WDR48

Summary

WDR48 (WD repeat domain 48, HGNC:30914) is a protein-coding gene on chromosome 3p22.2, encoding WD repeat-containing protein 48 (Q8TAF3). Regulator of deubiquitinating complexes, which acts as a strong activator of USP1, USP12 and USP46. It is a selective cancer dependency (DepMap: 37.1% of cell lines).

The protein encoded by this gene has been shown to interact with ubiquitin specific peptidase 1 (USP1), activating the deubiquitinating activity of USP1 and allowing it to remove the ubiquitin moiety from monoubiquitinated FANCD2. FANCD2 is ubiquitinated in response to DNA damage.

Source: NCBI Gene 57599 — RefSeq curated summary.

At a glance

• Gene–disease (curated): autosomal recessive spastic paraplegia type 60 (Supportive, GenCC)
• GWAS associations: 2
• Clinical variants (ClinVar): 64 total
• Phenotypes (HPO): 9
• Druggable target: yes — 4 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 37.1% of screened cell lines
• MANE Select transcript: NM_020839

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30914
Approved symbol	WDR48
Name	WD repeat domain 48
Location	3p22.2
Locus type	gene with protein product
Status	Approved
Aliases	UAF1, KIAA1449, P80, SPG60, Bun62
Ensembl gene	ENSG00000114742
Ensembl biotype	protein_coding
OMIM	612167
Entrez	57599

Gene structure

Transcript identifiers

Ensembl transcripts: 13 — 5 protein_coding, 4 nonsense_mediated_decay, 4 protein_coding_CDS_not_defined

ENST00000302313, ENST00000413099, ENST00000420940, ENST00000423296, ENST00000433841, ENST00000441361, ENST00000463198, ENST00000466405, ENST00000477197, ENST00000489838, ENST00000881529, ENST00000881530, ENST00000925430

RefSeq mRNA: 7 — MANE Select: NM_020839 NM_001303402, NM_001303403, NM_001346225, NM_001346226, NM_001346227, NM_001346228, NM_020839

CCDS: CCDS33738

Canonical transcript exons

ENST00000302313 — 19 exons

Exon	Start	End
ENSE00001311347	39094648	39096664
ENSE00003458653	39065811	39065889
ENSE00003462328	39078137	39078239
ENSE00003476624	39079711	39079808
ENSE00003497114	39077139	39077213
ENSE00003508317	39089231	39089318
ENSE00003512277	39091625	39091701
ENSE00003520395	39084155	39084262
ENSE00003523109	39052016	39052073
ENSE00003526478	39066548	39066630
ENSE00003533175	39088128	39088233
ENSE00003540503	39069643	39069744
ENSE00003555097	39093874	39094066
ENSE00003560885	39063050	39063190
ENSE00003586116	39068771	39068859
ENSE00003599724	39074726	39074950
ENSE00003651546	39085515	39085610
ENSE00003687037	39084645	39084741
ENSE00003687754	39066746	39066875

Expression profiles

Bgee: expression breadth ubiquitous, 291 present calls, max score 95.33.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 31.9863 / max 735.2328, expressed in 1794 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
36110	31.9863	1794

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ventricular zone	UBERON:0003053	95.33	gold quality
calcaneal tendon	UBERON:0003701	95.27	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	95.22	gold quality
ganglionic eminence	UBERON:0004023	95.12	gold quality
cortical plate	UBERON:0005343	94.82	gold quality
secondary oocyte	CL:0000655	94.19	gold quality
adrenal tissue	UBERON:0018303	93.80	gold quality
corpus callosum	UBERON:0002336	93.65	gold quality
male germ cell	CL:0000015	93.58	gold quality
sperm	CL:0000019	93.50	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	92.78	gold quality
testis	UBERON:0000473	92.53	gold quality
tendon	UBERON:0000043	92.24	gold quality
cranial nerve II	UBERON:0000941	92.08	gold quality
Brodmann (1909) area 23	UBERON:0013554	91.86	gold quality
left testis	UBERON:0004533	91.83	gold quality
embryo	UBERON:0000922	91.76	gold quality
right testis	UBERON:0004534	91.70	gold quality
rectum	UBERON:0001052	91.42	gold quality
bone marrow	UBERON:0002371	91.12	gold quality
smooth muscle tissue	UBERON:0001135	91.03	gold quality
endometrium	UBERON:0001295	91.01	gold quality
olfactory bulb	UBERON:0002264	90.78	silver quality
thyroid gland	UBERON:0002046	90.75	gold quality
body of uterus	UBERON:0009853	90.73	gold quality
left lobe of thyroid gland	UBERON:0001120	90.72	gold quality
right lobe of thyroid gland	UBERON:0001119	90.60	gold quality
mucosa of stomach	UBERON:0001199	90.47	gold quality
primary visual cortex	UBERON:0002436	90.46	gold quality
middle temporal gyrus	UBERON:0002771	90.40	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	8.36
E-MTAB-2983	no	440.98

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): NR1I2

miRNA regulators (miRDB)

118 targeting WDR48, 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-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-4776-3P	100.00	68.73	1340
HSA-MIR-4283	100.00	66.42	2097
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-1-3P	99.93	72.35	1914
HSA-MIR-206	99.93	72.50	1893
HSA-MIR-4778-3P	99.93	70.40	1818
HSA-MIR-218-5P	99.93	72.22	2103
HSA-MIR-381-3P	99.93	71.87	2854
HSA-MIR-300	99.92	71.76	2856
HSA-MIR-613	99.91	71.50	1710
HSA-MIR-3529-3P	99.90	73.55	3045
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-605-3P	99.88	69.22	1833
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-5582-3P	99.86	72.48	4221
HSA-MIR-548AR-3P	99.85	71.26	3889
HSA-MIR-548AZ-3P	99.82	70.56	3549
HSA-MIR-548BC	99.82	70.61	3524

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 37.1% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 20)

• These findings suggest that the interaction of human papillomavirus 11 and 31 E1 proteins with p80 is required for efficient maintenance of the viral episome in undifferentiated keratinocytes. (PMID:18032488)
• two novel multisubunit deubiquitinating enzyme complexes containing USP12 and USP46, respectively. Both complexes contain the UAF1 protein as a bona fide subunit. Interestingly, UAF1 (PMID:19075014)
• WDR20 serves as a stimulatory subunit for preserving and regulating the activity of the subset of the UAF1 x USP12 complexes (PMID:20147737)
• p80 is recruited to the viral origin in an E1- and E2-dependent manner. (PMID:22278251)
• USP1 and UAF1 form a complex in the cytoplasm that subsequently translocates to the nucleus through import mediated by USP1 nuclear localization signals. (PMID:22701671)
• Our findings revealed an intriguing mechanism of regulating USP1 activity that combines phosphorylation of a key serine residue in USP1 and the specific interaction of USP1 with a WD40-repeat protein UAF1 (PMID:23116119)
• our results reveal WDR48 and USP12 as novel PHLPP1 regulators and potential suppressors of tumor cell survival. (PMID:24145035)
• Coimmunoprecipitation experiments indicated that human papillomavirus type 31 E1 assembles into a ternary complex with UAF1 and any one of these three USPs: USP1, USP12 and USP46. (PMID:24850727)
• analysis of the function and regulation of the USP1-UAF1 complex (PMID:26758085)
• UAF1 and WDR20 interact with USP12 at two distinct sites far from its catalytic center, allosterically activating the enzyme. (PMID:27373336)
• USP1-UAF1 complex promotes homologous recombination repair via multiple mechanisms: through FANCD2 deubiquitination, as well as by interacting with RAD51AP1. (PMID:27463890)
• Our results highlight the interfaces essential for regulation of USP12 activity and show a conserved second binding of UAF1 which could be important for regulatory functions independent of USP12 activity. (PMID:27650958)
• There is evidence that USP1/WDR48 complex promotes cancer stem cell conservation and regulation of DNA damage repair. [REVIEW] (PMID:28302046)
• These results outline a novel mechanism for the control of TBK1 activity and suggest USP1-UAF1 complex as a potential target for the prevention of viral diseases. (PMID:29138248)
• In this report, the authors provide evidence that the previously described interaction between the viral E1 helicase and the cellular UAF1-USP1 deubiquitinating enzyme complex is required for the completion of the bidirectional theta replication of the human papilloma virus type 11 genome and the subsequent initiation of the unidirectional replication. (PMID:30890612)
• The DNA-binding activity of USP1-associated factor 1 is required for efficient RAD51-mediated homologous DNA pairing and homology-directed DNA repair. (PMID:32350107)
• ATAD5 suppresses centrosome over-duplication by regulating UAF1 and ID1. (PMID:32594826)
• USP1-WDR48 deubiquitinase complex enhances TGF-beta induced epithelial-mesenchymal transition of TNBC cells via stabilizing TAK1. (PMID:33461373)
• Structural basis of FANCD2 deubiquitination by USP1-UAF1. (PMID:33795880)
• The UAF1-USP1 Deubiquitinase Complex Stabilizes cGAS and Facilitates Antiviral Responses. (PMID:38054892)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	wdr48b	ENSDARG00000038543
		ENSDARG00000102302
danio_rerio	wdr48a	ENSDARG00000102734
mus_musculus	Wdr48	ENSMUSG00000032512
rattus_norvegicus	Wdr48	ENSRNOG00000016942
drosophila_melanogaster	CG9062	FBGN0033607
caenorhabditis_elegans		WBGENE00009441

Protein

Protein identifiers

WD repeat-containing protein 48 — Q8TAF3 (reviewed: Q8TAF3)

Alternative names: USP1-associated factor 1, WD repeat endosomal protein, p80

All UniProt accessions (7): A0A024R2L1, C9JC24, Q8TAF3, F8W6P2, F8W7Q3, F8W7Y5, F8W9K4

