SPOP

Summary

SPOP (speckle type BTB/POZ protein, HGNC:11254) is a protein-coding gene on chromosome 17q21.33, encoding Speckle-type POZ protein (O43791). Component of a cullin-RING-based BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complex that mediates the ubiquitination of target proteins, leading most often to their proteasomal degradation.

This gene encodes a protein that may modulate the transcriptional repression activities of death-associated protein 6 (DAXX), which interacts with histone deacetylase, core histones, and other histone-associated proteins. In mouse, the encoded protein binds to the putative leucine zipper domain of macroH2A1.2, a variant H2A histone that is enriched on inactivated X chromosomes. The BTB/POZ domain of this protein has been shown in other proteins to mediate transcriptional repression and to interact with components of histone deacetylase co-repressor complexes. Alternative splicing of this gene results in multiple transcript variants encoding the same protein.

Source: NCBI Gene 8405 — RefSeq curated summary.

At a glance

• Gene–disease (curated): neurodevelopmental disorder with relative macrocephaly and with or without cardiac or endocrine anomalies (Definitive, ClinGen) — +2 more curated relationships
• GWAS associations: 1
• Clinical variants (ClinVar): 243 total — 8 likely-pathogenic
• Phenotypes (HPO): 72
• Druggable target: yes
• Cancer driver (intOGen): activating (oncogene-like) across 5 cancer types
• MANE Select transcript: NM_001007228

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11254
Approved symbol	SPOP
Name	speckle type BTB/POZ protein
Location	17q21.33
Locus type	gene with protein product
Status	Approved
Aliases	TEF2, BTBD32
Ensembl gene	ENSG00000121067
Ensembl biotype	protein_coding
OMIM	602650
Entrez	8405

Gene structure

Transcript identifiers

Ensembl transcripts: 55 — 43 protein_coding, 6 nonsense_mediated_decay, 5 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000347630, ENST00000393328, ENST00000451526, ENST00000502385, ENST00000503676, ENST00000504102, ENST00000504212, ENST00000504889, ENST00000505581, ENST00000506399, ENST00000507551, ENST00000507970, ENST00000508805, ENST00000509079, ENST00000509765, ENST00000509869, ENST00000510476, ENST00000513080, ENST00000514121, ENST00000515508, ENST00000572686, ENST00000577134, ENST00000659760, ENST00000665825, ENST00000671445, ENST00000854669, ENST00000854670, ENST00000854671, ENST00000854672, ENST00000854673, ENST00000854674, ENST00000930000, ENST00000970752, ENST00000970753, ENST00000970754, ENST00000970755, ENST00000970756, ENST00000970757, ENST00000970758, ENST00000970759, ENST00000970760, ENST00000970761, ENST00000970762, ENST00000970763, ENST00000970764, ENST00000970765, ENST00000970766, ENST00000970767, ENST00000970768, ENST00000970769, ENST00000970770, ENST00000970771, ENST00000970772, ENST00000970773, ENST00000970774

RefSeq mRNA: 9 — MANE Select: NM_001007228 NM_001007226, NM_001007227, NM_001007228, NM_001007229, NM_001007230, NM_001370730, NM_001370731, NM_001370732, NM_003563

CCDS: CCDS11551

Canonical transcript exons

ENST00000504102 — 10 exons

Exon	Start	End
ENSE00002070429	49598884	49600522
ENSE00002082963	49677933	49678097
ENSE00002250870	49601865	49602007
ENSE00003597328	49618981	49619108
ENSE00003641865	49622733	49622876
ENSE00003672546	49607250	49607372
ENSE00003680879	49611280	49611457
ENSE00003784716	49607874	49607929
ENSE00003786237	49619234	49619385
ENSE00003787758	49621946	49622067

Expression profiles

Bgee: expression breadth ubiquitous, 295 present calls, max score 97.47.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 29.9850 / max 401.9012, expressed in 1822 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
166816	19.2760	1815
166817	10.4538	1769
208241	0.1490	67
166814	0.0429	18
166813	0.0399	17
166812	0.0233	6

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
blood vessel layer	UBERON:0004797	97.47	gold quality
nipple	UBERON:0002030	97.23	gold quality
muscle layer of sigmoid colon	UBERON:0035805	97.21	gold quality
saphenous vein	UBERON:0007318	97.00	gold quality
lower esophagus muscularis layer	UBERON:0035833	96.71	gold quality
lower esophagus	UBERON:0013473	96.69	gold quality
pylorus	UBERON:0001166	96.67	gold quality
seminal vesicle	UBERON:0000998	96.63	gold quality
popliteal artery	UBERON:0002250	96.57	gold quality
tibial artery	UBERON:0007610	96.56	gold quality
urethra	UBERON:0000057	96.46	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	96.30	gold quality
cortical plate	UBERON:0005343	96.29	gold quality
aorta	UBERON:0000947	96.13	gold quality
cardia of stomach	UBERON:0001162	96.10	gold quality
smooth muscle tissue	UBERON:0001135	95.99	gold quality
body of uterus	UBERON:0009853	95.65	gold quality
ascending aorta	UBERON:0001496	95.57	gold quality
thoracic aorta	UBERON:0001515	95.54	gold quality
lower lobe of lung	UBERON:0008949	95.44	gold quality
right coronary artery	UBERON:0001625	95.15	gold quality
vena cava	UBERON:0004087	95.11	gold quality
myometrium	UBERON:0001296	95.10	gold quality
sigmoid colon	UBERON:0001159	95.09	gold quality
colonic epithelium	UBERON:0000397	95.08	gold quality
fundus of stomach	UBERON:0001160	95.06	gold quality
rectum	UBERON:0001052	94.99	gold quality
left uterine tube	UBERON:0001303	94.93	gold quality
pericardium	UBERON:0002407	94.72	gold quality
cerebellum	UBERON:0002037	94.68	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	12.65

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

5 targets.

