KMT5A

Summary

KMT5A (lysine methyltransferase 5A, HGNC:29489) is a protein-coding gene on chromosome 12q24.31, encoding N-lysine methyltransferase KMT5A (Q9NQR1). Protein-lysine N-methyltransferase that monomethylates both histones and non-histone proteins. It is a selective cancer dependency (DepMap: 45.4% of cell lines).

The protein encoded by this gene is a protein-lysine N-methyltransferase that can monomethylate Lys-20 of histone H4 to effect transcriptional repression of some genes. The encoded protein is required for cell proliferation and plays a role in chromatin condensation.

Source: NCBI Gene 387893 — RefSeq curated summary.

At a glance

• GWAS associations: 17
• Clinical variants (ClinVar): 15 total
• Druggable target: yes
• Cancer driver (intOGen): activating (oncogene-like) across 1 cancer types
• Cancer dependency (DepMap): dependent in 45.4% of screened cell lines
• MANE Select transcript: NM_020382

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29489
Approved symbol	KMT5A
Name	lysine methyltransferase 5A
Location	12q24.31
Locus type	gene with protein product
Status	Approved
Aliases	SET8, SET07, PR-Set7
Ensembl gene	ENSG00000183955
Ensembl biotype	protein_coding
OMIM	607240
Entrez	387893

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 3 protein_coding_CDS_not_defined, 2 protein_coding, 2 retained_intron, 1 nonsense_mediated_decay

ENST00000402868, ENST00000437502, ENST00000437519, ENST00000461103, ENST00000462311, ENST00000478781, ENST00000485469, ENST00000537270

RefSeq mRNA: 7 — MANE Select: NM_020382 NM_001324504, NM_001324505, NM_001324506, NM_001367386, NM_001367388, NM_001367389, NM_020382

CCDS: CCDS9247

Canonical transcript exons

ENST00000402868 — 8 exons

Exon	Start	End
ENSE00001553402	123407493	123409353
ENSE00003460479	123396345	123396432
ENSE00003498187	123404884	123405074
ENSE00003632644	123395047	123395266
ENSE00003645811	123403573	123403632
ENSE00003661438	123390630	123390786
ENSE00003728128	123384132	123384208
ENSE00003751936	123389433	123389554

Expression profiles

Bgee: expression breadth ubiquitous, 191 present calls, max score 97.24.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 21.8897 / max 267.7466, expressed in 1815 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
128575	10.1092	1787
128574	9.1315	1582
128573	1.4063	799
128576	1.2428	872

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sural nerve	UBERON:0015488	97.24	gold quality
ventricular zone	UBERON:0003053	95.81	gold quality
lower esophagus mucosa	UBERON:0035834	95.61	gold quality
right coronary artery	UBERON:0001625	94.39	gold quality
thoracic aorta	UBERON:0001515	94.35	gold quality
ascending aorta	UBERON:0001496	94.34	gold quality
esophagus mucosa	UBERON:0002469	94.22	gold quality
descending thoracic aorta	UBERON:0002345	93.92	gold quality
aorta	UBERON:0000947	93.84	gold quality
calcaneal tendon	UBERON:0003701	93.83	gold quality
esophagus	UBERON:0001043	93.82	gold quality
right lobe of thyroid gland	UBERON:0001119	93.79	gold quality
body of pancreas	UBERON:0001150	93.77	gold quality
popliteal artery	UBERON:0002250	93.69	gold quality
tibial artery	UBERON:0007610	93.68	gold quality
left lobe of thyroid gland	UBERON:0001120	93.66	gold quality
lower esophagus	UBERON:0013473	93.58	gold quality
lower esophagus muscularis layer	UBERON:0035833	93.56	gold quality
body of uterus	UBERON:0009853	93.47	gold quality
left uterine tube	UBERON:0001303	93.43	gold quality
right uterine tube	UBERON:0001302	93.25	gold quality
thyroid gland	UBERON:0002046	93.15	gold quality
ectocervix	UBERON:0012249	93.00	gold quality
ganglionic eminence	UBERON:0004023	92.95	gold quality
smooth muscle tissue	UBERON:0001135	92.94	gold quality
left coronary artery	UBERON:0001626	92.93	gold quality
skin of leg	UBERON:0001511	92.91	gold quality
vagina	UBERON:0000996	92.82	gold quality
skin of abdomen	UBERON:0001416	92.79	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	92.76	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	10.26
E-GEOD-124858	no	45.74

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AR, PPARG, PRDM2, TCF12, TP53, TP63

miRNA regulators (miRDB)

132 targeting KMT5A, 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-4795-3P	100.00	74.62	4024
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-4673	100.00	66.64	1490
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-485-3P	99.98	70.68	1585
HSA-MIR-539-3P	99.98	70.74	1616
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-4645-5P	99.98	65.81	1284
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-7152-3P	99.97	67.47	849
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-23A-3P	99.95	74.24	3163

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 45.4% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 40)

