ITGB4

Summary

ITGB4 (integrin subunit beta 4, HGNC:6158) is a protein-coding gene on chromosome 17q25.1, encoding Integrin beta-4 (P16144). Integrin alpha-6/beta-4 is a receptor for laminin.

Integrins are heterodimers comprised of alpha and beta subunits, that are noncovalently associated transmembrane glycoprotein receptors. Different combinations of alpha and beta polypeptides form complexes that vary in their ligand-binding specificities. Integrins mediate cell-matrix or cell-cell adhesion, and transduced signals that regulate gene expression and cell growth. This gene encodes the integrin beta 4 subunit, a receptor for the laminins. This subunit tends to associate with alpha 6 subunit and is likely to play a pivotal role in the biology of invasive carcinoma. Mutations in this gene are associated with epidermolysis bullosa with pyloric atresia. Multiple alternatively spliced transcript variants encoding distinct isoforms have been found for this gene.

Source: NCBI Gene 3691 — RefSeq curated summary.

At a glance

• Gene–disease (curated): junctional epidermolysis bullosa with pyloric atresia (Definitive, GenCC) — +8 more curated relationships
• Clinical variants (ClinVar): 1,443 total — 75 pathogenic, 33 likely-pathogenic
• Phenotypes (HPO): 87
• Druggable target: yes
• MANE Select transcript: NM_000213

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6158
Approved symbol	ITGB4
Name	integrin subunit beta 4
Location	17q25.1
Locus type	gene with protein product
Status	Approved
Aliases	CD104
Ensembl gene	ENSG00000132470
Ensembl biotype	protein_coding
OMIM	147557
Entrez	3691

Gene structure

Transcript identifiers

Ensembl transcripts: 40 — 34 protein_coding, 3 retained_intron, 3 protein_coding_CDS_not_defined

ENST00000200181, ENST00000449880, ENST00000450894, ENST00000578318, ENST00000579211, ENST00000579662, ENST00000580542, ENST00000582629, ENST00000583327, ENST00000584025, ENST00000584374, ENST00000584558, ENST00000584939, ENST00000864026, ENST00000864027, ENST00000864028, ENST00000864029, ENST00000864030, ENST00000864031, ENST00000864032, ENST00000864033, ENST00000864034, ENST00000864035, ENST00000864036, ENST00000864037, ENST00000864038, ENST00000864039, ENST00000864040, ENST00000864041, ENST00000939590, ENST00000948785, ENST00000948786, ENST00000948787, ENST00000948788, ENST00000948789, ENST00000948790, ENST00000948791, ENST00000948792, ENST00000948793, ENST00000948794

RefSeq mRNA: 4 — MANE Select: NM_000213 NM_000213, NM_001005619, NM_001005731, NM_001321123

CCDS: CCDS11727, CCDS32736, CCDS58599

Canonical transcript exons

ENST00000200181 — 40 exons

Exon	Start	End
ENSE00001194868	75753765	75753974
ENSE00001241194	75721459	75721612
ENSE00002440616	75752446	75752577
ENSE00002461839	75750111	75750268
ENSE00002468909	75755701	75755850
ENSE00002471638	75756429	75756617
ENSE00002479213	75754576	75754815
ENSE00002495477	75750680	75750860
ENSE00002499762	75756704	75756859
ENSE00002504004	75750974	75751111
ENSE00002509631	75742582	75742761
ENSE00002516976	75757200	75757310
ENSE00002522553	75756943	75757107
ENSE00002687875	75757416	75757818
ENSE00003483067	75728377	75728473
ENSE00003487923	75733490	75733692
ENSE00003488931	75732163	75732239
ENSE00003496152	75731246	75731368
ENSE00003508634	75748841	75749045
ENSE00003511572	75731812	75731973
ENSE00003513990	75740358	75740461
ENSE00003521355	75736288	75736386
ENSE00003526568	75730241	75730504
ENSE00003529154	75743713	75743861
ENSE00003533968	75742341	75742489
ENSE00003534947	75729265	75729436
ENSE00003550260	75752174	75752356
ENSE00003561875	75739880	75740071
ENSE00003577134	75730875	75730964
ENSE00003584288	75737322	75737444
ENSE00003590514	75727404	75727505
ENSE00003607905	75727195	75727277
ENSE00003608996	75724694	75724782
ENSE00003626842	75740982	75741005
ENSE00003628124	75740793	75740851
ENSE00003633892	75727651	75727855
ENSE00003649290	75736565	75736694
ENSE00003650365	75737538	75737644
ENSE00003679819	75736051	75736154
ENSE00003692681	75739672	75739705

Expression profiles

Bgee: expression breadth ubiquitous, 267 present calls, max score 99.31.

FANTOM5 (CAGE): breadth broad, TPM avg 52.0945 / max 1627.9208, expressed in 841 samples.

FANTOM5 promoters (14 alternative TSS)

Promoter ID	TPM avg	Samples expressed
162777	31.5816	700
162776	14.7478	475
162775	1.4819	480
162778	1.4769	313
162774	1.1287	428
162792	0.4855	213
162773	0.4438	167
162791	0.2151	132
162781	0.1593	100
162796	0.1042	60

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
tibial nerve	UBERON:0001323	99.31	gold quality
minor salivary gland	UBERON:0001830	98.80	gold quality
skin of leg	UBERON:0001511	98.75	gold quality
sural nerve	UBERON:0015488	98.68	gold quality
skin of abdomen	UBERON:0001416	98.63	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	98.38	gold quality
mucosa of transverse colon	UBERON:0004991	98.21	gold quality
saliva-secreting gland	UBERON:0001044	98.20	gold quality
endometrium epithelium	UBERON:0004811	97.49	gold quality
lower esophagus mucosa	UBERON:0035834	97.37	gold quality
mouth mucosa	UBERON:0003729	97.24	gold quality
zone of skin	UBERON:0000014	96.89	gold quality
transverse colon	UBERON:0001157	96.88	gold quality
right uterine tube	UBERON:0001302	96.74	gold quality
body of stomach	UBERON:0001161	96.16	gold quality
esophagus mucosa	UBERON:0002469	96.11	gold quality
small intestine Peyer’s patch	UBERON:0003454	96.01	gold quality
mucosa of stomach	UBERON:0001199	95.85	gold quality
dorsal root ganglion	UBERON:0000044	95.44	gold quality
small intestine	UBERON:0002108	95.36	gold quality
spleen	UBERON:0002106	95.30	gold quality
parotid gland	UBERON:0001831	95.24	gold quality
trigeminal ganglion	UBERON:0001675	95.04	gold quality
ectocervix	UBERON:0012249	95.03	gold quality
vagina	UBERON:0000996	95.01	gold quality
olfactory bulb	UBERON:0002264	94.86	gold quality
esophagus	UBERON:0001043	94.77	gold quality
tendon of biceps brachii	UBERON:0008188	94.36	gold quality
muscle layer of sigmoid colon	UBERON:0035805	94.35	gold quality
endocervix	UBERON:0000458	94.27	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-8410	yes	405.65
E-CURD-114	yes	67.24
E-GEOD-135922	yes	21.78
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ANXA7, BHLHE23, F2RL1, PRKDC, RORA, SNAI1, SNAI2, ZEB1, ZKSCAN3

miRNA regulators (miRDB)

