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): 238 total — 3 pathogenic, 3 likely-pathogenic
• Regional missense constraint (gnomAD): 3 of 7 regions constrained (≈19% of expected missense variation)
• GTEx eGene: eQTL in 6 tissues, sQTL in 1 (q < 0.05)
• Phenotypes (HPO): 49
• Drug target: yes — 4 via a complex or family; 7 molecules with ChEMBL bioactivity
• Approved drugs acting on a complex or family including it: 3 — Lenalidomide, Pomalidomide, Thalidomide (CRL4(CRBN) E3 ubiquitin ligase)
• Cancer dependency (DepMap): dependent in 100.0% of screened cell lines (common-essential)
• Constraint (gnomAD): pLI 1.00 (loss-of-function intolerant), LOEUF 0.20 (highly constrained)
• MANE Select transcript: NM_001923
• Interaction hub: 3,439 STRING partners (top 2% of genes corpus-wide)

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: 86 — 39 protein_coding, 27 retained_intron, 18 nonsense_mediated_decay, 2 protein_coding_CDS_not_defined

MANE Select: ENST00000301764

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 1, TSL 2: 13, TSL 3: 6, TSL 4: 3, TSL 5: 1

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, ENST00000954149, ENST00000954150, ENST00000954151, ENST00000954152, ENST00000954153, ENST00000954155, ENST00000954156, ENST00000954157, ENST00000954158, ENST00001007530, ENST00001007531, ENST00001007532, ENST00001027365, ENST00001027368, ENST00001027373, ENST00001027375, ENST00001027378, ENST00001027381, ENST00001081238, ENST00001081241, ENST00001081243, ENST00001081244, ENST00001081245, ENST00001081246, ENST00001107332, ENST00001142230

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.

Highest expression (Bgee): adrenal gland, adrenal gland cortex, adrenal tissue, adrenal cortex, ventricular zone.

Genetic regulation across tissues (GTEx eQTL / sQTL)

DDB1 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 6 tissues and its splicing (sQTL) in 1 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

7 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Muscle Skeletal	eqtl	9.6e-07	+0.18	11:61318027:T:C
Brain Frontal Cortex BA9	eqtl	8.4e-03	+0.12	11:61008834:C:T
Adipose Subcutaneous	eqtl	1.2e-02	-0.08	11:61202856:A:G
Stomach	eqtl	1.8e-02	-0.41	11:60772207:T:C
Adipose Visceral Omentum	sqtl	2.7e-02	-1.23	11:61627652:G:A
Whole Blood	eqtl	2.9e-02	-0.32	11:61109118:C:T
Cells Cultured fibroblasts	eqtl	4.7e-02	-0.31	11:60843876:T:G

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

showing 100 of 300 tissues 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
hindlimb stylopod muscle	UBERON:0004252	96.98	gold quality
peripheral nervous system	UBERON:0000010	96.97	gold quality
nerve	UBERON:0001021	96.97	gold quality
left uterine tube	UBERON:0001303	96.97	gold quality
tibial nerve	UBERON:0001323	96.97	gold quality
placenta	UBERON:0001987	96.96	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	96.91	gold quality
testis	UBERON:0000473	96.89	gold quality
right hemisphere of cerebellum	UBERON:0014890	96.86	gold quality
metanephros cortex	UBERON:0010533	96.82	gold quality
body of stomach	UBERON:0001161	96.81	gold quality
lower esophagus muscularis layer	UBERON:0035833	96.80	gold quality
lower esophagus	UBERON:0013473	96.79	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	96.79	gold quality
body of uterus	UBERON:0009853	96.78	gold quality
mucosa of transverse colon	UBERON:0004991	96.77	gold quality
ectocervix	UBERON:0012249	96.77	gold quality
zone of skin	UBERON:0000014	96.76	gold quality
cerebellar hemisphere	UBERON:0002245	96.75	gold quality
embryo	UBERON:0000922	96.72	gold quality
cerebellar cortex	UBERON:0002129	96.71	gold quality
Brodmann (1909) area 9	UBERON:0013540	96.68	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	96.60	gold quality
right atrium auricular region	UBERON:0006631	96.60	gold quality
endocervix	UBERON:0000458	96.59	gold quality
cingulate cortex	UBERON:0003027	96.59	gold quality
minor salivary gland	UBERON:0001830	96.58	gold quality
anterior cingulate cortex	UBERON:0009835	96.52	gold quality
muscle layer of sigmoid colon	UBERON:0035805	96.49	gold quality
small intestine Peyer’s patch	UBERON:0003454	96.48	gold quality
mucosa of stomach	UBERON:0001199	96.43	gold quality
thyroid gland	UBERON:0002046	96.43	gold quality
stomach	UBERON:0000945	96.41	gold quality
muscle organ	UBERON:0001630	96.33	gold quality
tibial artery	UBERON:0007610	96.33	gold quality
skeletal muscle organ	UBERON:0014892	96.33	gold quality
type B pancreatic cell	CL:0000169	96.32	silver quality
popliteal artery	UBERON:0002250	96.32	gold quality
transverse colon	UBERON:0001157	96.26	gold quality
aorta	UBERON:0000947	96.24	gold quality
ascending aorta	UBERON:0001496	96.24	gold quality
body of pancreas	UBERON:0001150	96.23	gold quality
thoracic aorta	UBERON:0001515	96.23	gold quality
heart left ventricle	UBERON:0002084	96.23	gold quality
esophagus	UBERON:0001043	96.22	gold quality
amygdala	UBERON:0001876	96.21	gold quality
rectum	UBERON:0001052	96.16	gold quality
caudate nucleus	UBERON:0001873	96.15	gold quality
hypothalamus	UBERON:0001898	96.13	gold quality
cardiac atrium	UBERON:0002081	96.13	gold quality
pancreas	UBERON:0001264	96.08	gold quality
upper lobe of left lung	UBERON:0008952	96.05	gold quality
cardiac ventricle	UBERON:0002082	96.01	gold quality
right coronary artery	UBERON:0001625	95.99	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	95.98	gold quality
adult mammalian kidney	UBERON:0000082	95.95	gold quality
left coronary artery	UBERON:0001626	95.95	gold quality
descending thoracic aorta	UBERON:0002345	95.94	gold quality
small intestine	UBERON:0002108	95.92	gold quality
right lobe of liver	UBERON:0001114	95.90	gold quality
heart	UBERON:0000948	95.88	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	95.88	gold quality
omental fat pad	UBERON:0010414	95.85	gold quality
peritoneum	UBERON:0002358	95.84	gold quality
cerebellum	UBERON:0002037	95.81	gold quality
nucleus accumbens	UBERON:0001882	95.79	gold quality
esophagus mucosa	UBERON:0002469	95.78	gold quality
saliva-secreting gland	UBERON:0001044	95.72	gold quality
spleen	UBERON:0002106	95.70	gold quality
colonic epithelium	UBERON:0000397	95.67	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

