USP7

Summary

USP7 (ubiquitin specific peptidase 7, HGNC:12630) is a protein-coding gene on chromosome 16p13.2, encoding Ubiquitin carboxyl-terminal hydrolase 7 (Q93009). Hydrolase that deubiquitinates target proteins such as ARMC5, FOXO4, DEPTOR, KAT5, p53/TP53, MDM2, ERCC6, DNMT1, UHRF1, PTEN, KMT2E/MLL5 and DAXX. It is a selective cancer dependency (DepMap: 76.7% of cell lines) and haploinsufficient (ClinGen: sufficient evidence).

The protein encoded by this gene belongs to the peptidase C19 family, which includes ubiquitinyl hydrolases. This protein deubiquitinates target proteins such as p53 (a tumor suppressor protein) and WASH (essential for endosomal protein recycling), and regulates their activities by counteracting the opposing ubiquitin ligase activity of proteins such as HDM2 and TRIM27, involved in the respective process. Mutations in this gene have been implicated in a neurodevelopmental disorder.

Source: NCBI Gene 7874 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Hao-Fountain syndrome (Definitive, ClinGen) — +1 more curated relationship
• GWAS associations: 9
• Clinical variants (ClinVar): 602 total — 21 pathogenic, 31 likely-pathogenic
• Phenotypes (HPO): 66
• Druggable target: yes — 5 molecules with ChEMBL bioactivity
• Cancer driver (intOGen): loss-of-function (tumor-suppressor-like) across 2 cancer types
• Cancer dependency (DepMap): dependent in 76.7% of screened cell lines
• Dosage sensitivity (ClinGen): haploinsufficiency sufficient evidence, triplosensitivity no evidence
• MANE Select transcript: NM_003470

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:12630
Approved symbol	USP7
Name	ubiquitin specific peptidase 7
Location	16p13.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000187555
Ensembl biotype	protein_coding
OMIM	602519
Entrez	7874

Gene structure

Transcript identifiers

Ensembl transcripts: 29 — 14 protein_coding, 8 retained_intron, 5 nonsense_mediated_decay, 2 protein_coding_CDS_not_defined

ENST00000344836, ENST00000381886, ENST00000542333, ENST00000562051, ENST00000562615, ENST00000563043, ENST00000563085, ENST00000563961, ENST00000564117, ENST00000565455, ENST00000565883, ENST00000566004, ENST00000566131, ENST00000566224, ENST00000566273, ENST00000567113, ENST00000567329, ENST00000567692, ENST00000569230, ENST00000569448, ENST00000570256, ENST00000673704, ENST00000700579, ENST00000923078, ENST00000923079, ENST00000923080, ENST00000923081, ENST00000923082, ENST00000969523

RefSeq mRNA: 4 — MANE Select: NM_003470 NM_001286457, NM_001286458, NM_001321858, NM_003470

CCDS: CCDS32385, CCDS66941

Canonical transcript exons

ENST00000344836 — 31 exons

Exon	Start	End
ENSE00001404180	8892097	8894104
ENSE00001413420	8963207	8963906
ENSE00003459996	8904435	8904565
ENSE00003476284	8898360	8898437
ENSE00003481144	8895031	8895150
ENSE00003500377	8905187	8905331
ENSE00003505266	8910745	8910827
ENSE00003508057	8896999	8897099
ENSE00003511321	8906426	8906582
ENSE00003516714	8902381	8902482
ENSE00003526385	8894550	8894640
ENSE00003531178	8900530	8900630
ENSE00003531308	8902082	8902187
ENSE00003533400	8903268	8903402
ENSE00003536234	8908341	8908450
ENSE00003561472	8898531	8898639
ENSE00003563844	8894784	8894855
ENSE00003572127	8915445	8915525
ENSE00003583986	8899604	8899757
ENSE00003590561	8917026	8917156
ENSE00003591262	8919031	8919139
ENSE00003599364	8923215	8923413
ENSE00003604453	8920359	8920447
ENSE00003624363	8895642	8895741
ENSE00003632377	8930293	8930397
ENSE00003634768	8921157	8921295
ENSE00003640640	8916502	8916556
ENSE00003647183	8901142	8901234
ENSE00003648959	8899121	8899188
ENSE00003655656	8900990	8901057
ENSE00003658483	8915254	8915344

Expression profiles

Bgee: expression breadth ubiquitous, 294 present calls, max score 98.70.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 54.3519 / max 414.4374, expressed in 1825 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
156178	52.7834	1825
156177	1.4623	856
156180	0.0398	5
156175	0.0307	4
156181	0.0184	5
156176	0.0118	4
156174	0.0055	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
Brodmann (1909) area 23	UBERON:0013554	98.70	gold quality
middle temporal gyrus	UBERON:0002771	98.33	gold quality
calcaneal tendon	UBERON:0003701	97.80	gold quality
colonic epithelium	UBERON:0000397	97.77	gold quality
ventricular zone	UBERON:0003053	97.41	gold quality
cortical plate	UBERON:0005343	97.28	gold quality
rectum	UBERON:0001052	97.26	gold quality
skin of leg	UBERON:0001511	97.19	gold quality
skin of abdomen	UBERON:0001416	97.18	gold quality
secondary oocyte	CL:0000655	97.01	gold quality
ganglionic eminence	UBERON:0004023	96.83	gold quality
lymph node	UBERON:0000029	96.76	gold quality
left testis	UBERON:0004533	96.66	gold quality
zone of skin	UBERON:0000014	96.62	gold quality
tonsil	UBERON:0002372	96.59	gold quality
right testis	UBERON:0004534	96.55	gold quality
esophagus mucosa	UBERON:0002469	96.45	gold quality
trabecular bone tissue	UBERON:0002483	96.41	gold quality
body of uterus	UBERON:0009853	96.40	gold quality
ectocervix	UBERON:0012249	96.33	gold quality
sperm	CL:0000019	96.31	gold quality
transverse colon	UBERON:0001157	96.28	gold quality
vagina	UBERON:0000996	96.22	gold quality
lower esophagus mucosa	UBERON:0035834	96.19	gold quality
testis	UBERON:0000473	96.14	gold quality
endocervix	UBERON:0000458	96.10	gold quality
vermiform appendix	UBERON:0001154	96.09	gold quality
small intestine Peyer’s patch	UBERON:0003454	96.07	gold quality
male germ cell	CL:0000015	96.05	gold quality
monocyte	CL:0000576	96.01	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	8.35

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ATF1, FOS, FOXC1, GLI1, NPM1, SP1, STAT3, TCF3, TP53

miRNA regulators (miRDB)

79 targeting USP7, 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-1252-5P	100.00	69.80	2774
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-548AN	99.97	70.91	2817
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-1250-3P	99.96	70.04	4038
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-9718	99.94	68.91	918
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-329-3P	99.91	66.56	1234
HSA-MIR-362-3P	99.91	66.38	1267
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-6124	99.87	69.78	3551

Functional genomics

ClinGen dosage: haploinsufficiency 3 (sufficient evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map DepMap (CRISPR cell-line fitness): dependent in 76.7% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 40)

• Deubiquitination of p53 by HAUSP is an important pathway for p53 stabilization (PMID:11923872)
• analysis of protein interaction domains of the ubiquitin-specific protease, USP7/HAUSP (PMID:14506283)
• HAUSP regulates MDM2 and has a dynamic role in the p53-MDM2 pathway. (PMID:15053880)
• the net deubiquitination of the various targets of HAUSP determines the steady-state level of p53 (PMID:15058298)
• USP7 is an Epstein-Barr virus target [review] (PMID:15494000)
• crystal structure of the p53 binding domain of USP7 alone and bound to an EBNA1 peptide (PMID:15808506)
• Results suggest that impaired deubiquitination of Hdmx/Hdm2 by HAUSP contributes to the DNA damage-induced degradation of Hdmx and transient instability of Hdm2. (PMID:15916963)
• HAUSP regulates apoptosis of cervical adenocarcinoma cells (PMID:15942648)
• ICP0 targets USP7 for ubiquitination and proteasome-dependent degradation; concluded that USP7-mediated stabilization of ICP0 is dominant over ICP0-induced degradation of USP7 during productive HSV-1 infection (PMID:16160161)
• N-terminal domain of USP7 binds two closely spaced 4-residue sites in both p53 and MDM2, falling between p53 residues 359-367 and MDM2 residues 147-159. (PMID:16474402)
• Finding suggests that USP7-mediated deubiquitination of Chfr leads to its accumulation, which might be a key regulatory step for Chfr activation. (PMID:17442268)
• Data suggest that interaction partners might be required for USP7 nuclear import. (PMID:17651432)
• USP7 may have a role not only in transcriptional regulation but also in DNA replication, apoptosis, and possibly endosomal organization (PMID:17927229)
• MARCH7 can be stabilized by both USP9X and USP7, which deubiquitylate MARCH7 in the cytosol and nucleus, respectively (PMID:18410486)
• Our data suggest that changes in HAUSP modulate tumor growth and apoptotic sensitivity in vivo. (PMID:18418047)
• RASSF1A associates with MDM2 and death-domain-associated protein (DAXX) in the nucleus, thereby disrupting the interactions between MDM2, DAXX, and the deubiquitinase, HAUSP, and enhancing the self-ubiquitin ligase activity of MDM2. (PMID:18566590)
• Herpes simplex virus type-1 immediate early protein ICP0 can interact with a previously unidentified isoform of USP7 that is not a predominantly ubiquitinated, SUMO-modified, or phosphorylated but is expressed in a number of different cell types (PMID:18590780)
• results delineate a previously unknown PML-DAXX-HAUSP molecular network controlling PTEN deubiquitinylation and trafficking, which is perturbed by oncogenic cues in human cancer (PMID:18716620)
• PML disruption by EBNA1 requires binding to the cellular ubiquitin specific protease, USP7 or HAUSP, but is independent of p53. (PMID:18833293)
• USP7 is part of a negative feedback loop regulating TLR signaling and that ICP0 exploits this physiologic process to attenuate innate response to HSV. (PMID:18952891)
• USP7 specifically opposes the SCF(betaTrCP)- but not APC(Cdh1)-mediated degradation of Claspin. (PMID:19124652)
• USP7 can stimulate EBNA1-DNA interactions and EBNA1 can alter histone modification at oriP through recruitment of USP7. (PMID:19834552)
• These results reveal Mdm2 and Hausp as important regulators for Daxx functions by controlling Daxx ubiquitination and stability. (PMID:20153724)
• Ablation of either USP7 or USP11 in primary human fibroblasts results in de-repression of the INK4a tumour suppressor accompanied by loss of Polycomb repressive complex 1 binding at the locus and a senescence-like proliferative arrest. (PMID:20601937)
• The authors showed that USP7 N-terminal domain recognized two of six P/AxxS motifs of HdmX ((8)AQCS(11) and (398)AHSS(401)) and also identified an additional interaction site ((397)PSTS(400)) on Hdm2. (PMID:20713061)
• USP7 was identified as a deubiquitinating enzyme that regulates the ubiquitination state of RING1B. (PMID:20800574)
• Importance of p53 regulators in prostate cancer development and progression. (PMID:20855462)
• USP7 regulates the sequence-specific DNA binding mediated by the core domain of p53. (PMID:20885946)
• Studies indicate that the E3’s and DUBs can recognize substrates with the most specificity, and are thus of key interest as drug targets in cancer. (PMID:20930542)
• Data identify TSPYL5 as a suppressor of p53 function through its interaction with USP7. (PMID:21170034)
• These data demonstrate that HAUSP stabilizes REST through deubiquitylation and antagonizes beta-TrCP in regulating REST at the post-translational level. (PMID:21258371)
• Findings suggest that, by balancing Dnmt1 ubiquitination, Usp7 and Uhrf1 fine tune Dnmt1 stability. (PMID:21268065)
• Silencing of USP7 was found to increase the number of PML-NBs, to increase the levels of PML protein and to inhibit PML polyubiquitylation in nasopharyngeal carcinoma cells (PMID:21305000)
• Data show that following a period of 2 weeks storage at -80 degrees C, a clear decrease in USP7 activity was noted. (PMID:21468692)
• Studies indicate that USP7 inhibitors hold promise as a new strategy for the treatment of disease. (PMID:21468693)
• Studies indicate that DUBs recycle ubiquitin by processing polyubiquitin chains to generate free ubiquitin, and can be regulated by ubiquitination or phosphorylation. (PMID:21480003)
• Deubiquitylases (such as HAUSP) may play critical roles to stabilize stem cell transcription factors and promote maintenance of “stemness”. (PMID:21490432)
• results delineate a previously unknown USP7-HLTF-PCNA molecular network controlling DNA damage response (PMID:21845734)
• analysis of USP7/HAUSP activation by its C-terminal ubiquitin-like domain and allosteric regulation by GMP-synthetase (PMID:21981925)
• ATM-dependent downregulation of USP7/HAUSP by PPM1G activates p53 response to DNA damage (PMID:22361354)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	usp7	ENSDARG00000073710
mus_musculus	Usp7	ENSMUSG00000022710
rattus_norvegicus	Usp7	ENSRNOG00000025496
drosophila_melanogaster	Usp7	FBGN0030366