35 targeting ITGB4, 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-9-5P	100.00	72.28	2361
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-589-3P	99.91	69.62	2088
HSA-MIR-302A-3P	99.89	71.23	1777
HSA-MIR-302B-3P	99.89	71.23	1777
HSA-MIR-302C-3P	99.89	71.20	1778
HSA-MIR-302D-3P	99.89	71.25	1777
HSA-MIR-659-3P	99.85	70.69	1620
HSA-MIR-373-3P	99.84	70.68	1668
HSA-MIR-520E-3P	99.84	70.55	1698
HSA-MIR-372-3P	99.83	70.58	1691
HSA-MIR-520A-3P	99.83	70.59	1687
HSA-MIR-520B-3P	99.83	70.56	1699
HSA-MIR-520C-3P	99.83	70.56	1699
HSA-MIR-520D-3P	99.83	70.78	1676
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-4729	99.69	72.18	4233
HSA-MIR-6766-5P	99.68	67.70	2325
HSA-MIR-519A-3P	99.67	71.67	1868
HSA-MIR-519B-3P	99.67	71.67	1868
HSA-MIR-519C-3P	99.67	71.67	1870
HSA-MIR-487A-5P	98.85	69.37	993
HSA-MIR-487B-5P	98.85	69.48	987
HSA-MIR-4477A	98.83	69.75	2952
HSA-MIR-210-5P	98.57	64.37	832
HSA-MIR-4664-5P	98.17	65.07	1020
HSA-MIR-6801-3P	98.04	64.64	805
HSA-MIR-6810-3P	97.96	64.57	1023
HSA-MIR-296-5P	97.61	64.02	851

Literature-anchored findings (GeneRIF, showing 40)

• Reduction in integrin alpha6beta4 is related to changes seen during immortalization and malignant progression (PMID:11809527)
• Acute hyperglycaemia induces an up-regulation of seven major genes, four of which were not previously reported in the literature. Northern blot analyses, performed on these 4 genes, confirm macroarrays results for alphav, beta4, c-myc, and MUC18. (PMID:11848444)
• binding of beta 4 to plectin is essential for the proper formation and function of hemidesmosomes (PMID:11886501)
• The integrin beta4B and beta4C variants were found not to be expressed in a tissue-specific manner. (PMID:12023052)
• Integrin (alpha 6 beta 4) regulation of eIF-4E activity and VEGF translation (Integrin alpha6beta4) (PMID:12105188)
• integrin beta-4 expression in thyroid carcinoma may play a role in the development of gross lymph node metastasis of papillary carcinomas. (PMID:12167101)
• integrin beta4 expression is increased when ROR alpha is activated in prostate cancer cells (PMID:12168086)
• Data suggest that the stability of the interaction between alpha6beta4 and laminin-5 is influenced by the clustering of alpha6beta4 through the deposition of laminin-5 underneath the cells. (PMID:12429829)
• Results suggest that alpha6beta4 integrin-mediated interactions of astrocytes with beta(ig)-h3 transduce intracellular signals through the focal adhesion proteins, which may regulate certain aspects of astrocyte response to brain injury. (PMID:12499048)
• This study revealed detailed topography of integrins in malignant tumours derived from intercalated acinar segment of salivary gland which might be useful their diagnosis , especially of fine-needle aspiration products or from incisional biopsy. (PMID:12694355)
• extracellular domain of beta 4 integrin, through its ability to bind ligand, functions to integrate the divergent effects of growth factors on the cytoskeleton and adhesion receptors (PMID:12865436)
• Data show that macrophage stimulating protein (MSP) and its receptor (Ron) induce phosphorylation of both Ron and alpha6beta4 integrin, and result in activation of alpha3beta1 integrin. (PMID:12919677)
• integrin beta4/calcium-activated chloride channel ligation elicits selective signaling via focal adhesion kinase to promote metastatic growth (PMID:14512419)
• compartmentalization in lipid rafts is necessary to couple the alpha6beta4 integrin to a palmitoylated src family kinases and promote EGF-dependent mitogenesis. (PMID:14517202)
• Data demonstrate that alpha6beta4 integrin mediates pancreatic epithelial cell adhesion to Netrin-1, whereas recruitment of alpha6beta4 and alpha3beta1 regulate the migration of putative pancreatic progenitors on Netrin-1. (PMID:14602071)
• Pyloric atresia-junctional epidermolysis bullosa syndrome is caused by mutations in this gene in a case report. (PMID:15009117)
• alpha(6)beta(4) has a generic influence on the invasion of carcinoma cells that is not specific to Met (PMID:15161909)
• Results suggest that bacterial heat shock protein 60 may promote epithelial cell migration through activation of epidermal growth factor receptor and mitogen-activated protein kinases, and inhibition of alpha6beta4 integrin expression. (PMID:15194479)
• cAMP-Epac-Rap1 pathway regulates cell spreading and cell adhesion to laminin-5 through the alpha3beta1 integrin but not the alpha6beta4 integrin (PMID:15302884)
• link between the ligation of the beta(4) integrin and beta(1) integrin-mediated cell adhesion in carcinoma and pre-carcinoma cells. (PMID:15304080)
• high expression of HPV type 8 (HPV8) E2 in cultured primary keratinocytes leads to strong down-regulation of beta4-integrin expression levels (PMID:15367640)
• Blockage of beta4 integrin activity by antagonizing antibody abrogated ATV-induced endothelial death. (PMID:15381079)
• activation by E-selectin, thus modulating adhesion (PMID:15387376)
• These results provide genetic evidence that alpha6beta4 signaling promotes the onset of the invasive phase of pathological angiogenesis (PMID:15542431)
• alpha6beta4 can augment cell-cell adhesion and slow down haptotaxis over laminin-5 (PMID:15579904)
• The beta4 integrins is a functional connection between CD9, as evidenced by anti-CD9 antibody effects on beta4-dependent cell spreading. (PMID:15611341)
• immunohistochemistry clearly demonstrated colocalisation between calcium activated chloride channel 2 and integrin beta4 (PMID:15707651)
• the CH1 domain of the plectin-ABD associates with the groove between the two FNIII domains of beta4 (PMID:15817481)
• beta4ctd- form is lost from colon cancer cells, while the level of the wild-type form of beta4, which is functional for adhesion to laminin, is increased in primary tumors in relation with the expression of c-Myc (PMID:16007143)
• alpha6beta4 integrin is mobilized and activated durign carcinoma progression [review] (PMID:16258729)
• PMP22 forms a complex with alpha6beta4 integrin in cultured colonic adenocarcinoma cells. (PMID:16436605)
• EWI proteins EWI-2 and EWI-F, alpha3beta1 and alpha6beta4 integrins, and protein palmitoylation have contrasting effects on cell surface CD9 organization (PMID:16537545)
• Slug regulates integrin alpha3, beta1, and beta4 expression and cell proliferation in human epidermal keratinocytes (PMID:16707493)
• The results confirm the relevance of beta4 expression in mammary tumors and indicate this integrin as a relevant target for tumor therapy. (PMID:16740748)
• Ln-5 is an important regulator of ADPKD cell proliferation and cystogenesis; Ln-5 gamma(2) chain and Ln-5-alpha(6)beta(4) integrin interaction both contribute to these phenotypic changes (PMID:16870608)
• Both the beta4 integrin ligand-binding and cytoplasmic domains together with epidermal growth factor were required for the synergistic activation of a Rac-dependent signaling pathway that was essential for keratinocyte directional migration. (PMID:16914518)
• The role of PTHrP in breast cancer growth and metastasis may be mediated via upregulation of integrin alpha6beta4 expression and Akt activation, with consequent inactivation of GSK-3. (PMID:16965770)
• domain V of the gamma2 chain negatively regulates the integrin beta4 phosphorylation, probably through a syndecan-1-mediated signaling, leading to enhanced cell adhesion and suppressed cell motility (PMID:17314405)
• Data show that in bullous pemphigoid, expression of beta4 integrin was irregular and was detected mainly in dermal part of the blister. (PMID:17515951)
• analysis of the signaling functions of the beta4 integrin intracellular domain (PMID:17711859)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	itgb4	ENSDARG00000028507
mus_musculus	Itgb4	ENSMUSG00000020758
rattus_norvegicus	Itgb4	ENSRNOG00000005580

