GUSB

Summary

GUSB (glucuronidase beta, HGNC:4696) is a protein-coding gene on chromosome 7q11.21, encoding Beta-glucuronidase (P08236). Plays an important role in the degradation of dermatan and keratan sulfates.

This gene encodes a hydrolase that degrades glycosaminoglycans, including heparan sulfate, dermatan sulfate, and chondroitin-4,6-sulfate. The enzyme forms a homotetramer that is localized to the lysosome. Mutations in this gene result in mucopolysaccharidosis type VII. Alternative splicing results in multiple transcript variants. There are many pseudogenes of this locus in the human genome.

Source: NCBI Gene 2990 — RefSeq curated summary.

At a glance

• Gene–disease (curated): mucopolysaccharidosis type 7 (Definitive, ClinGen)
• GWAS associations: 1
• Clinical variants (ClinVar): 788 total — 54 pathogenic, 41 likely-pathogenic (top 4% of genes corpus-wide)
• Expression (HPA): Low tissue specificity — highest in liver, bone marrow, breast
• GTEx eGene: eQTL in 26 tissues, sQTL in 25 (q < 0.05)
• Phenotypes (HPO): 82
• ChEMBL bioactivity: 2 clinical-phase molecules tested; no curated mechanism-of-action drug
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 0.87 (unconstrained)
• MANE Select transcript: NM_000181
• Interaction hub: 2,240 STRING partners (top 6% of genes corpus-wide)

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4696
Approved symbol	GUSB
Name	glucuronidase beta
Location	7q11.21
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000169919
Ensembl biotype	protein_coding
OMIM	611499
Entrez	2990

Gene structure

Transcript identifiers

Ensembl transcripts: 156 — 95 nonsense_mediated_decay, 52 protein_coding, 5 protein_coding_CDS_not_defined, 4 retained_intron

MANE Select: ENST00000304895

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 3, TSL 2: 4, TSL 3: 5, TSL 4: 1, TSL 5: 1

ENST00000304895, ENST00000421103, ENST00000430730, ENST00000446111, ENST00000447929, ENST00000461622, ENST00000462371, ENST00000465785, ENST00000466883, ENST00000475316, ENST00000476486, ENST00000478118, ENST00000479038, ENST00000489482, ENST00000864776, ENST00000864777, ENST00000864778, ENST00000864779, ENST00000864780, ENST00000864781, ENST00000864782, ENST00000864783, ENST00000864784, ENST00000864785, ENST00000864786, ENST00000864787, ENST00000864788, ENST00000864789, ENST00000864790, ENST00000864791, ENST00000864792, ENST00000864793, ENST00000864794, ENST00000864795, ENST00000864796, ENST00000864797, ENST00000864798, ENST00000912571, ENST00000912572, ENST00000912573, ENST00000912574, ENST00000912575, ENST00000912576, ENST00000912577, ENST00000912578, ENST00000952458, ENST00000952459, ENST00000952460, ENST00000952461, ENST00000986740, ENST00000986741, ENST00000986742, ENST00000986743, ENST00000986744, ENST00000986745, ENST00000986746, ENST00000986747, ENST00000986748, ENST00000986749, ENST00000986750, ENST00000986751, ENST00000986752, ENST00000986753, ENST00000986754, ENST00000986755, ENST00000986756, ENST00000986757, ENST00001045075, ENST00001045076, ENST00001045077, ENST00001045078, ENST00001045079, ENST00001045080, ENST00001045081, ENST00001045082, ENST00001045083, ENST00001045084, ENST00001045085, ENST00001045086, ENST00001045087, ENST00001045088, ENST00001045089, ENST00001045090, ENST00001045091, ENST00001045092, ENST00001045093, ENST00001045094, ENST00001074594, ENST00001074595, ENST00001074596, ENST00001074597, ENST00001074598, ENST00001074599, ENST00001074600, ENST00001074601, ENST00001074602, ENST00001074603, ENST00001074604, ENST00001074605, ENST00001074606, ENST00001074607, ENST00001074608, ENST00001074609, ENST00001074610, ENST00001074611, ENST00001100599, ENST00001100600, ENST00001100601, ENST00001100602, ENST00001100603, ENST00001100604, ENST00001100605, ENST00001100606, ENST00001100607, ENST00001100608, ENST00001100609, ENST00001100610, ENST00001100611, ENST00001100612, ENST00001100613, ENST00001100614, ENST00001100615, ENST00001100616, ENST00001100617, ENST00001100618, ENST00001100619, ENST00001100620, ENST00001100621, ENST00001100622, ENST00001100623, ENST00001100624, ENST00001100625, ENST00001100626, ENST00001100627, ENST00001100628, ENST00001100629, ENST00001100630, ENST00001100631, ENST00001100632, ENST00001100633, ENST00001100634, ENST00001100635, ENST00001100636, ENST00001100637, ENST00001100638, ENST00001100639, ENST00001100640, ENST00001100641, ENST00001100642, ENST00001100643, ENST00001100644, ENST00001100645, ENST00001100646, ENST00001117597, ENST00001127385, ENST00001142510

RefSeq mRNA: 4 — MANE Select: NM_000181 NM_000181, NM_001284290, NM_001293104, NM_001293105

CCDS: CCDS5530, CCDS64665

Canonical transcript exons

ENST00000304895 — 12 exons

Exon	Start	End
ENSE00001131491	65960684	65961063
ENSE00001554367	65981974	65982213
ENSE00003467512	65974526	65974704
ENSE00003502074	65970282	65970366
ENSE00003534535	65979727	65979911
ENSE00003569314	65967731	65967907
ENSE00003569679	65976015	65976202
ENSE00003607665	65979399	65979541
ENSE00003630799	65974295	65974441
ENSE00003638618	65974919	65975071
ENSE00003683385	65964323	65964458
ENSE00003687473	65980224	65980409

Expression profiles

Bgee: expression breadth ubiquitous, 297 present calls, max score 98.96.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 28.3209 / max 245.7589, expressed in 1812 samples.

Highest expression (Bgee): endometrium epithelium, tendon of biceps brachii, tibia, visceral pleura, pleura.

Genetic regulation across tissues (GTEx eQTL / sQTL)

GUSB is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 26 tissues and its splicing (sQTL) in 25 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 51 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Skin Sun Exposed Lower leg	eqtl	8.3e-31	-0.32	7:65786330:G:A
Whole Blood	eqtl	7.2e-28	+0.38	7:65854580:G:T
Cells Cultured fibroblasts	sqtl	2.8e-25	-0.57	7:65747415:A:C
Thyroid	eqtl	2.2e-20	-0.32	7:65721024:G:C
Skin Not Sun Exposed Suprapubic	eqtl	7.0e-19	+0.32	7:66010744:G:A
Testis	sqtl	1.0e-18	+0.66	7:66008093:A:C
Artery Aorta	eqtl	3.3e-17	-0.34	7:65721024:G:C
Artery Tibial	eqtl	7.1e-17	+0.23	7:65979372:T:TGA
Thyroid	sqtl	8.0e-13	-0.49	7:66008093:A:C
Testis	eqtl	1.8e-12	-0.32	7:65986625:G:A
Cells Cultured fibroblasts	eqtl	1.1e-11	-0.23	7:65986434:C:T
Spleen	sqtl	2.4e-10	-0.69	7:65966699:A:G
Muscle Skeletal	eqtl	3.5e-09	+0.16	7:66010392:C:T
Lung	sqtl	7.2e-09	-0.39	7:66058027:G:A
Nerve Tibial	eqtl	1.2e-08	+0.21	7:65979372:T:TGA
Nerve Tibial	sqtl	2.3e-08	+0.26	7:65721024:G:C
Adipose Subcutaneous	eqtl	4.6e-08	+0.17	7:65979372:T:TGA
Heart Atrial Appendage	eqtl	6.6e-08	+0.21	7:66010392:C:T
Brain Cerebellar Hemisphere	sqtl	1.6e-06	-0.61	7:65966077:T:C
Pituitary	sqtl	1.8e-06	-0.54	7:65966699:A:G

FANTOM5 promoters

4 alternative TSS:

Promoter ID	TPM avg	Samples expressed
84213	25.4000	1808
84212	1.9217	1035
84211	0.8995	527
84210	0.0997	24

