ITGA9

Summary

ITGA9 (integrin subunit alpha 9, HGNC:6145) is a protein-coding gene on chromosome 3p22.2, encoding Integrin alpha-9 (Q13797). Integrin alpha-9/beta-1 (ITGA9:ITGB1) is a receptor for VCAM1, cytotactin and osteopontin.

This gene encodes an alpha integrin. Integrins are heterodimeric integral membrane glycoproteins composed of an alpha chain and a beta chain that mediate cell-cell and cell-matrix adhesion. The protein encoded by this gene, when bound to the beta 1 chain, forms an integrin that is a receptor for VCAM1, cytotactin and osteopontin. Expression of this gene has been found to be upregulated in small cell lung cancers.

Source: NCBI Gene 3680 — RefSeq curated summary.

At a glance

• GWAS associations: 15
• Clinical variants (ClinVar): 192 total
• Druggable target: yes
• MANE Select transcript: NM_002207

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6145
Approved symbol	ITGA9
Name	integrin subunit alpha 9
Location	3p22.2
Locus type	gene with protein product
Status	Approved
Aliases	RLC, ITGA4L, ALPHA-RLC
Ensembl gene	ENSG00000144668
Ensembl biotype	protein_coding
OMIM	603963
Entrez	3680

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 11 protein_coding, 1 retained_intron

ENST00000264741, ENST00000411817, ENST00000422441, ENST00000461533, ENST00000921363, ENST00000921364, ENST00000944256, ENST00000944257, ENST00000944258, ENST00000944259, ENST00000944260, ENST00000944261

RefSeq mRNA: 1 — MANE Select: NM_002207 NM_002207

CCDS: CCDS2669

Canonical transcript exons

ENST00000264741 — 28 exons

Exon	Start	End
ENSE00000825584	37777392	37777517
ENSE00000825586	37741730	37741819
ENSE00000923140	37784977	37785078
ENSE00000923143	37743926	37744034
ENSE00000923144	37736904	37736983
ENSE00000923145	37732712	37732798
ENSE00000966365	37481484	37481607
ENSE00000966366	37494501	37494568
ENSE00000966367	37503178	37503307
ENSE00000966370	37517504	37517609
ENSE00000966372	37523521	37523611
ENSE00000966377	37506000	37506085
ENSE00000966378	37513763	37513900
ENSE00000966379	37519260	37519354
ENSE00001011658	37526026	37526071
ENSE00001011672	37508559	37508627
ENSE00001011674	37629187	37629336
ENSE00001232677	37452141	37452559
ENSE00001293658	37683865	37684015
ENSE00001299653	37473354	37473460
ENSE00001300482	37803823	37803942
ENSE00001305415	37542425	37542585
ENSE00001306710	37653714	37653790
ENSE00001310316	37750462	37750569
ENSE00001311529	37779902	37780021
ENSE00001315011	37818891	37823507
ENSE00001320775	37533314	37533468
ENSE00001324836	37471007	37471134

Expression profiles

Bgee: expression breadth ubiquitous, 248 present calls, max score 96.37.

FANTOM5 (CAGE): breadth broad, TPM avg 3.8907 / max 508.7706, expressed in 574 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
36068	3.0819	514
36067	0.7067	297
36069	0.0963	48
36070	0.0058	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
urethra	UBERON:0000057	96.37	gold quality
saphenous vein	UBERON:0007318	94.00	gold quality
visceral pleura	UBERON:0002401	93.01	gold quality
adrenal tissue	UBERON:0018303	92.88	gold quality
heart right ventricle	UBERON:0002080	91.85	gold quality
descending thoracic aorta	UBERON:0002345	88.76	gold quality
tendon of biceps brachii	UBERON:0008188	88.41	gold quality
vena cava	UBERON:0004087	87.86	gold quality
thoracic aorta	UBERON:0001515	87.71	gold quality
ascending aorta	UBERON:0001496	87.44	gold quality
pleura	UBERON:0000977	86.27	gold quality
aorta	UBERON:0000947	85.86	gold quality
thyroid gland	UBERON:0002046	85.53	gold quality
tendon	UBERON:0000043	85.43	gold quality
right lobe of thyroid gland	UBERON:0001119	85.24	gold quality
seminal vesicle	UBERON:0000998	85.20	gold quality
parietal pleura	UBERON:0002400	85.18	gold quality
secondary oocyte	CL:0000655	85.05	gold quality
calcaneal tendon	UBERON:0003701	85.04	gold quality
synovial joint	UBERON:0002217	84.87	gold quality
middle temporal gyrus	UBERON:0002771	84.82	gold quality
left lobe of thyroid gland	UBERON:0001120	84.75	gold quality
tibial artery	UBERON:0007610	84.38	gold quality
popliteal artery	UBERON:0002250	84.37	gold quality
cardiac ventricle	UBERON:0002082	84.31	gold quality
adrenal gland	UBERON:0002369	84.27	gold quality
heart left ventricle	UBERON:0002084	84.08	gold quality
jejunal mucosa	UBERON:0000399	83.86	gold quality
trabecular bone tissue	UBERON:0002483	83.52	gold quality
oocyte	CL:0000023	83.42	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-CURD-119	yes	24.96
E-ANND-3	yes	6.92