Paralogs (8): ITGB5 (ENSG00000082781), ITGB8 (ENSG00000105855), ITGB6 (ENSG00000115221), ITGB7 (ENSG00000139626), ITGB1 (ENSG00000150093), ITGB2 (ENSG00000160255), ITGBL1 (ENSG00000198542), ITGB3 (ENSG00000259207)

Protein

Protein identifiers

Integrin beta-4 — P16144 (reviewed: P16144)

Alternative names: GP150

All UniProt accessions (4): P16144, J3KSH9, J3QQL2, J3QRK0

UniProt curated annotations — full annotation on UniProt →

Function. Integrin alpha-6/beta-4 is a receptor for laminin. Plays a critical structural role in the hemidesmosome of epithelial cells. Is required for the regulation of keratinocyte polarity and motility. ITGA6:ITGB4 binds to NRG1 (via EGF domain) and this binding is essential for NRG1-ERBB signaling. ITGA6:ITGB4 binds to IGF1 and this binding is essential for IGF1 signaling. ITGA6:ITGB4 binds to IGF2 and this binding is essential for IGF2 signaling.

Subunit / interactions. Heterodimer of an alpha and a beta subunit. Beta-4 associates with alpha-6. Interacts (via cytoplasmic region) with COL17A1 (via cytoplasmic region). Interacts (via cytoplasmic region) with DST isoform 3 (via N-terminus). Isoform beta-4a interacts (via cytoplasmic domain) with DST (via N-terminus). Interacts with RAC1. ITGA6:ITGB4 is found in a ternary complex with NRG1 and ERBB3. ITGA6:ITGB4 is found in a ternary complex with IGF1 and IGF1R. ITGA6:ITGB4 interacts with IGF2. Interacts with TMEM268; this interaction prevents ITGB4 degradation. Interacts (via C-terminus) with ARHGEF40 (via central region); the interaction may facilitate ITGB4 localization to hemidesmosomes and act as a linker to anchor keratin filaments to ITGB4 in hemidesmosomes.

Subcellular location. Cell membrane. Cell junction. Hemidesmosome.

Tissue specificity. Integrin alpha-6/beta-4 is predominantly expressed by epithelia. Isoform beta-4D is also expressed in colon and placenta. Isoform beta-4E is also expressed in epidermis, lung, duodenum, heart, spleen and stomach.

Post-translational modifications. Palmitoylated by DHHC3 at several cysteines of the membrane-proximal region, enhancing stability and cell surface expression. Palmitoylation also promotes secondary association with tertaspanins.

Disease relevance. Epidermolysis bullosa, junctional 5A, intermediate (JEB5A) [MIM:619816] A form of epidermolysis bullosa, a genodermatosis characterized by recurrent blistering, fragility of the skin and mucosal epithelia, and erosions caused by minor mechanical trauma. JEB5A is an autosomal recessive, intermediate form in which blistering lesions occur between the epidermis and the dermis at the lamina lucida level of the basement membrane zone. In intermediate forms of junctional epidermolysis bullosa, blistering does not lead to the formation of chronic granulation tissue and does not affect the lifespan of affected individuals. Nail dystrophy and dental enamel defects are present. Scarring or non-scarring alopecia and diffuse hair loss may occur. The disease is caused by variants affecting the gene represented in this entry. Epidermolysis bullosa, junctional 5B, with pyloric atresia (JEB5B) [MIM:226730] A form of epidermolysis bullosa, a genodermatosis characterized by recurrent blistering, fragility of the skin and mucosal epithelia, and erosions caused by minor mechanical trauma. Junctional epidermolysis bullosa is characterized by blistering that occurs at the level of the lamina lucida in the skin basement membrane. JEB5B is an autosomal recessive, severe, frequently lethal form with variable involvement of skin, nails, mucosa, and with variable effects on the digestive system. It is characterized by mucocutaneous fragility, aplasia cutis congenita, and gastrointestinal atresia, which most commonly affects the pylorus. Pyloric atresia is a primary manifestation rather than a scarring process secondary to epidermolysis bullosa. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. The VWFA domain (or beta I domain) contains three cation-binding sites: the ligand-associated metal ion-binding site (LIMBS or SyMBS), the metal ion-dependent adhesion site (MIDAS), and the adjacent MIDAS site (ADMIDAS). This domain is also part of the ligand-binding site. The fibronectin type-III-like domains bind BPAG1 and plectin and probably also recruit BP230.

Similarity. Belongs to the integrin beta chain family.

