ITGBL1

Summary

ITGBL1 (integrin subunit beta like 1, HGNC:6164) is a protein-coding gene on chromosome 13q33.1, encoding Integrin beta-like protein 1 (O95965).

This gene encodes a beta integrin-related protein that is a member of the EGF-like protein family. The encoded protein contains integrin-like cysteine-rich repeats. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 9358 — RefSeq curated summary.

At a glance

• GWAS associations: 5
• Clinical variants (ClinVar): 85 total — 2 pathogenic
• MANE Select transcript: NM_004791

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6164
Approved symbol	ITGBL1
Name	integrin subunit beta like 1
Location	13q33.1
Locus type	gene with protein product
Status	Approved
Aliases	TIED, OSCP
Ensembl gene	ENSG00000198542
Ensembl biotype	protein_coding
OMIM	604234
Entrez	9358

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 8 protein_coding, 1 retained_intron

ENST00000376162, ENST00000376180, ENST00000474233, ENST00000490242, ENST00000545560, ENST00000618057, ENST00000907748, ENST00000907749, ENST00000946855

RefSeq mRNA: 4 — MANE Select: NM_004791 NM_001271754, NM_001271755, NM_001271756, NM_004791

CCDS: CCDS61361, CCDS61362, CCDS73594, CCDS9499

Canonical transcript exons

ENST00000376180 — 11 exons

Exon	Start	End
ENSE00000940142	101453883	101454100
ENSE00001874473	101715563	101716446
ENSE00003467891	101575424	101575546
ENSE00003512431	101583216	101583356
ENSE00003514527	101598153	101598299
ENSE00003559129	101706756	101706902
ENSE00003577218	101579287	101579427
ENSE00003587489	101692585	101692701
ENSE00003617628	101452675	101452931
ENSE00003674171	101567699	101567845
ENSE00003695582	101714438	101714551

Expression profiles

Bgee: expression breadth ubiquitous, 243 present calls, max score 98.78.

FANTOM5 (CAGE): breadth broad, TPM avg 22.4430 / max 706.3805, expressed in 906 samples.

FANTOM5 promoters (13 alternative TSS)

Promoter ID	TPM avg	Samples expressed
135892	18.4979	827
135894	1.3293	349
135896	0.6986	277
135890	0.5924	187
135891	0.3142	147
135888	0.3051	104
135893	0.2212	109
135895	0.1493	75
135911	0.1076	51
135899	0.0763	33

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
frontal pole	UBERON:0002795	98.78	gold quality
paraflocculus	UBERON:0005351	98.56	gold quality
middle frontal gyrus	UBERON:0002702	98.46	gold quality
descending thoracic aorta	UBERON:0002345	97.74	gold quality
thoracic aorta	UBERON:0001515	97.70	gold quality
ascending aorta	UBERON:0001496	97.66	gold quality
calcaneal tendon	UBERON:0003701	97.35	gold quality
aorta	UBERON:0000947	96.66	gold quality
pericardium	UBERON:0002407	96.29	gold quality
synovial joint	UBERON:0002217	96.28	gold quality
right coronary artery	UBERON:0001625	96.17	gold quality
popliteal artery	UBERON:0002250	96.02	gold quality
tibial artery	UBERON:0007610	96.01	gold quality
visceral pleura	UBERON:0002401	95.66	gold quality
tendon	UBERON:0000043	95.30	gold quality
layer of synovial tissue	UBERON:0007616	94.92	gold quality
gall bladder	UBERON:0002110	94.33	gold quality
saphenous vein	UBERON:0007318	93.25	gold quality
left coronary artery	UBERON:0001626	93.22	gold quality
coronary artery	UBERON:0001621	92.88	gold quality
periodontal ligament	UBERON:0008266	92.68	gold quality
blood vessel layer	UBERON:0004797	92.06	gold quality
tendon of biceps brachii	UBERON:0008188	91.82	gold quality
tibia	UBERON:0000979	91.75	gold quality
endometrium epithelium	UBERON:0004811	90.41	silver quality
stromal cell of endometrium	CL:0002255	90.26	gold quality
mucosa of paranasal sinus	UBERON:0005030	89.31	gold quality
right lung	UBERON:0002167	88.31	gold quality
tibial nerve	UBERON:0001323	88.09	gold quality
skin of hip	UBERON:0001554	87.65	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-8322	yes	1316.92
E-ANND-3	yes	7.48

