TGFB1I1

Summary

TGFB1I1 (transforming growth factor beta 1 induced transcript 1, HGNC:11767) is a protein-coding gene on chromosome 16p11.2, encoding Transforming growth factor beta-1-induced transcript 1 protein (O43294). Functions as a molecular adapter coordinating multiple protein-protein interactions at the focal adhesion complex and in the nucleus.

This gene encodes a coactivator of the androgen receptor, a transcription factor which is activated by androgen and has a key role in male sexual differentiation. The encoded protein is thought to regulate androgen receptor activity and may have a role to play in the treatment of prostate cancer. Multiple transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 7041 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 76 total
• Transcription factor: yes — 13 downstream targets (CollecTRI)
• MANE Select transcript: NM_001042454

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11767
Approved symbol	TGFB1I1
Name	transforming growth factor beta 1 induced transcript 1
Location	16p11.2
Locus type	gene with protein product
Status	Approved
Aliases	Hic-5, TSC-5, ARA55, HIC-5
Ensembl gene	ENSG00000140682
Ensembl biotype	protein_coding
OMIM	602353
Entrez	7041

Gene structure

Transcript identifiers

Ensembl transcripts: 23 — 13 protein_coding, 7 retained_intron, 3 nonsense_mediated_decay

ENST00000361773, ENST00000394858, ENST00000394863, ENST00000561785, ENST00000562165, ENST00000562566, ENST00000563712, ENST00000564176, ENST00000564804, ENST00000565360, ENST00000565454, ENST00000567066, ENST00000567524, ENST00000567607, ENST00000568142, ENST00000569254, ENST00000569703, ENST00000902093, ENST00000902094, ENST00000965082, ENST00000965083, ENST00000965084, ENST00000965085

RefSeq mRNA: 3 — MANE Select: NM_001042454 NM_001042454, NM_001164719, NM_015927

CCDS: CCDS10713, CCDS42156

Canonical transcript exons

ENST00000394863 — 11 exons

Exon	Start	End
ENSE00002584392	31472152	31472201
ENSE00003539791	31477310	31477958
ENSE00003561846	31474152	31474239
ENSE00003612652	31473835	31473977
ENSE00003624262	31476862	31477010
ENSE00003630065	31476481	31476562
ENSE00003632927	31476012	31476185
ENSE00003669011	31474563	31474757
ENSE00003672774	31473441	31473556
ENSE00003675587	31473682	31473734
ENSE00003686367	31474350	31474455

Expression profiles

Bgee: expression breadth ubiquitous, 241 present calls, max score 99.34.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 33.8285 / max 350.8117, expressed in 1427 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
153834	30.4716	1417
153833	2.2217	913
153835	1.0299	582
153832	0.1053	34

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
saphenous vein	UBERON:0007318	99.34	gold quality
body of uterus	UBERON:0009853	99.09	gold quality
lower esophagus muscularis layer	UBERON:0035833	98.83	gold quality
myometrium	UBERON:0001296	98.80	gold quality
lower esophagus	UBERON:0013473	98.80	gold quality
popliteal artery	UBERON:0002250	98.78	gold quality
tibial artery	UBERON:0007610	98.77	gold quality
aorta	UBERON:0000947	98.73	gold quality
left uterine tube	UBERON:0001303	98.72	gold quality
thoracic aorta	UBERON:0001515	98.67	gold quality
right coronary artery	UBERON:0001625	98.67	gold quality
ascending aorta	UBERON:0001496	98.66	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	98.66	gold quality
cauda epididymis	UBERON:0004360	98.62	gold quality
descending thoracic aorta	UBERON:0002345	98.61	gold quality
urethra	UBERON:0000057	98.54	gold quality
muscle layer of sigmoid colon	UBERON:0035805	98.54	gold quality
seminal vesicle	UBERON:0000998	98.44	gold quality
mucosa of stomach	UBERON:0001199	98.36	gold quality
coronary artery	UBERON:0001621	98.28	gold quality
left coronary artery	UBERON:0001626	98.25	gold quality
blood vessel layer	UBERON:0004797	98.12	gold quality
endocervix	UBERON:0000458	97.37	gold quality
vena cava	UBERON:0004087	97.18	gold quality
right ovary	UBERON:0002118	97.16	gold quality
nipple	UBERON:0002030	97.12	gold quality
smooth muscle tissue	UBERON:0001135	97.05	gold quality
stromal cell of endometrium	CL:0002255	96.50	gold quality
fundus of stomach	UBERON:0001160	96.33	gold quality
left ovary	UBERON:0002119	96.19	gold quality

Single-cell (SCXA)

Detected in 12 experiment(s), a significant marker in 12.