Top tissues by expression

showing 100 of 299 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
endometrium epithelium	UBERON:0004811	98.96	gold quality
tendon of biceps brachii	UBERON:0008188	98.75	gold quality
tibia	UBERON:0000979	98.38	gold quality
visceral pleura	UBERON:0002401	97.62	gold quality
pleura	UBERON:0000977	96.66	gold quality
parietal pleura	UBERON:0002400	96.56	gold quality
trabecular bone tissue	UBERON:0002483	96.17	gold quality
palpebral conjunctiva	UBERON:0001812	96.15	gold quality
right lobe of liver	UBERON:0001114	96.11	gold quality
granulocyte	CL:0000094	96.03	gold quality
layer of synovial tissue	UBERON:0007616	95.93	gold quality
spleen	UBERON:0002106	95.85	gold quality
liver	UBERON:0002107	95.82	gold quality
placenta	UBERON:0001987	95.62	gold quality
parotid gland	UBERON:0001831	95.60	gold quality
eye	UBERON:0000970	95.57	gold quality
rectum	UBERON:0001052	95.55	gold quality
ileal mucosa	UBERON:0000331	95.52	gold quality
pylorus	UBERON:0001166	95.17	gold quality
monocyte	CL:0000576	95.15	gold quality
colonic mucosa	UBERON:0000317	95.15	gold quality
synovial joint	UBERON:0002217	95.15	gold quality
mucosa of transverse colon	UBERON:0004991	95.14	gold quality
mucosa of sigmoid colon	UBERON:0004993	95.14	gold quality
mononuclear cell	CL:0000842	95.07	gold quality
periodontal ligament	UBERON:0008266	95.04	gold quality
leukocyte	CL:0000738	95.03	gold quality
renal glomerulus	UBERON:0000074	95.00	gold quality
right lung	UBERON:0002167	94.98	gold quality
metanephric glomerulus	UBERON:0004736	94.91	gold quality
bone marrow	UBERON:0002371	94.49	gold quality
gall bladder	UBERON:0002110	94.28	gold quality
duodenum	UBERON:0002114	94.19	gold quality
germinal epithelium of ovary	UBERON:0001304	94.17	gold quality
cortex of kidney	UBERON:0001225	94.12	gold quality
saliva-secreting gland	UBERON:0001044	94.11	gold quality
nephron tubule	UBERON:0001231	94.10	gold quality
metanephros	UBERON:0000081	94.05	gold quality
transverse colon	UBERON:0001157	94.03	gold quality
small intestine Peyer’s patch	UBERON:0003454	94.03	gold quality
mammary gland	UBERON:0001911	94.02	gold quality
bone marrow cell	CL:0002092	93.97	gold quality
thoracic mammary gland	UBERON:0005200	93.97	gold quality
subcutaneous adipose tissue	UBERON:0002190	93.96	gold quality
left ovary	UBERON:0002119	93.93	gold quality
right lobe of thyroid gland	UBERON:0001119	93.92	gold quality
right ovary	UBERON:0002118	93.92	gold quality
stromal cell of endometrium	CL:0002255	93.88	gold quality
minor salivary gland	UBERON:0001830	93.87	gold quality
kidney epithelium	UBERON:0004819	93.87	gold quality
upper lobe of left lung	UBERON:0008952	93.81	gold quality
left lobe of thyroid gland	UBERON:0001120	93.79	gold quality
thyroid gland	UBERON:0002046	93.79	gold quality
upper lobe of lung	UBERON:0008948	93.72	gold quality
left testis	UBERON:0004533	93.71	gold quality
small intestine	UBERON:0002108	93.69	gold quality
nasal cavity mucosa	UBERON:0001826	93.64	gold quality
caecum	UBERON:0001153	93.63	gold quality
right testis	UBERON:0004534	93.56	gold quality
trachea	UBERON:0003126	93.55	gold quality
pigmented layer of retina	UBERON:0001782	93.50	gold quality
corpus epididymis	UBERON:0004359	93.50	gold quality
retina	UBERON:0000966	93.47	gold quality
body of stomach	UBERON:0001161	93.47	gold quality
adipose tissue of abdominal region	UBERON:0007808	93.44	gold quality
omental fat pad	UBERON:0010414	93.44	gold quality
peritoneum	UBERON:0002358	93.43	gold quality
body of pancreas	UBERON:0001150	93.42	gold quality
epithelium of mammary gland	UBERON:0003244	93.42	gold quality
adipose tissue	UBERON:0001013	93.39	gold quality
vermiform appendix	UBERON:0001154	93.36	gold quality
endometrium	UBERON:0001295	93.36	gold quality
skin of hip	UBERON:0001554	93.35	gold quality
connective tissue	UBERON:0002384	93.35	gold quality
tibial nerve	UBERON:0001323	93.27	gold quality
lymph node	UBERON:0000029	93.25	gold quality
mammary duct	UBERON:0001765	93.25	gold quality
pancreatic ductal cell	CL:0002079	93.23	gold quality
decidua	UBERON:0002450	93.20	gold quality
ovary	UBERON:0000992	93.19	gold quality
cardia of stomach	UBERON:0001162	93.16	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	93.15	gold quality
pancreas	UBERON:0001264	93.10	gold quality
epithelium of nasopharynx	UBERON:0001951	93.10	gold quality
mucosa of urinary bladder	UBERON:0001259	93.09	gold quality
intestine	UBERON:0000160	93.07	gold quality
colon	UBERON:0001155	93.06	gold quality
mouth mucosa	UBERON:0003729	93.06	gold quality
large intestine	UBERON:0000059	93.03	gold quality
prostate gland	UBERON:0002367	93.02	gold quality
blood	UBERON:0000178	93.00	gold quality
fundus of stomach	UBERON:0001160	92.94	gold quality
stomach	UBERON:0000945	92.87	gold quality
testis	UBERON:0000473	92.85	gold quality
lung	UBERON:0002048	92.84	gold quality
right hemisphere of cerebellum	UBERON:0014890	92.81	gold quality
caput epididymis	UBERON:0004358	92.76	gold quality
endocervix	UBERON:0000458	92.71	gold quality
cerebellar hemisphere	UBERON:0002245	92.69	gold quality
adult organism	UBERON:0007023	92.68	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-7303	no	895.60
E-ANND-3	no	0.00

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 79 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Liver	tissue	97.2	high
Bone marrow	tissue	79.5	low
Breast	tissue	76.1	medium
Placenta	tissue	45.4	low
Epididymis	tissue	39.8	high
Rectum	tissue	39.3	not detected
Stomach 1	tissue	35.9	low
Colon	tissue	35.8	low
Duodenum	tissue	34.0	low
Lung	tissue	33.7	medium
Spleen	tissue	32.0	not detected
Pancreas	tissue	31.7	medium
Salivary gland	tissue	31.1	low
Parathyroid gland	tissue	28.3	medium
Small intestine	tissue	28.0	medium
Ovary	tissue	26.0	not detected
Thyroid gland	tissue	25.9	not detected
Gallbladder	tissue	25.9	high
Urinary bladder	tissue	25.6	medium
Cervix	tissue	25.1	medium
Endometrium 1	tissue	24.6	high
Adipose tissue	tissue	24.5	not detected
Lymph node	tissue	24.0	low
Kidney	tissue	23.5	medium
Fallopian tube	tissue	23.1	medium
Tonsil	tissue	22.5	low
Thymus	tissue	21.1
Appendix	tissue	21.0	low
Seminal vesicle	tissue	20.0	not detected
Prostate	tissue	19.0	medium
Testis	tissue	18.2	medium
Smooth muscle	tissue	17.8	not detected
Vagina	tissue	16.3	not detected
Skin 1	tissue	16.0	not detected
Spinal cord	tissue	15.6
Adrenal gland	tissue	15.3	high
Esophagus	tissue	15.1	low
Heart muscle	tissue	14.2	low
Frontal cortex	tissue	13.9
Tongue	tissue	13.4
Cerebral cortex	tissue	13.3	medium
Occipital cortex	tissue	13.3
Substantia nigra	tissue	13.2
Pituitary gland	tissue	13.0
Hypothalamus	tissue	12.9
Somatosensory cortex	tissue	12.6
Choroid plexus	tissue	12.2
Periaqueductal gray	tissue	12.1
Superior colliculi	tissue	12.0
Medulla oblongata	tissue	11.9
Caudate putamen	tissue	11.9
Pons	tissue	11.7
Temporal cortex	tissue	11.6
Thalamus	tissue	11.5
Hippocampal formation	tissue	11.3
Entorhinal cortex	tissue	11.3
Septum	tissue	11.2
Midbrain	tissue	10.7
Amygdala	tissue	10.2
Motor cortex	tissue	9.9

Brain sub-regions (HPA Brain Atlas): detected in 192; highest nTPM — Blood vessel (22.6), Dorsal spinal cord (15.6), Ventral spinal cord (14.0), Nucleus raphe pallidus (10.2), Corpus callosum, genu (white matter) (10.1).

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ERF, NR1I2, NR4A3, TFAP2A, VSX2

miRNA regulators (miRDB)

Targeting GUSB by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

7 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-4255	99.72	67.70	1541
HSA-MIR-4527	99.66	67.43	714
HSA-MIR-587	99.64	70.86	2611
HSA-MIR-6503-5P	99.62	66.96	597
HSA-MIR-6071	99.16	67.77	1780
HSA-MIR-6889-5P	90.26	64.13	291

Functional genomics

gnomAD constraint: pLI 3.66e-11, LOEUF 0.871, missense Z 1.45 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000304895 splits into 2 regions with different missense tolerance; 0 are missense-constrained. Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. gnomAD

Region (GRCh38)	Missense obs / exp	o/e	Constrained
7:65,960,900–65,976,113	368 / 489.9	0.75	no
7:65,976,114–65,982,183	368 / 363.8	1.01	no

Literature-anchored findings (GeneRIF, showing 19)

• beta-glucuronidase mutations are associated with mucopolysaccharidosis type VII (PMID:12522561)
• Recombinant adeno-associated virus encoding human GUSB injected into the vitreous humor of young adult MPS VII mice increased GUSB activity and reduced lysosomal distension in regions of the thalamus and tectum (PMID:12716937)
• beta glucuronidase present in the synovial fluid of rheumatoid arthritis patients, may contribute to the depletion of glycosaminoglycans from cartilage allowing invasion of synovial cells. (PMID:12905469)
• Over-expression of beta-glucuronidase was related to the degree of cancer differentiation, but not to lymph node metastasis. (PMID:14612292)
• These results indicate that beta-glucuronidase transport into brain parenchyma in early postnatal life is mediated by the mannose 6-phosphate/insulin-like growth factor II receptor. (PMID:15314220)
• The genes GUS and PMM1 are recommended for normalization purposes in gene expression studies of liver tissue from patients with chronic hepatitis. (PMID:18591914)
• Study summarized information on the 49 unique, disease-causing mutations determined so far in the GUS gene. (PMID:19224584)
• Liver disease affects the expression of common HKGs; beta-glucuronidase and splicing factor arginine/serine-rich 4 are the most stable HKGs for studies of gene expression in HCV-infected human liver. (PMID:21073651)
• GUSB and ATP2B4 have been validated as a reliable gene combination for Cystic Fibrosis Transmembrane Conductance Regulator gene qPCR data normalization. (PMID:22525089)
• This assessment demonstrated that although butyrate dramatically increased beta-glucuronidase production in bioreactors, it adversely impacted the mannose-6-phosphorylation of this lysosomal storage diseasestherapeutic enzyme (PMID:24033810)
• expression of CES2, UGTA1A1, and GUSB varies in colorectal pathology tissues and that the expression of CES2 is somewhat related to tumor staging. (PMID:24195516)
• the efficacy of a helper-dependent (HD) canine adenovirus (CAV-2) vector harboring a human GUSB expression cassette (HD-RIGIE) in the MPS VII dog brain was tested (PMID:24343103)
• the use of in silico approaches provided a useful understanding of the effect of single point mutations on the structure-function relationship of GUSBp (PMID:26415878)
• Selective and amplified bG expression together with the prodrug DOXGA3 had an increased antitumor effect, showing great potential for prostate cancer therapy. (PMID:26648021)
• Results show that GUS mRNA changes in blood are significantly correlated with gait step length variability in premutation (PM) females patients with fragile X tremor ataxia syndrome . (PMID:27387142)
• We produced GUS from a CHO cell line grown in suspension in a 15 L perfused bioreactor and developed a three step purification procedure that yields approximately 99% pure enzyme with a recovery of more than 40%. (PMID:28734840)
• the beta-d-galactosidase, beta-d-glucuronidase and alpha-l-fucosidase activities in serums from hemolyzed blood, were determined. (PMID:29885630)
• Over-Expression of GUSB Leads to Primary Resistance of Anti-PD1 Therapy in Hepatocellular Carcinoma. (PMID:35812439)
• Macrophages and derived-TNF-alpha promote lipopolysaccharide-induced upregulation of endogenous beta-glucuronidase in the epithelial cells of the bile duct: A possible facilitator of hepatolithiasis formation. (PMID:36473630)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	gusb	ENSDARG00000063126
mus_musculus	Gusb	ENSMUSG00000025534
rattus_norvegicus	Gusb	ENSRNOG00000000913
drosophila_melanogaster	CG15117	FBGN0034417
drosophila_melanogaster	betaGlu	FBGN0270927
caenorhabditis_elegans	Y105E8B.9	WBGENE00013693

Paralogs (1): MANBA (ENSG00000109323)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:95872) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 39 distinct phenotype terms.

