAPK cascade	1
regulation of MAPK cascade	1
positive regulation of intracellular signal transduction	1
positive regulation of apoptotic process	1
regulation of neuron apoptotic process	1
neuron apoptotic process	1
leukocyte migration	1
neuron projection development	1
plasma membrane bounded cell projection morphogenesis	1
cell adhesion	1
cellular process	1
chemotaxis	1
cell migration	1
cellular response to chemical stimulus	1
protein binding	1
protein-containing complex binding	1
enzyme activator activity	1
phosphatase activity	1
phosphatase regulator activity	1
phosphatase binding	1
molecular transducer activity	1
cation binding	1
collagen binding	1
cell-matrix adhesion	1
cell-matrix adhesion mediator activity	1
binding	1
secretory granule	1
membrane	1

Protein interactions and networks

STRING

1838 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ITGA1	ITGB1	P05556	996
ITGA1	FN1	P02751	853
ITGA1	CDH1	P12830	851
ITGA1	VCAM1	P19320	846
ITGA1	ITGB3	P05106	801
ITGA1	COL4A1	P02462	749
ITGA1	ITGB5	P18084	740
ITGA1	SEMA7A	O75326	706
ITGA1	ITGB4	P16144	705
ITGA1	ITGA2	P17301	699
ITGA1	ITGB2	P05107	698
ITGA1	ITGB6	P18564	688
ITGA1	ICAM1	P05362	676
ITGA1	COL4A2	P08572	674
ITGA1	CXCR6	O00574	662

IntAct

40 interactions, top by confidence:

A	B	Type	Score
KCNJ2	KCNJ18	psi-mi:“MI:2364”(proximity)	0.660
CD81	C2orf72	psi-mi:“MI:0914”(association)	0.530
FBXO2	TMEM131L	psi-mi:“MI:0914”(association)	0.530
LGALS1	PODXL	psi-mi:“MI:0914”(association)	0.530
LGALS3	PODXL	psi-mi:“MI:0914”(association)	0.530
CST6	CTSV	psi-mi:“MI:0914”(association)	0.530
LGALS1	LAMA5	psi-mi:“MI:0914”(association)	0.530
	ITGA1	psi-mi:“MI:0915”(physical association)	0.520
ITGA1	PTPN2	psi-mi:“MI:0403”(colocalization)	0.460
ITGA1	PTPN2	psi-mi:“MI:0915”(physical association)	0.460
FABP3	ITGA1	psi-mi:“MI:0407”(direct interaction)	0.440
Sharpin	ITGA1	psi-mi:“MI:0915”(physical association)	0.400
Fabp3	ITGA1	psi-mi:“MI:0915”(physical association)	0.370
Hax1	DERL1	psi-mi:“MI:0914”(association)	0.350
Itgb1	SSR3	psi-mi:“MI:0914”(association)	0.350
Magoh	TRAPPC13	psi-mi:“MI:0914”(association)	0.350
Iqgap3	SRGAP3	psi-mi:“MI:0914”(association)	0.350
Csnk1d	WWP2	psi-mi:“MI:0914”(association)	0.350
Gnpnat1	SMCHD1	psi-mi:“MI:0914”(association)	0.350
LIMK1	SH3PXD2B	psi-mi:“MI:0914”(association)	0.350
SLF2	GCFC2	psi-mi:“MI:0914”(association)	0.350
LGALS8	SLC22A23	psi-mi:“MI:0914”(association)	0.350
LGALS3	PODXL	psi-mi:“MI:0914”(association)	0.350
LMAN2L	ACP2	psi-mi:“MI:0914”(association)	0.350
CD81	STX3	psi-mi:“MI:0914”(association)	0.350
CD81	PVR	psi-mi:“MI:0914”(association)	0.350