UniProt curated annotations — full annotation on UniProt →

Function. Regulator of deubiquitinating complexes, which acts as a strong activator of USP1, USP12 and USP46. Enhances the USP1-mediated deubiquitination of FANCD2; USP1 being almost inactive by itself. Activates deubiquitination by increasing the catalytic turnover without increasing the affinity of deubiquitinating enzymes for the substrate. Also activates deubiquitinating activity of complexes containing USP12. In complex with USP12, acts as a potential tumor suppressor by positively regulating PHLPP1 stability. Docks at the distal end of the USP12 fingers domain and induces a cascade of structural changes leading to the activation of the enzyme. Together with RAD51AP1, promotes DNA repair by stimulating RAD51-mediated homologous recombination. Binds single-stranded DNA (ssDNA) and double-stranded DNA (dsDNA). DNA-binding is required both for USP1-mediated deubiquitination of FANCD2 and stimulation of RAD51-mediated homologous recombination: both WDR48/UAF1 and RAD51AP1 have coordinated role in DNA-binding during these processes. Together with ATAD5 and by regulating USP1 activity, has a role in PCNA-mediated translesion synthesis (TLS) by deubiquitinating monoubiquitinated PCNA. Together with ATAD5, has a role in recruiting RAD51 to stalled forks during replication stress. (Microbial infection) In case of infection by Herpesvirus saimiri, may play a role in vesicular transport or membrane fusion events necessary for transport to lysosomes. Induces lysosomal vesicle formation via interaction with Herpesvirus saimiri tyrosine kinase-interacting protein (TIP). Subsequently, TIP recruits tyrosine-protein kinase LCK, resulting in down-regulation of T-cell antigen receptor TCR. May play a role in generation of enlarged endosomal vesicles via interaction with TIP. In case of infection by papillomavirus HPV11, promotes the maintenance of the viral genome via its interaction with HPV11 helicase E1.

Subunit / interactions. Interacts with USP46. Interacts with USP1. Interacts with USP12. Component of the USP12-WDR20-WDR48 deubiquitinating complex. Component of the USP12-DMWD-WDR48 deubiquitinating complex. Interacts with PHLPP1. Interacts with RAD51AP1; the interaction is direct and promotes formation of a trimeric complex with RAD51 via RAD51AP1. Interacts with ATAD5; the interaction regulates USP1-mediated PCNA deubiquitination. Interacts with RAD51; the interaction is enhanced under replication stress. Interacts with ITCH; the interaction is more efficient when both USP12 and WDR48/UAF1 are involved and may facilitate recruitment of the USP12 deubiquitinating complex to Notch. (Microbial infection) Interacts with papillomavirus HPV11 E1 protein. (Microbial infection) Interacts with Saimiriine herpesvirus TIP protein. (Microbial infection) Interacts with human cytomegalovirus protein UL138. (Microbial infection) Interacts with Epstein-Barr virus protein EBNA3.

Subcellular location. Nucleus. Cytoplasm. Lysosome. Late endosome.

Tissue specificity. Ubiquitous.

Domain organisation. N-terminal WD region interacts with TIP and C-terminal region mediates lysosomal localization. The WD repeats are required for the interaction with deubiquitinating enzymes USP1, USP12 and USP46.

Miscellaneous. Knockdown of WDR48 increases Akt activation.

Similarity. Belongs to the WD repeat WDR48 family.

Isoforms (5)

UniProt ID	Names	Canonical?
Q8TAF3-1	1	yes
Q8TAF3-2	2
Q8TAF3-3	3
Q8TAF3-4	4
Q8TAF3-5	5

RefSeq proteins (7): NP_001290331, NP_001290332, NP_001333154, NP_001333155, NP_001333156, NP_001333157, NP_065890* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001680	WD40_rpt	Repeat
IPR015943	WD40/YVTN_repeat-like_dom_sf	Homologous_superfamily
IPR019775	WD40_repeat_CS	Conserved_site
IPR020472	WD40_PAC1	Repeat
IPR021772	WDR48/Bun107_Ubl	Domain
IPR036322	WD40_repeat_dom_sf	Homologous_superfamily
IPR051246	WDR48	Family

Pfam: PF00400, PF11816

UniProt features (122 total): strand 49, mutagenesis site 23, helix 12, turn 11, repeat 8, splice variant 6, sequence conflict 5, modified residue 4, chain 1, compositionally biased region 1, sequence variant 1, region of interest 1

Structure

Experimental structures (PDB)

19 structures.

PDB	Method	Resolution (Å)
5K1A	X-RAY DIFFRACTION	2.3
5L8E	X-RAY DIFFRACTION	2.3
9DI2	ELECTRON MICROSCOPY	2.6
9DI1	ELECTRON MICROSCOPY	2.7
5L8W	X-RAY DIFFRACTION	2.79
8A9J	ELECTRON MICROSCOPY	2.8
8A9K	ELECTRON MICROSCOPY	2.85
5CVL	X-RAY DIFFRACTION	3
5K1C	X-RAY DIFFRACTION	3
9HNW	ELECTRON MICROSCOPY	3.04
6JLQ	X-RAY DIFFRACTION	3.1
9N9Y	X-RAY DIFFRACTION	3.15
7AY2	X-RAY DIFFRACTION	3.2
5K1B	X-RAY DIFFRACTION	3.3
9EBS	ELECTRON MICROSCOPY	3.3
5CVN	X-RAY DIFFRACTION	3.36
7AY0	X-RAY DIFFRACTION	3.6
7AY1	ELECTRON MICROSCOPY	3.7
5CVO	X-RAY DIFFRACTION	3.88

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8TAF3-F1	89.06	0.75

Functional residue map

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

Post-translational modifications (4): 28, 214, 578, 613

Mutagenesis-validated functional residues (23):

Position	Phenotype
30	in uaf1(3a); impaired dna-binding; when associated with a-50 and a-168. in uaf1(3a); does not affect ability to promote
50	in uaf1(3a); impaired dna-binding; when associated with a-30 and a-168. in uaf1(3a); does not affect ability to promote
77	impaired binding to usp12; when associated with ala-256.
117	in uaf1(11a); impaired dna-binding; when associated with a-30, a-50, a-161, a-168, a-230, a-272, a-274, a-275, a-318 and
119	impaired binding to usp12; when associated with ala-172.
161	in uaf1(11a); impaired dna-binding; when associated with a-30, a-50, a-117, a-168, a-230, a-272, a-274, a-275, a-318 and
168	in uaf1(3a); impaired dna-binding; when associated with a-30 and a-50. in uaf1(3a); does not affect ability to promote u
170	strongly reduces interaction with usp46 and abolishes stimulation of usp46 enzyme activity.
172	impaired binding to usp12; when associated with ala-119.
214	strongly reduces interaction with usp12 or usp46 and abolishes stimulation of their enzyme activity; when associated wit
230	in uaf1(11a); impaired dna-binding; when associated with a-30, a-50, a-117, a-161, a-168, a-272, a-274, a-275, a-318 and
256	strongly reduces interaction with usp12 or usp46 and abolishes stimulation of their enzyme activity; when associated wit
272	in uaf1(11a); impaired dna-binding; when associated with a-30, a-50, a-117, a-161, a-168, a-230, a-274, a-275, a-318 and
272	strongly reduces interaction with usp12 or usp46 and abolishes stimulation of their enzyme activity; when associated wit
274	in uaf1(11a); impaired dna-binding; when associated with a-30, a-50, a-117, a-161, a-168, a-230, a-272, a-275, a-318 and
275	in uaf1(11a); impaired dna-binding; when associated with a-30, a-50, a-117, a-161, a-168, a-230, a-272, a-274, a-318 and
318	in uaf1(11a); impaired dna-binding; when associated with a-30, a-50, a-117, a-161, a-168, a-230, a-272, a-274, a-275 and
363	in uaf1(11a); impaired dna-binding; when associated with a-30, a-50, a-117, a-161, a-168, a-230, a-272, a-274, a-275 and
459	decreased interaction with rad51ap1.
580	impaired binding to phlpp1. defective in stabilizing phlpp1.
595–599	decreased interaction with rad51ap1.
595	does not affect interaction with rad51ap1.
599	does not affect interaction with rad51ap1.

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-110314	Recognition of DNA damage by PCNA-containing replication complex
R-HSA-5689880	Ub-specific processing proteases
R-HSA-6783310	Fanconi Anemia Pathway
R-HSA-9673766	Signaling by cytosolic PDGFRA and PDGFRB fusion proteins

MSigDB gene sets: 246 (showing top): PID_FANCONI_PATHWAY, GSE18804_SPLEEN_MACROPHAGE_VS_BRAIN_TUMORAL_MACROPHAGE_UP, GSE37336_LY6C_POS_VS_NEG_NAIVE_CD4_TCELL_UP, GSE18804_BRAIN_VS_COLON_TUMORAL_MACROPHAGE_UP, GOBP_REGULATION_OF_DOUBLE_STRAND_BREAK_REPAIR, GOBP_SINGLE_FERTILIZATION, AGGAAGC_MIR5163P, GOBP_REGULATION_OF_DNA_RECOMBINATION, GOBP_SKELETAL_SYSTEM_DEVELOPMENT, GOBP_GROWTH, CREBP1_Q2, GOBP_REGULATION_OF_DOUBLE_STRAND_BREAK_REPAIR_VIA_HOMOLOGOUS_RECOMBINATION, GOBP_REGULATION_OF_WNT_SIGNALING_PATHWAY, GOBP_MALE_GAMETE_GENERATION, GOBP_CELL_SURFACE_RECEPTOR_SIGNALING_PATHWAY_VIA_JAK_STAT