Mouse phenotype (MP)	Records
short limbs	6
decreased body size	5
abnormal lysosome morphology	5
shortened head	4
postnatal growth retardation	4
short snout	3
thick tail	3
short tail	3
premature death	3
abnormal lactation	2
male infertility	2
disproportionate dwarf	2
abnormal skeleton morphology	2
increased urine glycosaminoglycan level	2
abnormal neurocranium morphology	1
abnormal cell morphology	1
decreased body length	1
abnormal gait	1
decreased white adipose tissue amount	1
deafness	1
postnatal lethality	1
abnormal axial skeleton morphology	1
abnormal limb bone morphology	1
abnormal sexual interaction	1
abnormal long bone morphology	1

+14 more (showing top 25).

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Pongo abelii	Q5R5N6	96.8%	Diamond
Chlorocebus aethiops	O77695	93.8%	Diamond
Canis lupus familiaris	O18835	91.7%	Diamond
Felis catus	O97524	91.7%	Diamond
Sus scrofa	Q4FAT7	87.6%	Diamond
Streptococcus agalactiae 2603V/R	Q8E0N2	52.0%	Diamond
Clostridium perfringens str. 13	Q8XP19	52.0%	Diamond
Paenibacillus borealis	A0A089LCJ8	51.8%	Diamond
Escherichia coli K-12	P05804	48.2%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
VKORC1L1	protein-coding	154807
ASL	protein-coding	435
LINC03129	ncRNA	84214
CRCP	protein-coding	27297

Protein

Protein identifiers

Beta-glucuronidase — P08236 (reviewed: P08236)

Alternative names: Beta-G1

All UniProt accessions (3): P08236, F2Z3L6, F8WBK6

UniProt curated annotations — full annotation on UniProt →

Function. Plays an important role in the degradation of dermatan and keratan sulfates.

Subunit / interactions. Homotetramer.

Subcellular location. Lysosome.

Post-translational modifications. N-linked glycosylated with 3 to 4 oligosaccharide chains.

Disease relevance. Mucopolysaccharidosis 7 (MPS7) [MIM:253220] A form of mucopolysaccharidosis, a group of lysosomal storage diseases characterized by defective degradation of glycosaminoglycans, resulting in their excessive accumulation and secretion. The diseases are progressive and often display a wide spectrum of clinical severity. MPS7 is an autosomal recessive form with a highly variable phenotype, ranging from severe lethal hydrops fetalis to mild forms with survival into adulthood. Most patients with the intermediate phenotype show hepatomegaly, skeletal anomalies, coarse facies, and variable degrees of mental impairment. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Inhibited by L-aspartic acid.

Similarity. Belongs to the glycosyl hydrolase 2 family.

Isoforms (3)

UniProt ID	Names	Canonical?
P08236-1	1, Long	yes
P08236-2	2, Short
P08236-3	3

RefSeq proteins (4): NP_000172, NP_001271219, NP_001280033, NP_001280034 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR006101	Glyco_hydro_2	Family
IPR006102	Ig-like_GH2	Domain
IPR006103	Glyco_hydro_2_cat	Domain
IPR006104	Glyco_hydro_2_N	Domain
IPR008979	Galactose-bd-like_sf	Homologous_superfamily
IPR013783	Ig-like_fold	Homologous_superfamily
IPR017853	GH_hydrolase_sf	Homologous_superfamily
IPR023230	Glyco_hydro_2_CS	Conserved_site
IPR023232	Glyco_hydro_2_AS	Active_site
IPR036156	Beta-gal/glucu_dom_sf	Homologous_superfamily

Pfam: PF00703, PF02836, PF02837

Enzyme classification (BRENDA)

• EC 3.2.1.31 — beta-glucuronidase (BRENDA: 70 organisms, 139 substrates, 75 inhibitors, 71 Km, 35 kcat entries)

Substrate kinetics (BRENDA)

33 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
GLYCYRRHIZIN	0.78–7.72	9
4-METHYLUMBELLIFERYL-BETA-D-GLUCURONIDE	1.04–2.76	7
4-NITROPHENYL BETA-D-GLUCURONIDE	0.0046–0.36	5
GLYCYRRHETINIC ACID 3-O-MONO-BETA-D-GLUCURONIDE	0.91–1.1	4
4-NITROPHENYL BETA-D-GLUCOSIDE	0.0304–145	3
4-NITROPHENYL-BETA-D-GLUCURONIDE	0.208–1.4	3
4-METHYLUMBELLIFERYL BETA-D-GLUCURONIDE	0.54–0.58	2
GLCABETA(1-6)GAL	0.378–0.422	2
P-NITROPHENYL-BETA-D-GLUCURONIDE	0.22–0.23	2
1-DEOXY-1-(6-THIOPURINYL)-BETA-D-GLUCOPYRANOSIDE	1.49	1
1-DEOXY-1-(6-THIOPURINYL)-BETA-D-GLUCOPYRANOSIDU	9.25	1
4-ME-BETA-GLCA-(1-6)-BETA-GAL-(1-6)-BETA-GAL-(1-	1.4	1
4-ME-BETA-GLCA-(1-6)-BETA-GAL-(1-6)-GAL	1.9	1
4-ME-BETA-GLCA-(1-6)-GAL	3.6	1
4-METHYLUMBELLIFERYL-BETA-D-GLUCURONIC ACID	1.25	1

Catalyzed reactions (Rhea)

• a beta-D-glucuronoside + H2O = D-glucuronate + an alcohol (RHEA:17633)

UniProt features (110 total): sequence variant 40, strand 35, helix 19, turn 7, glycosylation site 4, splice variant 2, signal peptide 1, chain 1, active site 1

Structure

Experimental structures (PDB)

2 structures by resolution:

PDB	Title	Method	Resolution (Å)
3HN3	Human beta-glucuronidase at 1.7 A resolution	X-RAY DIFFRACTION	1.7
1BHG	HUMAN BETA-GLUCURONIDASE AT 2.6 A RESOLUTION	X-RAY DIFFRACTION	2.53

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P08236-F1	94.35	0.93

Human Protein Atlas

Protein class: Enzymes, ENZYME proteins, Hydrolases, Metabolic proteins, Predicted intracellular proteins, Plasma proteins, Cancer-related genes, Mutated cancer genes, Disease related genes, Potential drug targets, Human disease related genes, Congenital disorders of metabolism, Congenital disorders of glycan/glycoprotein metabolism

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): vesicles

Antibody reliability (HPA): IH approved · IF supported

Functional residue map

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

Catalytic / active sites (1)

Position	Role
451	proton donor

Glycosylation sites (4)

Type	Positions
N-linked (glcnac…) asparagine	173, 272, 420, 631

Function

Pathways and Gene Ontology

Reactome pathways

5 curated (TAS) of 16; 6 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

16 pathways:

ID	Pathway	Evidence
R-HSA-9953080	MPS VII - Sly syndrome (CS/DS degradation) ⚕	curated
R-HSA-2206292	MPS VII - Sly syndrome (Hyaluronan metabolism) ⚕	curated
R-HSA-2024101	CS/DS degradation	curated
R-HSA-2160916	Hyaluronan degradation	curated
R-HSA-6798695	Neutrophil degranulation	curated
R-HSA-1643685	Disease ⚕	—
R-HSA-5663084	Diseases of carbohydrate metabolism ⚕	—
R-HSA-5668914	Diseases of metabolism ⚕	—
R-HSA-2206281	Mucopolysaccharidoses ⚕	—
R-HSA-1793185	Chondroitin sulfate/dermatan sulfate metabolism	—
R-HSA-1630316	Glycosaminoglycan metabolism	—
R-HSA-2142845	Hyaluronan metabolism	—
R-HSA-168256	Immune System	—
R-HSA-168249	Innate Immune System	—
R-HSA-1430728	Metabolism	—
R-HSA-71387	Metabolism of carbohydrates and carbohydrate derivatives	—

MSigDB gene sets: 505 (showing top): GOBP_MYELOID_CELL_DIFFERENTIATION, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOBP_PHOSPHOLIPID_METABOLIC_PROCESS, REACTOME_INNATE_IMMUNE_SYSTEM, GOBP_PHOSPHATIDYLINOSITOL_METABOLIC_PROCESS, GOBP_CARTILAGE_DEVELOPMENT, GOBP_VACUOLE_ORGANIZATION, GOBP_SKELETAL_SYSTEM_DEVELOPMENT, GOBP_INFLAMMATORY_RESPONSE, PAL_PRMT5_TARGETS_UP, GOCC_SECRETORY_GRANULE, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_UP, GOBP_GROWTH

GO Biological Process (5): carbohydrate metabolic process (GO:0005975), glycosaminoglycan catabolic process (GO:0006027), heparan sulfate proteoglycan catabolic process (GO:0030200), chondroitin sulfate proteoglycan catabolic process (GO:0030207), hyaluronan catabolic process (GO:0030214)

GO Molecular Function (7): beta-glucuronidase activity (GO:0004566), signaling receptor binding (GO:0005102), protein domain specific binding (GO:0019904), carbohydrate binding (GO:0030246), hydrolase activity, hydrolyzing O-glycosyl compounds (GO:0004553), hydrolase activity (GO:0016787), hydrolase activity, acting on glycosyl bonds (GO:0016798)

GO Cellular Component (8): extracellular region (GO:0005576), endoplasmic reticulum (GO:0005783), membrane (GO:0016020), azurophil granule lumen (GO:0035578), lysosomal lumen (GO:0043202), extracellular exosome (GO:0070062), ficolin-1-rich granule lumen (GO:1904813), lysosome (GO:0005764)

Reactome top-level categories

11 top-level categories:

Category	Pathways
Mucopolysaccharidoses	2
Glycosaminoglycan metabolism	2
Chondroitin sulfate/dermatan sulfate metabolism	1
Hyaluronan metabolism	1
Innate Immune System	1
Metabolism of carbohydrates and carbohydrate derivatives	1
Immune System	1
Diseases of carbohydrate metabolism	1
Diseases of metabolism	1
Disease	1
Metabolism	1

GO top-level categories

26 GO namespaces:

Category	Terms
proteoglycan catabolic process	2
protein binding	2
cellular anatomical structure	2
vacuolar lumen	2
primary metabolic process	1
aminoglycan catabolic process	1
glycosaminoglycan metabolic process	1
heparan sulfate proteoglycan metabolic process	1
chondroitin sulfate proteoglycan metabolic process	1
glycosaminoglycan catabolic process	1
hyaluronan metabolic process	1
glucuronidase activity	1
binding	1
hydrolase activity, acting on glycosyl bonds	1
catalytic activity	1
hydrolase activity	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1
secretory granule lumen	1
azurophil granule	1
lysosome	1
extracellular vesicle	1
intracellular organelle lumen	1
ficolin-1-rich granule	1
lytic vacuole	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 6 of 21 annotations. The rest are phylogenetic / computational / electronic (IEA).