Isoforms (5)

UniProt ID	Names	Canonical?
P16144-1	Beta-4C	yes
P16144-2	Beta-4A
P16144-3	Beta-4B
P16144-4	Beta-4D
P16144-5	Beta-4E

RefSeq proteins (4): NP_000204, NP_001005619, NP_001005731, NP_001308052 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000742	EGF	Domain
IPR002369	Integrin_bsu_VWA	Domain
IPR003644	Calx_beta	Domain
IPR003961	FN3_dom	Domain
IPR012013	Integrin_bsu-4	Family
IPR012896	Integrin_bsu_tail	Domain
IPR013783	Ig-like_fold	Homologous_superfamily
IPR015812	Integrin_bsu	Family
IPR016201	PSI	Domain
IPR033760	Integrin_beta_N	Domain
IPR036116	FN3_sf	Homologous_superfamily
IPR036349	Integrin_bsu_tail_dom_sf	Homologous_superfamily
IPR036465	vWFA_dom_sf	Homologous_superfamily
IPR038081	CalX-like_sf	Homologous_superfamily
IPR040622	EGF_integrin_1	Domain
IPR057243	Integrin_I-EGF_CS	Conserved_site

Pfam: PF00041, PF00362, PF03160, PF07965, PF17205, PF18372, PF23106

UniProt features (159 total): strand 45, disulfide bond 23, sequence variant 20, binding site 12, domain 11, modified residue 10, sequence conflict 8, region of interest 6, glycosylation site 5, splice variant 5, turn 4, helix 3, topological domain 2, compositionally biased region 2, signal peptide 1, chain 1, transmembrane region 1

Structure

Experimental structures (PDB)

13 structures.

PDB	Method	Resolution (Å)
3FSO	X-RAY DIFFRACTION	1.41
3FQ4	X-RAY DIFFRACTION	1.49
4WTX	X-RAY DIFFRACTION	1.5
6GVK	X-RAY DIFFRACTION	1.55
4WTW	X-RAY DIFFRACTION	1.61
3H6A	X-RAY DIFFRACTION	1.61
3F7Q	X-RAY DIFFRACTION	1.75
3F7R	X-RAY DIFFRACTION	2.04
6GVL	X-RAY DIFFRACTION	2.05
1QG3	X-RAY DIFFRACTION	2.15
3F7P	X-RAY DIFFRACTION	2.75
4Q58	X-RAY DIFFRACTION	4
2YRZ	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P16144-F1	69.04	0.14

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): 139 (in midas binding site); 141 (in admidas binding site); 141 (in midas binding site); 144 (in admidas binding site); 145 (in admidas binding site); 176 (in limbs binding site); 228 (in limbs binding site); 230 (in limbs binding site); 232 (in limbs binding site); 233 (in limbs binding site); 233 (in midas binding site); 350 (in admidas binding site)

Post-translational modifications (10): 771, 1069, 1119, 1454, 1457, 1474, 1487, 1494, 1530, 1791

Disulfide bonds (23): 30–48, 38–455, 41–61, 51–72, 245–288, 457–476, 468–479, 481–490, 492–520, 503–518, 512–523, 525–536, 543–557, 551–562, 564–573, 575–598, 582–596, 590–601, 603–614, 626–671 …

Glycosylation sites (5): 327, 491, 579, 617, 695

Function

Pathways and Gene Ontology

Reactome pathways

12 pathways

ID	Pathway
R-HSA-2022090	Assembly of collagen fibrils and other multimeric structures
R-HSA-3000157	Laminin interactions
R-HSA-3000170	Syndecan interactions
R-HSA-446107	Type I hemidesmosome assembly
R-HSA-9725554	Differentiation of Keratinocytes in Interfollicular Epidermis in Mammalian Skin
R-HSA-1266738	Developmental Biology
R-HSA-1474244	Extracellular matrix organization
R-HSA-1474290	Collagen formation
R-HSA-1500931	Cell-Cell communication
R-HSA-3000171	Non-integrin membrane-ECM interactions
R-HSA-446728	Cell junction organization
R-HSA-9734767	Developmental Cell Lineages

MSigDB gene sets: 477 (showing top): GU_PDEF_TARGETS_DN, GOBP_FORMATION_OF_PRIMARY_GERM_LAYER, JAEGER_METASTASIS_DN, GCANCTGNY_MYOD_Q6, AREB6_03, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_UP, GOBP_GLIAL_CELL_DEVELOPMENT, GOCC_CELL_SURFACE, WEIGEL_OXIDATIVE_STRESS_BY_TBH_AND_H2O2, GOBP_NEUROGENESIS, TOMLINS_PROSTATE_CANCER_DN, HUMMERICH_SKIN_CANCER_PROGRESSION_UP, GOBP_AMEBOIDAL_TYPE_CELL_MIGRATION, SHEPARD_BMYB_MORPHOLINO_DN

GO Biological Process (18): autophagy (GO:0006914), cell adhesion (GO:0007155), cell-matrix adhesion (GO:0007160), integrin-mediated signaling pathway (GO:0007229), response to wounding (GO:0009611), cell migration (GO:0016477), hemidesmosome assembly (GO:0031581), peripheral nervous system myelin formation (GO:0032290), cell adhesion mediated by integrin (GO:0033627), nail development (GO:0035878), skin morphogenesis (GO:0043589), filopodium assembly (GO:0046847), mesodermal cell differentiation (GO:0048333), cell motility (GO:0048870), trophoblast cell migration (GO:0061450), cell-cell adhesion (GO:0098609), cell communication (GO:0007154), myelination in peripheral nervous system (GO:0022011)

GO Molecular Function (6): G protein-coupled receptor binding (GO:0001664), integrin binding (GO:0005178), metal ion binding (GO:0046872), protein binding (GO:0005515), insulin-like growth factor I binding (GO:0031994), neuregulin binding (GO:0038132)

GO Cellular Component (15): basement membrane (GO:0005604), nucleolus (GO:0005730), plasma membrane (GO:0005886), focal adhesion (GO:0005925), integrin complex (GO:0008305), basal plasma membrane (GO:0009925), cell surface (GO:0009986), cell junction (GO:0030054), hemidesmosome (GO:0030056), cell leading edge (GO:0031252), nuclear membrane (GO:0031965), signaling receptor complex (GO:0043235), extracellular exosome (GO:0070062), membrane (GO:0016020), anchoring junction (GO:0070161)

Reactome top-level categories

Rollup of top-7 pathways:

Category	Pathways
Extracellular matrix organization	3
Collagen formation	1
Non-integrin membrane-ECM interactions	1
Cell junction organization	1
Developmental Cell Lineages of the Integumentary System	1
Cell-Cell communication	1
Developmental Biology	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
cellular process	3
cell adhesion	2
signaling receptor binding	2
cell-substrate junction	2
catabolic process	1
transmembrane transport	1
process utilizing autophagic mechanism	1
cell-substrate adhesion	1
cell surface receptor signaling pathway	1
response to stress	1
cell motility	1
cell-substrate junction assembly	1
myelination in peripheral nervous system	1
myelin assembly	1
anatomical structure development	1
limb development	1
animal organ morphogenesis	1
skin development	1
plasma membrane bounded cell projection assembly	1
mesoderm formation	1
cell differentiation	1
ameboidal-type cell migration	1
embryo implantation	1
Schwann cell development	1
peripheral nervous system axon ensheathment	1
myelination	1
protein-containing complex binding	1
cell adhesion molecule binding	1
cation binding	1
binding	1
insulin-like growth factor binding	1
growth factor binding	1
extracellular matrix	1
nuclear lumen	1
intracellular membraneless organelle	1
membrane	1
cell periphery	1
protein complex involved in cell adhesion	1
plasma membrane signaling receptor complex	1