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): MEIS1, PROX1, TBX5

miRNA regulators (miRDB)

109 targeting ITGA9, 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-3163	100.00	77.23	8605
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-4425	100.00	67.59	1049
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-5680	99.91	69.83	3421
HSA-MIR-3151-5P	99.86	63.83	1069
HSA-MIR-6875-3P	99.82	70.26	2983
HSA-MIR-520F-3P	99.82	71.32	1216
HSA-MIR-4659A-3P	99.80	72.62	4248
HSA-MIR-4659B-3P	99.80	72.62	4248
HSA-MIR-636	99.80	69.58	1500
HSA-MIR-8076	99.78	68.52	1170
HSA-MIR-4658	99.77	64.94	514
HSA-MIR-6790-5P	99.77	65.24	505
HSA-MIR-4319	99.76	69.83	2586
HSA-MIR-3617-5P	99.75	69.41	1968
HSA-MIR-641	99.75	69.35	1975
HSA-MIR-4320	99.75	65.80	793
HSA-MIR-148A-3P	99.74	73.77	1700
HSA-MIR-148B-3P	99.74	73.75	1700
HSA-MIR-152-3P	99.74	73.75	1703
HSA-MIR-4446-5P	99.72	69.19	2544
HSA-MIR-378G	99.71	64.90	1106
HSA-MIR-5580-3P	99.70	69.41	2052

Literature-anchored findings (GeneRIF, showing 40)