BioGRID (65): ITGA1 (Affinity Capture-MS), ITGA1 (Affinity Capture-MS), ITGA1 (Affinity Capture-MS), ITGA1 (Affinity Capture-MS), ITGA1 (Affinity Capture-MS), ITGA1 (Affinity Capture-MS), ITGA1 (Affinity Capture-MS), ITGA1 (Affinity Capture-MS), ITGA1 (Affinity Capture-MS), ITGA1 (Affinity Capture-MS), BIN1 (Two-hybrid), ITGA1 (Affinity Capture-MS), ITGA1 (Affinity Capture-MS), ITGA1 (Affinity Capture-MS), ITGA1 (Reconstituted Complex)

ESM2 similar proteins: D3ZTD8, O15537, O35276, O35375, O35474, O42163, O43405, O43854, O60462, O75882, P02469, P07224, P07225, P07942, P18614, P21956, P48740, P55245, P56199, P70490, P79385, P98064, P98118, Q01279, Q01635, Q08431, Q13591, Q28520, Q2VWQ2, Q3V3R4, Q5E9T6, Q5EA64, Q5R7K9, Q62217, Q62507, Q63604, Q6IS24, Q7TT15, Q8CHN8, Q8R4G0

Diamond homologs: A2AX52, A6H584, A6NMZ7, A8TX70, E1BMV3, E7FF10, O00339, O08746, O35701, O42401, O75578, P12111, P13944, P15989, P17301, P18614, P20785, P32018, P34576, P51942, P53710, P56199, P61622, P84552, Q02388, Q05707, Q13349, Q21281, Q21540, Q28902, Q3V3R4, Q5EA64, Q60847, Q62469, Q63870, Q641F3, Q642A6, Q801S8, Q80X19, Q8C6K9

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
ITGA1	“form complex”	“A1/b1 integrin”	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	196
Likely benign	6
Benign	7

Top pathogenic / likely-pathogenic (0)

SpliceAI

4636 predictions. Top by Δscore:

Variant	Effect	Δscore
5:52801403:TTCTA:T	acceptor_loss	1.0000
5:52801405:CTA:C	acceptor_loss	1.0000
5:52801406:TAGGT:T	acceptor_loss	1.0000
5:52801407:A:AC	acceptor_loss	1.0000
5:52801408:GGTAC:G	acceptor_gain	1.0000
5:52801646:G:GT	donor_gain	1.0000
5:52849359:CTAAA:C	acceptor_loss	1.0000
5:52849360:TAAAG:T	acceptor_loss	1.0000
5:52849361:A:AG	acceptor_gain	1.0000
5:52849361:AAAG:A	acceptor_loss	1.0000
5:52849362:A:G	acceptor_gain	1.0000
5:52849362:AAGT:A	acceptor_loss	1.0000
5:52849363:A:G	acceptor_gain	1.0000
5:52849363:A:T	acceptor_loss	1.0000
5:52849363:AGTT:A	acceptor_gain	1.0000
5:52849364:G:A	acceptor_loss	1.0000
5:52849364:G:GT	acceptor_gain	1.0000
5:52849364:GT:G	acceptor_gain	1.0000
5:52849364:GTT:G	acceptor_gain	1.0000
5:52849364:GTTG:G	acceptor_gain	1.0000
5:52849483:ATGG:A	donor_loss	1.0000
5:52849486:G:A	donor_loss	1.0000
5:52849486:G:GG	donor_gain	1.0000
5:52864758:TTTAG:T	acceptor_loss	1.0000
5:52864759:TTA:T	acceptor_loss	1.0000
5:52864760:TAGTT:T	acceptor_loss	1.0000
5:52864761:A:AG	acceptor_gain	1.0000
5:52864762:G:GG	acceptor_gain	1.0000
5:52864762:GT:G	acceptor_gain	1.0000
5:52864762:GTT:G	acceptor_gain	1.0000