6 experimentally-supported GO terms:

GO term	NS	Evidence
hyaluronan catabolic process	BP	direct assay
extracellular exosome	CC	high-throughput assay
membrane	CC	high-throughput assay
beta-glucuronidase activity	MF	direct assay
protein domain specific binding	MF	physical interaction
signaling receptor binding	MF	physical interaction

Protein interactions and networks

STRING

showing 15 of 2,240 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GUSB	OGA	O60502	837
GUSB	KL	Q9UEF7	783
GUSB	GAPDH	P00354	774
GUSB	TRPV5	Q9NQA5	766
GUSB	ARSA	P15289	764
GUSB	MPI	P34949	755
GUSB	B2M	P01884	752
GUSB	IDUA	P35475	748
GUSB	TRPV6	Q9H1D0	746
GUSB	TBP	P20226	743
GUSB	GLB1	P16278	743
GUSB	CES1	P23141	734
GUSB	POTEF	A5A3E0	715
GUSB	HPRT1	P00492	705
GUSB	GLA	P06280	697

IntAct

Human interaction partners of GUSB in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

12 partners by confidence:

Partner	Interaction type	MIscore	Records
BRAF	proximity	0.470	2
VRK1	physical association	0.400	1
GIT2	physical association	0.370	1
FBXW7	proximity	0.270	4
SMAD4	proximity	0.270	4
SPOP	proximity	0.270	4
SMARCA4	proximity	0.270	2
AKT1	proximity	0.270	1
EGFR	proximity	0.270	1
PTEN	proximity	0.270	1
PTPN11	proximity	0.270	1
TP53	proximity	0.270	1

BioGRID (89 interactions; top human partners by supporting records): CDK4 (Affinity Capture-MS; 4 records), IDS (Affinity Capture-MS; 3 records), FBXO6 (Affinity Capture-MS; 2 records), HOXA3 (Affinity Capture-MS; 2 records), PMEL (Affinity Capture-MS; 2 records), TAZ (Affinity Capture-MS; 2 records), TMEM25 (Affinity Capture-MS; 2 records), ADAMTS4 (Affinity Capture-MS), ALPP (Affinity Capture-MS), ALPPL2 (Affinity Capture-MS), ATG9A (Proximity Label-MS), BCAN (Affinity Capture-MS), BCAR1 (Affinity Capture-MS), BTNL2 (Affinity Capture-MS), C1orf54 (Affinity Capture-MS)

SIGNOR signaling

2 signaling interactions:

A	Effect	B	Mechanism
TFEB	“up-regulates quantity by expression”	GUSB	“transcriptional regulation”
ACSS2	“up-regulates quantity by expression”	GUSB	“transcriptional regulation”

Disease & clinical

Genetic variants

Variant evidence for GUSB: 788 ClinVar records (95 pathogenic / likely pathogenic); 1 GWAS association. Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	54
Likely pathogenic	41
Uncertain significance	219
Likely benign	381
Benign	15

Top pathogenic / likely-pathogenic (15)

Showing the 15 best-reviewed of 95 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
905	NM_000181.4(GUSB):c.526C>T (p.Leu176Phe)	Pathogenic	criteria provided, multiple submitters, no conflicts	11
900	NM_000181.4(GUSB):c.1521G>A (p.Trp507Ter)	Pathogenic	criteria provided, multiple submitters, no conflicts	5
495724	NM_000181.4(GUSB):c.1337G>A (p.Trp446Ter)	Pathogenic	criteria provided, multiple submitters, no conflicts	3
633257	NM_000181.4(GUSB):c.1874_1875del (p.Arg625fs)	Pathogenic	criteria provided, multiple submitters, no conflicts	2
975000	NM_000181.4(GUSB):c.1244+1G>A	Pathogenic	criteria provided, multiple submitters, no conflicts	2
2731024	NM_000181.4(GUSB):c.1455dup (p.Asn486Ter)	Pathogenic	criteria provided, multiple submitters, no conflicts	2
2863642	NM_000181.4(GUSB):c.507dup (p.Ile170fs)	Pathogenic	criteria provided, multiple submitters, no conflicts	2
590813	NM_000181.4(GUSB):c.104C>A (p.Ser35Ter)	Pathogenic	criteria provided, single submitter	2
1027384	NM_000181.4(GUSB):c.1651C>T (p.Gln551Ter)	Pathogenic	criteria provided, single submitter	2
92592	NM_000181.4(GUSB):c.866G>A (p.Trp289Ter)	Pathogenic	criteria provided, single submitter	1
618670	NM_000181.4(GUSB):c.1A>C (p.Met1Leu)	Pathogenic	criteria provided, single submitter	1
2087077	NM_000181.4(GUSB):c.932dup (p.Ser312fs)	Pathogenic	criteria provided, single submitter	1
2111403	NM_000181.4(GUSB):c.24del (p.Trp9fs)	Pathogenic	criteria provided, single submitter	1
2117122	NM_000181.4(GUSB):c.604C>T (p.Gln202Ter)	Pathogenic	criteria provided, single submitter	1
2231212	NM_000181.4(GUSB):c.1583G>A (p.Trp528Ter)	Pathogenic	criteria provided, single submitter	1

Per-variant reference — Sugi Variant

Explore GUSB’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 21 predictions of 1,140):

Position(s)	Effect	Δscore	Sites
7:65964459	acceptor_gain	1.0000
7:65964459–65964460	acceptor_loss	1.0000	2
7:65964468	acceptor_gain	1.0000
7:65964473	acceptor_gain	1.0000
7:65967729–65967730	donor_loss	1.0000	5
7:65974293–65974294	donor_loss	1.0000	3
7:65974556	donor_gain	1.0000
7:65976203	acceptor_gain	1.0000
7:65976203–65976204	acceptor_loss	1.0000	5
7:65979490	acceptor_gain	1.0000

AlphaMissense

1,627 missense substitutions predicted likely pathogenic (of 4,252 scored), across 423 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
H385	8	0.982	0.995
H351	8	0.980	0.992
D369	8	0.978	0.995
D591	8	0.972	0.993
D207	8	0.967	0.985
D353	8	0.964	0.995
H426	8	0.955	0.982
D318	8	0.948	0.978
N450	8	0.935	0.994
F47	8	0.931	0.984
D497	8	0.931	0.993
F592	8	0.931	0.996
D437	8	0.930	0.976
N502	8	0.929	0.991
N604	8	0.905	0.987
D474	8	0.900	0.946
D50	8	0.896	0.965
F589	8	0.896	0.972
D85	8	0.887	0.968
D490	8	0.861	0.976

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

2 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	8.02e-05
Kidney Chromophobe (TCGA)	unfavorable	0.000676

Disease associations

OMIM: gene MIM:611499 | disease phenotypes: MIM:236750 (Hydrops fetalis, nonimmune), MIM:253200 (Mucopolysaccharidosis, type VI), MIM:253220 (Mucopolysaccharidosis VII)

GenCC curated gene-disease

1 curated gene-disease records:

Disease	Classification	Inheritance	Records
mucopolysaccharidosis type 7	Definitive	Autosomal recessive	5

ClinGen Gene-Disease Validity

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

1 validity classifications:

Disease	Classification	Inheritance
mucopolysaccharidosis type 7	Definitive	AR

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (15 panels, 15 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

15 panels:

Panel	Rating
DDG2P	green
Fetal anomalies	green
Fetal hydrops	green
Hydrocephalus	green
Hypotonic infant	green
Intellectual disability	green
Leukodystrophy, childhood onset	green
Likely inborn error of metabolism	green
Lysosomal storage disorder	green
Mucopolysaccharideosis, Gaucher, Fabry	green
Paediatric disorders	green
Paediatric or syndromic cardiomyopathy	green
Skeletal dysplasia	green
Undiagnosed metabolic disorders	green
Unexplained death in infancy and sudden unexplained death in childhood	green

Mondo (3): mucopolysaccharidosis type 7 (MONDO:0009662), non-immune hydrops fetalis (MONDO:0009369), mucopolysaccharidosis type 6 (MONDO:0009661)

Orphanet (3): Non-immune hydrops fetalis (Orphanet:363999), Mucopolysaccharidosis type 6 (Orphanet:583), Mucopolysaccharidosis type 7 (Orphanet:584)

HPO phenotypes

showing 60 of 82 phenotypes (HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000023	Inguinal hernia
HP:0000158	Macroglossia
HP:0000212	Gingival overgrowth
HP:0000238	Hydrocephalus
HP:0000256	Macrocephaly
HP:0000280	Coarse facial features
HP:0000286	Epicanthus
HP:0000324	Facial asymmetry
HP:0000365	Hearing impairment
HP:0000403	Recurrent otitis media
HP:0000407	Sensorineural hearing impairment
HP:0000470	Short neck
HP:0000505	Visual impairment
HP:0000574	Thick eyebrow
HP:0000613	Photophobia
HP:0000687	Widely spaced teeth
HP:0000767	Pectus excavatum
HP:0000768	Pectus carinatum
HP:0000926	Platyspondyly
HP:0000943	Dysostosis multiplex
HP:0001004	Lymphedema
HP:0001007	Hirsutism
HP:0001249	Intellectual disability
HP:0001252	Hypotonia
HP:0001270	Motor delay
HP:0001371	Flexion contracture
HP:0001376	Limitation of joint mobility
HP:0001387	Joint stiffness
HP:0001537	Umbilical hernia
HP:0001538	Protuberant abdomen
HP:0001540	Diastasis recti
HP:0001541	Ascites
HP:0001638	Cardiomyopathy
HP:0001654	Abnormal heart valve morphology
HP:0001744	Splenomegaly
HP:0001762	Talipes equinovarus
HP:0001789	Hydrops fetalis
HP:0001840	Metatarsus adductus
HP:0002103	Abnormal pleura morphology
HP:0002159	Heparan sulfate excretion in urine
HP:0002180	Neurodegeneration
HP:0002205	Recurrent respiratory infections
HP:0002208	Coarse hair
HP:0002240	Hepatomegaly
HP:0002465	Poor speech
HP:0002650	Scoliosis
HP:0002680	J-shaped sella turcica
HP:0002788	Recurrent upper respiratory tract infections
HP:0002808	Kyphosis
HP:0002857	Genu valgum
HP:0002870	Obstructive sleep apnea
HP:0003272	Abnormal hip bone morphology
HP:0003311	Hypoplasia of the odontoid process
HP:0003375	Narrow greater sciatic notch
HP:0003510	Severe short stature
HP:0003541	Urinary glycosaminoglycan excretion
HP:0003593	Infantile onset
HP:0004322	Short stature
HP:0004469	Chronic bronchitis