Paralogs (71): USP2 (ENSG00000036672), USP28 (ENSG00000048028), USP36 (ENSG00000055483), USP13 (ENSG00000058056), USP33 (ENSG00000077254), USP40 (ENSG00000085982), USP48 (ENSG00000090686), USP14 (ENSG00000101557), USP11 (ENSG00000102226), USP10 (ENSG00000103194), USP31 (ENSG00000103404), USP42 (ENSG00000106346), USP5 (ENSG00000111667), USP4 (ENSG00000114316), USP9Y (ENSG00000114374), USP34 (ENSG00000115464), USP35 (ENSG00000118369), USP45 (ENSG00000123552), USP22 (ENSG00000124422), USP9X (ENSG00000124486), USP6 (ENSG00000129204), USP29 (ENSG00000131864), USP26 (ENSG00000134588), USP30 (ENSG00000135093), USP15 (ENSG00000135655), USP37 (ENSG00000135913), USP44 (ENSG00000136014), USP20 (ENSG00000136878), USP8 (ENSG00000138592), USP3 (ENSG00000140455), USP21 (ENSG00000143258), USP43 (ENSG00000154914), USP25 (ENSG00000155313), USP16 (ENSG00000156256), USP24 (ENSG00000162402), USP1 (ENSG00000162607), USP49 (ENSG00000164663), USP38 (ENSG00000170185), USP50 (ENSG00000170236), USP47 (ENSG00000170242)

Protein

Protein identifiers

Ubiquitin carboxyl-terminal hydrolase 7 — Q93009 (reviewed: Q93009)

Alternative names: Deubiquitinating enzyme 7, Herpesvirus-associated ubiquitin-specific protease, Ubiquitin thioesterase 7, Ubiquitin-specific-processing protease 7

All UniProt accessions (12): A0A669KBL1, Q93009, F5H2X1, H3BMF6, H3BND8, H3BQD1, H3BRA2, H3BRI4, H3BTM1, H3BUV0, H3BVA7, I3L2D8

UniProt curated annotations — full annotation on UniProt →

Function. Hydrolase that deubiquitinates target proteins such as ARMC5, FOXO4, DEPTOR, KAT5, p53/TP53, MDM2, ERCC6, DNMT1, UHRF1, PTEN, KMT2E/MLL5 and DAXX. Together with DAXX, prevents MDM2 self-ubiquitination and enhances the E3 ligase activity of MDM2 towards p53/TP53, thereby promoting p53/TP53 ubiquitination and proteasomal degradation. Deubiquitinates p53/TP53, preventing degradation of p53/TP53, and enhances p53/TP53-dependent transcription regulation, cell growth repression and apoptosis. Deubiquitinates p53/TP53 and MDM2 and strongly stabilizes p53/TP53 even in the presence of excess MDM2, and also induces p53/TP53-dependent cell growth repression and apoptosis. Deubiquitination of FOXO4 in presence of hydrogen peroxide is not dependent on p53/TP53 and inhibits FOXO4-induced transcriptional activity. In association with DAXX, is involved in the deubiquitination and translocation of PTEN from the nucleus to the cytoplasm, both processes that are counteracted by PML. Deubiquitinates KMT2E/MLL5 preventing KMT2E/MLL5 proteasomal-mediated degradation. Involved in cell proliferation during early embryonic development. Involved in transcription-coupled nucleotide excision repair (TC-NER) in response to UV damage: recruited to DNA damage sites following interaction with KIAA1530/UVSSA and promotes deubiquitination of ERCC6, preventing UV-induced degradation of ERCC6. Involved in maintenance of DNA methylation via its interaction with UHRF1 and DNMT1: acts by mediating deubiquitination of UHRF1 and DNMT1, preventing their degradation and promoting DNA methylation by DNMT1. Deubiquitinates alkylation repair enzyme ALKBH3. OTUD4 recruits USP7 and USP9X to stabilize ALKBH3, thereby promoting the repair of alkylated DNA lesions. Acts as a chromatin regulator via its association with the Polycomb group (PcG) multiprotein PRC1-like complex; may act by deubiquitinating components of the PRC1-like complex. Able to mediate deubiquitination of histone H2B; it is however unsure whether this activity takes place in vivo. Exhibits a preference towards ‘Lys-48’-linked ubiquitin chains. Increases regulatory T-cells (Treg) suppressive capacity by deubiquitinating and stabilizing the transcription factor FOXP3 which is crucial for Treg cell function. Plays a role in the maintenance of the circadian clock periodicity via deubiquitination and stabilization of the CRY1 and CRY2 proteins. Deubiquitinates REST, thereby stabilizing REST and promoting the maintenance of neural progenitor cells. Deubiquitinates SIRT7, inhibiting SIRT7 histone deacetylase activity and regulating gluconeogenesis. Involved in the regulation of WASH-dependent actin polymerization at the surface of endosomes and the regulation of endosomal protein recycling. It maintains optimal WASH complex activity and precise F-actin levels via deubiquitination of TRIM27 and WASHC1. Mediates the deubiquitination of phosphorylated DEPTOR, promoting its stability and leading to decreased mTORC1 signaling. (Microbial infection) Contributes to the overall stabilization and trans-activation capability of the herpesvirus 1 trans-acting transcriptional protein ICP0/VMW110 during HSV-1 infection. (Microbial infection) Upon infection with Epstein-Barr virus, the interaction with viral EBNA1 increases the association of USP7 with PML proteins, which is required for the polyubiquitylation and degradation of PML.

Subunit / interactions. Monomer. Homodimer. Part of a complex with DAXX, MDM2, RASSF1 and USP7. Part of a complex with DAXX, MDM2 and USP7. Interacts with MDM2; the interaction is independent of p53/TP53. Interacts with DAXX; the interaction is direct and independent of MDM2 and p53/TP53. Component of a complex composed of KMT2E/MLL5 (isoform 3), OGT (isoform 1) and USP7; the complex stabilizes KMT2E/MLL5, preventing KMT2E/MLL5 ubiquitination and proteasomal-mediated degradation. Interacts (via MATH domain) with KMT2E/MLL5 isoform 3. Interacts with OGT isoform 1. Interacts with FOXO4; the interaction is enhanced in presence of hydrogen peroxide and occurs independently of p53/TP53. Interacts with p53/TP53; the interaction is enhanced in response to DNA damage. Interacts with TSPYL5; this impairs interaction with p53/TP53. Interacts with PTEN; the interaction is direct. Interacts with ATXN1 and the strength of interaction is influenced by the length of the poly-Gln region in ATXN1. A weaker interaction seen with mutants having longer poly-Gln regions. Interacts with KIAA1530/UVSSA. Interacts with ABRAXAS2; the interaction is direct. Identified in a complex with TP53/p53 and ABRAXAS2. Interacts with MEX3C and antagonizes its ability to degrade mRNA. Interacts with DNMT1 and UHRF1. Interacts with FOXP3. Interacts (via MATH domain) with RNF220. Associated component of the Polycomb group (PcG) multiprotein PRC1-like complex. Interacts with EPOP. Interacts with OTUD4 and USP9X; the interaction is direct. Interacts with CRY2. Interacts with REST. Interacts with ERCC6. Part of a complex consisting of USP7, MAGEL2 and TRIM27; directly interacts with MAGEL2; directly interacts with TRIM27. (Microbial infection) Isoform 1 and isoform 2 interact with herpesvirus 1 trans-acting transcriptional protein ICP0/VMW110. Binding to ICP0/VMW110 may modulate the substrate specificity or activity of USP7 to stabilize viral proteins. (Microbial infection) Interacts with Epstein-Barr virus EBNA1; the interaction is independent and simultaneous to EBNA1 interaction with USP7 as well as necessary for PML nuclear bodies disruption by EBNA1. EBNA1, USP7 and CSNK2B form a ternary complex. EBNA1 shows a 10-fold higher affinity than p53/TP53 and can compete with it for USP7 binding. (Microbial infection) Interacts with human cytomegalovirus proteins UL35 and UL35A; these interactions inhibit the ability of USP7 to form nuclear bodies. (Microbial infection) Interacts with herpes virus 8/HHV-8 proteins vIRF-1 and vIRF-3; these interactions may disrupt TP53 signaling pathway during viral infection by decreasing the availability of USP7 for deubiquitinating and stabilizing TP53. (Microbial infection) Interacts with herpes virus 8/HHV-8 protein vIRF-2; this interaction modulates antiviral signaling via disruption of USP7 interactions with innate immune signaling proteins TRAF3 and TRAF6 thus affecting their ubiquitination.

Subcellular location. Nucleus. Cytoplasm. PML body. Chromosome.

Tissue specificity. Expressed in neural progenitor cells (at protein level). Widely expressed. Overexpressed in prostate cancer.

Post-translational modifications. Isoform 1: Phosphorylated. Isoform 1 is phosphorylated at positions Ser-18 and Ser-963. Isoform 2: Not phosphorylated. Isoform 1: Polyneddylated. Isoform 2: Not Polyneddylated. Isoform 1 and isoform 2: Not sumoylated. Isoform 1 and isoform 2: Polyubiquitinated by herpesvirus 1 trans-acting transcriptional protein ICP0/VMW110; leading to its subsequent proteasomal degradation. Isoform 1: Ubiquitinated at Lys-869.

Disease relevance. Hao-Fountain syndrome (HAFOUS) [MIM:616863] An autosomal dominant neurodevelopmental disorder characterized by global developmental delay, varying degrees of intellectual disability, autism spectrum disorder, poor or absent speech, and mild facial dysmorphism. Most patients develop seizures. Additional variable features include hypotonia, hypogonadism in males, and ocular anomalies. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Inhibited by N-ethyl-maleimide (NEM) and divalent cations. Tolerates high concentrations of NaCl but is inhibited at concentrations of 195 mM and higher.

Domain organisation. The C-terminus plays a role in its oligomerization.

Induction. Up-regulated in regulatory T-cells (Treg). Down-regulated during neural progenitor cell differentiation.