• role in chemotaxis in conjuction with plasmin (PMID:15247268)
• spermidine acetyltransferase directly binds to the alpha9 cytoplasmic domain and mediates alpha9-dependent enhancement of cell migration (PMID:15479742)
• VEGF-C and VEGF-D are ligands for the integrin alpha9beta1 (PMID:15590642)
• integrin alphavbeta6, alphavbeta3, alphavbeta5, alpha5beta1 and alpha9beta1 binding to osteopontin is controlled by specific structural motifs that are recognized by extracellular proteases (PMID:16005200)
• The integrin receptors of tenascin (TN) and fibronectin (FN) may be involved in cell processes such as growth, adhesion, migration and apoptosis. (PMID:16430945)
• Data found that alpha9beta1 is a receptor for nerve growth factor and two other neurotrophins, and interaction of alpha9beta1 with NGF was confirmed in an ELISA assay by direct binding to purified integrin. (PMID:18230652)
• tumor-cell expressions of alpha9 and beta1 integrins in combination with extracellular tenascin are necessary for medulloblastoma adhesion to the leptomeninges. (PMID:18794852)
• Possible link between ITGA9 missens mutation and human fetuses with severe chylothorax. (PMID:18973153)
• Down-regulation of RBSP3/CTDSPL, NPRL2/G21, RASSF1A, ITGA9, HYAL1 and HYAL2 genes in non-small cell lung cancer (PMID:19140316)
• Polymerization of OPN generates a novel alpha9beta1-binding site and that the interaction of this site with the alpha9beta1 integrin is critical to the neutrophil chemotaxis induced by polymeric OPN. (PMID:19346516)
• After forced expression of alpha9 integrin, extensive neurite outgrowth from PC12 cells and adult rat dorsal root ganglion neurons occurs. (PMID:19403822)
• A genetic variation(s) in ITGA9 may influence susceptibility to nasopharyngeal carcinoma in the Malaysian Chinese population. (PMID:19478819)
• Inhibition of alpha(9) integrin function with an anti-alpha(9) integrin Ab significantly reduces the production of arthrogenic cytokines and chemokines and ameliorates ongoing arthritis (PMID:19494327)
• The integrin alpha9beta1 is expressed on hematopoietic stem cells, and contributes to adhesion and differentiation of hematopoietic stem cells in the endosteal stem cell niche (PMID:19608669)
• Results reveal an important role for integrin-alpha9 signaling during lymphatic valve morphogenesis and implicate it as a candidate gene for primary lymphedema caused by valve defects. (PMID:19686679)
• although alpha9beta1 integrin can induce and localise to focal adhesions in a high activation state, its intermediate activity state normally supports cell adhesion consistent with migration. (PMID:19796635)
• Expression and activation of alpha9 integrin greatly enhances the ability of retinal pigment epithelial cells to adhere to wet age-related macular degeneration-affected Bruch’s membranes. (PMID:20159768)
• Data show that alpha9beta1 integrin engagement leads to the activation of integrin signaling pathways and potently reduces neutrophil spontaneous apoptosis, and that these effects are dependent on the activation of PI3K and MAPK pathways. (PMID:20362630)
• up-regulation of alpha9beta1 expression among all beta1 integrins during neutrophil activation and transendothelial migration and a synergy between alpha9beta1 and beta2 integrins in stabilizing neutrophil adhesion to endothelium under flow conditions (PMID:20435742)
• the three-amino acid sequence, EYP, encoded by exon 3 of VEGF-A is essential for binding of VEGF to integrin alpha9beta1 and induces adhesion and migration of endothelial and cancer cells (PMID:21071450)
• expression of alpha9beta1 in breast cancer; alpha9beta1 acts as novel marker of basal-like breast cancer subtype; expression associated with reduced survival; its ability to promote cell migration and invasion suggests it contributes to aggressiveness of this subtype (PMID:21341269)
• endostatin reduces colorectal tumor-induced lymphangiogenesis, at least in part, by inhibiting EDA-integrin alpha9 pathway. (PMID:21465533)
• rs189897 and rs2212020 genotypes of the ITGA9 are closely related to cerebral infarction, and the A-C haplotype is a protective factor against cerebral infarction. (PMID:21764681)
• Integrin alpha9 (ITGA9) expression and epigenetic silencing in human breast tumors (PMID:21975548)
• integrin alpha9beta1 is expressed in primary small cell lung cancer and patients having a high expression of alpha9beta1 demonstrated significantly worse long-term survival compared with patients with low alpha9beta1 expression (PMID:22370635)
• Differential capacity for VEGF-D production and integrin alpha 9 beta 1 expression by human breast cancer cell line MDA-MB-468LN jointly contributed to their lymphatic metastatic phenotype. (PMID:22545097)
• Neuronal cadherin and alpha9-integrin are postulated as leading actors in the association between the Notch pathway and promotion of cell adhesion, motility and invasion in rhabdomyosarcoma cells (PMID:22976797)
• alpha9beta1 integrin acts as a critical intrinsic regulator of human rheumatoid arthritis. (PMID:24241034)
• p75(NTR) and alpha9 integrin subunit are not closely associated through their cytoplasmic domains, most probably because of the molecular interference with other cytoplasmic proteins such as paxillin. (PMID:25748048)
• ITGA9 gene promoter is hypermethylated and downregulated in nasopharyngeal carcinoma. (PMID:26372814)
• our results demonstrate that upregulation of ITGA9 in response to the decrease in miR-125b in metastatic melanoma is responsible for melanoma tumor cell migration and invasion. (PMID:26596831)
• the expression levels of DLEC1 and ITGA9 were prominently decreased in lung tumor samples (PMID:27287342)
• findings identify a novel physiological context for combinatorial integrin signaling, laying the foundation for therapeutic strategies that manipulate alpha9beta1 and/or alpha3beta1 during wound healing (PMID:28416479)
• ITGA9 expression was found to be increased in the suprabasal psoriatic epidermis. (PMID:28844950)
• Metastatic prostate cancer cells cultured on osteo-mimetic surfaces coated with tenascin C exhibited enhanced adhesion and colony formation as mediated by integrin alpha9beta1. (PMID:28916657)
• this study demonstrates the central role of alpha9 in pathogenic behaviors of rheumatoid arthritis fibroblast-like synoviocytes (PMID:29038247)
• Our data suggest ITGA9, as a suppressor of HCC, prevents tumor cell migration and invasiveness through FAK/Src-Rac1/RhoA signaling. (PMID:29951557)
• This review summarises the known shared and specific roles for alpha4 and alpha9 integrins and highlights the importance of these receptors in controlling cell migration within both homeostatic and disease settings. (PMID:30819933)
• rs2212020 and rs189897 polymorphisms of the ITGA9 gene is associated with epithelial ovarian cancer. (PMID:30945681)
• ITGA9 level is significantly higher in triple-negative breast cancer (TNBC) than other breast cancer subtypes. Hhigher ITGA9 level is associated with significantly worse metastasis- and recurrence-free survival. Experimentally, ITGA9 KO significantly reduced TNBC cell cancer stem cell-like property, tumor angiogenesis, tumor growth and metastasis by promoting beta-catenin degradation through ILK/PKA/GSK3 pathway. (PMID:31008533)