GO Biological Process (19): double-strand break repair via homologous recombination (GO:0000724), DNA damage response (GO:0006974), spermatogenesis (GO:0007283), single fertilization (GO:0007338), multicellular organism growth (GO:0035264), skin development (GO:0043588), positive regulation of receptor signaling pathway via JAK-STAT (GO:0046427), embryonic organ development (GO:0048568), skeletal system morphogenesis (GO:0048705), homeostasis of number of cells (GO:0048872), positive regulation of epithelial cell proliferation (GO:0050679), seminiferous tubule development (GO:0072520), regulation of protein monoubiquitination (GO:1902525), positive regulation of double-strand break repair via homologous recombination (GO:1905168), DNA repair (GO:0006281), cell surface receptor signaling pathway via JAK-STAT (GO:0007259), male gonad development (GO:0008584), regulation of macromolecule metabolic process (GO:0060255), regulation of primary metabolic process (GO:0080090)

GO Molecular Function (6): DNA binding (GO:0003677), double-stranded DNA binding (GO:0003690), single-stranded DNA binding (GO:0003697), deubiquitinase activator activity (GO:0035800), ubiquitin binding (GO:0043130), protein binding (GO:0005515)

GO Cellular Component (7): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), lysosome (GO:0005764), late endosome (GO:0005770), cytosol (GO:0005829), endosome (GO:0005768)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
DNA Damage Bypass	1
Deubiquitination	1
DNA Repair	1
Signaling by PDGFR in disease	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
animal organ development	2
regulation of metabolic process	2
DNA binding	2
recombinational repair	1
double-strand break repair	1
cellular response to stress	1
developmental process involved in reproduction	1
male gamete generation	1
fertilization	1
multicellular organismal process	1
developmental growth	1
cell surface receptor signaling pathway via JAK-STAT	1
regulation of receptor signaling pathway via JAK-STAT	1
positive regulation of receptor signaling pathway via STAT	1
embryo development	1
skeletal system development	1
animal organ morphogenesis	1
multicellular organismal-level homeostasis	1
positive regulation of cell population proliferation	1
epithelial cell proliferation	1
regulation of epithelial cell proliferation	1
male gonad development	1
tube development	1
reproductive structure development	1
protein monoubiquitination	1
regulation of protein ubiquitination	1
double-strand break repair via homologous recombination	1
regulation of double-strand break repair via homologous recombination	1
positive regulation of DNA recombination	1
positive regulation of double-strand break repair	1
DNA metabolic process	1
DNA damage response	1
cell surface receptor signaling pathway via STAT	1
gonad development	1
development of primary male sexual characteristics	1
macromolecule metabolic process	1
primary metabolic process	1
nucleic acid binding	1
peptidase activator activity	1

Protein interactions and networks

STRING

1910 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
WDR48	USP1	O94782	998
WDR48	USP12	O75317	990
WDR48	USP46	P62068	985
WDR48	RAD51AP1	Q96B01	969
WDR48	WDR20	Q8TBZ3	959
WDR48	FANCI	Q9NVI1	959
WDR48	ATAD5	Q96QE3	928
WDR48	FANCD2	Q9BXW9	831
WDR48	USP7	Q93009	758
WDR48	ZUP1	Q96AP4	705
WDR48	PHLPP1	O60346	628
WDR48	FANCM	Q8IYD8	618
WDR48	DMWD	Q09019	598
WDR48	UBE2T	Q9NPD8	595
WDR48	FANCL	Q9NW38	595

IntAct

109 interactions, top by confidence:

A	B	Type	Score
STK25	STRN	psi-mi:“MI:0914”(association)	0.900
USP1	WDR48	psi-mi:“MI:0915”(physical association)	0.820
WDR20	USP12	psi-mi:“MI:0914”(association)	0.800
PHLPP2	NHERF1	psi-mi:“MI:0914”(association)	0.760
USP1	PHLPP1	psi-mi:“MI:0914”(association)	0.740
USP46	PHLPP1	psi-mi:“MI:0914”(association)	0.740
VSX1	USP12	psi-mi:“MI:0914”(association)	0.730
CCT2	TXNDC9	psi-mi:“MI:0914”(association)	0.730
WDR20	PHLPP1	psi-mi:“MI:0914”(association)	0.670
KPNA1	TCERG1	psi-mi:“MI:0914”(association)	0.640
WDR20	YWHAH	psi-mi:“MI:0914”(association)	0.640
TSPYL6	USP12	psi-mi:“MI:0914”(association)	0.640
USP12	PHLPP1	psi-mi:“MI:0914”(association)	0.570
PHLPP1	USP12	psi-mi:“MI:0914”(association)	0.570
KSR2	POLR3A	psi-mi:“MI:0914”(association)	0.530
TSPYL6	NME4	psi-mi:“MI:0914”(association)	0.530
WDR48	USP12	psi-mi:“MI:0914”(association)	0.530
KPNB1	POM121C	psi-mi:“MI:0914”(association)	0.530
RABIF	RAB13	psi-mi:“MI:0914”(association)	0.530
RNF19B	PIK3R2	psi-mi:“MI:0914”(association)	0.530
RAD51AP1	USP12	psi-mi:“MI:0914”(association)	0.530
VSX2	USP12	psi-mi:“MI:0914”(association)	0.530

BioGRID (315): USP1 (Affinity Capture-Western), WDR48 (Affinity Capture-Western), WDR48 (Affinity Capture-Western), USP1 (Affinity Capture-MS), USP12 (Affinity Capture-MS), USP46 (Affinity Capture-MS), USP1 (Affinity Capture-Western), USP12 (Affinity Capture-Western), USP46 (Affinity Capture-Western), WDR48 (Affinity Capture-MS), WDR48 (Affinity Capture-MS), WDR48 (Affinity Capture-MS), BASP1 (Co-fractionation), YARS (Co-fractionation), WDR48 (Affinity Capture-Western)

ESM2 similar proteins: A0JP70, A2CEH0, B0X2V9, B3MET8, B3NSK1, B4GIJ0, B4HND9, B4J8H6, B4KRQ4, B4MFM2, B4P7H8, B4QB64, D3ZW91, F6ZT52, O00423, O61585, Q05B17, Q05BC3, Q16MY0, Q1LZ08, Q28I85, Q28YY2, Q2TBP4, Q32PG3, Q4R2Z6, Q4V7Y7, Q4V7Z1, Q4V8C3, Q5F3K4, Q5RAW8, Q5RD06, Q5ZIU8, Q5ZLG9, Q6NVM2, Q6PFM9, Q6PJI9, Q6S7B0, Q7T0P4, Q7ZUV2, Q7ZVF0

Diamond homologs: A1CF18, A6ZPA9, A7RHG8, A8IR43, B0W517, B0XAF3, B3MJV8, B3N534, B3RQN1, B4GT01, B4HWV6, B4JPT9, B4KKN1, B4LS78, B4MU54, B4P116, B4Q9T6, B5DG67, B6K1G6, B6QC06, B7PY76, C4JZS6, C4R6H3, D1ZEM6, D5GBI7, G0SA60, O14021, O35142, O35828, O48847, O54929, O55029, P40066, P41318, P53699, P57737, P61480, Q04305, Q05B17, Q0D0X6

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
WDR48	“up-regulates activity”	USP1	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	36
Likely benign	7
Benign	4

Top pathogenic / likely-pathogenic (0)

SpliceAI

3135 predictions. Top by Δscore:

Variant	Effect	Δscore
3:39063046:TCA:T	acceptor_loss	1.0000
3:39063048:AGGT:A	acceptor_loss	1.0000
3:39063049:G:GA	acceptor_loss	1.0000
3:39065805:TTTCA:T	acceptor_loss	1.0000
3:39065806:TTCA:T	acceptor_loss	1.0000
3:39065807:TCAGC:T	acceptor_loss	1.0000
3:39065808:CA:C	acceptor_loss	1.0000
3:39065809:A:AG	acceptor_gain	1.0000
3:39065810:G:GA	acceptor_loss	1.0000
3:39065810:G:GG	acceptor_gain	1.0000
3:39065810:GCAA:G	acceptor_gain	1.0000
3:39065886:ACAT:A	donor_gain	1.0000
3:39065890:G:GG	donor_gain	1.0000
3:39066543:TCTA:T	acceptor_loss	1.0000
3:39066544:CTAGT:C	acceptor_loss	1.0000
3:39066545:TAG:T	acceptor_loss	1.0000
3:39066546:A:AG	acceptor_gain	1.0000
3:39066546:A:C	acceptor_loss	1.0000
3:39066547:G:GA	acceptor_gain	1.0000
3:39066547:GT:G	acceptor_gain	1.0000
3:39066547:GTA:G	acceptor_gain	1.0000
3:39066547:GTAA:G	acceptor_gain	1.0000
3:39066547:GTAAT:G	acceptor_gain	1.0000
3:39066626:ATAAG:A	donor_loss	1.0000
3:39066627:TAAGG:T	donor_loss	1.0000
3:39066628:AAGGT:A	donor_loss	1.0000
3:39066629:AG:A	donor_loss	1.0000
3:39066630:GGTA:G	donor_loss	1.0000
3:39066631:G:A	donor_loss	1.0000
3:39066632:T:A	donor_loss	1.0000