Similarity. Belongs to the peptidase C19 family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q93009-1	1	yes
Q93009-2	2, USP7 beta
Q93009-3	3

RefSeq proteins (4): NP_001273386, NP_001273387, NP_001308787, NP_003461* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001394	Peptidase_C19_UCH	Domain
IPR002083	MATH/TRAF_dom	Domain
IPR008974	TRAF-like	Homologous_superfamily
IPR018200	USP_CS	Conserved_site
IPR024729	USP7_ICP0-binding_dom	Domain
IPR028889	USP	Domain
IPR029346	USP_C	Domain
IPR038765	Papain-like_cys_pep_sf	Homologous_superfamily
IPR050164	Peptidase_C19	Family

Pfam: PF00443, PF12436, PF14533, PF22486

UniProt features (170 total): strand 67, helix 45, turn 15, sequence variant 10, modified residue 6, mutagenesis site 6, region of interest 5, sequence conflict 5, cross-link 3, domain 2, active site 2, compositionally biased region 2, chain 1, splice variant 1

Structure

Experimental structures (PDB)

84 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
4YSI	X-RAY DIFFRACTION	1.02
5KYC	X-RAY DIFFRACTION	1.43
5KYF	X-RAY DIFFRACTION	1.45
2FOJ	X-RAY DIFFRACTION	1.6
2XXN	X-RAY DIFFRACTION	1.6
5KYD	X-RAY DIFFRACTION	1.62
2F1W	X-RAY DIFFRACTION	1.65
1YY6	X-RAY DIFFRACTION	1.7
2F1Y	X-RAY DIFFRACTION	1.7
4KG9	X-RAY DIFFRACTION	1.7
5N9T	X-RAY DIFFRACTION	1.73
9DEM	X-RAY DIFFRACTION	1.77
3MQR	X-RAY DIFFRACTION	1.8
5VSB	X-RAY DIFFRACTION	1.85
4JJQ	X-RAY DIFFRACTION	1.95
5KYE	X-RAY DIFFRACTION	1.97
9SZN	X-RAY DIFFRACTION	1.99
1YZE	X-RAY DIFFRACTION	2
9DEK	X-RAY DIFFRACTION	2
2FOP	X-RAY DIFFRACTION	2.1
7XHH	X-RAY DIFFRACTION	2.1
6F5H	X-RAY DIFFRACTION	2.16
4M5X	X-RAY DIFFRACTION	2.19
2FOO	X-RAY DIFFRACTION	2.2
5KYB	X-RAY DIFFRACTION	2.2
5N9R	X-RAY DIFFRACTION	2.23
5UQX	X-RAY DIFFRACTION	2.23
4M5W	X-RAY DIFFRACTION	2.24
7CM2	X-RAY DIFFRACTION	2.25
6M1K	X-RAY DIFFRACTION	2.25

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q93009-F1	86.50	0.64

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 (2): 223 (nucleophile); 464 (proton acceptor)

Post-translational modifications (9): 18, 49, 869, 963, 1084, 1096, 869, 869, 882

Mutagenesis-validated functional residues (6):

Position	Phenotype
164	decreased binding to p53/tp53 and mdm2.
165	loss of binding to p53/tp53 and mdm2.
223	complete loss of activity. localized in the nucleus and does not inhibit foxo4-dependent transcriptional activity. loss
223	catalytically inactive mutant. no effect on p53/tp53 and pten binding but is defective in deubiquitinating p53/tp53 and
456	complete loss of activity.
464	complete loss of activity.

Function

Pathways and Gene Ontology

Reactome pathways

8 pathways

ID	Pathway
R-HSA-5689880	Ub-specific processing proteases
R-HSA-6781823	Formation of TC-NER Pre-Incision Complex
R-HSA-6781827	Transcription-Coupled Nucleotide Excision Repair (TC-NER)
R-HSA-6782135	Dual incision in TC-NER
R-HSA-6782210	Gap-filling DNA repair synthesis and ligation in TC-NER
R-HSA-6804757	Regulation of TP53 Degradation
R-HSA-8866652	Synthesis of active ubiquitin: roles of E1 and E2 enzymes
R-HSA-8948747	Regulation of PTEN localization

MSigDB gene sets: 417 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_BRAIN_TUMORAL_MACROPHAGE_DN, GSE18804_SPLEEN_MACROPHAGE_VS_TUMORAL_MACROPHAGE_DN, GOBP_CIRCADIAN_RHYTHM, GOBP_CHROMOSOME_ORGANIZATION, GOBP_NEGATIVE_REGULATION_OF_PROTEOLYSIS, GOBP_REGULATION_OF_PROTEASOMAL_UBIQUITIN_DEPENDENT_PROTEIN_CATABOLIC_PROCESS, GOBP_TELOMERE_CAPPING, GOBP_RESPONSE_TO_PEPTIDE, GOBP_TRANSCRIPTION_COUPLED_NUCLEOTIDE_EXCISION_REPAIR, GOBP_ESTABLISHMENT_OF_PROTEIN_LOCALIZATION_TO_CHROMOSOME, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, IVANOVA_HEMATOPOIESIS_MATURE_CELL, GOBP_TELOMERE_ORGANIZATION, MITSIADES_RESPONSE_TO_APLIDIN_DN, GOBP_VESICLE_MEDIATED_TRANSPORT

GO Biological Process (27): transcription-coupled nucleotide-excision repair (GO:0006283), DNA alkylation repair (GO:0006307), proteolysis (GO:0006508), protein ubiquitination (GO:0016567), protein deubiquitination (GO:0016579), regulation of protein stability (GO:0031647), negative regulation of proteasomal ubiquitin-dependent protein catabolic process (GO:0032435), monoubiquitinated protein deubiquitination (GO:0035520), regulation of circadian rhythm (GO:0042752), negative regulation of gene expression via chromosomal CpG island methylation (GO:0044027), negative regulation of gluconeogenesis (GO:0045721), rhythmic process (GO:0048511), protein stabilization (GO:0050821), obsolete regulation of DNA-binding transcription factor activity (GO:0051090), regulation of establishment of protein localization to telomere (GO:0070203), symbiont-mediated disruption of host cell PML body (GO:0075342), regulation of signal transduction by p53 class mediator (GO:1901796), negative regulation of TORC1 signaling (GO:1904262), regulation of telomere capping (GO:1904353), regulation of retrograde transport, endosome to Golgi (GO:1905279), autophagosome assembly (GO:0000045), DNA repair (GO:0006281), DNA damage response (GO:0006974), negative regulation of autophagy (GO:0010507), positive regulation of autophagy (GO:0010508), cellular response to nutrient levels (GO:0031669), TORC1 signaling (GO:0038202)

GO Molecular Function (9): p53 binding (GO:0002039), cysteine-type endopeptidase activity (GO:0004197), cysteine-type deubiquitinase activity (GO:0004843), deubiquitinase activity (GO:0101005), K48-linked deubiquitinase activity (GO:1990380), protein binding (GO:0005515), peptidase activity (GO:0008233), cysteine-type peptidase activity (GO:0008234), hydrolase activity (GO:0016787)

GO Cellular Component (8): nucleus (GO:0005634), nucleoplasm (GO:0005654), chromosome (GO:0005694), cytosol (GO:0005829), nuclear body (GO:0016604), PML body (GO:0016605), protein-containing complex (GO:0032991), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-6 pathways:

Category	Pathways
Transcription-Coupled Nucleotide Excision Repair (TC-NER)	3
Deubiquitination	1
Nucleotide Excision Repair	1
Regulation of TP53 Expression and Degradation	1
Protein ubiquitination	1
PTEN Regulation	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
cysteine-type peptidase activity	2
deubiquitinase activity	2
intracellular membraneless organelle	2
nucleotide-excision repair	1
DNA repair	1
protein metabolic process	1
protein modification by small protein conjugation	1
cysteine-type deubiquitinase activity	1
protein modification by small protein removal	1
regulation of biological quality	1
regulation of proteasomal ubiquitin-dependent protein catabolic process	1
proteasome-mediated ubiquitin-dependent protein catabolic process	1
negative regulation of proteasomal protein catabolic process	1
negative regulation of ubiquitin-dependent protein catabolic process	1
protein deubiquitination	1
circadian rhythm	1
regulation of biological process	1
negative regulation of gene expression, epigenetic	1
gluconeogenesis	1
regulation of gluconeogenesis	1
negative regulation of biosynthetic process	1
negative regulation of carbohydrate metabolic process	1
negative regulation of small molecule metabolic process	1
biological_process	1
regulation of protein stability	1
establishment of protein localization to telomere	1
regulation of establishment of protein localization to chromosome	1
symbiont-mediated disruption of host cellular anatomical structure	1
signal transduction by p53 class mediator	1
regulation of intracellular signal transduction	1
negative regulation of TOR signaling	1
TORC1 signaling	1
regulation of TORC1 signaling	1
telomere capping	1
regulation of telomere maintenance	1
regulation of intracellular transport	1
retrograde transport, endosome to Golgi	1
regulation of vesicle-mediated transport	1
protein binding	1

Protein interactions and networks

STRING

3614 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
USP7	MDM2	Q00987	995
USP7	DAXX	Q9UER7	994
USP7	GMPS	P49915	987
USP7	UVSSA	Q2YD98	981
USP7	TP53	P04637	973
USP7	DNMT1	P26358	920
USP7	UHRF1	Q96T88	918
USP7	MAGEL2	Q9UJ55	905
USP7	TRIM27	P14373	898
USP7	TSPYL5	Q86VY4	867
USP7	HDAC1	Q13547	860
USP7	ZUP1	Q96AP4	837
USP7	SKP1	P34991	829
USP7	USP11	P51784	815
USP7	USP14	P54578	811

IntAct

494 interactions, top by confidence:

A	B	Type	Score
MDM2	USP7	psi-mi:“MI:0915”(physical association)	0.970
USP7	TP53	psi-mi:“MI:0407”(direct interaction)	0.970
USP7	MDM2	psi-mi:“MI:0407”(direct interaction)	0.970
RYBP	BMI1	psi-mi:“MI:0914”(association)	0.850
USP7	EBNA1	psi-mi:“MI:0407”(direct interaction)	0.810
TSEN15	TSEN54	psi-mi:“MI:0914”(association)	0.740

BioGRID (1788): PEPD (Two-hybrid), USP7 (Affinity Capture-Western), TPP1 (Affinity Capture-Western), HUWE1 (Affinity Capture-Western), USP7 (Affinity Capture-MS), FAM175B (Affinity Capture-Western), USP7 (Affinity Capture-Western), USP7 (Affinity Capture-Western), USP7 (Reconstituted Complex), USP7 (Affinity Capture-Western), RNF220 (Affinity Capture-Western), PLA2G2A (Biochemical Activity), USP7 (Affinity Capture-MS), USP7 (Affinity Capture-Western), RB1 (Biochemical Activity)

ESM2 similar proteins: A0AUR5, A8XDJ2, B0WTN3, B2RYG6, B3MCZ5, B3NRC6, B4GDM5, B4HR14, B4JW83, B4KT65, B4LJT9, B4MY75, B4P6M6, B4QFD2, P38747, P52788, P97355, Q05B57, Q0IH43, Q0V9S0, Q17D30, Q17QF2, Q292F0, Q29FC9, Q3SZA5, Q4VSI4, Q567B1, Q5ZJM3, Q6A4J8, Q6IE21, Q6NTW6, Q6NX27, Q6U7I1, Q7JVI3, Q7L8S5, Q7Q068, Q7TQI3, Q7ZV00, Q803R5, Q93009

Diamond homologs: A0A0R4IB93, A0JM59, A1CIL1, A1CW53, A2XDG4, A3AF13, A5PN09, A6QNM7, A7Z056, B1WBD7, B2GUZ1, B8NSV5, D3ZJ96, F6Z5C0, O22207, O60079, O94966, Q0CT11, Q0E2F9, Q0VA64, Q13107, Q2HJE4, Q2UUG8, Q3UJD6, Q3V0C5, Q4VSI4, Q5I043, Q5R5Z6, Q5RCD3, Q5ZM45, Q60MK8, Q6A4J8, Q6J1Y9, Q6PAW2, Q6U7I1, Q6ZQ93, Q70CQ2, Q76LT8, Q7JKC3, Q84WU2

SIGNOR signaling

13 interactions.

A	Effect	B	Mechanism
USP7	up-regulates	MDM2	deubiquitination
USP7	up-regulates	MDM4	deubiquitination
USP7	up-regulates	TP53	deubiquitination
USP7	“up-regulates quantity”	UBA52	cleavage
USP7	“up-regulates quantity”	RPS27A	cleavage
USP7	“up-regulates quantity”	Ubiquitin	cleavage
USP7	“up-regulates quantity by stabilization”	CHFR	deubiquitination
PPM1G	“down-regulates activity”	USP7	dephosphorylation
CSNK2A1	“up-regulates quantity by stabilization”	USP7	phosphorylation
PPM1G	“down-regulates quantity by destabilization”	USP7	dephosphorylation
BCR-ABL	“up-regulates activity”	USP7	phosphorylation
USP7	“down-regulates activity”	PTEN	deubiquitination
USP7	“up-regulates quantity by stabilization”	DEPTOR	deubiquitination

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 207 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
Stabilization of p53	5	27.8×	7e-05
Regulation of TP53 Activity through Methylation	5	19.9×	2e-04
Regulation of TP53 Degradation	7	15.0×	5e-05
Transcriptional Regulation by E2F6	7	15.0×	5e-05
Oncogene Induced Senescence	6	14.7×	2e-04
RHO GTPases activate PKNs	6	13.9×	2e-04
RHOH GTPase cycle	6	13.5×	3e-04
Signaling by CSF1 (M-CSF) in myeloid cells	5	12.6×	1e-03

GO biological processes:

GO term	Partners	Fold	FDR
cellular response to estrogen stimulus	5	26.3×	2e-04
negative regulation of extrinsic apoptotic signaling pathway	6	14.2×	6e-04
T cell costimulation	5	10.5×	7e-03
cellular response to UV	6	10.0×	3e-03
forebrain development	5	9.9×	9e-03
epidermal growth factor receptor signaling pathway	7	9.8×	9e-04
positive regulation of protein ubiquitination	8	9.6×	3e-04
somatic stem cell population maintenance	6	8.3×	6e-03

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: loss-of-function (tumor-suppressor-like) across 2 cancer types — BL, PCM.