Protein interactions and networks

STRING

2256 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ITGB4	ITGA6	P23229	999
ITGB4	PLEC	Q15149	997
ITGB4	COL17A1	Q9UMD9	986
ITGB4	DST	Q03001	973
ITGB4	ERBB2	P04626	939
ITGB4	LAMB3	Q13751	939
ITGB4	ITGA3	P26006	890
ITGB4	LAMC2	Q13753	881
ITGB4	LAMA3	Q16787	830
ITGB4	ZKSCAN3	Q9BRR0	830
ITGB4	ITGA5	P08648	819
ITGB4	SFTPC	P11686	811
ITGB4	CD151	P48509	798
ITGB4	ERBIN	Q96RT1	789
ITGB4	LAMA4	Q16363	767

IntAct

135 interactions, top by confidence:

A	B	Type	Score
ITGA6	ITGB4	psi-mi:“MI:0915”(physical association)	0.750
ITGA6	ITGB4	psi-mi:“MI:0403”(colocalization)	0.750
EGFR	CTNND1	psi-mi:“MI:0914”(association)	0.750
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
Plec	ITGB4	psi-mi:“MI:0407”(direct interaction)	0.650
DKKL1	DENND11	psi-mi:“MI:0914”(association)	0.640
KLK5	DENND11	psi-mi:“MI:0914”(association)	0.640
CFTR	HAX1	psi-mi:“MI:0914”(association)	0.610
PDGFRB	PIK3R2	psi-mi:“MI:0914”(association)	0.610
CD151	ITGB4	psi-mi:“MI:0915”(physical association)	0.600
CD151	ITGB4	psi-mi:“MI:0403”(colocalization)	0.600
ITGA6	ITGB1	psi-mi:“MI:0914”(association)	0.560
ITGB4	PLEC	psi-mi:“MI:0407”(direct interaction)	0.560
PLEC	ITGB4	psi-mi:“MI:0407”(direct interaction)	0.560
ILK	HAX1	psi-mi:“MI:0914”(association)	0.530

BioGRID (145): ITGB4 (Affinity Capture-Western), ITGB4 (Affinity Capture-Western), SEL1L (Affinity Capture-Western), ITGB4 (Affinity Capture-Western), ITGB4 (Affinity Capture-MS), ITGB4 (Affinity Capture-MS), ITGB4 (Affinity Capture-MS), ITGB4 (Affinity Capture-MS), ITGB4 (Affinity Capture-MS), ITGB4 (Affinity Capture-MS), ITGB4 (Affinity Capture-MS), ITGB4 (Affinity Capture-MS), ITGB4 (Affinity Capture-MS), ITGB4 (Affinity Capture-MS), ITGB4 (Affinity Capture-MS)

ESM2 similar proteins: A0A0R4IKU3, A0A8M9PFP2, A1A5Y0, A2A863, A2VCU8, A5A6L1, B0S5G3, L7VG99, O00622, O08841, O35118, O42493, O93512, P08163, P08833, P16042, P16144, P17668, P18406, Q07663, Q0VCN6, Q13753, Q501P1, Q53RD9, Q5R9Q9, Q61220, Q61592, Q64632, Q6DDW2, Q7T3Q2, Q7ZV46, Q7ZXL5, Q8R4Y4, Q8R553, Q8VDA1, Q91166, Q91167, Q91713, Q99JH7, Q9BQT9

Diamond homologs: A2A863, A5Z1X6, B0FYY4, O08680, O54890, O70309, P05106, P05107, P05556, P07228, P09055, P11584, P11835, P12606, P12607, P16144, P18084, P18563, P18564, P26010, P26011, P26012, P29319, P29320, P32592, P49134, P53712, P53713, P53714, P80747, Q07409, Q07441, Q09062, Q0VBD0, Q1RPR6, Q27591, Q27874, Q2VJ42, Q3UH53, Q3UV74

SIGNOR signaling

18 interactions.

A	Effect	B	Mechanism
PRKCA	down-regulates	ITGB4	phosphorylation
PRKACA	down-regulates	ITGB4	phosphorylation
ITGB4	up-regulates	PI3K	binding
F2RL1	“down-regulates quantity by repression”	ITGB4	“transcriptional regulation”
ITGB1BP1	“down-regulates activity”	ITGB4	binding
DOK1	“down-regulates activity”	ITGB4	binding
ITGB4	“up-regulates activity”	PTK2
Kindlin	“up-regulates activity”	ITGB4	binding
RTKs	“up-regulates activity”	ITGB4	phosphorylation
NEU1	“down-regulates activity”	ITGB4
ITGB4	up-regulates	PIK3CA	binding
ITGB4	up-regulates	PIK3CB	binding
ITGB4	up-regulates	PIK3CD	binding
ITGB4	up-regulates	PIK3CG	binding
ITGB4	“up-regulates activity”	PMP22	binding
TLN1	“up-regulates activity”	ITGB4	binding
ITGB4	“form complex”	“A6/b4 integrin”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 88 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

GO biological processes:

GO term	Partners	Fold	FDR
integrin-mediated signaling pathway	5	12.0×	8e-03
positive regulation of cell migration	10	9.2×	9e-05
cell-cell adhesion	6	9.1×	8e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

1443 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	75
Likely pathogenic	33
Uncertain significance	418
Likely benign	673
Benign	78