GWAS associations

1 association:

Study	Trait	p-value
GCST90013406_176	Liver enzyme levels (alkaline phosphatase)	3e-15

EFO canonical traits (from GWAS)

1 canonical traits:

EFO ID	Trait name
EFO:0004533	alkaline phosphatase measurement

MeSH disease descriptors

2 disease descriptors:

Descriptor	Name	Tree numbers
D009087	Mucopolysaccharidosis VI	C16.320.565.202.715.670; C16.320.565.595.600.670; C17.300.550.575.670; C18.452.648.202.715.670; C18.452.648.595.600.670
D016538	Mucopolysaccharidosis VII	C16.320.565.202.715.675; C16.320.565.595.600.675; C17.300.550.575.675; C18.452.648.202.715.675; C18.452.648.595.600.675

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2728 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

Phase ≥1, by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 49,947 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

2 molecules by phase:

Molecule	Name	Phase	Patents
CHEMBL90593	PRASTERONE	4	23,701
CHEMBL150	KAEMPFEROL	1	26,246

PharmGKB: 1 entry (CPIC guideline: no)

Binding affinities (BindingDB)

339 measured of 370 human assays (411 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
4-(13-piperazin-1-yl-11-thia-9,14,15,16-tetrazatetracyclo[8.7.0.02,7.012,17]heptadeca-1(10),2(7),8,12(17),13,15-hexaen-8-yl)morpholine	IC50	1.2 nM	US-9334288: Selective β-glucuronidase inhibitors as a treatment for side effects of camptothecin antineoplastic agents
CHEMBL5409470	IC50	8 nM
CHEMBL5273557	IC50	9.8 nM
4-chloro-N-(naphthalen-1-ylmethyl)-5-(3-piperazin-1-ylphenoxy)thiophene-2-sulfonamide	IC50	20 nM	US-9617239: Phenoxy thiophene sulfonamides and their use as inhibitors of glucuronidase
4-chloro-N-[(4-chlorophenyl)methyl]-5-(3-piperazin-1-ylphenoxy)thiophene-2-sulfonamide	IC50	30 nM	US-9617239: Phenoxy thiophene sulfonamides and their use as inhibitors of glucuronidase
4-chloro-N-[(3-methylphenyl)methyl]-5-(3-piperazin-1-ylphenoxy)thiophene-2-sulfonamide	IC50	30 nM	US-9617239: Phenoxy thiophene sulfonamides and their use as inhibitors of glucuronidase
4-chloro-N-[(2-chlorophenyl)methyl]-5-(3-piperazin-1-ylphenoxy)thiophene-2-sulfonamide	IC50	40 nM	US-9617239: Phenoxy thiophene sulfonamides and their use as inhibitors of glucuronidase
4-chloro-N-[(3-fluorophenyl)methyl]-5-(3-piperazin-1-ylphenoxy)thiophene-2-sulfonamide	IC50	40 nM	US-9617239: Phenoxy thiophene sulfonamides and their use as inhibitors of glucuronidase
4-chloro-N-(3-methoxyphenyl)-5-(3-piperazin-1-ylphenoxy)thiophene-2-sulfonamide	IC50	70 nM	US-9617239: Phenoxy thiophene sulfonamides and their use as inhibitors of glucuronidase
4-chloro-N-(3-chlorophenyl)-5-(3-piperazin-1-ylphenoxy)thiophene-2-sulfonamide	IC50	70 nM	US-9617239: Phenoxy thiophene sulfonamides and their use as inhibitors of glucuronidase
4-chloro-N-[(3-chlorophenyl)methyl]-5-(3-piperazin-1-ylphenoxy)thiophene-2-sulfonamide	IC50	90 nM	US-9617239: Phenoxy thiophene sulfonamides and their use as inhibitors of glucuronidase
N-(naphthalen-1-ylmethyl)-5-(3-piperazin-1-ylphenoxy)thiophene-2-sulfonamide	IC50	90 nM	US-9617239: Phenoxy thiophene sulfonamides and their use as inhibitors of glucuronidase
2-(4-(Di(1H-indol-3-yl)methyl)benzoyl)-N-(2-fluorophenyl)hydrazinecarbothioamide (2)	IC50	100 nM
4-chloro-N-[(4-methoxyphenyl)methyl]-5-(3-piperazin-1-ylphenoxy)thiophene-2-sulfonamide	IC50	100 nM	US-9617239: Phenoxy thiophene sulfonamides and their use as inhibitors of glucuronidase
CHEMBL4168635	IC50	100 nM
CHEMBL4165927	IC50	100 nM
2-(4-(di(1H-indol-3-yl)methyl)benzoyl)-N-(4(trifluoromethyl)phenyl)hydrazinecarbothioamide (17)	IC50	120 nM
5-(3-piperazin-1-ylphenoxy)-N-(2-pyrrolidin-1-ylethyl)thiophene-2-sulfonamide	IC50	120 nM	US-9617239: Phenoxy thiophene sulfonamides and their use as inhibitors of glucuronidase
4-chloro-N-methyl-N-(naphthalen-1-ylmethyl)-5-(3-piperazin-1-ylphenoxy)thiophene-2-sulfonamide	IC50	120 nM	US-9617239: Phenoxy thiophene sulfonamides and their use as inhibitors of glucuronidase
4-chloro-N-[(3,5-dichlorophenyl)methyl]-5-(3-piperazin-1-ylphenoxy)thiophene-2-sulfonamide	IC50	130 nM	US-9617239: Phenoxy thiophene sulfonamides and their use as inhibitors of glucuronidase
N-[3-(dimethylamino)propyl]-5-(3-piperazin-1-ylphenoxy)thiophene-2-sulfonamide	IC50	150 nM	US-9617239: Phenoxy thiophene sulfonamides and their use as inhibitors of glucuronidase
4-chloro-N-(4-methoxyphenyl)-5-(3-piperazin-1-ylphenoxy)thiophene-2-sulfonamide	IC50	170 nM	US-9617239: Phenoxy thiophene sulfonamides and their use as inhibitors of glucuronidase
4-chloro-N-[2-(3,4-dimethoxyphenyl)ethyl]-5-(3-piperazin-1-ylphenoxy)thiophene-2-sulfonamide	IC50	190 nM	US-9617239: Phenoxy thiophene sulfonamides and their use as inhibitors of glucuronidase
N-[2-(N-ethyl-3-methylanilino)ethyl]-5-(3-piperazin-1-ylphenoxy)thiophene-2-sulfonamide	IC50	200 nM	US-9617239: Phenoxy thiophene sulfonamides and their use as inhibitors of glucuronidase
CHEMBL4177204	IC50	200 nM
N-[(2-bromophenyl)methyl]-4-chloro-5-(3-piperazin-1-ylphenoxy)thiophene-2-sulfonamide	IC50	210 nM	US-9617239: Phenoxy thiophene sulfonamides and their use as inhibitors of glucuronidase
N-[(2,4-dimethylphenyl)methyl]-5-(3-piperazin-1-ylphenoxy)thiophene-2-sulfonamide	IC50	210 nM	US-9617239: Phenoxy thiophene sulfonamides and their use as inhibitors of glucuronidase
N-(1,3-benzodioxol-5-ylmethyl)-5-(3-piperazin-1-ylphenoxy)thiophene-2-sulfonamide	IC50	220 nM	US-9617239: Phenoxy thiophene sulfonamides and their use as inhibitors of glucuronidase
N-(4-methoxyphenyl)-5-(3-piperazin-1-ylphenoxy)thiophene-2-sulfonamide	IC50	230 nM	US-9617239: Phenoxy thiophene sulfonamides and their use as inhibitors of glucuronidase
N-[2-(4-chlorophenyl)ethyl]-5-(3-piperazin-1-ylphenoxy)thiophene-2-sulfonamide	IC50	240 nM	US-9617239: Phenoxy thiophene sulfonamides and their use as inhibitors of glucuronidase
4-chloro-N-[2-(2-fluorophenyl)ethyl]-5-(3-piperazin-1-ylphenoxy)thiophene-2-sulfonamide	IC50	270 nM	US-9617239: Phenoxy thiophene sulfonamides and their use as inhibitors of glucuronidase
N-(cyclohexylmethyl)-5-(3-piperazin-1-ylphenoxy)thiophene-2-sulfonamide	IC50	270 nM	US-9617239: Phenoxy thiophene sulfonamides and their use as inhibitors of glucuronidase
N-benzyl-4-chloro-5-(3-piperazin-1-ylphenoxy)thiophene-2-sulfonamide	IC50	280 nM	US-9617239: Phenoxy thiophene sulfonamides and their use as inhibitors of glucuronidase
N-[(3,4-dimethoxyphenyl)methyl]-5-(3-piperazin-1-ylphenoxy)thiophene-2-sulfonamide	IC50	290 nM	US-9617239: Phenoxy thiophene sulfonamides and their use as inhibitors of glucuronidase
4-chloro-5-(3-piperazin-1-ylphenoxy)-N-[[3-(trifluoromethyl)phenyl]methyl]thiophene-2-sulfonamide	IC50	290 nM	US-9617239: Phenoxy thiophene sulfonamides and their use as inhibitors of glucuronidase
4-chloro-N-(naphthalen-1-ylmethyl)-5-(4-piperazin-1-ylphenoxy)thiophene-2-sulfonamide	IC50	300 nM	US-9617239: Phenoxy thiophene sulfonamides and their use as inhibitors of glucuronidase
CHEMBL4172421	IC50	300 nM
CHEMBL4173852	IC50	300 nM
4-chloro-N-[(3,5-dimethoxyphenyl)methyl]-5-(3-piperazin-1-ylphenoxy)thiophene-2-sulfonamide	IC50	310 nM	US-9617239: Phenoxy thiophene sulfonamides and their use as inhibitors of glucuronidase
N-[3-(2-oxopyrrolidin-1-yl)propyl]-5-(3-piperazin-1-ylphenoxy)thiophene-2-sulfonamide	IC50	320 nM	US-9617239: Phenoxy thiophene sulfonamides and their use as inhibitors of glucuronidase
N-(1,3-benzodioxol-5-ylmethyl)-4-chloro-5-(3-piperazin-1-ylphenoxy)thiophene-2-sulfonamide	IC50	320 nM	US-9617239: Phenoxy thiophene sulfonamides and their use as inhibitors of glucuronidase
N-[2-(2-fluorophenyl)ethyl]-5-(3-piperazin-1-ylphenoxy)thiophene-2-sulfonamide	IC50	330 nM	US-9617239: Phenoxy thiophene sulfonamides and their use as inhibitors of glucuronidase
4-chloro-5-(3-piperazin-1-ylphenoxy)thiophene-2-sulfonamide	IC50	330 nM	US-9617239: Phenoxy thiophene sulfonamides and their use as inhibitors of glucuronidase
4-chloro-N-[(3,4-dimethoxyphenyl)methyl]-5-(3-piperazin-1-ylphenoxy)thiophene-2-sulfonamide	IC50	340 nM	US-9617239: Phenoxy thiophene sulfonamides and their use as inhibitors of glucuronidase
4-chloro-N-[(3-methoxyphenyl)methyl]-5-(3-piperazin-1-ylphenoxy)thiophene-2-sulfonamide	IC50	350 nM	US-9617239: Phenoxy thiophene sulfonamides and their use as inhibitors of glucuronidase
CHEMBL1370584	IC50	350 nM
N-(3-methylsulfanylpropyl)-5-(3-piperazin-1-ylphenoxy)thiophene-2-sulfonamide	IC50	390 nM	US-9617239: Phenoxy thiophene sulfonamides and their use as inhibitors of glucuronidase
4-chloro-N-[(2,4-dimethylphenyl)methyl]-5-(3-piperazin-1-ylphenoxy)thiophene-2-sulfonamide	IC50	410 nM	US-9617239: Phenoxy thiophene sulfonamides and their use as inhibitors of glucuronidase
4-chloro-N-(4-phenylbutan-2-yl)-5-(3-piperazin-1-ylphenoxy)thiophene-2-sulfonamide	IC50	430 nM	US-9617239: Phenoxy thiophene sulfonamides and their use as inhibitors of glucuronidase
N-(2-Chlorophenyl)-2-(4-(di(1H-indol-3-yl)methyl)benzoyl)hydrazinecarbothioamide (3)	IC50	500 nM