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	21
Likely pathogenic	31
Uncertain significance	242
Likely benign	211
Benign	49

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1321986	NM_003470.3(USP7):c.3052C>T (p.Arg1018Ter)	Pathogenic
1713161	NM_003470.3(USP7):c.247_250del (p.Glu83fs)	Pathogenic
1805368	NM_003470.3(USP7):c.701dup (p.Thr235fs)	Pathogenic
224721	NM_003470.3(USP7):c.429C>G (p.Tyr143Ter)	Pathogenic
2256895	NM_003470.3(USP7):c.845C>G (p.Ser282Ter)	Pathogenic
2683752	NM_003470.3(USP7):c.1722del (p.Gln574fs)	Pathogenic
3027370	NM_003470.3(USP7):c.1749del (p.Met583fs)	Pathogenic
3236128	NM_003470.3(USP7):c.3111+1G>A	Pathogenic
3255088	NM_003470.3(USP7):c.1463del (p.Cys488fs)	Pathogenic
3393543	NM_003470.3(USP7):c.523-1G>A	Pathogenic
4085995	NM_003470.3(USP7):c.1079-1_1079delinsTG	Pathogenic
440942	NM_003470.3(USP7):c.675G>A (p.Met225Ile)	Pathogenic
4535166	NM_003470.3(USP7):c.2551_2675del125 (p.Asn851fs)	Pathogenic
4537329	NC_000016.9:g.(9024255_9057063)(9057764?)del	Pathogenic
4685497	NM_003470.3(USP7):c.786_787del (p.Arg262fs)	Pathogenic
4818900	NM_003470.3(USP7):c.383+1G>A	Pathogenic
801403	NM_003470.3(USP7):c.715C>T (p.Arg239Ter)	Pathogenic
871804	NM_003470.3(USP7):c.1522C>T (p.Arg508Ter)	Pathogenic
917892	NM_003470.3(USP7):c.1728T>A (p.Cys576Ter)	Pathogenic
917895	NM_003470.3(USP7):c.3202+1G>T	Pathogenic
992882	NM_003470.3(USP7):c.1794dup (p.Asn599fs)	Pathogenic
1068189	NM_003470.3(USP7):c.352T>C (p.Phe118Leu)	Likely pathogenic
1164067	NM_003470.3(USP7):c.1175G>C (p.Gly392Ala)	Likely pathogenic
1172643	NM_003470.3(USP7):c.1225_1243del (p.Phe409fs)	Likely pathogenic
1299454	NM_003470.3(USP7):c.1033G>A (p.Glu345Lys)	Likely pathogenic
1320052	NM_003470.3(USP7):c.862_863del (p.Leu288fs)	Likely pathogenic
1331543	NM_003470.3(USP7):c.3281T>G (p.Leu1094Arg)	Likely pathogenic
1526154	NM_003470.3(USP7):c.1157T>A (p.Leu386Ter)	Likely pathogenic
1713170	NM_003470.3(USP7):c.992A>G (p.Tyr331Cys)	Likely pathogenic
1713185	NM_003470.3(USP7):c.835T>G (p.Leu279Val)	Likely pathogenic

SpliceAI

4217 predictions. Top by Δscore:

Variant	Effect	Δscore
16:8894543:CCCTT:C	donor_loss	1.0000
16:8894544:CCTTA:C	donor_loss	1.0000
16:8894545:CTTAC:C	donor_loss	1.0000
16:8894546:TTAC:T	donor_loss	1.0000
16:8894547:TA:T	donor_loss	1.0000
16:8894548:A:AC	donor_gain	1.0000
16:8894549:C:CC	donor_gain	1.0000
16:8894549:CCGGG:C	donor_gain	1.0000
16:8894636:TTAAA:T	acceptor_gain	1.0000
16:8894637:TAAA:T	acceptor_gain	1.0000
16:8894638:AAA:A	acceptor_gain	1.0000
16:8894639:AA:A	acceptor_gain	1.0000
16:8894640:ACTAA:A	acceptor_loss	1.0000
16:8894641:C:CC	acceptor_gain	1.0000
16:8894641:CTA:C	acceptor_loss	1.0000
16:8894783:CCTT:C	donor_gain	1.0000
16:8894790:AAACT:A	donor_gain	1.0000
16:8894852:CGCC:C	acceptor_gain	1.0000
16:8894853:GCCC:G	acceptor_loss	1.0000
16:8894854:CC:C	acceptor_gain	1.0000
16:8894855:CC:C	acceptor_gain	1.0000
16:8894855:CCTAG:C	acceptor_loss	1.0000
16:8894856:C:CC	acceptor_gain	1.0000
16:8894856:CTA:C	acceptor_loss	1.0000
16:8894857:T:A	acceptor_loss	1.0000
16:8894861:A:AC	acceptor_gain	1.0000
16:8895025:GCATA:G	donor_loss	1.0000
16:8895026:CATAC:C	donor_loss	1.0000
16:8895027:ATAC:A	donor_loss	1.0000
16:8895028:TA:T	donor_loss	1.0000

AlphaMissense

7438 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:8894008:A:C	I1100S	1.000
16:8894008:A:G	I1100T	1.000
16:8894008:A:T	I1100N	1.000
16:8894014:A:T	I1098N	1.000
16:8894071:A:G	L1079P	1.000
16:8894071:A:T	L1079H	1.000
16:8894074:C:T	G1078E	1.000
16:8894075:C:A	G1078W	1.000
16:8894075:C:G	G1078R	1.000
16:8894075:C:T	G1078R	1.000
16:8894081:A:G	W1076R	1.000
16:8894081:A:T	W1076R	1.000
16:8895053:G:C	P1006R	1.000
16:8895053:G:T	P1006Q	1.000
16:8895059:C:T	G1004E	1.000
16:8895061:G:C	F1003L	1.000
16:8895061:G:T	F1003L	1.000
16:8895063:A:G	F1003L	1.000
16:8895080:T:A	K997I	1.000
16:8895085:G:C	F995L	1.000
16:8895085:G:T	F995L	1.000
16:8895087:A:G	F995L	1.000
16:8895649:C:G	R971P	1.000
16:8897056:A:G	L921P	1.000
16:8897065:A:T	V918D	1.000
16:8898436:A:G	L881P	1.000
16:8898535:T:G	Q879P	1.000
16:8898539:A:C	Y878D	1.000
16:8898544:A:G	L876P	1.000
16:8898580:A:G	L864P	1.000

dbSNP variants (sampled 300 via entrez): RS1000000143 (16:8956731 C>A,G), RS1000034147 (16:8934856 C>T), RS1000038852 (16:8956529 C>T), RS1000047668 (16:8920742 G>A), RS1000072500 (16:8923776 C>A,T), RS1000091043 (16:8923963 C>A,T), RS1000091704 (16:8952012 C>T), RS1000092667 (16:8893155 C>A,T), RS1000108743 (16:8951906 T>G), RS1000152812 (16:8925546 G>GAGTAC), RS1000155543 (16:8964291 C>T), RS1000176636 (16:8910604 A>G), RS1000223481 (16:8939300 A>G), RS1000234495 (16:8935136 C>G), RS1000237539 (16:8909219 G>T)

Disease associations

OMIM: gene MIM:602519 | disease phenotypes: MIM:616863

GenCC curated gene-disease

Disease	Classification	Inheritance
Hao-Fountain syndrome	Definitive	Autosomal dominant
Hao-Fountain syndrome due to USP7 mutation	Strong	Autosomal dominant

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
Hao-Fountain syndrome	Definitive	AD

Mondo (4): Hao-Fountain syndrome (MONDO:0014805), intellectual disability (MONDO:0001071), neurodevelopmental disorder (MONDO:0700092), Hao-Fountain syndrome due to USP7 mutation (MONDO:0958071)

Orphanet (3): Hao-Fountain syndrome (Orphanet:643549), Hao-Fountain syndrome due to USP7 mutation (Orphanet:643538), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

66 total (30 of 66 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000028	Cryptorchidism
HP:0000054	Micropenis
HP:0000135	Hypogonadism
HP:0000238	Hydrocephalus
HP:0000239	Large fontanelles
HP:0000243	Trigonocephaly
HP:0000248	Brachycephaly
HP:0000252	Microcephaly
HP:0000270	Delayed cranial suture closure
HP:0000365	Hearing impairment
HP:0000369	Low-set ears
HP:0000486	Strabismus
HP:0000545	Myopia
HP:0000565	Esotropia
HP:0000639	Nystagmus
HP:0000718	Aggressive behavior
HP:0000729	Autistic behavior
HP:0000750	Delayed speech and language development
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001252	Hypotonia
HP:0001263	Global developmental delay
HP:0001288	Gait disturbance
HP:0001290	Generalized hypotonia
HP:0001319	Neonatal hypotonia
HP:0001344	Absent speech
HP:0001357	Plagiocephaly
HP:0001371	Flexion contracture
HP:0001385	Hip dysplasia

GWAS associations

9 associations (top):

Study	Trait	p-value
GCST004603_239	Platelet count	5.000000e-09
GCST004616_66	Platelet distribution width	1.000000e-12
GCST007576_153	Chronotype	7.000000e-09
GCST90000025_83	Appendicular lean mass	2.000000e-10
GCST90002388_162	Lymphocyte count	7.000000e-09
GCST90002395_187	Mean platelet volume	8.000000e-16
GCST90002400_169	Plateletcrit	1.000000e-11
GCST90002401_108	Platelet distribution width	3.000000e-38
GCST90002402_178	Platelet count	4.000000e-18

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0004309	platelet count
EFO:0007984	platelet component distribution width
EFO:0008328	chronotype measurement
EFO:0004980	appendicular lean mass
EFO:0004587	lymphocyte count
EFO:0007985	platelet crit

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D065886	Neurodevelopmental Disorders	F03.625

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (3): CHEMBL2157850 (SINGLE PROTEIN), CHEMBL5739549 (PROTEIN-PROTEIN INTERACTION), CHEMBL6066139 (PROTEIN-PROTEIN INTERACTION)

Molecules with ChEMBL bioactivity

5 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 96,314 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL296419	ASTEMIZOLE	4	21,577
CHEMBL809	SERTRALINE	4	51,342
CHEMBL1762621	BARDOXOLONE METHYL	3	1,032
CHEMBL1232461	MOLIBRESIB	2	1,538
CHEMBL169	URSOLIC ACID	2	20,825

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

Binding affinities (BindingDB)