Target	Regulation
COL1A1	Activation
GLI3	Repression
PTCH1	Activation
PTHLH	Activation
SP7	Activation

miRNA regulators (miRDB)

132 targeting SPOP, 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-4768-5P	100.00	69.49	2861
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-4673	100.00	66.64	1490
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-4645-5P	99.98	65.81	1284
HSA-MIR-512-3P	99.97	67.35	1049
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-1236-3P	99.94	68.04	1695
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-145-5P	99.92	71.13	1836
HSA-MIR-5195-3P	99.92	70.92	1877
HSA-MIR-450B-5P	99.92	71.48	3175
HSA-MIR-1305	99.91	71.43	3443

Literature-anchored findings (GeneRIF, showing 40)

• Mutagenesis study suggests that the ability of SPOP to self-associate as well as its ability to bind with Daxx was important for the modulation of Daxx-mediated transcriptional repression. (PMID:15240113)
• Here, we report that the E3 ubiquitin ligase consisting of SPOP and CULLIN3 is able to ubiquitinate the Polycomb group protein BMI1. (PMID:15897469)
• SPOP/Cul3-ubiquitin ligase plays an essential role in the control of Daxx level and, thus, in the regulation of Daxx-mediated cellular processes, including transcriptional regulation and apoptosis (PMID:16524876)
• define a novel mechanism whereby the phosphoinositide phosphatidylinositol 5-phosphate leads to stimulation of Cul3-SPOP ubiquitin ligase activity (PMID:18218622)
• The study first proposes the proapoptotic aspect of the BTB/POZ domain of SPOP protein based on the finding that cells expressing the C-terminal fragment of SPOP containing the BTB/POZ domain underwent apoptosis. (PMID:18997279)
• study found that SPOP plays a conserved role in TNF-mediated JNK signaling and was highly expressed in 99% of clear cell renal cell carcinomas (PMID:19164706)
• The study provides a molecular understanding of how SPOP and other MATH-BTB proteins recruit substrates to Cul3 and how their dimerization and conformational variability may facilitate avid interactions with diverse substrates. (PMID:19818708)
• SPOP expression inhibited SRC-3-mediated oncogenic signaling and tumorigenesis. (PMID:21577200)
• These results suggest that the novel regulatory mechanism of BRMS1 by Cul3-SPOP complex is important for breast cancer progression. (PMID:22085717)
• Adaptor protein self-assembly provides a graded level of regulation of the SPOP/Cul3 E3 ligase toward its multiple protein substrates. (PMID:22632832)
• Loss of expression of SPOP gene might play a role in cancer pathogenesis by altering tumor suppressor gene functions of SPOP. (PMID:23216165)
• SPOP plays a critical tumor suppressor role in prostate cancer cells, promoting the turnover of SRC-3 protein and suppressing androgen receptor transcriptional activity. (PMID:23559371)
• Prevalence of SPOP gene mutation varies depending on cancer types. It is common in prostate cancer and endometrial cancer, and rare in breast cancer, lung cancer, liver cancer, and acute leukemias. (PMID:23654205)
• Crystal structure of the high-order SPOP oligomer is presented depicting a helical organization that could enhance the efficiency of substrate ubiquitination. (PMID:23999291)
• Dzip1-dependent stabilization of Spop/HIB is evolutionarily conserved and essential for proper regulation of Gli/Ci proteins in the Hh pathway. (PMID:24072710)
• Prostate-cancer-associated SPOP mutants cannot bind to and promote androgen receptor degradation. (PMID:24508459)
• the Speckle-Type POZ Protein (SPOP) gene is mutated in prostate cancer in a manner that is not specific for ethnicity, clinical, or pathologic parameters (PMID:24563616)
• Results indicate that SPOP serves as a regulatory hub to promote ccRCC tumorigenesis. (PMID:24656772)
• a novel mutation in SPOP that tracks with prostate cancer within a family and is predicted to be deleterious. Taken together, our results implicate SPOP as a candidate gene for hereditary prostate cancer (PMID:24796539)
• miR-145 has a role in post-transcriptional regulation of SPOP expression in selected tissues. (PMID:24845504)
• This study reveals novel molecular events underlying the regulation of DDIT3 protein homeostasis and provides insight in understanding the relationship between SPOP mutations and ER stress dysregulation in prostate cancer. (PMID:24990631)
• SPOP mutations and novel variants were detected in 5 of 27 aggressive PCa and one of 22 less aggressive PCa (PMID:24994784)
• SPOP mutations contribute to prostate cancer development by altering the steady-state levels of key components in the androgen-signaling pathway; mutations are also observed in endometrial cancers (PMID:25058385)
• SPOP plays critical roles in suppressing gastric tumorigenesis through inhibiting Hh/Gli2 signaling pathway. It may provide an alternative strategy for developing therapeutic agents of gastric cancer in future. (PMID:25204354)
• The present study demonstrates that prognosis varies depending on SPOP expression and mutational status, hence, defining a new biotype of PCa associated with a worse prognosis. (PMID:25204806)
• studies highlight the AR axis as the key transcriptional output of SPOP in prostate adenocarcinoma and provide an explanation for the prostate-specific tumor suppressor role of wt-SPOP (PMID:25274033)
• SPOP mutants impaired ubiquitylation of a subset of proteins in a dominant-negative fashion. (PMID:25278611)
• SPOP has potential use as novel biomarker of glioma and may serve as an independent predictive factor for prognosis of glioma patients. (PMID:25351530)
• Our study revealed novel molecular mechanisms underlying the regulation of ERa protein and provided insights in understanding the relationship between SPOP mutations and the development of endometrial cancer. (PMID:25766326)
• results suggest that SPOP plays a pivotal role in colorectal cancer (CRC) through mesenchymal-epithelial transition and matrix metalloproteases. (PMID:26022775)
• our findings emphasize the critical role of SPOP in the regulation of proliferation and migration in liver cancer (PMID:26156804)
• SPOP functions as a tumor suppressor to negatively regulate the stability of the ERG oncoprotein in prostate cancer. (PMID:26344095)
• Overcoming ERG resistance to SPOP-mediated degradation represents a viable strategy for treatment of prostate cancers expressing either mutated SPOP or truncated ERG. (PMID:26344096)
• Data indicate that a mutation in the SPOP gene may not be associated with breast cancer, particularly in Chinese women. (PMID:26505385)
• SPOP acts as a tumor suppressor by promoting senescence through degrading SENP7. (PMID:26527005)
• While wild-type SPOP localizes to liquid nuclear speckles, self-association-deficient SPOP mutants have a diffuse distribution in the nucleus. SPOP oligomerizes through its BTB and BACK domains. (PMID:27220849)
• Results show that SPOP is highly expressed in clear cell renal cell carcinoma (RCC) and associated with disease progression. In vitro, SPOP promotes the invasiveness of RCC. (PMID:27572476)
• SPOP-containing complex regulates SETD2 stability and H3K36me3-coupled alternative splicing. (PMID:27614073)
• Prostate cancer-derived SPOP mutants failed to interact with Cdc20 to promote its degradation. As a result, SPOP-deficient prostate cancer cells with elevated Cdc20 expression became resistant to a pharmacological Cdc20 inhibitor. (PMID:27780719)
• methylation status of SPOP promoter can be used as a novel epigenetic biomarker and a therapeutic target in colorectal cancer. (PMID:28032859)