ChEMBL bioactivities

278 potent at pChembl≥5 of 416 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.01	IC50	0.984	nM	CHEMBL3980115
8.93	IC50	1.17	nM	CHEMBL3980115
8.47	EC50	3.41	nM	CHEMBL3980115
8.45	EC50	3.58	nM	CHEMBL3980115
8.10	IC50	8	nM	CHEMBL5409470
8.01	IC50	9.75	nM	CHEMBL5273557
7.75	EC50	17.7	nM	CHEMBL3903683
7.70	IC50	20	nM	CHEMBL4635113
7.55	EC50	28.3	nM	CHEMBL1236932
7.54	EC50	29	nM	CHEMBL3903683
7.52	IC50	30	nM	CHEMBL4635884
7.52	IC50	30	nM	CHEMBL4633508
7.48	EC50	33.2	nM	CHEMBL1236932
7.40	IC50	40	nM	CHEMBL4649028
7.40	IC50	40	nM	CHEMBL4647420
7.16	IC50	70	nM	CHEMBL3289121
7.16	IC50	70	nM	CHEMBL5863393
7.16	IC50	70	nM	CHEMBL5915942
7.05	IC50	90	nM	CHEMBL4648659
7.05	IC50	90	nM	CHEMBL4635113
7.05	IC50	90	nM	CHEMBL4634028
7.03	EC50	92.4	nM	CHEMBL2335167
7.00	EC50	99.9	nM	CHEMBL2335167
7.00	IC50	100	nM	CHEMBL4165927
7.00	IC50	100	nM	CHEMBL4168635
7.00	IC50	100	nM	CHEMBL4642327
7.00	IC50	100	nM	CHEMBL4644220
6.93	IC50	118	nM	CHEMBL4642420
6.92	IC50	120	nM	CHEMBL4632976
6.92	IC50	120	nM	CHEMBL6014082
6.92	IC50	120	nM	CHEMBL4642704
6.89	IC50	130	nM	CHEMBL4643487
6.85	IC50	142	nM	CHEMBL4641808
6.82	IC50	150	nM	CHEMBL5950647
6.77	IC50	170	nM	CHEMBL5965722
6.72	IC50	190	nM	CHEMBL5864563
6.70	IC50	200	nM	CHEMBL4177204
6.70	IC50	200	nM	CHEMBL4643914
6.70	IC50	200	nM	CHEMBL5840028
6.68	IC50	210	nM	CHEMBL5992833
6.68	IC50	210	nM	CHEMBL5953913
6.67	IC50	212.6	nM	CHEMBL2335167
6.66	EC50	221.2	nM	CHEMBL1236933
6.66	IC50	220	nM	CHEMBL5907131
6.64	IC50	230.6	nM	CHEMBL2335167
6.64	IC50	230	nM	CHEMBL5866010
6.63	EC50	233.2	nM	CHEMBL1236933
6.62	IC50	240	nM	CHEMBL6031655
6.57	IC50	270	nM	CHEMBL5928918
6.57	IC50	270	nM	CHEMBL5956299