• crystal structure of SET8 bound to a histone H4 peptide bearing Lys-20 and the product cofactor S-adenosylhomocysteine (PMID:15933070)
• coordination between the amino acid sequence RHRK20VLRDN and the SET domain of SET8 determines the substrate specificity and multiplicity of methylation of lysine 20 of H4 (PMID:15964846)
• This study identifies SET8 as a p53-modifying enzyme, monomethylating p53 at lysine 382(p53K382me1) and identifying (p53K382me1) as a regulatory posttranslational modification of p53. (PMID:17707234)
• Overall, we show that SET8 is essential for genomic stability in mammalian cells and that decreased expression of SET8 results in DNA damage and Chk1-dependent S-phase arrest. (PMID:18166648)
• the SET8 and PCNA interaction couples H4-K20 methylation with DNA replication (PMID:18319261)
• H4K20 monomethylation and PR-SET7 are important for L3MBTL1 function (PMID:18408754)
• SET8 plays a role in controlling G1/S transition by blocking lysine acetylation in histone through binding to H4 N-terminal tail. (PMID:18418072)
• PR-Set7 enzymatic activity is essential for mammalian cell cycle progression and for the maintenance of genomic stability, most likely by monomethylating histone H4K20. (PMID:18480059)
• Data show that bond-order computations establish that the H4-K20 monomethylation in SET8 is a concerted linear S(N)2 displacement reaction. (PMID:18512960)
• The miR-502-binding site single-nucleotide polymorphism in the 3’-UTR of SET8 modulates SET8 expression and contributes to the early development of breast cancer. (PMID:19789321)
• SET8-mediated methylation of p53 at Lys-382 promotes the interaction between L3MBTL1 and p53 in cells. (PMID:20870725)
• Results demonstrate a central role of CRL4(Cdt2)-dependent cell-cycle regulation of Set8 for the maintenance of a stable epigenetic state essential for cell viability. (PMID:20932471)
• This study identifies CRL4-Cdt2 ubiquitin ligase to promote the ubiquitin-dependent proteolysis of the histone H4 methyltransferase Set8 during S-phase of the cell cycle and after UV-irradiation in a reaction that is dependent on PCNA. (PMID:20932471)
• CRL4(Cdt2)-dependent destruction of Set8 in S phase preserves genome stability by preventing aberrant chromatin compaction during DNA synthesis. (PMID:20932472)
• The results elucidate a critical role for PR-Set7 and H4K20me1 in the chromatin events that regulate replication origins. (PMID:20953199)
• PR-Set7 is transiently recruited to laser-induced DNA damage sites through its interaction with PCNA, after which 53BP1 is recruited dependent on PR-Set7 catalytic activity. (PMID:21035370)
• [review] PR-Set7/Set8/KMT5a is the sole histone methyltransferase responsible for the monomethylation of histone H4 lysine 20 (H4K20me1) in higher eukaryotes. (PMID:21200139)
• The turnover of SET8 is accelerated after ultraviolet irradiation dependent on the CRL4(CDT2) ubiquitin ligase and PCNA. (PMID:21220508)
• SET8 is a Wnt signaling mediator and is recruited by LEF1/TCF4 to regulate the transcription of Wnt-activated genes, possibly through H4K20 monomethylation at the target gene promoters. (PMID:21282610)
• in breast carcinoma samples, SET8 expression is positively correlated with metastasis (PMID:21983900)
• SET8 modifies hepatocellular carcinoma outcome by altering its expression, which depends, at least in part, on its binding affinity with miR-502. (PMID:22095217)
• An increase of methylated PCNA was found in cancer cells, and the expression levels of SETD8 and PCNA were correlated in cancer tissue samples (PMID:22556262)
• long recognition sequence of SET8 makes it difficult to methylate a lysine in a folded region of a protein (PMID:22583696)
• SET8 CC genotype was associated with a decreased risk of EOC in this case-control study. The analysis of genetic polymorphisms in miRNA binding sites may help identify subgroups of populations that are at high risk for EOC (PMID:22867998)
• PR-Set7 is an important downstream effector of CRL4(Cdt2) function during origin of DNA replication licensing, dependent on Suv4-20h1/2 activity (PMID:23152447)
• miR-502-binding SNP in SET8 may modulate SET8 expression and contribute to early development of breast cancer. (PMID:23291132)
• Data indicate that DDX21, a nucleolar protein, was confirmed to associate with SET8. (PMID:23419719)
• Migration of epithelial cells is stimulated by CRL1(FBXO11)-mediated downregulation of Cdt2 and the consequent stabilization of Set8. (PMID:23478445)
• Data indicate the Set8-Numb-p53 signaling axis as an important regulatory pathway for apoptosis and suggests a therapeutic strategy by targeting Numb methylation. (PMID:23706821)
• a molecular mechanism for the regulation of SET8 and extend the biological function of microRNA-7 to DNA damage response (PMID:23720754)
• all of the H3K36-specific methyltransferases, including ASH1L, HYPB, NSD1, and NSD2 were inhibited by ubH2A, whereas the other histone methyltransferases, including PRC2, G9a, and Pr-Set7 were not affected by ubH2A. (PMID:24019522)
• Genetic variation in a microRNA-502 minding site in SET8 gene confers clinical outcome of non-small cell lung cancer in a Chinese population. (PMID:24146953)
• significant association between the polymorphism (rs16917496) of the miR-502-binding site in the 3’-UTR of SET8 and TP53 codon 72 polymorphism and the risk of developing NSCLC. (PMID:24374662)
• PR-SET7 and H4K20me1 are required for establishing both the H4K16Ac and H4K20me3 marks and have a dual role in the local regulation of Pol II pausing (PMID:24459145)
• Therefore, we conclude that SET8 is involved in AR-mediated transcription activation, possibly through its interaction with AR and H4K20me1 modification. (PMID:24937452)
• Our results demonstrated that SETD8 rs16917496 C/T polymorphism was associated with decreased risk of developing pediatric acute lymphoblastic leukemia (PMID:25048968)
• commonality of SPS8I1-3 against SETD8, together with their distinct structures and mechanisms for SETD8 inhibition, argues for the collective application of these compounds as SETD8 inhibitors (PMID:25137013)
• These data suggest that there are significant associations between the miR-502-binding site single nucleotide polymorphism in the 3’-UTR of SET8 and the TP53 codon 72 polymorphism with cervical cancer in Chinese, and there is a gene-gene interaction. (PMID:25169478)
• SET8 is required for 53BP1 recruitment and efficient repair of DSB. (PMID:25252681)
• The SNP in the miR502 binding site of the SET8 3’-untranslated region seems to influence survival of non-Hodgkin’s lymphoma. (PMID:25343552)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
mus_musculus	Kmt5a	ENSMUSG00000049327
rattus_norvegicus	AABR07010705.1	ENSRNOG00000032715
rattus_norvegicus	Kmt5a	ENSRNOG00000064318