Cross-species orthologs

39 orthologs

Organism	Symbol	Gene ID
danio_rerio	spop	ENSDARG00000100519
mus_musculus	Spop	ENSMUSG00000057522
mus_musculus	Tdpoz3	ENSMUSG00000058005
mus_musculus	Tdpoz4	ENSMUSG00000060256
mus_musculus	Gm5773	ENSMUSG00000068879
mus_musculus	Spopfm2	ENSMUSG00000074424
mus_musculus	Spopfm3	ENSMUSG00000090268
mus_musculus	Tdpoz1	ENSMUSG00000094084
mus_musculus	Tdpoz5	ENSMUSG00000094163
mus_musculus	Tdpoz9	ENSMUSG00000094328
mus_musculus	Tdpoz7	ENSMUSG00000095251
mus_musculus	Tdpoz9-ps1	ENSMUSG00000095822
mus_musculus	Tdpoz8	ENSMUSG00000096879
mus_musculus	Tdpoz2	ENSMUSG00000103362
rattus_norvegicus	Spop	ENSRNOG00000004686
rattus_norvegicus		ENSRNOG00000071369
rattus_norvegicus		ENSRNOG00000071734
rattus_norvegicus		ENSRNOG00000072165
rattus_norvegicus		ENSRNOG00000072589
rattus_norvegicus		ENSRNOG00000073644
rattus_norvegicus		ENSRNOG00000074034
rattus_norvegicus		ENSRNOG00000077984
rattus_norvegicus		ENSRNOG00000079210
rattus_norvegicus	Spopfm2l1	ENSRNOG00000080285
rattus_norvegicus		ENSRNOG00000081034
rattus_norvegicus		ENSRNOG00000082881
rattus_norvegicus		ENSRNOG00000084634
rattus_norvegicus		ENSRNOG00000085189
rattus_norvegicus		ENSRNOG00000085967
rattus_norvegicus		ENSRNOG00000086343
rattus_norvegicus		ENSRNOG00000088118
rattus_norvegicus		ENSRNOG00000088911
rattus_norvegicus		ENSRNOG00000089625
rattus_norvegicus		ENSRNOG00000089833
rattus_norvegicus		ENSRNOG00000090182
drosophila_melanogaster	BTBD9	FBGN0030228
drosophila_melanogaster	CG17068	FBGN0031098
drosophila_melanogaster	lute	FBGN0262871
caenorhabditis_elegans		WBGENE00015463

Paralogs (11): BTBD1 (ENSG00000064726), ABTB1 (ENSG00000114626), KBTBD4 (ENSG00000123444), BTBD3 (ENSG00000132640), BTBD2 (ENSG00000133243), SPOPL (ENSG00000144228), ABTB3 (ENSG00000151136), ABTB2 (ENSG00000166016), KLHL11 (ENSG00000178502), BTBD9 (ENSG00000183826), BTBD6 (ENSG00000184887)

Protein

Protein identifiers

Speckle-type POZ protein — O43791 (reviewed: O43791)

Alternative names: HIB homolog 1, Roadkill homolog 1

All UniProt accessions (10): A0A590UJA7, D6RA79, D6RBR3, D6RD94, D6RDG8, D6RFL7, D6RGZ4, D6RIS7, O43791, H0Y977