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

42 targeting ITGBL1, 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-3662	99.99	73.82	5684
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-185-3P	99.95	67.01	1743
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-576-5P	99.84	70.46	2582
HSA-MIR-1299	99.77	71.24	2389
HSA-MIR-6745	99.74	65.33	1321
HSA-MIR-875-3P	99.63	69.47	2548
HSA-MIR-3609	99.52	69.89	2587
HSA-MIR-548AH-5P	99.52	69.73	2626
HSA-MIR-486-5P	99.51	70.39	707
HSA-MIR-363-5P	99.46	64.51	1015
HSA-MIR-580-5P	99.28	70.94	1776
HSA-MIR-4263	99.18	69.25	2236
HSA-MIR-892C-5P	99.16	70.56	2116
HSA-MIR-8066	99.05	68.66	1532
HSA-MIR-26B-3P	98.71	67.49	1102
HSA-MIR-581	98.39	67.42	835
HSA-MIR-6773-3P	98.17	65.51	1213
HSA-MIR-1245B-3P	98.01	68.91	1387
HSA-MIR-876-5P	97.99	68.49	1345
HSA-MIR-744-3P	97.99	67.76	637
HSA-MIR-1255B-2-3P	97.80	67.04	880
HSA-MIR-376A-5P	97.70	65.61	863
HSA-MIR-6501-5P	97.41	68.24	712
HSA-MIR-7855-5P	97.39	67.18	925
HSA-MIR-6748-3P	97.20	65.66	836

Literature-anchored findings (GeneRIF, showing 18)

• Data indicate the transforming growth factor beta (TGFbeta) signaling pathway as a downstream effector of integrin beta-like 1 (ITGBL1) and the transcription factor Runx2 as an upstream activator of ITGBL1 expression. (PMID:26060017)
• our results suggest that ITGBL1 is a novel tumor suppressor in non-small cell lung cancer progression. (PMID:26307393)
• ITGBL1 might be a novel biomarker for ovarian cancer diagnosis. (PMID:27261588)
• Characterization of gene expression profiles in hepatitis B-related liver fibrosis patients identified ITGBL1 and its interactions with TGFB1 as key regulators of fibrogenesis. (PMID:28262670)
• ITGBL1 was associated with cell adhesion. (PMID:29772438)
• These results reveal ITGBL1 signaling as an underlying mechanism of protection against destructive cartilage disorders (PMID:30305454)
• he ITGBL1 hypermethylation is a potential biomarker for predicting prognosis and monitoring disease status in patients with acute myeloid leukemia. (PMID:30317626)
• High ITGBL1 expression correlated with shorter relapse-free survival in stage II colorectal cancer patients. (PMID:30717807)
• Our findings indicate that upregulation of ITGBL1 has important clinical significance and drives chemoresistance in ovarian cancer. Detection and depletion of ITGBL1 might be the potential approaches for diagnosis and therapy for ovarian cancer patients. (PMID:31683459)
• the primary colorectal cancer-derived ITGBL1-enriched extracellular vesicles stimulate the TNFAIP3-mediated NF-kappaB signaling pathway to activate fibroblasts. (PMID:32139701)
• ITGBL1 could be a promising prognostic biomarker, as well as a potential therapeutic target in HCC. (PMID:32537856)
• ITGBL1 promotes gastric cancer cell proliferation and invasion via Akt signal pathway. (PMID:33049688)
• ITGBL1 is a new immunomodulator that favors development of melanoma tumors by inhibiting natural killer cells cytotoxicity. (PMID:33413419)
• Screening differentially expressed genes between endometriosis and ovarian cancer to find new biomarkers for endometriosis. (PMID:34409913)
• Integrin beta-like 1 protein (ITGBL1) promotes cell migration by preferentially inhibiting integrin-ECM binding at the trailing edge. (PMID:35066808)
• ITGBL1 transcriptionally inhibited by JDP2 promotes the development of pancreatic cancer through the TGF-beta/Smad pathway. (PMID:35584452)
• A comprehensive analysis of potential gastric cancer prognostic biomarker ITGBL1 associated with immune infiltration and epithelial-mesenchymal transition. (PMID:35596183)
• ITGBL1 promotes anoikis resistance and metastasis in human gastric cancer via the AKT/FBLN2 axis. (PMID:38332530)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	itgbl1	ENSDARG00000040985
mus_musculus	Itgbl1	ENSMUSG00000032925
rattus_norvegicus	Itgbl1	ENSRNOG00000004516
drosophila_melanogaster	Itgbn	FBGN0010395
caenorhabditis_elegans		WBGENE00015472

