ITGAE

Summary

ITGAE (integrin subunit alpha E, HGNC:6147) is a protein-coding gene on chromosome 17p13.2, encoding Integrin alpha-E (P38570). Integrin ITGAE/ITGB7 (alpha-E/beta-7) is a receptor for E-cadherin.

Integrins are heterodimeric integral membrane proteins composed of an alpha chain and a beta chain. This gene encodes an I-domain-containing alpha integrin that undergoes post-translational cleavage in the extracellular domain, yielding disulfide-linked heavy and light chains. In combination with the beta 7 integrin, this protein forms the E-cadherin binding integrin known as the human mucosal lymphocyte-1 antigen. This protein is preferentially expressed in human intestinal intraepithelial lymphocytes (IEL), and in addition to a role in adhesion, it may serve as an accessory molecule for IEL activation.

Source: NCBI Gene 3682 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 246 total
• MANE Select transcript: NM_002208

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6147
Approved symbol	ITGAE
Name	integrin subunit alpha E
Location	17p13.2
Locus type	gene with protein product
Status	Approved
Aliases	CD103, HUMINAE
Ensembl gene	ENSG00000083457
Ensembl biotype	protein_coding
OMIM	604682
Entrez	3682

Gene structure

Transcript identifiers

Ensembl transcripts: 14 — 7 protein_coding, 4 protein_coding_CDS_not_defined, 3 retained_intron

ENST00000263087, ENST00000570360, ENST00000570415, ENST00000571185, ENST00000571937, ENST00000572121, ENST00000572179, ENST00000572433, ENST00000574026, ENST00000868855, ENST00000868856, ENST00000868857, ENST00000949198, ENST00000949199

RefSeq mRNA: 3 — MANE Select: NM_002208 NM_001425071, NM_001425072, NM_002208

CCDS: CCDS32531

Canonical transcript exons

ENST00000263087 — 31 exons

Exon	Start	End
ENSE00000670178	3745764	3745927
ENSE00000670181	3747922	3748052
ENSE00000670185	3750352	3750482
ENSE00000670188	3751650	3751874
ENSE00000670204	3757706	3757859
ENSE00000670206	3759402	3759553
ENSE00000670211	3761013	3761177
ENSE00000670215	3761915	3761982
ENSE00000670216	3763869	3763960
ENSE00001136261	3743489	3743617
ENSE00001136305	3755117	3755261
ENSE00001136313	3755830	3755897
ENSE00001136323	3756984	3757134
ENSE00001136344	3760172	3760287
ENSE00001136358	3761403	3761520
ENSE00001196605	3777540	3777660
ENSE00001213603	3729478	3729555
ENSE00001356766	3801111	3801188
ENSE00002754207	3739805	3739878
ENSE00003461352	3753783	3753925
ENSE00003461922	3720307	3720402
ENSE00003467493	3732368	3732466
ENSE00003481419	3723288	3723383
ENSE00003501924	3716688	3716798
ENSE00003521991	3727919	3728026
ENSE00003536903	3714628	3714942
ENSE00003576939	3753290	3753430
ENSE00003603969	3723688	3723744
ENSE00003615636	3731104	3731183
ENSE00003627099	3728105	3728168
ENSE00003642902	3734817	3734949

Expression profiles

Bgee: expression breadth ubiquitous, 293 present calls, max score 97.91.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 13.5551 / max 154.1944, expressed in 1800 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
163871	12.8966	1793
163878	0.3307	120
163877	0.2214	98
163879	0.0467	19
163873	0.0310	10
163874	0.0207	7
163872	0.0058	3
163875	0.0022	1