AlphaMissense

4473 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:39063051:T:A	V17D	1.000
3:39063053:T:C	S18P	1.000
3:39063066:G:C	R22P	1.000
3:39063090:G:C	R30P	1.000
3:39063096:G:A	G32E	1.000
3:39063099:T:A	V33D	1.000
3:39063141:C:A	T47K	1.000
3:39063144:C:A	A48D	1.000
3:39063146:G:C	G49R	1.000
3:39063147:G:A	G49D	1.000
3:39063147:G:T	G49V	1.000
3:39063152:G:C	D51H	1.000
3:39063152:G:T	D51Y	1.000
3:39063153:A:C	D51A	1.000
3:39063153:A:T	D51V	1.000
3:39063162:T:A	I54K	1.000
3:39063162:T:G	I54R	1.000
3:39063165:G:C	R55T	1.000
3:39063165:G:T	R55I	1.000
3:39063166:A:C	R55S	1.000
3:39063166:A:T	R55S	1.000
3:39063170:T:A	W57R	1.000
3:39063170:T:C	W57R	1.000
3:39065838:C:G	H73D	1.000
3:39065839:A:G	H73R	1.000
3:39065840:C:A	H73Q	1.000
3:39065840:C:G	H73Q	1.000
3:39065841:C:G	H74D	1.000
3:39065842:A:G	H74R	1.000
3:39065843:T:A	H74Q	1.000

dbSNP variants (sampled 300 via entrez): RS1000131012 (3:39056705 G>A), RS1000146311 (3:39094824 C>A), RS1000183950 (3:39057044 C>T), RS1000222276 (3:39075935 A>G), RS1000227679 (3:39064581 A>G,T), RS1000271527 (3:39064428 C>T), RS1000401594 (3:39063428 G>A), RS1000449493 (3:39051023 C>T), RS1000541 (3:39069237 A>C), RS1000657176 (3:39082362 A>G), RS1000688624 (3:39063645 A>G), RS1000773014 (3:39082114 C>A,T), RS1000855842 (3:39058896 G>A), RS1000920394 (3:39054447 G>A), RS1000945342 (3:39088979 T>A)

Disease associations

OMIM: gene MIM:612167 | disease phenotypes: MIM:303350

GenCC curated gene-disease

Disease	Classification	Inheritance
autosomal recessive spastic paraplegia type 60	Supportive	Autosomal recessive

Mondo (2): hereditary spastic paraplegia (MONDO:0019064), autosomal recessive spastic paraplegia type 60 (MONDO:0018417)

Orphanet (1): Hereditary spastic paraplegia (Orphanet:685)

HPO phenotypes

9 total (9 of 9 shown, HPO-id order):

HPO	Term
HP:0000639	Nystagmus
HP:0001256	Mild intellectual disability
HP:0001258	Spastic paraplegia
HP:0001288	Gait disturbance
HP:0002061	Lower limb spasticity
HP:0002064	Spastic gait
HP:0002166	Impaired vibration sensation in the lower limbs
HP:0002509	Limb hypertonia
HP:0007002	Motor axonal neuropathy

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST002367_11	Social communication problems	9.000000e-09
GCST009602_88	Metabolic syndrome	4.000000e-08

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0005427	social communication impairment
EFO:0000195	metabolic syndrome

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D015419	Spastic Paraplegia, Hereditary	C10.500.300.820; C10.574.500.495.820; C10.668.829.800.300.820; C16.131.666.300.820; C16.320.400.375.820

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (4): CHEMBL3351203 (SINGLE PROTEIN), CHEMBL3430885 (PROTEIN COMPLEX), CHEMBL5291970 (PROTEIN COMPLEX), CHEMBL5291973 (PROTEIN COMPLEX)

Molecules with ChEMBL bioactivity

4 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 38,892 (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
CHEMBL1423	PIMOZIDE	4	17,310
CHEMBL422	TRIFLUOPERAZINE	4	20,044
CHEMBL6066864	FLUPENTIXOL	3
CHEMBL1232461	MOLIBRESIB	2	1,538

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

Binding affinities (BindingDB)