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 80 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Parathyroid gland	tissue	218.5	high
Retina	tissue	150.8
Adrenal gland	tissue	144.2	high
Caudate putamen	tissue	139.5
Frontal cortex	tissue	126.2
Placenta	tissue	121.9	low
Tongue	tissue	116.9
Skeletal muscle	tissue	112.3	medium
Choroid plexus	tissue	100.6
Thalamus	tissue	82.7
Spinal cord	tissue	82.7
Locus coeruleus	tissue	80.5
Pons	tissue	79.2
Midbrain	tissue	78.7
Superior colliculi	tissue	78.0
Substantia nigra	tissue	77.1
Ovary	tissue	76.4	high
Thymus	tissue	75.7
Epididymis	tissue	75.3	low
Medulla oblongata	tissue	74.9
Fallopian tube	tissue	73.7	medium
Hippocampal formation	tissue	73.4
Cerebral cortex	tissue	69.6	high
Somatosensory cortex	tissue	69.6
Hypothalamus	tissue	67.1
Seminal vesicle	tissue	66.9	high
Corpus callosum	tissue	65.4
Putamen	tissue	65.3
Prefrontal cortex	tissue	65.2
Hippocampus	tissue	65.1	high
Motor cortex	tissue	65.0
Testis	tissue	64.7	medium
Postcentral gyrus	tissue	62.6
Tonsil	tissue	62.4	medium
Occipital cortex	tissue	62.2
Ventral forebrain	tissue	61.8
Periaqueductal gray	tissue	61.2
Septum	tissue	61.1
Heart muscle	tissue	60.9	high
Basal ganglia	tissue	60.8	high
Thyroid gland	tissue	60.8	low
Kidney	tissue	60.5	high
Nucleus accumbens	tissue	59.8
Retrosplenial and cingulate cortex	tissue	59.0
Entorhinal cortex	tissue	58.7
Retrosplenial cortex	tissue	57.9
Smooth muscle	tissue	57.8	not detected
Cervix	tissue	57.7	medium
Skin 1	tissue	57.4	medium
Temporal cortex	tissue	57.0
Breast	tissue	55.3	high
Urinary bladder	tissue	54.8	medium
Insular cortex	tissue	54.6
Olfactory bulb	tissue	53.5
Prostate	tissue	53.1	medium
Cerebellum	tissue	52.5	high
Liver	tissue	52.3	medium
Salivary gland	tissue	51.0	medium
Amygdala	tissue	50.1
Duodenum	tissue	50.0	medium

Brain sub-regions (HPA Brain Atlas): detected in 192; highest nTPM — Superior vestibular nucleus (89.6), Arcuate nucleus (87.0), Supraoptic nucleus (84.6), Dorsal funiculus (white matter) (84.5), Dorsal raphe nucleus (82.8).

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)

Targeting DDB1 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 70 miRNAs:

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

gnomAD constraint: pLI 1, LOEUF 0.195, missense Z 6.46 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000301764 splits into 7 regions with different missense tolerance; 3 are missense-constrained (≈19% of the expected missense variation). Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. gnomAD

Region (GRCh38)	Missense obs / exp	o/e	Constrained
11:61,300,139–61,303,070	116 / 221.6	0.52	no
11:61,303,071–61,309,059	36 / 139.9	0.26	yes (p 1.6e-18)
11:61,309,060–61,316,538	396 / 554.1	0.71	no
11:61,316,539–61,323,043	35 / 123.3	0.28	yes (p 1.8e-15)
11:61,323,044–61,324,066	35 / 57.5	0.61	no
11:61,324,067–61,324,110	0 / 17.9	0.00	yes (p 2.3e-05)
11:61,324,111–61,332,968	210 / 344.8	0.61	no
DepMap (CRISPR cell-line fitness): dependent in 100.0% of screened cell lines, common-essential.

Most-dependent cell lines (DepMap gene-effect, lower = stronger; ≤ −0.5 shown): T-47D (-3.028), NCI-H1581 (-2.991), NOMO-1 (-2.988), THP-1 (-2.944), NIH:OVCAR-3 (-2.905), JH-EsoAd1 (-2.867), BT-12 (-2.855), Lu-65 (-2.773), SNU-213 (-2.74), NCI-H2170 (-2.722), SNU-869 (-2.716), SNU-1196 (-2.715), SNU-1033 (-2.707), NCI-H2887 (-2.705), TE-10 (-2.688).