AlphaMissense

7753 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:52864974:T:C	C130R	0.999
5:52865028:T:C	C148R	0.999
5:52865030:T:G	C148W	0.999
5:52905841:G:A	G463D	0.999
5:52905841:G:T	G463V	0.999
5:52908914:G:A	G491D	0.999
5:52925314:T:A	C814S	0.999
5:52925315:G:C	C814S	0.999
5:52927626:T:A	C886S	0.999
5:52927627:G:C	C886S	0.999
5:52947408:A:C	S1148R	0.999
5:52947410:T:A	S1148R	0.999
5:52947410:T:G	S1148R	0.999
5:52864975:G:A	C130Y	0.998
5:52864976:T:G	C130W	0.998
5:52865028:T:A	C148S	0.998
5:52865029:G:A	C148Y	0.998
5:52865029:G:C	C148S	0.998
5:52865751:G:C	W186C	0.998
5:52865751:G:T	W186C	0.998
5:52898282:G:A	G403E	0.998
5:52898282:G:T	G403V	0.998
5:52898383:G:C	G437R	0.998
5:52905823:C:A	P457H	0.998
5:52905840:G:T	G463C	0.998
5:52908910:T:C	F490L	0.998
5:52908912:T:A	F490L	0.998
5:52908912:T:G	F490L	0.998
5:52908965:T:C	L508P	0.998
5:52908971:T:A	V510D	0.998

dbSNP variants (sampled 300 via entrez): RS1000029607 (5:52807553 C>A), RS1000036176 (5:52803938 T>C), RS1000051789 (5:52850202 A>G), RS1000056122 (5:52933644 A>C), RS1000132753 (5:52957068 A>G), RS1000135690 (5:52953373 G>T), RS1000139366 (5:52958235 A>C,T), RS1000141363 (5:52894264 T>A,C), RS1000158130 (5:52891594 A>G), RS1000223573 (5:52913495 C>A), RS1000232606 (5:52874151 G>A), RS1000240011 (5:52914506 C>G,T), RS1000241024 (5:52909112 C>A,T), RS1000284342 (5:52845098 C>A), RS1000286603 (5:52871621 A>G)

Disease associations

OMIM: gene MIM:192968 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

48 associations (top):

Study	Trait	p-value
GCST001248_17	Pulmonary function	2.000000e-06
GCST001277_14	Liver enzyme levels (gamma-glutamyl transferase)	3.000000e-10
GCST001291_1	Response to platinum-based agents	2.000000e-06
GCST001784_36	Pulmonary function (smoking interaction)	2.000000e-07
GCST001868_4	Alzheimer’s disease biomarkers	1.000000e-06
GCST002481_13	Acne (severe)	5.000000e-09
GCST002707_5	Serum thyroid-stimulating hormone levels	4.000000e-06
GCST003470_4	Coronary artery disease	6.000000e-07
GCST003471_4	Myocardial infarction	2.000000e-08
GCST004185_11	Lung function (FEV1/FVC)	2.000000e-18
GCST004778_1	Attention deficit hyperactivity disorder	3.000000e-06
GCST005989_12	Serum total protein levels	3.000000e-09
GCST006019_49	Gamma glutamyl transferase levels	2.000000e-16
GCST006484_5	Type 2 diabetes	4.000000e-06
GCST006612_43	LDL cholesterol	5.000000e-11
GCST006614_64	Total cholesterol levels	2.000000e-10
GCST006629_97	Pulse pressure	2.000000e-11
GCST006979_774	Heel bone mineral density	2.000000e-15
GCST007269_280	Pulse pressure	4.000000e-09
GCST007430_105	Peak expiratory flow	4.000000e-14
GCST007431_97	Lung function (FEV1/FVC)	1.000000e-41
GCST007432_136	FEV1	7.000000e-09
GCST007692_52	Chronic obstructive pulmonary disease	6.000000e-10
GCST007847_119	Type 2 diabetes	2.000000e-08
GCST009379_277	Type 2 diabetes	1.000000e-08
GCST009379_278	Type 2 diabetes	8.000000e-11
GCST009379_279	Type 2 diabetes	6.000000e-06
GCST009391_1197	Metabolite levels	6.000000e-06
GCST009732_2	Type 2 diabetes	2.000000e-08
GCST010118_43	Type 2 diabetes	1.000000e-08