253 measured of 267 human assays (267 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
2-(4-Chloro-1-isopropyl-1H-pyrazol- 5-yl)-N-(4-(1-methyl-4- (trifluoromethyl)-1H-imidazol-2- yl)benzyl)furo[3,2-d]pyrimidin-4- amine	IC50	0.45 nM	US-20250289799: PYRIMIDINE COMPOUND, METHOD FOR PREPARING SAME, AND PHARMACEUTICAL USE THEREOF
5-Ethynyl-2-(2-isopropylphenyl)-N- (4-(1-methyl-4-(trifluoromethyl)-1H- imidazol-2-yl)benzyl)pyrimidin-4- amine	IC50	0.47 nM	US-20250289799: PYRIMIDINE COMPOUND, METHOD FOR PREPARING SAME, AND PHARMACEUTICAL USE THEREOF
2-(2-Cyclopropylphenyl)-5- methoxy-N-(4-(1-methyl-4- (trifluoromethyl)-1H-imidazol-2- yl)benzyl)pyrimidin-4-amine	IC50	0.8 nM	US-20250289799: PYRIMIDINE COMPOUND, METHOD FOR PREPARING SAME, AND PHARMACEUTICAL USE THEREOF
2-(2-Cyclopropylphenyl)-N-(4-(1- methyl-4-(trifluoromethyl)-1H- imidazol-2-yl)benzyl)furo[3,2- d]pyrimidin-4-amine	IC50	1 nM	US-20250289799: PYRIMIDINE COMPOUND, METHOD FOR PREPARING SAME, AND PHARMACEUTICAL USE THEREOF
4-[[4-[1-methyl-4-(trifluoromethyl)imidazol-2-yl]phenyl]methylamino]-2-(2-propan-2-ylphenyl)pyrimidine-5-carbonitrile	IC50	1.1 nM	US-20250289799: PYRIMIDINE COMPOUND, METHOD FOR PREPARING SAME, AND PHARMACEUTICAL USE THEREOF
5-(Difluoromethoxy)-2-(2- isopropylphenyl)-N-(4-(1-methyl-4- (trifluoromethyl)-1H-imidazol-2- yl)benzyl)pyrimidin-4-amine	IC50	1.1 nM	US-20250289799: PYRIMIDINE COMPOUND, METHOD FOR PREPARING SAME, AND PHARMACEUTICAL USE THEREOF
2-(4-Chloro-1-isopropyl-1H-pyrazol- 5-yl)-5-methoxy-N-(4-(1-methyl-4- (trifluoromethyl)-1H-imidazol-2- yl)benzyl)pyrimidin-4-amine	IC50	1.1 nM	US-20250289799: PYRIMIDINE COMPOUND, METHOD FOR PREPARING SAME, AND PHARMACEUTICAL USE THEREOF
5-methoxy-N-[[4-[1-methyl-4-(trifluoromethyl)imidazol-2-yl]phenyl]methyl]-2-(2-propan-2-ylphenyl)pyrimidin-4-amine	IC50	1.2 nM	US-20250289799: PYRIMIDINE COMPOUND, METHOD FOR PREPARING SAME, AND PHARMACEUTICAL USE THEREOF
5-methoxy-N-[[4-[1-methyl-4-(trifluoromethyl)imidazol-2-yl]cyclohexyl]methyl]-2-(2-propan-2-ylphenyl)pyrimidin-4-amine	IC50	1.2 nM	US-20250289799: PYRIMIDINE COMPOUND, METHOD FOR PREPARING SAME, AND PHARMACEUTICAL USE THEREOF
N-[[4-[1-methyl-4-(trifluoromethyl)imidazol-2-yl]phenyl]methyl]-2-(2-propan-2-ylphenyl)furo[3,2-d]pyrimidin-4-amine	IC50	1.2 nM	US-20250289799: PYRIMIDINE COMPOUND, METHOD FOR PREPARING SAME, AND PHARMACEUTICAL USE THEREOF
2-(4-Chloro-1-isopropyl-1H-pyrazol- 5-yl)-N-(4-(5-methyl-3- (trifluoromethyl)-1H-pyrazol-1- yl)benzyl)furo[3,2-d]pyrimidin-4- amine	IC50	1.2 nM	US-20250289799: PYRIMIDINE COMPOUND, METHOD FOR PREPARING SAME, AND PHARMACEUTICAL USE THEREOF
Methyl 2-(2-(2-isopropylphenyl)-4- ((4-(1-methyl-4-(trifluoromethyl)- 1H-imidazol-2- yl)benzyl)amino)pyrimidin-5- yl)acetate	IC50	1.3 nM	US-20250289799: PYRIMIDINE COMPOUND, METHOD FOR PREPARING SAME, AND PHARMACEUTICAL USE THEREOF
2-(4-cyclopropyl-6-methoxypyrimidin-5-yl)-5-methoxy-N-methyl-N-[[4-[1-methyl-4-(trifluoromethyl)imidazol-2-yl]phenyl]methyl]pyrimidin-4-amine	IC50	1.4 nM	US-20250289799: PYRIMIDINE COMPOUND, METHOD FOR PREPARING SAME, AND PHARMACEUTICAL USE THEREOF
2-(4-Chloro-1-isopropyl-1H-pyrazol- 5-yl)-5-methoxy-N-(4-(5-methyl-3- (trifluoromethyl)-1H-pyrazol-1- yl)benzyl)pyrimidin-4-amine	IC50	1.4 nM	US-20250289799: PYRIMIDINE COMPOUND, METHOD FOR PREPARING SAME, AND PHARMACEUTICAL USE THEREOF
5-Ethynyl-2-(1-isopropyl-4-methyl- 1H-pyrazol-5-yl)-N-(4-(1-methyl-4- (trifluoromethyl)-1H-imidazol-2- yl)benzyl)pyrimidin-4-amine	IC50	1.4 nM	US-20250289799: PYRIMIDINE COMPOUND, METHOD FOR PREPARING SAME, AND PHARMACEUTICAL USE THEREOF
2-(4-cyclopropyl-6-methoxypyrimidin-5-yl)-N-[[4-[1-cyclopropyl-4-(trifluoromethyl)imidazol-2-yl]cuban-1-yl]methyl]-5-methoxypyrimidin-4-amine	IC50	1.4 nM	US-20250289799: PYRIMIDINE COMPOUND, METHOD FOR PREPARING SAME, AND PHARMACEUTICAL USE THEREOF
4’-Cyclopropyl-N-(4-(1-isopropyl-4- (trifluoromethyl)-1H-imidazol-2- yl)benzyl)-5,6’-dimethoxy-N- methyl-[2,5’-bipyrimidin]-4-amine	IC50	1.5 nM	US-20250289799: PYRIMIDINE COMPOUND, METHOD FOR PREPARING SAME, AND PHARMACEUTICAL USE THEREOF
2-(4-chloro-1-propan-2-ylpyrazol-5-yl)-5-methoxy-N-[[1-[1-methyl-4-(trifluoromethyl)imidazol-2-yl]-2-oxabicyclo[2.2.2]octan-4-yl]methyl]pyrimidin-4-amine	IC50	1.6 nM	US-20250289799: PYRIMIDINE COMPOUND, METHOD FOR PREPARING SAME, AND PHARMACEUTICAL USE THEREOF
2-(2-Isopropylphenyl)-N-(3- methoxy-4-(1-methyl-4- (trifluoromethyl)-1H-imidazol-2- yl)benzyl)furo[3,2-d]pyrimidin-4- amine	IC50	1.7 nM	US-20250289799: PYRIMIDINE COMPOUND, METHOD FOR PREPARING SAME, AND PHARMACEUTICAL USE THEREOF
2-(2-(Dimethylamino)phenyl)-5- methoxy-N-(4-(1-methyl-4- (trifluoromethyl)-1H-imidazol-2- yl)benzyl)pyrimidin-4-amine	IC50	1.7 nM	US-20250289799: PYRIMIDINE COMPOUND, METHOD FOR PREPARING SAME, AND PHARMACEUTICAL USE THEREOF
8-[[4-[1-methyl-4-(trifluoromethyl)imidazol-2-yl]cyclohexyl]methyl]-2-(2-propan-2-ylphenyl)-6,7-dihydropyrimido[5,4-b][1,4]oxazine	IC50	1.9 nM	US-20250289799: PYRIMIDINE COMPOUND, METHOD FOR PREPARING SAME, AND PHARMACEUTICAL USE THEREOF
2-(2-Isopropylphenyl)-5-methoxy-N- methyl-N-((1-(1-methyl-4- (trifluoromethyl)-1H-imidazol-2- yl)piperidin-4-yl)methyl)pyrimidin- 4-amine	IC50	2.1 nM	US-20250289799: PYRIMIDINE COMPOUND, METHOD FOR PREPARING SAME, AND PHARMACEUTICAL USE THEREOF
2-(2-Isopropylphenyl)-5-methoxy-N- ((1-(1-methyl-4-(trifluoromethyl)- 1H-imidazol-2-yl)piperidin-4- yl)methyl)pyrimidin-4-amine	IC50	2.1 nM	US-20250289799: PYRIMIDINE COMPOUND, METHOD FOR PREPARING SAME, AND PHARMACEUTICAL USE THEREOF
2-(2-Isopropylpyridin-3-yl)-5- methoxy-N-(4-(5-methyl-3- (trifluoromethyl)-1H-pyrazol-1- yl)benzyl)pyrimidin-4-amine	IC50	2.1 nM	US-20250289799: PYRIMIDINE COMPOUND, METHOD FOR PREPARING SAME, AND PHARMACEUTICAL USE THEREOF
2-(4-Chloro-1-isopropyl-1H-pyrazol- 5-yl)-N-(4-(pyridin-2- yl)benzyl)furo[3,2-d]pyrimidin-4- amine	IC50	2.1 nM	US-20250289799: PYRIMIDINE COMPOUND, METHOD FOR PREPARING SAME, AND PHARMACEUTICAL USE THEREOF
2-(2-Cyclopropylpyridin-3-yl)-5- (difluoromethoxy)-N-(4-(1-methyl- 4-(trifluoromethyl)-1H-imidazol-2- yl)benzyl)pyrimidin-4-amine	IC50	2.2 nM	US-20250289799: PYRIMIDINE COMPOUND, METHOD FOR PREPARING SAME, AND PHARMACEUTICAL USE THEREOF
2-(4-cyclopropyl-6-methoxypyrimidin-5-yl)-5-methoxy-N-[[4-[1-methyl-4-(trifluoromethyl)imidazol-2-yl]cuban-1-yl]methyl]pyrimidin-4-amine	IC50	2.2 nM	US-20250289799: PYRIMIDINE COMPOUND, METHOD FOR PREPARING SAME, AND PHARMACEUTICAL USE THEREOF
N-[[4-[1-methyl-4-(trifluoromethyl)imidazol-2-yl]phenyl]methyl]-2-(2-propan-2-ylphenyl)pyrido[3,2-d]pyrimidin-4-amine	IC50	2.3 nM	US-20250289799: PYRIMIDINE COMPOUND, METHOD FOR PREPARING SAME, AND PHARMACEUTICAL USE THEREOF
2-(4-Chloro-1-isopropyl-1H-pyrazol- 5-yl)-5-methoxy-N-((1-(1-methyl-4- (trifluoromethyl)-1H-imidazol-2- yl)piperidin-4-yl)methyl)pyrimidin- 4-amine	IC50	2.3 nM	US-20250289799: PYRIMIDINE COMPOUND, METHOD FOR PREPARING SAME, AND PHARMACEUTICAL USE THEREOF
2-(2-Cyclopropylphenyl)-5- methoxy-N-(2-methoxy-4-(1- methyl-4-(trifluoromethyl)-1H- imidazol-2-yl)benzyl)pyrimidin-4- amine	IC50	2.3 nM	US-20250289799: PYRIMIDINE COMPOUND, METHOD FOR PREPARING SAME, AND PHARMACEUTICAL USE THEREOF
4’-Cyclopropyl-N-(4-(1-cyclopropyl- 4-(trifluoromethyl)-1H-imidazol-2- yl)benzyl)-5-fluoro-6’-methoxy-N- (methyl-d3)-[2,5’-bipyrimidin]-4- amine	IC50	2.6 nM	US-20250289799: PYRIMIDINE COMPOUND, METHOD FOR PREPARING SAME, AND PHARMACEUTICAL USE THEREOF
5-methoxy-N-methyl-N-[[4-[1-methyl-4-(trifluoromethyl)imidazol-2-yl]phenyl]methyl]-2-(2-propan-2-ylphenyl)pyrimidin-4-amine	IC50	2.8 nM	US-20250289799: PYRIMIDINE COMPOUND, METHOD FOR PREPARING SAME, AND PHARMACEUTICAL USE THEREOF
2-(2-propan-2-ylphenyl)-N-[(4-pyridin-2-ylphenyl)methyl]furo[3,2-d]pyrimidin-4-amine	IC50	2.8 nM	US-20250289799: PYRIMIDINE COMPOUND, METHOD FOR PREPARING SAME, AND PHARMACEUTICAL USE THEREOF
4-[[4-[1-methyl-4-(trifluoromethyl)imidazol-2-yl]phenyl]methylamino]-2-(2-propan-2-ylphenyl)pyrimidine-5-carbonitrile	IC50	2.8 nM	US-20250289799: PYRIMIDINE COMPOUND, METHOD FOR PREPARING SAME, AND PHARMACEUTICAL USE THEREOF
2-(1-Isopropyl-4-methyl-1H- pyrazol-5-yl)-5-methoxy-N-methyl- N-(4-(1-methyl-4-(trifluoromethyl)- 1H-imidazol-2-yl)benzyl)pyrimidin- 4-amine	IC50	2.8 nM	US-20250289799: PYRIMIDINE COMPOUND, METHOD FOR PREPARING SAME, AND PHARMACEUTICAL USE THEREOF
4’-Cyclopropyl-N-(4-(1-isopropyl-4- (trifluoromethyl)-1H-imidazol-2- yl)benzyl)-5,6’-dimethoxy-[2,5’- bipyrimidin]-4-amine	IC50	2.9 nM	US-20250289799: PYRIMIDINE COMPOUND, METHOD FOR PREPARING SAME, AND PHARMACEUTICAL USE THEREOF
2-(2-Isopropylpyridin-3-yl)-5- methoxy-N-(4-(1-methyl-4- (trifluoromethyl)-1H-imidazol-2- yl)benzyl)pyrimidin-4-amine	IC50	2.9 nM	US-20250289799: PYRIMIDINE COMPOUND, METHOD FOR PREPARING SAME, AND PHARMACEUTICAL USE THEREOF
2-(2-Cyclopropylphenyl)-5- methoxy-N-(4-(5-methyl-3- (trifluoromethyl)-1H-pyrazol-1- yl)benzyl)pyrimidin-4-amine	IC50	2.9 nM	US-20250289799: PYRIMIDINE COMPOUND, METHOD FOR PREPARING SAME, AND PHARMACEUTICAL USE THEREOF
2-(1-Isopropyl-4-methyl-1H- pyrazol-5-yl)-5-methoxy-N-(4-(1- methyl-4-(trifluoromethyl)-1H- imidazol-2-yl)benzyl)pyrimidin-4- amine	IC50	3 nM	US-20250289799: PYRIMIDINE COMPOUND, METHOD FOR PREPARING SAME, AND PHARMACEUTICAL USE THEREOF
5-Chloro-4’-cyclopropyl-N-(4-(1- cyclopropyl-4-(trifluoromethyl)-1H- imidazol-2-yl)benzyl)-6’-methoxy- [2,5’-bipyrimidin]-4-amine	IC50	3.1 nM	US-20250289799: PYRIMIDINE COMPOUND, METHOD FOR PREPARING SAME, AND PHARMACEUTICAL USE THEREOF
N-(4-(2-Ethoxyethoxy)benzyl)-2-(2- isopropylphenyl)-5- methoxypyrimidin-4-amine	IC50	3.2 nM	US-20250289799: PYRIMIDINE COMPOUND, METHOD FOR PREPARING SAME, AND PHARMACEUTICAL USE THEREOF
4’-Cyclopropyl-5-(difluoromethoxy)- 6’-methoxy-N-(4-(1-methyl-4- (trifluoromethyl)-1H-imidazol-2- yl)benzyl)-[2,5’-bipyrimidin]-4- amine	IC50	3.2 nM	US-20250289799: PYRIMIDINE COMPOUND, METHOD FOR PREPARING SAME, AND PHARMACEUTICAL USE THEREOF
4’-Cyclopropyl-5-(difluoromethoxy)- 6’-methoxy-N-(4-(5-methyl-3- (trifluoromethyl)-1H-pyrazol-1- yl)benzyl)-[2,5’-bipyrimidin]-4- amine	IC50	3.2 nM	US-20250289799: PYRIMIDINE COMPOUND, METHOD FOR PREPARING SAME, AND PHARMACEUTICAL USE THEREOF
2-(1-Cyclopropyl-4-methyl-1H- pyrazol-5-yl)-5-methoxy-N-methyl- N-(4-(1-methyl-4-(trifluoromethyl)- 1H-imidazol-2-yl)benzyl)pyrimidin- 4-amine	IC50	3.2 nM	US-20250289799: PYRIMIDINE COMPOUND, METHOD FOR PREPARING SAME, AND PHARMACEUTICAL USE THEREOF
2-(2-Isopropylphenyl)-5-methoxy-N- ((4-(pyridin-2- yl)cyclohexyl)methyl)pyrimidin-4- amine	IC50	3.3 nM	US-20250289799: PYRIMIDINE COMPOUND, METHOD FOR PREPARING SAME, AND PHARMACEUTICAL USE THEREOF
4’-Cyclopropyl-5,6’-dimethoxy-N- methyl-N-((1-(1-methyl-4- (trifluoromethyl)-1H-imidazol-2- yl)piperidin-4-yl)methyl)-[2,5’- bipyrimidin]-4-amine	IC50	3.3 nM	US-20250289799: PYRIMIDINE COMPOUND, METHOD FOR PREPARING SAME, AND PHARMACEUTICAL USE THEREOF
2-(2-Cyclopropylpyridin-3-yl)-5- methoxy-N-(4-(1-methyl-4- (trifluoromethyl)-1H-imidazol-2- yl)benzyl)pyrimidin-4-amine	IC50	3.4 nM	US-20250289799: PYRIMIDINE COMPOUND, METHOD FOR PREPARING SAME, AND PHARMACEUTICAL USE THEREOF
[2-(4-cyclopropyl-6-methoxypyrimidin-5-yl)-5-methoxypyrimidin-4-yl]-[[4-[1-methyl-4-(trifluoromethyl)imidazol-2-yl]phenyl]methyl]cyanamide	IC50	3.5 nM	US-20250289799: PYRIMIDINE COMPOUND, METHOD FOR PREPARING SAME, AND PHARMACEUTICAL USE THEREOF
2-(4-cyclopropyl-6-methoxypyrimidin-5-yl)-5-methoxy-N-methyl-N-[[4-[1-methyl-4-(trifluoromethyl)imidazol-2-yl]cuban-1-yl]methyl]pyrimidin-4-amine	IC50	3.5 nM	US-20250289799: PYRIMIDINE COMPOUND, METHOD FOR PREPARING SAME, AND PHARMACEUTICAL USE THEREOF
5-Isopropoxy-2-(2-isopropylphenyl)- N-(4-(1-methyl-4-(trifluoromethyl)- 1H-imidazol-2-yl)benzyl)pyrimidin- 4-amine	IC50	3.6 nM	US-20250289799: PYRIMIDINE COMPOUND, METHOD FOR PREPARING SAME, AND PHARMACEUTICAL USE THEREOF