Experiment	Marker?	Max mean expression
E-HCAD-13	yes	229.81
E-MTAB-6701	yes	119.92
E-HCAD-10	yes	50.19
E-MTAB-10287	yes	40.16
E-HCAD-1	yes	37.28
E-MTAB-8410	yes	33.67
E-MTAB-6678	yes	26.60
E-GEOD-135922	yes	25.71
E-HCAD-11	yes	19.31
E-GEOD-134144	yes	11.13
E-ANND-3	yes	9.69
E-HCAD-9	yes	4.98

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

13 targets.

Target	Regulation
AR
BMP4
CCN2
CDKN1A
FGF7
FOS
ID1
MAPK15
MYC
NR2C2
TGFB1
TGFB1I1
VIM

Upstream regulators (CollecTRI, top): AR, ID1, NCOA2, NR2C2, PHF20, TGFB1I1

miRNA regulators (miRDB)

24 targeting TGFB1I1, 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-4283	100.00	66.42	2097
HSA-MIR-196A-5P	100.00	68.16	684
HSA-MIR-196B-5P	100.00	68.16	681
HSA-MIR-6759-5P	99.99	66.54	785
HSA-MIR-6793-5P	99.97	65.95	758
HSA-MIR-106A-5P	99.90	73.94	2683
HSA-MIR-17-5P	99.89	73.83	2665
HSA-MIR-106B-5P	99.88	74.72	2795
HSA-MIR-20A-5P	99.88	74.76	2769
HSA-MIR-20B-5P	99.88	74.01	2621
HSA-MIR-519D-3P	99.88	73.97	2607
HSA-MIR-526B-3P	99.88	74.06	2587
HSA-MIR-93-5P	99.88	73.98	2606
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-6766-5P	99.68	67.70	2325
HSA-MIR-6134	99.63	65.68	1537
HSA-MIR-361-3P	99.19	66.45	1381
HSA-MIR-4650-3P	99.01	68.39	1062
HSA-MIR-12114	98.70	63.45	730
HSA-MIR-6831-5P	98.26	67.20	990
HSA-MIR-3927-3P	97.68	66.76	892
HSA-MIR-6846-3P	94.80	65.19	389
HSA-MIR-1268A	87.06	61.46	145
HSA-MIR-1268B	87.06	61.46	145

Literature-anchored findings (GeneRIF, showing 40)

