DDB1

Summary

DDB1 (damage specific DNA binding protein 1, HGNC:2717) is a protein-coding gene on chromosome 11q12.2, encoding DNA damage-binding protein 1 (Q16531). Protein, which is both involved in DNA repair and protein ubiquitination, as part of the UV-DDB complex and DCX (DDB1-CUL4-X-box) complexes, respectively. It is a common-essential gene (DepMap: required in 100.0% of cancer cell lines).

The protein encoded by this gene is the large subunit (p127) of the heterodimeric DNA damage-binding (DDB) complex while another protein (p48) forms the small subunit. This protein complex functions in nucleotide-excision repair and binds to DNA following UV damage. Defective activity of this complex causes the repair defect in patients with xeroderma pigmentosum complementation group E (XPE) - an autosomal recessive disorder characterized by photosensitivity and early onset of carcinomas. However, it remains for mutation analysis to demonstrate whether the defect in XPE patients is in this gene or the gene encoding the small subunit. In addition, Best vitelliform mascular dystrophy is mapped to the same region as this gene on 11q, but no sequence alternations of this gene are demonstrated in Best disease patients. The protein encoded by this gene also functions as an adaptor molecule for the cullin 4 (CUL4) ubiquitin E3 ligase complex by facilitating the binding of substrates to this complex and the ubiquitination of proteins.

Source: NCBI Gene 1642 — RefSeq curated summary.

At a glance

• Gene–disease (curated): White-Kernohan syndrome (Strong, GenCC)
• Clinical variants (ClinVar): 207 total — 3 pathogenic, 3 likely-pathogenic
• Phenotypes (HPO): 49
• Druggable target: yes — 7 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 100.0% of screened cell lines (common-essential)
• MANE Select transcript: NM_001923

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2717
Approved symbol	DDB1
Name	damage specific DNA binding protein 1
Location	11q12.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000167986
Ensembl biotype	protein_coding
OMIM	600045
Entrez	1642

Gene structure

Transcript identifiers

Ensembl transcripts: 71 — 38 protein_coding, 27 retained_intron, 4 nonsense_mediated_decay, 2 protein_coding_CDS_not_defined

ENST00000301764, ENST00000414411, ENST00000451943, ENST00000535147, ENST00000535174, ENST00000535283, ENST00000535967, ENST00000537120, ENST00000537877, ENST00000538129, ENST00000538280, ENST00000538470, ENST00000539332, ENST00000539426, ENST00000539712, ENST00000539739, ENST00000540166, ENST00000540784, ENST00000541513, ENST00000542337, ENST00000543162, ENST00000543658, ENST00000545894, ENST00000545930, ENST00000679588, ENST00000679712, ENST00000679855, ENST00000680075, ENST00000680096, ENST00000680250, ENST00000680345, ENST00000680357, ENST00000680367, ENST00000680452, ENST00000680602, ENST00000680717, ENST00000680881, ENST00000680959, ENST00000681067, ENST00000681188, ENST00000681368, ENST00000681580, ENST00000681803, ENST00000681815, ENST00000681935, ENST00000867657, ENST00000867658, ENST00000867659, ENST00000867660, ENST00000920436, ENST00000920437, ENST00000920438, ENST00000920439, ENST00000920440, ENST00000920441, ENST00000920442, ENST00000920443, ENST00000920444, ENST00000920445, ENST00000920446, ENST00000920447, ENST00000954149, ENST00000954150, ENST00000954151, ENST00000954152, ENST00000954153, ENST00000954154, ENST00000954155, ENST00000954156, ENST00000954157, ENST00000954158

RefSeq mRNA: 1 — MANE Select: NM_001923 NM_001923

CCDS: CCDS31576

Canonical transcript exons

ENST00000301764 — 27 exons

Exon	Start	End
ENSE00001063027	61313862	61313969
ENSE00001063028	61313499	61313706
ENSE00001063041	61308983	61309077
ENSE00001063044	61310295	61310418
ENSE00001145090	61303046	61303155
ENSE00001145096	61303865	61304035
ENSE00001145124	61311989	61312084
ENSE00001198074	61302582	61302751
ENSE00001198106	61311784	61311895
ENSE00001506452	61300809	61300932
ENSE00001506453	61302257	61302359
ENSE00001766096	61332908	61333105
ENSE00002321622	61299451	61300219
ENSE00003458891	61321595	61321697
ENSE00003487770	61323011	61323094
ENSE00003488555	61329958	61330074
ENSE00003490913	61322296	61322412
ENSE00003494536	61314308	61314486
ENSE00003557995	61325611	61325708
ENSE00003588869	61309796	61309960
ENSE00003593046	61323979	61324137
ENSE00003611361	61331543	61331691
ENSE00003642261	61314047	61314210
ENSE00003642698	61316285	61316393
ENSE00003656067	61316492	61316567
ENSE00003691599	61329363	61329584
ENSE00003789035	61326779	61326893

Expression profiles

Bgee: expression breadth ubiquitous, 296 present calls, max score 99.20.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 112.7839 / max 678.6344, expressed in 1827 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
119972	111.2117	1827
119966	0.5242	313
119965	0.4178	224
119973	0.3622	186
119975	0.1839	83
119974	0.0444	9
119964	0.0396	14

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right adrenal gland	UBERON:0001233	99.20	gold quality
right adrenal gland cortex	UBERON:0035827	99.19	gold quality
left adrenal gland	UBERON:0001234	99.13	gold quality
left adrenal gland cortex	UBERON:0035825	99.12	gold quality
adrenal tissue	UBERON:0018303	98.99	gold quality
adrenal gland	UBERON:0002369	98.97	gold quality
adrenal cortex	UBERON:0001235	98.94	gold quality
ventricular zone	UBERON:0003053	98.52	gold quality
stromal cell of endometrium	CL:0002255	98.14	gold quality
right testis	UBERON:0004534	98.13	gold quality
ganglionic eminence	UBERON:0004023	98.12	gold quality
left testis	UBERON:0004533	98.08	gold quality
right uterine tube	UBERON:0001302	98.02	gold quality
adenohypophysis	UBERON:0002196	97.95	gold quality
right ovary	UBERON:0002118	97.82	gold quality
skin of leg	UBERON:0001511	97.73	gold quality
left ovary	UBERON:0002119	97.70	gold quality
gastrocnemius	UBERON:0001388	97.64	gold quality
islet of Langerhans	UBERON:0000006	97.61	gold quality
skin of abdomen	UBERON:0001416	97.60	gold quality
apex of heart	UBERON:0002098	97.60	gold quality
endometrium epithelium	UBERON:0004811	97.53	gold quality
muscle of leg	UBERON:0001383	97.51	gold quality
pituitary gland	UBERON:0000007	97.50	gold quality
right frontal lobe	UBERON:0002810	97.29	gold quality
cortical plate	UBERON:0005343	97.24	gold quality
smooth muscle tissue	UBERON:0001135	97.19	gold quality
right lobe of thyroid gland	UBERON:0001119	97.16	gold quality
left lobe of thyroid gland	UBERON:0001120	97.02	gold quality
prefrontal cortex	UBERON:0000451	96.99	gold quality

Single-cell (SCXA)

Detected in 6 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-MTAB-5061	yes	836.64
E-MTAB-6701	yes	113.81
E-GEOD-137537	yes	16.84
E-MTAB-9689	no	282.70
E-MTAB-7316	no	33.62
E-ANND-3	no	0.00

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

1 targets.

Target	Regulation
CDKN2A	Unknown

Upstream regulators (CollecTRI, top): MYCN, NF1, PARP1, SP1, TP53

miRNA regulators (miRDB)

70 targeting DDB1, 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-8485	100.00	77.57	4731
HSA-MIR-574-5P	100.00	66.01	989
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AD-5P	99.94	71.23	3502
HSA-MIR-548AE-5P	99.94	71.23	3502
HSA-MIR-548AK	99.94	71.24	3488
HSA-MIR-548AM-5P	99.94	71.24	3488
HSA-MIR-548AP-5P	99.94	71.14	3489
HSA-MIR-548AQ-5P	99.94	71.34	3426
HSA-MIR-548AR-5P	99.94	71.28	3515
HSA-MIR-548AS-5P	99.94	71.22	3482
HSA-MIR-548AU-5P	99.94	71.24	3488
HSA-MIR-548AY-5P	99.94	71.23	3502
HSA-MIR-548B-5P	99.94	71.23	3502
HSA-MIR-548BB-5P	99.94	71.27	3509
HSA-MIR-548C-5P	99.94	71.24	3488
HSA-MIR-548D-5P	99.94	71.23	3502
HSA-MIR-548H-5P	99.94	71.24	3488
HSA-MIR-548I	99.94	71.25	3481
HSA-MIR-548J-5P	99.94	71.14	3489
HSA-MIR-548O-5P	99.94	71.24	3488
HSA-MIR-548W	99.94	71.24	3488

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 100.0% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 40)