UniProt curated annotations — full annotation on UniProt →

Function. Component of a cullin-RING-based BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complex that mediates the ubiquitination of target proteins, leading most often to their proteasomal degradation. In complex with CUL3, involved in ubiquitination and proteasomal degradation of BRMS1, DAXX, PDX1/IPF1, GLI2 and GLI3. In complex with CUL3, involved in ubiquitination of MACROH2A1 and BMI1; this does not lead to their proteasomal degradation. Inhibits transcriptional activation of PDX1/IPF1 targets, such as insulin, by promoting PDX1/IPF1 degradation. The cullin-RING-based BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complex containing homodimeric SPOP has higher ubiquitin ligase activity than the complex that contains the heterodimer formed by SPOP and SPOPL. Involved in the regulation of bromodomain and extra-terminal motif (BET) proteins BRD2, BRD3, BRD4 stability. Plays an essential role for proper translation, but not for their degradation, of critical DNA replication licensing factors CDT1 and CDC6, thereby participating in DNA synthesis and cell proliferation. Regulates interferon regulatory factor 1/IRF1 proteasomal turnover by targeting S/T-rich degrons in IRF1. Facilitates the lysosome-dependent degradation of enterovirus EV71 protease 2A by inducing its ‘Lys-48’-linked polyubiquitination, which ultimately restricts EV71 replication. Acts as an antiviral factor also against hepatitis B virus/HBV by promoting ubiquitination and subsequent degradation of HNF1A. In turn, inhibits HBV transcription and replication by preventing HNF1A stimulating activity of HBV preS1 promoter and enhancer II. Involved in ubiquitination of BRDT and promotes its degradation, thereby regulates histone removal in early condensing spermatids prior to histone-to-protamine exchange.

Subunit / interactions. Interacts with GLI2 and GLI3. Homodimer and homooligomer. Heterodimer with SPOPL. Each dimer interacts with two CUL3 molecules. Part of cullin-RING-based BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complexes that contain CUL3 and homodimeric SPOP, or the heterodimer formed by SPOP and SPOPL, plus a target protein, such as MACROH2A1, PDX1/IPF1, BMI1, BRMS1 and DAXX. Interacts with IRF1; this interaction mediates IRF1 proteasomal degradation. Interacts with HNF1A.

Subcellular location. Nucleus. Nucleus speckle. Cytoplasm.

Tissue specificity. Widely expressed.

Disease relevance. Nabais Sa-de Vries syndrome 1 (NSDVS1) [MIM:618828] An autosomal dominant disorder characterized by global developmental delay, impaired intellectual development, speech delay, and variable behavioral abnormalities. Affected individuals show congenital microcephaly and dysmorphic facial features, including round face, small palpebral fissures, highly arched eyebrows, and short nose. The disease is caused by variants affecting the gene represented in this entry. Nabais Sa-de Vries syndrome 2 (NSDVS2) [MIM:618829] An autosomal dominant disorder characterized by global developmental delay apparent from birth, impaired intellectual development, speech delay, dysmorphic facial features, and additional anomalies including congenital heart defects, sleep disturbances, hypotonia, and variable endocrine abnormalities. The disease is caused by variants affecting distinct genetic loci, including the gene represented in this entry.

Domain organisation. The BTB (POZ) domain mediates dimerization and interaction with CUL3. The MATH domain mediates interaction with protein-ubiquitin ligase substrates, such as MACROH2A1 and BMI1.

Pathway. Protein modification; protein ubiquitination.

Miscellaneous. Antigen recognized by serum from scleroderma patient.

Similarity. Belongs to the Tdpoz family.

RefSeq proteins (9): NP_001007227, NP_001007228, NP_001007229, NP_001007230, NP_001007231, NP_001357659, NP_001357660, NP_001357661, NP_003554 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000210	BTB/POZ_dom	Domain
IPR002083	MATH/TRAF_dom	Domain
IPR008974	TRAF-like	Homologous_superfamily
IPR011333	SKP1/BTB/POZ_sf	Homologous_superfamily
IPR034089	SPOP_C	Domain
IPR056423	BACK_BPM_SPOP	Domain

Pfam: PF00651, PF22486, PF24570

UniProt features (60 total): helix 20, strand 16, mutagenesis site 9, sequence variant 6, region of interest 4, domain 2, chain 1, sequence conflict 1, turn 1

Structure

Experimental structures (PDB)

36 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
3IVV	X-RAY DIFFRACTION	1.25
3HSV	X-RAY DIFFRACTION	1.43
7LIN	X-RAY DIFFRACTION	1.44
7D3D	X-RAY DIFFRACTION	1.45
9HFV	X-RAY DIFFRACTION	1.45
7LIP	X-RAY DIFFRACTION	1.48
4HS2	X-RAY DIFFRACTION	1.53
3HQL	X-RAY DIFFRACTION	1.66
3HQM	X-RAY DIFFRACTION	1.74
3IVB	X-RAY DIFFRACTION	1.75
6I5P	X-RAY DIFFRACTION	1.81
6I68	X-RAY DIFFRACTION	1.85
6I41	X-RAY DIFFRACTION	1.9
9HGG	X-RAY DIFFRACTION	1.9
7LIQ	X-RAY DIFFRACTION	1.98
4O1V	X-RAY DIFFRACTION	2
6F8F	X-RAY DIFFRACTION	2
6F8G	X-RAY DIFFRACTION	2.03
3IVQ	X-RAY DIFFRACTION	2.1
6I7A	X-RAY DIFFRACTION	2.2
3HQH	X-RAY DIFFRACTION	2.3
4EOZ	X-RAY DIFFRACTION	2.4
4J8Z	X-RAY DIFFRACTION	2.42
3HTM	X-RAY DIFFRACTION	2.5
3HQI	X-RAY DIFFRACTION	2.62
3HU6	X-RAY DIFFRACTION	2.7
7LIO	X-RAY DIFFRACTION	3.01
9OUW	ELECTRON MICROSCOPY	3.2
7KLZ	X-RAY DIFFRACTION	3.4
8DWU	ELECTRON MICROSCOPY	3.4