147 measured of 173 human assays (173 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
6-chloro-3-[[1-[(3R)-4,4-difluoro-3-phenylbutanoyl]-4-hydroxypiperidin-4-yl]methyl]-7-[4-[(2S)-1,4-dioxan-2-yl]phenyl]pyrrolo[2,3-d]pyrimidin-4-one	IC50	6 nM	US-20250122223: HETEROCYCLIC COMPOUNDS AS UBIQUITIN SPECIFIC PROTEASE 7 INHIBITORS
6-chloro-3-[[1-[(3R)-4,4-difluoro-3-phenylbutanoyl]-4-hydroxypiperidin-4-yl]methyl]-7-[4-[(3R)-morpholin-3-yl]phenyl]pyrrolo[2,3-d]pyrimidin-4-one	IC50	6 nM	US-20250122223: HETEROCYCLIC COMPOUNDS AS UBIQUITIN SPECIFIC PROTEASE 7 INHIBITORS
6-chloro-3-[[4-hydroxy-1-[(3R)-4,4,4-trifluoro-3-phenylbutanoyl]piperidin-4-yl]methyl]-7-[4-[(3R)-morpholin-3-yl]phenyl]pyrrolo[2,3-d]pyrimidin-4-one	IC50	15 nM	US-20250122223: HETEROCYCLIC COMPOUNDS AS UBIQUITIN SPECIFIC PROTEASE 7 INHIBITORS
6-chloro-3-[[4-hydroxy-1-[(3R)-4,4,4-trifluoro-3-phenylbutanoyl]piperidin-4-yl]methyl]-7-[4-[(3R,6S)-6-methylmorpholin-3-yl]phenyl]pyrrolo[2,3-d]pyrimidin-4-one	IC50	16 nM	US-20250122223: HETEROCYCLIC COMPOUNDS AS UBIQUITIN SPECIFIC PROTEASE 7 INHIBITORS
6-chloro-3-[[4-hydroxy-1-[(3R)-4,4,4-trifluoro-3-phenylbutanoyl]piperidin-4-yl]methyl]-7-[4-[(3S)-morpholin-3-yl]phenyl]pyrrolo[2,3-d]pyrimidin-4-one	IC50	16 nM	US-20250122223: HETEROCYCLIC COMPOUNDS AS UBIQUITIN SPECIFIC PROTEASE 7 INHIBITORS
6-chloro-7-[4-[(3S)-6,6-dimethylmorpholin-3-yl]phenyl]-3-[[4-hydroxy-1-[(3R)-4,4,4-trifluoro-3-phenylbutanoyl]piperidin-4-yl]methyl]pyrrolo[2,3-d]pyrimidin-4-one	IC50	17 nM	US-20250122223: HETEROCYCLIC COMPOUNDS AS UBIQUITIN SPECIFIC PROTEASE 7 INHIBITORS
6-chloro-3-[[4-hydroxy-1-[(3R)-4,4,4-trifluoro-3-phenylbutanoyl]piperidin-4-yl]methyl]-7-[3-methyl-4-[(3S,6R)-6-methylmorpholin-3-yl]phenyl]pyrrolo[2,3-d]pyrimidin-4-one	IC50	18 nM	US-20250122223: HETEROCYCLIC COMPOUNDS AS UBIQUITIN SPECIFIC PROTEASE 7 INHIBITORS
6-chloro-3-[[4-hydroxy-1-(1-methylcyclopropanecarbonyl)piperidin-4-yl]methyl]-7-[3-methyl-4-[(3S)-morpholin-3-yl]phenyl]pyrrolo[2,3-d]pyrimidin-4-one	IC50	18 nM	US-20250122223: HETEROCYCLIC COMPOUNDS AS UBIQUITIN SPECIFIC PROTEASE 7 INHIBITORS
6-chloro-3-[[1-[(1R,2R)-2-(difluoromethyl)-1-methylcyclopropanecarbonyl]-4-hydroxypiperidin-4-yl]methyl]-7-[4-[(3R,6S)-6-methylmorpholin-3-yl]phenyl]pyrrolo[2,3-d]pyrimidin-4-one	IC50	18 nM	US-20250122223: HETEROCYCLIC COMPOUNDS AS UBIQUITIN SPECIFIC PROTEASE 7 INHIBITORS
6-chloro-3-[[4-hydroxy-1-(1-methylcyclopropanecarbonyl)piperidin-4-yl]methyl]-7-[4-[(3S)-morpholin-3-yl]phenyl]pyrrolo[2,3-d]pyrimidin-4-one	IC50	22 nM	US-20250122223: HETEROCYCLIC COMPOUNDS AS UBIQUITIN SPECIFIC PROTEASE 7 INHIBITORS
6-chloro-3-[[4-hydroxy-1-[(3R)-4,4,4-trifluoro-3-phenylbutanoyl]piperidin-4-yl]methyl]-7-[4-[(3S,6R)-6-methylmorpholin-3-yl]phenyl]pyrrolo[2,3-d]pyrimidin-4-one	IC50	28 nM	US-20250122223: HETEROCYCLIC COMPOUNDS AS UBIQUITIN SPECIFIC PROTEASE 7 INHIBITORS
6-chloro-3-[[4-hydroxy-1-[1-methyl-2-(trifluoromethyl)cyclopropanecarbonyl]piperidin-4-yl]methyl]-7-[4-[(3S)-morpholin-3-yl]phenyl]pyrrolo[2,3-d]pyrimidin-4-one	IC50	28 nM	US-20250122223: HETEROCYCLIC COMPOUNDS AS UBIQUITIN SPECIFIC PROTEASE 7 INHIBITORS
6-chloro-3-[[4-hydroxy-1-(1-methylcyclopropanecarbonyl)piperidin-4-yl]methyl]-7-[4-[(6S)-6-methylmorpholin-3-yl]phenyl]pyrrolo[2,3-d]pyrimidin-4-one	IC50	30 nM	US-20250122223: HETEROCYCLIC COMPOUNDS AS UBIQUITIN SPECIFIC PROTEASE 7 INHIBITORS
6-chloro-3-[[1-[(1R,2R)-1,2-dimethylcyclopropanecarbonyl]-4-hydroxypiperidin-4-yl]methyl]-7-[4-[(3R,6S)-6-ethylmorpholin-3-yl]phenyl]pyrrolo[2,3-d]pyrimidin-4-one	IC50	37 nM	US-20250122223: HETEROCYCLIC COMPOUNDS AS UBIQUITIN SPECIFIC PROTEASE 7 INHIBITORS
Structure	IC50	38 nM	US-20250122223: HETEROCYCLIC COMPOUNDS AS UBIQUITIN SPECIFIC PROTEASE 7 INHIBITORS
6-chloro-3-[[1-(4-chlorobenzoyl)-4-hydroxypiperidin-4-yl]methyl]-7-[4-[(3S)-morpholin-3-yl]phenyl]pyrrolo[2,3-d]pyrimidin-4-one	IC50	38 nM	US-20250122223: HETEROCYCLIC COMPOUNDS AS UBIQUITIN SPECIFIC PROTEASE 7 INHIBITORS
6-chloro-3-[[1-(1-cyclopropylcyclopropanecarbonyl)-4-hydroxypiperidin-4-yl]methyl]-7-[4-[(3S)-morpholin-3-yl]phenyl]pyrrolo[2,3-d]pyrimidin-4-one	IC50	39 nM	US-20250122223: HETEROCYCLIC COMPOUNDS AS UBIQUITIN SPECIFIC PROTEASE 7 INHIBITORS
6-chloro-3-[[1-(1-cyclopropylcyclopropanecarbonyl)-4-hydroxypiperidin-4-yl]methyl]-7-[4-[(3R)-morpholin-3-yl]phenyl]pyrrolo[2,3-d]pyrimidin-4-one	IC50	41 nM	US-20250122223: HETEROCYCLIC COMPOUNDS AS UBIQUITIN SPECIFIC PROTEASE 7 INHIBITORS
6-chloro-3-[[4-hydroxy-1-[(1R,2R)-1-methyl-2-(trifluoromethyl)cyclopropanecarbonyl]piperidin-4-yl]methyl]-7-[4-[(3S,6R)-6-methylmorpholin-3-yl]phenyl]pyrrolo[2,3-d]pyrimidin-4-one	IC50	42 nM	US-20250122223: HETEROCYCLIC COMPOUNDS AS UBIQUITIN SPECIFIC PROTEASE 7 INHIBITORS
6-chloro-3-[[4-hydroxy-1-[1-methyl-2-(trifluoromethyl)cyclopropanecarbonyl]piperidin-4-yl]methyl]-7-[4-[(3R)-morpholin-3-yl]phenyl]pyrrolo[2,3-d]pyrimidin-4-one	IC50	45 nM	US-20250122223: HETEROCYCLIC COMPOUNDS AS UBIQUITIN SPECIFIC PROTEASE 7 INHIBITORS
6-chloro-7-[4-[(3R)-6,6-dimethylmorpholin-3-yl]phenyl]-3-[[4-hydroxy-1-(1-methylcyclopropanecarbonyl)piperidin-4-yl]methyl]pyrrolo[2,3-d]pyrimidin-4-one	IC50	45 nM	US-20250122223: HETEROCYCLIC COMPOUNDS AS UBIQUITIN SPECIFIC PROTEASE 7 INHIBITORS
6-chloro-3-[[4-hydroxy-1-(1-methylcyclopropanecarbonyl)piperidin-4-yl]methyl]-7-[4-[(3R,5S)-5-methylmorpholin-3-yl]phenyl]pyrrolo[2,3-d]pyrimidin-4-one	IC50	46 nM	US-20250122223: HETEROCYCLIC COMPOUNDS AS UBIQUITIN SPECIFIC PROTEASE 7 INHIBITORS
Structure	IC50	48 nM	US-20250122223: HETEROCYCLIC COMPOUNDS AS UBIQUITIN SPECIFIC PROTEASE 7 INHIBITORS
6-chloro-3-[[1-(4-chlorobenzoyl)-4-hydroxypiperidin-4-yl]methyl]-7-[4-[(2S,3S)-2-methylmorpholin-3-yl]phenyl]pyrrolo[2,3-d]pyrimidin-4-one	IC50	50 nM	US-20250122223: HETEROCYCLIC COMPOUNDS AS UBIQUITIN SPECIFIC PROTEASE 7 INHIBITORS
6-chloro-3-[[1-(1-cyclopropylcyclopropanecarbonyl)-4-hydroxypiperidin-4-yl]methyl]-7-[4-[(7R)-5-oxa-8-azaspiro[3.5]nonan-7-yl]phenyl]pyrrolo[2,3-d]pyrimidin-4-one	IC50	50 nM	US-20250122223: HETEROCYCLIC COMPOUNDS AS UBIQUITIN SPECIFIC PROTEASE 7 INHIBITORS
6-chloro-3-[[4-hydroxy-1-(1-methylcyclobutanecarbonyl)piperidin-4-yl]methyl]-7-[4-[(3R,6S)-6-methylmorpholin-3-yl]phenyl]pyrrolo[2,3-d]pyrimidin-4-one	IC50	50 nM	US-20250122223: HETEROCYCLIC COMPOUNDS AS UBIQUITIN SPECIFIC PROTEASE 7 INHIBITORS
6-chloro-3-[[1-(4-chlorobenzoyl)-4-hydroxypiperidin-4-yl]methyl]-7-[4-[(3R)-morpholin-3-yl]phenyl]pyrrolo[2,3-d]pyrimidin-4-one	IC50	52 nM	US-20250122223: HETEROCYCLIC COMPOUNDS AS UBIQUITIN SPECIFIC PROTEASE 7 INHIBITORS
structure	IC50	53 nM	US-20250122223: HETEROCYCLIC COMPOUNDS AS UBIQUITIN SPECIFIC PROTEASE 7 INHIBITORS
6-chloro-3-[[4-hydroxy-1-(1-methylcyclopropanecarbonyl)piperidin-4-yl]methyl]-7-[4-[(3R,6S)-6-methylmorpholin-3-yl]phenyl]pyrrolo[2,3-d]pyrimidin-4-one	IC50	57 nM	US-20250122223: HETEROCYCLIC COMPOUNDS AS UBIQUITIN SPECIFIC PROTEASE 7 INHIBITORS
[4-[(Z)-(3-acetamido-4-oxo-2-sulfanylidene-1,3-thiazolidin-5-ylidene)methyl]-2-methoxyphenyl] furan-2-carboxylate	IC50	60 nM	US-12503453: USP7 inhibition
4-chloro-5-(4-methoxyphenoxy)-2-(4-methylphenyl)pyridazin-3-one	IC50	60 nM	US-12503453: USP7 inhibition
tert-butyl 4-[5-chloro-2-(4-methylphenyl)-3-oxopyridazin-4-yl]oxypiperidine-1-carboxylate	IC50	60 nM	US-12503453: USP7 inhibition
4-(4-aminophenoxy)-5-chloro-2-(4-propan-2-ylphenyl)pyridazin-3-one	IC50	60 nM	US-12503453: USP7 inhibition
5-chloro-4-(4-chlorophenoxy)-2-(4-propan-2-ylphenyl)pyridazin-3-one	IC50	60 nM	US-12503453: USP7 inhibition
5-chloro-4-(4-hydroxyphenoxy)-2-phenylpyridazin-3-one	IC50	60 nM	US-12503453: USP7 inhibition
5-chloro-2-(4-fluorophenyl)-4-(4-hydroxyphenoxy)pyridazin-3-one	IC50	60 nM	US-12503453: USP7 inhibition
4-(4-methoxyphenoxy)-2-(4-methylphenyl)-5-thiophen-2-ylpyridazin-3-one	IC50	60 nM	US-12503453: USP7 inhibition
5-chloro-4-(4-methoxyphenoxy)-2-[3-(trifluoromethyl)phenyl]pyridazin-3-one	IC50	60 nM	US-12503453: USP7 inhibition
2-[3,5-bis(trifluoromethyl)phenyl]-5-chloro-4-(4-methoxyphenoxy)pyridazin-3-one	IC50	60 nM	US-12503453: USP7 inhibition
3-[4-chloro-5-(4-methoxyphenoxy)-6-oxopyridazin-1-yl]benzonitrile	IC50	60 nM	US-12503453: USP7 inhibition
[1-[(4-chlorophenyl)methyl]piperidin-2-yl]-[4-(4-nitrophenyl)piperazin-1-yl]methanone	IC50	60 nM	US-12503453: USP7 inhibition
4,5-dichloro-6-methoxy-2-(3-methylphenyl)pyridazin-3-one	IC50	60 nM	US-12503453: USP7 inhibition
3,4-dichloro-1-(4-methylphenyl)pyridin-2-one	IC50	60 nM	US-12503453: USP7 inhibition
5-chloro-4-[2-(3,4-diethoxyphenyl)ethoxy]-2-phenylpyridazin-3-one	IC50	60 nM	US-12503453: USP7 inhibition
4-(4-methoxyphenoxy)-5-methyl-2-phenylpyridazin-3-one	IC50	60 nM	US-12503453: USP7 inhibition
5-(1H-benzimidazol-2-ylsulfanylmethyl)-3-phenyl-1,2-oxazole	IC50	60 nM	US-12503453: USP7 inhibition
1-(4-chlorophenyl)-2-(7H-purin-6-ylsulfanyl)ethanone	IC50	60 nM	US-12503453: USP7 inhibition
ethyl 1-ethyl-6-fluoro-7-morpholin-4-yl-4-oxoquinoline-3-carboxylate	IC50	60 nM	US-12503453: USP7 inhibition
1-[(3-chlorophenyl)methyl]-2-oxo-4-phenylpyridine-3-carbonitrile	IC50	60 nM	US-12503453: USP7 inhibition
N-[2,2,2-trichloro-1-[(4-chlorophenyl)carbamothioylamino]ethyl]furan-2-carboxamide	IC50	60 nM	US-12503453: USP7 inhibition