ChEMBL bioactivities

187 potent at pChembl≥5 of 196 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.64	IC50	2.3	nM	CHEMBL6167416
8.42	IC50	3.8	nM	CHEMBL6169078
8.15	IC50	7.1	nM	CHEMBL5593758
8.15	Ki	7	nM	CHEMBL5595820
8.06	IC50	8.8	nM	CHEMBL5595820
7.95	IC50	11.2	nM	CHEMBL5593526
7.88	IC50	13.1	nM	CHEMBL5583831
7.85	IC50	14.2	nM	CHEMBL6145929
7.79	IC50	16.1	nM	CHEMBL5592698
7.77	IC50	17	nM	CHEMBL3182437
7.73	IC50	18.8	nM	CHEMBL5594891
7.67	IC50	21.3	nM	KSQ-4279
7.64	IC50	22.8	nM	CHEMBL5595458
7.63	IC50	23.3	nM	CHEMBL5593671
7.52	IC50	30.3	nM	CHEMBL6146416
7.51	Kd	31	nM	MOLIBRESIB
7.47	IC50	33.9	nM	CHEMBL5592420
7.47	IC50	34	nM	CHEMBL5970286
7.46	IC50	34.4	nM	CHEMBL6146209
7.40	IC50	39.8	nM	CHEMBL5592802
7.37	IC50	43	nM	CHEMBL6039837
7.37	IC50	43	nM	CHEMBL3182033
7.32	IC50	48	nM	CHEMBL3181856
7.30	IC50	50	nM	CHEMBL3182033
7.24	IC50	57.5	nM	CHEMBL6147190
7.22	IC50	59.9	nM	CHEMBL5595535
7.21	IC50	61	nM	CHEMBL5820850
7.21	IC50	61	nM	CHEMBL3183916
7.21	IC50	61	nM	CHEMBL3185589
7.17	IC50	68	nM	CHEMBL5802303
7.16	IC50	70	nM	CHEMBL3185589
7.16	IC50	70	nM	CHEMBL3187668
7.16	IC50	68.9	nM	CHEMBL6164325
7.15	IC50	71.3	nM	CHEMBL6150294
7.13	IC50	74.5	nM	CHEMBL6147601
7.12	IC50	76	nM	CHEMBL3182437
7.10	IC50	80	nM	CHEMBL3182908
7.10	IC50	80	nM	CHEMBL3183916
7.10	IC50	80	nM	CHEMBL3181856
7.10	IC50	80	nM	MOLIBRESIB
7.08	IC50	83.9	nM	CHEMBL5594765
7.07	IC50	86	nM	CHEMBL5802443
7.05	IC50	90	nM	CHEMBL3182895
7.00	IC50	100	nM	CHEMBL3356519
6.98	IC50	105	nM	CHEMBL6133089
6.96	IC50	110	nM	CHEMBL3188490
6.96	IC50	110	nM	CHEMBL3181906
6.96	IC50	110	nM	CHEMBL3189120
6.96	IC50	110	nM	CHEMBL6165355
6.93	IC50	118.7	nM	CHEMBL6144924