Protein

Protein identifiers

N-lysine methyltransferase KMT5A — Q9NQR1 (reviewed: Q9NQR1)

Alternative names: H4-K20-HMTase KMT5A, Histone-lysine N-methyltransferase KMT5A, Lysine N-methyltransferase 5A, Lysine-specific methylase 5A, PR/SET domain-containing protein 07, SET domain-containing protein 8

All UniProt accessions (3): C9JKQ0, F8WC45, Q9NQR1

UniProt curated annotations — full annotation on UniProt →

Function. Protein-lysine N-methyltransferase that monomethylates both histones and non-histone proteins. Specifically monomethylates ‘Lys-20’ of histone H4 (H4K20me1). H4K20me1 is enriched during mitosis and represents a specific tag for epigenetic transcriptional repression. Mainly functions in euchromatin regions, thereby playing a central role in the silencing of euchromatic genes. Required for cell proliferation, probably by contributing to the maintenance of proper higher-order structure of DNA during mitosis. Involved in chromosome condensation and proper cytokinesis. Nucleosomes are preferred as substrate compared to free histones. Mediates monomethylation of p53/TP53 at ‘Lys-382’, leading to repress p53/TP53-target genes. Plays a negative role in TGF-beta response regulation and a positive role in cell migration.

Subunit / interactions. Interacts with L3MBTL1. Interacts with SIRT2 (phosphorylated form); the interaction is direct, stimulates KMT5A-mediated methyltransferase activity at histone H4 ‘Lys-20’ (H4K20me1) and is increased in a H(2)O(2)-induced oxidative stress-dependent manner.

Subcellular location. Nucleus. Chromosome.

Post-translational modifications. Acetylated at Lys-162; does not affect methyltransferase activity. Deacetylated at Lys-162 possibly by SIRT2; does not change methyltransferase activity. Ubiquitinated and degraded by the DCX(DTL) complex.

Domain organisation. Although the SET domain contains the active site of enzymatic activity, both sequences upstream and downstream of the SET domain are required for methyltransferase activity.

Induction. By HCFC1 C-terminal chain, independently of HCFC1 N-terminal chain. Transiently induced by TGF-beta and during the cell cycle.

Similarity. Belongs to the class V-like SAM-binding methyltransferase superfamily. Histone-lysine methyltransferase family. PR/SET subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9NQR1-1	1	yes
Q9NQR1-2	2

RefSeq proteins (7): NP_001311433, NP_001311434, NP_001311435, NP_001354315, NP_001354317, NP_001354318, NP_065115* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001214	SET_dom	Domain
IPR016858	KMT5A-like	Family
IPR046341	SET_dom_sf	Homologous_superfamily
IPR047266	KMT5A-like_SET	Domain
IPR051760	KMT5A	Family

Pfam: PF00856

Enzyme classification (BRENDA):

• EC 2.1.1.361 — [histone H4]-lysine20 N-methyltransferase (BRENDA: 4 organisms, 17 substrates, 2 inhibitors, 0 Km, 0 kcat entries)
• EC 2.1.1.362 — [histone H4]-N-methyl-L-lysine20 N-methyltransferase (BRENDA: 4 organisms, 9 substrates, 0 inhibitors, 0 Km, 0 kcat entries)

Catalyzed reactions (Rhea), 2 shown:

• L-lysyl-[protein] + S-adenosyl-L-methionine = N(6)-methyl-L-lysyl-[protein] + S-adenosyl-L-homocysteine + H(+) (RHEA:51736)
• L-lysyl(20)-[histone H4] + S-adenosyl-L-methionine = N(6)-methyl-L-lysyl(20)-[histone H4] + S-adenosyl-L-homocysteine + H(+) (RHEA:60344)

UniProt features (53 total): mutagenesis site 13, strand 10, helix 7, sequence conflict 5, binding site 3, modified residue 3, compositionally biased region 3, splice variant 2, region of interest 2, turn 2, chain 1, domain 1, coiled-coil region 1

Structure

Experimental structures (PDB)

18 structures.