• Sequential binding of UV DNA damage binding factor and degradation of the p48 subunit as early events after UV irradiation (PMID:12034848)
• findings substantiate the physical and functional connection between the hepatitis B virus X protein and the DDB1-DDB2 heterodimer, leading to the regulation of the pool of the viral protein (PMID:12050362)
• These findings indicate that hepatitis B virus X protein acts through a pathway that involves a DDB2-independent nuclear function of DDB1 and that this activity will depend on the relative concentration of DDB1 and DDB2 in cells. (PMID:12151405)
• essential for the targeted degradation of STAT1 by the V protein of the paramyxovirus simian virus 5. DDB1 may form a multiprotein complex with STAT1, STAT2, and V for this degradation. (PMID:12388698)
• SV5-V and HBx have evolved to bind DDB1 to achieve distinct functions in their life cycle, both by a mechanism that does not involve DDB2. (PMID:12743284)
• DET1 promotes ubiquitination and degradation of c-Jun by assembling a multisubunit ubiquitin ligase containing DNA Damage Binding Protein-1 (DDB1), cullin 4A (CUL4A), Regulator of Cullins-1 (ROC1), and constitutively photomorphogenic-1 (PMID:14739464)
• Damaged DNA binding protein 1 is a component of the centromere complex in interphase cells. (PMID:15009096)
• results show that HBx in association with DDB1 acts in the nucleus and stimulates hepatitis B virus replication mainly by enhancing viral mRNA levels (PMID:15767425)
• DDB1-DDB2 protein complex recognizes DNA mismatches and lesions (PMID:16223728)
• PCNA is involved in mediating Cdt1 degradation by the Cul4-Ddb1 ligase in response to DNA damage. (PMID:16407242)
• Cdt1 degradation requires predominant use of the PCNA/Cul4/Ddb1 ubiquitin ligase pathway after DNA damage (PMID:16407252)
• Monoubiquitinated histone H2A in native chromatin coimmunoprecipitates with the endogenous DDB1-CUL4A(DDB2) complex in response to UV irradiation. (PMID:16473935)
• The F-box protein Skp2, in addition to utilizing Cul1-Skp1, utilizes Cul4A-DDB1 to induce proteolysis of p27Kip1. (PMID:16537899)
• This study uncovers CUL4-DDB-ROC1 as a histone ubiquitin ligase and demonstrate that histone H3 and H4 ubiquitylation participates in the cellular response to DNA damage. (PMID:16678110)
• PCNA, L2DTL and the DDB1-CUL4A complex play critical and differential roles in regulating the protein stability of p53 and MDM2/HDM2 in unstressed and stressed cells. (PMID:16861890)
• L2DTL and PCNA interact with CUL4/DDB1 complexes and are involved in CDT1 degradation after DNA damage. (PMID:16861906)
• Results suggest that DDB1 prevents DNA lesions from accumulating in replicating human cells, in part by regulating Cdt1 degradation. (PMID:16940174)
• These studies uncover diverse substrate receptors for Cul4 and identify Cdt2 as a conserved component of the Cul4-Ddb1 E3 that is essential to destroy Cdt1 and ensure proper cell cycle regulation of DNA replication. (PMID:16949367)
• DDB1 aids in recruiting the ubiquitin ligase activity to the damaged sites for successful commencement of lesion processing by nucleotide excision repair. (PMID:16951172)
• X ray crystallography shows that DDB1 uses one beta-propeller domain for cullin scaffold binding and a variably attached separate double-beta-propeller fold for substrate presentation (PMID:16964240)
• A protein motif, the DWD box (DDB1-binding WD40 protein) was identified, and the binding of 15 DWD proteins with DDB1-CUL4A was demonstrated. (PMID:17079684)
• the interaction with DDB1 mediates Vpr-induced apoptosis and UNG2/SMUG1 degradation and impairs the repair of UV-damaged DNA, which could account for G(2) arrest and apoptosis (PMID:17360488)
• The Cul4-DDB1[VprBP] E3 ubiquitin ligase complex is identified as the downstream effector of lentiviral Vpr for the induction of cell cycle arrest in G2 phase. (PMID:17609381)
• The HIV1 protein Vpr acts to promote G2 cell cycle arrest by engaging a DDB1 and Cullin4A-containing ubiquitin ligase complex using VprBP/DCAF1 as an adaptor. (PMID:17620334)
• Vpr assembles with DDB1 through interaction with DCAF1 to form an E3 ubiquitin ligase that targets cellular substrates for proteasome-mediated degradation and G2 arrest (PMID:17626091)
• CUL4-DDB1 ubiquitin ligase interacts with Raptor and regulates the mTORC1-mediated signaling pathway through ubiquitin-dependent proteolysis. (PMID:18235224)
• DDB1 has a role in preventing the HBx-siRNA-mediated inhibition of HBV replication (PMID:18289873)
• VprBP depletion abolished the in vivo interaction of Merlin and Roc1-Cullin4A-DDB1, which resulted in Merlin stabilization and inhibited ERK and Rac activation (PMID:18332868)
• Results indicate that FBW5-DDB1-CUL4-ROC1 is an E3 ubiquitin ligase regulating TSC2 protein stability and TSC complex turnover. (PMID:18381890)
• Cul4A-DDB1DCAF1 ubiquitin ligase assembly protects HIV-1 Vpr from proteasomal degradation (PMID:18524771)
• LMP1 triggers the PI3K/Akt pathway to inactivate FOXO3a and decrease DDB1, which can lead to repression of DNA repair and may contribute to genomic instability in human epithelial cells (PMID:18524825)
• DDB1-CUL4B(DDB2) E3 ligase may have a distinctive function in modifying the chromatin structure at the site of UV lesions to promote efficient NER. (PMID:18593899)
• Data show that human immunodeficiency virus type 1 Vpr-binding protein VprBP binds stoichiometrically with DDB1 through its WD40 domain and through DDB1 to CUL4A, subunits of the COP9/signalsome. (PMID:18606781)
• CDK inhibitor p21 is degraded by a proliferating cell nuclear antigen-coupled Cul4-DDB1Cdt2 pathway during S phase and after UV irradiation (PMID:18703516)
• Results suggest a model in which UV-dependent degradation of DDB2 is important for the release of DDB1 from continuous association to unrepaired DNA and makes DDB1 available for its other DNA damage response functions. (PMID:18936169)
• The structure DDB1-DDB2 complex provides insights into damage recognition in chromatin and suggests a mechanism by which the DDB1-associated CUL4 ubiquitin ligase targets proteins surrounding the site of damage. (PMID:19109893)
• DDB1-CUL4 and MLL1 complexes constitute a novel pathway that mediates p16 activation during oncogenic checkpoint response. (PMID:19208841)
• Chk1 abundance is regulated by the Cul4A/DDB1 ubiquitin ligase during an unperturbed cell division cycle, in response to replicative stress and on heat shock protein 90 inhibition. (PMID:19276361)
• Data show that REDD1 is subject to ubiquitin-mediated degradation mediated by the CUL4A-DDB1-ROC1-beta-TRCP E3 ligase complex and through the activity of glycogen synthase kinase 3beta. (PMID:19557001)
• The data suggest that DDB1 could potentially be developed into biomarkers of resistance to acyl sulfonamide-based cancer drugs. This will require clinical validation in a series of patients treated with R3200. (PMID:19723642)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	ddb1	ENSDARG00000074431
mus_musculus	Ddb1	ENSMUSG00000024740
rattus_norvegicus	Ddb1	ENSRNOG00000020715
drosophila_melanogaster	pic	FBGN0260962
caenorhabditis_elegans		WBGENE00010890

Paralogs (2): CPSF1 (ENSG00000071894), SF3B3 (ENSG00000189091)

Protein

Protein identifiers

DNA damage-binding protein 1 — Q16531 (reviewed: Q16531)

Alternative names: DDB p127 subunit, DNA damage-binding protein a, Damage-specific DNA-binding protein 1, HBV X-associated protein 1, UV-damaged DNA-binding factor, UV-damaged DNA-binding protein 1, XPE-binding factor, Xeroderma pigmentosum group E-complementing protein

All UniProt accessions (14): A0A7P0T870, A0A7P0T965, A0A7P0TAK7, A0A7P0TAX4, A0A7P0TB30, A0A7P0Z3Z5, A0A7P0Z4B9, A0A7P0Z4L2, Q16531, F5GWI0, F5GY55, F5GZY8, F5H198, F5H2L3

UniProt curated annotations — full annotation on UniProt →

Function. Protein, which is both involved in DNA repair and protein ubiquitination, as part of the UV-DDB complex and DCX (DDB1-CUL4-X-box) complexes, respectively. Core component of the UV-DDB complex (UV-damaged DNA-binding protein complex), a complex that recognizes UV-induced DNA damage and recruit proteins of the nucleotide excision repair pathway (the NER pathway) to initiate DNA repair. The UV-DDB complex preferentially binds to cyclobutane pyrimidine dimers (CPD), 6-4 photoproducts (6-4 PP), apurinic sites and short mismatches. Also functions as a component of numerous distinct DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complexes which mediate the ubiquitination and subsequent proteasomal degradation of target proteins. The functional specificity of the DCX E3 ubiquitin-protein ligase complex is determined by the variable substrate recognition component recruited by DDB1. DCX(DDB2) (also known as DDB1-CUL4-ROC1, CUL4-DDB-ROC1 and CUL4-DDB-RBX1) may ubiquitinate histone H2A, histone H3 and histone H4 at sites of UV-induced DNA damage. The ubiquitination of histones may facilitate their removal from the nucleosome and promote subsequent DNA repair. DCX(DDB2) also ubiquitinates XPC, which may enhance DNA-binding by XPC and promote NER. DCX(DTL) plays a role in PCNA-dependent polyubiquitination of CDT1 and MDM2-dependent ubiquitination of TP53 in response to radiation-induced DNA damage and during DNA replication. DCX(ERCC8) (the CSA complex) plays a role in transcription-coupled repair (TCR). The DDB1-CUL4A-DTL E3 ligase complex regulates the circadian clock function by mediating the ubiquitination and degradation of CRY1. DDB1-mediated CRY1 degradation promotes FOXO1 protein stability and FOXO1-mediated gluconeogenesis in the liver. By acting on TET dioxygenses, essential for oocyte maintenance at the primordial follicle stage, hence essential for female fertility. Maternal factor required for proper zygotic genome activation and genome reprogramming.

Subunit / interactions. Component of the UV-DDB complex which includes DDB1 and DDB2; the heterodimer dimerizes to give rise to a heterotetramer when bound to damaged DNA. The UV-DDB complex interacts with monoubiquitinated histone H2A and binds to XPC via the DDB2 subunit. Component of numerous DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complexes which consist of a core of DDB1, CUL4A or CUL4B and RBX1. DDB1 may recruit specific substrate targeting subunits to the DCX complex. These substrate targeting subunits are generally known as DCAF (DDB1- and CUL4-associated factor) or CDW (CUL4-DDB1-associated WD40-repeat) proteins. Interacts with AMBRA1, ATG16L1, BTRC, CRBN, DCAF1, DCAF4, DCAF5, DCAF6, DCAF7, DCAF8, DCAF9, DCAF10, DCAF11, DCAF12, DCAF15, DCAF16, DCAF17, DDA1, DET1, DTL, ERCC8, FBXW5, FBXW8, GRWD1, KATNB1, NLE1, NUP43, PAFAH1B1, PHIP, PWP1, RBBP4, RBBP5, RBBP7, COP1, SNRNP40, DCAF1, WDR5, WDR5B, WDR12, WDR26, WDR39, WDR42, WDR53, WDR59, WDR61, WSB1, WSB2, LRWD1 and WDTC1. DCX complexes may associate with the COP9 signalosome, and this inhibits the E3 ubiquitin-protein ligase activity of the complex. Interacts with NF2, TSC1 and TSC2. Interacts with AGO1 and AGO2. Associates with the E3 ligase complex containing DYRK2, EDD/UBR5, DDB1 and DCAF1 proteins (EDVP complex). Interacts directly with DYRK2. DCX(DTL) complex interacts with FBXO11; does not ubiquitinate and degradate FBXO11. Interacts with TRPC4AP. Interacts with CRY1 and CRY2. The DDB1-CUL4A complex interacts with CRY1. May also interact with DCUN1D1, DCUN1D2, DCUN1D3 and DCUN1D5. Component of the DCX(DCAF13) E3 ubiquitin ligase complex, at least composed of CUL4 (CUL4A or CUL4B), DDB1, DCAF13 and RBX1. Interacts with DCAF13 (via WD40 domain). Interacts with FBXO44. (Microbial infection) Interacts with Simian virus 5 protein V. (Microbial infection) Interacts with hepatitis B virus protein HBX; the viral protein contains a short helical motif that competes for the same binding site as the N-terminal helical motif found in endogenous DCAF proteins. (Microbial infection) Interacts with human cytomegalovirus protein UL145; this interaction promotes STAT2 degradation. (Microbial infection) Interacts with human cytomegalovirus protein RL1; this interaction allows RL1 to recruit the cullin4-RING E3 ubiquitin ligase (CRL4) complex and promote SLN11 degradation.

Subcellular location. Cytoplasm. Nucleus.

Post-translational modifications. Phosphorylated by ABL1. Ubiquitinated by CUL4A. Subsequently degraded by ubiquitin-dependent proteolysis. Acetylated, promoting interaction with CUL4 (CUL4A or CUL4B) and subsequent formation of DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complexes. Deacetylation by SIRT7 impairs the interaction with CUL4 (CUL4A or CUL4B) and formation of DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complexes.