PubChem BioAssay actives

105 with measured affinity, of 170 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
2-(4-cyclopropyl-6-methoxypyrimidin-5-yl)-8-[[4-[1-propan-2-yl-4-(trifluoromethyl)imidazol-2-yl]phenyl]methyl]pyrido[2,3-d]pyrimidin-7-one	2116480: Inhibition of USP1/UAF1 complex (unknown origin) using Ub-7-amido-4-methylcoumarin as substrate assessed as inhibition constant incubated for 120 mins by Lineweaver-burk plot analysis	ki	0.0070	uM
2-(4-cyclopropyl-6-methoxypyrimidin-5-yl)-8-[[4-[5-methyl-3-(trifluoromethyl)pyrazol-1-yl]phenyl]methyl]pyrido[2,3-d]pyrimidin-7-one	2116468: Inhibition of USP1-UAF1 complex (unknown origin) using Ub-7-amido-4-methylcoumarin as substrate incubated for 2 hrs by fluorescence based analysis	ic50	0.0071	uM
2-(4-cyclopropyl-6-methoxypyrimidin-5-yl)-8-[[4-[1-(cyclopropylmethyl)-4-(trifluoromethyl)imidazol-2-yl]phenyl]methyl]pyrido[2,3-d]pyrimidin-7-one	2116468: Inhibition of USP1-UAF1 complex (unknown origin) using Ub-7-amido-4-methylcoumarin as substrate incubated for 2 hrs by fluorescence based analysis	ic50	0.0112	uM
2-(4-cyclopropyl-6-methoxypyrimidin-5-yl)-8-[[4-[1-ethyl-4-(trifluoromethyl)imidazol-2-yl]phenyl]methyl]pyrido[2,3-d]pyrimidin-7-one	2116468: Inhibition of USP1-UAF1 complex (unknown origin) using Ub-7-amido-4-methylcoumarin as substrate incubated for 2 hrs by fluorescence based analysis	ic50	0.0131	uM
2-(4-cyclopropyl-6-methoxypyrimidin-5-yl)-8-[[4-[1-methyl-4-(trifluoromethyl)imidazol-2-yl]phenyl]methyl]pyrido[2,3-d]pyrimidin-7-one	2116468: Inhibition of USP1-UAF1 complex (unknown origin) using Ub-7-amido-4-methylcoumarin as substrate incubated for 2 hrs by fluorescence based analysis	ic50	0.0161	uM
2-(2,6-dimethoxyphenyl)-8-[[4-[1-propan-2-yl-4-(trifluoromethyl)imidazol-2-yl]phenyl]methyl]pyrido[2,3-d]pyrimidin-7-one	2116468: Inhibition of USP1-UAF1 complex (unknown origin) using Ub-7-amido-4-methylcoumarin as substrate incubated for 2 hrs by fluorescence based analysis	ic50	0.0188	uM
6-(4-cyclopropyl-6-methoxypyrimidin-5-yl)-1-[[4-[1-propan-2-yl-4-(trifluoromethyl)imidazol-2-yl]phenyl]methyl]pyrazolo[3,4-d]pyrimidine	2116468: Inhibition of USP1-UAF1 complex (unknown origin) using Ub-7-amido-4-methylcoumarin as substrate incubated for 2 hrs by fluorescence based analysis	ic50	0.0213	uM
2-(4-cyclopropyl-6-methoxypyrimidin-5-yl)-8-[[3-fluoro-4-[1-propan-2-yl-4-(trifluoromethyl)imidazol-2-yl]phenyl]methyl]pyrido[2,3-d]pyrimidin-7-one	2116468: Inhibition of USP1-UAF1 complex (unknown origin) using Ub-7-amido-4-methylcoumarin as substrate incubated for 2 hrs by fluorescence based analysis	ic50	0.0228	uM
2-(2-fluoro-6-methoxyphenyl)-8-[[4-[1-propan-2-yl-4-(trifluoromethyl)imidazol-2-yl]phenyl]methyl]pyrido[2,3-d]pyrimidin-7-one	2116468: Inhibition of USP1-UAF1 complex (unknown origin) using Ub-7-amido-4-methylcoumarin as substrate incubated for 2 hrs by fluorescence based analysis	ic50	0.0233	uM
2-[(4S)-6-(4-chlorophenyl)-8-methoxy-1-methyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl]-N-ethylacetamide	2179211: Binding affinity against WDR48 (unknown origin) assessed as apparent dissociation constant incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	kd	0.0310	uM
2-(2-propan-2-ylphenyl)-8-[[4-[1-propan-2-yl-4-(trifluoromethyl)imidazol-2-yl]phenyl]methyl]pyrido[2,3-d]pyrimidin-7-one	2116468: Inhibition of USP1-UAF1 complex (unknown origin) using Ub-7-amido-4-methylcoumarin as substrate incubated for 2 hrs by fluorescence based analysis	ic50	0.0339	uM
8-[[4-[1-propan-2-yl-4-(trifluoromethyl)imidazol-2-yl]phenyl]methyl]-2-[2-(trifluoromethoxy)phenyl]pyrido[2,3-d]pyrimidin-7-one	2116468: Inhibition of USP1-UAF1 complex (unknown origin) using Ub-7-amido-4-methylcoumarin as substrate incubated for 2 hrs by fluorescence based analysis	ic50	0.0398	uM
5-methyl-N-[[4-(6-methyl-3-pyridinyl)phenyl]methyl]-2-(2-propan-2-ylphenyl)pyrimidin-4-amine	1164708: Inhibition of human USP1/UAF1 using Ub-AMC substrate by fluorescence assay	ic50	0.0500	uM
2-(4-cyclopropyl-6-methoxypyrimidin-5-yl)-8-[[4-[6-(trifluoromethyl)-2-pyridinyl]phenyl]methyl]pyrido[2,3-d]pyrimidin-7-one	2116468: Inhibition of USP1-UAF1 complex (unknown origin) using Ub-7-amido-4-methylcoumarin as substrate incubated for 2 hrs by fluorescence based analysis	ic50	0.0599	uM
5-methoxy-2-(2-propan-2-ylphenyl)-N-[(4-pyridin-3-ylphenyl)methyl]pyrimidin-4-amine	1164708: Inhibition of human USP1/UAF1 using Ub-AMC substrate by fluorescence assay	ic50	0.0700	uM
5-methyl-2-(2-propan-2-ylphenyl)-N-[(4-pyridin-3-ylphenyl)methyl]pyrimidin-4-amine	1164708: Inhibition of human USP1/UAF1 using Ub-AMC substrate by fluorescence assay	ic50	0.0700	uM
5-methyl-2-(2-propan-2-ylphenyl)-N-[[4-(triazol-1-yl)phenyl]methyl]pyrimidin-4-amine	1164708: Inhibition of human USP1/UAF1 using Ub-AMC substrate by fluorescence assay	ic50	0.0760	uM
N-[[4-(6-fluoro-3-pyridinyl)phenyl]methyl]-5-methyl-2-(2-propan-2-ylphenyl)pyrimidin-4-amine	1164708: Inhibition of human USP1/UAF1 using Ub-AMC substrate by fluorescence assay	ic50	0.0800	uM
5-methyl-2-(2-propan-2-ylphenyl)-N-[(1-pyridin-3-ylpiperidin-4-yl)methyl]pyrimidin-4-amine	1164708: Inhibition of human USP1/UAF1 using Ub-AMC substrate by fluorescence assay	ic50	0.0800	uM
2-(2-propan-2-ylphenyl)-N-[(4-pyridin-3-ylphenyl)methyl]furo[3,2-d]pyrimidin-4-amine	1164708: Inhibition of human USP1/UAF1 using Ub-AMC substrate by fluorescence assay	ic50	0.0800	uM
2-(4-cyclopropyl-6-methoxypyrimidin-5-yl)-8-[1-[4-[1-propan-2-yl-4-(trifluoromethyl)imidazol-2-yl]phenyl]ethyl]pyrido[2,3-d]pyrimidin-7-one	2116468: Inhibition of USP1-UAF1 complex (unknown origin) using Ub-7-amido-4-methylcoumarin as substrate incubated for 2 hrs by fluorescence based analysis	ic50	0.0839	uM
5-methyl-N-[[1-(6-methyl-3-pyridinyl)piperidin-4-yl]methyl]-2-(2-propan-2-ylphenyl)pyrimidin-4-amine	1164708: Inhibition of human USP1/UAF1 using Ub-AMC substrate by fluorescence assay	ic50	0.0900	uM
2-[2-(1,1,1,2,3,3,3-heptadeuteriopropan-2-yl)phenyl]-5-methyl-N-[[4-(triazol-1-yl)phenyl]methyl]pyrimidin-4-amine	1164708: Inhibition of human USP1/UAF1 using Ub-AMC substrate by fluorescence assay	ic50	0.1000	uM
2-(2-propan-2-ylphenyl)-N-[(4-pyridin-3-ylphenyl)methyl]thieno[3,2-d]pyrimidin-4-amine	1164708: Inhibition of human USP1/UAF1 using Ub-AMC substrate by fluorescence assay	ic50	0.1100	uM
5-fluoro-2-(2-propan-2-ylphenyl)-N-[(4-pyridin-3-ylphenyl)methyl]pyrimidin-4-amine	1164708: Inhibition of human USP1/UAF1 using Ub-AMC substrate by fluorescence assay	ic50	0.1100	uM
5-methylsulfanyl-2-(2-propan-2-ylphenyl)-N-[(4-pyridin-3-ylphenyl)methyl]pyrimidin-4-amine	1164708: Inhibition of human USP1/UAF1 using Ub-AMC substrate by fluorescence assay	ic50	0.1100	uM
N-[dideuterio-[4-(triazol-1-yl)phenyl]methyl]-5-methyl-2-(2-propan-2-ylphenyl)pyrimidin-4-amine	1164708: Inhibition of human USP1/UAF1 using Ub-AMC substrate by fluorescence assay	ic50	0.1200	uM
2-(2-propan-2-ylphenyl)-N-[(4-pyridin-3-ylphenyl)methyl]-7H-purin-6-amine	1164708: Inhibition of human USP1/UAF1 using Ub-AMC substrate by fluorescence assay	ic50	0.1200	uM
5,6-dimethyl-2-(2-propan-2-ylphenyl)-N-[(4-pyridin-3-ylphenyl)methyl]pyrimidin-4-amine	1164708: Inhibition of human USP1/UAF1 using Ub-AMC substrate by fluorescence assay	ic50	0.1200	uM
5-methyl-N-[(3-methylphenyl)methyl]-2-(2-propan-2-ylphenyl)pyrimidin-4-amine	1164708: Inhibition of human USP1/UAF1 using Ub-AMC substrate by fluorescence assay	ic50	0.1300	uM
2-[2-(1,1,1,3,3,3-hexadeuteriopropan-2-yl)phenyl]-5-methyl-N-[[4-(triazol-1-yl)phenyl]methyl]pyrimidin-4-amine	1164708: Inhibition of human USP1/UAF1 using Ub-AMC substrate by fluorescence assay	ic50	0.1400	uM
5-methyl-2-(2-propan-2-ylphenyl)-N-[(1-pyrazin-2-ylpiperidin-4-yl)methyl]pyrimidin-4-amine	1164708: Inhibition of human USP1/UAF1 using Ub-AMC substrate by fluorescence assay	ic50	0.1400	uM
2-(2-propan-2-ylphenyl)-N-[(4-pyridin-3-ylphenyl)methyl]pyrimidin-4-amine	1164708: Inhibition of human USP1/UAF1 using Ub-AMC substrate by fluorescence assay	ic50	0.1500	uM
2-(2-propan-2-ylphenyl)-N-[(4-pyridin-3-ylphenyl)methyl]-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-amine	1164708: Inhibition of human USP1/UAF1 using Ub-AMC substrate by fluorescence assay	ic50	0.1600	uM
2-(2-cyclobutylphenyl)-5-methyl-N-[[4-(triazol-1-yl)phenyl]methyl]pyrimidin-4-amine	1164708: Inhibition of human USP1/UAF1 using Ub-AMC substrate by fluorescence assay	ic50	0.1800	uM
2-(2-cyclopropylphenyl)-5-methyl-N-[(4-pyridin-3-ylphenyl)methyl]pyrimidin-4-amine	1164708: Inhibition of human USP1/UAF1 using Ub-AMC substrate by fluorescence assay	ic50	0.1800	uM
2-(2-propan-2-ylphenyl)-N-[(4-pyridin-3-ylphenyl)methyl]quinazolin-4-amine	1164708: Inhibition of human USP1/UAF1 using Ub-AMC substrate by fluorescence assay	ic50	0.1800	uM
N-[dideuterio-[4-(triazol-1-yl)phenyl]methyl]-2-[2-(1,1,1,2,3,3,3-heptadeuteriopropan-2-yl)phenyl]-5-methylpyrimidin-4-amine	1164708: Inhibition of human USP1/UAF1 using Ub-AMC substrate by fluorescence assay	ic50	0.1900	uM
5-N,5-N-dimethyl-2-(2-propan-2-ylphenyl)-4-N-[(4-pyridin-3-ylphenyl)methyl]pyrimidine-4,5-diamine	1164708: Inhibition of human USP1/UAF1 using Ub-AMC substrate by fluorescence assay	ic50	0.1900	uM
8-[[4-[1-propan-2-yl-4-(trifluoromethyl)imidazol-2-yl]phenyl]methyl]-2-[2-(trifluoromethyl)phenyl]pyrido[2,3-d]pyrimidin-7-one	2116468: Inhibition of USP1-UAF1 complex (unknown origin) using Ub-7-amido-4-methylcoumarin as substrate incubated for 2 hrs by fluorescence based analysis	ic50	0.1946	uM
6-methyl-2-(2-propan-2-ylphenyl)-N-[(4-pyridin-3-ylphenyl)methyl]pyrimidin-4-amine	1164708: Inhibition of human USP1/UAF1 using Ub-AMC substrate by fluorescence assay	ic50	0.2100	uM
2-(4-cyclopropyl-6-methoxypyrimidin-5-yl)-8-[[2,6-difluoro-4-[1-propan-2-yl-4-(trifluoromethyl)imidazol-2-yl]phenyl]methyl]pyrido[2,3-d]pyrimidin-7-one	2116468: Inhibition of USP1-UAF1 complex (unknown origin) using Ub-7-amido-4-methylcoumarin as substrate incubated for 2 hrs by fluorescence based analysis	ic50	0.2457	uM
2-(4-cyclopropyl-6-methoxypyrimidin-5-yl)-8-[(4-pyridin-2-ylphenyl)methyl]pyrido[2,3-d]pyrimidin-7-one	2116468: Inhibition of USP1-UAF1 complex (unknown origin) using Ub-7-amido-4-methylcoumarin as substrate incubated for 2 hrs by fluorescence based analysis	ic50	0.2528	uM
2-(2-propan-2-ylphenyl)-N-[(4-pyridin-3-ylphenyl)methyl]pyrrolo[2,1-f][1,2,4]triazin-4-amine	1164708: Inhibition of human USP1/UAF1 using Ub-AMC substrate by fluorescence assay	ic50	0.2600	uM
5-methyl-2-(2-propan-2-ylphenyl)-N-(thiophen-2-ylmethyl)pyrimidin-4-amine	1164708: Inhibition of human USP1/UAF1 using Ub-AMC substrate by fluorescence assay	ic50	0.2700	uM
2-(2-propan-2-ylphenyl)-N-[(4-pyridin-3-ylphenyl)methyl]thieno[2,3-d]pyrimidin-4-amine	1164708: Inhibition of human USP1/UAF1 using Ub-AMC substrate by fluorescence assay	ic50	0.2800	uM
N-[(4-imidazol-1-ylphenyl)methyl]-5-methyl-2-(2-propan-2-ylphenyl)pyrimidin-4-amine	1164708: Inhibition of human USP1/UAF1 using Ub-AMC substrate by fluorescence assay	ic50	0.3000	uM
2-(2-propan-2-ylphenyl)-4-N-[(4-pyridin-3-ylphenyl)methyl]pyrimidine-4,5-diamine	1164708: Inhibition of human USP1/UAF1 using Ub-AMC substrate by fluorescence assay	ic50	0.3100	uM
2-(4-cyclopropyl-6-methoxypyrimidin-5-yl)-8-[[2-methoxy-4-[1-propan-2-yl-4-(trifluoromethyl)imidazol-2-yl]phenyl]methyl]pyrido[2,3-d]pyrimidin-7-one	2116468: Inhibition of USP1-UAF1 complex (unknown origin) using Ub-7-amido-4-methylcoumarin as substrate incubated for 2 hrs by fluorescence based analysis	ic50	0.3190	uM
5-methyl-2-(2-propan-2-ylphenyl)-N-[[4-[2-(trifluoromethyl)-4-pyridinyl]phenyl]methyl]pyrimidin-4-amine	1164708: Inhibition of human USP1/UAF1 using Ub-AMC substrate by fluorescence assay	ic50	0.3200	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases expression	3
sodium arsenite	decreases expression	2
GSK-J4	increases expression	1
FR900359	affects phosphorylation	1
dicrotophos	decreases expression	1
testosterone enanthate	affects expression	1
di-n-butylphosphoric acid	affects expression	1
cylindrospermopsin	increases expression	1
monomethylarsonous acid	increases expression	1
ICG 001	decreases expression	1
abrine	increases expression	1
Bortezomib	increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Sunitinib	increases expression	1
Arsenic	affects methylation	1
Caffeine	decreases phosphorylation	1
Doxorubicin	decreases expression	1
Drugs, Chinese Herbal	increases expression	1
Formaldehyde	increases expression	1
Naphthoquinones	increases expression	1
Phenobarbital	affects expression	1
Plant Extracts	affects cotreatment, increases expression	1
Testosterone	decreases expression	1
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	increases expression	1