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
oocyte	CL:0000023	97.91	gold quality
secondary oocyte	CL:0000655	97.15	gold quality
gluteal muscle	UBERON:0002000	96.49	gold quality
biceps brachii	UBERON:0001507	95.58	gold quality
putamen	UBERON:0001874	95.22	gold quality
triceps brachii	UBERON:0001509	95.20	gold quality
caudate nucleus	UBERON:0001873	95.08	gold quality
monocyte	CL:0000576	94.99	gold quality
mononuclear cell	CL:0000842	94.93	gold quality
adult organism	UBERON:0007023	94.85	gold quality
leukocyte	CL:0000738	94.60	gold quality
lymph node	UBERON:0000029	94.53	gold quality
jejunal mucosa	UBERON:0000399	94.50	gold quality
nucleus accumbens	UBERON:0001882	94.50	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	94.06	gold quality
granulocyte	CL:0000094	93.99	gold quality
jejunum	UBERON:0002115	93.98	gold quality
deltoid	UBERON:0001476	93.91	gold quality
pylorus	UBERON:0001166	93.63	gold quality
spleen	UBERON:0002106	93.61	gold quality
tibia	UBERON:0000979	93.42	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	93.23	gold quality
right adrenal gland cortex	UBERON:0035827	93.21	gold quality
small intestine Peyer’s patch	UBERON:0003454	93.18	gold quality
right adrenal gland	UBERON:0001233	93.13	gold quality
visceral pleura	UBERON:0002401	93.12	gold quality
adipose tissue	UBERON:0001013	93.09	gold quality
vastus lateralis	UBERON:0001379	93.06	gold quality
tibialis anterior	UBERON:0001385	93.02	gold quality
parietal pleura	UBERON:0002400	92.97	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-CURD-122	yes	17.19
E-ANND-3	yes	10.33
E-CURD-88	yes	4.06
E-GEOD-124858	no	115.25

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): GFI1, ID2, RUNX3

miRNA regulators (miRDB)

27 targeting ITGAE, 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-1252-5P	100.00	69.80	2774
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-507	99.97	70.11	1915
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-557	99.96	70.01	1640
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-374C-5P	99.80	72.06	2910
HSA-MIR-655-3P	99.80	72.19	2909
HSA-MIR-3913-5P	99.78	67.26	968
HSA-MIR-518A-5P	99.70	69.01	2209
HSA-MIR-527	99.70	69.01	2209
HSA-MIR-3122	99.50	66.33	821
HSA-MIR-6840-3P	98.68	65.95	1923
HSA-MIR-1301-5P	98.09	66.62	495
HSA-MIR-6502-5P	98.09	66.73	495
HSA-MIR-1302	97.92	67.27	844
HSA-MIR-3129-3P	97.85	67.63	1246
HSA-MIR-4298	97.26	66.59	765
HSA-MIR-5694	97.06	67.70	682
HSA-MIR-6736-3P	96.98	65.22	1342
HSA-MIR-4793-5P	96.88	65.90	872

Literature-anchored findings (GeneRIF, showing 40)