ChEMBL bioactivities

647 potent at pChembl≥5 of 840 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.80	IC50	0.16	nM	CHEMBL4634092
9.74	IC50	0.18	nM	CHEMBL4640002
9.74	IC50	0.18	nM	CHEMBL4635160
9.59	IC50	0.26	nM	CHEMBL4649132
9.49	IC50	0.32	nM	CHEMBL4638458
9.47	IC50	0.34	nM	CHEMBL5723362
9.42	IC50	0.38	nM	CHEMBL4643330
9.41	IC50	0.39	nM	CHEMBL4640729
9.36	IC50	0.44	nM	CHEMBL4647217
9.11	IC50	0.78	nM	CHEMBL4638998
8.96	IC50	1.1	nM	CHEMBL4648116
8.96	IC50	1.1	nM	CHEMBL4638573
8.92	IC50	1.2	nM	CHEMBL4641569
8.89	IC50	1.3	nM	CHEMBL4643112
8.82	IC50	1.5	nM	CHEMBL4590454
8.82	IC50	1.5	nM	CHEMBL4633860
8.82	IC50	1.5	nM	CHEMBL4648623
8.82	IC50	1.5	nM	CHEMBL4288150
8.82	IC50	1.5	nM	CHEMBL5281187
8.82	IC50	1.5	nM	CHEMBL5558202
8.68	IC50	2.1	nM	CHEMBL4644317
8.62	IC50	2.4	nM	CHEMBL4642862
8.47	IC50	3.4	nM	CHEMBL4640563
8.34	IC50	4.6	nM	CHEMBL4635798
8.22	IC50	6	nM	CHEMBL4288150
8.21	Kd	6.158	nM	CHEMBL3752910
8.21	ED50	6.158	nM	CHEMBL3752910
8.18	IC50	6.6	nM	CHEMBL4638688
8.12	IC50	7.6	nM	CHEMBL5182862
8.10	IC50	8	nM	CHEMBL4632475
8.09	IC50	8.2	nM	CHEMBL5200808
8.05	IC50	9	nM	CHEMBL4646914
7.89	IC50	13	nM	CHEMBL4642308
7.87	IC50	13.39	nM	CHEMBL5723354
7.82	IC50	15.2	nM	CHEMBL5184307
7.74	IC50	18.1	nM	CHEMBL5180062
7.74	IC50	18.3	nM	CHEMBL4288150
7.71	IC50	19.7	nM	CHEMBL4750176
7.71	IC50	19.6	nM	CHEMBL5830425
7.68	IC50	20.9	nM	CHEMBL5171419
7.68	IC50	20.9	nM	CHEMBL4288150
7.66	IC50	22	nM	CHEMBL4283787
7.63	IC50	23.3	nM	CHEMBL5618574
7.62	IC50	24	nM	CHEMBL4290015
7.60	IC50	25	nM	CHEMBL4641488
7.60	EC50	25	nM	CHEMBL4647217
7.58	IC50	26	nM	CHEMBL4642553
7.57	IC50	27	nM	CHEMBL4633562
7.54	IC50	29.1	nM	CHEMBL5181400
7.54	IC50	28.7	nM	CHEMBL6037259