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)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1202384) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 35 distinct phenotype terms.

Mouse phenotype (MP)	Records
abnormal urinary bladder morphology	1
abnormal thymus morphology	1
enlarged thymus	1
decreased brain size	1
abnormal cerebral cortex morphology	1
abnormal olfactory bulb morphology	1
abnormal lateral ventricle morphology	1
abnormal fourth ventricle morphology	1
small cerebellum	1
abnormal cerebellum external granule cell layer morphology	1
small testis	1
abnormal lens morphology	1
cataract	1
hyperactivity	1
intracranial hemorrhage	1
intracerebral hemorrhage	1
abnormal skin morphology	1
abnormal seminiferous tubule morphology	1
oligozoospermia	1
abnormal neuron apoptosis	1
dilated vasculature	1
abnormal brain vasculature morphology	1
decreased Sertoli cell number	1
abnormal cerebral aqueduct morphology	1
cerebellum hemorrhage	1

+10 more (showing top 25).

Additional cross-species homologs

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

Organism	UniProt	Identity	Method
Chlorocebus aethiops	P33194	99.9%	Diamond
Pongo abelii	Q5R649	99.8%	Diamond
Bos taurus	A1A4K3	99.7%	Diamond
Solanum cheesmaniae	Q6E7D1	99.5%	Diamond
Solanum lycopersicum	Q6QNU4	99.5%	Diamond
Gallus gallus	Q805F9	96.8%	Diamond
Xenopus laevis	Q6P6Z0	93.4%	Diamond
Arabidopsis thaliana	O49552	91.3%	Diamond
Oryza sativa Japonica Group	Q6L4S0	83.6%	Diamond
Dictyostelium discoideum	B0M0P5	44.5%	Diamond

Genomic neighbors (locus context)

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

Symbol	Type	Entrez
VWCE	protein-coding	220001
CYB561A3	protein-coding	220002
TKFC	protein-coding	26007
PGA5	protein-coding	5222
PGA4	protein-coding	643847
TMEM138	protein-coding	51524
TMEM216	protein-coding	51259
CPSF7	protein-coding	79869
PGA3	protein-coding	643834

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 (182 total): strand 123, helix 18, turn 13, 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)

showing 30 of 219 structures by resolution:

PDB	Title	Method	Resolution (Å)
9BBG	Co-crystal structure of human DDB1 bound to fragment UB028671	X-RAY DIFFRACTION	1.7
9EJQ	Crystal structure of DDB1 in complex with XS381952	X-RAY DIFFRACTION	1.87
9BBI	Co-crystal structure of human DDB1 bound to fragment UB028669	X-RAY DIFFRACTION	1.9
9BZ0	Structure of an STK19-containing TC-NER complex	ELECTRON MICROSCOPY	1.9
9BBE	Co-crystal structure of human DDB1 bound to fragment UB028668	X-RAY DIFFRACTION	2
9BBH	Co-crystal structure of human DDB1 bound to fragment UB028670	X-RAY DIFFRACTION	2
9FJX	Crystal structure of human CRBN-DDB1 in complex with Lenalidomide	X-RAY DIFFRACTION	2
9ZXN	DDB1 delta with compound 26	X-RAY DIFFRACTION	2.07
9ZXM	DDB1 delta with compound 6	X-RAY DIFFRACTION	2.19
8G46	Cryo-EM structure of DDB1deltaB-DDA1-DCAF16-BRD4(BD2)-MMH2	ELECTRON MICROSCOPY	2.2
8ZSW	Crystal Structure of Human DDB1, a Component of the E3 Ubiquitin Ligase Complex	X-RAY DIFFRACTION	2.25
3EI3	Structure of the hsDDB1-drDDB2 complex	X-RAY DIFFRACTION	2.3
6UD7	Crystal structure of full-length human DCAF15-DDB1(deltaBPB)-DDA1-RBM39 in complex with …	X-RAY DIFFRACTION	2.3
9PTU	Cryo-EM structure of the DCAF11 E3 ligase bound to the DDX18 helicase mediated by GSH-M12	ELECTRON MICROSCOPY	2.38
9SFM	Crystal structure of Cereblon-DDB1 in complex with SB-405483 and Lenalidomide	X-RAY DIFFRACTION	2.39
3E0C	Crystal Structure of DNA Damage-Binding protein 1(DDB1)	X-RAY DIFFRACTION	2.41
8TNQ	Cryo-EM structure of DDB1dB:CRBN:PT-179:SD40, conformation 1	ELECTRON MICROSCOPY	2.41
5FQD	Structural basis of Lenalidomide induced CK1a degradation by the crl4crbn ubiquitin ligase	X-RAY DIFFRACTION	2.45
8OIZ	Crystal structure of human CRBN-DDB1 in complex with Pomalidomide	X-RAY DIFFRACTION	2.5
8TNR	Cryo-EM structure of DDB1dB:CRBN:PT-179:SD40, conformation 2	ELECTRON MICROSCOPY	2.5
9OS2	Cryo-EM structure of the DDB1/CRBN-MRT-5702-G3BP2 ternary complex	ELECTRON MICROSCOPY	2.5
6ZX9	Crystal structure of SIV Vpr,fused to T4 lysozyme, isolated from moustached monkey, bound …	X-RAY DIFFRACTION	2.52
9SAF	Ternary PROTAC-mediated complex of BRD4-BD1/CRBN/DDB1 and JQ1-AcQ bifunctional degrader	ELECTRON MICROSCOPY	2.55
3EI2	Structure of hsDDB1-drDDB2 bound to a 16 bp abasic site containing DNA-duplex	X-RAY DIFFRACTION	2.6
8B3D	Structure of the Pol II-TCR-ELOF1 complex.	ELECTRON MICROSCOPY	2.6
6UE5	Crystal structure of full-length human DCAF15-DDB1-deltaPBP-DDA1-RBM39 in complex with …	X-RAY DIFFRACTION	2.61
8TL6	Cryo-EM structure of DDB1deltaB-DDA1-DCAF5	ELECTRON MICROSCOPY	2.63
9LTJ	Cryo-EM structure of DDB1-DDA1-DET1 complex	ELECTRON MICROSCOPY	2.65
9SAI	Ternary PROTAC-mediated complex consisting of Cereblon, DDB1 and BRD4-BD1, non-covalently …	ELECTRON MICROSCOPY	2.66
9J6K	HBx complexed with DDB1	ELECTRON MICROSCOPY	2.68