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O43791-F1	90.38	0.78

Functional residue map

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

Mutagenesis-validated functional residues (9):

Position	Phenotype
87	strongly reduced affinity for substrate proteins.
123	strongly reduced affinity for substrate proteins.
130	strongly reduced affinity for substrate proteins.
131	strongly reduced affinity for substrate proteins.
133	strongly reduced affinity for substrate proteins.
186	strongly reduced homodimerization. reduces the activity of the cullin-ring-based bcr (btb-cul3-rbx1) e3 ubiquitin-protei
190	strongly reduced homodimerization. reduces the activity of the cullin-ring-based bcr (btb-cul3-rbx1) e3 ubiquitin-protei
193	strongly reduced homodimerization. reduces the activity of the cullin-ring-based bcr (btb-cul3-rbx1) e3 ubiquitin-protei
217	strongly reduced homodimerization. reduces the activity of the cullin-ring-based bcr (btb-cul3-rbx1) e3 ubiquitin-protei

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-5632684	Hedgehog ‘on’ state
R-HSA-9929491	SPOP-mediated proteasomal degradation of PD-L1(CD274)
R-HSA-162582	Signal Transduction
R-HSA-5358351	Signaling by Hedgehog

MSigDB gene sets: 427 (showing top): JI_RESPONSE_TO_FSH_UP, TGCGCANK_UNKNOWN, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, GCANCTGNY_MYOD_Q6, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, AP2_Q3, GGGTGGRR_PAX4_03, CAGCTG_AP4_Q5, ATGTTAA_MIR302C, MYOD_01, BLALOCK_ALZHEIMERS_DISEASE_UP, TGCTGAY_UNKNOWN, GATA6_01

GO Biological Process (5): protein polyubiquitination (GO:0000209), regulation of proteolysis (GO:0030162), proteasome-mediated ubiquitin-dependent protein catabolic process (GO:0043161), protein ubiquitination (GO:0016567), protein catabolic process (GO:0030163)

GO Molecular Function (4): ubiquitin protein ligase binding (GO:0031625), identical protein binding (GO:0042802), molecular function inhibitor activity (GO:0140678), protein binding (GO:0005515)

GO Cellular Component (5): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), nuclear speck (GO:0016607), Cul3-RING ubiquitin ligase complex (GO:0031463)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Signaling by Hedgehog	1
Regulation of PD-L1(CD274) Post-translational modification	1
Signal Transduction	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
protein ubiquitination	1
proteolysis	1
regulation of protein metabolic process	1
ubiquitin-dependent protein catabolic process	1
proteasomal protein catabolic process	1
protein modification by small protein conjugation	1
macromolecule catabolic process	1
protein metabolic process	1
ubiquitin-like protein ligase binding	1
protein binding	1
molecular function regulator activity	1
binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
intracellular anatomical structure	1
nuclear ribonucleoprotein granule	1
cullin-RING ubiquitin ligase complex	1

Protein interactions and networks

STRING

3751 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SPOP	CUL3	Q13618	997
SPOP	RBX1	P62877	961
SPOP	DAXX	Q9UER7	876
SPOP	GLI1	P08151	856
SPOP	AR	P10275	788
SPOP	TRIM24	O15164	705
SPOP	FOXA1	P55317	696
SPOP	GLI2	P10070	693
SPOP	EVX1	P49640	685
SPOP	CHD1	O14646	668
SPOP	TMPRSS2	O15393	654
SPOP	CD274	Q9NZQ7	652
SPOP	PTEN	P60484	644
SPOP	CDK4	P11802	621
SPOP	SUFU	Q9UMX1	617

IntAct

1333 interactions, top by confidence:

A	B	Type	Score
CUL3	SPOP	psi-mi:“MI:0915”(physical association)	0.890
SPOP	CUL3	psi-mi:“MI:0407”(direct interaction)	0.890
CUL3	SPOP	psi-mi:“MI:0407”(direct interaction)	0.890
SPOP	CUL3	psi-mi:“MI:2364”(proximity)	0.890
MYD88	SPOP	psi-mi:“MI:0915”(physical association)	0.880
SPOP	MYD88	psi-mi:“MI:0915”(physical association)	0.880
SPOP	MYD88	psi-mi:“MI:0403”(colocalization)	0.880
NUP50	KPNA4	psi-mi:“MI:0914”(association)	0.830
NUP50	KPNA3	psi-mi:“MI:0914”(association)	0.780
SPOP	DAXX	psi-mi:“MI:0915”(physical association)	0.760
DAXX	SPOP	psi-mi:“MI:0915”(physical association)	0.760
SPOP	DAXX	psi-mi:“MI:0403”(colocalization)	0.760
SPOP	DAXX	psi-mi:“MI:2364”(proximity)	0.760
NCOA3	SPOP	psi-mi:“MI:0915”(physical association)	0.740
SPOP	NCOA3	psi-mi:“MI:0407”(direct interaction)	0.740
NCOA3	SPOP	psi-mi:“MI:0407”(direct interaction)	0.740
SPOP	NCOA3	psi-mi:“MI:0915”(physical association)	0.740
NCOA3	SPOP	psi-mi:“MI:0914”(association)	0.740