EFO canonical traits (17, from GWAS)

EFO ID	Trait name
EFO:0003892	pulmonary function measurement
EFO:0004713	FEV/FVC ratio
EFO:0004532	serum gamma-glutamyl transferase measurement
EFO:0005194	amyloid-beta measurement
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0004574	total cholesterol measurement
EFO:0005763	pulse pressure measurement
EFO:0009270	heel bone mineral density
EFO:0009718	peak expiratory flow
EFO:0004314	forced expiratory volume
EFO:0009765	alanine measurement
EFO:0004615	apolipoprotein B measurement
EFO:0004348	hematocrit
EFO:0004509	hemoglobin measurement
EFO:0007986	reticulocyte count
EFO:0004305	erythrocyte count
EFO:0004533	alkaline phosphatase measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (3): CHEMBL3137278 (PROTEIN COMPLEX), CHEMBL3682 (SINGLE PROTEIN), CHEMBL5465394 (PROTEIN COMPLEX)

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs830884	ITGA1		0.00	0

GtoPdb / IUPHAR curated pharmacology

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

Target class: catalytic receptor — Integrins

ChEMBL bioactivities

11 potent at pChembl≥5 of 19 total, top 11 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.28	IC50	5.2	nM	CHEMBL88478
8.08	IC50	8.4	nM	CHEMBL88478
7.48	IC50	33	nM	CHEMBL3115061
7.33	IC50	46.7	nM	CHEMBL5419935
7.27	IC50	53.9	nM	CHEMBL5419935
7.08	IC50	83.3	nM	CHEMBL5410616
7.01	EC50	98.2	nM	CHEMBL5410616
6.19	IC50	652	nM	CHEMBL5395825
6.15	IC50	710	nM	CHEMBL5395825
6.05	IC50	897	nM	CHEMBL5408335
5.96	IC50	1110	nM	CHEMBL5408335