Disease relevance. White-Kernohan syndrome (WHIKERS) [MIM:619426] An autosomal dominant disorder characterized by global developmental delay, variably impaired intellectual development, hypotonia, and characteristic facial features. Some patients may have genitourinary and skeletal abnormalities. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. The core of the protein consists of three WD40 beta-propeller domains.

Pathway. Protein modification; protein ubiquitination.

Similarity. Belongs to the DDB1 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q16531-1	1	yes
Q16531-2	2

RefSeq proteins (1): NP_001914* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004871	RSE1/DDB1/CPSF1_C	Domain
IPR015943	WD40/YVTN_repeat-like_dom_sf	Homologous_superfamily
IPR018846	Beta-prop_RSE1/DDB1/CPSF1_1st	Domain
IPR036322	WD40_repeat_dom_sf	Homologous_superfamily
IPR050358	RSE1/DDB1/CFT1	Family
IPR058543	Beta-prop_RSE1/DDB1/CPSF1_2nd	Domain

Pfam: PF03178, PF10433, PF23726

UniProt features (177 total): strand 121, turn 17, helix 11, sequence variant 6, mutagenesis site 6, region of interest 5, sequence conflict 4, modified residue 3, initiator methionine 1, chain 1, cross-link 1, splice variant 1

Structure

Experimental structures (PDB)

205 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
9BBG	X-RAY DIFFRACTION	1.7
9EJQ	X-RAY DIFFRACTION	1.87
9BBI	X-RAY DIFFRACTION	1.9
9BZ0	ELECTRON MICROSCOPY	1.9
9BBE	X-RAY DIFFRACTION	2
9BBH	X-RAY DIFFRACTION	2
9FJX	X-RAY DIFFRACTION	2
9ZXN	X-RAY DIFFRACTION	2.07
9ZXM	X-RAY DIFFRACTION	2.19
8G46	ELECTRON MICROSCOPY	2.2
8ZSW	X-RAY DIFFRACTION	2.25
3EI3	X-RAY DIFFRACTION	2.3
6UD7	X-RAY DIFFRACTION	2.3
9SFM	X-RAY DIFFRACTION	2.39
3E0C	X-RAY DIFFRACTION	2.41
8TNQ	ELECTRON MICROSCOPY	2.41
5FQD	X-RAY DIFFRACTION	2.45
8OIZ	X-RAY DIFFRACTION	2.5
8TNR	ELECTRON MICROSCOPY	2.5
9OS2	ELECTRON MICROSCOPY	2.5
6ZX9	X-RAY DIFFRACTION	2.52
9SAF	ELECTRON MICROSCOPY	2.55
3EI2	X-RAY DIFFRACTION	2.6
8B3D	ELECTRON MICROSCOPY	2.6
6UE5	X-RAY DIFFRACTION	2.61
8TL6	ELECTRON MICROSCOPY	2.63
9LTJ	ELECTRON MICROSCOPY	2.65
9SAI	ELECTRON MICROSCOPY	2.66
9J6K	ELECTRON MICROSCOPY	2.68
9OUK	ELECTRON MICROSCOPY	2.69

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q16531-F1	92.14	0.78

Functional residue map

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

Post-translational modifications (4): 1121, 2, 1067, 1125

Mutagenesis-validated functional residues (6):

Position	Phenotype
316–319	impairs interaction with dda1.
537	slightly impairs interaction with cul4a.
561	strongly impairs interaction with cul4a.
840–842	impairs interaction with ambra1, dtl, det1, dcaf1, dcaf5, dcaf11 and dcaf8.
910–913	impairs interaction with ambra1, dtl and dcaf5.
953	impairs interaction with ambra1, ercc8, dcaf5 and dcaf11.

Function

Pathways and Gene Ontology

Reactome pathways

9 pathways

ID	Pathway
R-HSA-110314	Recognition of DNA damage by PCNA-containing replication complex
R-HSA-5696394	DNA Damage Recognition in GG-NER
R-HSA-5696395	Formation of Incision Complex in GG-NER
R-HSA-5696400	Dual Incision in GG-NER
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-8951664	Neddylation

MSigDB gene sets: 0 (showing top):

GO Biological Process (29): DNA repair (GO:0006281), nucleotide-excision repair (GO:0006289), ubiquitin-dependent protein catabolic process (GO:0006511), apoptotic process (GO:0006915), DNA damage response (GO:0006974), spindle assembly involved in female meiosis (GO:0007056), proteasomal protein catabolic process (GO:0010498), Wnt signaling pathway (GO:0016055), protein ubiquitination (GO:0016567), viral release from host cell (GO:0019076), cellular response to UV (GO:0034644), ectopic germ cell programmed cell death (GO:0035234), regulation of circadian rhythm (GO:0042752), negative regulation of apoptotic process (GO:0043066), proteasome-mediated ubiquitin-dependent protein catabolic process (GO:0043161), epigenetic programming in the zygotic pronuclei (GO:0044725), positive regulation of viral genome replication (GO:0045070), positive regulation of gluconeogenesis (GO:0045722), positive regulation of protein catabolic process (GO:0045732), positive regulation by virus of viral protein levels in host cell (GO:0046726), rhythmic process (GO:0048511), negative regulation of developmental process (GO:0051093), biological process involved in interaction with symbiont (GO:0051702), UV-damage excision repair (GO:0070914), regulation of mitotic cell cycle phase transition (GO:1901990), negative regulation of reproductive process (GO:2000242), negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction (GO:0051898), type I interferon-mediated signaling pathway (GO:0060337), base-excision repair, AP site formation via deaminated base removal (GO:0097510)

GO Molecular Function (9): DNA binding (GO:0003677), damaged DNA binding (GO:0003684), protein-macromolecule adaptor activity (GO:0030674), protein-containing complex binding (GO:0044877), WD40-repeat domain binding (GO:0071987), cullin family protein binding (GO:0097602), ubiquitin ligase complex scaffold activity (GO:0160072), nucleic acid binding (GO:0003676), protein binding (GO:0005515)

GO Cellular Component (15): chromosome, telomeric region (GO:0000781), obsolete extracellular space (GO:0005615), nucleus (GO:0005634), nucleoplasm (GO:0005654), nucleolus (GO:0005730), cytoplasm (GO:0005737), Cul4A-RING E3 ubiquitin ligase complex (GO:0031464), Cul4B-RING E3 ubiquitin ligase complex (GO:0031465), protein-containing complex (GO:0032991), site of double-strand break (GO:0035861), extracellular exosome (GO:0070062), Cul4-RING E3 ubiquitin ligase complex (GO:0080008), sperm midpiece (GO:0097225), sperm principal piece (GO:0097228), sperm end piece (GO:0097229)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
Global Genome Nucleotide Excision Repair (GG-NER)	3
Transcription-Coupled Nucleotide Excision Repair (TC-NER)	3
DNA Damage Bypass	1
Nucleotide Excision Repair	1
Post-translational protein modification	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
binding	3
sperm flagellum	3
protein catabolic process	2
positive regulation of viral process	2
protein binding	2
nuclear lumen	2
Cul4-RING E3 ubiquitin ligase complex	2
DNA metabolic process	1
DNA damage response	1
DNA repair	1
protein ubiquitination	1
modification-dependent protein catabolic process	1
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
cellular response to stress	1
female meiotic nuclear division	1
meiotic spindle assembly	1
cell surface receptor signaling pathway	1
protein modification by small protein conjugation	1
viral process	1
viral life cycle	1
exit from host cell	1
response to UV	1
cellular response to light stimulus	1
developmental process involved in reproduction	1
programmed cell death involved in cell development	1
circadian rhythm	1
regulation of biological process	1
apoptotic process	1
regulation of apoptotic process	1
negative regulation of programmed cell death	1
ubiquitin-dependent protein catabolic process	1
proteasomal protein catabolic process	1
epigenetic programming of gene expression	1
viral genome replication	1
regulation of viral genome replication	1
gluconeogenesis	1
regulation of gluconeogenesis	1

Protein interactions and networks

STRING

3761 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DDB1	RBX1	P62877	999
DDB1	CRBN	Q96SW2	999
DDB1	DDB2	Q92466	999
DDB1	CUL4A	Q13619	999
DDB1	CUL4B	Q13620	999
DDB1	DET1	Q7L5Y6	999
DDB1	DCAF1	Q9Y4B6	999
DDB1	DTL	Q9NZJ0	998
DDB1	DCAF11	Q8TEB1	997
DDB1	DDA1	Q9BW61	992
DDB1	FBXW5	Q969U6	976
DDB1	BTRC	Q9Y297	973
DDB1	CUL1	Q13616	955
DDB1	CDT1	Q9H211	949
DDB1	DCAF15	Q66K64	945

IntAct

462 interactions, top by confidence:

A	B	Type	Score
DDB2	DDB1	psi-mi:“MI:0915”(physical association)	0.970
DDB1	DDB2	psi-mi:“MI:0407”(direct interaction)	0.970
DDB1	DDB2	psi-mi:“MI:0915”(physical association)	0.970
DDB2	DDB1	psi-mi:“MI:0407”(direct interaction)	0.970
RBBP5	WDR5	psi-mi:“MI:0914”(association)	0.960
CUL4B	DDB1	psi-mi:“MI:0914”(association)	0.940
NEDD8	UBE2M	psi-mi:“MI:0914”(association)	0.940
DDB1	CUL4A	psi-mi:“MI:0914”(association)	0.920
DDB1	CUL4A	psi-mi:“MI:0915”(physical association)	0.920
DDB1	DCAF8	psi-mi:“MI:0407”(direct interaction)	0.910
DDB1	DCAF8	psi-mi:“MI:0915”(physical association)	0.910
DCAF8	DDB1	psi-mi:“MI:0914”(association)	0.910
DDB2	CUL4A	psi-mi:“MI:0914”(association)	0.900
GPS1	COPS2	psi-mi:“MI:0915”(physical association)	0.860
DDB1	DCAF4	psi-mi:“MI:0407”(direct interaction)	0.790
CUL4B	COPS2	psi-mi:“MI:0914”(association)	0.790

BioGRID (1587): HDAC1 (Affinity Capture-Western), HDAC2 (Affinity Capture-Western), SIN3A (Affinity Capture-Western), ARID4B (Affinity Capture-Western), SAP130 (Affinity Capture-Western), SUDS3 (Affinity Capture-Western), SAP30 (Affinity Capture-Western), RBP1 (Affinity Capture-Western), DDB1 (Affinity Capture-Western), DDB1 (Affinity Capture-Western), DDB1 (Affinity Capture-Western), DDB1 (Affinity Capture-Western), DDB1 (Affinity Capture-Western), DDB1 (Affinity Capture-Western), DDB1 (Affinity Capture-Western)

ESM2 similar proteins: A0A0R4IC37, A1A4K3, A2CEI4, B1WC10, E9PY46, F1QEB7, F4IDS7, O08658, O13046, O75694, O75717, O95876, P33194, P37199, P59328, Q08D69, Q10569, Q10570, Q16531, Q32NR9, Q3U1J4, Q4ADV7, Q566H4, Q5DQR4, Q5R649, Q5U1Z0, Q5ZLG9, Q6P6Z0, Q6PGF3, Q6PJI9, Q7XWP1, Q802U2, Q805F9, Q8BMG7, Q8C0M0, Q8C456, Q8CEC0, Q8CJF7, Q8K1X1, Q8NFP9

Diamond homologs: A1A4K3, B0M0P5, O49552, P33194, Q16531, Q21554, Q3U1J4, Q5R649, Q6E7D1, Q6L4S0, Q6P6Z0, Q6QNU4, Q805F9, Q9ESW0, Q9M0V3, Q9XYZ5

SIGNOR signaling

9 interactions.