Cross-species orthologs

8 orthologs

Organism	Symbol	Gene ID
danio_rerio	itga9	ENSDARG00000032435
mus_musculus	Itga9	ENSMUSG00000039115
rattus_norvegicus	Itga9	ENSRNOG00000043167
drosophila_melanogaster	if	FBGN0001250
drosophila_melanogaster	ItgaPS4	FBGN0034005
drosophila_melanogaster	ItgaPS5	FBGN0034880
drosophila_melanogaster	scb	FBGN0286785
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), ITGAD (ENSG00000156886), ITGA5 (ENSG00000161638), ITGA2 (ENSG00000164171), ITGAM (ENSG00000169896), ITGA1 (ENSG00000213949)

Protein

Protein identifiers

Integrin alpha-9 — Q13797 (reviewed: Q13797)

Alternative names: Integrin alpha-RLC

All UniProt accessions (3): Q13797, E9PDS3, H7C2L1

UniProt curated annotations — full annotation on UniProt →

Function. Integrin alpha-9/beta-1 (ITGA9:ITGB1) is a receptor for VCAM1, cytotactin and osteopontin. It recognizes the sequence A-E-I-D-G-I-E-L in cytotactin. ITGA9:ITGB1 may play a crucial role in SVEP1/polydom-mediated myoblast cell adhesion. Integrin ITGA9:ITGB1 represses PRKCA-mediated L-type voltage-gated channel Ca(2+) influx and ROCK-mediated calcium sensitivity in vascular smooth muscle cells via its interaction with SVEP1, thereby inhibiting vasocontraction.

Subunit / interactions. Heterodimer of an alpha and a beta subunit. Alpha-9 (ITGA9) associates with beta-1 (ITGB1). Integrin ITGA9:ITGB1 interacts with FBLN5 (via N-terminus). Integrin ITGA9:ITGB1 interacts with SPP1/OPN (via N-terminus). Integrin ITGA9:ITGB1 interacts with TNC/TNFN3 (via the 3rd Fibronectin type-III domain). Integrin ITGA9:ITGB1 interacts with SVEP1/polydom (via Sushi domain 21); thereby inhibits Ca(2+) intracellular signaling and as a result represses vasocontraction.

Subcellular location. Membrane.

Tissue specificity. Expressed in vascular smooth muscle cells (at protein level). Expressed in the airway epithelium (at protein level).

Miscellaneous. Expression is increased in small cell lung cancers (SCLC).

Similarity. Belongs to the integrin alpha chain family.

RefSeq proteins (1): NP_002198* (*=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 (48 total): binding site 12, glycosylation site 11, disulfide bond 9, repeat 7, topological domain 2, sequence variant 2, signal peptide 1, chain 1, short sequence motif 1, site 1, transmembrane region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q13797-F1	84.98	0.49

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): 565–566 (cleavage)

Ligand- & substrate-binding residues (12): 312; 314; 316; 320; 373; 375; 377; 381; 435; 437; 439; 443

Disulfide bonds (9): 87–97, 142–162, 179–194, 482–491, 497–555, 620–625, 696–706, 855–891, 898–903