Predicted structure (AlphaFold)

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

Human Protein Atlas

Protein class: Predicted intracellular proteins, Plasma proteins, Disease related genes, Human disease related genes, Congenital malformations, Other congenital malformations, Essential proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): nucleoplasm; end piece; mid piece; principal piece

Antibody reliability (HPA): IH approved · IF enhanced

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)

Type	Positions
Glycyl lysine isopeptide (lys-gly) (interchain with g-cter in sumo2)	1121
N-acetylserine	2
N6-acetyllysine	1067
Phosphothreonine	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

10 curated (TAS) of 16; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

16 pathways:

ID	Pathway	Evidence
R-HSA-5696394	DNA Damage Recognition in GG-NER	curated
R-HSA-5696400	Dual Incision in GG-NER	curated
R-HSA-6782135	Dual incision in TC-NER	curated
R-HSA-5696395	Formation of Incision Complex in GG-NER	curated
R-HSA-6781823	Formation of TC-NER Pre-Incision Complex	curated
R-HSA-6782210	Gap-filling DNA repair synthesis and ligation in TC-NER	curated
R-HSA-8951664	Neddylation	curated
R-HSA-9974237	Negative Regulation of DNA Double Strand Break Response	curated
R-HSA-110314	Recognition of DNA damage by PCNA-containing replication complex	curated
R-HSA-6781827	Transcription-Coupled Nucleotide Excision Repair (TC-NER)	curated
R-HSA-73893	DNA Damage Bypass	—
R-HSA-73894	DNA Repair	—
R-HSA-5696399	Global Genome Nucleotide Excision Repair (GG-NER)	—
R-HSA-392499	Metabolism of proteins	—
R-HSA-5696398	Nucleotide Excision Repair	—
R-HSA-597592	Post-translational protein modification	—

MSigDB gene sets: 0 (showing top):

GO Biological Process (36): DNA repair (GO:0006281), nucleotide-excision repair (GO:0006289), ubiquitin-dependent protein catabolic process (GO:0006511), DNA damage response (GO:0006974), spindle assembly involved in female meiosis (GO:0007056), spermatogenesis (GO:0007283), cell population proliferation (GO:0008283), proteasomal protein catabolic process (GO:0010498), regulation of autophagy (GO:0010506), protein ubiquitination (GO:0016567), viral release from host cell (GO:0019076), regulation of DNA-templated DNA replication initiation (GO:0030174), replication fork processing (GO:0031297), regulation of natural killer cell activation (GO:0032814), cellular response to UV (GO:0034644), epigenetic regulation of gene expression (GO:0040029), regulation of cell population proliferation (GO:0042127), regulation of circadian rhythm (GO:0042752), regulation of apoptotic process (GO:0042981), 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), regulation of embryonic development (GO:0045995), positive regulation by virus of viral protein levels in host cell (GO:0046726), rhythmic process (GO:0048511), biological process involved in interaction with symbiont (GO:0051702), regulation of miRNA-mediated gene silencing (GO:0060964), UV-damage excision repair (GO:0070914), regulation of cellular response to stress (GO:0080135), regulation of cell cycle phase transition (GO:1901987), regulation of mitotic cell cycle phase transition (GO:1901990), regulation of mitotic cytokinesis (GO:1902412), negative regulation of adipose tissue development (GO:1904178), regulation of stem cell population maintenance (GO:2000036)

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 (11): chromosome, telomeric region (GO:0000781), 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)

Reactome top-level categories

8 top-level categories:

Category	Pathways
Global Genome Nucleotide Excision Repair (GG-NER)	3
Transcription-Coupled Nucleotide Excision Repair (TC-NER)	3
Nucleotide Excision Repair	2
DNA Repair	2
DNA Damage Bypass	1
Post-translational protein modification	1
DNA Double Strand Break Response	1
Metabolism of proteins	1

GO top-level categories

53 GO namespaces:

Category	Terms
binding	3
protein binding	2
nuclear lumen	2
cellular anatomical structure	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
cellular response to stress	1
female meiotic nuclear division	1
meiotic spindle assembly	1
developmental process involved in reproduction	1
male gamete generation	1
cellular process	1
protein catabolic process	1
autophagy	1
regulation of catabolic process	1
protein modification by small protein conjugation	1
viral process	1
viral life cycle	1
exit from host cell	1
DNA replication initiation	1
regulation of DNA-templated DNA replication	1
DNA-templated DNA replication maintenance of fidelity	1
natural killer cell activation	1
regulation of lymphocyte activation	1
response to UV	1
cellular response to light stimulus	1
chromatin remodeling	1
regulation of gene expression	1
cell population proliferation	1
regulation of cellular process	1
circadian rhythm	1
regulation of biological process	1
apoptotic process	1
regulation of programmed cell death	1
ubiquitin-dependent protein catabolic process	1
proteasomal protein catabolic process	1
nucleic acid binding	1
DNA binding	1
molecular adaptor activity	1
protein domain specific binding	1
protein complex scaffold activity	1
chromosomal region	1
intracellular membrane-bounded organelle	1
intracellular membraneless organelle	1
intracellular anatomical structure	1
cellular_component	1
site of DNA damage	1
extracellular vesicle	1
cullin-RING ubiquitin ligase complex	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 30 of 57 annotations. The rest are phylogenetic / computational / electronic (IEA).