A	Effect	B	Mechanism
DDB1	“form complex”	“DCX DET1-COP1”	binding
DDB1	“form complex”	Cullin4-RBX1-DDB1	binding
DDB1	“form complex”	EDVP	binding
DDB1	“form complex”	DDB2/DDB1	binding
DDB1	up-regulates	E2F1	binding
“UVB radiation”	up-regulates	DDB1
DDB1	up-regulates	RAD23A
DDB1	up-regulates	RAD23B
SIRT7	“down-regulates activity”	DDB1	deacetylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 149 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
DNA Damage Recognition in GG-NER	11	28.8×	2e-11
RHOBTB1 GTPase cycle	5	21.8×	4e-04
Formation of TC-NER Pre-Incision Complex	7	13.6×	2e-04
Neddylation	28	12.2×	3e-20
Formation of Incision Complex in GG-NER	5	11.6×	7e-03
NOTCH1 Intracellular Domain Regulates Transcription	5	10.9×	8e-03
Deactivation of the beta-catenin transactivating complex	5	10.7×	8e-03
Antigen processing: Ubiquitination & Proteasome degradation	11	3.8×	8e-03

GO biological processes:

GO term	Partners	Fold	FDR
protein neddylation	8	44.9×	2e-09
regulation of protein neddylation	5	37.5×	3e-05
cellular response to UV	7	16.6×	3e-05
protein monoubiquitination	6	16.5×	2e-04
SCF-dependent proteasomal ubiquitin-dependent protein catabolic process	5	15.0×	2e-03
intrinsic apoptotic signaling pathway	5	14.3×	2e-03
positive regulation of proteasomal ubiquitin-dependent protein catabolic process	6	10.1×	2e-03
G1/S transition of mitotic cell cycle	6	9.6×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	3
Likely pathogenic	3
Uncertain significance	132
Likely benign	16
Benign	5

Top pathogenic / likely-pathogenic (6)

Variant ID	HGVS	Classification
1183954	NG_032697.2:g.20705_20713del	Pathogenic
1183956	NM_001923.5(DDB1):c.563G>A (p.Arg188Gln)	Pathogenic
1183958	NM_001923.5(DDB1):c.1285T>G (p.Phe429Val)	Pathogenic
1183957	NM_001923.5(DDB1):c.637G>A (p.Glu213Lys)	Likely pathogenic
1700082	NM_001923.5(DDB1):c.341G>A (p.Arg114His)	Likely pathogenic
3384139	NM_001923.5(DDB1):c.2353G>A (p.Glu785Lys)	Likely pathogenic

SpliceAI

5789 predictions. Top by Δscore:

Variant	Effect	Δscore
11:61300218:TA:T	acceptor_gain	1.0000
11:61300220:C:CC	acceptor_gain	1.0000
11:61300803:GCTCA:G	donor_loss	1.0000
11:61300804:CTCAC:C	donor_loss	1.0000
11:61300806:CACCT:C	donor_loss	1.0000
11:61300929:CCAGG:C	acceptor_gain	1.0000
11:61300930:C:T	acceptor_gain	1.0000
11:61300933:G:GC	acceptor_gain	1.0000
11:61300937:A:AC	acceptor_gain	1.0000
11:61302181:T:TA	donor_gain	1.0000
11:61302226:C:A	donor_gain	1.0000
11:61302273:T:TA	donor_gain	1.0000
11:61302576:CCTTA:C	donor_loss	1.0000
11:61302577:CTTAC:C	donor_loss	1.0000
11:61302578:TTAC:T	donor_loss	1.0000
11:61302579:TA:T	donor_loss	1.0000
11:61302580:ACCT:A	donor_loss	1.0000
11:61302581:C:CA	donor_loss	1.0000
11:61302747:CAGCG:C	acceptor_gain	1.0000
11:61302749:GCG:G	acceptor_gain	1.0000
11:61302750:CG:C	acceptor_gain	1.0000
11:61302750:CGC:C	acceptor_gain	1.0000
11:61302752:C:CC	acceptor_gain	1.0000
11:61303041:CTCA:C	donor_loss	1.0000
11:61303042:TCA:T	donor_loss	1.0000
11:61303043:CA:C	donor_loss	1.0000
11:61303045:C:CG	donor_loss	1.0000
11:61303152:CAAT:C	acceptor_gain	1.0000
11:61303153:AATC:A	acceptor_loss	1.0000
11:61303154:ATC:A	acceptor_loss	1.0000

AlphaMissense

7531 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:61300152:A:G	L1136P	1.000
11:61300876:C:A	G1091V	1.000
11:61300876:C:T	G1091D	1.000
11:61300877:C:A	G1091C	1.000
11:61300877:C:G	G1091R	1.000
11:61300926:T:A	R1074S	1.000
11:61300926:T:G	R1074S	1.000
11:61300927:C:G	R1074T	1.000
11:61302275:C:T	G1066E	1.000
11:61302276:C:A	G1066W	1.000
11:61302276:C:G	G1066R	1.000
11:61302276:C:T	G1066R	1.000
11:61302299:A:G	L1058P	1.000
11:61302359:C:T	G1038E	1.000
11:61302590:C:A	G1035V	1.000
11:61302590:C:T	G1035D	1.000
11:61302591:C:G	G1035R	1.000
11:61302602:C:T	G1031D	1.000
11:61302603:C:G	G1031R	1.000
11:61303131:A:G	W953R	1.000
11:61303131:A:T	W953R	1.000
11:61303152:C:G	A946P	1.000
11:61303899:A:G	L933P	1.000
11:61303902:A:G	L932P	1.000
11:61303920:A:G	L926P	1.000
11:61303923:T:A	D925V	1.000
11:61303923:T:G	D925A	1.000
11:61303924:C:G	D925H	1.000
11:61303926:C:T	G924D	1.000
11:61303927:C:G	G924R	1.000

dbSNP variants (sampled 300 via entrez): RS1000166510 (11:61301708 G>A), RS1000265033 (11:61324165 G>C), RS1000432082 (11:61311292 A>G), RS1000463962 (11:61312412 T>G), RS1000506153 (11:61305326 G>A), RS1000525419 (11:61304961 A>G), RS1000683231 (11:61334253 C>G), RS1000729320 (11:61311316 C>T), RS1000797200 (11:61312630 T>C), RS1001336440 (11:61328832 C>T), RS1001390272 (11:61329092 A>G), RS1001410184 (11:61305924 A>G), RS1001652656 (11:61317600 G>A), RS1001727962 (11:61300374 C>T), RS1001768512 (11:61317420 G>C,T)

Disease associations

OMIM: gene MIM:600045 | disease phenotypes: MIM:619426

GenCC curated gene-disease

Disease	Classification	Inheritance
White-Kernohan syndrome	Strong	Autosomal dominant

Mondo (2): White-Kernohan syndrome (MONDO:0859169), syndromic intellectual disability (MONDO:0000508)

Orphanet (1): Rare genetic syndromic intellectual disability (Orphanet:183763)

HPO phenotypes

49 total (30 of 49 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000072	Hydroureter
HP:0000085	Horseshoe kidney
HP:0000126	Hydronephrosis
HP:0000143	Rectovaginal fistula
HP:0000154	Wide mouth
HP:0000219	Thin upper lip vermilion
HP:0000278	Retrognathia
HP:0000286	Epicanthus
HP:0000293	Full cheeks
HP:0000369	Low-set ears
HP:0000400	Macrotia
HP:0000403	Recurrent otitis media
HP:0000430	Underdeveloped nasal alae
HP:0000463	Anteverted nares
HP:0000506	Telecanthus
HP:0000527	Long eyelashes
HP:0000537	Epicanthus inversus
HP:0000574	Thick eyebrow
HP:0000582	Upslanted palpebral fissure
HP:0000601	Hypotelorism
HP:0000637	Long palpebral fissure
HP:0000639	Nystagmus
HP:0000664	Synophrys
HP:0000739	Anxiety
HP:0000821	Hypothyroidism
HP:0001249	Intellectual disability
HP:0001252	Hypotonia
HP:0001382	Joint hypermobility
HP:0001385	Hip dysplasia

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (9): CHEMBL3833061 (PROTEIN COMPLEX), CHEMBL4296145 (PROTEIN-PROTEIN INTERACTION), CHEMBL4524003 (PROTEIN-PROTEIN INTERACTION), CHEMBL4630734 (PROTEIN-PROTEIN INTERACTION), CHEMBL4888446 (PROTEIN COMPLEX), CHEMBL5291685 (PROTEIN-PROTEIN INTERACTION), CHEMBL5465550 (SINGLE PROTEIN), CHEMBL6195574 (PROTEIN-PROTEIN INTERACTION), CHEMBL6196201 (PROTEIN-PROTEIN INTERACTION)

Molecules with ChEMBL bioactivity

7 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 119,382 (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
CHEMBL43452	POMALIDOMIDE	4	13,354
CHEMBL468	THALIDOMIDE	4	97,393
CHEMBL848	LENALIDOMIDE	4	5,256
CHEMBL3989927	IBERDOMIDE	3	1,300
CHEMBL4648616	MEZIGDOMIDE	3	477
CHEMBL3989934	AVADOMIDE	2	1,506
CHEMBL4297459	CC-11006	1	96

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

Binding affinities (BindingDB)