• has a role in mucosal immunity and graft rejection (PMID:12370249)
• Involvement of the adhesive ligand pair CD103-E-cadherin in human thymocyte cell proliferation (PMID:12414996)
• Differential up-regulation of CD103 expression on lamina propria lymphocytes in Crohn’s disease may indicate differential humoral or cellular regulation in inducing CD103 molecules on lymphocytes in patients with this disease (PMID:14532999)
• CD103 promotes destruction of renal allografts by CD8 T cells (PMID:15196058)
• Integrin/activation marker CD103 (alphaEbeta7) is expressed on Epstein-Barr virus-specific tonsil-resident (but not peripheral blood mononuclear leukocyte-derived) cytotoxic T lymphocytes. (PMID:16177076)
• CD103 expression on dendritic cells influences the balance between effector and regulatory T cell activity in the intestine. (PMID:16216886)
• human alloantigen-induced CD103+ CD8+ T cells possess functional features of regulatory T cells (PMID:16920912)
• CD8+/CD103+ tumor-reactive T lymphocytes infiltrating epithelial tumors most likely play a major role in antitumor cytotoxic response through alphaEbeta7-E-cadherin interactions. (PMID:17325197)
• An investigation to evaluate the diagnostic value of relative number of CD103 expressing CD4(+) T-lymphocytes in the BAL fluid of patients with a variety of interstitial lung diseases, including pulmonary sarcoidosis, is reported. (PMID:18182176)
• integrin alpha(E)(CD103)beta(7) is not only involved in epithelial retention, but also in shaping and proper intraepithelial morphogenesis of some leukocytes. (PMID:18492951)
• Phenotypic analysis of peripheral blood and decidual CD8+ T cells showed the presence of activated CD8+ T cells as well as a population of CD8+CD103+ T cells in decidual tissue (PMID:19150377)
• A higher proportion of CD103+CD4+ T cells and ITGAE -1088 AA genotype might be associated with fibrosis formation in pulmonary sarcoidosis. (PMID:19604725)
• results show that binding of the human alphaE I domain to oral and skin keratinocytes is independent of E-cadherin (PMID:20875079)
• Studies indicate that the mechanisms that regulate the retention of tissue-resident memory T cells include TGF-beta-mediated induction of CD103 and downregulation of CCR7. (PMID:21739671)
• These findings support the usefulness of CD123 and CD103 to aid in the differential diagnosis of B-cell lymphoproliferative disorders (PMID:21917686)
• Lymphoid tissue (LT)-resident CD8alpha-positive dendritic cells (DCs) and non(LT)-derived CD103-positive DCs express transgenic XCR1 and are characterized by a unique transcriptional fingerprint, irrespective of their tissue of origin. (PMID:21948982)
• Memory CD103+ CD8 T cells that persist within the brain after an acute infection with vesicular stomatitis virus are bona fide tissue resident memory cells. (PMID:22922816)
• Tumor-infiltrating lymphocytes expressing the tissue resident memory marker CD103 are associated with increased survival in high-grade serous ovarian cancer. (PMID:24190978)
• Using a human CTL system model based on a CD8(+)/CD103(-) T cell clone specific of a lung tumor-associated Ag, we demonstrated that the transcription factors Smad2/3 and NFAT-1 are two critical regulators of this process. (PMID:24477908)
• Report CD103 expression occurs most frequently in gastrointestinal T-cell lymphomas. (PMID:25025448)
• Cell-sorting experiments demonstrated that IDO1 expression is found in a subset of CD1a(+)CD14(-)langerin(+) cells, expressing CD103 (PMID:25584868)
• This report highlights the diagnostic difficulties and the need of consensus in categorizing clonal CD103(+) lymphocytosis in patients with refractory celiac disease. (PMID:25637255)
• PD-1(+)CD103(+) CD8 TIL might regain functional antitumor activity, an effect that potentially could be augmented by immune modulation. (PMID:25957117)
• Levels of GZMA and ITGAE mRNAs in colon tissues can identify patients with UC who are most likely to benefit from etrolizumab; expression levels decrease with etrolizumab administration in biomarker(high) patients. (PMID:26522261)
• detected CD103 tumor cells in 41% (16/39) of lymph node-involved adult T-cell leukemia/lymphoma (PMID:26813744)
• The CD103+CD4+/CD4+ ratio does not accurately discriminate between sarcoidosis and other causes of lymphocytic alveolitis, neither alone nor in combination with the CD4+/CD8+ ratio, and is not a powerful marker for the diagnosis of sarcoidosis. (PMID:27230039)
• AEbeta7 is of key relevance for gut trafficking of inflammatory bowel disease (IBD) CD8(+) T cells and CD4(+) Th9 cells in vivo and mainly retention might account for this effect. These findings indicate that blockade of alphaEbeta7 in addition to alpha4beta7 may be particularly effective in intestinal disorders with expansion of CD8(+) and Th9 cells such as IBD. (PMID:27543429)
• CD103 expression in human dendritic cells is regulated differentially by retinoic acid and Toll-like receptor ligands. (PMID:28087652)
• Pxn binding to the CD103 cytoplasmic tail triggers alphaEbeta7 integrin outside-in signaling that promotes CD8(+) T-cell migratory behavior and effector functions. (PMID:29021139)
• Indeterminate pediatric acute liver failure (iPALF) cases are characterized by a perforin+CD103+CD8+ T-cell predominant hepatic infiltrate consistent with expansion of a Trm CD8+ T-cell phenotype, which is clearly different from noninflammatory causes of PALF. (PMID:29603342)
• alphaE gene expression levels were significantly higher in ileal compared with colonic biopsies in both Crohn’s disease and Ulcerative colitis, as well as in healthy subjects. (PMID:29912405)
• Co-expression of CD39 and CD103 identifies tumor-reactive CD8 T cells in human solid tumors. (PMID:30006565)
• ITGAE+ lymphocytes tended to associate with the epithelial-mesenchymal transition (EMT) with decreased Snail and increased E-cadherin expression accompanied. (PMID:30100393)
• Study data indicate that CD103 engages in dendritic cell (DC)-epithelial cell interactions upon contact with epithelial E-cadherin but is not a major driver of DC adhesion to gastrointestinal epithelia. (PMID:30622531)
• FGL2 promotes tumor progression in the brain by suppressing CD103-expressing dendritic cell differentiation. (PMID:30683885)
• CD103-expressing cancer stem cells exosomes acted to guide them to target cancer cells and organs, conferring the higher metastatic capacity of clear cell renal cell carcinoma to lungs. (PMID:30975145)
• Self-Maintaining CD103(+) Cancer-Specific T Cells Are Highly Energetic with Rapid Cytotoxic and Effector Responses. (PMID:31771983)
• Intravenous CBD-CCL4 administration recruits CD103(+) DCs and CD8(+) T cells and improves the antitumor effect of CPI immunotherapy in multiple tumor models, including poor responders to CPI. (PMID:31844672)
• KLRG1 and CD103 Expressions Define Distinct Intestinal Tissue-Resident Memory CD8 T Cell Subsets Modulated in Crohn’s Disease. (PMID:32477365)
• CD8+CD103+ tissue-resident memory T cells convey reduced protective immunity in cutaneous squamous cell carcinoma. (PMID:33479027)