Glycosylation sites (11): 225, 476, 493, 612, 654, 658, 672, 676, 807, 854, 904

Function

Pathways and Gene Ontology

Reactome pathways

8 pathways

ID	Pathway
R-HSA-216083	Integrin cell surface interactions
R-HSA-3000178	ECM proteoglycans
R-HSA-445144	Signal transduction by L1
R-HSA-1266738	Developmental Biology
R-HSA-1474244	Extracellular matrix organization
R-HSA-373760	L1CAM interactions
R-HSA-422475	Axon guidance
R-HSA-9675108	Nervous system development

MSigDB gene sets: 222 (showing top): GOBP_MYELOID_LEUKOCYTE_MIGRATION, GOBP_CIRCULATORY_SYSTEM_PROCESS, GOBP_CELL_CHEMOTAXIS, GOCC_CELL_SURFACE, PID_INTEGRIN_A9B1_PATHWAY, GOBP_LEUKOCYTE_CHEMOTAXIS, GOBP_CELL_CELL_ADHESION, GOBP_TAXIS, MARTINEZ_RB1_TARGETS_UP, PICCALUGA_ANGIOIMMUNOBLASTIC_LYMPHOMA_UP, GOBP_LEUKOCYTE_MIGRATION, GOBP_REGULATION_OF_ANATOMICAL_STRUCTURE_SIZE, PID_CXCR4_PATHWAY, GOBP_NEGATIVE_REGULATION_OF_MULTICELLULAR_ORGANISMAL_PROCESS, SHETH_LIVER_CANCER_VS_TXNIP_LOSS_PAM4

GO Biological Process (6): cell adhesion (GO:0007155), cell-matrix adhesion (GO:0007160), integrin-mediated signaling pathway (GO:0007229), neutrophil chemotaxis (GO:0030593), negative regulation of vasoconstriction (GO:0045906), cell-cell adhesion (GO:0098609)

GO Molecular Function (4): signaling receptor activity (GO:0038023), metal ion binding (GO:0046872), integrin binding involved in cell-matrix adhesion (GO:0098640), protein binding (GO:0005515)

GO Cellular Component (6): plasma membrane (GO:0005886), integrin complex (GO:0008305), basal plasma membrane (GO:0009925), cell surface (GO:0009986), integrin alpha9-beta1 complex (GO:0034679), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-5 pathways:

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

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
cellular process	1
cell-substrate adhesion	1
cell surface receptor signaling pathway	1
granulocyte chemotaxis	1
neutrophil migration	1
regulation of vasoconstriction	1
vasoconstriction	1
negative regulation of multicellular organismal process	1
cell adhesion	1
molecular transducer activity	1
cation binding	1
integrin binding	1
cell-matrix adhesion	1
cell-matrix adhesion mediator activity	1
binding	1
membrane	1
cell periphery	1
protein complex involved in cell adhesion	1
plasma membrane signaling receptor complex	1
basal part of cell	1
plasma membrane region	1
integrin complex	1

Protein interactions and networks

STRING

1174 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ITGA9	ITGB1	P05556	918
ITGA9	VCAM1	P19320	889
ITGA9	FN1	P02751	852
ITGA9	SPP1	P10451	798
ITGA9	SAT1	P21673	722
ITGA9	FOXC2	Q99958	704
ITGA9	ITGB7	P26010	697
ITGA9	LYVE1	Q9Y5Y7	691
ITGA9	ITGB3	P05106	685
ITGA9	ADAM12	O43184	658
ITGA9	FLT4	P35916	655
ITGA9	PXN	P49023	639
ITGA9	VEGFC	P49767	608
ITGA9	THBS1	P07996	579
ITGA9	TLN1	Q9Y490	558

IntAct

5 interactions, top by confidence:

A	B	Type	Score
LGALS1	PODXL	psi-mi:“MI:0914”(association)	0.530
PPM1G	H2BC12	psi-mi:“MI:0914”(association)	0.420
PPM1G	H2BC12	psi-mi:“MI:2364”(proximity)	0.420
ITGA9	IGLL5	psi-mi:“MI:0914”(association)	0.350