• coregulator of androgen receptor coativation, suppresssed by Pyk2 (PMID:11856738)
• that hic-5 plays a role in the initial stage of myogenic differentiation. (PMID:11937715)
• Results suggest that paxillin and Hic-5 associate with GIT1 with different binding modes. (PMID:12153727)
• a key element in the transduction of signals from the cell surface to the nucleus under oxidative stress-review (PMID:12400158)
• results suggest that Hic-5 participates in the transcriptional regulation of c-fos as a scaffold in transcriptional complexes. (PMID:12445807)
• Results show that Hic-5 accumulates in the nucleus in response to oxidants such as hydrogen peroxide (PMID:12631731)
• Higher ARA55 expression may result in unfavorable recurrence-free survival and overall survival in hormone-refractory prostate cancer (PMID:12858356)
• the C terminus of ARA55 is critical for suppression of Smad3 activity (PMID:15561701)
• Hic-5/ARA55 is required for optimal GR-mediated gene expression possibly by providing a scaffold that organizes or stabilizes coactivator complexes at some hormone-responsive promoters. (PMID:16141357)
• human ERK8 has a role as a negative regulator of human GRalpha, acting through Hic-5 (PMID:16624805)
• Small interfering RNA ablation experiments established endogenous Hic-5/ARA55 as a coactivator for both viral and endogenous cellular AR-regulated genes. (PMID:16849583)
• Review highlights the role that Hic-5 may play in regulating androgen-induced growth factor signaling and/or cytokine expression in the prostate. (PMID:17166536)
• Hic-5/ARA55 is a molecular regulator for androgen sensitivity in human hair follicles. (PMID:17508020)
• autocrine production of TGF-beta1 upregulates the expression of Hic-5, which is essential for perpetuating the decreased proliferation seen in pathogenic myofibroblast (PMID:17671518)
• The increased expression of ARA55 is a feature of nonobstructive azoospermia. (PMID:17919607)
• Silencing Hic-5 in hypertrophic scar fibroblasts reduces TGF-beta1 production, decreases generation of supermature focal adhesions, reduces expression of smooth-muscle cell alpha-actin and decreases collagen contraction and extracellular matrix synthesis. (PMID:18401422)
• The level of Smad7 is modulated by its physical interaction with Hic-5 and targeted to a degradation pathway not likely to be proteasomal (PMID:18762808)
• The data suggest that the proposed progesterone resistance in endometrium from women with endometriosis derives, in part, from impaired expression of the PR coactivator, Hic-5, in endometrial tissue and cultured endometrial stromal fibroblasts. (PMID:19389829)
• Hic-5/ARA55 has roles in keloids through Smad pathway and profibrotic transcription (PMID:20395114)
• Hydrogen peroxide-inducible clone 5 is expressed predominantly in pyramidal neurons of human hippocampus. (PMID:20448481)
• Hic-5/ARA55 expression in response to castration-enabled epithelial regression through the repression of c-myc gene at the chromatin level. (PMID:20818421)
• Hic-5 is essential for adhesion formation in 3D extracellular matrices. (PMID:21148292)
• Androgen receptor transactivity is potentiated by TGF-beta1 through Smad3 but checked by its coactivator Hic-5/ARA55 in balding dermal papilla cells. (PMID:21924870)
• Transforming growth factor-beta1-induced transcript 1 protein, a novel marker for smooth muscle contractile phenotype, is regulated by serum response factor/myocardin protein. (PMID:21984848)
• these results provide the first evidence for a physical and mutual functional interaction between Hic-5 and the BMP signaling pathway. (PMID:21996749)
• Findings suggest that hydrogen peroxide-inducible clone-5 (Hic-5) is involved in changes in the mesangial cells (MCs) phenotype to produce abnormal extracellular matrix remodeling in glomerulonephritis (GN). (PMID:22286178)
• It plays a roll in extracellular matrix remodeling and the signal transduction via reactive oxygen species. (review) (PMID:22712231)
• the HIC-5- and KLF4-dependent mechanism transactivates p21(Cip1) in response to anchorage loss (PMID:23007394)
• Hic-5 can potentially exercise multiple functions in growth, differentiation, migration and adhesion of keratinocytes, partially via nuclear-cell membrane shuttling. (PMID:23062781)
• The ubiquitin ligase activity of Cbl-c by the direct interaction of the LIM zinc coordinating domain of Hic5 is demonstrated. (PMID:23145173)
• Hic5 coordinates AR signaling with adhesion and extracellular matrix contacts to regulate cell behavior in the tumor microenvironment. (PMID:24440747)
• Hic-5 suppresses senescence and profibrotic activities of myofibroblasts by down-regulating Nox4 expression. (PMID:24831009)
• Studies in vitro and in vivo using TGF-beta1 and TGFB1I1 shRNA demonstrated that TGFB1I1 is required for TGF-beta stimulated EMT that contributes to malignant progression of astrocytomas. (PMID:25333259)
• Endothelial Hic-5 plays an important role in the formation of microvilli-like structures and in the interaction between ECs and monocytes, leading to monocyte recruitment and subsequent development of atherosclerosis. (PMID:25587044)
• Hic-5 influences the genomic occupancy of multiple steroid receptors and thereby blocks some aspects of hormonal regulation. (PMID:25763609)
• Hic-5 siRNA also suppressed TGF-beta2-induced fibrogenic activity and dexamethasone-induced myocilin expression in HTM cells. (PMID:26313302)
• Hic-5 plays a central role in the positive feedback ROS-JNK signaling cascade that regulates hepatocellular carcinoma progression. (PMID:26416447)
• Hic-5 appears to enhance complex formation between MT1-MMP and FAK in activated endothelial cells, which likely coordinates matrix proteolysis and cell motility. (PMID:26769900)
• As aging increased, more ARA55 were expressed in PZ stromal cells, leading to more sensitive androgen/androgen receptor (AR) signal pathway, then constituting a more feasible environment to cancer cells. (PMID:27178620)
• Isolated Hic-5(-/-);PyMT CAFs were defective in stress fiber organization and exhibited reduced contractility. These cells also failed to efficiently deposit and organize the ECM in two and three dimensions. This, in turn, impacted three-dimensional MDA-MB-231 tumor cell migration behavior (PMID:27893716)

Cross-species orthologs

10 orthologs

Organism	Symbol	Gene ID
mus_musculus	Tgfb1i1	ENSMUSG00000030782
rattus_norvegicus	Tgfb1i1	ENSRNOG00000019965
drosophila_melanogaster	Pax	FBGN0041789
drosophila_melanogaster	CG30178	FBGN0050178
drosophila_melanogaster	CG31624	FBGN0051624
drosophila_melanogaster	CG31988	FBGN0051988
drosophila_melanogaster	CG34325	FBGN0085354
caenorhabditis_elegans		WBGENE00016197
caenorhabditis_elegans	C34B2.4	WBGENE00016389
caenorhabditis_elegans	F33D11.1	WBGENE00018000

Paralogs (2): PXN (ENSG00000089159), LPXN (ENSG00000110031)

Protein

Protein identifiers

Transforming growth factor beta-1-induced transcript 1 protein — O43294 (reviewed: O43294)

Alternative names: Androgen receptor coactivator 55 kDa protein, Androgen receptor-associated protein of 55 kDa, Hydrogen peroxide-inducible clone 5 protein

All UniProt accessions (7): O43294, H3BN49, H3BQC4, H3BRP2, H3BS04, H3BSN4, I3L209

UniProt curated annotations — full annotation on UniProt →

Function. Functions as a molecular adapter coordinating multiple protein-protein interactions at the focal adhesion complex and in the nucleus. Links various intracellular signaling modules to plasma membrane receptors and regulates the Wnt and TGFB signaling pathways. May also regulate SLC6A3 and SLC6A4 targeting to the plasma membrane hence regulating their activity. In the nucleus, functions as a nuclear receptor coactivator regulating glucocorticoid, androgen, mineralocorticoid and progesterone receptor transcriptional activity. May play a role in the processes of cell growth, proliferation, migration, differentiation and senescence. May have a zinc-dependent DNA-binding activity.

Subunit / interactions. Homooligomer. Interacts with PPARG. Interacts with TRAF4. Interacts with CRIP2. Interacts with HSPB1. Interacts with ILK. Interacts with LIMS1 and LIMS2. Interacts with NCK2. Interacts with NUDT16L1. Interacts with PAK. Interacts with PTPN12. Interacts with TCF3. Interacts with TCF7L2. Interacts with VCL. Interacts (via LD motif 3) with GIT1. Also interacts with GIT2. Forms a complex with ARHGEF7. Interacts with AR/androgen receptor in a ligand-dependent manner. Interacts with CSK. Interacts with PTK2/FAK1 and PTK2B/PYK2. Interacts with SLC6A3 and SLC6A4. Interacts with NR3C1. Interacts with SMAD3. Interacts with MAPK15. Interacts with SRC. Interacts with LYN. Interacts with talin. Interacts (via LIM zinc-binding domain 2) with CBLC (via RING-type zinc finger); the interaction is direct and enhances CBLC E3 ubiquitin-protein ligase activity. Interacts with PARVA. Interacts with PXN.

Subcellular location. Cell junction. Focal adhesion. Nucleus matrix. Cytoplasm. Cytoskeleton.

Tissue specificity. Expressed in platelets, smooth muscle and prostate stromal cells (at protein level).

Post-translational modifications. Phosphorylated by gonadotropin-releasing hormone-activated SRC.

Domain organisation. The LIM zinc-binding domains mediate glucocorticoid receptor coactivation and interaction with AR, CRIP2, ILK, LIMS1, NR3C1, PPARG, TCF3, TCF7L2, SLC6A3 and SMAD3. The LIM zinc-binding 2 and LIM zinc-binding 3 domains mediate targeting to focal adhesions and actin stress fibers. The LIM zinc-binding 3 and LIM zinc-binding 4 domains mediate interaction with TRAF4 and MAPK15. The LIM zinc-binding 4 domain mediates interaction with HSPB1, homooligomerization and targeting to the nuclear matrix. The LIM zinc-binding 3 domain mediates interaction with PTPN12. The LD (leucine and aspartate-rich) motif 3 mediates interaction with GIT1 and functions as a nuclear export signal.

Induction. Up-regulated by TNF and hydrogen peroxide.

Similarity. Belongs to the paxillin family.

Isoforms (2)

UniProt ID	Names	Canonical?
O43294-1	1	yes
O43294-2	2

RefSeq proteins (3): NP_001035919, NP_001158191, NP_057011 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001781	Znf_LIM	Domain
IPR017305	Tgfb1i1/Leupaxin/TGFB1I1	Family
IPR047075	Paxillin_TGFB1I1_LIM_dom1	Domain

Pfam: PF00412, PF03535

UniProt features (50 total): modified residue 16, mutagenesis site 9, region of interest 6, sequence conflict 5, domain 4, short sequence motif 4, compositionally biased region 3, chain 1, splice variant 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O43294-F1	72.34	0.46

Functional residue map

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

Post-translational modifications (16): 1, 33, 38, 60, 68, 137, 140, 141, 143, 164, 186, 188, 192, 194, 403, 407

Mutagenesis-validated functional residues (9):

Position	Phenotype
60	prevents phosphorylation by fak2 and fyn. prevents interaction with csk.
287	abolishes interaction with cblc and enhancement of cblc e3 ubiquitin-protein ligase activity.
313	no effect on interaction with cblc.
338–342	loss of interaction with ar; when associated with 456-a–a-460.
369	loss of ar coactivation; when associated with s-372.
372	loss of ar coactivation; when associated with s-369.
428	loss of ar coactivation; when associated with s-431.
431	loss of ar coactivation; when associated with s-428.
456–460	loss of interaction with ar; when associated with 338-a–a-342.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 231 (showing top): GOBP_MORPHOGENESIS_OF_AN_EPITHELIUM, RNGTGGGC_UNKNOWN, VERHAAK_AML_WITH_NPM1_MUTATED_DN, GOBP_REGULATION_OF_CELLULAR_RESPONSE_TO_GROWTH_FACTOR_STIMULUS, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_REGULATION_OF_FAT_CELL_DIFFERENTIATION, BERTUCCI_MEDULLARY_VS_DUCTAL_BREAST_CANCER_DN, GOBP_POSITIVE_REGULATION_OF_EPITHELIAL_TO_MESENCHYMAL_TRANSITION, GOBP_NEGATIVE_REGULATION_OF_FAT_CELL_DIFFERENTIATION, KAAB_HEART_ATRIUM_VS_VENTRICLE_UP, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, TOMLINS_PROSTATE_CANCER_DN, GRAHAM_CML_QUIESCENT_VS_NORMAL_QUIESCENT_DN, GOBP_MORPHOGENESIS_OF_EMBRYONIC_EPITHELIUM, GOBP_POSITIVE_REGULATION_OF_CELLULAR_RESPONSE_TO_TRANSFORMING_GROWTH_FACTOR_BETA_STIMULUS

GO Biological Process (13): cell adhesion (GO:0007155), negative regulation of cell population proliferation (GO:0008285), positive regulation of epithelial to mesenchymal transition (GO:0010718), Wnt signaling pathway (GO:0016055), morphogenesis of embryonic epithelium (GO:0016331), positive regulation of transforming growth factor beta receptor signaling pathway (GO:0030511), epithelial cell differentiation (GO:0030855), cell fate commitment (GO:0045165), fat cell differentiation (GO:0045444), negative regulation of fat cell differentiation (GO:0045599), positive regulation of DNA-templated transcription (GO:0045893), positive regulation of ubiquitin-dependent protein catabolic process (GO:2000060), cell differentiation (GO:0030154)

GO Molecular Function (6): transcription coactivator activity (GO:0003713), metal ion binding (GO:0046872), Roundabout binding (GO:0048495), nuclear androgen receptor binding (GO:0050681), I-SMAD binding (GO:0070411), protein binding (GO:0005515)

GO Cellular Component (8): cytosol (GO:0005829), cytoskeleton (GO:0005856), focal adhesion (GO:0005925), nuclear matrix (GO:0016363), extracellular matrix (GO:0031012), nucleus (GO:0005634), cytoplasm (GO:0005737), anchoring junction (GO:0070161)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cell differentiation	3
cellular anatomical structure	3
cellular developmental process	2
cellular process	1
cell population proliferation	1
regulation of cell population proliferation	1
negative regulation of cellular process	1
epithelial to mesenchymal transition	1
regulation of epithelial to mesenchymal transition	1
positive regulation of cell differentiation	1
positive regulation of multicellular organismal process	1
cell surface receptor signaling pathway	1
morphogenesis of an epithelium	1
embryonic morphogenesis	1
transforming growth factor beta receptor signaling pathway	1
regulation of transforming growth factor beta receptor signaling pathway	1
positive regulation of transmembrane receptor protein serine/threonine kinase signaling pathway	1
positive regulation of cellular response to transforming growth factor beta stimulus	1
epithelium development	1
fat cell differentiation	1
negative regulation of cell differentiation	1
regulation of fat cell differentiation	1
DNA-templated transcription	1
regulation of DNA-templated transcription	1
positive regulation of RNA biosynthetic process	1
ubiquitin-dependent protein catabolic process	1
positive regulation of protein catabolic process	1
regulation of ubiquitin-dependent protein catabolic process	1
transcription coregulator activity	1
positive regulation of DNA-templated transcription	1
cation binding	1
signaling receptor binding	1
nuclear receptor binding	1
SMAD binding	1
binding	1
cytoplasm	1
intracellular membraneless organelle	1
cell-substrate junction	1
nuclear lumen	1
external encapsulating structure	1

Protein interactions and networks

STRING

1500 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TGFB1I1	PTK2B	Q14289	930
TGFB1I1	VCL	P18206	914
TGFB1I1	AR	P10275	851
TGFB1I1	NCF1	P14598	839
TGFB1I1	TRAF4	Q9BUZ4	825
TGFB1I1	TLN2	Q9Y4G6	774
TGFB1I1	RNF14	Q9UBS8	747
TGFB1I1	TLN1	Q9Y490	739
TGFB1I1	PARVA	Q9NVD7	683
TGFB1I1	NCOA4	Q13772	681
TGFB1I1	ILK	P57043	670
TGFB1I1	PTPN12	Q05209	653
TGFB1I1	MAPK15	Q8TD08	646
TGFB1I1	SLC9A3	P48764	631
TGFB1I1	SRC	P12931	626

IntAct

53 interactions, top by confidence:

A	B	Type	Score
PTK2	TGFB1I1	psi-mi:“MI:0915”(physical association)	0.680
PTK2	TGFB1I1	psi-mi:“MI:0914”(association)	0.680
TGFB1I1	PTK2	psi-mi:“MI:0915”(physical association)	0.680
CCDC120	AIP	psi-mi:“MI:0914”(association)	0.640
TGFB1I1	TRAF4	psi-mi:“MI:0915”(physical association)	0.600
TGFB1I1	TRAF4	psi-mi:“MI:0403”(colocalization)	0.600
PTK2B	TGFB1I1	psi-mi:“MI:0914”(association)	0.530
YPMT1.25Ac	TGFB1I1	psi-mi:“MI:0915”(physical association)	0.510
TGFB1I1	YPMT1.25Ac	psi-mi:“MI:0915”(physical association)	0.510
ITCH	TGFB1I1	psi-mi:“MI:0407”(direct interaction)	0.440
NEDD4	TGFB1I1	psi-mi:“MI:0407”(direct interaction)	0.440
YAP1	TGFB1I1	psi-mi:“MI:0407”(direct interaction)	0.440
TGFB1I1	ITGA4	psi-mi:“MI:0915”(physical association)	0.400
ITGB1	TGFB1I1	psi-mi:“MI:0915”(physical association)	0.400
TGFB1I1	yopN	psi-mi:“MI:0915”(physical association)	0.370
TGFB1I1		psi-mi:“MI:0915”(physical association)	0.370
TGFB1I1	HOXA1	psi-mi:“MI:0915”(physical association)	0.370
TGFB1I1	CDKN2B	psi-mi:“MI:0915”(physical association)	0.370
PLA2G3	TGFB1I1	psi-mi:“MI:0915”(physical association)	0.370
TGFB1I1	HIPK3	psi-mi:“MI:0915”(physical association)	0.370
Xpo1	IFT56	psi-mi:“MI:0914”(association)	0.350
	VWA8	psi-mi:“MI:0914”(association)	0.350
	IPO5	psi-mi:“MI:0914”(association)	0.350

BioGRID (85): SMAD3 (Affinity Capture-Western), TGFB1I1 (Affinity Capture-MS), TGFB1I1 (Affinity Capture-MS), PTK2B (Two-hybrid), PTK2B (Two-hybrid), TGFB1I1 (Affinity Capture-MS), TGFB1I1 (Affinity Capture-MS), TGFB1I1 (Affinity Capture-MS), TGFB1I1 (Reconstituted Complex), TGFB1I1 (Two-hybrid), TGFB1I1 (Affinity Capture-Western), TGFB1I1 (Reconstituted Complex), TGFB1I1 (Two-hybrid), TGFB1I1 (Affinity Capture-Western), TGFB1I1 (Affinity Capture-MS)

ESM2 similar proteins: A0A1L8F1M4, A8WH69, B1AK53, D3ZQL6, E1BBG2, O43294, O60711, O75112, P36202, P49023, P49024, P50479, P70271, Q09476, Q0VA45, Q2TCH4, Q3MHZ4, Q3SX40, Q3T005, Q3TJD7, Q4V882, Q5R7I1, Q5U464, Q62219, Q62920, Q63618, Q66H76, Q679P3, Q6INU3, Q6P7E4, Q80VP1, Q8BGT6, Q8BYZ1, Q8CI51, Q8K382, Q8N3F8, Q8TDY4, Q8TEH3, Q8VI36, Q91W69

Diamond homologs: A0A1L8F1M4, A0M8R4, A0M8S5, A0M8U6, A1Z6W3, A8WH69, O43294, O43900, P47226, Q00PK1, Q04650, Q07DW1, Q07DX3, Q07DY3, Q07DZ4, Q07E27, Q07E40, Q07E51, Q09YI0, Q09YJ2, Q09YK3, Q09YL5, Q09YN8, Q108U9, Q174I2, Q17QE2, Q28FG2, Q292U2, Q292U5, Q2IBA3, Q2IBC3, Q2IBH0, Q2LAP6, Q2QL92, Q2QLA1, Q2QLB2, Q2QLC3, Q2QLE3, Q2QLF4, Q2QLG8

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
FYN	“up-regulates activity”	TGFB1I1	phosphorylation
PTK2B	“up-regulates activity”	TGFB1I1	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 43 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
positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	5	12.2×	8e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	65
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1449 predictions. Top by Δscore:

Variant	Effect	Δscore
16:31473422:T:TA	acceptor_gain	1.0000
16:31474236:GCCT:G	donor_gain	1.0000
16:31474240:G:GG	donor_gain	1.0000
16:31474262:GGC:G	donor_gain	1.0000
16:31474271:A:G	donor_gain	1.0000
16:31474456:G:GG	donor_gain	1.0000
16:31474560:CA:C	acceptor_loss	1.0000
16:31474561:A:AG	acceptor_gain	1.0000
16:31474561:AGCTT:A	acceptor_loss	1.0000
16:31474562:G:GG	acceptor_gain	1.0000
16:31474562:GC:G	acceptor_gain	1.0000
16:31474754:GCAA:G	donor_gain	1.0000
16:31474758:G:GG	donor_gain	1.0000
16:31476006:TCGCA:T	acceptor_loss	1.0000
16:31476007:CGCAG:C	acceptor_loss	1.0000
16:31476008:GCA:G	acceptor_loss	1.0000
16:31476009:CAGGT:C	acceptor_loss	1.0000
16:31476010:A:C	acceptor_loss	1.0000
16:31476011:G:GC	acceptor_loss	1.0000
16:31476230:A:T	donor_gain	1.0000
16:31477006:GCAGG:G	donor_gain	1.0000
16:31477009:GG:G	donor_gain	1.0000
16:31477010:G:GT	donor_gain	1.0000
16:31477293:C:CA	acceptor_gain	1.0000
16:31477294:G:A	acceptor_gain	1.0000
16:31472447:G:GT	donor_gain	0.9900
16:31472447:G:T	donor_gain	0.9900
16:31473425:T:TA	acceptor_gain	0.9900
16:31473833:A:AG	acceptor_gain	0.9900
16:31473833:AGCAC:A	acceptor_gain	0.9900

AlphaMissense

2993 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:31473951:T:C	L100P	1.000
16:31476156:T:C	C287R	1.000
16:31476166:G:A	C290Y	1.000
16:31476524:T:C	F311S	1.000
16:31476864:T:C	F325L	1.000
16:31476866:C:A	F325L	1.000
16:31476866:C:G	F325L	1.000
16:31476927:T:A	C346S	1.000
16:31476927:T:C	C346R	1.000
16:31476928:G:A	C346Y	1.000
16:31476928:G:C	C346S	1.000
16:31476929:C:G	C346W	1.000
16:31476964:T:A	I358N	1.000
16:31476984:T:A	W365R	1.000
16:31476984:T:C	W365R	1.000
16:31476986:G:C	W365C	1.000
16:31476986:G:T	W365C	1.000
16:31476996:T:C	C369R	1.000
16:31476997:G:A	C369Y	1.000
16:31476998:T:G	C369W	1.000
16:31476999:T:C	F370L	1.000
16:31477000:T:C	F370S	1.000
16:31477000:T:G	F370C	1.000
16:31477001:C:A	F370L	1.000
16:31477001:C:G	F370L	1.000
16:31477005:T:C	C372R	1.000
16:31477340:T:C	F384L	1.000
16:31477342:T:A	F384L	1.000
16:31477342:T:G	F384L	1.000
16:31477403:T:C	C405R	1.000

dbSNP variants (sampled 300 via entrez): RS1000574636 (16:31477548 A>G), RS1000749458 (16:31477152 C>T), RS1002209755 (16:31475740 A>C,G,T), RS1002244053 (16:31475709 G>A,C), RS1002422226 (16:31475313 A>G), RS1002612500 (16:31470384 A>G), RS1003095154 (16:31472300 A>C), RS1003166151 (16:31477070 G>C), RS1003286798 (16:31472567 A>G), RS1003884882 (16:31475804 G>A), RS1004061141 (16:31477757 C>G), RS1004554019 (16:31470848 C>T), RS1004558469 (16:31477984 G>T), RS1004705318 (16:31477806 C>A), RS1005178191 (16:31470597 C>T)

Disease associations

OMIM: gene MIM:602353 | 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
GCST009391_520	Metabolite levels	4.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0010117	pyruvate measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases methylation, increases expression, increases methylation	4
Valproic Acid	affects cotreatment, increases expression, affects expression, decreases expression	4
sodium arsenite	increases expression, affects cotreatment, decreases expression, increases abundance	3
bisphenol AF	increases expression, affects binding, affects folding, increases reaction, decreases reaction	3
Tetrachlorodibenzodioxin	affects expression, increases expression	3
Cyclosporine	increases expression	3
Cadmium Chloride	decreases expression, increases expression	3
bisphenol A	decreases reaction, affects binding, affects folding, increases reaction	2
entinostat	increases expression, affects cotreatment	2
bisphenol S	decreases reaction, affects binding, affects folding, increases reaction	2
Panobinostat	affects cotreatment, increases expression	2
Air Pollutants	affects cotreatment, increases abundance, increases oxidation, decreases expression	2
Doxorubicin	decreases expression, affects response to substance	2
Estradiol	affects cotreatment, increases expression, affects binding, decreases reaction	2
Ozone	increases expression, affects cotreatment, increases oxidation, increases abundance	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Tretinoin	increases expression, decreases expression	2
Aflatoxin B1	affects expression, increases expression	2
tert-Butylhydroperoxide	affects expression, increases expression	2
Particulate Matter	decreases expression, increases abundance, increases expression	2
aristolochic acid I	decreases expression	1
4-oxoretinoic acid	increases expression	1
2,4,6-tribromophenol	decreases expression	1
daidzein	increases activity, increases reaction	1
triphenyl phosphate	affects expression	1
alpha-pinene	increases abundance, affects cotreatment, increases oxidation	1
decabromobiphenyl ether	decreases expression	1
ethyl-p-hydroxybenzoate	increases expression	1
trichostatin A	increases expression	1
cinnamaldehyde	decreases expression	1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_E0QT	Ubigene HeLa TGFB1I1 KO	Cancer cell line	Female

Clinical trials (associated diseases)

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