Cross-species orthologs

11 orthologs

Organism	Symbol	Gene ID
danio_rerio	itgae.2	ENSDARG00000057787
danio_rerio	itgae.1	ENSDARG00000098012
mus_musculus	Itgae	ENSMUSG00000005947
rattus_norvegicus	Itgae	ENSRNOG00000046639
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), ITGA6 (ENSG00000091409), ITGA4 (ENSG00000115232), ITGA7 (ENSG00000135424), 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-E — P38570 (reviewed: P38570)

Alternative names: HML-1 antigen, Integrin alpha-IEL, Mucosal lymphocyte 1 antigen

All UniProt accessions (2): P38570, K7EQU0

UniProt curated annotations — full annotation on UniProt →

Function. Integrin ITGAE/ITGB7 (alpha-E/beta-7) is a receptor for E-cadherin. It mediates adhesion of intra-epithelial T-lymphocytes to epithelial cell monolayers.

Subunit / interactions. Heterodimer of an alpha and a beta subunit. ITGAE/alpha-E associates with ITGB7/beta-7. In the absence of the E-cadherin ligand, the heterodimer shows an overall half-bent conformation, an intermediate between closed and open conformations, with the alpha-I domain of ITGAE/alpha-E, which is responsible for ligand binding, covering the headpiece domain.

Subcellular location. Membrane.

Tissue specificity. Expressed on a subclass of T-lymphocytes known as intra-epithelial lymphocytes which are located between mucosal epithelial cells.

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

Induction. Integrin ITGAE/ITGB7 (alpha-E/beta-7) is induced by TGFB1.

Similarity. Belongs to the integrin alpha chain family.