PubChem BioAssay actives

201 with measured affinity, of 502 total; 50 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
4-(13-piperazin-1-yl-11-thia-9,14,15,16-tetrazatetracyclo[8.7.0.02,7.012,17]heptadeca-1(10),2(7),8,12(17),13,15-hexaen-8-yl)morpholine	1656436: Inhibition of beta-glucuronidase (unknown origin)	ic50	0.0012	uM
(5S,6R,7S,8S)-6,7,8-trihydroxy-2-[2-(3-phenoxyphenyl)ethyl]-5,6,7,8-tetrahydroimidazo[1,2-a]pyridine-5-carboxylic acid	2018409: Inhibition of recombinant human GUSbeta using 4-MUG as substrate pre-incubated for 10 mins followed by substrate addition and measured after 60 mins by fluorescence based assay	ic50	0.0080	uM
(5S,6R,7S,8S)-6,7,8-trihydroxy-2-[2-[4-(trifluoromethyl)phenyl]ethyl]-5,6,7,8-tetrahydroimidazo[1,2-a]pyridine-5-carboxylic acid	1922231: Inhibition of human beta-glucuronidase	ic50	0.0097	uM
4-chloro-N-(naphthalen-1-ylmethyl)-5-(3-piperazin-1-ylphenoxy)thiophene-2-sulfonamide	1656436: Inhibition of beta-glucuronidase (unknown origin)	ic50	0.0200	uM
2-(2-ethoxyphenyl)-3H-quinazolin-4-one	1656455: Inhibition of beta-glucuronidase (unknown origin) using p-nitrophenyl-beta-d-glucuronide as substrate after 30 mins	ic50	0.0700	uM
1-[[4-[bis(1H-indol-3-yl)methyl]benzoyl]amino]-3-(2-fluorophenyl)thiourea	1656455: Inhibition of beta-glucuronidase (unknown origin) using p-nitrophenyl-beta-d-glucuronide as substrate after 30 mins	ic50	0.1000	uM
N-[(E)-(2,3-dihydroxyphenyl)methylideneamino]-3-[[5-[[(E)-(2,3-dihydroxyphenyl)methylideneamino]carbamoyl]-1H-indol-3-yl]-(4-methylphenyl)methyl]-1H-indole-5-carboxamide	1494144: Inhibition of human beta-glucuronidase	ic50	0.1000	uM
3-[(4-methylphenyl)-[5-[[(E)-(2,4,5-trihydroxyphenyl)methylideneamino]carbamoyl]-1H-indol-3-yl]methyl]-N-[(E)-(2,4,5-trihydroxyphenyl)methylideneamino]-1H-indole-5-carboxamide	1494144: Inhibition of human beta-glucuronidase	ic50	0.1000	uM
1-[(6,8-dimethyl-2-oxo-1H-quinolin-3-yl)methyl]-1-(2-hydroxyethyl)-3-(2-methylphenyl)urea	1656436: Inhibition of beta-glucuronidase (unknown origin)	ic50	0.1180	uM
1-[[4-[bis(1H-indol-3-yl)methyl]benzoyl]amino]-3-(3,4-dichlorophenyl)thiourea	1801941: β-Glucuronidase Bioassay from Article 10.1016/j.bioorg.2016.07.008: “Synthesis, ß-glucuronidase inhibition and molecular docking studies of hybrid bisindole-thiosemicarbazides analogs.”	ic50	0.1200	uM
1-[[4-[bis(1H-indol-3-yl)methyl]benzoyl]amino]-3-[4-(trifluoromethyl)phenyl]thiourea	1656455: Inhibition of beta-glucuronidase (unknown origin) using p-nitrophenyl-beta-d-glucuronide as substrate after 30 mins	ic50	0.1200	uM
1-[(6,8-dimethyl-2-oxo-1H-quinolin-3-yl)methyl]-3-(4-fluoro-2-methylphenyl)-1-(2-hydroxyethyl)urea	1656436: Inhibition of beta-glucuronidase (unknown origin)	ic50	0.1420	uM
3-[(4-methylphenyl)-[5-[[(E)-(2,4,6-trihydroxyphenyl)methylideneamino]carbamoyl]-1H-indol-3-yl]methyl]-N-[(E)-(2,4,6-trihydroxyphenyl)methylideneamino]-1H-indole-5-carboxamide	1494144: Inhibition of human beta-glucuronidase	ic50	0.2000	uM
1-[(6,8-dimethyl-2-oxo-1H-quinolin-3-yl)methyl]-3-(4-ethoxyphenyl)-1-(2-hydroxyethyl)thiourea	1656436: Inhibition of beta-glucuronidase (unknown origin)	ic50	0.2800	uM
N-[(E)-(3,4-dihydroxyphenyl)methylideneamino]-3-[[5-[[(E)-(3,4-dihydroxyphenyl)methylideneamino]carbamoyl]-1H-indol-3-yl]-(4-methylphenyl)methyl]-1H-indole-5-carboxamide	1494144: Inhibition of human beta-glucuronidase	ic50	0.3000	uM
N-[(E)-(2,4-dihydroxyphenyl)methylideneamino]-3-[[5-[[(E)-(2,4-dihydroxyphenyl)methylideneamino]carbamoyl]-1H-indol-3-yl]-(4-methylphenyl)methyl]-1H-indole-5-carboxamide	1494144: Inhibition of human beta-glucuronidase	ic50	0.3000	uM
3-(2-bromophenyl)-1-[(6,8-dimethyl-2-oxo-1H-quinolin-3-yl)methyl]-1-(2-hydroxyethyl)urea	1656436: Inhibition of beta-glucuronidase (unknown origin)	ic50	0.3470	uM
N,N-diethyl-6-methyl-2-sulfanylidene-4-thiophen-2-yl-3,4-dihydro-1H-pyrimidine-5-carboxamide	1667339: Inhibition of beta-glucuronidase (unknown origin) using p-nitrophenyl-beta-D-glucuronide as substrate pre-incubated for 30 mins followed by substrate addition by spectrophotometric method	ic50	0.3500	uM
1-[(6,8-dimethyl-2-oxo-1H-quinolin-3-yl)methyl]-1-(2-hydroxyethyl)-3-(4-methoxyphenyl)thiourea	1656436: Inhibition of beta-glucuronidase (unknown origin)	ic50	0.3700	uM
1-[(6,8-dimethyl-2-oxo-1H-quinolin-3-yl)methyl]-1-(2-hydroxyethyl)-3-(2-propan-2-ylphenyl)urea	1656436: Inhibition of beta-glucuronidase (unknown origin)	ic50	0.4680	uM
1-[[4-[bis(1H-indol-3-yl)methyl]benzoyl]amino]-3-(2-chlorophenyl)thiourea	1656455: Inhibition of beta-glucuronidase (unknown origin) using p-nitrophenyl-beta-d-glucuronide as substrate after 30 mins	ic50	0.5000	uM
5-chloro-N-[(E)-(2,4,5-trihydroxyphenyl)methylideneamino]-1H-indole-2-carboxamide	1656455: Inhibition of beta-glucuronidase (unknown origin) using p-nitrophenyl-beta-d-glucuronide as substrate after 30 mins	ic50	0.5000	uM
3-[5-(1H-indol-5-yl)-1,3,4-thiadiazol-2-yl]benzene-1,2-diol	1656436: Inhibition of beta-glucuronidase (unknown origin)	ic50	0.5000	uM
2,7-dimethyl-4-piperazin-1-yl-4b,5,6,7,8,8a-hexahydro-[1]benzothiolo[2,3-d]pyrimidine	1656436: Inhibition of beta-glucuronidase (unknown origin)	ic50	0.5400	uM
9-[[1-(pyridin-3-ylmethyl)triazol-4-yl]methyl]carbazole	1656436: Inhibition of beta-glucuronidase (unknown origin)	ic50	0.5500	uM
(E)-3-(4-chlorophenyl)-1-(2,5-dihydroxyphenyl)prop-2-en-1-one	1656436: Inhibition of beta-glucuronidase (unknown origin)	ic50	0.6000	uM
2-(3,4-dimethoxyphenyl)-3H-quinazolin-4-one	1153850: Inhibition of beta-glucuronidase activity (unknown origin) assessed as p-nitrophenol formation after 30 mins using p-nitrophenyl-beta-D-glucuronide as substrate by spectrophotometry	ic50	0.6000	uM
N,N-diethyl-6-methyl-4-(3-nitrophenyl)-2-sulfanylidene-3,4-dihydro-1H-pyrimidine-5-carboxamide	1667339: Inhibition of beta-glucuronidase (unknown origin) using p-nitrophenyl-beta-D-glucuronide as substrate pre-incubated for 30 mins followed by substrate addition by spectrophotometric method	ic50	0.6000	uM
N,N-diethyl-4-(3-hydroxyphenyl)-6-methyl-2-sulfanylidene-3,4-dihydro-1H-pyrimidine-5-carboxamide	1667339: Inhibition of beta-glucuronidase (unknown origin) using p-nitrophenyl-beta-D-glucuronide as substrate pre-incubated for 30 mins followed by substrate addition by spectrophotometric method	ic50	0.7200	uM
1-(3-bromo-4-hydroxyphenyl)-2-[4-(carbazol-9-ylmethyl)triazol-1-yl]ethanone	1656436: Inhibition of beta-glucuronidase (unknown origin)	ic50	0.7500	uM
3-(2-cyclopropylphenyl)-1-[(6,8-dimethyl-2-oxo-1H-quinolin-3-yl)methyl]-1-(2-hydroxyethyl)urea	1656436: Inhibition of beta-glucuronidase (unknown origin)	ic50	0.7590	uM
4,4-dimethyl-14-sulfanylidene-5-oxa-8-thia-10,12,13,15-tetrazatetracyclo[7.7.0.02,7.011,15]hexadeca-1(9),2(7),10-trien-16-one	1656436: Inhibition of beta-glucuronidase (unknown origin)	ic50	0.7590	uM
N,N-diethyl-4-(3-hydroxy-4-methoxyphenyl)-6-methyl-2-sulfanylidene-3,4-dihydro-1H-pyrimidine-5-carboxamide	1667339: Inhibition of beta-glucuronidase (unknown origin) using p-nitrophenyl-beta-D-glucuronide as substrate pre-incubated for 30 mins followed by substrate addition by spectrophotometric method	ic50	0.7600	uM
2-[4-[5-(2-fluorophenyl)-1,3,4-oxadiazol-2-yl]phenyl]chromen-4-one	1656436: Inhibition of beta-glucuronidase (unknown origin)	ic50	0.8000	uM
(5S,6R,7R,8S)-7,8-dihydroxy-6-methoxy-2-[2-(3-phenoxyphenyl)ethyl]-5,6,7,8-tetrahydroimidazo[1,2-a]pyridine-5-carboxylic acid	2018409: Inhibition of recombinant human GUSbeta using 4-MUG as substrate pre-incubated for 10 mins followed by substrate addition and measured after 60 mins by fluorescence based assay	ic50	0.8390	uM
1-(3-bromo-4-methoxyphenyl)-2-[4-(carbazol-9-ylmethyl)triazol-1-yl]ethanone	1656436: Inhibition of beta-glucuronidase (unknown origin)	ic50	0.8500	uM
(E)-4,4,4-triethoxy-1-[3-methyl-4-phenyl-5-[(E)-4,4,4-triethoxybut-2-enoyl]thieno[2,3-b]thiophen-2-yl]but-2-en-1-one	1165427: Inhibition of beta-glucuronidase (unknown origin) using p-nitrophenyl-beta-D-glucuronide substrate incubated for 30 mins by spectrophotometry	ic50	0.9000	uM
3-[5-(1H-indol-2-ylmethyl)-1,3,4-oxadiazol-2-yl]benzene-1,2-diol	1656436: Inhibition of beta-glucuronidase (unknown origin)	ic50	0.9000	uM
3-methoxy-4-[5-[4-[5-(2,4,6-trichlorophenyl)-1,3,4-thiadiazol-2-yl]phenyl]-1,3,4-oxadiazol-2-yl]phenol	1545107: Inhibition of human beta-glucuronidase pre-incubated for 30 mins before p-nitrophenyl-beta-D-glucuronide substrate addition by spectrophotometry	ic50	0.9600	uM
methyl 2-[[2-hydroxyethyl-[(6-methyl-2-oxo-1H-quinolin-3-yl)methyl]carbamothioyl]amino]benzoate	1656455: Inhibition of beta-glucuronidase (unknown origin) using p-nitrophenyl-beta-d-glucuronide as substrate after 30 mins	ic50	1.0600	uM
2-(4-methoxyphenyl)-3H-quinazolin-4-one	1153850: Inhibition of beta-glucuronidase activity (unknown origin) assessed as p-nitrophenol formation after 30 mins using p-nitrophenyl-beta-D-glucuronide as substrate by spectrophotometry	ic50	1.1000	uM
4-[5-(1H-indol-5-yl)-1,3,4-thiadiazol-2-yl]benzene-1,2-diol	1656436: Inhibition of beta-glucuronidase (unknown origin)	ic50	1.1000	uM
N-[(E)-(2,4-dichlorophenyl)methylideneamino]-3-[[5-[[(E)-(2,4-dichlorophenyl)methylideneamino]carbamoyl]-1H-indol-3-yl]-(4-methylphenyl)methyl]-1H-indole-5-carboxamide	1494144: Inhibition of human beta-glucuronidase	ic50	1.1000	uM
2-[4-[5-(4-fluorophenyl)-1,3,4-oxadiazol-2-yl]phenyl]chromen-4-one	1656436: Inhibition of beta-glucuronidase (unknown origin)	ic50	1.1000	uM
N-[(E)-(2,5-dihydroxyphenyl)methylideneamino]-3-[[5-[[(E)-(2,5-dihydroxyphenyl)methylideneamino]carbamoyl]-1H-indol-3-yl]-(4-methylphenyl)methyl]-1H-indole-5-carboxamide	1494144: Inhibition of human beta-glucuronidase	ic50	1.1400	uM
2-(3-ethoxy-4-hydroxyphenyl)-3H-quinazolin-4-one	1153850: Inhibition of beta-glucuronidase activity (unknown origin) assessed as p-nitrophenol formation after 30 mins using p-nitrophenyl-beta-D-glucuronide as substrate by spectrophotometry	ic50	1.1700	uM
2-(2-methyl-5-nitroimidazol-1-yl)ethyl 2-chloro-4,5-difluorobenzoate	1667338: Inhibition of beta-glucuronidase (unknown origin)	ic50	1.2000	uM
N-[(E)-(2-fluorophenyl)methylideneamino]-3-[[5-[[(E)-(2-fluorophenyl)methylideneamino]carbamoyl]-1H-indol-3-yl]-(4-methylphenyl)methyl]-1H-indole-5-carboxamide	1494144: Inhibition of human beta-glucuronidase	ic50	1.2000	uM
3-[(5-bromo-1H-indol-3-yl)-(6-bromo-1H-indol-3-yl)methyl]benzene-1,2-diol	1656436: Inhibition of beta-glucuronidase (unknown origin)	ic50	1.2000	uM
4-[5-(1H-indol-2-ylmethyl)-1,3,4-oxadiazol-2-yl]benzene-1,2-diol	1656436: Inhibition of beta-glucuronidase (unknown origin)	ic50	1.2000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	increases expression, affects cotreatment	3
sodium arsenite	affects expression, decreases expression, increases abundance	3
Ozone	affects cotreatment, increases expression, increases oxidation, increases abundance, affects expression	3
Valproic Acid	increases expression, increases methylation	3
methacrylaldehyde	affects cotreatment, increases expression, increases oxidation, increases abundance	2
epigallocatechin gallate	increases secretion, affects cotreatment, increases expression, decreases reaction	2
Acetaminophen	increases expression	2
Acrolein	affects cotreatment, increases expression, increases oxidation, increases abundance	2
Air Pollutants	affects cotreatment, increases abundance, increases expression, increases oxidation, affects expression	2
Benzo(a)pyrene	decreases methylation, affects reaction, increases expression, increases reaction	2
Doxorubicin	decreases expression, affects response to substance	2
bisphenol F	increases expression	1
PF-06840003	decreases expression, decreases reaction	1
ginger extract	increases abundance, increases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	increases oxidation, increases abundance, affects cotreatment, increases expression	1
benoxaprofen	increases secretion	1
potassium chromate(VI)	increases expression, affects cotreatment	1
mannose-6-phosphate	affects reaction, increases expression	1
Am 580	increases expression	1
6-((2-(4-imidazolyl)ethyl)amino)heptanoic acid 4-toluidide	increases expression, increases reaction	1
fexofenadine	affects binding, decreases reaction, increases activity, increases expression	1
ICG 001	increases expression	1
bisphenol B	increases expression	1
jinfukang	increases expression	1
picoxystrobin	increases expression	1
bisphenol AF	increases expression	1
Rosiglitazone	increases expression	1
Sunitinib	decreases expression	1
Arsenic	decreases expression, increases abundance	1