PDB	Method	Resolution (Å)
3F9X	X-RAY DIFFRACTION	1.25
5TEG	X-RAY DIFFRACTION	1.3
1ZKK	X-RAY DIFFRACTION	1.45
2BQZ	X-RAY DIFFRACTION	1.5
3F9Y	X-RAY DIFFRACTION	1.5
3F9W	X-RAY DIFFRACTION	1.6
3F9Z	X-RAY DIFFRACTION	1.6
5W1Y	X-RAY DIFFRACTION	1.7
5TH7	X-RAY DIFFRACTION	1.95
4IJ8	X-RAY DIFFRACTION	2
5V2N	X-RAY DIFFRACTION	2
9CR7	X-RAY DIFFRACTION	2.05
5T5G	X-RAY DIFFRACTION	2.1
6BOZ	X-RAY DIFFRACTION	2.4
7D20	ELECTRON MICROSCOPY	3
7D1Z	ELECTRON MICROSCOPY	3.15
7XPX	ELECTRON MICROSCOPY	3.2
5HQ2	X-RAY DIFFRACTION	4.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NQR1-F1	65.33	0.43

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 (3): 339–340; 267–269; 312

Post-translational modifications (3): 100, 162, 181

Mutagenesis-validated functional residues (13):

Position	Phenotype
162	does not affect the interaction with sirt2. increases the number of mitotic foci formation. does not affect methyltransf
162	increases the interaction with sirt2. reduces the number of mitotic foci formation. does not affect methyltransferase ac
286	strongly reduces affinity for histone h4 and abolishes methyltransferase activity.
300	strongly reduces affinity for histone h4.
311	strongly reduces affinity for histone h4.
336	abolishes methyltransferase activity.
340	strongly decreases methyltransferase activity.
375	strongly reduces affinity for histone h4 and methyltransferase activity.
375	alters methyltransferase activity, so that both monomethylation and dimethylation take place.
379	abolishes histone h4 binding and methyltransferase activity.
385–393	abolishes methyltransferase activity.
388	strongly reduces affinity for histone h4.
388	increases affinity for histone h4.

Function

Pathways and Gene Ontology

Reactome pathways

15 pathways

ID	Pathway
R-HSA-2299718	Condensation of Prophase Chromosomes
R-HSA-3214841	PKMTs methylate histone lysines
R-HSA-6804760	Regulation of TP53 Activity through Methylation
R-HSA-9764725	Negative Regulation of CDH1 Gene Transcription
R-HSA-1640170	Cell Cycle
R-HSA-212436	Generic Transcription Pathway
R-HSA-3247509	Chromatin modifying enzymes
R-HSA-3700989	Transcriptional Regulation by TP53
R-HSA-4839726	Chromatin organization
R-HSA-5633007	Regulation of TP53 Activity
R-HSA-68875	Mitotic Prophase
R-HSA-68886	M Phase
R-HSA-69278	Cell Cycle, Mitotic
R-HSA-73857	RNA Polymerase II Transcription
R-HSA-74160	Gene expression (Transcription)

MSigDB gene sets: 284 (showing top): GOBP_REGULATION_OF_DOUBLE_STRAND_BREAK_REPAIR, GGGACCA_MIR133A_MIR133B, GCACCTT_MIR18A_MIR18B, GOBP_CHROMOSOME_ORGANIZATION, AGGAAGC_MIR5163P, E2F_Q4_01, GOBP_REGULATION_OF_DNA_RECOMBINATION, E2F4DP1_01, TTTGTAG_MIR520D, GOBP_NEGATIVE_REGULATION_OF_DNA_REPAIR, GOBP_NEGATIVE_REGULATION_OF_DNA_RECOMBINATION, GAUSSMANN_MLL_AF4_FUSION_TARGETS_A_UP, GOBP_REGULATION_OF_DOUBLE_STRAND_BREAK_REPAIR_VIA_HOMOLOGOUS_RECOMBINATION, GOBP_CHROMOSOME_CONDENSATION, GOBP_REGULATION_OF_DNA_REPAIR

GO Biological Process (15): negative regulation of transcription by RNA polymerase II (GO:0000122), regulation of transcription by RNA polymerase II (GO:0006357), mitotic chromosome condensation (GO:0007076), peptidyl-lysine monomethylation (GO:0018026), regulation of DNA damage response, signal transduction by p53 class mediator (GO:0043516), negative regulation of DNA-templated transcription (GO:0045892), cell division (GO:0051301), regulation of signal transduction by p53 class mediator (GO:1901796), negative regulation of double-strand break repair via homologous recombination (GO:2000042), double-strand break repair via homologous recombination (GO:0000724), chromatin organization (GO:0006325), chromatin remodeling (GO:0006338), replication fork processing (GO:0031297), methylation (GO:0032259), protein localization to chromatin (GO:0071168)

GO Molecular Function (10): transcription corepressor activity (GO:0003714), lysine N-methyltransferase activity (GO:0016278), protein-lysine N-methyltransferase activity (GO:0016279), histone methyltransferase activity (GO:0042054), histone H4K20 methyltransferase activity (GO:0042799), histone H4 methyltransferase activity (GO:0140939), histone H4K20 monomethyltransferase activity (GO:0140944), protein binding (GO:0005515), methyltransferase activity (GO:0008168), transferase activity (GO:0016740)

GO Cellular Component (6): chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654), polytene chromosome (GO:0005700), cytosol (GO:0005829), chromosome (GO:0005694)