30 experimentally-supported GO terms:

GO term	NS	Evidence
DNA damage response	BP	mutant phenotype
UV-damage excision repair	BP	direct assay
biological process involved in interaction with symbiont	BP	direct assay
cellular response to UV	BP	experiment
epigenetic programming in the zygotic pronuclei	BP	direct assay
positive regulation by virus of viral protein levels in host cell	BP	mutant phenotype
positive regulation of protein catabolic process	BP	direct assay
positive regulation of viral genome replication	BP	mutant phenotype
proteasomal protein catabolic process	BP	mutant phenotype
proteasome-mediated ubiquitin-dependent protein catabolic process	BP	direct assay
protein ubiquitination	BP	direct assay
regulation of mitotic cell cycle phase transition	BP	mutant phenotype
spindle assembly involved in female meiosis	BP	direct assay
ubiquitin-dependent protein catabolic process	BP	direct assay
viral release from host cell	BP	mutant phenotype
Cul4-RING E3 ubiquitin ligase complex	CC	direct assay
Cul4A-RING E3 ubiquitin ligase complex	CC	direct assay
Cul4B-RING E3 ubiquitin ligase complex	CC	direct assay
chromosome, telomeric region	CC	high-throughput assay
cytoplasm	CC	direct assay
extracellular exosome	CC	high-throughput assay
nucleolus	CC	direct assay
nucleoplasm	CC	direct assay
nucleus	CC	direct assay
protein-containing complex	CC	direct assay
WD40-repeat domain binding	MF	physical interaction
cullin family protein binding	MF	direct assay
protein-containing complex binding	MF	physical interaction
protein-macromolecule adaptor activity	MF	physical interaction
ubiquitin ligase complex scaffold activity	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 3,439 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DDB1	CUL4A	Q13619	985
DDB1	DDB2	Q92466	972
DDB1	RBX1	P62877	962
DDB1	CRBN	Q96SW2	955
DDB1	DET1	Q7L5Y6	955
DDB1	DCAF1	Q9Y4B6	945
DDB1	DTL	Q9NZJ0	928
DDB1	CDT1	Q9H211	912
DDB1	CUL4B	Q13620	900
DDB1	DCAF11	Q8TEB1	899
DDB1	NEDD8	Q15843	804
DDB1	CUL1	Q13616	785
DDB1	XPA	P23025	781
DDB1	FBXW5	Q969U6	777
DDB1	SKP1	P34991	770

IntAct

Human interaction partners of DDB1 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

showing 30 of 61 partners by confidence:

Partner	Interaction type	MIscore	Records
DDB2	physical association	0.970	14
CUL4B	association	0.940	5
CUL4A	association	0.920	5
DCAF8	direct interaction	0.910	5
DCAF4	direct interaction	0.790	3
DDA1	direct interaction	0.780	3
DCAF11	direct interaction	0.760	1
DTL	association	0.740	2
CRBN	physical association	0.720	5
DCAF1	physical association	0.690	3
WDTC1	direct interaction	0.670	2
COPS3	physical association	0.660	1
DCAF12	direct interaction	0.590	1
DCAF5	direct interaction	0.590	1
DCAF6	direct interaction	0.590	1
ACTR5	association	0.580	4
INO80	association	0.580	4
EED	physical association	0.560	4
X	direct interaction	0.540	3
RBX1	association	0.530	2
COP1	association	0.530	1
STAT1	physical association	0.510	2
FBXW5	physical association	0.500	1
L3MBTL3	physical association	0.500	1
TLE2	physical association	0.500	1
DDIT4	association	0.460	2
TRPC4AP	direct interaction	0.410	1
INVS	physical association	0.400	1
NPHP4	physical association	0.400	1
NUDCD3	physical association	0.400	1

BioGRID (1,600 interactions; top human partners by supporting records in a sample of 600 records): CUL4B (Co-fractionation; 33 records), CUL4A (Affinity Capture-Western; 31 records), DDB2 (Affinity Capture-Western; 18 records), CRBN (Affinity Capture-Western; 16 records), VPRBP (Affinity Capture-Western; 15 records), DCAF11 (Affinity Capture-Western; 10 records), DCAF8 (Affinity Capture-Western; 10 records), DTL (Affinity Capture-MS; 10 records), ERCC8 (Affinity Capture-Western; 9 records), PHIP (Affinity Capture-Western; 9 records), AMBRA1 (Affinity Capture-Western; 8 records), DET1 (Affinity Capture-Western; 6 records), SIRT7 (Affinity Capture-MS; 6 records), DCAF15 (Affinity Capture-Western; 5 records), DCAF4 (Affinity Capture-Western; 5 records)

SIGNOR signaling

9 signaling 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

Protein complexes (CORUM) (30)

Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).