Paralogs (8): ITGB5 (ENSG00000082781), ITGB8 (ENSG00000105855), ITGB6 (ENSG00000115221), ITGB4 (ENSG00000132470), ITGB7 (ENSG00000139626), ITGB1 (ENSG00000150093), ITGB2 (ENSG00000160255), ITGB3 (ENSG00000259207)

Protein

Protein identifiers

Integrin beta-like protein 1 — O95965 (reviewed: O95965)

Alternative names: Osteoblast-specific cysteine-rich protein, Ten integrin EGF-like repeat domain-containing protein

All UniProt accessions (3): O95965, A0A087WY35, U3KPX5

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Secreted.

Tissue specificity. Widely expressed in many tissues, but readily detectable only in aorta.

Domain organisation. Contains ten tandem EGF-like repeats strikingly similar to those found in the cysteine rich ‘stalk-like’ structure of integrin beta-subunits.

Isoforms (3)

UniProt ID	Names	Canonical?
O95965-1	1	yes
O95965-2	2
O95965-3	3

RefSeq proteins (4): NP_001258683, NP_001258684, NP_001258685, NP_004782* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000742	EGF	Domain
IPR013111	EGF_extracell	Domain
IPR015812	Integrin_bsu	Family
IPR057073	EGF_integrin_2	Domain
IPR057243	Integrin_I-EGF_CS	Conserved_site

Pfam: PF07974, PF23105

UniProt features (69 total): disulfide bond 40, domain 10, repeat 10, splice variant 2, sequence conflict 2, signal peptide 1, chain 1, region of interest 1, glycosylation site 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O95965-F1	84.28	0.51

Functional residue map

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

Disulfide bonds (40): 40–71, 51–69, 63–74, 76–89, 91–112, 96–110, 104–115, 117–126, 132–159, 143–157, 151–162, 164–178, 180–202, 185–200, 194–205, 207–216, 220–247, 231–245, 239–250, 252–269 …

Glycosylation sites (1): 405

Function

Pathways and Gene Ontology

Reactome pathways

5 pathways

ID	Pathway
R-HSA-8941332	RUNX2 regulates genes involved in cell migration
R-HSA-212436	Generic Transcription Pathway
R-HSA-73857	RNA Polymerase II Transcription
R-HSA-74160	Gene expression (Transcription)
R-HSA-8878166	Transcriptional regulation by RUNX2

MSigDB gene sets: 182 (showing top): GOCC_CELL_SURFACE, TAL1ALPHAE47_01, MORF_RAD51L3, SENESE_HDAC1_AND_HDAC2_TARGETS_DN, GOBP_CELL_CELL_ADHESION, FINAK_BREAST_CANCER_SDPP_SIGNATURE, KOYAMA_SEMA3B_TARGETS_UP, MORF_CTSB, MORF_IL4, MORF_PRKCA, TGACATY_UNKNOWN, ONDER_CDH1_TARGETS_2_UP, HELLER_HDAC_TARGETS_SILENCED_BY_METHYLATION_UP, MORF_THPO, AACTTT_UNKNOWN

GO Biological Process (6): cell adhesion (GO:0007155), cell-matrix adhesion (GO:0007160), integrin-mediated signaling pathway (GO:0007229), cell migration (GO:0016477), cell adhesion mediated by integrin (GO:0033627), cell-cell adhesion (GO:0098609)

GO Molecular Function (1): integrin binding (GO:0005178)

GO Cellular Component (5): extracellular region (GO:0005576), plasma membrane (GO:0005886), focal adhesion (GO:0005925), integrin complex (GO:0008305), cell surface (GO:0009986)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
Transcriptional regulation by RUNX2	1
RNA Polymerase II Transcription	1
Gene expression (Transcription)	1
Generic Transcription Pathway	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cell adhesion	2
cellular anatomical structure	2
cellular process	1
cell-substrate adhesion	1
cell surface receptor signaling pathway	1
cell motility	1
signaling receptor binding	1
protein-containing complex binding	1
cell adhesion molecule binding	1
membrane	1
cell periphery	1
cell-substrate junction	1
protein complex involved in cell adhesion	1
plasma membrane signaling receptor complex	1