PubChem BioAssay actives

494 with measured affinity, of 987 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
3-[[7-[5-chloro-3-methyl-2-[(3S,4R)-3-methylpiperidin-4-yl]oxyphenyl]thieno[3,2-b]pyridin-2-yl]methyl]-6,6-dimethyl-3-azabicyclo[3.1.0]hexane-2,4-dione	1649101: Inhibition of recombinant full length USP7 (unknown origin) using ubiquintin-rhodamine as substrate preincubated for 30 mins followed by substrate addition measured after 1 hr by fluorescence-based Envision plate reader assay	ic50	0.0002	uM
3-[[7-[5-chloro-3-methyl-2-[[(2R)-morpholin-2-yl]methyl]phenyl]thieno[3,2-b]pyridin-2-yl]methyl]-3-azabicyclo[3.1.0]hexane-2,4-dione	1649101: Inhibition of recombinant full length USP7 (unknown origin) using ubiquintin-rhodamine as substrate preincubated for 30 mins followed by substrate addition measured after 1 hr by fluorescence-based Envision plate reader assay	ic50	0.0002	uM
1-[[7-[(2R)-5-chloro-2-(piperazine-1-carbonyl)-2,3-dihydro-1-benzofuran-7-yl]thieno[3,2-b]pyridin-2-yl]methyl]pyrrolidine-2,5-dione	1649101: Inhibition of recombinant full length USP7 (unknown origin) using ubiquintin-rhodamine as substrate preincubated for 30 mins followed by substrate addition measured after 1 hr by fluorescence-based Envision plate reader assay	ic50	0.0002	uM
3-[[7-[5-chloro-3-methyl-2-[(3S,4R)-3-methylpiperidin-4-yl]oxyphenyl]thieno[3,2-b]pyridin-2-yl]methyl]-1-(2,2,2-trifluoroethyl)pyrimidine-2,4-dione	1649101: Inhibition of recombinant full length USP7 (unknown origin) using ubiquintin-rhodamine as substrate preincubated for 30 mins followed by substrate addition measured after 1 hr by fluorescence-based Envision plate reader assay	ic50	0.0003	uM
1-[[7-[5-chloro-2-[[(2S,6S)-2,6-dimethylpiperazin-1-yl]methyl]-3-methylphenyl]thieno[3,2-b]pyridin-2-yl]methyl]pyrrolidine-2,5-dione	1649101: Inhibition of recombinant full length USP7 (unknown origin) using ubiquintin-rhodamine as substrate preincubated for 30 mins followed by substrate addition measured after 1 hr by fluorescence-based Envision plate reader assay	ic50	0.0003	uM
3-[[7-[5-chloro-3-methyl-2-[[(2R)-morpholin-2-yl]methyl]phenyl]thieno[3,2-b]pyridin-2-yl]methyl]-6,6-dimethyl-3-azabicyclo[3.1.0]hexane-2,4-dione	1649101: Inhibition of recombinant full length USP7 (unknown origin) using ubiquintin-rhodamine as substrate preincubated for 30 mins followed by substrate addition measured after 1 hr by fluorescence-based Envision plate reader assay	ic50	0.0004	uM
3-[[7-[5-chloro-3-methyl-2-[[(2R,6R)-6-methylmorpholin-2-yl]methyl]phenyl]thieno[3,2-b]pyridin-2-yl]methyl]-3-azabicyclo[3.1.0]hexane-2,4-dione	1649101: Inhibition of recombinant full length USP7 (unknown origin) using ubiquintin-rhodamine as substrate preincubated for 30 mins followed by substrate addition measured after 1 hr by fluorescence-based Envision plate reader assay	ic50	0.0004	uM
1-[[7-[(2R)-5-chloro-2-(4,5,6,7-tetrahydro-[1,2]oxazolo[4,3-c]pyridin-3-yl)-2,3-dihydro-1-benzofuran-7-yl]thieno[3,2-b]pyridin-2-yl]methyl]pyrrolidine-2,5-dione	1649101: Inhibition of recombinant full length USP7 (unknown origin) using ubiquintin-rhodamine as substrate preincubated for 30 mins followed by substrate addition measured after 1 hr by fluorescence-based Envision plate reader assay	ic50	0.0004	uM
3-[[7-[5-chloro-3-methyl-2-(piperidin-3-ylamino)phenyl]thieno[3,2-b]pyridin-2-yl]methyl]-6,6-dimethyl-3-azabicyclo[3.1.0]hexane-2,4-dione	1649101: Inhibition of recombinant full length USP7 (unknown origin) using ubiquintin-rhodamine as substrate preincubated for 30 mins followed by substrate addition measured after 1 hr by fluorescence-based Envision plate reader assay	ic50	0.0008	uM
3-[[7-[5-chloro-3-methyl-2-[(3S,4R)-3-methylpiperidin-4-yl]oxyphenyl]thieno[3,2-b]pyridin-2-yl]methyl]-3-azabicyclo[3.1.0]hexane-2,4-dione	1649101: Inhibition of recombinant full length USP7 (unknown origin) using ubiquintin-rhodamine as substrate preincubated for 30 mins followed by substrate addition measured after 1 hr by fluorescence-based Envision plate reader assay	ic50	0.0011	uM
1-[[7-[(2R)-5-chloro-2-(2-methyl-4,5,6,7-tetrahydropyrazolo[4,3-c]pyridin-3-yl)-2,3-dihydro-1-benzofuran-7-yl]thieno[3,2-b]pyridin-2-yl]methyl]pyrrolidine-2,5-dione	1649101: Inhibition of recombinant full length USP7 (unknown origin) using ubiquintin-rhodamine as substrate preincubated for 30 mins followed by substrate addition measured after 1 hr by fluorescence-based Envision plate reader assay	ic50	0.0011	uM
1-[[7-[5-chloro-2-[(3R,4S)-4-fluoropyrrolidin-3-yl]oxy-3-methylphenyl]thieno[3,2-b]pyridin-2-yl]methyl]pyrrolidine-2,5-dione	1649101: Inhibition of recombinant full length USP7 (unknown origin) using ubiquintin-rhodamine as substrate preincubated for 30 mins followed by substrate addition measured after 1 hr by fluorescence-based Envision plate reader assay	ic50	0.0012	uM
3-[[7-[5-chloro-3-methyl-2-(piperidin-3-ylmethyl)phenyl]thieno[3,2-b]pyridin-2-yl]methyl]-6,6-dimethyl-3-azabicyclo[3.1.0]hexane-2,4-dione	1649101: Inhibition of recombinant full length USP7 (unknown origin) using ubiquintin-rhodamine as substrate preincubated for 30 mins followed by substrate addition measured after 1 hr by fluorescence-based Envision plate reader assay	ic50	0.0013	uM
3-[4-(aminomethyl)phenyl]-6-[[4-hydroxy-1-[(3R)-3-phenylbutanoyl]piperidin-4-yl]methyl]-2-methylpyrazolo[4,3-d]pyrimidin-7-one	1930785: Inhibition of human USP7 using Ub-Rho110 as substrate by SPR analysis	ic50	0.0015	uM
1-[[7-[5-chloro-2-[(3-fluoroazetidin-3-yl)methoxy]-3-methylphenyl]thieno[3,2-b]pyridin-2-yl]methyl]pyrrolidine-2,5-dione	1649101: Inhibition of recombinant full length USP7 (unknown origin) using ubiquintin-rhodamine as substrate preincubated for 30 mins followed by substrate addition measured after 1 hr by fluorescence-based Envision plate reader assay	ic50	0.0015	uM
3-[4-(aminomethyl)phenyl]-6-[[4-hydroxy-1-(3-phenylbutanoyl)piperidin-4-yl]methyl]-2-methylpyrazolo[4,3-d]pyrimidin-7-one	2080121: Inhibition of USP7 (unknown origin) using Ub-Rh110 substrate by fluorescence based analysis	ic50	0.0015	uM
3-[[7-[5-chloro-3-methyl-2-[[(2R,3R)-3-methylmorpholin-2-yl]methyl]phenyl]thieno[3,2-b]pyridin-2-yl]methyl]-3-azabicyclo[3.1.0]hexane-2,4-dione	1649101: Inhibition of recombinant full length USP7 (unknown origin) using ubiquintin-rhodamine as substrate preincubated for 30 mins followed by substrate addition measured after 1 hr by fluorescence-based Envision plate reader assay	ic50	0.0015	uM
3-[[4-(aminomethyl)phenyl]methyl]-6-[[4-hydroxy-1-[(3R)-4,4,4-trifluoro-3-phenylbutanoyl]piperidin-4-yl]methyl]-2-methylpyrazolo[4,3-d]pyrimidin-7-one	1558730: Inhibition of USP7 (unknown origin) using Ub-Rh110 substrate	ic50	0.0015	uM
3-[4-(aminomethyl)phenyl]-6-[[4-hydroxy-1-[(3R)-4,4,4-trifluoro-3-phenylbutanoyl]piperidin-4-yl]methyl]-1H-pyrazolo[4,3-d]pyrimidin-7-one	1930801: Inhibition of human USP7 using Ub-Rho110 as substrate by fluorescence based SPR analysis	ic50	0.0015	uM
1-[[7-[5-chloro-3-methyl-2-[(3S,4R)-3-methylpiperidin-4-yl]oxyphenyl]thieno[3,2-b]pyridin-2-yl]methyl]pyrrolidine-2,5-dione	1649101: Inhibition of recombinant full length USP7 (unknown origin) using ubiquintin-rhodamine as substrate preincubated for 30 mins followed by substrate addition measured after 1 hr by fluorescence-based Envision plate reader assay	ic50	0.0021	uM
3-[[7-(5-chloro-3-methyl-2-piperidin-3-yloxyphenyl)thieno[3,2-b]pyridin-2-yl]methyl]-6,6-dimethyl-3-azabicyclo[3.1.0]hexane-2,4-dione	1649101: Inhibition of recombinant full length USP7 (unknown origin) using ubiquintin-rhodamine as substrate preincubated for 30 mins followed by substrate addition measured after 1 hr by fluorescence-based Envision plate reader assay	ic50	0.0024	uM
1-[[7-[2-(3-aminocyclobutyl)oxy-5-chloro-3-methylphenyl]thieno[3,2-b]pyridin-2-yl]methyl]pyrrolidine-2,5-dione	1649101: Inhibition of recombinant full length USP7 (unknown origin) using ubiquintin-rhodamine as substrate preincubated for 30 mins followed by substrate addition measured after 1 hr by fluorescence-based Envision plate reader assay	ic50	0.0034	uM
1-[[7-[5-chloro-3-methyl-2-[(3S)-piperidin-3-yl]oxyphenyl]thieno[3,2-b]pyridin-2-yl]methyl]pyrrolidine-2,5-dione	1649101: Inhibition of recombinant full length USP7 (unknown origin) using ubiquintin-rhodamine as substrate preincubated for 30 mins followed by substrate addition measured after 1 hr by fluorescence-based Envision plate reader assay	ic50	0.0046	uM
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149747: Binding affinity to human USP7 incubated for 45 mins by Kinobead based pull down assay	kd	0.0062	uM
1-[[7-[5-chloro-3-methyl-2-[[(2S)-2-methylpiperazin-1-yl]methyl]phenyl]thieno[3,2-b]pyridin-2-yl]methyl]pyrrolidine-2,5-dione	1649101: Inhibition of recombinant full length USP7 (unknown origin) using ubiquintin-rhodamine as substrate preincubated for 30 mins followed by substrate addition measured after 1 hr by fluorescence-based Envision plate reader assay	ic50	0.0066	uM
6-[[1-[[2-chloro-4-(furan-2-yl)phenyl]methyl]-4-hydroxypiperidin-4-yl]methyl]-2-methyl-3-[4-(methylaminomethyl)phenyl]pyrazolo[4,3-d]pyrimidin-7-one	1897517: Inhibition of full-length USP7 (unknown origin) using ubiquitin-rhodamine 110 as substrate preincubated for 30 mins followed by substrate addition and measured after 2 hrs by microplate spectrophotometer analysis	ic50	0.0076	uM
1-[[7-(5-chloro-3-methyl-2-piperidin-4-yloxyphenyl)thieno[3,2-b]pyridin-2-yl]methyl]pyrrolidine-2,5-dione	1649101: Inhibition of recombinant full length USP7 (unknown origin) using ubiquintin-rhodamine as substrate preincubated for 30 mins followed by substrate addition measured after 1 hr by fluorescence-based Envision plate reader assay	ic50	0.0080	uM
6-[[1-[[2-chloro-4-(furan-2-yl)phenyl]methyl]-4-hydroxypiperidin-4-yl]methyl]-3-[4-[(2-hydroxyethylamino)methyl]phenyl]-2-methylpyrazolo[4,3-d]pyrimidin-7-one;dihydrochloride	1897517: Inhibition of full-length USP7 (unknown origin) using ubiquitin-rhodamine 110 as substrate preincubated for 30 mins followed by substrate addition and measured after 2 hrs by microplate spectrophotometer analysis	ic50	0.0082	uM
[(2R)-5-chloro-7-[2-(1-chloro-2,3-dihydroxypropan-2-yl)thieno[3,2-b]pyridin-7-yl]-2,3-dihydro-1-benzofuran-2-yl]-piperazin-1-ylmethanone	1649101: Inhibition of recombinant full length USP7 (unknown origin) using ubiquintin-rhodamine as substrate preincubated for 30 mins followed by substrate addition measured after 1 hr by fluorescence-based Envision plate reader assay	ic50	0.0090	uM
1-[[7-[(2R)-2-[4-(azetidin-1-ylmethyl)-1,3-oxazol-5-yl]-5-chloro-2,3-dihydro-1-benzofuran-7-yl]thieno[3,2-b]pyridin-2-yl]methyl]pyrrolidine-2,5-dione	1649101: Inhibition of recombinant full length USP7 (unknown origin) using ubiquintin-rhodamine as substrate preincubated for 30 mins followed by substrate addition measured after 1 hr by fluorescence-based Envision plate reader assay	ic50	0.0130	uM
6-[[1-[[2-chloro-4-(furan-2-yl)phenyl]methyl]-4-hydroxypiperidin-4-yl]methyl]-3-[4-(ethylaminomethyl)phenyl]-2-methylpyrazolo[4,3-d]pyrimidin-7-one;dihydrochloride	1897517: Inhibition of full-length USP7 (unknown origin) using ubiquitin-rhodamine 110 as substrate preincubated for 30 mins followed by substrate addition and measured after 2 hrs by microplate spectrophotometer analysis	ic50	0.0152	uM
3-[4-(aminomethyl)phenyl]-6-[[1-[[2-chloro-4-(furan-2-yl)phenyl]methyl]-4-hydroxypiperidin-4-yl]methyl]-2-methylpyrazolo[4,3-d]pyrimidin-7-one;dihydrochloride	1897517: Inhibition of full-length USP7 (unknown origin) using ubiquitin-rhodamine 110 as substrate preincubated for 30 mins followed by substrate addition and measured after 2 hrs by microplate spectrophotometer analysis	ic50	0.0181	uM
3-[4-(aminomethyl)phenyl]-6-[[4-hydroxy-1-[(3R)-3-phenylbutanoyl]piperidin-4-yl]methyl]-2-methylpyrazolo[4,3-d]pyrimidin-7-one;2,2,2-trifluoroacetic acid	1692423: Inhibition of recombinant human N-terminal His6-tagged full length USP7 expressed in baculovirus infected Sf21 cells using monoubiquitinated ubiquitin-rhodamine as substrate incubated for 30 mins followed by Ub-Rho addition and measured after 2 hrs by spectrophotometry	ic50	0.0197	uM
N-[[4-[6-[[1-[[2-chloro-4-(furan-2-yl)phenyl]methyl]-4-hydroxypiperidin-4-yl]methyl]-2-methyl-7-oxopyrazolo[4,3-d]pyrimidin-3-yl]phenyl]methyl]formamide	1897517: Inhibition of full-length USP7 (unknown origin) using ubiquitin-rhodamine 110 as substrate preincubated for 30 mins followed by substrate addition and measured after 2 hrs by microplate spectrophotometer analysis	ic50	0.0209	uM
3-[4-(aminomethyl)phenyl]-6-[[4-hydroxy-1-[(3R)-4,4,4-trifluoro-3-phenylbutanoyl]piperidin-4-yl]methyl]-2-methylpyrazolo[4,3-d]pyrimidin-7-one	1409861: Inhibition of USP7 (unknown origin) by biochemical assay	ic50	0.0220	uM
7-[4-(aminomethyl)phenyl]-3-[[4-hydroxy-1-[(3R)-3-phenylbutanoyl]piperidin-4-yl]methyl]pyrrolo[2,3-d]pyrimidin-4-one	2128997: Inhibition of USP7 (unknown origin) using Ub-AFC as substrate assessed as substrate cleavage preincubated for 15 mins followed by substrate addition and measured after 1 hrs by fluorescence assay	ic50	0.0233	uM
3-(3-aminophenyl)-6-[[4-hydroxy-1-[(3R)-3-phenylbutanoyl]piperidin-4-yl]methyl]-2-methylpyrazolo[4,3-d]pyrimidin-7-one	1409861: Inhibition of USP7 (unknown origin) by biochemical assay	ic50	0.0240	uM
N-[[7-[(2R)-5-chloro-2-(piperazine-1-carbonyl)-2,3-dihydro-1-benzofuran-7-yl]thieno[3,2-b]pyridin-2-yl]methyl]acetamide	1649101: Inhibition of recombinant full length USP7 (unknown origin) using ubiquintin-rhodamine as substrate preincubated for 30 mins followed by substrate addition measured after 1 hr by fluorescence-based Envision plate reader assay	ic50	0.0250	uM
1-[[7-[(2R)-5-chloro-2-(piperazine-1-carbonyl)-2,3-dihydro-1-benzofuran-7-yl]thieno[3,2-b]pyridin-2-yl]methyl]pyrrolidin-2-one	1649101: Inhibition of recombinant full length USP7 (unknown origin) using ubiquintin-rhodamine as substrate preincubated for 30 mins followed by substrate addition measured after 1 hr by fluorescence-based Envision plate reader assay	ic50	0.0260	uM
3-[[7-[(2R)-5-chloro-2-(piperazine-1-carbonyl)-2,3-dihydro-1-benzofuran-7-yl]thieno[3,2-b]pyridin-2-yl]methyl]pyrimidin-4-one	1649101: Inhibition of recombinant full length USP7 (unknown origin) using ubiquintin-rhodamine as substrate preincubated for 30 mins followed by substrate addition measured after 1 hr by fluorescence-based Envision plate reader assay	ic50	0.0270	uM
6-[[1-[[2-chloro-4-(furan-2-yl)phenyl]methyl]-4-hydroxypiperidin-4-yl]methyl]-2-methyl-3-[4-[(propan-2-ylamino)methyl]phenyl]pyrazolo[4,3-d]pyrimidin-7-one;dihydrochloride	1897517: Inhibition of full-length USP7 (unknown origin) using ubiquitin-rhodamine 110 as substrate preincubated for 30 mins followed by substrate addition and measured after 2 hrs by microplate spectrophotometer analysis	ic50	0.0291	uM
6-[[4-hydroxy-1-[(3R)-3-phenylbutanoyl]piperidin-4-yl]methyl]-2-methyl-3-phenylpyrazolo[4,3-d]pyrimidin-7-one	1409861: Inhibition of USP7 (unknown origin) by biochemical assay	ic50	0.0300	uM
3-[6-[[4-hydroxy-1-[(3R)-3-phenylbutanoyl]piperidin-4-yl]methyl]-2-methyl-7-oxopyrazolo[4,3-d]pyrimidin-3-yl]benzamide	1409861: Inhibition of USP7 (unknown origin) by biochemical assay	ic50	0.0300	uM
1-[[7-[5-chloro-3-methyl-2-(piperazin-1-ylmethyl)phenyl]thieno[3,2-b]pyridin-2-yl]methyl]pyrrolidine-2,5-dione	1649101: Inhibition of recombinant full length USP7 (unknown origin) using ubiquintin-rhodamine as substrate preincubated for 30 mins followed by substrate addition measured after 1 hr by fluorescence-based Envision plate reader assay	ic50	0.0320	uM
2-(2,6-dioxopiperidin-3-yl)-4-[11-[[4-[6-[[4-hydroxy-1-[(3R)-3-phenylbutanoyl]piperidin-4-yl]methyl]-2-methyl-7-oxopyrazolo[4,3-d]pyrimidin-3-yl]phenyl]methylamino]undecylamino]isoindole-1,3-dione	1934638: Induction of degradation of USP7 (unknown origin)	ec50	0.0330	uM
6-[[4-hydroxy-1-[(3R)-3-phenylbutanoyl]piperidin-4-yl]methyl]-2-methyl-3-(1H-pyrazol-5-yl)pyrazolo[4,3-d]pyrimidin-7-one	1409861: Inhibition of USP7 (unknown origin) by biochemical assay	ic50	0.0350	uM
3-[4-(aminomethyl)phenyl]-6-[[1-[(2-chloro-4-thiophen-2-ylphenyl)methyl]-4-hydroxypiperidin-4-yl]methyl]-2-methylpyrazolo[4,3-d]pyrimidin-7-one;dihydrochloride	1897517: Inhibition of full-length USP7 (unknown origin) using ubiquitin-rhodamine 110 as substrate preincubated for 30 mins followed by substrate addition and measured after 2 hrs by microplate spectrophotometer analysis	ic50	0.0386	uM
3-(3-hydroxyphenyl)-6-[[4-hydroxy-1-[(3R)-3-phenylbutanoyl]piperidin-4-yl]methyl]-2-methylpyrazolo[4,3-d]pyrimidin-7-one	1409861: Inhibition of USP7 (unknown origin) by biochemical assay	ic50	0.0390	uM
3-[4-(hydroxymethyl)phenyl]-6-[[4-hydroxy-1-[(3R)-3-phenylbutanoyl]piperidin-4-yl]methyl]-2-methylpyrazolo[4,3-d]pyrimidin-7-one	1409861: Inhibition of USP7 (unknown origin) by biochemical assay	ic50	0.0400	uM
methyl 4-[[4-[[3-[4-(aminomethyl)phenyl]-2-methyl-7-oxopyrazolo[4,3-d]pyrimidin-6-yl]methyl]-4-hydroxypiperidin-1-yl]methyl]-3-chlorobenzoate	2080123: Inhibition of USP7 (unknown origin)	ic50	0.0408	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Arsenic	affects cotreatment, decreases reaction, increases ubiquitination, affects binding, decreases activity (+7 more)	3
Valproic Acid	affects expression, decreases expression, increases methylation	3
bisphenol A	decreases expression, decreases methylation	2
benzyloxycarbonylleucyl-leucyl-leucine aldehyde	increases expression, affects reaction, decreases reaction, increases ubiquitination, affects cotreatment (+3 more)	2
Benzo(a)pyrene	affects reaction, decreases ubiquitination, affects cotreatment, increases abundance, increases expression (+3 more)	2
Aflatoxin B1	decreases expression, increases methylation	2
aristolochic acid I	decreases expression	1
FR900359	increases phosphorylation	1
bisphenol F	increases expression	1
TAK-243	decreases sumoylation	1
2,4,6-tribromophenol	decreases expression	1
methylmercuric chloride	decreases expression	1
deoxynivalenol	increases expression	1
trichostatin A	affects expression	1
arsenite	affects binding, decreases reaction	1
sodium arsenite	increases expression, affects reaction, decreases cleavage, decreases ubiquitination, affects cotreatment (+2 more)	1
butyraldehyde	decreases expression	1
tetrabromobisphenol A	decreases expression	1
pinosylvin	increases expression	1
azoxystrobin	decreases expression	1
pyrimidifen	decreases expression	1
bisphenol B	increases expression	1
ABT-737	affects cotreatment, affects reaction, decreases cleavage, increases abundance	1
bisphenol S	affects cotreatment, increases expression	1
jinfukang	decreases expression	1
picoxystrobin	decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Wortmannin	affects cotreatment, decreases reaction, increases abundance, increases expression	1
Sunitinib	increases expression	1
Arsenic Trioxide	increases expression	1