30 complexes by size:

Complex	Subunits	Members
CEN complex	37	SUPT16H, BMI1, CENPC, CENPU, FBL, RNF2, COBLL1, CUL4A, DDB1, HSPA5, NUP93, KIF23, ZFP91, CENPI, CENPK, RACGAP1, SSRP1, ZC3H13, CENPH, CENPM, HSPA8, VIRMA, CBX3, CENPB, SMARCA5, SRRT, CBX8, CENPA, CENPO, PLPPR3, RSF1, WDR11, WTAP, CENPL, DHX38, RING1, SHCBP1
★ SNW1 complex	18	SNW1, TUBB, ABCF2, DDB1, DDX23, EEF1A1, HSPA5, PFKL, CDC5L, EFTUD2, PRPF8, SFPQ, MATR3, MSH2, UBR5, EEF1G, HNRNPU, SNRNP200
CSA-POLIIa complex	13	COPS3, COPS4, COPS5, COPS7A, CUL4A, ERCC8, RBX1, COPS2, COPS6, COPS8, DDB1, GPS1, POLR2A
DDB2 complex	12	COPS7A, CUL4A, DDB1, DDB2, COPS4, COPS6, COPS8, GPS1, RBX1, COPS2, COPS3, COPS5
CSA complex	12	COPS5, COPS7A, CUL4A, DDB1, GPS1, RBX1, COPS2, COPS6, COPS8, ERCC8, COPS3, COPS4
★ UV-DDB complex	8	PARP1, COPS4, COPS7A, CUL4A, CUL4B, DDB1, DDB2, GPS1
Ubiquitin E3 ligase (AHR, ARNT, DDB1, TBL3, CUL4B, RBX1)	6	RBX1, TBL3, AHR, ARNT, CUL4B, DDB1
★ PARP1-XPC-DDB ligase complex	6	CUL4A, DDB1, DDB2, PARP1, RBX1, XPC
Ubiquitin E3 ligase (DDB1, DDB2, CUL4A, CUL4B, RBX1)	5	DDB2, RBX1, CUL4A, CUL4B, DDB1
Ubiquitin E3 ligase (DET1, DDB1, CUL4A, RBX1, COP1)	5	COP1, CUL4A, DDB1, DET1, RBX1
CUL4B-DDB1-DTL-CSN complex	5	DDB1, DTL, GPS1, COPS2, CUL4B
WDTC1-DDB1-CUL4-ROC1 E3 ligase complex	5	CUL4A, CUL4B, DDB1, RBX1, WDTC1
Ubiquitin E3 ligase (CDT1, DDB1, CUL4A, RBX1)	4	CDT1, CUL4A, DDB1, RBX1
Ubiquitin E3 ligase (DDB1, DYRK2, EDD, VPRBP)	4	UBR5, DCAF1, DDB1, DYRK2
Ubiquitin E3 ligase (DDIT4, DDB1, BTRC, CUL4A)	4	BTRC, CUL4A, DDB1, DDIT4
★ CRBN-DDB1-CUL4A-RBX1 E3 ubiquitin ligase	4	CRBN, CUL4A, DDB1, RBX1
Ubiquitin E3 ligase (DDB1, CUL4A, RBX1)	3	DDB1, RBX1, CUL4A
CUL4A-DDB1-DTL complex	3	DTL, CUL4A, DDB1
CUL4B-DDB1-TLE2 complex	3	CUL4B, DDB1, TLE2
CUL4A-DDB1-EED complex	3	CUL4A, DDB1, EED
CUL4A-DDB1-WDR5 complex	3	CUL4A, DDB1, WDR5
CUL4B-DDB1-WDR26 complex	3	CUL4B, DDB1, WDR26
CUL4A-DDB1-RBBP5 complex	3	CUL4A, DDB1, RBBP5
CUL4A-DDB1-WDR5B complex	3	WDR5B, CUL4A, DDB1
CUL4A-DDB1-WDR57 complex	3	SNRNP40, CUL4A, DDB1
CUL4A-DDB1-WDR61 complex	3	CUL4A, DDB1, SKIC8
CUL4B-DDB1-GRWD1 complex	3	CUL4B, DDB1, GRWD1
CUL4B-DDB1-TLE1 complex	3	CUL4A, DDB1, TLE1
CUL4B-DDB1-TLE3 complex	3	CUL4B, DDB1, TLE3
DDB complex	2	DDB1, DDB2

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 61 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	7	38.4×	9e-08
Neddylation	17	15.5×	8e-14
PRC2 methylates histones and DNA	5	14.6×	1e-03
Regulation of PD-L1(CD274) transcription	6	12.6×	1e-03
Activation of anterior HOX genes in hindbrain development during early embryogenesis	6	10.5×	1e-03

GO biological processes:

GO term	Partners	Fold	FDR
cellular response to UV	5	25.1×	1e-04
positive regulation of protein catabolic process	5	17.2×	8e-04
protein polyubiquitination	7	13.7×	8e-05
MAPK cascade	5	13.0×	2e-03
protein ubiquitination	17	11.9×	2e-11
negative regulation of canonical Wnt signaling pathway	5	10.0×	5e-03
proteasome-mediated ubiquitin-dependent protein catabolic process	10	8.8×	3e-05
positive regulation of canonical NF-kappaB signal transduction	7	8.6×	9e-04

Disease & clinical

Genetic variants

Variant evidence for DDB1: 238 ClinVar records (6 pathogenic / likely pathogenic). Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	3
Likely pathogenic	3
Uncertain significance	149
Likely benign	29
Benign	5

Top pathogenic / likely-pathogenic (6)

Showing all 6 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
1183956	NM_001923.5(DDB1):c.563G>A (p.Arg188Gln)	Pathogenic	criteria provided, single submitter	2
1183957	NM_001923.5(DDB1):c.637G>A (p.Glu213Lys)	Likely pathogenic	criteria provided, single submitter	2
1700082	NM_001923.5(DDB1):c.341G>A (p.Arg114His)	Likely pathogenic	criteria provided, single submitter	1
3384139	NM_001923.5(DDB1):c.2353G>A (p.Glu785Lys)	Likely pathogenic	criteria provided, single submitter	1
1183954	NG_032697.2:g.20705_20713del	Pathogenic	no assertion criteria provided	1
1183958	NM_001923.5(DDB1):c.1285T>G (p.Phe429Val)	Pathogenic	no assertion criteria provided	1