758 measured of 1090 human assays (1090 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
3-(1-oxo-5-(7-(pyrrolidin-1- ylmethyl)imidazo[1,5-a]pyridin-5- yl)isoindolin-2-yl)piperidine-2,6- dione	IC50	20 nM	US-20250214991: BICYCLIC HETEROARYL-CONTAINING COMPOUNDS AS IKZF2 DEGRADERS
3-(5-(6-(((2,6-dichloro- phenethyl)amino)methyl)imi- dazo[1,2-a]pyridin-8-yl)-1- oxoisoindolin-2-yl)piperidine-2,6- dione	IC50	20 nM	US-20250214991: BICYCLIC HETEROARYL-CONTAINING COMPOUNDS AS IKZF2 DEGRADERS
3-(5-(7-(azetidin-1- ylmethyl)imidazo[1,5-a]pyridin-5- yl)-1-oxoisoindolin-2- yl)piperidine-2,6-dione	IC50	20 nM	US-20250214991: BICYCLIC HETEROARYL-CONTAINING COMPOUNDS AS IKZF2 DEGRADERS
3-(1-oxo-5-(7-(piperidin-1- ylmethyl)imidazo[1,5-a]pyridin-5- yl)isoindolin-2-yl)piperidine-2,6- dione	IC50	20 nM	US-20250214991: BICYCLIC HETEROARYL-CONTAINING COMPOUNDS AS IKZF2 DEGRADERS
3-(5-(6-(((2-chloro- phenethyl)amino)methyl)imi- dazo[1,2-a]pyridin-8-yl)-1- oxoisoindolin-2-yl)piperidine-2,6- dione	IC50	20 nM	US-20250214991: BICYCLIC HETEROARYL-CONTAINING COMPOUNDS AS IKZF2 DEGRADERS
3-(1-oxo-5-(6-(((1- phenylethyl)amino)methyl)imidazo [1,2-a]pyridin-8-yl)isoindolin-2- yl)piperidine-2,6-dione	IC50	20 nM	US-20250214991: BICYCLIC HETEROARYL-CONTAINING COMPOUNDS AS IKZF2 DEGRADERS
3-(5-(7-((3-methylpyrrolidin-1- yl)methyl)imidazo[1,5-a]pyridin-5- yl)-1-oxoisoindolin-2- yl)piperidine-2,6-dione	IC50	20 nM	US-20250214991: BICYCLIC HETEROARYL-CONTAINING COMPOUNDS AS IKZF2 DEGRADERS
3-(1-oxo-5-(6-(((2-phenylpropan- 2-yl)amino)methyl)imidazo[1,2- a]pyridin-8-yl)isoindolin-2- yl)piperidine-2,6-dione	IC50	20 nM	US-20250214991: BICYCLIC HETEROARYL-CONTAINING COMPOUNDS AS IKZF2 DEGRADERS
3-(1-oxo-5-(6-((2- phenylpyrrolidin-1- yl)methyl)imidazo[1,2-a]pyridin-8- yl)isoindolin-2-yl)piperidine-2,6- dione	IC50	20 nM	US-20250214991: BICYCLIC HETEROARYL-CONTAINING COMPOUNDS AS IKZF2 DEGRADERS
3-(5-(6-(((2- chlorophenethyl)amino)methyl)-1- methyl-1H-benzo[d]imidazol-4- yl)-1-oxoisoindolin-2- yl)piperidine-2,6-dione	IC50	20 nM	US-20250214991: BICYCLIC HETEROARYL-CONTAINING COMPOUNDS AS IKZF2 DEGRADERS
3-(5-(7-((diethylamino)methyl) imidazo[1,5-a]pyridin-5-yl)-1- oxoisoindolin-2-yl)piperidine-2,6- dione	IC50	20 nM	US-20250214991: BICYCLIC HETEROARYL-CONTAINING COMPOUNDS AS IKZF2 DEGRADERS
3-(5-(7- ((benzylamino)methyl)imidazo[1,5- a]pyridin-5-yl)-1-oxoisoindolin-2- yl)piperidine-2,6-dione	IC50	20 nM	US-20250214991: BICYCLIC HETEROARYL-CONTAINING COMPOUNDS AS IKZF2 DEGRADERS
3-(1-oxo-5-(7-((((S*)-1- phenylethyl)amino)methyl)imidazo [1,5-a]pyridin-5-yl)isoindolin-2- yl)piperidine-2,6-dione	IC50	20 nM	US-20250214991: BICYCLIC HETEROARYL-CONTAINING COMPOUNDS AS IKZF2 DEGRADERS
3-(5-(1-methyl-4-(pyrrolidin-1- ylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-1-oxoisoindolin-2- yl)piperidine-2,6-dione	IC50	20 nM	US-20250214991: BICYCLIC HETEROARYL-CONTAINING COMPOUNDS AS IKZF2 DEGRADERS
3-(5-(1-methyl-4-(piperidin-1- ylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-1-oxoisoindolin-2- yl)piperidine-2,6-dione	IC50	20 nM	US-20250214991: BICYCLIC HETEROARYL-CONTAINING COMPOUNDS AS IKZF2 DEGRADERS
3-(1-oxo-5-(4-(pyrrolidin-1- ylmethyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)isoindolin-2- yl)piperidine-2,6-dione	IC50	20 nM	US-20250214991: BICYCLIC HETEROARYL-CONTAINING COMPOUNDS AS IKZF2 DEGRADERS
3-(5-(7-(((2- chlorophenethyl)amino)methyl)imi- dazo[1,5-a]pyridin-5-yl)-1- oxoisoindolin-2-yl)piperidine-2,6- dione	IC50	20 nM	US-20250214991: BICYCLIC HETEROARYL-CONTAINING COMPOUNDS AS IKZF2 DEGRADERS
3-(5-(1-methyl-4- (thiomorpholinomethyl)-1H- pyrrolo[2,3-b]pyridin-6-yl)-1- oxoisoindolin-2-yl)piperidine-2,6- dione	IC50	20 nM	US-20250214991: BICYCLIC HETEROARYL-CONTAINING COMPOUNDS AS IKZF2 DEGRADERS
3-(5-(1-methyl-4-((tetrahydro-1H- furo[3,4-c]pyrrol-5(3H)- yl)methyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-1-oxoisoindolin-2- yl)piperidine-2,6-dione	IC50	20 nM	US-20250214991: BICYCLIC HETEROARYL-CONTAINING COMPOUNDS AS IKZF2 DEGRADERS
3-(5-(4-((6-azaspiro[2.5]octan-6- yl)methyl)-1-methyl-1H- pyrrolo[2,3-b]pyridin-6-yl)-1- oxoisoindolin-2-yl)piperidine-2,6- dione	IC50	20 nM	US-20250214991: BICYCLIC HETEROARYL-CONTAINING COMPOUNDS AS IKZF2 DEGRADERS
3-(5-(7-((((1-methyl-1H-indol-7- yl)methyl)amino)methyl)imi- dazo[1,5-a]pyridin-5-yl)-1- oxoisoindolin- 2-yl)piperidine-2,6-dione	IC50	20 nM	US-20250214991: BICYCLIC HETEROARYL-CONTAINING COMPOUNDS AS IKZF2 DEGRADERS
3-(5-(4-((3,4-dihydroisoquinolin- 2(1H)-yl)methyl)-1-methyl-1H- pyrrolo[2,3-b]pyridin-6-yl)-1- oxoisoindolin-2-yl)piperidine-2,6- dione	IC50	20 nM	US-20250214991: BICYCLIC HETEROARYL-CONTAINING COMPOUNDS AS IKZF2 DEGRADERS
3-(1-oxo-5-(7-((2- phenylpyrrolidin-1- yl)methyl)imidazo[1,5-a]pyridin-5- yl)isoindolin-2-yl)piperidine-2,6- dione	IC50	20 nM	US-20250214991: BICYCLIC HETEROARYL-CONTAINING COMPOUNDS AS IKZF2 DEGRADERS
3-(5-(4-((3- azabicyclo[3.1.0]hexan-3- yl)methyl)-1-methyl-1H- pyrrolo[2,3-b]pyridin-6-yl)-1- oxoisoindolin-2-yl)piperidine-2,6- dione	IC50	20 nM	US-20250214991: BICYCLIC HETEROARYL-CONTAINING COMPOUNDS AS IKZF2 DEGRADERS
3-(5-(4-((7-azaspiro[3.5]nonan-7- yl)methyl)-1-methyl-1H- pyrrolo[2,3-b]pyridin-6-yl)-1- oxoisoindolin-2-yl)piperidine-2,6- dione	IC50	20 nM	US-20250214991: BICYCLIC HETEROARYL-CONTAINING COMPOUNDS AS IKZF2 DEGRADERS
3-(4-methoxy-1-oxo-5-(7- (pyrrolidin-1- ylmethyl)imidazo[1,5-a]pyridin-5- yl)isoindolin-2-yl)piperidine-2,6- dione	IC50	20 nM	US-20250214991: BICYCLIC HETEROARYL-CONTAINING COMPOUNDS AS IKZF2 DEGRADERS
3-(5-(1-methyl-4-((2- phenylazetidin-1-yl)methyl)-1H- pyrrolo[2,3-b]pyridin-6-yl)-1- oxoisoindolin-2-yl)piperidine-2,6- dione	IC50	20 nM	US-20250214991: BICYCLIC HETEROARYL-CONTAINING COMPOUNDS AS IKZF2 DEGRADERS
3-(7-methoxy-1-oxo-5-(7- (pyrrolidin-1- ylmethyl)imidazo[1,5-a]pyridin-5- yl)isoindolin-2-yl)piperidine-2,6- dione	IC50	20 nM	US-20250214991: BICYCLIC HETEROARYL-CONTAINING COMPOUNDS AS IKZF2 DEGRADERS
3-(5-(4- ((hexahydrocyclopenta[c]pyrrol- 2(1H)-yl)methyl)-1-methyl-1H- pyrrolo[2,3-b]pyridin-6-yl)-1- oxoisoindolin-2-yl)piperidine-2,6- dione	IC50	20 nM	US-20250214991: BICYCLIC HETEROARYL-CONTAINING COMPOUNDS AS IKZF2 DEGRADERS
3-(1-oxo-5-(6-(piperidin-1- ylmethyl)imidazo[1,2-a]pyridin-8- yl)isoindolin-2-yl)piperidine-2,6- dione	IC50	20 nM	US-20250214991: BICYCLIC HETEROARYL-CONTAINING COMPOUNDS AS IKZF2 DEGRADERS
3-(5-(4-((2-oxa-7- azaspiro[3.5]nonan-7-yl)methyl)-1- methyl-1H-pyrrolo[2,3-b]pyridin- 6-yl)-1-oxoisoindolin-2- yl)piperidine-2,6-dione	IC50	20 nM	US-20250214991: BICYCLIC HETEROARYL-CONTAINING COMPOUNDS AS IKZF2 DEGRADERS
3-(5-(6-((4,4-difluoropiperidin-1- yl)methyl)imidazo[1,2-a]pyridin-8- yl)-1-oxoisoindolin-2- yl)piperidine-2,6-dione	IC50	20 nM	US-20250214991: BICYCLIC HETEROARYL-CONTAINING COMPOUNDS AS IKZF2 DEGRADERS
3-(4-fluoro-5-(1-methyl-4- (pyrrolidin-1-ylmethyl)-1H- pyrrolo[2,3-b]pyridin-6-yl)-1- oxoisoindolin-2-yl)piperidine-2,6- dione	IC50	20 nM	US-20250214991: BICYCLIC HETEROARYL-CONTAINING COMPOUNDS AS IKZF2 DEGRADERS
3-(5-(6-((4,4-dimethylpiperidin-1- yl)methyl)imidazo[1,2-a]pyridin-8- yl)-1-oxoisoindolin-2- yl)piperidine-2,6-dione	IC50	20 nM	US-20250214991: BICYCLIC HETEROARYL-CONTAINING COMPOUNDS AS IKZF2 DEGRADERS
3-(5-(6-(((2-chloro- benzyl)amino)methyl)imidazo [1,2-a]pyridin-8-yl)-1- oxoisoindolin-2-yl)piperidine-2,6- dione	IC50	20 nM	US-20250214991: BICYCLIC HETEROARYL-CONTAINING COMPOUNDS AS IKZF2 DEGRADERS
3-(1-oxo-5-(4-(pyrrolidin-1- ylmethyl)-5,6,7,8- tetrahydroquinolin-2-yl)isoindolin- 2-yl)piperidine-2,6-dione	IC50	20 nM	US-20250214991: BICYCLIC HETEROARYL-CONTAINING COMPOUNDS AS IKZF2 DEGRADERS
3-(5-(6-(((2,4-dichloro- phenethyl)amino)methyl)imi- dazo[1,2-a]pyridin-8-yl)-1- oxoisoindolin-2-yl)piperidine-2,6- dione	IC50	20 nM	US-20250214991: BICYCLIC HETEROARYL-CONTAINING COMPOUNDS AS IKZF2 DEGRADERS
3-(1-oxo-5-(4-(pyrrolidin-1- ylmethyl)-6,7-dihydro-5H- cyclopenta[b]pyridin-2- yl)isoindolin-2-yl)piperidine-2,6- dione	IC50	20 nM	US-20250214991: BICYCLIC HETEROARYL-CONTAINING COMPOUNDS AS IKZF2 DEGRADERS
3-(1-oxo-5-(4-(pyrrolidin-1- ylmethyl)-1-(tetrahydro-2H-pyran- 4-yl)-1H-pyrrolo[2,3-b]pyridin-6- yl)isoindolin-2-yl)piperidine-2,6- dione	IC50	20 nM	US-20250214991: BICYCLIC HETEROARYL-CONTAINING COMPOUNDS AS IKZF2 DEGRADERS
3-(5-(4-((3-methoxyazetidin-1- yl)methyl)-1-methyl-1H- pyrrolo[2,3-b]pyridin-6-yl)-1- oxoisoindolin-2-yl)piperidine-2,6- dione	IC50	20 nM	US-20250214991: BICYCLIC HETEROARYL-CONTAINING COMPOUNDS AS IKZF2 DEGRADERS
3-(5-(1-methyl-4-(1-(pyrrolidin-1- yl)ethyl)-1H-pyrrolo[2,3-b]pyridin- 6-yl)-1-oxoisoindolin-2- yl)piperidine-2,6-dione	IC50	20 nM	US-20250214991: BICYCLIC HETEROARYL-CONTAINING COMPOUNDS AS IKZF2 DEGRADERS
3-(5-(1-methyl-4-((4- (trifluoromethyl)piperidin-1- yl)methyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-1-oxoisoindolin-2- yl)piperidine-2,6-dione	IC50	20 nM	US-20250214991: BICYCLIC HETEROARYL-CONTAINING COMPOUNDS AS IKZF2 DEGRADERS
3-(5-(4-((3-methoxypyrrolidin-1- yl)methyl)-1-methyl-1H- pyrrolo[2,3-b]pyridin-6-yl)-1- oxoisoindolin-2-yl)piperidine-2,6- dione	IC50	20 nM	US-20250214991: BICYCLIC HETEROARYL-CONTAINING COMPOUNDS AS IKZF2 DEGRADERS
3-(5-(1-(oxetan-3-yl)-4- ((tetrahydro-1H-furo[3,4-c]pyrrol- 5(3H)-yl)methyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-1-oxoisoindolin-2- yl)piperidine-2,6-dione	IC50	20 nM	US-20250214991: BICYCLIC HETEROARYL-CONTAINING COMPOUNDS AS IKZF2 DEGRADERS
3-(5-(4-((4-fluoropiperidin-1- yl)methyl)-1-(oxetan-3-yl)-1H- pyrrolo[2,3-b]pyridin-6-yl)-1- oxoisoindolin-2-yl)piperidine-2,6- dione	IC50	20 nM	US-20250214991: BICYCLIC HETEROARYL-CONTAINING COMPOUNDS AS IKZF2 DEGRADERS
3-(5-(4-((hexahydropyrrolo[1,2- a]pyrazin-2(1H)-yl)methyl)-1- methyl-1H-pyrrolo[2,3-b]pyridin- 6-yl)-1-oxoisoindolin-2- yl)piperidine-2,6-dione	IC50	20 nM	US-20250214991: BICYCLIC HETEROARYL-CONTAINING COMPOUNDS AS IKZF2 DEGRADERS
3-(5-(4-((3- (hydroxymethyl)pyrrolidin-1- yl)methyl)-1-methyl-1H- pyrrolo[2,3-b]pyridin-6-yl)-1- oxoisoindolin-2-yl)piperidine-2,6- dione	IC50	20 nM	US-20250214991: BICYCLIC HETEROARYL-CONTAINING COMPOUNDS AS IKZF2 DEGRADERS
3-(5-(4-((4-methoxypiperidin-1- yl)methyl)-1-(oxetan-3-yl)-1H- pyrrolo[2,3-b]pyridin-6-yl)-1- oxoisoindolin-2-yl)piperidine-2,6- dione	IC50	20 nM	US-20250214991: BICYCLIC HETEROARYL-CONTAINING COMPOUNDS AS IKZF2 DEGRADERS
3-(5-(4-((4- (dimethylamino)piperidin-1- yl)methyl)-1-(oxetan-3-yl)-1H- pyrrolo[2,3-b]pyridin-6-yl)-1- oxoisoindolin-2-yl)piperidine-2,6- dione	IC50	20 nM	US-20250214991: BICYCLIC HETEROARYL-CONTAINING COMPOUNDS AS IKZF2 DEGRADERS
3-(5-(1-methyl-4-((4-(1-methyl- 1H-imidazol-2-yl)piperazin-1- yl)methyl)-1H-pyrrolo[2,3- b]pyridin-6-yl)-1-oxoisoindolin-2- yl)piperidine-2,6-dione	IC50	20 nM	US-20250214991: BICYCLIC HETEROARYL-CONTAINING COMPOUNDS AS IKZF2 DEGRADERS