Reactome top-level categories

Rollup of top-12 pathways:

Category	Pathways
Mitotic Prophase	1
Chromatin modifying enzymes	1
Regulation of TP53 Activity	1
Regulation of CDH1 Gene Transcription	1
RNA Polymerase II Transcription	1
Chromatin organization	1
Generic Transcription Pathway	1
Transcriptional Regulation by TP53	1
M Phase	1
Cell Cycle, Mitotic	1
Cell Cycle	1
Gene expression (Transcription)	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
transcription by RNA polymerase II	2
negative regulation of DNA-templated transcription	2
regulation of DNA-templated transcription	2
protein methyltransferase activity	2
chromosome	2
regulation of transcription by RNA polymerase II	1
mitotic sister chromatid segregation	1
mitotic cell cycle	1
chromosome condensation	1
mitotic cell cycle process	1
peptidyl-lysine methylation	1
DNA damage response, signal transduction by p53 class mediator	1
regulation of cellular response to stress	1
regulation of signal transduction by p53 class mediator	1
DNA-templated transcription	1
negative regulation of RNA biosynthetic process	1
cellular process	1
signal transduction by p53 class mediator	1
regulation of intracellular signal transduction	1
double-strand break repair via homologous recombination	1
regulation of double-strand break repair via homologous recombination	1
negative regulation of DNA recombination	1
negative regulation of double-strand break repair	1
recombinational repair	1
double-strand break repair	1
cellular component organization	1
chromatin organization	1
DNA-templated DNA replication maintenance of fidelity	1
metabolic process	1
protein localization to chromosome	1
transcription coregulator activity	1
N-methyltransferase activity	1
S-adenosylmethionine-dependent methyltransferase activity	1
lysine N-methyltransferase activity	1
histone modifying activity	1
protein-lysine N-methyltransferase activity	1
histone H4 methyltransferase activity	1
histone methyltransferase activity	1
histone H4K20 methyltransferase activity	1

Protein interactions and networks

STRING

2414 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
KMT5A	L3MBTL1	Q9Y468	925
KMT5A	H4C7	Q99525	919
KMT5A	H4C16	P02304	915
KMT5A	KMT5B	Q4FZB7	842
KMT5A	SETD7	Q8WTS6	838
KMT5A	KMT5C	Q86Y97	811
KMT5A	SMYD2	Q9NRG4	780
KMT5A	DTL	Q9NZJ0	717
KMT5A	CDT1	Q9H211	661
KMT5A	DOT1L	Q8TEK3	626
KMT5A	PRMT3	O60678	585
KMT5A	TP53BP1	Q12888	583
KMT5A	SETDB1	Q15047	578
KMT5A	SMYD3	Q9H7B4	572
KMT5A	SETD6	Q8TBK2	531

IntAct

16 interactions, top by confidence:

A	B	Type	Score
KMT5A	H4C16	psi-mi:“MI:0407”(direct interaction)	0.780
H4C16	KMT5A	psi-mi:“MI:0407”(direct interaction)	0.780
KMT5A	TWIST1	psi-mi:“MI:0915”(physical association)	0.630
KMT5A	TWIST1	psi-mi:“MI:0407”(direct interaction)	0.630
KMT5A	HNRNPC	psi-mi:“MI:0915”(physical association)	0.560
FAM9A	KMT5A	psi-mi:“MI:0915”(physical association)	0.370
Mecom	ESYT2	psi-mi:“MI:0914”(association)	0.350
SNCA	CALU	psi-mi:“MI:0914”(association)	0.350
KMT5A	RSL1D1	psi-mi:“MI:0914”(association)	0.350
H4C16	MTA2	psi-mi:“MI:0914”(association)	0.350
TWIST1	PPP2CA	psi-mi:“MI:0914”(association)	0.350

BioGRID (135): LEF1 (Affinity Capture-Western), TCF7L2 (Affinity Capture-Western), SETD8 (Reconstituted Complex), SETD8 (Affinity Capture-Western), BTRC (Affinity Capture-MS), PCNA (Affinity Capture-MS), BTRC (Affinity Capture-Western), SETD8 (Affinity Capture-Western), SETD8 (Reconstituted Complex), SKP1 (Affinity Capture-Western), RBX1 (Affinity Capture-Western), CUL1 (Affinity Capture-Western), CUL4A (Affinity Capture-Western), SETD8 (Biochemical Activity), CSNK1D (Affinity Capture-Western)

ESM2 similar proteins: A0A1L8GR68, A2CG63, A2VE56, D3ZHS6, E6ZGB4, F7AQ22, O75376, O88974, P0C6S7, P57768, P57769, Q15047, Q2YDJ8, Q2YDW7, Q4KKX4, Q4LE39, Q52L14, Q5F3F2, Q5F3N6, Q5FWF5, Q5R6Q7, Q5VVJ2, Q60974, Q66JB6, Q68FE8, Q69Z61, Q69Z66, Q69Z69, Q6N043, Q6NXK2, Q7Z6G8, Q86YI8, Q8BIZ1, Q8C080, Q8K2W6, Q8QFX1, Q92560, Q96N64, Q98925, Q99PU7

Diamond homologs: A7E2Z2, A8XI75, C6KTD2, F4K1J4, O08550, O14686, O65312, O96028, P0CB22, P0CO26, P0CO27, P20659, P46995, P55200, P70351, Q03164, Q071E0, Q08AY6, Q08BS4, Q0V9E9, Q10MI4, Q15910, Q22795, Q24742, Q28D84, Q294B9, Q297V5, Q2GWF3, Q2LAE1, Q2UTN6, Q2YDJ8, Q2YDW7, Q498E6, Q4IB50, Q4PB36, Q4PBL3, Q4R381, Q4V863, Q4WTT2, Q54HS3

SIGNOR signaling

4 interactions.