Per-variant reference — Sugi Variant

Explore DDB1’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 27 predictions of 2,339):

Position(s)	Effect	Δscore	Sites
11:61300807–61300808	donor_loss	1.0000	5
11:61300930	acceptor_gain	1.0000
11:61302226	donor_gain	1.0000
11:61302580–61302581	donor_loss	1.0000	5
11:61303044–61303045	donor_loss	1.0000	5
11:61303156–61303157	acceptor_loss	1.0000	3
11:61303157	acceptor_gain	1.0000
11:61303168	acceptor_gain	1.0000
11:61303171	acceptor_gain	1.0000
11:61303863–61303864	donor_loss	1.0000	4

AlphaMissense

4,533 missense substitutions predicted likely pathogenic (of 7,531 scored), across 973 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
M679	9	0.935	0.998
M927	9	0.919	0.996
M954	9	0.833	0.998
D925	8	0.999	1.000
D110	8	0.998	1.000
F650	8	0.998	1.000
D654	8	0.998	1.000
H711	8	0.998	1.000
F641	8	0.996	1.000
D1090	8	0.996	0.999
D608	8	0.995	1.000
D705	8	0.994	0.999
D1092	8	0.994	0.999
D125	8	0.993	0.998
D318	8	0.993	0.999
F668	8	0.990	1.000
H1140	8	0.990	0.998
H189	8	0.988	0.999
F429	8	0.986	0.999
D948	8	0.984	0.994

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

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

1 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	2.28e-08

Disease associations

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

GenCC curated gene-disease

1 curated gene-disease records:

Disease	Classification	Inheritance	Records
White-Kernohan syndrome	Strong	Autosomal dominant	3

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (5 panels, 5 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

5 panels:

Panel	Rating
DDG2P	green
Hypotonic infant	green
Intellectual disability	green
Leukodystrophy, childhood onset	green
Paediatric disorders	green

Mondo (1): White-Kernohan syndrome (MONDO:0859169)

HPO phenotypes

49 phenotypes (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
HP:0001513	Obesity
HP:0001545	Anteriorly placed anus
HP:0002020	Gastroesophageal reflux
HP:0002870	Obstructive sleep apnea
HP:0003196	Short nose
HP:0003593	Infantile onset
HP:0003621	Juvenile onset
HP:0005280	Depressed nasal bridge
HP:0006989	Dysplastic corpus callosum
HP:0007018	Attention deficit hyperactivity disorder
HP:0010804	Tented upper lip vermilion
HP:0011228	Horizontal eyebrow
HP:0011330	Metopic synostosis
HP:0011463	Childhood onset
HP:0011800	Midface retrusion
HP:0012745	Short palpebral fissure
HP:0020045	Esodeviation
HP:0020206	Simple ear
HP:0034003	Broad medial eyebrow

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)

Drugs acting on a complex or family that includes this protein

Curated ChEMBL mechanism-of-action drugs whose target is a protein complex or family of ≤10 members that includes DDB1 — the drug acts on the assembly or class, not necessarily on this subunit alone.

4 drugs via a complex or family:

Drug	Target (ChEMBL)	Members	Max phase
LENALIDOMIDE	CRL4(CRBN) E3 ubiquitin ligase	4	4
POMALIDOMIDE	CRL4(CRBN) E3 ubiquitin ligase	4	4
THALIDOMIDE	CRL4(CRBN) E3 ubiquitin ligase	4	4
IBERDOMIDE	CRL4(CRBN) E3 ubiquitin ligase	4	3

Molecules with ChEMBL bioactivity

Phase ≥1, by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 121,497 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

7 molecules by phase:

Molecule	Name	Phase	Patents
CHEMBL848	LENALIDOMIDE	4	5,405
CHEMBL43452	POMALIDOMIDE	4	13,944
CHEMBL468	THALIDOMIDE	4	98,570
CHEMBL3989927	IBERDOMIDE	3	1,379
CHEMBL4648616	MEZIGDOMIDE	3	517
CHEMBL3989934	AVADOMIDE	2	1,583
CHEMBL4297459	CC-11006	1	99

PharmGKB: 1 entry (CPIC guideline: no)

Binding affinities (BindingDB)