ChEMBL screening assays

41 unique, capped per target: 38 binding, 3 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1071205	Binding	Inhibition of beta-glucuronidase at 10 uM	Synthesis and biological evaluation of nitrogen-containing chalcones as possible anti-inflammatory and antioxidant agents. — *Bioorg Med Chem Lett*
CHEMBL4026921	ADMET	Inhibition of N-terminal His-tagged human beta-glucuronidase expressed in Escherichia coli BL21 (DE3) assessed as residual activity using pNPG as substrate at 10 uM preincubated for 30 mins followed by substrate addition measured after 1 hr	Specific Inhibition of Bacterial β-Glucuronidase by Pyrazolo[4,3-c]quinoline Derivatives via a pH-Dependent Manner To Suppress Chemotherapy-Induced Intestinal Toxicity. — *J Med Chem*

Cellosaurus cell lines

9 cell lines: 6 cancer cell line, 3 finite cell line

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

Cellosaurus	Name	Category	Sex
CVCL_0P00	GM02074	Finite cell line	Female
CVCL_D1MZ	Abcam K-562 GUSB KO	Cancer cell line	Female
CVCL_D2JJ	Abcam Raji GUSB KO	Cancer cell line	Male
CVCL_D5ET	HeLa::TMEM192-3xHA GUSB KO	Cancer cell line	Female
CVCL_M988	GM01850	Finite cell line	Male
CVCL_SQ73	HAP1 GUSB (-) 1	Cancer cell line	Male
CVCL_SQ74	HAP1 GUSB (-) 2	Cancer cell line	Male
CVCL_UQ66	Abcam Jurkat GUSB KO	Cancer cell line	Male
CVCL_V751	GM00121	Finite cell line	Male

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

showing 60 of 300 trials:

NCT	Phase	Status	Title
NCT00029224	Phase 4	COMPLETED	Treatment With Zoledronic Acid in Patients With Breast Cancer, Multiple Myeloma, and Prostate Cancer With Cancer Related Bone Lesions
NCT00035997	Phase 4	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	Phase 4	COMPLETED	The Effect of Zoledronic Acid on Bone Loss in Prostate Cancer Patients Undergoing Androgen Deprivation Therapy
NCT00103623	Phase 4	SUSPENDED	The Plenaxis® Experience Study
NCT00106392	Phase 4	COMPLETED	A Safety and Efficacy Study of Prograf in the Prevention of Erectile Dysfunction After Radical Prostatectomy
NCT00185029	Phase 4	UNKNOWN	MR-Lymphography and Lymph Node Staging in Prostate Cancer
NCT00199485	Phase 4	COMPLETED	Angelica Sinensis for the Treatment of Hot Flashes in Men Undergoing LHRH Therapy for Prostate Cancer
NCT00219219	Phase 4	COMPLETED	Zoledronic Acid in the Prevention of Skeletal-related Events in Hormone Refractory and Hormone-sensitive Prostate Cancer Patients With Bone Metastases
NCT00219271	Phase 4	COMPLETED	Effect Of Zoledronic Acid On Circulating And Bone Marrow-Residing Prostate Cancer Cells In Patients With Clinically Localized Prostate Cancer
NCT00237146	Phase 4	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	Phase 4	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	Phase 4	COMPLETED	Docetaxel in the Treatment of Hormone Refractory Prostate Cancer
NCT00293696	Phase 4	COMPLETED	Casodex/Zoladex Biomarkers in Localised Prostate Cancer
NCT00334139	Phase 4	COMPLETED	Effect of Zoledronic Acid on Bone Metabolism in Patients With Bone Metastasis and Prostate or Breast Cancer
NCT00375765	Phase 4	COMPLETED	Effects On Dihydrotestosterone Regulated Gene Expression In Benign Prostatic Hyperplasia Or Prostate Cancer
NCT00391690	Phase 4	COMPLETED	Evaluation of Bone Markers as Diagnostic Tools for Early Detection of Bone Metastases in Patients With High Risk Prostate Cancer
NCT00422708	Phase 4	COMPLETED	Local Anesthesia for Prostate Biopsy
NCT00526331	Phase 4	COMPLETED	Evaluation of Arterial Pressure Based Cardiac Output for Goal-Directed Perioperative Therapy
NCT00590213	Phase 4	COMPLETED	Compare the Value of Prophylactic Versus Therapeutic Breast Radiotherapy in CASODEX
NCT00629330	Phase 4	TERMINATED	Dissemination of Prostate Cancer Screening to PCP’s in African American Communities
NCT00771966	Phase 4	COMPLETED	Radical Prostatectomy and Perioperative Fluid Therapy
NCT00805701	Phase 4	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	Phase 4	COMPLETED	Effect Of Risedronate On Bone Mass In Older Men Receiving Neoadjuvant Therapy For Prostate Cancer
NCT00906269	Phase 4	UNKNOWN	Can Hyperbaric Oxygen Improve Erectile Function Following Surgery for Prostate Cancer
NCT00953277	Phase 4	COMPLETED	Study of Nerve Reconstruction Using AVANCE in Subjects Who Undergo Robotic Assisted Prostatectomy for Treatment of Prostate Cancer
NCT00982800	Phase 4	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	Phase 4	COMPLETED	Global Performance Evaluation of the AMS CONTINUUM™ Device
NCT01136226	Phase 4	COMPLETED	Evaluate Recovery of Testosterone for Patients Using Eligard
NCT01161563	Phase 4	COMPLETED	Randomized Crossover Trial to Assess the Tolerability of Gonadotropin Releasing Hormone (GnRH) Analogue Administration
NCT01230905	Phase 4	COMPLETED	Study to Monitor the Effects of Androgen Suppression Treatment on the Heart
NCT01296672	Phase 4	COMPLETED	3 Month Finasteride Challenge Test Can Significantly Improve the Performance of Screening for Prostate Cancer
NCT01365143	Phase 4	TERMINATED	Prospective Randomized Trial Comparing Robotic Versus Open Radical Prostatectomy
NCT01379742	Phase 4	UNKNOWN	Comparison of Between ThinSeed™ and OncoSeed™ for Permanent Prostate Brachytherapy
NCT01486563	Phase 4	COMPLETED	Hydroxyethyl Starch and Renal Function After Radical Prostatectomy
NCT01511874	Phase 4	COMPLETED	Efficacy and Safety Study of ELIGARD 22.5mg With Prostate Cancer
NCT01512472	Phase 4	TERMINATED	Firmagon (Degarelix) Intermittent Therapy
NCT01547416	Phase 4	COMPLETED	The Effect of Combined General/Epidural Anesthesia Versus General Anesthesia on Diaphragmatic Function
NCT01571544	Phase 4	COMPLETED	The Use of Thermal Suits as Preventing Hypothermia During Surgery
NCT01581749	Phase 4	UNKNOWN	Evaluation of Truebeam for Low-Intermediate Risk Prostate Cancer
NCT01649635	Phase 4	COMPLETED	Study of Cabazitaxel Combined With Prednisone and Prophylaxis of Neutropenia Complications in the Treatment of Patients With Metastatic Castration-resistant Prostate Cancer
NCT01673984	Phase 4	TERMINATED	GP Extended Action Triptorelin
NCT01753297	Phase 4	COMPLETED	A Study of Immediate 9 Months Adjuvant Hormone Therapy With Triptorelin 11.25 mg Versus Active Surveillance After Radical Prostatectomy in High Risk Prostate Cancer Patients.
NCT01794793	Phase 4	COMPLETED	Study to Allow Access to Pasireotide for Patients Benefiting From Pasireotide Treatment in Novartis-sponsored Studies
NCT01950871	Phase 4	TERMINATED	Prostate Guided Biopsy Study Evaluating the Diagnostic Performance of Prostate HistoScanning
NCT01995513	Phase 4	COMPLETED	Safety Study of Continued Enzalutamide Treatment In Prostate Cancer Patients
NCT02102646	Phase 4	COMPLETED	MRI Substudy; Metabolic Changes Due to Iatrogenic Hypogonadism
NCT02116582	Phase 4	COMPLETED	A Study to Evaluate Enzalutamide After Abiraterone in Metastatic Castration-Resistant Prostate Cancer
NCT02149628	Phase 4	COMPLETED	The Effect of Propofol Based Total Intravenous Anesthesia on Oxidative Stress and Nitric Oxide
NCT02405858	Phase 4	COMPLETED	A Study of Abiraterone Acetate in Metastatic Castration-Resistant Prostate Cancer Participants Who Responded Poorly to the First-line Combined Androgen Blockade Therapy
NCT02441517	Phase 4	TERMINATED	A Study of Enzalutamide Re-treatment in Metastatic Castration-resistant Prostate Cancer After Docetaxel and/or Cabazitaxel Treatment
NCT02441894	Phase 4	COMPLETED	Combination of Cabazitaxel With Prednisolone With Primary Prophylaxis With PEG-G-CSF in Treatment of Patients With Prostate Cancer
NCT02475057	Phase 4	COMPLETED	Endothelial Function in Prostate Cancer Patients on Degarelix vs. Luteinizing Hormone-Releasing Hormone Agonists
NCT02511665	Phase 4	UNKNOWN	Metformin And Longevity
NCT02651948	Phase 4	COMPLETED	Transperineal, MRI-guided, Prostate Biopsy
NCT02721433	Phase 4	COMPLETED	4-weekly Versus 12-weekly Administration of Bone-targeted Agents in Patients With Bone Metastases
NCT02726009	Phase 4	COMPLETED	A Trial to Evaluate Safety of Firmagon® (Degarelix) in Indian Patients Diagnosed With Advanced Hormone-dependent Prostate Cancer
NCT02749825	Phase 4	TERMINATED	Comparison of Trelstar Versus Lupron or Zoladex in Advanced Prostate Cancer
NCT02757365	Phase 4	UNKNOWN	Efficiency Study of Aspirin to Prevent the Occurrence of Prostate Cancer
NCT02773251	Phase 4	COMPLETED	The Effect of Guardix-solution for the Prevention of Postoperative Intestinal Adhesion and Intestinal Obstruction After Laparoscopic Pelvic Cavity Surgery
NCT02812186	Phase 4	COMPLETED	Deep Versus Moderate Neuromuscular Blockade During Laparoscopic Surgery

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for GUSB across ~30M SureChEMBL compounds — explore on Sugi Predict.