A	Effect	B	Mechanism
CyclinB/CDK1	“up-regulates quantity by stabilization”	KMT5A	phosphorylation
CDC14B	“down-regulates quantity by destabilization”	KMT5A	dephosphorylation
CDC14A	“down-regulates quantity by destabilization”	KMT5A	dephosphorylation
CDK1	“up-regulates quantity by stabilization”	KMT5A	phosphorylation

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: activating (oncogene-like) across 1 cancer types — BRCA.

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	3
Likely benign	4
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1312 predictions. Top by Δscore:

Variant	Effect	Δscore
12:123390628:A:AG	acceptor_gain	1.0000
12:123390629:G:GG	acceptor_gain	1.0000
12:123390783:GAAG:G	donor_gain	1.0000
12:123390784:AAGG:A	donor_loss	1.0000
12:123390786:GGTAA:G	donor_loss	1.0000
12:123390787:G:GG	donor_gain	1.0000
12:123390787:GT:G	donor_loss	1.0000
12:123390788:T:A	donor_loss	1.0000
12:123395262:AAAAA:A	donor_gain	1.0000
12:123395263:AAAA:A	donor_gain	1.0000
12:123395263:AAAAG:A	donor_loss	1.0000
12:123395264:AAA:A	donor_gain	1.0000
12:123395265:AA:A	donor_gain	1.0000
12:123395265:AAGT:A	donor_loss	1.0000
12:123395266:AGT:A	donor_loss	1.0000
12:123395267:G:GG	donor_gain	1.0000
12:123396339:A:AG	acceptor_gain	1.0000
12:123396340:C:G	acceptor_gain	1.0000
12:123396342:CA:C	acceptor_loss	1.0000
12:123396343:A:AC	acceptor_loss	1.0000
12:123396343:A:AG	acceptor_gain	1.0000
12:123396344:G:GT	acceptor_gain	1.0000
12:123396344:GA:G	acceptor_gain	1.0000
12:123396344:GAGC:G	acceptor_gain	1.0000
12:123396344:GAGCT:G	acceptor_gain	1.0000
12:123396411:G:GT	donor_gain	1.0000
12:123396428:TGCAG:T	donor_loss	1.0000
12:123396429:GCAGG:G	donor_loss	1.0000
12:123396430:CAGGT:C	donor_loss	1.0000
12:123396431:AGGTA:A	donor_loss	1.0000

AlphaMissense

2309 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000396139 (12:123387777 T>C), RS1000455265 (12:123390383 G>A,C,T), RS1000677631 (12:123392547 C>G), RS1000739465 (12:123388204 C>G,T), RS1000743861 (12:123394109 T>TA,TC), RS1000880999 (12:123400748 G>A,T), RS1000910820 (12:123395106 A>G), RS1000915437 (12:123409555 T>A,C), RS1001014883 (12:123400486 A>C,G), RS1001287123 (12:123388139 A>G), RS1001293425 (12:123393513 C>T), RS1001309361 (12:123395767 G>GT), RS1001353007 (12:123399429 A>C), RS1001563809 (12:123405096 G>A), RS1001603856 (12:123401369 C>A,T)

Disease associations

OMIM: gene MIM:607240 | 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

17 associations (top):

Study	Trait	p-value
GCST002149_20	Schizophrenia	2.000000e-08
GCST002539_19	Schizophrenia	2.000000e-14
GCST002598_15	Educational attainment	7.000000e-08
GCST004521_72	Autism spectrum disorder or schizophrenia	8.000000e-12
GCST004627_145	Lymphocyte count	6.000000e-13
GCST004946_85	Schizophrenia	6.000000e-18
GCST006005_21	High density lipoprotein cholesterol levels	2.000000e-09
GCST006803_10	Schizophrenia	6.000000e-16
GCST007269_321	Pulse pressure	4.000000e-08
GCST007277_17	Tourette syndrome	2.000000e-06
GCST010703_43	Brain morphology (MOSTest)	1.000000e-08
GCST90000025_1007	Appendicular lean mass	6.000000e-38
GCST90002381_64	Eosinophil count	8.000000e-14
GCST90002402_208	Platelet count	1.000000e-11
GCST90002407_299	White blood cell count	4.000000e-11
GCST90011898_12	Alanine aminotransferase levels	2.000000e-15
GCST90020028_1117	Hip circumference adjusted for BMI	4.000000e-09

EFO canonical traits (9, from GWAS)

EFO ID	Trait name
EFO:0004784	self reported educational attainment
EFO:0004587	lymphocyte count
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0005763	pulse pressure measurement
EFO:0004346	neuroimaging measurement
EFO:0004980	appendicular lean mass
EFO:0004842	eosinophil count
EFO:0004309	platelet count
EFO:0008039	BMI-adjusted hip circumference

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: yes

ChEMBL targets (1): CHEMBL1795176 (SINGLE PROTEIN)