RefSeq proteins (3): NP_001412000, NP_001412001, NP_002199* (*=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
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

Pfam: PF00092, PF00357, PF01839, PF20805

UniProt features (142 total): strand 62, helix 18, binding site 12, glycosylation site 11, disulfide bond 8, turn 7, sequence variant 7, repeat 5, region of interest 2, topological domain 2, mutagenesis site 2, signal peptide 1, chain 1, short sequence motif 1, compositionally biased region 1, transmembrane region 1, domain 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
8ZJF	ELECTRON MICROSCOPY	2.7
9P97	ELECTRON MICROSCOPY	2.92
9P98	ELECTRON MICROSCOPY	2.93
9P99	ELECTRON MICROSCOPY	3.37

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P38570-F1	80.57	0.34

Antibody-complex structures (SAbDab): 2 — 9P97, 9P98

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): 522; 524; 526; 530; 586; 588; 590; 594; 654; 656; 658; 662

Disulfide bonds (8): 70–79, 107–126, 236–239, 706–762, 742–748, 775–779, 823–829, 893–907

Glycosylation sites (11): 49, 271, 321, 444, 726, 782, 857, 934, 954, 1065, 1096

Mutagenesis-validated functional residues (2):

Position	Phenotype
208	loss of e-cadherin binding.
316	loss of e-cadherin binding.

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-216083	Integrin cell surface interactions
R-HSA-1474244	Extracellular matrix organization

MSigDB gene sets: 264 (showing top): BROWNE_HCMV_INFECTION_6HR_DN, GOCC_CELL_SURFACE, MODULE_412, GOBP_CELL_CELL_ADHESION, GARCIA_TARGETS_OF_FLI1_AND_DAX1_DN, SANSOM_APC_TARGETS_DN, FUJII_YBX1_TARGETS_DN, CAIRO_HEPATOBLASTOMA_UP, PID_ECADHERIN_NASCENT_AJ_PATHWAY, GOBP_CELL_SUBSTRATE_ADHESION, GOBP_CELL_MATRIX_ADHESION, GOBP_INTEGRIN_MEDIATED_SIGNALING_PATHWAY, REACTOME_INTEGRIN_CELL_SURFACE_INTERACTIONS, JAZAERI_BREAST_CANCER_BRCA1_VS_BRCA2_DN, LEE_CALORIE_RESTRICTION_MUSCLE_DN

GO Biological Process (4): cell-matrix adhesion (GO:0007160), integrin-mediated signaling pathway (GO:0007229), cell-cell adhesion (GO:0098609), cell adhesion (GO:0007155)

GO Molecular Function (2): signaling receptor activity (GO:0038023), metal ion binding (GO:0046872)

GO Cellular Component (6): plasma membrane (GO:0005886), integrin complex (GO:0008305), external side of plasma membrane (GO:0009897), cell surface (GO:0009986), integrin alphaE-beta7 complex (GO:0034691), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Extracellular matrix organization	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
cell-substrate adhesion	1
cell surface receptor signaling pathway	1
cell adhesion	1
cellular process	1
molecular transducer activity	1
cation binding	1
membrane	1
cell periphery	1
protein complex involved in cell adhesion	1
plasma membrane signaling receptor complex	1
plasma membrane	1
cell surface	1
side of membrane	1
integrin complex	1

Protein interactions and networks

STRING

1918 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ITGAE	ITGB7	P26010	996
ITGAE	CDH1	P12830	993
ITGAE	CD8A	P01732	907
ITGAE	FOXP3	Q9BZS1	865
ITGAE	SELL	P14151	847
ITGAE	CD4	P01730	840
ITGAE	KLRG1	Q96E93	821
ITGAE	CD69	Q07108	815
ITGAE	TNFRSF18	Q9Y5U5	797
ITGAE	BATF3	Q9NR55	794
ITGAE	PTPRC	P08575	785
ITGAE	CTLA4	P16410	781
ITGAE	FLT3LG	P49771	777
ITGAE	CCR7	P32248	774
ITGAE	IFNG	P01579	770

IntAct

5 interactions, top by confidence:

A	B	Type	Score
ITGAE	ITGB7	psi-mi:“MI:0407”(direct interaction)	0.360
KLHL22	TRAV18	psi-mi:“MI:0914”(association)	0.350
TRIM54	ITGAE	psi-mi:“MI:0915”(physical association)	0.000
CHFR	ITGAE	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (7): ITGAE (Affinity Capture-RNA), ITGAE (Co-purification), ITGAE (Affinity Capture-MS), EED (Two-hybrid), ITGAE (Two-hybrid), ITGAE (Affinity Capture-MS), ITGAE (Affinity Capture-MS)