ChEMBL bioactivities

338 potent at pChembl≥5 of 507 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.61	IC50	0.244	nM	CHEMBL5178566
9.18	IC50	0.667	nM	CHEMBL4848064
9.00	IC50	1	nM	CHEMBL5084281
8.85	IC50	1.41	nM	CHEMBL4854720
8.85	IC50	1.4	nM	CHEMBL5270900
8.80	IC50	1.57	nM	CHEMBL5904309
8.70	Kd	2	nM	CHEMBL5921578
8.52	IC50	3	nM	CHEMBL5078971
8.52	Kd	3	nM	CHEMBL5754385
8.51	IC50	3.09	nM	CHEMBL4094346
8.49	EC50	3.2	nM	CHEMBL5172193
8.44	IC50	3.62	nM	CHEMBL5984956
8.40	Kd	4	nM	CHEMBL5775791
8.31	IC50	4.84	nM	CHEMBL5797819
8.30	IC50	5	nM	CHEMBL6078355
8.22	IC50	6.05	nM	CHEMBL5856424
8.22	Kd	6	nM	CHEMBL5966302
8.19	IC50	6.41	nM	CHEMBL5988642
8.15	IC50	7.1	nM	CHEMBL5276245
8.15	Kd	7	nM	CHEMBL5772946
8.14	IC50	7.3	nM	CHEMBL5875774
8.14	IC50	7.21	nM	CHEMBL5938943
8.05	IC50	9	nM	CHEMBL5078004
8.05	EC50	9	nM	POMALIDOMIDE
8.00	IC50	10	nM	CHEMBL5079426
8.00	Kd	10	nM	CHEMBL6008645
8.00	Kd	10	nM	CHEMBL5830320
7.99	IC50	10.3	nM	CHEMBL5757694
7.98	IC50	10.4	nM	CHEMBL5890447
7.97	IC50	10.7	nM	CHEMBL6060396
7.96	IC50	11	nM	CHEMBL5073414
7.96	EC50	11	nM	CHEMBL5183717
7.96	IC50	11	nM	CHEMBL5904309
7.92	IC50	12.1	nM	CHEMBL5786105
7.91	IC50	12.4	nM	CHEMBL5861696
7.90	IC50	12.7	nM	CHEMBL5741676
7.88	IC50	13.2	nM	CHEMBL5883980
7.85	EC50	14	nM	CHEMBL5201283
7.85	IC50	14	nM	CHEMBL4303781
7.83	IC50	14.8	nM	CHEMBL5899236
7.82	IC50	15	nM	CHEMBL5094191
7.82	EC50	15	nM	CHEMBL5208953
7.82	IC50	15	nM	CHEMBL5899236
7.82	IC50	15.2	nM	CHEMBL475060
7.82	Kd	15	nM	CHEMBL5842876
7.80	IC50	16	nM	CHEMBL5084741
7.77	EC50	17	nM	CHEMBL5205527
7.77	IC50	17	nM	IBERDOMIDE
7.77	IC50	17.1	nM	CHEMBL6005015
7.75	IC50	18	nM	CHEMBL4170596