ChEMBL screening assays

268 unique, capped per target: 264 binding, 4 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL2162864	Binding	Inhibition of recombinant USP7 expressed in Sf9 cells by Ub-CHOP reporter assay	Selective Dual Inhibitors of the Cancer-Related Deubiquitylating Proteases USP7 and USP47. — ACS Med Chem Lett
CHEMBL5723298	Functional	Affinity Biochemical interaction: (inhibition of enzyme activity in cleaving fluorogenic ubiquitin-rhodamine substrate) EUB0002755a USP7	Affinity Biochemical Literature for EUbOPEN Chemogenomic Library

Cellosaurus cell lines

10 cell lines: 8 cancer cell line, 2 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B3L2	Abcam HEK293T USP7 KO	Transformed cell line	Female
CVCL_D7J9	Ubigene A-375 USP7 KO	Cancer cell line	Female
CVCL_D9VK	Ubigene HEK293 USP7 KO	Transformed cell line	Female
CVCL_E0SN	Ubigene HeLa USP7 KO	Cancer cell line	Female
CVCL_E1J1	HyCyte A-549 KO-hUSP7	Cancer cell line	Male
CVCL_HD64	DLD-1 USP7(-/-)	Cancer cell line	Male
CVCL_HD98	HCT 116 USP7(+/-)	Cancer cell line	Male
CVCL_HD99	HCT 116 USP7(-/-)	Cancer cell line	Male
CVCL_KU19	HeLa SilenciX USP7	Cancer cell line	Female
CVCL_TX13	HAP1 USP7 (-)	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT05657860	PHASE4	COMPLETED	Guanfacine Extended Release for the Reduction of Aggression and Self-injurious Behavior Associated With Prader-Willi Syndrome
NCT05744479	PHASE4	RECRUITING	Metformin for Antipsychotic-induced Weight Gain in Adults With Intellectual Disability
NCT06107829	PHASE4	WITHDRAWN	Valbenazine Treatment of Tardive Dyskinesia in Adults With Intellectual/Developmental Disabilities
NCT06997198	PHASE4	NOT_YET_RECRUITING	Deutetrabenazine Treatment for Tardive Dyskinesia in Intellectual/Developmental Disabilities
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,
NCT02270736	PHASE3	COMPLETED	Clinical Study to Investigate the Efficacy and Safety of NT 201 Compared to Placebo in the Treatment of Chronic Troublesome Drooling Associated With Neurological Disorders and/or Intellectual Disability
NCT02559102	PHASE3	COMPLETED	Dexmedetomidine Sedation Versus General Anaesthesia for Inguinal Hernia Surgery in Infants
NCT02757079	PHASE3	COMPLETED	Study of the Efficacy and Safety of NPC-15 for Sleep Disorders of Children With Neurodevelopmental Disorders
NCT06915480	PHASE3	RECRUITING	Reducing Missed Appointments
NCT07377032	PHASE3	RECRUITING	TAP-GRIN: Interventional Study on Patients With GRIN-related Neurodevelopmental Disorders
NCT02304302	PHASE2	COMPLETED	Down Syndrome Memantine Follow-up Study
NCT03862950	PHASE2	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome (Met)
NCT04529226	PHASE2	UNKNOWN	Study to Compare Clozapine vs Treatment as Usual in People With Intellectual Disability & Treatment-resistant Psychosis
NCT04821856	PHASE2	COMPLETED	Evaluation of the Effectiveness of Cannabidiol in Treating Severe Behavioural Problems in Children and Adolescents With Intellectual Disability
NCT02909959	PHASE2	COMPLETED	Sulforaphane for the Treatment of Young Men With Autism Spectrum Disorder
NCT06081348	PHASE2	RECRUITING	Sertraline vs. Placebo in the Treatment of Anxiety in Children and AdoLescents With NeurodevelopMental Disorders
NCT06352372	PHASE2	COMPLETED	Safety and Efficacy of tPBM for Epileptiform Activity in Autism
NCT05273320	PHASE1	COMPLETED	Clinical Trial of Nabilone for Aggression in Adults With Intellectual and Developmental Disabilities
NCT05301361	PHASE1	ENROLLING_BY_INVITATION	Sensitivity of the NIH Toolbox to Stimulant Treatment in Intellectual Disabilities
NCT06016764	PHASE1	COMPLETED	Use of MRI and cTBS for Catatonia in Autism
NCT06586827	PHASE1	COMPLETED	Impact of Competency-Based Training and Technical Assistance Employment Outcomes of Individuals With ID/DD
NCT07531940	PHASE1	NOT_YET_RECRUITING	Escalating Doses of Memantine in Down Syndrome (MEDS-123)
NCT00503191	PHASE1	COMPLETED	NeuroModulation Technique Treatment of Autism
NCT04475848	PHASE1	COMPLETED	A Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Food Effect of RO6953958 in Healthy Participants
NCT06300398	PHASE1	COMPLETED	IAMA-6 Oral Dose Study in Healthy Adults
NCT03479476	PHASE2/PHASE3	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome
NCT02616796	PHASE1/PHASE2	COMPLETED	Effects of Social Gaze Training on Brain and Behavior in Fragile X Syndrome
NCT06860672	EARLY_PHASE1	RECRUITING	Clinical Trial of the Dual Vector Base Editor for the Treatment of the CHD3-R1025W Mutation
NCT00597948	Not specified	COMPLETED	Healthy Lifestyles for People With Intellectual Disabilities
NCT01087320	Not specified	RECRUITING	Genome Medical Sequencing for Gene Discovery
NCT01652963	Not specified	UNKNOWN	Picture-based Computerised Assessment and Training of Cognitive Behaviour Therapy Skills
NCT01695395	Not specified	COMPLETED	Mental Health Care Provision for Adults With Intellectual Disability and a Mental Disorder
NCT01867554	Not specified	COMPLETED	Research and Characterization of New Genes Involved in Intellectual Disability
NCT01915381	Not specified	COMPLETED	Improving Adherence Healthy Lifestyle With a Smartphone Application Based on Adults With Intellectual Disabilities
NCT01988623	Not specified	COMPLETED	Pivotal Response Treatment for Individuals With Intellectual Disabilities
NCT02099773	Not specified	COMPLETED	Support Staff-client Interactions With Augmentative and Alternative Communication
NCT02136849	Not specified	COMPLETED	Inter-regional Project of the Great Western Exploration Approach for Exome Molecular Causes Severe Intellectual Disability Isolated or Syndromic
NCT02225041	Not specified	COMPLETED	Sedation Strategy and Cognitive Outcome After Critical Illness in Early Childhood
NCT02414438	Not specified	COMPLETED	Establishing the Clinical Utility of First StepDx PLUS and NextStepDx PLUS Study