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1048031	NM_000213.5(ITGB4):c.472_566+184del	Pathogenic
1048032	NM_000213.5(ITGB4):c.701G>T (p.Gly234Val)	Pathogenic
1048060	NM_000213.5(ITGB4):c.847C>T (p.Arg283Cys)	Pathogenic
1048062	NM_000213.5(ITGB4):c.1370G>A (p.Cys457Tyr)	Pathogenic
1048063	NM_000213.5(ITGB4):c.2012G>C (p.Cys671Ser)	Pathogenic
1048064	NM_000213.5(ITGB4):c.2465T>C (p.Leu822Ser)	Pathogenic
1048066	NM_000213.5(ITGB4):c.3040C>T (p.Arg1014Trp)	Pathogenic
1048067	NM_000213.5(ITGB4):c.3321_3331del (p.Asp1109fs)	Pathogenic
1048068	NM_000213.5(ITGB4):c.3707_3725del (p.Thr1236fs)	Pathogenic
1077026	NM_000213.5(ITGB4):c.2524C>T (p.Gln842Ter)	Pathogenic
1252046	NM_000213.5(ITGB4):c.3793+1G>C	Pathogenic
1292044	NM_000213.5(ITGB4):c.794dup (p.Ala266fs)	Pathogenic
1323126	NM_000213.5(ITGB4):c.882_886delinsGAACCA (p.Thr295fs)	Pathogenic
14730	ITGB4, 1-BP DEL, 1150G	Pathogenic
14732	NM_000213.5(ITGB4):c.467T>C (p.Leu156Pro)	Pathogenic
14733	NM_000213.5(ITGB4):c.1660C>T (p.Arg554Ter)	Pathogenic
14736	NM_000213.5(ITGB4):c.3793+1G>A	Pathogenic
14738	NM_000213.5(ITGB4):c.112T>C (p.Cys38Arg)	Pathogenic
14740	NM_000213.5(ITGB4):c.2792G>A (p.Gly931Asp)	Pathogenic
14744	NM_000213.5(ITGB4):c.3279_3793+180del	Pathogenic
1941230	NM_000213.5(ITGB4):c.928del (p.Leu310fs)	Pathogenic
2505622	NM_000213.5(ITGB4):c.1234dup (p.Leu412fs)	Pathogenic
2694300	NM_000213.5(ITGB4):c.26G>A (p.Trp9Ter)	Pathogenic
2696609	NM_000213.5(ITGB4):c.209del (p.Ala70fs)	Pathogenic
2697720	NM_000213.5(ITGB4):c.1736dup (p.Asn579fs)	Pathogenic
2698051	NM_000213.5(ITGB4):c.1454G>A (p.Trp485Ter)	Pathogenic
2698718	NM_000213.5(ITGB4):c.1614_1615del (p.Tyr538_Asp539delinsTer)	Pathogenic
2701505	NM_000213.5(ITGB4):c.2936dup (p.Asn980fs)	Pathogenic
2709560	NM_000213.5(ITGB4):c.1641del (p.Phe549fs)	Pathogenic
2729661	NM_000213.5(ITGB4):c.310C>T (p.Gln104Ter)	Pathogenic

SpliceAI

7268 predictions. Top by Δscore:

Variant	Effect	Δscore
17:75727181:A:AG	acceptor_gain	1.0000
17:75727181:ATCT:A	acceptor_gain	1.0000
17:75727182:T:G	acceptor_gain	1.0000
17:75727184:T:TA	acceptor_gain	1.0000
17:75727190:CCCA:C	acceptor_loss	1.0000
17:75727193:A:AG	acceptor_gain	1.0000
17:75727193:A:AT	acceptor_loss	1.0000
17:75727194:G:GG	acceptor_gain	1.0000
17:75727194:GC:G	acceptor_gain	1.0000
17:75727194:GCA:G	acceptor_gain	1.0000
17:75727194:GCAA:G	acceptor_gain	1.0000
17:75727194:GCAAA:G	acceptor_gain	1.0000
17:75727275:GAG:G	donor_gain	1.0000
17:75727277:GGTG:G	donor_loss	1.0000
17:75727278:G:A	donor_loss	1.0000
17:75727278:G:GG	donor_gain	1.0000
17:75727397:T:A	acceptor_gain	1.0000
17:75727398:G:A	acceptor_gain	1.0000
17:75727402:A:AG	acceptor_gain	1.0000
17:75727402:AGAT:A	acceptor_gain	1.0000
17:75727403:G:GT	acceptor_gain	1.0000
17:75727403:GA:G	acceptor_gain	1.0000
17:75727403:GAT:G	acceptor_gain	1.0000
17:75727403:GATG:G	acceptor_gain	1.0000
17:75727403:GATGT:G	acceptor_gain	1.0000
17:75727483:A:T	donor_gain	1.0000
17:75727503:G:GT	donor_gain	1.0000
17:75727503:GAG:G	donor_gain	1.0000
17:75727640:ACT:A	acceptor_gain	1.0000
17:75727640:ACTG:A	acceptor_gain	1.0000

AlphaMissense

11917 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:75751036:T:A	W1240R	1.000
17:75751036:T:C	W1240R	1.000
17:75752266:T:G	Y1296D	1.000
17:75755784:T:A	W1548R	1.000
17:75755784:T:C	W1548R	1.000
17:75756513:T:C	F1598S	1.000
17:75756787:T:A	W1661R	1.000
17:75756787:T:C	W1661R	1.000
17:75756789:G:C	W1661C	1.000
17:75756789:G:T	W1661C	1.000
17:75757030:T:C	F1714S	1.000
17:75727796:A:C	D137A	0.999
17:75727796:A:T	D137V	0.999
17:75727802:C:T	S139F	0.999
17:75728427:T:C	F174L	0.999
17:75728429:T:A	F174L	0.999
17:75728429:T:G	F174L	0.999
17:75739999:T:A	W792R	0.999
17:75739999:T:C	W792R	0.999
17:75750233:T:A	W1147R	0.999
17:75750233:T:C	W1147R	0.999
17:75750986:C:A	P1223Q	0.999
17:75751001:T:C	F1228S	0.999
17:75751031:T:C	L1238P	0.999
17:75751037:G:C	W1240S	0.999
17:75751038:G:C	W1240C	0.999
17:75751038:G:T	W1240C	0.999
17:75751046:C:A	P1243Q	0.999
17:75751072:G:C	A1252P	0.999
17:75751075:T:G	Y1253D	0.999

dbSNP variants (sampled 300 via entrez): RS1000024205 (17:75733555 G>A), RS1000046649 (17:75749062 G>A), RS1000137556 (17:75756273 A>C), RS1000221686 (17:75749168 T>C), RS1000268923 (17:75743605 C>A,T), RS1000345219 (17:75738308 C>T), RS1000353070 (17:75722643 G>A), RS1000455687 (17:75738842 G>A), RS1000537516 (17:75744405 C>A,G,T), RS1000601611 (17:75742845 G>A,T), RS1000764310 (17:75726978 T>C,G), RS1000948422 (17:75721431 A>G,T), RS1000997150 (17:75732036 A>G), RS1000999508 (17:75728319 C>T), RS1001001221 (17:75747510 C>T)

Disease associations

OMIM: gene MIM:147557 | disease phenotypes: MIM:226730, MIM:619816, MIM:131800, MIM:226650, MIM:617519, MIM:230200

GenCC curated gene-disease

Disease	Classification	Inheritance
junctional epidermolysis bullosa with pyloric atresia	Definitive	Autosomal recessive
epidermolysis bullosa simplex	Definitive	Autosomal dominant
junctional epidermolysis bullosa, non-Herlitz type	Strong	Autosomal recessive
epidermolysis bullosa, junctional 5A, intermediate	Strong	Semidominant
aplasia cutis congenita	Supportive	Autosomal dominant
epidermolysis bullosa simplex 5C, with pyloric atresia	Supportive	Autosomal recessive
localized junctional epidermolysis bullosa, non-Herlitz type	Supportive	Autosomal recessive
generalized junctional epidermolysis bullosa non-Herlitz type	Supportive	Autosomal recessive
epidermolysis bullosa simplex 1C, localized	Limited	Unknown