PubChem BioAssay actives

11 with measured affinity, of 27 total; 6 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
(2S)-1-[(2S)-2-[[(2S)-3-carboxy-2-[[(2S)-4-methyl-2-[[2-[4-[(2-methylphenyl)carbamoylamino]phenyl]acetyl]amino]pentanoyl]amino]propanoyl]amino]-3-methylbutanoyl]pyrrolidine-2-carboxylic acid	2029966: Binding affinity to alpha1beta2 integrin receptor (unknown origin) preincubated for 30 mins followed by 30 mins incubation in ICAM-1 coated wells by fluorescence based assay	ic50	0.0052	uM
(4S,11E)-18-chloro-2-oxo-14-oxa-3,7,9-triazatricyclo[13.3.1.16,9]icosa-1(18),6(20),7,11,15(19),16-hexaene-4-carboxylic acid;hydrochloride	1067601: Antagonist activity at integrin alpha1beta1 receptor (unknown origin) assessed as inhibition of interaction with biotinylated collagen type-1 after 3 hrs by solid phase ELISA-type assay	ic50	0.0330	uM
(2R,5S,8S,11S,14R)-8-(carboxymethyl)-2-[[4-[(2-methylphenyl)carbamoylamino]phenyl]methyl]-5-(2-methylpropyl)-3,6,9,12,16-pentaoxo-11-propan-2-yl-1,4,7,10,13-pentazacyclohexadecane-14-carboxylic acid	2029966: Binding affinity to alpha1beta2 integrin receptor (unknown origin) preincubated for 30 mins followed by 30 mins incubation in ICAM-1 coated wells by fluorescence based assay	ic50	0.0467	uM
(2S,5S,8S,11S,14S)-8-(carboxymethyl)-2-[[4-[(2-methylphenyl)carbamoylamino]phenyl]methyl]-5-(2-methylpropyl)-3,6,9,12,16-pentaoxo-11-propan-2-yl-1,4,7,10,13-pentazacyclohexadecane-14-carboxylic acid	2029966: Binding affinity to alpha1beta2 integrin receptor (unknown origin) preincubated for 30 mins followed by 30 mins incubation in ICAM-1 coated wells by fluorescence based assay	ic50	0.0833	uM
(2R,5S,8S,11S,14S)-8-(carboxymethyl)-2-[[4-[(2-methylphenyl)carbamoylamino]phenyl]methyl]-5-(2-methylpropyl)-3,6,9,12,16-pentaoxo-11-propan-2-yl-1,4,7,10,13-pentazacyclohexadecane-14-carboxylic acid	2029966: Binding affinity to alpha1beta2 integrin receptor (unknown origin) preincubated for 30 mins followed by 30 mins incubation in ICAM-1 coated wells by fluorescence based assay	ic50	0.6520	uM
(2S,5S,8S,11S,14R)-8-(carboxymethyl)-2-[[4-[(2-methylphenyl)carbamoylamino]phenyl]methyl]-5-(2-methylpropyl)-3,6,9,12,16-pentaoxo-11-propan-2-yl-1,4,7,10,13-pentazacyclohexadecane-14-carboxylic acid	2029966: Binding affinity to alpha1beta2 integrin receptor (unknown origin) preincubated for 30 mins followed by 30 mins incubation in ICAM-1 coated wells by fluorescence based assay	ic50	0.8970	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Cisplatin	decreases response to substance, increases expression, increases response to substance, affects cotreatment, decreases expression	4
Doxorubicin	increases response to substance, decreases expression, increases expression	4
sodium arsenite	decreases expression, increases expression	3
Tobacco Smoke Pollution	decreases methylation, increases expression, decreases expression	3
Valproic Acid	increases expression	3
trichostatin A	affects expression, increases expression	2
Benzo(a)pyrene	increases expression	2
Methotrexate	increases response to substance, increases expression	2
Tetrachlorodibenzodioxin	increases expression	2
Tretinoin	increases expression	2
Particulate Matter	decreases expression, increases abundance, increases expression	2
aristolochic acid I	decreases expression	1
GSK-J4	decreases expression	1
TL8-506	affects cotreatment, increases expression	1
geldanamycin	increases expression	1
bisphenol A	affects cotreatment, affects methylation, decreases methylation	1
beta-lapachone	decreases expression	1
cobaltous chloride	increases expression	1
perfluorooctanoic acid	decreases expression	1
perfluorodecanoic acid	affects expression	1
S-(1,2-dichlorovinyl)cysteine	decreases expression	1
perfluorooctanesulfonamide	affects expression	1
di-n-butylphosphoric acid	affects expression	1
perfluoro-n-heptanoic acid	affects expression	1
3-nitrobenzanthrone	decreases expression	1
entinostat	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	increases expression	1
quinocetone	increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	increases expression	1
perfluorododecanoic acid	affects expression	1

ChEMBL screening assays

12 unique, capped per target: 12 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3116954	Binding	Antagonist activity at integrin alpha1beta1 receptor (unknown origin) assessed as inhibition of interaction with biotinylated collagen type-1 after 3 hrs by solid phase ELISA-type assay	Small Macrocycles As Highly Active Integrin α2β1 Antagonists. — ACS Med Chem Lett

Cellosaurus cell lines

5 cell lines: 5 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D7SK	Ubigene A-549 ITGA1 KO	Cancer cell line	Male
CVCL_ST17	HAP1 ITGA1 (-) 1	Cancer cell line	Male
CVCL_ST18	HAP1 ITGA1 (-) 2	Cancer cell line	Male
CVCL_ST19	HAP1 ITGA1 (-) 3	Cancer cell line	Male
CVCL_ST20	HAP1 ITGA1 (-) 4	Cancer cell line	Male

Clinical trials (associated diseases)

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