BioGRID (815): SPOP (Affinity Capture-Western), SPOP (Affinity Capture-Western), SPOP (Affinity Capture-Western), SPOP (Reconstituted Complex), CUL3 (Affinity Capture-Western), SPOP (Affinity Capture-Western), AR (Affinity Capture-Western), SPOP (Reconstituted Complex), SPOP (Affinity Capture-Western), BRMS1 (Affinity Capture-Western), SPOP (Reconstituted Complex), DEK (Biochemical Activity), DEK (Affinity Capture-Western), SPOP (Affinity Capture-MS), SPOP (Affinity Capture-MS)

ESM2 similar proteins: A0JMG1, A2VE52, D3K5L7, E0CZ16, E1C6Q1, E2R222, F1LZ52, F1LZF0, F1MBP6, O13016, O35345, O43791, O60684, O95164, O95198, O95544, P35815, P36993, P54797, P58058, P63143, P63144, Q0IHH9, Q0V7M0, Q0VCW1, Q15645, Q28528, Q28F89, Q2M2N2, Q2TA46, Q3UA06, Q4PJK1, Q5BL35, Q5NVK7, Q5RBV0, Q5REP9, Q5U1X1, Q5XHZ9, Q6GR09, Q6IQ16

Diamond homologs: A0JMG1, A1YEX3, B0WWP2, B3DIV9, B3M9V8, B3NDN0, B4GRJ2, B4HIK1, B4J045, B4L0G9, B4LIG6, B4MXW3, B4PD06, B4QLQ2, B7U179, D3Z8N4, D4A2K4, E0CZ16, E7F6F9, F1LZF0, F1MBP6, O14682, O22286, O35709, O43791, O81432, O95198, P0DMR5, P0DMR6, P24278, P28575, P34568, P58544, P58545, Q08DK3, Q08DS0, Q0D2A9, Q0IHH9, Q0VCW1, Q16RL8

SIGNOR signaling

24 interactions.

A	Effect	B	Mechanism
SPOP	“down-regulates quantity by destabilization”	NCOA3	binding
SPOP	“down-regulates quantity by destabilization”	EGLN2	ubiquitination
SPOP	“down-regulates quantity”	BRMS1	ubiquitination
SPOP	“down-regulates quantity”	DAXX	ubiquitination
SPOP	“down-regulates quantity”	GLI2	ubiquitination
SPOP	“down-regulates quantity”	GLI3	ubiquitination
SPOP	“down-regulates quantity”	HDAC6	ubiquitination
“1-phosphatidyl-1D-myo-inositol 5-phosphate(3-)”	“up-regulates activity”	SPOP	binding
SPOP	“down-regulates activity”	GMNN	ubiquitination
SPOP	“up-regulates activity”	CUL3	binding
SPOP	“up-regulates activity”	MACROH2A1	binding
SPOP	“up-regulates activity”	BMI1	binding
SPOP	“up-regulates activity”	“Cullin 3-RBX1-Skp1”	binding
SPOP	“down-regulates activity”	INF2	binding
SPOP	up-regulates	“Cullin 3-RBX1-Skp1”	binding
SPOP	“down-regulates quantity by destabilization”	GLYR1	binding
SPOP	“down-regulates quantity by destabilization”	TRIM24	binding
SPOP	“down-regulates quantity by destabilization”	DEK	binding
SPOP	“down-regulates quantity”	CD274	ubiquitination
LIMK2	“down-regulates activity”	SPOP	phosphorylation
SPOP	“down-regulates quantity”	PDX1	ubiquitination

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 129 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.

Reactome pathways:

Pathway	Partners	Fold	FDR
Defective binding of RB1 mutants to E2F1,(E2F2, E2F3)	7	40.7×	6e-08
Aberrant regulation of mitotic cell cycle due to RB1 defects	6	22.4×	2e-05
G1 Phase	6	21.7×	2e-05
Diseases of mitotic cell cycle	6	21.7×	2e-05
Cyclin D associated events in G1	9	19.2×	2e-07
NS1 Mediated Effects on Host Pathways	6	15.7×	1e-04
Oncogene Induced Senescence	5	15.4×	6e-04
Mitotic G1 phase and G1/S transition	8	13.5×	2e-05

GO biological processes:

GO term	Partners	Fold	FDR
NLS-bearing protein import into nucleus	8	52.2×	8e-10
G1/S transition of mitotic cell cycle	12	19.6×	8e-10
positive regulation of G1/S transition of mitotic cell cycle	6	19.6×	9e-05
positive regulation of fibroblast proliferation	5	12.0×	6e-03
protein import into nucleus	10	11.7×	4e-06
cell surface receptor protein tyrosine kinase signaling pathway	6	8.5×	7e-03
protein autophosphorylation	7	8.3×	2e-03
regulation of cell population proliferation	8	7.5×	2e-03

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: activating (oncogene-like) across 5 cancer types — NHL, PRAD, PROSTATE, UCEC, UCS.