Mondo (16): junctional epidermolysis bullosa with pyloric atresia (MONDO:0009183), epidermolysis bullosa, junctional 5A, intermediate (MONDO:0030768), epidermolysis bullosa simplex 1C, localized (MONDO:0007551), junctional epidermolysis bullosa, non-Herlitz type (MONDO:0009180), junctional epidermolysis bullosa (MONDO:0017612), myoepithelial tumor (MONDO:0002380), nephrotic syndrome (MONDO:0005377), focal segmental glomerulosclerosis (MONDO:0100313), neurodevelopmental disorder with hypotonia, neuropathy, and deafness (MONDO:0060496), galactokinase deficiency (MONDO:0009255), multiple sclerosis (MONDO:0005301), aplasia cutis congenita (MONDO:0007145), epidermolysis bullosa simplex 5C, with pyloric atresia (MONDO:0012807), localized junctional epidermolysis bullosa, non-Herlitz type (MONDO:0016673), generalized junctional epidermolysis bullosa non-Herlitz type (MONDO:0019307)

Orphanet (10): Junctional epidermolysis bullosa with pyloric atresia (Orphanet:79403), Localized epidermolysis bullosa simplex (Orphanet:79400), Localized junctional epidermolysis bullosa (Orphanet:251393), Intermediate generalized junctional epidermolysis bullosa (Orphanet:79402), Junctional epidermolysis bullosa inversa (Orphanet:79405), OBSOLETE: Junctional epidermolysis bullosa, non-Herlitz type (Orphanet:89840), Junctional epidermolysis bullosa (Orphanet:305), Galactosemia (Orphanet:352), Galactokinase deficiency (Orphanet:79237), NON RARE IN EUROPE: Multiple sclerosis (Orphanet:802)

HPO phenotypes

87 total (30 of 87 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000070	Ureterocele
HP:0000075	Renal duplication
HP:0000079	Abnormality of the urinary system
HP:0000096	Glomerular sclerosis
HP:0000110	Renal dysplasia
HP:0000126	Hydronephrosis
HP:0000656	Ectropion
HP:0000790	Hematuria
HP:0000795	Abnormality of the urethra
HP:0000982	Palmoplantar keratoderma
HP:0000987	Atypical scarring of skin
HP:0001000	Abnormality of skin pigmentation
HP:0001030	Fragile skin
HP:0001056	Milia
HP:0001057	Aplasia cutis congenita
HP:0001059	Pterygium
HP:0001060	Axillary pterygium
HP:0001075	Atrophic scars
HP:0001362	Calvarial skull defect
HP:0001371	Flexion contracture
HP:0001510	Growth delay
HP:0001522	Death in infancy
HP:0001561	Polyhydramnios
HP:0001581	Recurrent skin infections
HP:0001770	Toe syndactyly
HP:0001798	Anonychia
HP:0001805	Onychogryphosis
HP:0001810	Dystrophic toenail
HP:0001903	Anemia

GWAS associations

0 associations (top):

MeSH disease descriptors (8)

Descriptor	Name	Tree numbers
D016110	Epidermolysis Bullosa Simplex	C16.131.831.493.180; C16.320.850.275.180; C17.800.804.493.180; C17.800.827.275.180; C17.800.865.410.180
D016109	Epidermolysis Bullosa, Junctional	C16.131.831.493.170; C16.320.850.275.170; C17.800.804.493.170; C17.800.827.275.170; C17.800.865.410.170
D005923	Glomerulosclerosis, Focal Segmental	C12.050.351.968.419.570.363.640; C12.200.777.419.570.363.660; C12.950.419.570.363.640
D009103	Multiple Sclerosis	C10.114.375.500; C10.314.350.500; C20.111.258.250.500
D009208	Myoepithelioma	C04.557.435.585
D009404	Nephrotic Syndrome	C12.050.351.968.419.630.643; C12.200.777.419.630.643; C12.950.419.630.643
C567408	Epidermolysis Bullosa Simplex With Pyloric Atresia (supp.)
C535377	Epidermolysis bullosa with pyloric atresia (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6066233 (SINGLE PROTEIN)

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: catalytic receptor — Integrins

ChEMBL bioactivities

2 potent at pChembl≥5 of 3 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
5.46	Kd	3507	nM	CHEMBL3752910
5.46	ED50	3507	nM	CHEMBL3752910

PubChem BioAssay actives

1 with measured affinity, of 5 total; 1 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
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148611: Binding affinity to human ITGB4 incubated for 45 mins by Kinobead based pull down assay	kd	3.5068	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases abundance, affects cotreatment, increases expression, affects binding, increases reaction (+2 more)	7
Cadmium Chloride	decreases expression, increases abundance, increases expression, affects cotreatment	4
Particulate Matter	increases expression, affects cotreatment, affects expression, decreases expression, increases abundance	4
Air Pollutants	decreases expression, increases expression, affects cotreatment, increases abundance, increases oxidation	3
Benzo(a)pyrene	decreases expression, decreases methylation, increases expression, affects methylation	3
Doxorubicin	increases expression, decreases expression	3
Tobacco Smoke Pollution	affects expression, decreases expression, increases expression	3
bisphenol A	decreases expression, increases expression	2
nickel sulfate	increases expression	2
epigallocatechin gallate	decreases expression, affects cotreatment	2
chloropicrin	decreases expression	2
Cisplatin	affects cotreatment, increases expression	2
Estradiol	increases expression, decreases expression, affects cotreatment	2
Methylnitronitrosoguanidine	decreases expression	2
Mustard Gas	affects binding, affects expression, decreases expression	2
Progesterone	affects activity, affects expression, affects cotreatment, decreases expression, increases expression	2
Smoke	decreases expression	2
Cyclosporine	decreases expression, increases expression	2
Simvastatin	affects expression, increases expression	2
tert-Butylhydroperoxide	decreases expression	2
afuresertib	increases expression	1
sotorasib	affects cotreatment, decreases expression	1
2,4,6-tribromophenol	increases expression	1
apocarotenal	decreases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
propionaldehyde	increases expression	1
glycidyl methacrylate	increases expression	1
lead acetate	affects cotreatment, increases expression	1
methylselenic acid	decreases expression	1

ChEMBL screening assays

2 unique, capped per target: 2 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5638571	Binding	Inhibition of integrin beta-4 in human MDA-MB-231 cells assessed as decrease in sialylation level incubated for 48 hrs by Western blot analysis	Biological evaluation of sulfonate and sulfate analogues of lithocholic acid: A bioisosterism-guided approach towards the discovery of potential sialyltransferase inhibitors for antimetastatic study. — Bioorg Med Chem Lett