BioGRID (46): ITGA9 (Affinity Capture-MS), ALDH1A3 (Affinity Capture-MS), LCN2 (Affinity Capture-MS), SERPINB4 (Affinity Capture-MS), SPRR1B (Affinity Capture-MS), ITGB1 (Affinity Capture-MS), PCYOX1L (Affinity Capture-MS), SMOC1 (Affinity Capture-MS), IGLL5 (Affinity Capture-MS), KLK10 (Affinity Capture-MS), IVL (Affinity Capture-MS), HSPA5 (Affinity Capture-MS), CALML5 (Affinity Capture-MS), EVPL (Affinity Capture-MS), IGKC (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: B8JK39, O70362, P13612, P20701, P24063, P26008, P61625, Q00651, Q13797, Q91687, A2ARA8, F1MMS9, O75578, P08514, P08648, P11688, P12080, P23229, P26006, P26007, P26009, P34446, P38570, P53708, P80108, P80109, Q06274, Q13683, Q24247, Q27977, Q60677, Q61738, Q61739, Q63258, Q8R2H5, Q9QUM0, Q9W1M8, A2AX52, A6H584, A6NMZ7

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
ITGA9	“form complex”	“A9/b1 integrin”	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	137
Likely benign	22
Benign	18

Top pathogenic / likely-pathogenic (0)

SpliceAI

5230 predictions. Top by Δscore:

Variant	Effect	Δscore
3:37452556:GCTG:G	donor_gain	1.0000
3:37452560:G:GA	donor_loss	1.0000
3:37452560:G:GG	donor_gain	1.0000
3:37452561:T:A	donor_loss	1.0000
3:37471002:T:A	acceptor_gain	1.0000
3:37471002:TGCA:T	acceptor_loss	1.0000
3:37471003:GCA:G	acceptor_loss	1.0000
3:37471004:CA:C	acceptor_loss	1.0000
3:37471005:A:AG	acceptor_gain	1.0000
3:37471005:AG:A	acceptor_gain	1.0000
3:37471006:G:GT	acceptor_gain	1.0000
3:37471006:GG:G	acceptor_gain	1.0000
3:37471133:AGG:A	donor_loss	1.0000
3:37471135:G:GC	donor_loss	1.0000
3:37471136:T:G	donor_loss	1.0000
3:37473352:AG:A	acceptor_gain	1.0000
3:37473353:GG:G	acceptor_gain	1.0000
3:37473457:GTTG:G	donor_gain	1.0000
3:37473459:TG:T	donor_gain	1.0000
3:37473460:GG:G	donor_gain	1.0000
3:37473461:G:C	donor_loss	1.0000
3:37473461:G:GG	donor_gain	1.0000
3:37481478:CTTTA:C	acceptor_loss	1.0000
3:37481479:TTTA:T	acceptor_loss	1.0000
3:37481480:TTA:T	acceptor_loss	1.0000
3:37481481:TAGG:T	acceptor_loss	1.0000
3:37481482:A:C	acceptor_loss	1.0000
3:37481483:G:T	acceptor_loss	1.0000
3:37481483:GGCCT:G	acceptor_gain	1.0000
3:37481604:GAAG:G	donor_gain	1.0000

AlphaMissense

6824 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:37803889:A:C	S986R	1.000
3:37803891:T:A	S986R	1.000
3:37803891:T:G	S986R	1.000
3:37803901:G:A	G990R	1.000
3:37803901:G:C	G990R	1.000
3:37803902:G:A	G990E	1.000
3:37471080:T:A	C87S	0.999
3:37471081:G:C	C87S	0.999
3:37471110:T:A	C97S	0.999
3:37471111:G:C	C97S	0.999
3:37481497:G:C	R145P	0.999
3:37481547:T:C	C162R	0.999
3:37481548:G:A	C162Y	0.999
3:37481549:C:G	C162W	0.999
3:37494537:G:A	C194Y	0.999
3:37494545:G:T	G197W	0.999
3:37653721:T:G	F616C	0.999
3:37732760:T:A	C706S	0.999
3:37732760:T:C	C706R	0.999
3:37732761:G:C	C706S	0.999
3:37803874:T:A	W981R	0.999
3:37803874:T:C	W981R	0.999
3:37803884:C:A	A984D	0.999
3:37803926:C:A	A998D	0.999
3:37803935:T:C	L1001P	0.999
3:37818897:T:C	F1006L	0.999
3:37818899:C:A	F1006L	0.999
3:37818899:C:G	F1006L	0.999
3:37818900:T:C	F1007L	0.999
3:37818902:T:A	F1007L	0.999

dbSNP variants (sampled 300 via entrez): RS1000011496 (3:37522620 G>A), RS1000021975 (3:37612956 G>A), RS1000028414 (3:37563882 C>T), RS1000034479 (3:37726658 A>G,T), RS1000036311 (3:37471470 G>A,C), RS1000056549 (3:37703130 C>A,G,T), RS1000063263 (3:37529436 A>G), RS1000065043 (3:37687855 G>A), RS1000073627 (3:37660239 A>G), RS1000083238 (3:37714223 G>A), RS1000083563 (3:37560413 T>C), RS1000100148 (3:37481214 C>A,T), RS1000101250 (3:37508059 G>A), RS1000108444 (3:37703470 A>T), RS1000112360 (3:37746027 T>C)