PubChem BioAssay actives

113 with measured affinity, of 246 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
(4S)-1-[4-[4-[3-[2-[2-[2-[[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-4-yl]amino]ethoxy]ethoxy]ethoxy]propanoyl]piperazin-1-yl]phenyl]-7,8-dimethoxy-N,4-dimethyl-4,5-dihydro-2,3-benzodiazepine-3-carboxamide	1852448: Protac activity at His-tagged CRBN/FLAG-tagged DDB1 (unknown origin) in presence of Cy5-labeled thalidomide incubated for 60 min by TR-FRET assay	ic50	0.0002	uM
(4S)-1-[4-[4-[5-[[2-[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-4-yl]oxyacetyl]amino]pentanoyl]piperazin-1-yl]phenyl]-7,8-dimethoxy-N,4-dimethyl-4,5-dihydro-2,3-benzodiazepine-3-carboxamide	1852448: Protac activity at His-tagged CRBN/FLAG-tagged DDB1 (unknown origin) in presence of Cy5-labeled thalidomide incubated for 60 min by TR-FRET assay	ic50	0.0007	uM
3-chloro-N-[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-5-yl]-4-methylbenzenesulfonamide	1814571: Displacement of Cy5-O-Len probe from 6XHis-tagged CRBN/DDB1 (unknown origin) incubated in dark for 1 hr by fluorescence polarization assay	ic50	0.0010	uM
(4S)-1-[4-[4-[2-[2-[2-[[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-4-yl]amino]-2-oxoethoxy]ethoxy]acetyl]piperazin-1-yl]phenyl]-7,8-dimethoxy-N,4-dimethyl-4,5-dihydro-2,3-benzodiazepine-3-carboxamide	1852448: Protac activity at His-tagged CRBN/FLAG-tagged DDB1 (unknown origin) in presence of Cy5-labeled thalidomide incubated for 60 min by TR-FRET assay	ic50	0.0014	uM
N-(2-chloro-6-methylphenyl)-2-[[6-[4-[3-[[2-[4-(2,6-dioxopiperidin-3-yl)phenoxy]acetyl]amino]propyl]piperazin-1-yl]-2-methylpyrimidin-4-yl]amino]-1,3-thiazole-5-carboxamide	1923057: Displacement of Cy5-O-Len from 6His-tagged CRBN/DDB1 (unknown origin) incubated for 1 hr under dark condition by fluorescence polarization assay	ic50	0.0014	uM
N-[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-5-yl]benzenesulfonamide	1814571: Displacement of Cy5-O-Len probe from 6XHis-tagged CRBN/DDB1 (unknown origin) incubated in dark for 1 hr by fluorescence polarization assay	ic50	0.0030	uM
N-[3-tert-butyl-5-[[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-4-yl]amino]phenyl]acetamide	1893698: Displacement of BODIPY FL thalidomide from 6His-tagged CRBN/DDB1 (unknown origin) expressed in baculovirus infected Sf9 insect cells incubated for 1 min under shaking condition followed by 60 mins incubation under dark condition by TR-FRET assay	ec50	0.0032	uM
N-(2-chloro-6-methylphenyl)-2-[[6-[4-[4-[4-[4-(2,6-dioxopiperidin-3-yl)phenyl]piperazin-1-yl]-4-oxobutyl]piperazin-1-yl]-2-methylpyrimidin-4-yl]amino]-1,3-thiazole-5-carboxamide	1923057: Displacement of Cy5-O-Len from 6His-tagged CRBN/DDB1 (unknown origin) incubated for 1 hr under dark condition by fluorescence polarization assay	ic50	0.0071	uM
Pomalidomide	1893698: Displacement of BODIPY FL thalidomide from 6His-tagged CRBN/DDB1 (unknown origin) expressed in baculovirus infected Sf9 insect cells incubated for 1 min under shaking condition followed by 60 mins incubation under dark condition by TR-FRET assay	ec50	0.0090	uM
N-[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-5-yl]-4-(trifluoromethoxy)benzenesulfonamide	1814571: Displacement of Cy5-O-Len probe from 6XHis-tagged CRBN/DDB1 (unknown origin) incubated in dark for 1 hr by fluorescence polarization assay	ic50	0.0090	uM
N-[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-5-yl]-3-(trifluoromethoxy)benzenesulfonamide	1814571: Displacement of Cy5-O-Len probe from 6XHis-tagged CRBN/DDB1 (unknown origin) incubated in dark for 1 hr by fluorescence polarization assay	ic50	0.0100	uM
N-[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-5-yl]-2-methylbenzenesulfonamide	1814571: Displacement of Cy5-O-Len probe from 6XHis-tagged CRBN/DDB1 (unknown origin) incubated in dark for 1 hr by fluorescence polarization assay	ic50	0.0110	uM
N-[3-tert-butyl-5-[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-4-yl]oxyphenyl]acetamide	1893698: Displacement of BODIPY FL thalidomide from 6His-tagged CRBN/DDB1 (unknown origin) expressed in baculovirus infected Sf9 insect cells incubated for 1 min under shaking condition followed by 60 mins incubation under dark condition by TR-FRET assay	ec50	0.0110	uM
4-(3-amino-5-tert-butylphenoxy)-2-(2,6-dioxopiperidin-3-yl)isoindole-1,3-dione	1893698: Displacement of BODIPY FL thalidomide from 6His-tagged CRBN/DDB1 (unknown origin) expressed in baculovirus infected Sf9 insect cells incubated for 1 min under shaking condition followed by 60 mins incubation under dark condition by TR-FRET assay	ec50	0.0140	uM
N-[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-5-yl]-2-(trifluoromethoxy)benzenesulfonamide	1814571: Displacement of Cy5-O-Len probe from 6XHis-tagged CRBN/DDB1 (unknown origin) incubated in dark for 1 hr by fluorescence polarization assay	ic50	0.0150	uM
N-[3-tert-butyl-5-[[2-[[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-4-yl]amino]acetyl]amino]phenyl]-1-(2,5-dimethoxyphenyl)-5-methyltriazole-4-carboxamide	1893698: Displacement of BODIPY FL thalidomide from 6His-tagged CRBN/DDB1 (unknown origin) expressed in baculovirus infected Sf9 insect cells incubated for 1 min under shaking condition followed by 60 mins incubation under dark condition by TR-FRET assay	ec50	0.0150	uM
3-chloro-N-[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-5-yl]-2-methylbenzenesulfonamide	1814571: Displacement of Cy5-O-Len probe from 6XHis-tagged CRBN/DDB1 (unknown origin) incubated in dark for 1 hr by fluorescence polarization assay	ic50	0.0160	uM
[3-tert-butyl-5-[[1-(2,5-dimethoxyphenyl)-5-methyltriazole-4-carbonyl]amino]phenyl] 2-[[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-4-yl]amino]acetate	1893698: Displacement of BODIPY FL thalidomide from 6His-tagged CRBN/DDB1 (unknown origin) expressed in baculovirus infected Sf9 insect cells incubated for 1 min under shaking condition followed by 60 mins incubation under dark condition by TR-FRET assay	ec50	0.0170	uM
(3S)-3-[7-[[4-(morpholin-4-ylmethyl)phenyl]methoxy]-3-oxo-1H-isoindol-2-yl]piperidine-2,6-dione	2023107: Displacement of Cy5-labeled tracer CC0782985 from 6His-tagged CRBN (1 to 442 residues)/DDB1 (1 to 1140 residues) (unknown origin) incubated for 20 mins by TR-FRET assay	ic50	0.0170	uM
1-(3-chloro-4-methylphenyl)-3-[[2-(2,6-dioxopiperidin-3-yl)-1-oxo-3H-isoindol-5-yl]methyl]urea	1814571: Displacement of Cy5-O-Len probe from 6XHis-tagged CRBN/DDB1 (unknown origin) incubated in dark for 1 hr by fluorescence polarization assay	ic50	0.0180	uM
3-chloro-N-[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-5-yl]benzenesulfonamide	1814571: Displacement of Cy5-O-Len probe from 6XHis-tagged CRBN/DDB1 (unknown origin) incubated in dark for 1 hr by fluorescence polarization assay	ic50	0.0230	uM
N-[3-tert-butyl-5-[2-[[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-4-yl]amino]ethoxy]phenyl]-1-(2,5-dimethoxyphenyl)-5-methyltriazole-4-carboxamide	1893698: Displacement of BODIPY FL thalidomide from 6His-tagged CRBN/DDB1 (unknown origin) expressed in baculovirus infected Sf9 insect cells incubated for 1 min under shaking condition followed by 60 mins incubation under dark condition by TR-FRET assay	ec50	0.0230	uM
N-[3-tert-butyl-5-[2-[[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-4-yl]amino]ethylamino]phenyl]-1-(2,5-dimethoxyphenyl)-5-methyltriazole-4-carboxamide	1893698: Displacement of BODIPY FL thalidomide from 6His-tagged CRBN/DDB1 (unknown origin) expressed in baculovirus infected Sf9 insect cells incubated for 1 min under shaking condition followed by 60 mins incubation under dark condition by TR-FRET assay	ec50	0.0240	uM
4-[4-[[4-[[2-[(3S)-2,6-dioxopiperidin-3-yl]-1-oxo-3H-isoindol-4-yl]oxymethyl]phenyl]methyl]piperazin-1-yl]-3-fluorobenzonitrile	1667521: Displacement of Cy5-conjugated CELMoD from N-terminal 6-His tagged CRBN (1 to 442 residues) (unknown origin)/DDB1 (1 to 1140 residues) (unknown origin) incubated for 10 mins by FRET assay	ic50	0.0300	uM
N-[3-tert-butyl-5-[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-4-yl]oxyphenyl]-1-(2,5-dimethoxyphenyl)-5-methyltriazole-4-carboxamide	1893698: Displacement of BODIPY FL thalidomide from 6His-tagged CRBN/DDB1 (unknown origin) expressed in baculovirus infected Sf9 insect cells incubated for 1 min under shaking condition followed by 60 mins incubation under dark condition by TR-FRET assay	ec50	0.0310	uM
Thalidomide	1893698: Displacement of BODIPY FL thalidomide from 6His-tagged CRBN/DDB1 (unknown origin) expressed in baculovirus infected Sf9 insect cells incubated for 1 min under shaking condition followed by 60 mins incubation under dark condition by TR-FRET assay	ec50	0.0360	uM
2-[(9S)-7-(4-chlorophenyl)-4,5,13-trimethyl-3-thia-1,8,11,12-tetrazatricyclo[8.3.0.02,6]trideca-2(6),4,7,10,12-pentaen-9-yl]-N-[5-[4-[2-(2,6-dioxopiperidin-3-yl)-1-oxo-3H-isoindol-5-yl]piperidin-1-yl]pentyl]acetamide	2025620: Displacement of Cy5-labeled lenalidomide from N-terminal His-Avi-tagged full-length CRBN (1 to 442 residues)/DDB1 (1 to 1140 residues) (unknown origin) expressed in Tni(Hi5) insect cells measured after 40 mins by TR-FRET assay	ic50	0.0366	uM
2-[(9S)-7-(4-chlorophenyl)-4,5,13-trimethyl-3-thia-1,8,11,12-tetrazatricyclo[8.3.0.02,6]trideca-2(6),4,7,10,12-pentaen-9-yl]-N-[6-[4-[2-(2,6-dioxopiperidin-3-yl)-1-oxo-3H-isoindol-5-yl]piperidin-1-yl]hexyl]acetamide	2025620: Displacement of Cy5-labeled lenalidomide from N-terminal His-Avi-tagged full-length CRBN (1 to 442 residues)/DDB1 (1 to 1140 residues) (unknown origin) expressed in Tni(Hi5) insect cells measured after 40 mins by TR-FRET assay	ic50	0.0368	uM
(3S)-3-[7-[[4-[[4-(2,4-difluorophenyl)piperazin-1-yl]methyl]phenyl]methoxy]-3-oxo-1H-isoindol-2-yl]piperidine-2,6-dione	1667521: Displacement of Cy5-conjugated CELMoD from N-terminal 6-His tagged CRBN (1 to 442 residues) (unknown origin)/DDB1 (1 to 1140 residues) (unknown origin) incubated for 10 mins by FRET assay	ic50	0.0370	uM