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — 2.1.1.43 Histone methyltransferases (HMTs)

Most potent curated ligand interactions (2 total), top 2:

Ligand	Action	Affinity	Parameter
Cdk4 inhibitor III	Inhibition	6.3	pIC50
nahuoic acid A	Inhibition	5.7	pKi

ChEMBL bioactivities

34 potent at pChembl≥5 of 65 total, top 22 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.30	Ki	50	nM	CHEMBL3934996
6.68	IC50	210	nM	CHEMBL337173
6.48	IC50	330	nM	CHEMBL3934996
6.43	IC50	370	nM	CHEMBL290904
6.30	IC50	500	nM	CHEMBL3414625
6.30	IC50	500	nM	CHEMBL290904
6.16	IC50	700	nM	CHEMBL580421
6.09	IC50	804	nM	CHEMBL4791952
5.89	Kd	1300	nM	CHEMBL4793474
5.72	IC50	1900	nM	CHEMBL4793474
5.70	Ki	2000	nM	CHEMBL3318284
5.19	IC50	6500	nM	CHEMBL3318284
5.16	IC50	6900	nM	CHEMBL4791952
5.14	IC50	7300	nM	CHEMBL3318285
5.10	IC50	7900	nM	CHEMBL3318289
5.10	IC50	7900	nM	CHEMBL3318290
5.10	IC50	8000	nM	CHEMBL3621701
5.10	IC50	7900	nM	CHEMBL3621706
5.06	IC50	8700	nM	CHEMBL3621704
5.05	IC50	9000	nM	CHEMBL3318285
5.04	IC50	9200	nM	CHEMBL3318301
5.02	IC50	9500	nM	CHEMBL3622290