ESM2 similar proteins: A0EQL2, A2AJ76, A2AJA7, A6H8M9, A8T650, A8T682, A8T688, A8T6A6, D3ZLH5, F1QVU0, O08628, O75173, O88839, P04278, P08514, P08689, P0DV84, P15196, P20701, P29376, P32970, P38570, P60882, P80012, P97497, P97793, Q13444, Q15113, Q5RFQ8, Q5TM20, Q61398, Q63191, Q6UXC1, Q7Z304, Q7Z442, Q7Z7M0, Q8BNJ2, Q8CG85, Q8K1S7, Q8NBP7

Diamond homologs: A2ARA8, F1MMS9, O70362, O75578, P08514, P08648, P11688, P12080, P20701, P23229, P26006, P26007, P26009, P34446, P38570, P53708, P80108, P80109, Q00651, Q06274, Q13683, Q13797, Q24247, Q27977, Q60677, Q61738, Q61739, Q63258, Q8R2H5, Q91687, Q9QUM0, Q9W1M8, A2AX52, A6H584, A6NMZ7, A6QLN9, A8TX70, E1BMV3, O00339, O08746

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
ITGAE	“form complex”	“AE/b7 integrin”	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	186
Likely benign	26
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

4851 predictions. Top by Δscore:

Variant	Effect	Δscore
17:3714938:CCACA:C	acceptor_gain	1.0000
17:3714939:CACA:C	acceptor_gain	1.0000
17:3714939:CACAC:C	acceptor_gain	1.0000
17:3714940:ACA:A	acceptor_gain	1.0000
17:3714941:CA:C	acceptor_gain	1.0000
17:3714941:CAC:C	acceptor_gain	1.0000
17:3714943:C:CC	acceptor_gain	1.0000
17:3716683:CTGA:C	donor_loss	1.0000
17:3716685:GACC:G	donor_loss	1.0000
17:3716686:A:AC	donor_gain	1.0000
17:3716687:C:CA	donor_loss	1.0000
17:3716687:C:CC	donor_gain	1.0000
17:3716794:GTGAT:G	acceptor_gain	1.0000
17:3716795:TGAT:T	acceptor_gain	1.0000
17:3716796:GAT:G	acceptor_gain	1.0000
17:3716797:AT:A	acceptor_gain	1.0000
17:3716797:ATC:A	acceptor_loss	1.0000
17:3716798:TCTA:T	acceptor_loss	1.0000
17:3716799:C:CC	acceptor_gain	1.0000
17:3716799:CTAG:C	acceptor_loss	1.0000
17:3716804:C:CT	acceptor_gain	1.0000
17:3716805:A:T	acceptor_gain	1.0000
17:3716809:C:CT	acceptor_gain	1.0000
17:3720399:GTAA:G	acceptor_gain	1.0000
17:3720400:TAA:T	acceptor_gain	1.0000
17:3720401:AACT:A	acceptor_loss	1.0000
17:3720402:ACTA:A	acceptor_loss	1.0000
17:3720403:C:A	acceptor_loss	1.0000
17:3720403:C:CC	acceptor_gain	1.0000
17:3727914:AATAC:A	donor_loss	1.0000