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	8
Uncertain significance	198
Likely benign	11
Benign	1

Top pathogenic / likely-pathogenic (8)

Variant ID	HGVS	Classification
1067938	NM_001007228.2(SPOP):c.257T>C (p.Leu86Pro)	Likely pathogenic
1341399	NM_001007228.2(SPOP):c.79-1G>C	Likely pathogenic
1685452	NM_001007228.2(SPOP):c.312C>A (p.Phe104Leu)	Likely pathogenic
2500332	NM_001007228.2(SPOP):c.352G>A (p.Glu118Lys)	Likely pathogenic
2584445	NM_001007228.2(SPOP):c.468_469insAA (p.Leu157fs)	Likely pathogenic
3773986	NM_001007228.2(SPOP):c.622G>T (p.Gly208Cys)	Likely pathogenic
830357	NM_001007228.2(SPOP):c.395G>T (p.Gly132Val)	Likely pathogenic
830360	NM_001007228.2(SPOP):c.248A>G (p.Tyr83Cys)	Likely pathogenic

SpliceAI

2574 predictions. Top by Δscore:

Variant	Effect	Δscore
17:49601863:A:AC	donor_gain	1.0000
17:49601864:C:CC	donor_gain	1.0000
17:49601883:G:GA	donor_gain	1.0000
17:49602004:CATA:C	acceptor_gain	1.0000
17:49602006:TA:T	acceptor_gain	1.0000
17:49602008:C:CC	acceptor_gain	1.0000
17:49607244:TCTTA:T	donor_loss	1.0000
17:49607245:CTTA:C	donor_loss	1.0000
17:49607246:TTA:T	donor_loss	1.0000
17:49607247:TA:T	donor_loss	1.0000
17:49607248:ACCTT:A	donor_loss	1.0000
17:49607249:C:CT	donor_loss	1.0000
17:49607368:CGATT:C	acceptor_gain	1.0000
17:49607371:TT:T	acceptor_gain	1.0000
17:49607373:C:CC	acceptor_gain	1.0000
17:49611278:A:T	donor_loss	1.0000
17:49611279:CCT:C	donor_loss	1.0000
17:49611453:CTCAC:C	acceptor_gain	1.0000
17:49611454:TCAC:T	acceptor_gain	1.0000
17:49611455:CAC:C	acceptor_gain	1.0000
17:49611455:CACC:C	acceptor_gain	1.0000
17:49611456:AC:A	acceptor_gain	1.0000
17:49611457:CC:C	acceptor_gain	1.0000
17:49611458:CTGTG:C	acceptor_loss	1.0000
17:49611460:G:GC	acceptor_gain	1.0000
17:49618976:CTCA:C	donor_loss	1.0000
17:49618977:TCAC:T	donor_loss	1.0000
17:49618978:CACCT:C	donor_loss	1.0000
17:49618979:A:AC	donor_gain	1.0000
17:49618980:C:CC	donor_gain	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000010363 (17:49621346 G>A), RS1000062024 (17:49679936 T>C,G), RS1000079345 (17:49628108 G>A), RS1000085880 (17:49627998 T>G), RS1000148417 (17:49629447 T>G), RS1000149010 (17:49608474 G>A), RS1000151724 (17:49629448 C>A,G), RS1000154146 (17:49673048 A>C), RS1000182079 (17:49608900 C>CAT), RS1000235080 (17:49654682 G>A), RS1000250452 (17:49635614 T>C), RS1000336256 (17:49601779 C>T), RS1000336327 (17:49642227 G>C), RS1000339044 (17:49647734 G>A), RS1000345092 (17:49678264 T>G)

Disease associations

OMIM: gene MIM:602650 | disease phenotypes: MIM:618828, MIM:618829

GenCC curated gene-disease

Disease	Classification	Inheritance
neurodevelopmental disorder with microcephaly and dysmorphic facies	Strong	Autosomal dominant
neurodevelopmental disorder	Strong	Autosomal dominant
neurodevelopmental disorder with relative macrocephaly and with or without cardiac or endocrine anomalies	Strong	Autosomal dominant

ClinGen Gene-Disease Validity (2)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
neurodevelopmental disorder with microcephaly and dysmorphic facies	Moderate	AD
neurodevelopmental disorder with relative macrocephaly and with or without cardiac or endocrine anomalies	Definitive	AD

Mondo (4): prostate cancer (MONDO:0008315), neurodevelopmental disorder with microcephaly and dysmorphic facies (MONDO:0032942), neurodevelopmental disorder with relative macrocephaly and with or without cardiac or endocrine anomalies (MONDO:0032943), neurodevelopmental disorder (MONDO:0700092)

Orphanet (3): Familial prostate cancer (Orphanet:1331), Microcephaly-hearing loss-facial dysmorphism-intellectual disability syndrome (Orphanet:662179), Macrocephaly-congenital heart disease-facial dysmorphism-intellectual disability syndrome (Orphanet:662175)

HPO phenotypes

72 total (30 of 72 shown, HPO-id order):

HPO	Term
HP:0000003	Multicystic kidney dysplasia
HP:0000006	Autosomal dominant inheritance
HP:0000076	Vesicoureteral reflux
HP:0000218	High palate
HP:0000233	Thin vermilion border
HP:0000248	Brachycephaly
HP:0000286	Epicanthus
HP:0000294	Low anterior hairline
HP:0000307	Pointed chin
HP:0000316	Hypertelorism
HP:0000319	Smooth philtrum
HP:0000325	Triangular face
HP:0000341	Narrow forehead
HP:0000347	Micrognathia
HP:0000358	Posteriorly rotated ears
HP:0000365	Hearing impairment
HP:0000369	Low-set ears
HP:0000391	Thickened helices
HP:0000411	Protruding ear
HP:0000414	Bulbous nose
HP:0000426	Prominent nasal bridge
HP:0000448	Prominent nose
HP:0000463	Anteverted nares
HP:0000486	Strabismus
HP:0000490	Deeply set eye
HP:0000494	Downslanted palpebral fissures
HP:0000506	Telecanthus
HP:0000527	Long eyelashes
HP:0000609	Optic nerve hypoplasia
HP:0000637	Long palpebral fissure

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST001942_17	Prostate cancer	2.000000e-09