PubChem BioAssay actives

37 with measured affinity, of 221 total; 16 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
(2S)-2-[[(2S)-2-[[(2S)-2-[2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-acetamido-6-aminohexanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-3-(1H-imidazol-5-yl)propanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]hexanoylamino]-3-methylbutanoyl]amino]-4-methylpentanoyl]amino]-5-(diaminomethylideneamino)pentanoic acid	1326000: Competitive inhibition of human SETD8 (186 to 352 residues) using biotin-labeled H4K20 (1 to 24 residues) as substrate after 1 hr in presence of 3H-SAM by scintillation proximity assay	ki	0.0500	uM
6-chloro-7-(2-morpholin-4-ylethylamino)quinoline-5,8-dione	1199210: Inhibition of N-terminal His6-tagged human SETD8 (191 to 352) assessed as incorporation of [3H]-methyl group from [3H-Me]-SAM to biotinylated H4K20 peptide substrate preincubated for 10 mins followed by substrate addition by liquid scintillation counting analysis	ic50	0.2100	uM
2-methyl-5-(4-methylanilino)-1,3-benzothiazole-4,7-dione	1868498: Inhibition of SETD8 (unknown origin) using [3H]SAM and HeLa nucleosomes as substrates incubated for 1 hr	ic50	0.3700	uM
2-methyl-5-(4-methylphenyl)imino-1,3-benzothiazole-4,7-dione	1199210: Inhibition of N-terminal His6-tagged human SETD8 (191 to 352) assessed as incorporation of [3H]-methyl group from [3H-Me]-SAM to biotinylated H4K20 peptide substrate preincubated for 10 mins followed by substrate addition by liquid scintillation counting analysis	ic50	0.5000	uM
3,3-dimethyl-1H-benzo[g]indole-2,4,5-trione	1199210: Inhibition of N-terminal His6-tagged human SETD8 (191 to 352) assessed as incorporation of [3H]-methyl group from [3H-Me]-SAM to biotinylated H4K20 peptide substrate preincubated for 10 mins followed by substrate addition by liquid scintillation counting analysis	ic50	0.7000	uM
N-[3-[(6,7-dimethoxy-2-pyrrolidin-1-ylquinazolin-4-yl)amino]propyl]prop-2-enamide	1679201: Inhibition of recombinant SETD8 catalytic domain (unknown origin) (232 to 393 residues) expressed in Escherichia coli assessed as reduction in incorporation of [3H]-labeled methyl group into biotinylated H4 (1 to 24) peptide measured after 5 hrs using [3H-SAM] by scintillation proximity assay	ic50	0.8040	uM
7-(2-aminoethoxy)-6-methoxy-2-pyrrolidin-1-yl-N-(5-pyrrolidin-1-ylpentyl)quinazolin-4-amine	1679204: Binding affinity to recombinant SETD8 catalytic domain (unknown origin) (232 to 393 residues) expressed in Escherichia coli assessed as dissociation constant by isothermal titration calorimetric method	kd	1.3000	uM
(E)-3-[(1R,2R,4aR,5R,7R,8R,8aS)-5,7-dihydroxy-3,4a,8-trimethyl-2-[(5S,7R,8S,9S)-5,7,9-trihydroxy-8,10-dimethylundec-2-en-2-yl]-2,5,6,7,8,8a-hexahydro-1H-naphthalen-1-yl]-2-methylprop-2-enoic acid	1199209: Competitive inhibition of SETD8 (unknown origin) using H4 (1 to 24) as substrate assessed as incorporation of [3H]-methyl group from [3H-Me]-SAM to peptide substrate after 1 hr by Lineweaver-Burk plot analysis in presence of SAM	ki	2.0000	uM
6,7-dimethoxy-2-pyrrolidin-1-yl-N-(5-pyrrolidin-1-ylpentyl)quinazolin-4-amine	1183921: Inhibition of SETD8 (unknown origin) catalytic domain expressed in Escherichia coli using biotinylated H4 (1-24) peptide substrate after 1 hr by scintillation proximity assay	ic50	7.3000	uM
N-[5-(azepan-1-yl)pentyl]-6,7-dimethoxy-2-pyrrolidin-1-ylquinazolin-4-amine	1249163: Inhibition of human SETD8 catalytic domain expressed in Escherichia coli assessed as reduction in transfer of tritiated methyl group from [3H]SAM to biotinylated H4 (1 to 24) peptide substrate by scintillation proximity assay	ic50	7.9000	uM
6,7-dimethoxy-N-(5-piperidin-1-ylpentyl)-2-pyrrolidin-1-ylquinazolin-4-amine	1183921: Inhibition of SETD8 (unknown origin) catalytic domain expressed in Escherichia coli using biotinylated H4 (1-24) peptide substrate after 1 hr by scintillation proximity assay	ic50	7.9000	uM
N-(6,7-dimethoxy-2-pyrrolidin-1-ylquinazolin-4-yl)-N’,N’-dimethylpentane-1,5-diamine	1183921: Inhibition of SETD8 (unknown origin) catalytic domain expressed in Escherichia coli using biotinylated H4 (1-24) peptide substrate after 1 hr by scintillation proximity assay	ic50	7.9000	uM
6-methoxy-7-(2-methoxyethoxy)-2-pyrrolidin-1-yl-N-(5-pyrrolidin-1-ylpentyl)quinazolin-4-amine	1249163: Inhibition of human SETD8 catalytic domain expressed in Escherichia coli assessed as reduction in transfer of tritiated methyl group from [3H]SAM to biotinylated H4 (1 to 24) peptide substrate by scintillation proximity assay	ic50	8.0000	uM
N-[2-[6-methoxy-2-pyrrolidin-1-yl-4-(5-pyrrolidin-1-ylpentylamino)quinazolin-7-yl]oxyethyl]formamide	1249163: Inhibition of human SETD8 catalytic domain expressed in Escherichia coli assessed as reduction in transfer of tritiated methyl group from [3H]SAM to biotinylated H4 (1 to 24) peptide substrate by scintillation proximity assay	ic50	8.7000	uM
6,7-dimethoxy-2-N,2-N-dimethyl-4-N-(5-pyrrolidin-1-ylpentyl)quinazoline-2,4-diamine	1183921: Inhibition of SETD8 (unknown origin) catalytic domain expressed in Escherichia coli using biotinylated H4 (1-24) peptide substrate after 1 hr by scintillation proximity assay	ic50	9.2000	uM
6-ethoxy-7-methoxy-2-pyrrolidin-1-yl-N-(5-pyrrolidin-1-ylpentyl)quinazolin-4-amine	1249163: Inhibition of human SETD8 catalytic domain expressed in Escherichia coli assessed as reduction in transfer of tritiated methyl group from [3H]SAM to biotinylated H4 (1 to 24) peptide substrate by scintillation proximity assay	ic50	9.5000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases abundance, increases expression, decreases expression	3
bisphenol A	decreases expression, increases expression, decreases reaction, increases response to substance	2
Estradiol	increases expression, decreases reaction, decreases expression	2
6,7-dimethoxy-2-(pyrrolidin-1-yl)-N-(5-(pyrrolidin-1-yl)pentyl)quinazolin-4-amine	decreases expression	1
methylmercuric chloride	increases expression	1
triphenyl phosphate	affects expression	1
cobaltous chloride	increases expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	increases expression	1
CGP 52608	affects binding, increases reaction	1
Fulvestrant	decreases expression, decreases reaction, increases response to substance	1
Ethanol	decreases expression	1
Arsenic	increases abundance, increases expression	1
Benzo(a)pyrene	affects methylation	1
Berberine	increases expression	1
Cadmium	decreases expression	1
Curcumin	decreases expression	1
Diethylstilbestrol	increases expression	1
Doxorubicin	decreases expression	1
Endosulfan	increases expression	1
Lead	affects expression	1
Smoke	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Tretinoin	decreases expression	1
Valproic Acid	increases expression	1
Zearalenone	increases expression	1
Cyclosporine	increases expression	1
Aflatoxin B1	increases expression	1
Okadaic Acid	increases expression	1
Copper Sulfate	increases expression	1

ChEMBL screening assays

99 unique, capped per target: 99 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1217461	Binding	Activity at methyl transferase activity SET8/preSet7 by enzyme coupled S-adenocylehomocystein detection assay	Protein lysine methyltransferase G9a inhibitors: design, synthesis, and structure activity relationships of 2,4-diamino-7-aminoalkoxy-quinazolines. — J Med Chem

Cellosaurus cell lines

4 cell lines: 3 cancer cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B1B5	Abcam HEK293 KMT5A KO	Transformed cell line	Female
CVCL_B8JH	Abcam HCT 116 KMT5A KO	Cancer cell line	Male
CVCL_TK70	HAP1 SETD8 (-) 1	Cancer cell line	Male
CVCL_XS61	HAP1 SETD8 (-) 2	Cancer cell line	Male

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