Protein interactions and networks

STRING

1082 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ITGBL1	TNFAIP3	P21580	631
ITGBL1	EGF	P01133	581
ITGBL1	TGFB1	P01137	536
ITGBL1	ITGA8	P53708	528
ITGBL1	MMP3	P08254	485
ITGBL1	MXRA5	Q9NR99	459
ITGBL1	COL14A1	Q05707	453
ITGBL1	ITGA11	Q9UKX5	447
ITGBL1	GAPDH	P00354	444
ITGBL1	TAGLN	Q01995	422
ITGBL1	ITGA7	Q13683	402
ITGBL1	ITGB3BP	Q13352	400
ITGBL1	MYH10	P35580	396
ITGBL1	KIF3A	Q9Y496	395
ITGBL1	ACTA2	P03996	388

IntAct

2 interactions, top by confidence:

A	B	Type	Score
ITGBL1	SHANK3	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (2): ITGBL1 (Affinity Capture-RNA), ITGBL1 (Two-hybrid)

ESM2 similar proteins: A0A6I8RMG7, A0JM12, A0JP86, A2VCU8, A5YT95, A6QR11, E9QJQ6, O54890, O70309, O73775, O95965, P02468, P02469, P05106, P11047, P18084, P23142, P26013, P31515, P35555, P35556, P80747, P98133, Q07441, Q08879, Q0VBD0, Q1LVF0, Q2VWQ2, Q5M9B3, Q5PQQ8, Q5R3Z7, Q61220, Q61554, Q61555, Q62918, Q62919, Q6DIB5, Q6PFE7, Q7ZXL5, Q8IYR6

Diamond homologs: A2A863, A5Z1X6, B0FYY4, O54890, O70309, O95965, P05106, P05107, P05556, P07228, P09055, P11584, P11835, P12606, P12607, P16144, P18084, P18563, P18564, P26010, P26011, P26012, P26013, P32592, P49134, P53712, P53713, P53714, P80747, Q07441, Q09062, Q0VBD0, Q1RPR6, Q27591, Q27874, Q2VJ42, Q3UV74, Q5PQQ8, Q5RCA9, Q5VI41

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	0
Uncertain significance	69
Likely benign	0
Benign	4

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
1074668	NC_000013.10:g.(?92002837)(103343314_?)del	Pathogenic
1704304	GRCh37/hg19 13q33.1(chr13:102250764-102412039)x1	Pathogenic

SpliceAI

2796 predictions. Top by Δscore:

Variant	Effect	Δscore
13:101567693:CCCCA:C	acceptor_loss	1.0000
13:101567694:CCCA:C	acceptor_loss	1.0000
13:101567695:CCAG:C	acceptor_loss	1.0000
13:101567696:CAGGC:C	acceptor_loss	1.0000
13:101567697:A:T	acceptor_loss	1.0000
13:101567698:G:GT	acceptor_loss	1.0000
13:101568567:T:TA	donor_gain	1.0000
13:101568568:A:AA	donor_gain	1.0000
13:101575547:G:GC	donor_loss	1.0000
13:101575548:T:G	donor_loss	1.0000
13:101579279:G:A	acceptor_gain	1.0000
13:101583211:C:G	acceptor_gain	1.0000
13:101583211:CCTA:C	acceptor_loss	1.0000
13:101583212:CTA:C	acceptor_loss	1.0000
13:101583213:TA:T	acceptor_loss	1.0000
13:101583214:A:AG	acceptor_gain	1.0000
13:101583214:AG:A	acceptor_gain	1.0000
13:101583214:AGG:A	acceptor_gain	1.0000
13:101583214:AGGG:A	acceptor_loss	1.0000
13:101583215:G:GC	acceptor_gain	1.0000
13:101583215:GG:G	acceptor_gain	1.0000
13:101583215:GGG:G	acceptor_gain	1.0000
13:101583215:GGGA:G	acceptor_gain	1.0000
13:101583215:GGGAC:G	acceptor_gain	1.0000
13:101583355:AGGTA:A	donor_loss	1.0000
13:101583356:GGT:G	donor_loss	1.0000
13:101583357:GTA:G	donor_loss	1.0000
13:101583358:T:G	donor_loss	1.0000
13:101598134:T:TA	acceptor_gain	1.0000
13:101598259:G:GT	donor_gain	1.0000