Cellosaurus cell lines

8 cell lines: 6 cancer cell line, 2 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D1X4	Abcam A-549 ITGB4 KO	Cancer cell line	Male
CVCL_D2BD	Abcam HCT 116 ITGB4 KO	Cancer cell line	Male
CVCL_D7SQ	Ubigene A-549 ITGB4 KO	Cancer cell line	Male
CVCL_ST46	HAP1 ITGB4 (-) 1	Cancer cell line	Male
CVCL_ST47	HAP1 ITGB4 (-) 2	Cancer cell line	Male
CVCL_ST48	HAP1 ITGB4 (-) 3	Cancer cell line	Male
CVCL_WW23	PA-JEB/beta4	Transformed cell line	Sex unspecified
CVCL_WW24	PA-JEB/beta4-EGFP	Transformed cell line	Sex unspecified

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00308321	PHASE4	UNKNOWN	Long Term Tapering or Standard Steroids for Nephrotic Syndrome
NCT01021540	PHASE4	COMPLETED	Prospective Study Evaluating the Effect of Repository Corticotropin in the Treatment of Various Nephrotic Syndromes
NCT01028287	PHASE4	COMPLETED	Adrenocorticotropic Hormone (ACTH) Treatment of Nephrotic Range Proteinuria in Diabetic Nephropathy (NRDN)
NCT01162005	PHASE4	COMPLETED	Therapeutic Effect of Tacrolimus on Primary Nephrotic Syndrome in Children
NCT01895894	PHASE4	COMPLETED	Mycophenolate Mofetil in Pediatric Steroid Dependent Nephrotic Syndrome
NCT02238418	PHASE4	COMPLETED	Efficacy of Usual Vitamin D Supplementation and Its Impact on Children and Adolescents Calciuria.
NCT02382575	PHASE4	UNKNOWN	Efficacy and Safety of Rituximab to That of Calcineurin Inhibitors in Children With Steroid Resistant Nephrotic Syndrome
NCT02427880	PHASE4	COMPLETED	Role of Acetazolamide and Hydrochlorothiazide Followed by Furosemide in Treating Nephrotic Edema
NCT03210688	PHASE4	COMPLETED	Active Vitamin D And Reduced Dose Prednisolone for Treatment in Minimal Change Nephropathy
NCT03347357	PHASE4	COMPLETED	Pharmacokinetics of Tacrolimus in Children
NCT05696977	PHASE4	UNKNOWN	Effect of Obesity on Cyclosporine Blood Trough Level in Nephrotic Syndrome Patients
NCT05966818	PHASE4	UNKNOWN	Effect of Dapagliflozin in Non-Diabetic Patients With Nephrotic Syndrome.
NCT06026787	PHASE4	COMPLETED	Clinical Value of Adding Dapagliflozin in Patients With Nephrotic Syndrome
NCT01129557	PHASE4	TERMINATED	Aldosterone Breakthrough During Diovan, Tekturna, and Combination Therapy in Patients With Proteinuric Kidney Disease
NCT02399462	PHASE4	WITHDRAWN	Acthar for Treatment of Post-transplant FSGS
NCT02585804	PHASE4	COMPLETED	Treating to Reduce Albuminuria and Normalize Hemodynamic Function in Focal ScLerosis With dApagliflozin Trial Effects
NCT02633046	PHASE4	COMPLETED	Acthar for Treatment-Resistant or Treatment-Intolerant Proteinuria
NCT07219121	PHASE4	RECRUITING	Sparsentan in Posttransplant Immunoglobulin A Nephropathy or Focal Segmental Glomerulosclerosis
NCT00037102	PHASE4	COMPLETED	Combination Therapy With Avonex and BiMonthly High Dose Intravenous Methotrexate in Multiple Sclerosis
NCT00037115	PHASE4	WITHDRAWN	Induction Therapy With a Single High Dose Bolus of Intravenous Methotrexate With Leucovorin Rescue, Prior to Initiation of AVONEX® Treatment, in Patients Presenting With a First Acute Demyelinating Event.
NCT00146068	PHASE4	COMPLETED	EARLY IFNB-1a and Simvastatin Combination Therapy in Clinically Isolated Syndrome Suggestive of Multiple Sclerosis
NCT00151294	PHASE4	TERMINATED	The Efficacy and Safety of Escitalopram for Depression in Multiple Sclerosis
NCT00176592	PHASE4	COMPLETED	Phase IV Study, Betaseron Versus Copaxone for Relapsing Remitting or CIS Forms of MS Using Triple Dose Gad 3 T MRI
NCT00179478	PHASE4	COMPLETED	Long Term Study of Avonex Therapy Following a First Attack of Multiple Sclerosis
NCT00220922	PHASE4	COMPLETED	A Study to Evaluate the Impact on Skin (Injection Site) Reactions of Using Alcohol Wipes Prior to Daily Injections of Copaxone®.
NCT00239993	PHASE4	COMPLETED	A Study to Evaluate the Impact of Using Warm Compress Prior to Daily Injections of Copaxone®
NCT00240006	PHASE4	COMPLETED	A Study Comparing Shared Solutions® Plus MS Center Support Versus Shared Solutions® Alone
NCT00240032	PHASE4	COMPLETED	A Study to Evaluate the Impact on Skin (Injection Site) Reactions of Taking an Antihistamine (Zyrtec®) or Placebo Prior to Daily Injections of Copaxone®.
NCT00246324	PHASE4	COMPLETED	Safety and Efficacy Study of Doxycycline in Combination With Interferon-B-1a to Treat Multiple Sclerosis
NCT00267319	PHASE4	COMPLETED	FOCUS Fatigue Outcome in Copaxone USers
NCT00381264	PHASE4	COMPLETED	Evaluation of the Efficacy of Cesamet™ for the Treatment of Pain in Patients With Multiple Sclerosis
NCT00414453	PHASE4	TERMINATED	Trial of Analgesia With Lidocaine or Extended-release Oxycodone for Neuropathic Pain Treatment in Multiple Sclerosis
NCT00423527	PHASE4	COMPLETED	Levetiracetam in Central Pain in Multiple Sclerosis(MS)
NCT00480181	PHASE4	COMPLETED	Efficacy and Safety Evaluation of Nabilone as Adjunctive Therapy to Gabapentin for the Management of Neuropathic Pain in Multiple Sclerosis
NCT00492765	PHASE4	COMPLETED	Simvastatin as an Add-on Treatment to Interferon-beta-1a for the Treatment of Relapsing-Remitting Multiple Sclerosis
NCT00493077	PHASE4	COMPLETED	Safety of Avonex Treatment in Multiple Sclerosis Patients With Neutralizing Antibodies to Interferon Beta Therapy
NCT00536120	PHASE4	COMPLETED	The Effects of Tysabri Treatment on Vaccination Response and Lymphocyte Subsets in Subjects With Relapsing Forms of Multiple Sclerosis
NCT00629642	PHASE4	COMPLETED	Clinical Study of Solifenacin Succinate in Patients With Bladder Symptoms Due to Spinal Cord Injury or Multiple Sclerosis
NCT00638027	PHASE4	COMPLETED	Memantine for Spasticity in MS Patients
NCT00744679	PHASE4	COMPLETED	A Pharmacokinetic (PK) Study of Natalizumab (Tysabri) at Steady State