AlphaMissense

7756 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:3760214:G:C	F224L	0.993
17:3760214:G:T	F224L	0.993
17:3760216:A:G	F224L	0.993
17:3760232:A:C	F218L	0.992
17:3760232:A:T	F218L	0.992
17:3760233:A:C	F218C	0.992
17:3760234:A:G	F218L	0.992
17:3731165:A:G	W925R	0.991
17:3731165:A:T	W925R	0.991
17:3759417:G:T	A284D	0.990
17:3760250:G:C	S212R	0.990
17:3760250:G:T	S212R	0.990
17:3760252:T:G	S212R	0.990
17:3760266:A:G	L207P	0.990
17:3759544:C:G	A242P	0.989
17:3760263:T:A	D208V	0.989
17:3760275:G:T	A204D	0.989
17:3757797:A:G	L310P	0.988
17:3760225:C:G	A221P	0.988
17:3760262:A:C	D208E	0.988
17:3760262:A:T	D208E	0.988
17:3757713:G:T	A338D	0.987
17:3759418:C:G	A284P	0.987
17:3760220:T:A	K222N	0.987
17:3760220:T:G	K222N	0.987
17:3757082:G:T	A358D	0.986
17:3757710:A:T	I339N	0.986
17:3757715:A:C	F337L	0.986
17:3757715:A:T	F337L	0.986
17:3757717:A:G	F337L	0.986

dbSNP variants (sampled 300 via entrez): RS1000021781 (17:3758941 T>C), RS1000062386 (17:3723509 C>A,T), RS1000076146 (17:3729228 G>A,T), RS1000087857 (17:3764971 C>G), RS1000090084 (17:3798271 C>G), RS1000113097 (17:3792432 A>G), RS1000179324 (17:3754792 A>C,G), RS1000195167 (17:3717876 C>T), RS1000200269 (17:3759171 G>A), RS1000204600 (17:3788186 T>C), RS1000227251 (17:3774690 A>G), RS1000239118 (17:3719048 A>G), RS1000245987 (17:3717654 C>T), RS1000270805 (17:3793543 A>G), RS1000271226 (17:3764678 C>T)

Disease associations

OMIM: gene MIM:604682 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST000246_23	Attention deficit hyperactivity disorder	1.000000e-07

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

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects expression, affects methylation, affects cotreatment, increases expression, decreases expression	4
bisphenol A	decreases methylation, decreases expression, affects cotreatment	2
arsenite	affects binding, increases reaction, increases methylation	2
Cadmium Chloride	increases expression, decreases expression	2
Particulate Matter	decreases expression, increases abundance, affects cotreatment	2
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
lead acetate	affects cotreatment, increases expression	1
manganese chloride	decreases expression, increases abundance	1
benzo(e)pyrene	decreases methylation	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, increases expression	1
di-n-butylphosphoric acid	affects expression	1
Am 580	increases expression	1
chloropicrin	decreases expression	1
pyrimidifen	increases expression	1
2-(1H-indazol-4-yl)-6-(4-methanesulfonylpiperazin-1-ylmethyl)-4-morpholin-4-ylthieno(3,2-d)pyrimidine	decreases expression, increases response to substance	1
picoxystrobin	increases expression	1
Irinotecan	increases response to substance	1
Rosiglitazone	increases expression	1
Fulvestrant	decreases methylation, affects cotreatment	1
Glyphosate	increases expression	1
Air Pollutants	decreases expression, increases abundance	1
Arsenic	affects methylation	1
Cisplatin	increases response to substance	1
Coumestrol	affects cotreatment, increases expression	1
Diuron	decreases expression	1
Gasoline	increases abundance, affects cotreatment, decreases expression	1
Manganese	increases abundance, decreases expression	1
Methapyrilene	decreases methylation	1
Methyl Methanesulfonate	increases expression	1

Cellosaurus cell lines

8 cell lines: 7 cancer cell line, 1 spontaneously immortalized cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B8IR	Abcam HCT 116 ITGAE KO	Cancer cell line	Male
CVCL_B8XL	Abcam MCF-7 ITGAE KO	Cancer cell line	Female
CVCL_B9L1	Abcam A-549 ITGAE KO	Cancer cell line	Male
CVCL_E5IM	CHO-K1/ITGAE	Spontaneously immortalized cell line	Female
CVCL_ST39	HAP1 ITGAE (-) 1	Cancer cell line	Male
CVCL_ST40	HAP1 ITGAE (-) 2	Cancer cell line	Male
CVCL_ST41	HAP1 ITGAE (-) 3	Cancer cell line	Male
CVCL_ST42	HAP1 ITGAE (-) 4	Cancer cell line	Male

Clinical trials (associated diseases)

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