ChEMBL screening assays

43 unique, capped per target: 43 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5476516	Binding	Selectivity interaction (PWWP, WD40, and Tudor domain panel (DSLS measurements, literature)) EUB0000270b WDR48	Selectivity Literature for EUbOPEN Chemogenomic Library

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_E2P3	HAP1 WDR48 (-) 1	Cancer cell line	Male
CVCL_E2P4	HAP1 WDR48 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT07542548	PHASE4	COMPLETED	D-Cycloserine for Serine Palmitoyltransferase Inhibition
NCT03961906	PHASE2	COMPLETED	Physiotherapy in Hereditary Spastic Paraplegia
NCT04768166	PHASE2	COMPLETED	Testing Miglustat Administration in Subjects With Spastic Paraplegia 11
NCT06117020	PHASE1	COMPLETED	Single and Multiple Ascending Dose Study of MTR-601 in Healthy Individuals
NCT02604186	PHASE2/PHASE3	COMPLETED	Effects of Botulinum Toxin Injections in Patients With Hereditary Spastic Paraplegia
NCT05518188	PHASE1/PHASE2	RECRUITING	Melpida: Recombinant Adeno-associated Virus (serotype 9) Encoding a Codon Optimized Human AP4M1 Transgene (hAP4M1opt)
NCT06948019	PHASE1/PHASE2	NOT_YET_RECRUITING	Safety and Efficacy of AAV9/AP4B1 (BFB-101) For Patients With AP4B1-related Hereditary Spastic Paraplegia Type 47 (SPG47)
NCT06478238	EARLY_PHASE1	RECRUITING	Calcium Folinate Treatment of Spastic Paraplegia 56
NCT00023075	Not specified	COMPLETED	Nuclear Magnetic Spectroscopy Imaging to Evaluate Primary Lateral Sclerosis, Hereditary Spastic Paraplegia and Amyotrophic Lateral Sclerosis
NCT00136630	Not specified	COMPLETED	Natural History, Genetic Bases and Phenotype-genotype Correlations in Autosomal Dominant Spinocerebellar Degenerations
NCT00140829	Not specified	COMPLETED	SPATAX: Clinical and Genetic Analysis of Cerebellar Ataxias and Spastic Paraplegias
NCT00677768	Not specified	COMPLETED	Validation of Biomarkers in Amyotrophic Lateral Sclerosis (ALS)
NCT01568658	Not specified	ACTIVE_NOT_RECRUITING	Genetic and Physical Study of Childhood Nerve and Muscle Disorders
NCT02327845	Not specified	ENROLLING_BY_INVITATION	Phenotype, Genotype & Biomarkers in ALS and Related Disorders
NCT02852278	Not specified	COMPLETED	A Patient Centric Motor Neuron Disease Activities of Daily Living Scale
NCT02859428	Not specified	TERMINATED	Disease Natural History and Biomarkers of SPG3A, SPG4A, and SPG31
NCT03104088	Not specified	COMPLETED	Studying Cognition in SPG4
NCT03206190	Not specified	RECRUITING	The preSPG4 Study - Studying the Prodromal and Early Phase of SPG4
NCT03627416	Not specified	COMPLETED	Repetitive Transcranial Magnetic Stimulation as Therapy in Hereditary Spastic Paraplegia and Adrenomyeloneuropathy
NCT03981276	Not specified	RECRUITING	Phenotypes, Biomarkers and Pathophysiology in Hereditary Spastic Paraplegias and Related Disorders
NCT04006418	Not specified	RECRUITING	A Registered Cohort Study on Spastic Paraplegia
NCT04180098	Not specified	COMPLETED	Improving Gait Adaptability in Hereditary Spastic Paraplegia
NCT04256681	Not specified	COMPLETED	SNAP: Measurement of the Subjective Perception of the Symptom in Hereditary Spastic Paraparesis (HSP)
NCT04712812	Not specified	RECRUITING	Registry and Natural History Study for Early Onset Hereditary Spastic Paraplegia
NCT04875416	Not specified	ACTIVE_NOT_RECRUITING	Phenotype, Genotype and Biomarkers 2
NCT04912609	Not specified	COMPLETED	Trehalose Administration in Subjects With Spastic Paraplegia 11 (3AL-SPG11)
NCT05354622	Not specified	RECRUITING	Hereditary Spastic Paraplegia Genomic Sequencing Initiative (HSPseq)
NCT05373082	Not specified	COMPLETED	Identification of Modifying Factors in Hereditary Spastic Paraplegia
NCT05411627	Not specified	WITHDRAWN	A Pilot Study of Shockwave Therapy in HSP
NCT05432999	Not specified	COMPLETED	Extracorporeal Shockwave Therapy for Spasticity in People With Spinal Cord Injury
NCT05613114	Not specified	COMPLETED	Effect of Dalfampridine in Patients With Hereditary Spastic Paraplegia
NCT05767268	Not specified	COMPLETED	Assessment of the Psychophysical State During Rehabilitation Treatment With Lokomat
NCT05848271	Not specified	RECRUITING	Natural History Study of Patients with HPDL Mutations
NCT06156813	Not specified	RECRUITING	Turkish Lower-Extremity Motor Activity Log (LE-MAL)
NCT06229626	Not specified	RECRUITING	Evaluation of an Intensive Training Program for Patients with Hereditary Spastic Paraparesis SPG4/Spast
NCT06260982	Not specified	UNKNOWN	Cognitive Disorders in Hereditary Spastic Paraplegia Type 4
NCT06553976	Not specified	RECRUITING	Spastic Paraplegia - Centers of Excellence Research Network
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