2-[(9S)-7-(4-chlorophenyl)-4,5,13-trimethyl-3-thia-1,8,11,12-tetrazatricyclo[8.3.0.02,6]trideca-2(6),4,7,10,12-pentaen-9-yl]-N-[2-[3-[4-[2-(2,6-dioxopiperidin-3-yl)-1-oxo-3H-isoindol-5-yl]piperidin-1-yl]azetidin-1-yl]ethyl]acetamide	2025620: Displacement of Cy5-labeled lenalidomide from N-terminal His-Avi-tagged full-length CRBN (1 to 442 residues)/DDB1 (1 to 1140 residues) (unknown origin) expressed in Tni(Hi5) insect cells measured after 40 mins by TR-FRET assay	ic50	0.0375	uM
2-[(9S)-7-(4-chlorophenyl)-4,5,13-trimethyl-3-thia-1,8,11,12-tetrazatricyclo[8.3.0.02,6]trideca-2(6),4,7,10,12-pentaen-9-yl]-N-[3-[4-[2-(2,6-dioxopiperidin-3-yl)-1-oxo-3H-isoindol-5-yl]piperidin-1-yl]propyl]acetamide	2025620: Displacement of Cy5-labeled lenalidomide from N-terminal His-Avi-tagged full-length CRBN (1 to 442 residues)/DDB1 (1 to 1140 residues) (unknown origin) expressed in Tni(Hi5) insect cells measured after 40 mins by TR-FRET assay	ic50	0.0410	uM
2-[(9S)-7-(4-chlorophenyl)-4,5,13-trimethyl-3-thia-1,8,11,12-tetrazatricyclo[8.3.0.02,6]trideca-2(6),4,7,10,12-pentaen-9-yl]-N-[4-[4-[2-(2,6-dioxopiperidin-3-yl)-1-oxo-3H-isoindol-5-yl]piperidin-1-yl]butyl]acetamide	2025620: Displacement of Cy5-labeled lenalidomide from N-terminal His-Avi-tagged full-length CRBN (1 to 442 residues)/DDB1 (1 to 1140 residues) (unknown origin) expressed in Tni(Hi5) insect cells measured after 40 mins by TR-FRET assay	ic50	0.0432	uM
N-(2-chloro-6-methylphenyl)-2-[[6-[4-[3-[[2-[4-(2,4-dioxo-1,3-diazinan-1-yl)phenoxy]acetyl]amino]propyl]piperazin-1-yl]-2-methylpyrimidin-4-yl]amino]-1,3-thiazole-5-carboxamide	1923057: Displacement of Cy5-O-Len from 6His-tagged CRBN/DDB1 (unknown origin) incubated for 1 hr under dark condition by fluorescence polarization assay	ic50	0.0520	uM
2-[(9S)-7-(4-chlorophenyl)-4,5,13-trimethyl-3-thia-1,8,11,12-tetrazatricyclo[8.3.0.02,6]trideca-2(6),4,7,10,12-pentaen-9-yl]-N-[4-[[2-(2,6-dioxopiperidin-3-yl)-1-oxo-3H-isoindol-5-yl]methyl]phenyl]acetamide	2025620: Displacement of Cy5-labeled lenalidomide from N-terminal His-Avi-tagged full-length CRBN (1 to 442 residues)/DDB1 (1 to 1140 residues) (unknown origin) expressed in Tni(Hi5) insect cells measured after 40 mins by TR-FRET assay	ic50	0.0524	uM
2-[(9S)-7-(4-chlorophenyl)-4,5,13-trimethyl-3-thia-1,8,11,12-tetrazatricyclo[8.3.0.02,6]trideca-2(6),4,7,10,12-pentaen-9-yl]-N-[2-[4-[2-(2,6-dioxopiperidin-3-yl)-1-oxo-3H-isoindol-5-yl]piperidin-1-yl]ethyl]acetamide	2025620: Displacement of Cy5-labeled lenalidomide from N-terminal His-Avi-tagged full-length CRBN (1 to 442 residues)/DDB1 (1 to 1140 residues) (unknown origin) expressed in Tni(Hi5) insect cells measured after 40 mins by TR-FRET assay	ic50	0.0538	uM
2-[(9S)-7-(4-chlorophenyl)-4,5,13-trimethyl-3-thia-1,8,11,12-tetrazatricyclo[8.3.0.02,6]trideca-2(6),4,7,10,12-pentaen-9-yl]-N-[2-[7-[2-(2,6-dioxopiperidin-3-yl)-1-oxo-3H-isoindol-5-yl]-2-azaspiro[3.5]nonan-2-yl]ethyl]acetamide	2025620: Displacement of Cy5-labeled lenalidomide from N-terminal His-Avi-tagged full-length CRBN (1 to 442 residues)/DDB1 (1 to 1140 residues) (unknown origin) expressed in Tni(Hi5) insect cells measured after 40 mins by TR-FRET assay	ic50	0.0538	uM
3-[7-[[4-[[4-(2,4-difluorophenyl)piperazin-1-yl]methyl]phenyl]methoxy]-3-oxo-1H-isoindol-2-yl]piperidine-2,6-dione	1667521: Displacement of Cy5-conjugated CELMoD from N-terminal 6-His tagged CRBN (1 to 442 residues) (unknown origin)/DDB1 (1 to 1140 residues) (unknown origin) incubated for 10 mins by FRET assay	ic50	0.0551	uM
2-[(9S)-7-(4-chlorophenyl)-4,5,13-trimethyl-3-thia-1,8,11,12-tetrazatricyclo[8.3.0.02,6]trideca-2(6),4,7,10,12-pentaen-9-yl]-N-[2-[9-[2-(2,6-dioxopiperidin-3-yl)-1-oxo-3H-isoindol-5-yl]-3-azaspiro[5.5]undecan-3-yl]ethyl]acetamide	2025620: Displacement of Cy5-labeled lenalidomide from N-terminal His-Avi-tagged full-length CRBN (1 to 442 residues)/DDB1 (1 to 1140 residues) (unknown origin) expressed in Tni(Hi5) insect cells measured after 40 mins by TR-FRET assay	ic50	0.0552	uM
2-[(9S)-7-(4-chlorophenyl)-4,5,13-trimethyl-3-thia-1,8,11,12-tetrazatricyclo[8.3.0.02,6]trideca-2(6),4,7,10,12-pentaen-9-yl]-N-[2-[4-[[2-(2,6-dioxopiperidin-3-yl)-1-oxo-3H-isoindol-5-yl]methyl]anilino]ethyl]acetamide	2025620: Displacement of Cy5-labeled lenalidomide from N-terminal His-Avi-tagged full-length CRBN (1 to 442 residues)/DDB1 (1 to 1140 residues) (unknown origin) expressed in Tni(Hi5) insect cells measured after 40 mins by TR-FRET assay	ic50	0.0571	uM
2-[(9S)-7-(4-chlorophenyl)-4,5,13-trimethyl-3-thia-1,8,11,12-tetrazatricyclo[8.3.0.02,6]trideca-2(6),4,7,10,12-pentaen-9-yl]-N-[4-[4-[[2-(2,6-dioxopiperidin-3-yl)-1-oxo-3H-isoindol-5-yl]methyl]anilino]butyl]acetamide	2025620: Displacement of Cy5-labeled lenalidomide from N-terminal His-Avi-tagged full-length CRBN (1 to 442 residues)/DDB1 (1 to 1140 residues) (unknown origin) expressed in Tni(Hi5) insect cells measured after 40 mins by TR-FRET assay	ic50	0.0594	uM
2-[(9S)-7-(4-chlorophenyl)-4,5,13-trimethyl-3-thia-1,8,11,12-tetrazatricyclo[8.3.0.02,6]trideca-2(6),4,7,10,12-pentaen-9-yl]-N-[3-[4-[[2-(2,6-dioxopiperidin-3-yl)-1-oxo-3H-isoindol-5-yl]methyl]anilino]propyl]acetamide	2025620: Displacement of Cy5-labeled lenalidomide from N-terminal His-Avi-tagged full-length CRBN (1 to 442 residues)/DDB1 (1 to 1140 residues) (unknown origin) expressed in Tni(Hi5) insect cells measured after 40 mins by TR-FRET assay	ic50	0.0723	uM
2-[(9S)-7-(4-chlorophenyl)-4,5,13-trimethyl-3-thia-1,8,11,12-tetrazatricyclo[8.3.0.02,6]trideca-2(6),4,7,10,12-pentaen-9-yl]-N-[5-[4-[[2-(2,6-dioxopiperidin-3-yl)-1-oxo-3H-isoindol-5-yl]methyl]anilino]pentyl]acetamide	2025620: Displacement of Cy5-labeled lenalidomide from N-terminal His-Avi-tagged full-length CRBN (1 to 442 residues)/DDB1 (1 to 1140 residues) (unknown origin) expressed in Tni(Hi5) insect cells measured after 40 mins by TR-FRET assay	ic50	0.0792	uM
2-[(9S)-7-(4-chlorophenyl)-4,5,13-trimethyl-3-thia-1,8,11,12-tetrazatricyclo[8.3.0.02,6]trideca-2(6),4,7,10,12-pentaen-9-yl]-N-[6-[4-[[2-(2,6-dioxopiperidin-3-yl)-3-oxo-1H-isoindol-5-yl]methyl]anilino]hexyl]acetamide	2025620: Displacement of Cy5-labeled lenalidomide from N-terminal His-Avi-tagged full-length CRBN (1 to 442 residues)/DDB1 (1 to 1140 residues) (unknown origin) expressed in Tni(Hi5) insect cells measured after 40 mins by TR-FRET assay	ic50	0.0966	uM
3-(6-amino-1-methylindazol-3-yl)piperidine-2,6-dione	2023107: Displacement of Cy5-labeled tracer CC0782985 from 6His-tagged CRBN (1 to 442 residues)/DDB1 (1 to 1140 residues) (unknown origin) incubated for 20 mins by TR-FRET assay	ic50	0.1000	uM
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148208: Binding affinity to human DDB1 incubated for 45 mins by Kinobead based pull down assay	kd	0.1216	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148208: Binding affinity to human DDB1 incubated for 45 mins by Kinobead based pull down assay	kd	0.1389	uM
3-(1-methylindazol-3-yl)piperidine-2,6-dione	2023107: Displacement of Cy5-labeled tracer CC0782985 from 6His-tagged CRBN (1 to 442 residues)/DDB1 (1 to 1140 residues) (unknown origin) incubated for 20 mins by TR-FRET assay	ic50	0.1500	uM
Lenalidomide	2028111: Binding affinity to recombinant human CRBN/DDB1 assessed as dissociation constant incubated for 20 mins by fluorescence polarization assay	kd	0.1700	uM
3-(7-amino-1-methylindazol-3-yl)piperidine-2,6-dione	2023107: Displacement of Cy5-labeled tracer CC0782985 from 6His-tagged CRBN (1 to 442 residues)/DDB1 (1 to 1140 residues) (unknown origin) incubated for 20 mins by TR-FRET assay	ic50	0.1900	uM
3-[7-[[4-[[4-(2,4-difluorophenyl)piperazin-1-yl]methyl]phenyl]methylamino]-3-oxo-1H-isoindol-2-yl]piperidine-2,6-dione	1667521: Displacement of Cy5-conjugated CELMoD from N-terminal 6-His tagged CRBN (1 to 442 residues) (unknown origin)/DDB1 (1 to 1140 residues) (unknown origin) incubated for 10 mins by FRET assay	ic50	0.1940	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Dronabinol	decreases expression, increases expression	3
Cadmium Chloride	decreases expression, increases abundance, increases expression	3
bisphenol A	increases methylation, decreases expression, affects cotreatment	2
Doxorubicin	decreases expression, increases expression	2
Smoke	decreases expression	2
triphenyl phosphate	affects expression	1
pyrithione zinc	increases expression	1
beta-lapachone	decreases expression, increases expression	1
sodium arsenite	decreases expression	1
perfluorooctanoic acid	decreases expression	1
antimony trichloride	decreases expression	1
usnic acid	affects cotreatment, decreases expression	1
monomethylarsonous acid	decreases expression	1
nutlin 3	increases expression	1
(+)-JQ1 compound	affects binding	1
bisphenol AF	increases expression	1
Oxaliplatin	increases expression	1
Arsenic Trioxide	increases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Lenalidomide	affects binding	1
Acetaminophen	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Arsenic	increases ubiquitination	1
Benzo(a)pyrene	decreases expression	1
Cadmium	increases abundance, increases expression	1
Carbamazepine	affects expression	1
Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone	decreases expression	1
Diazinon	increases methylation	1
Diethylstilbestrol	increases expression	1
Ivermectin	decreases expression	1

ChEMBL screening assays

71 unique, capped per target: 71 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4219406	Binding	Induction of CRBN/DDB1-mediated BRD4 protein degradation in human NCI-H661 cells assessed as drug level causing 50% cellular protein depletion incubated for 4 hrs by MSD assay	A “Click Chemistry Platform” for the Rapid Synthesis of Bispecific Molecules for Inducing Protein Degradation. — J Med Chem

Clinical trials (associated diseases)

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