AlphaMissense

3283 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
13:101715609:G:C	W480C	0.999
13:101715609:G:T	W480C	0.999
13:101567833:T:A	C151S	0.998
13:101567834:G:C	C151S	0.998
13:101579346:T:A	C216S	0.998
13:101579347:G:C	C216S	0.998
13:101714545:T:A	C463S	0.998
13:101714545:T:C	C463R	0.998
13:101714546:G:C	C463S	0.998
13:101715622:T:A	C485S	0.998
13:101715623:G:A	C485Y	0.998
13:101715623:G:C	C485S	0.998
13:101715624:T:G	C485W	0.998
13:101567809:T:A	C143S	0.997
13:101567810:G:C	C143S	0.997
13:101579333:G:C	W211C	0.997
13:101579333:G:T	W211C	0.997
13:101714546:G:A	C463Y	0.997
13:101714547:T:G	C463W	0.997
13:101715622:T:C	C485R	0.997
13:101715623:G:T	C485F	0.997
13:101567833:T:C	C151R	0.996
13:101567835:C:G	C151W	0.996
13:101575492:T:A	C178S	0.996
13:101575493:G:A	C178Y	0.996
13:101575493:G:C	C178S	0.996
13:101579346:T:C	C216R	0.996
13:101583350:T:A	C288S	0.996
13:101583351:G:C	C288S	0.996
13:101715595:T:A	C476S	0.996

dbSNP variants (sampled 300 via entrez): RS1000015899 (13:101578815 A>G), RS1000021619 (13:101617452 A>C), RS1000023264 (13:101543461 C>A,G), RS1000037970 (13:101572763 A>C,G), RS1000059946 (13:101618651 T>C), RS1000060122 (13:101648106 G>A), RS1000065031 (13:101590365 C>G), RS1000071528 (13:101583531 T>C), RS1000082798 (13:101538314 C>T), RS1000089464 (13:101694346 A>G), RS1000090061 (13:101496830 T>C), RS1000101921 (13:101700789 T>G), RS1000104093 (13:101530194 T>G), RS1000107284 (13:101489310 T>C), RS1000151723 (13:101539514 G>A)

Disease associations

OMIM: gene MIM:604234 | disease phenotypes: MIM:609637, MIM:609307

GenCC curated gene-disease

Mondo (2): holoprosencephaly 5 (MONDO:0012322), spinocerebellar ataxia type 27 (MONDO:0012247)

Orphanet (2): Holoprosencephaly (Orphanet:2162), Spinocerebellar ataxia type 27A (Orphanet:98764)

HPO phenotypes

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

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST001762_204	Obesity-related traits	9.000000e-06
GCST002211_8	Psychosis (atypical)	3.000000e-06
GCST004582_1	Waist-to-hip circumference ratio (dietary energy interaction)	2.000000e-07
GCST009391_1279	Metabolite levels	7.000000e-06
GCST012489_100	Heel bone mineral density x serum urate levels interaction	1.000000e-08

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0004343	waist-hip ratio
EFO:0008111	diet measurement
EFO:0010546	uridine measurement
EFO:0004531	urate measurement
EFO:0009270	heel bone mineral density

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
C566464	Holoprosencephaly 5 (supp.)
C537204	Spinocerebellar ataxia 27 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs1436260	ITGBL1		0.00	0

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Estradiol	increases expression, decreases expression, decreases reaction, affects cotreatment	4
Progesterone	increases expression, decreases expression, decreases reaction, affects cotreatment	3
bisphenol A	affects methylation, affects cotreatment, increases methylation, decreases expression	2
Air Pollutants	increases expression, decreases expression, increases abundance	2
Benzo(a)pyrene	affects methylation, increases methylation	2
Nickel	decreases expression	2
Aflatoxin B1	decreases methylation	2
propionaldehyde	increases expression	1
deoxynivalenol	decreases expression	1
sodium arsenite	increases expression	1
potassium chromate(VI)	decreases expression	1
aflatoxin B2	increases methylation	1
triadimefon	decreases expression	1
rofecoxib	affects expression	1
mirdametinib	decreases expression, affects cotreatment	1
NSC 689534	decreases expression, affects binding	1
(+)-JQ1 compound	affects cotreatment, decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Arsenic Trioxide	decreases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Vehicle Emissions	decreases expression, increases abundance	1
Calcitriol	decreases expression	1
Copper	affects binding, decreases expression	1
Folic Acid	increases expression	1
Ibuprofen	affects expression	1
Methotrexate	decreases expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Rifampin	decreases expression	1
Silicon Dioxide	increases expression	1
T-2 Toxin	decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT01793168	Not specified	RECRUITING	Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford