ITIH5

Summary

ITIH5 (inter-alpha-trypsin inhibitor heavy chain 5, HGNC:21449) is a protein-coding gene on chromosome 10p14, encoding Inter-alpha-trypsin inhibitor heavy chain H5 (Q86UX2). May act as a tumor suppressor.

This gene encodes a heavy chain component of one of the inter-alpha-trypsin inhibitor (ITI) family members. ITI proteins are involved in extracellular matrix stabilization and in the prevention of tumor metastasis. They are also structurally related plasma serine protease inhibitors and are composed of a light chain and varying numbers of heavy chains. This family member is thought to function as a tumor suppressor in breast and thyroid cancers. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 80760 — RefSeq curated summary.

At a glance

• GWAS associations: 5
• Clinical variants (ClinVar): 188 total
• MANE Select transcript: NM_030569

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:21449
Approved symbol	ITIH5
Name	inter-alpha-trypsin inhibitor heavy chain 5
Location	10p14
Locus type	gene with protein product
Status	Approved
Aliases	MGC10848
Ensembl gene	ENSG00000123243
Ensembl biotype	protein_coding
OMIM	609783
Entrez	80760

Gene structure

Transcript identifiers

Ensembl transcripts: 20 — 14 protein_coding, 3 retained_intron, 2 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000397145, ENST00000397146, ENST00000434980, ENST00000461751, ENST00000468389, ENST00000473591, ENST00000476417, ENST00000492668, ENST00000613909, ENST00000884048, ENST00000884049, ENST00000884050, ENST00000884051, ENST00000884052, ENST00000884053, ENST00000884054, ENST00000884055, ENST00000884056, ENST00000945639, ENST00000945640

RefSeq mRNA: 3 — MANE Select: NM_030569 NM_001001851, NM_030569, NM_032817

CCDS: CCDS31139, CCDS31140

Canonical transcript exons

ENST00000397146 — 14 exons

Exon	Start	End
ENSE00001527484	7559270	7563384
ENSE00003495625	7585901	7586069
ENSE00003547240	7576453	7577012
ENSE00003554501	7615982	7616098
ENSE00003558936	7579755	7580064
ENSE00003559848	7573142	7573195
ENSE00003569893	7617113	7617282
ENSE00003577280	7640754	7640855
ENSE00003609990	7637228	7637478
ENSE00003660421	7641927	7642090
ENSE00003689754	7655631	7655675
ENSE00003724391	7666803	7666966
ENSE00003746621	7569668	7569784
ENSE00003757037	7566030	7566407

Expression profiles

Bgee: expression breadth ubiquitous, 260 present calls, max score 96.80.

FANTOM5 (CAGE): breadth broad, TPM avg 10.9744 / max 1053.5131, expressed in 495 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
108194	7.1998	434
108193	3.6821	290
108190	0.0925	34

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
subcutaneous adipose tissue	UBERON:0002190	96.80	gold quality
placenta	UBERON:0001987	96.35	gold quality
adipose tissue	UBERON:0001013	96.27	gold quality
renal glomerulus	UBERON:0000074	95.48	gold quality
connective tissue	UBERON:0002384	95.31	gold quality
metanephric glomerulus	UBERON:0004736	95.16	gold quality
mucosa of stomach	UBERON:0001199	94.91	gold quality
skin of hip	UBERON:0001554	94.50	gold quality
popliteal artery	UBERON:0002250	94.39	gold quality
muscle layer of sigmoid colon	UBERON:0035805	94.39	gold quality
tibial artery	UBERON:0007610	94.37	gold quality
endothelial cell	CL:0000115	94.02	gold quality
adipose tissue of abdominal region	UBERON:0007808	93.94	gold quality
saphenous vein	UBERON:0007318	93.83	gold quality
colonic epithelium	UBERON:0000397	93.74	gold quality
omental fat pad	UBERON:0010414	93.71	gold quality
peritoneum	UBERON:0002358	93.64	gold quality
urinary bladder	UBERON:0001255	92.73	gold quality
gall bladder	UBERON:0002110	91.81	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	91.77	gold quality
blood vessel layer	UBERON:0004797	91.76	gold quality
aorta	UBERON:0000947	91.47	gold quality
cartilage tissue	UBERON:0002418	90.73	gold quality
mucosa of urinary bladder	UBERON:0001259	90.52	gold quality
right coronary artery	UBERON:0001625	90.41	gold quality
thoracic mammary gland	UBERON:0005200	90.00	gold quality
secondary oocyte	CL:0000655	89.98	gold quality
mammary gland	UBERON:0001911	89.95	gold quality
synovial joint	UBERON:0002217	89.41	gold quality
vena cava	UBERON:0004087	89.40	gold quality

Single-cell (SCXA)

Detected in 10 experiment(s), a significant marker in 8.

Experiment	Marker?	Max mean expression
E-GEOD-114530	yes	440.81
E-MTAB-6701	yes	123.51
E-GEOD-135922	yes	27.38
E-HCAD-35	yes	17.69
E-MTAB-6678	yes	17.52
E-ANND-3	yes	12.74
E-CURD-114	yes	9.86
E-GEOD-137537	yes	7.53
E-HCAD-30	no	169.51
E-MTAB-10137	no	4.76

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

114 targeting ITIH5, 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-4425	100.00	67.59	1049
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-9-3P	99.96	70.88	2068
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-3910	99.95	71.13	2227
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AD-5P	99.94	71.23	3502
HSA-MIR-548AE-5P	99.94	71.23	3502
HSA-MIR-548AK	99.94	71.24	3488
HSA-MIR-548AM-5P	99.94	71.24	3488
HSA-MIR-548AP-5P	99.94	71.14	3489
HSA-MIR-548AQ-5P	99.94	71.34	3426
HSA-MIR-548AR-5P	99.94	71.28	3515

Literature-anchored findings (GeneRIF, showing 23)

• expression is consistantly lost or strongly downregulated in invasive ductal carcinoma; proposed that loss of ITIH5 expression may be involved in breast cancer development (PMID:14744536)
• Promoter methylation-mediated loss of ITIH5 expression is associated with unfavourable outcome in breast cancer patients. (PMID:17653090)
• Both ITIH5 protein expression and ITIH5 promoter methylation may serve as prognostic biomarkers, thereby helping improve clinical patient outcome. (PMID:18810445)
• ITIH-5 is highly expressed in sc adipose tissue, increased in obesity, down regulated after weight loss, and associated with measures of body size and metabolism. (PMID:21852814)
• ITIH5 gene expression is regulated both by obesity and by the region between visceral and subcutaneous adipose tissue. (PMID:22616691)
• Tumor-specific methylation of the three-gene panel (ITIH5, DKK3, and RASSF1A) might be a valuable biomarker for the early detection of breast cancer. (PMID:23320751)
• provide evidence that down-regulation of ITIH5 by aberrant DNA hypermethylation may provoke invasive phenotypes in human bladder cancer (PMID:24265292)
• ITIH5 expression is decreased in gastric cancer and that low expression of this protein is associated with poor clinical outcome. (PMID:24913813)
• ITIH5 is a novel putative tumor suppressor gene in colon cancer with a potential impact in the CIMP-related pathway. (PMID:25093535)
• Hence, we can strengthen the presumption that ITIH5 may constitute a novel regulatory molecule of the human skin that could play an important role in in fl ammation via its interaction with hyaluronic acid. (PMID:25809190)
• ITIH5 may be a novel putative tumor suppressor gene in NSCLC with a potential molecular significance in the squamoid ADC subtype and further clinical impact for risk stratification of adenocarcinoma patients. (PMID:26252352)
• The current study describes a novel mechanism linking the TSG-6 transfer of the newly described HC5 to the HA-dependent control of cell phenotype. The interaction of HC5 with cell surface HA was essential for TGFbeta1-dependent differentiation of fibroblasts to myofibroblasts, highlighting its importance as a novel potential therapeutic target. (PMID:27143355)
• This is the first study so far showing a putative tumor suppressive function of ITIH5 in cervical carcinogenesis. (PMID:28059468)
• Results provide evidence that ITIH5 triggers a reprogramming of breast cancer cells through global epigenetic changes effecting DAPK1. ITIH5 may represent an ECM modulator in epithelial breast tissue mediating suppression of tumor initiating cancer cell characteristics which are thought being responsible for the metastasis of breast cancer. (PMID:28231808)
• Low ITIH5 expression is associated with liver metastasis in pancreatic cancer. (PMID:28289921)
• ITIH5 may represent a novel modulator of TGF-beta superfamily signaling. (PMID:28940371)
• The results demonstrated that the MIR31HG-miR-31-ITIH5-PIK3CG pathway plays a role in the pathogenesis of Hirschsprung disease. (PMID:29626357)
• Genetic effects on planum temporale asymmetry and their limited relevance to neurodevelopmental disorders, intelligence or educational attainment. (PMID:31887566)
• Inter-alpha-Trypsin Inhibitor Heavy Chain 5 (ITIH5) Is a Natural Stabilizer of Hyaluronan That Modulates Biological Processes in the Skin. (PMID:32799206)
• Suppression of pancreatic cancer liver metastasis by secretion-deficient ITIH5. (PMID:33024269)
• The ECM Modulator ITIH5 Affects Cell Adhesion, Motility and Chemotherapeutic Response of Basal/Squamous-Like (BASQ) Bladder Cancer Cells. (PMID:33924987)
• ITIH5, a p53-responsive gene, inhibits the growth and metastasis of melanoma cells by downregulating the transcriptional activity of KLF4. (PMID:33935281)
• ITIH5 as a multifaceted player in pancreatic cancer suppression, impairing tyrosine kinase signaling, cell adhesion and migration. (PMID:38375974)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	itih5	ENSDARG00000045517
mus_musculus	Itih5	ENSMUSG00000025780
rattus_norvegicus	Itih5	ENSRNOG00000049614

Paralogs (11): ITIH4 (ENSG00000055955), ITIH1 (ENSG00000055957), ITIH6 (ENSG00000102313), PARP4 (ENSG00000102699), VWA5A (ENSG00000110002), VWA5B2 (ENSG00000145198), ITIH2 (ENSG00000151655), VWA5B1 (ENSG00000158816), ITIH3 (ENSG00000162267), VWA3B (ENSG00000168658), VWA3A (ENSG00000175267)

Protein

Protein identifiers

Inter-alpha-trypsin inhibitor heavy chain H5 — Q86UX2 (reviewed: Q86UX2)

All UniProt accessions (4): A0A096LP62, C9J2H1, G5E9D8, H7C5A6

UniProt curated annotations — full annotation on UniProt →

Function. May act as a tumor suppressor.

Subcellular location. Secreted.

Tissue specificity. Abundantly expressed in placenta. Less abundant expression in mammary gland and ovary. Expression is barely detectable levels in all other tissues tested.

Induction. Down-regulated in breast tumors.

Similarity. Belongs to the ITIH family.

Isoforms (4)

UniProt ID	Names	Canonical?
Q86UX2-1	1	yes
Q86UX2-2	2
Q86UX2-3	3
Q86UX2-4	4

RefSeq proteins (3): NP_001001851, NP_085046, NP_116206 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002035	VWF_A	Domain
IPR010600	ITI_HC_C	Domain
IPR013694	VIT	Domain
IPR036465	vWFA_dom_sf	Homologous_superfamily
IPR050934	ITIH	Family

Pfam: PF00092, PF06668, PF08487

UniProt features (34 total): glycosylation site 8, splice variant 8, sequence variant 7, sequence conflict 4, region of interest 3, domain 2, signal peptide 1, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q86UX2-F1	78.89	0.48

Functional residue map

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

Glycosylation sites (8): 421, 508, 776, 795, 862, 97, 127, 231

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 201 (showing top): WALLACE_PROSTATE_CANCER_RACE_UP, BENPORATH_ES_WITH_H3K27ME3, WHITEHURST_PACLITAXEL_SENSITIVITY, GAUSSMANN_MLL_AF4_FUSION_TARGETS_A_DN, CHANDRAN_METASTASIS_DN, ACEVEDO_LIVER_CANCER_WITH_H3K27ME3_UP, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, CAIRO_HEPATOBLASTOMA_CLASSES_DN, MARTINEZ_RB1_TARGETS_UP, GOBP_HYALURONAN_METABOLIC_PROCESS, SHETH_LIVER_CANCER_VS_TXNIP_LOSS_PAM3, BOQUEST_STEM_CELL_CULTURED_VS_FRESH_DN, DELYS_THYROID_CANCER_DN, GOBP_AMINOGLYCAN_METABOLIC_PROCESS, NAKAYAMA_SOFT_TISSUE_TUMORS_PCA2_DN

GO Biological Process (2): hyaluronan metabolic process (GO:0030212), uterus development (GO:0060065)

GO Molecular Function (2): serine-type endopeptidase inhibitor activity (GO:0004867), peptidase inhibitor activity (GO:0030414)

GO Cellular Component (2): extracellular region (GO:0005576), extracellular matrix (GO:0031012)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
glycosaminoglycan metabolic process	1
animal organ development	1
reproductive structure development	1
serine-type endopeptidase activity	1
endopeptidase inhibitor activity	1
enzyme inhibitor activity	1
peptidase activity	1
peptidase regulator activity	1
cellular anatomical structure	1
external encapsulating structure	1

Protein interactions and networks

STRING

1316 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ITIH5	TNFAIP6	P98066	660
ITIH5	RASAL3	Q86YV0	497
ITIH5	GLOD5	A6NK44	461
ITIH5	HOXD10	P28358	380
ITIH5	RASSF1	Q9NS23	370
ITIH5	TMEM231	Q9H6L2	361
ITIH5	PPFIBP2	Q8ND30	326
ITIH5	GRAMD1B	Q3KR37	309
ITIH5	NKX2-6	A6NCS4	300
ITIH5	CST6	Q15828	298
ITIH5	PDCD5	O14737	285
ITIH5	VGLL3	A8MV65	284
ITIH5	AMBP	P00977	281
ITIH5	GAREM1	Q9H706	279
ITIH5	DKK3	Q9UBP4	276

IntAct

10 interactions, top by confidence:

A	B	Type	Score
BAG4	ITIH5	psi-mi:“MI:0915”(physical association)	0.370
CHEK2	ITIH5	psi-mi:“MI:0915”(physical association)	0.370
ESR2	ITIH5	psi-mi:“MI:0915”(physical association)	0.370
ITIH5	HMMR	psi-mi:“MI:0915”(physical association)	0.370
ITIH5	NOTCH2	psi-mi:“MI:0915”(physical association)	0.370
ITIH5	PPM1D	psi-mi:“MI:0915”(physical association)	0.370
ITIH5	RAD51	psi-mi:“MI:0915”(physical association)	0.370
ITIH5	RB1CC1	psi-mi:“MI:0915”(physical association)	0.370
ITIH5	XRCC3	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (11): ITIH5 (Two-hybrid), ITIH5 (Two-hybrid), ITIH5 (Two-hybrid), ITIH5 (Two-hybrid), ITIH5 (Two-hybrid), ITIH5 (Two-hybrid), ITIH5 (Two-hybrid), ITIH5 (Two-hybrid), ITIH5 (Two-hybrid), ITIH5 (Affinity Capture-MS), ITIH5 (Two-hybrid)

ESM2 similar proteins: A2VDP6, A4D0V7, B1WB06, F1N2K1, O43548, P06802, P15396, P22413, P50127, P79949, P97259, Q05004, Q08834, Q08BN9, Q09328, Q14C87, Q14DG7, Q2TU62, Q3L7M0, Q3U095, Q52KP5, Q5R748, Q5RCA5, Q5XI89, Q5ZLK4, Q6AX23, Q6DNG6, Q6UWF7, Q6ZXA0, Q76HP2, Q76HP3, Q86UX2, Q8BG22, Q8C7K6, Q8K1B9, Q8N323, Q8NCG5, Q8NHY0, Q8R4G6, Q8VI38

Diamond homologs: A2VE29, A6X935, O02668, P19823, P19827, P56652, P79263, P97278, P97279, P97280, Q06033, Q0VCM5, Q14624, Q29052, Q3T052, Q5RB37, Q5RER0, Q61702, Q61703, Q61704, Q63416, Q6UXX5, Q86UX2, Q8BJD1, Q9GLY5, P56651, A1A5Q7, Q5RJF7, A6NCI4, Q8CFG5, Q8IZS8, Q9Z1L5, Q3UVV9, A8XP97, P34374, Q9ZQ46

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	147
Likely benign	16
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

3129 predictions. Top by Δscore:

Variant	Effect	Δscore
10:7569666:A:AC	donor_gain	1.0000
10:7569667:C:CC	donor_gain	1.0000
10:7569781:TCCA:T	acceptor_gain	1.0000
10:7569782:CCA:C	acceptor_gain	1.0000
10:7569782:CCAC:C	acceptor_gain	1.0000
10:7569783:CAC:C	acceptor_gain	1.0000
10:7569785:C:CC	acceptor_gain	1.0000
10:7569789:C:CT	acceptor_gain	1.0000
10:7569790:A:T	acceptor_gain	1.0000
10:7569794:C:CT	acceptor_gain	1.0000
10:7569795:A:T	acceptor_gain	1.0000
10:7569804:C:CT	acceptor_gain	1.0000
10:7569805:G:T	acceptor_gain	1.0000
10:7576449:GTACC:G	donor_loss	1.0000
10:7576450:TA:T	donor_loss	1.0000
10:7576452:C:CT	donor_loss	1.0000
10:7576452:CCTGG:C	donor_gain	1.0000
10:7579776:T:TA	donor_gain	1.0000
10:7579779:T:TA	donor_gain	1.0000
10:7579782:T:TA	donor_gain	1.0000
10:7585934:T:A	donor_gain	1.0000
10:7585940:C:A	donor_gain	1.0000
10:7586070:C:CC	acceptor_gain	1.0000
10:7617111:ACC:A	donor_loss	1.0000
10:7617112:CC:C	donor_loss	1.0000
10:7617279:TCAT:T	acceptor_gain	1.0000
10:7617279:TCATC:T	acceptor_loss	1.0000
10:7617280:CAT:C	acceptor_gain	1.0000
10:7617280:CATC:C	acceptor_gain	1.0000
10:7617281:AT:A	acceptor_gain	1.0000

AlphaMissense

6194 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:7586001:A:C	F336L	0.999
10:7586001:A:T	F336L	0.999
10:7586003:A:G	F336L	0.999
10:7569729:G:C	C696W	0.997
10:7616012:A:C	S303R	0.997
10:7616012:A:T	S303R	0.997
10:7616014:T:G	S303R	0.997
10:7569730:C:G	C696S	0.996
10:7569730:C:T	C696Y	0.996
10:7569731:A:G	C696R	0.996
10:7569731:A:T	C696S	0.996
10:7579954:C:A	G407W	0.996
10:7616013:C:A	S303I	0.996
10:7641972:A:G	F85S	0.996
10:7563200:G:C	C904W	0.995
10:7569726:G:C	F697L	0.995
10:7569726:G:T	F697L	0.995
10:7569728:A:G	F697L	0.995
10:7569765:A:C	F684L	0.995
10:7569765:A:T	F684L	0.995
10:7569767:A:G	F684L	0.995
10:7569775:T:C	D681G	0.995
10:7616003:C:A	M306I	0.995
10:7616003:C:G	M306I	0.995
10:7616003:C:T	M306I	0.995
10:7616013:C:T	S303N	0.995
10:7616028:A:G	F298S	0.995
10:7563201:C:G	C904S	0.994
10:7563202:A:T	C904S	0.994
10:7579953:C:A	G407V	0.994

dbSNP variants (sampled 300 via entrez): RS1000059143 (10:7648329 A>T), RS1000067676 (10:7666890 C>A,G,T), RS1000072706 (10:7642374 A>G), RS1000073385 (10:7584439 G>A), RS1000098404 (10:7667879 C>T), RS1000102931 (10:7659923 CT>C), RS1000105232 (10:7567665 AGTT>A), RS1000115114 (10:7567454 C>A), RS1000179908 (10:7571439 C>T), RS1000211669 (10:7597833 T>C), RS1000316403 (10:7571277 G>T), RS1000316632 (10:7604739 A>T), RS1000331999 (10:7586125 C>T), RS1000332628 (10:7610780 G>A), RS1000376147 (10:7661154 C>G)

Disease associations

OMIM: gene MIM:609783 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): prostate cancer (MONDO:0008315)

Orphanet (1): Familial prostate cancer (Orphanet:1331)

HPO phenotypes

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

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST006585_47	Blood protein levels	9.000000e-12
GCST009391_1426	Metabolite levels	4.000000e-06
GCST009459_2	Planum temporale asymmetry index	2.000000e-15
GCST010703_302	Brain morphology (MOSTest)	7.000000e-28
GCST90010427_14	Left–right brain asymmetry	5.000000e-38

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0010407	triacylglycerol 48:4 measurement
EFO:0004346	neuroimaging measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D011471	Prostatic Neoplasms	C04.588.945.440.770; C12.100.500.260.750; C12.100.500.565.625; C12.200.294.260.750; C12.200.294.565.625; C12.200.758.409.750; C12.900.619.750

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression	8
Benzo(a)pyrene	affects methylation, increases expression, increases methylation	4
mercuric bromide	increases expression, affects cotreatment	2
entinostat	increases expression, affects cotreatment	2
belinostat	increases expression, affects cotreatment	2
Panobinostat	affects cotreatment, increases expression	2
Nickel	decreases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Cyclosporine	decreases expression	2
triphenyl phosphate	increases expression	1
bisphenol A	affects binding, increases reaction	1
deoxynivalenol	decreases expression	1
trichostatin A	increases expression	1
arsenite	increases methylation	1
mono-(2-ethylhexyl)phthalate	increases expression	1
cobaltous chloride	increases expression	1
benzo(e)pyrene	increases methylation	1
aflatoxin B2	increases methylation	1
CGP 52608	affects binding, increases reaction	1
chloropicrin	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
nutlin 3	affects cotreatment, increases expression, increases secretion	1
abrine	decreases expression	1
ormosil	affects binding, decreases expression	1
dorsomorphin	affects cotreatment, increases expression	1
jinfukang	affects cotreatment, increases expression	1
incobotulinumtoxinA	decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Vorinostat	increases expression	1
Arsenic	affects methylation	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00029224	PHASE4	COMPLETED	Treatment With Zoledronic Acid in Patients With Breast Cancer, Multiple Myeloma, and Prostate Cancer With Cancer Related Bone Lesions
NCT00035997	PHASE4	COMPLETED	Open-label Trial on the Effect of I.V. Zoledronic Acid 4 mg on Bone Density in Hormone Sensitive Prostate Cancer Patients With Bone Metastasis
NCT00063609	PHASE4	COMPLETED	The Effect of Zoledronic Acid on Bone Loss in Prostate Cancer Patients Undergoing Androgen Deprivation Therapy
NCT00103623	PHASE4	SUSPENDED	The Plenaxis® Experience Study
NCT00106392	PHASE4	COMPLETED	A Safety and Efficacy Study of Prograf in the Prevention of Erectile Dysfunction After Radical Prostatectomy
NCT00185029	PHASE4	UNKNOWN	MR-Lymphography and Lymph Node Staging in Prostate Cancer
NCT00199485	PHASE4	COMPLETED	Angelica Sinensis for the Treatment of Hot Flashes in Men Undergoing LHRH Therapy for Prostate Cancer
NCT00219219	PHASE4	COMPLETED	Zoledronic Acid in the Prevention of Skeletal-related Events in Hormone Refractory and Hormone-sensitive Prostate Cancer Patients With Bone Metastases
NCT00219271	PHASE4	COMPLETED	Effect Of Zoledronic Acid On Circulating And Bone Marrow-Residing Prostate Cancer Cells In Patients With Clinically Localized Prostate Cancer
NCT00237146	PHASE4	COMPLETED	Study to Evaluate Zoledronic Acid on Quality of Life and Skeletal-related Events as Adjuvant Treatment in Patients With Hormone-naïve Prostate Cancer and Bone Metastasis Who Have Undergone Orchiectomy
NCT00242554	PHASE4	COMPLETED	Open-label Phase IV Clinical Trial to Evaluate the Safety and Tolerability of Zoledronic Acid in Patients With Prostate Cancer and Bone Metastases
NCT00280098	PHASE4	COMPLETED	Docetaxel in the Treatment of Hormone Refractory Prostate Cancer
NCT00293696	PHASE4	COMPLETED	Casodex/Zoladex Biomarkers in Localised Prostate Cancer
NCT00334139	PHASE4	COMPLETED	Effect of Zoledronic Acid on Bone Metabolism in Patients With Bone Metastasis and Prostate or Breast Cancer
NCT00375765	PHASE4	COMPLETED	Effects On Dihydrotestosterone Regulated Gene Expression In Benign Prostatic Hyperplasia Or Prostate Cancer
NCT00391690	PHASE4	COMPLETED	Evaluation of Bone Markers as Diagnostic Tools for Early Detection of Bone Metastases in Patients With High Risk Prostate Cancer
NCT00422708	PHASE4	COMPLETED	Local Anesthesia for Prostate Biopsy
NCT00526331	PHASE4	COMPLETED	Evaluation of Arterial Pressure Based Cardiac Output for Goal-Directed Perioperative Therapy
NCT00590213	PHASE4	COMPLETED	Compare the Value of Prophylactic Versus Therapeutic Breast Radiotherapy in CASODEX
NCT00629330	PHASE4	TERMINATED	Dissemination of Prostate Cancer Screening to PCP’s in African American Communities
NCT00771966	PHASE4	COMPLETED	Radical Prostatectomy and Perioperative Fluid Therapy
NCT00805701	PHASE4	COMPLETED	Study Assessing The Efficacy And Safety Of Avodart (Dutasteride) At Improving Urinary Symptoms In Men With Prostate Cancer Who Are Undergoing Seed Implantation
NCT00859027	PHASE4	COMPLETED	Effect Of Risedronate On Bone Mass In Older Men Receiving Neoadjuvant Therapy For Prostate Cancer
NCT00906269	PHASE4	UNKNOWN	Can Hyperbaric Oxygen Improve Erectile Function Following Surgery for Prostate Cancer
NCT00953277	PHASE4	COMPLETED	Study of Nerve Reconstruction Using AVANCE in Subjects Who Undergo Robotic Assisted Prostatectomy for Treatment of Prostate Cancer
NCT00982800	PHASE4	COMPLETED	Does Postoperative Gabapentin Reduce Pain, Opioid Consumption and Anxiety and Have a Positive Effect on Health Related Quality of Life After Radical Prostatectomy?
NCT01083199	PHASE4	COMPLETED	Global Performance Evaluation of the AMS CONTINUUM™ Device
NCT01136226	PHASE4	COMPLETED	Evaluate Recovery of Testosterone for Patients Using Eligard
NCT01161563	PHASE4	COMPLETED	Randomized Crossover Trial to Assess the Tolerability of Gonadotropin Releasing Hormone (GnRH) Analogue Administration
NCT01230905	PHASE4	COMPLETED	Study to Monitor the Effects of Androgen Suppression Treatment on the Heart
NCT01296672	PHASE4	COMPLETED	3 Month Finasteride Challenge Test Can Significantly Improve the Performance of Screening for Prostate Cancer
NCT01365143	PHASE4	TERMINATED	Prospective Randomized Trial Comparing Robotic Versus Open Radical Prostatectomy
NCT01379742	PHASE4	UNKNOWN	Comparison of Between ThinSeed™ and OncoSeed™ for Permanent Prostate Brachytherapy
NCT01486563	PHASE4	COMPLETED	Hydroxyethyl Starch and Renal Function After Radical Prostatectomy
NCT01511874	PHASE4	COMPLETED	Efficacy and Safety Study of ELIGARD 22.5mg With Prostate Cancer
NCT01512472	PHASE4	TERMINATED	Firmagon (Degarelix) Intermittent Therapy
NCT01547416	PHASE4	COMPLETED	The Effect of Combined General/Epidural Anesthesia Versus General Anesthesia on Diaphragmatic Function
NCT01571544	PHASE4	COMPLETED	The Use of Thermal Suits as Preventing Hypothermia During Surgery
NCT01581749	PHASE4	UNKNOWN	Evaluation of Truebeam for Low-Intermediate Risk Prostate Cancer
NCT01649635	PHASE4	COMPLETED	Study of Cabazitaxel Combined With Prednisone and Prophylaxis of Neutropenia Complications in the Treatment of Patients With Metastatic Castration-resistant Prostate Cancer