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D065886	Neurodevelopmental Disorders	F03.625
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 (5): CHEMBL4523140 (SINGLE PROTEIN), CHEMBL4523606 (PROTEIN-PROTEIN INTERACTION), CHEMBL6195607 (PROTEIN-PROTEIN INTERACTION), CHEMBL6195608 (PROTEIN-PROTEIN INTERACTION), CHEMBL6195609 (PROTEIN-PROTEIN INTERACTION)

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

ChEMBL bioactivities

6 potent at pChembl≥5 of 25 total, top 6 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.24	IC50	580	nM	CHEMBL5432865
5.81	Kd	1540	nM	CHEMBL5432865
5.35	IC50	4510	nM	CHEMBL6190856
5.27	IC50	5350	nM	CHEMBL5429033
5.20	IC50	6330	nM	CHEMBL5439373
5.15	IC50	7030	nM	CHEMBL5397319

PubChem BioAssay actives

5 with measured affinity, of 123 total; 4 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
(6R,7R)-7-[[5-(chloromethyl)furan-2-carbonyl]amino]-3-ethenyl-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid	2006983: Inhibition of GST-tagged human SPOP MATH domain (28 to 166 residues) expressed in Escherichia coli BL21 CodonPlus (DE3)-RIPL cells using FITC-LACDEVTSTTSSSTA peptide as substrate assessed as inhibition of substrate binding to SPOP preincubated with compound for 30 mins followed by substrate addition and measured immediately by fluorescence polarization assay	ic50	0.5800	uM
(6R,7R)-7-[[5-[(4-bromo-2-chlorophenoxy)methyl]furan-2-carbonyl]amino]-3-ethenyl-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid	2006983: Inhibition of GST-tagged human SPOP MATH domain (28 to 166 residues) expressed in Escherichia coli BL21 CodonPlus (DE3)-RIPL cells using FITC-LACDEVTSTTSSSTA peptide as substrate assessed as inhibition of substrate binding to SPOP preincubated with compound for 30 mins followed by substrate addition and measured immediately by fluorescence polarization assay	ic50	5.3500	uM
(6R,7R)-3-ethenyl-8-oxo-7-[[5-(phenoxymethyl)furan-2-carbonyl]amino]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid	2006983: Inhibition of GST-tagged human SPOP MATH domain (28 to 166 residues) expressed in Escherichia coli BL21 CodonPlus (DE3)-RIPL cells using FITC-LACDEVTSTTSSSTA peptide as substrate assessed as inhibition of substrate binding to SPOP preincubated with compound for 30 mins followed by substrate addition and measured immediately by fluorescence polarization assay	ic50	6.3300	uM
(6R,7R)-3-ethenyl-7-[[5-[(4-fluorophenoxy)methyl]furan-2-carbonyl]amino]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid	2006983: Inhibition of GST-tagged human SPOP MATH domain (28 to 166 residues) expressed in Escherichia coli BL21 CodonPlus (DE3)-RIPL cells using FITC-LACDEVTSTTSSSTA peptide as substrate assessed as inhibition of substrate binding to SPOP preincubated with compound for 30 mins followed by substrate addition and measured immediately by fluorescence polarization assay	ic50	7.0300	uM

CTD chemical–gene interactions

24 total (human), top 24 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
trichostatin A	affects cotreatment, decreases expression	2
TAK-243	increases sumoylation	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
bisphenol A	increases methylation	1
arsenite	affects binding, increases reaction	1
cobaltous chloride	decreases expression	1
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	1
beta-methylcholine	affects expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
abrine	increases expression	1
dorsomorphin	decreases expression, affects cotreatment	1
Resveratrol	affects cotreatment, increases expression	1
Glyphosate	decreases expression	1
Acrolein	affects cotreatment, increases oxidation, increases abundance	1
Air Pollutants	affects cotreatment, increases abundance, increases oxidation	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Doxorubicin	decreases expression	1
Ozone	affects cotreatment, increases oxidation, increases abundance	1
Plant Extracts	affects cotreatment, increases expression	1
Valproic Acid	decreases expression	1
Antirheumatic Agents	increases expression	1
Cadmium Chloride	decreases expression	1
Volatile Organic Compounds	affects cotreatment, increases oxidation	1

ChEMBL screening assays

82 unique, capped per target: 82 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4406284	Binding	Inhibition of SPOP signalling in human OS-RC2 cells assessed as accumulation of DUSP7 incubated for 12 hrs by Western blot analysis	Structure-Activity Relationship of SPOP Inhibitors against Kidney Cancer. — J Med Chem

Cellosaurus cell lines

6 cell lines: 5 cancer cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B2H7	Abcam HeLa SPOP KO	Cancer cell line	Female
CVCL_D7IV	Ubigene 5637 SPOP KO	Cancer cell line	Male
CVCL_E1FU	Abcam HEK293 SPOP KO	Transformed cell line	Female
CVCL_E1KX	HyCyte HeLa KO-hSPOP	Cancer cell line	Female
CVCL_VL77	FDOV1	Cancer cell line	Female
CVCL_XT78	HAP1 SPOP (-)	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04586348	PHASE4	UNKNOWN	Prenatal Iodine Supplementation and Early Childhood Neurodevelopment
NCT04873115	PHASE4	UNKNOWN	Double-blind, Placebo-controlled, Randomized Clinical Trial Comparing the Efficacy and Safety of Sialanar Plus orAl rehabiLitation Against Placebo Plus Oral Rehabilitation for chIldren and Adolescents With seVere Sialorrhoea and Neurodisabilties,
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