Disease associations

OMIM: gene MIM:603963 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

15 associations (top):

Study	Trait	p-value
GCST000413_1	Nasopharyngeal carcinoma	7.000000e-08
GCST001414_7	Phospholipid levels (plasma)	2.000000e-08
GCST001735_4	PR interval	4.000000e-11
GCST002337_175	Amyotrophic lateral sclerosis (sporadic)	3.000000e-08
GCST003817_3	Mortality in sepsis	2.000000e-06
GCST006629_87	Pulse pressure	8.000000e-15
GCST006979_60	Heel bone mineral density	2.000000e-10
GCST007059_6	Response to antidepressants (symptom improvement)	2.000000e-06
GCST007267_105	Systolic blood pressure	1.000000e-11
GCST007269_26	Pulse pressure	6.000000e-11
GCST010397_17	Gut microbiota (bacterial taxa, rank normal transformation method)	1.000000e-06
GCST90002402_304	Platelet count	4.000000e-11
GCST90006903_2	Anti-human herpes virus 6 IE1A IgG seropositivity	5.000000e-08
GCST90020026_192	Hip index	3.000000e-08
GCST90020028_793	Hip circumference adjusted for BMI	5.000000e-10

EFO canonical traits (9, from GWAS)

EFO ID	Trait name
EFO:0004462	PR interval
EFO:0004352	mortality
EFO:0005763	pulse pressure measurement
EFO:0009270	heel bone mineral density
EFO:0006335	systolic blood pressure
EFO:0007874	gut microbiome measurement
EFO:0004309	platelet count
EFO:0007048	human herpesvirus 6 seropositivity
EFO:0008039	BMI-adjusted hip circumference

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL3170 (SINGLE PROTEIN), CHEMBL3885597 (PROTEIN COMPLEX)

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs11709385	ITGA9		0.00	0

GtoPdb / IUPHAR curated pharmacology

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

Target class: catalytic receptor — Integrins

Most potent curated ligand interactions (1 total), top 1:

Ligand	Action	Affinity	Parameter
BOP	Antagonist	11.52	pKd

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, decreases methylation	7
trichostatin A	affects cotreatment, increases expression	3
entinostat	increases expression, affects cotreatment	2
Vorinostat	affects cotreatment, increases expression	2
Panobinostat	affects cotreatment, increases expression	2
Benzo(a)pyrene	affects methylation, increases methylation	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Tretinoin	increases expression	2
propionaldehyde	decreases expression	1
bisphenol A	affects methylation, decreases methylation, affects cotreatment	1
sodium arsenite	affects methylation	1
benzo(e)pyrene	increases methylation	1
aflatoxin B2	increases methylation	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
quinocetone	increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
bisphenol S	decreases methylation	1
Sunitinib	increases expression	1
Arsenic Trioxide	decreases expression	1
Fulvestrant	affects methylation, affects cotreatment	1
Air Pollutants	increases abundance, increases expression	1
Cisplatin	increases expression	1
Doxorubicin	decreases expression	1
Estradiol	affects cotreatment, increases expression	1
Methapyrilene	increases methylation	1
Methotrexate	decreases expression	1
Dihydrotestosterone	increases expression	1
Testosterone	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Vanadates	decreases expression	1

ChEMBL screening assays

3 unique, capped per target: 3 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1013694	Binding	Binding affinity to integrin alpha9 expressed in human K562 cells at 1 uM for 30 mins by flow cytometry	Discovery of targeting ligands for breast cancer cells using the one-bead one-compound combinatorial method. — J Med Chem

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_ST37	HAP1 ITGA9 (-) 1	Cancer cell line	Male
CVCL_ST38	HAP1 ITGA9 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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