1636 measured of 2378 human assays (2390 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
6-(2-quinolin-4-ylimidazol-1-yl)-1,6-dihydrobenzimidazol-2-one	KD	1 nM	US-11787802: Dihydrobenzimidazolones for medical treatment
5-(2,3-dihydroindole-1-carbonyl)-1,3,3a,4,5,6,7,7a-octahydrobenzimidazol-2-one	KD	1 nM	US-11787802: Dihydrobenzimidazolones for medical treatment
1-methyl-2-oxo-N-phenyl-3H-imidazo[4,5-b]pyridine-6-carboxamide	KD	1 nM	US-11787802: Dihydrobenzimidazolones for medical treatment
N-methyl-3-(2-oxo-3,5-dihydrobenzimidazol-5-yl)-2-propan-2-ylbenzimidazole-5-carboxamide	KD	1 nM	US-11787802: Dihydrobenzimidazolones for medical treatment
2-(4-aminophenyl)-N-(2-oxo-1,3,3a,4,5,6,7,7a-octahydrobenzimidazol-5-yl)acetamide	KD	1 nM	US-11787802: Dihydrobenzimidazolones for medical treatment
2-[4-(methylsulfamoyl)phenyl]-N-(2-oxobenzimidazol-5-yl)acetamide	KD	1 nM	US-11787802: Dihydrobenzimidazolones for medical treatment
N-[(3S)-2,6-dioxopiperidin-3-yl]-6,7-dihydro-5H-cyclopenta[b]pyridine-5-carboxamide	KD	1 nM	US-11802131: Glutarimides for medical treatment
N-[(3S)-2,6-dioxopiperidin-3-yl]-1-benzofuran-3-carboxamide	KD	1 nM	US-11802131: Glutarimides for medical treatment
N-[(3S)-2,6-dioxopiperidin-3-yl]imidazo[1,2-a]pyridine-3-carboxamide	KD	1 nM	US-11802131: Glutarimides for medical treatment
2-Isopropyl-N-methyl-1-(2-oxoindolin-6-yl)benzimidazole-5-carboxamide	KD	2 nM	US-12528797: Heterocyclic compounds for medical treatment
6-(4-Hydroxyisoindoline-2-carbonyl)-3H-1,3-benzoxazol-2-one	KD	2 nM	US-12528797: Heterocyclic compounds for medical treatment
methyl 6-(2,4-dioxo-1,3,7- triazaspiro[4.4]nonan-7- yl)nicotinate	KD	2 nM	US-11623929: Spirocyclic compounds
N-(1-acetylpiperidin-4-yl)-2-oxo-1,7a-dihydroimidazo[4,5-b]pyridine-6-carboxamide	KD	2 nM	US-11787802: Dihydrobenzimidazolones for medical treatment
4-acetamido-N-(2-oxo-1,3,3a,4,5,6,7,7a-octahydrobenzimidazol-5-yl)benzamide	KD	2 nM	US-11787802: Dihydrobenzimidazolones for medical treatment
N-(2,6-dioxopiperidin-3-yl)-2,3-dihydroindole-1-carboxamide	KD	2 nM	US-11802131: Glutarimides for medical treatment
N-(2,6-dioxopiperidin-3-yl)-1-benzofuran-3-carboxamide	KD	2 nM	US-11802131: Glutarimides for medical treatment
N-[(3R)-2,6-dioxopiperidin-3-yl]indolizine-3-carboxamide	KD	2 nM	US-11802131: Glutarimides for medical treatment
2-Isopropyl-N-methyl-1-(2-oxoindolin-5-yl)benzimidazole-5-carboxamide	KD	3 nM	US-12528797: Heterocyclic compounds for medical treatment
7-((S)-1,2,3,4- tetrahydronaphthalene-1-carbonyl)- 1,3,7-triazaspiro[4.4]nonane-2,4- dione	KD	3 nM	US-11623929: Spirocyclic compounds
N-(1-acetylpiperidin-4-yl)-2-oxo-3,5-dihydrobenzimidazole-5-carboxamide	KD	3 nM	US-11787802: Dihydrobenzimidazolones for medical treatment
methyl 1-(2-oxo-3,3a-dihydrobenzimidazol-5-yl)benzimidazole-2-carboxylate	KD	3 nM	US-11787802: Dihydrobenzimidazolones for medical treatment
6-(benzimidazol-1-yl)-1,7a-dihydrobenzimidazol-2-one	KD	3 nM	US-11787802: Dihydrobenzimidazolones for medical treatment
6-[2-(1-hydroxyethyl)benzimidazol-1-yl]-1,7a-dihydrobenzimidazol-2-one	KD	3 nM	US-11787802: Dihydrobenzimidazolones for medical treatment
5-[2-[hydroxy(phenyl)methyl]benzimidazol-1-yl]-1,3,3a,4,5,6,7,7a-octahydrobenzimidazol-2-one	KD	3 nM	US-11787802: Dihydrobenzimidazolones for medical treatment
N-[1-[(2-oxo-1,3,3a,4,5,6,7,7a-octahydrobenzimidazol-5-yl)methyl]-2,3-dihydroindol-5-yl]acetamide	KD	3 nM	US-11787802: Dihydrobenzimidazolones for medical treatment
N-(2,6-dioxopiperidin-3-yl)-N-methyl-1H-indole-3-carboxamide	KD	3 nM	US-11802131: Glutarimides for medical treatment
N-[(3R)-2,6-dioxopiperidin-3-yl]-6,7-dihydro-5H-cyclopenta[b]pyridine-5-carboxamide	KD	3 nM	US-11802131: Glutarimides for medical treatment
(1S)-N-[(3S)-2,6-dioxopiperidin-3-yl]-1,2,3,4-tetrahydronaphthalene-1-carboxamide	KD	3 nM	US-11802131: Glutarimides for medical treatment
N-[(3R)-2,6-dioxopiperidin-3-yl]imidazo[1,5-a]pyridine-3-carboxamide	KD	3 nM	US-11802131: Glutarimides for medical treatment
2-(3-acetamidophenyl)-N-[(3R)-2,6-dioxopiperidin-3-yl]acetamide	KD	3 nM	US-11802131: Glutarimides for medical treatment
N-[(3R)-2,6-dioxopiperidin-3-yl]-2-(2-oxo-1,3-dihydroindol-5-yl)acetamide	KD	3 nM	US-11802131: Glutarimides for medical treatment
N-(2-Oxo-3H-1,3-benzoxazol-6-yl)benzamide	KD	4 nM	US-12528797: Heterocyclic compounds for medical treatment
6-(Indoline-1-carbonyl)-3H-1,3-benzoxazol-2-one	KD	4 nM	US-12528797: Heterocyclic compounds for medical treatment
7-benzoyl-1,3,7- triazaspiro[4.4]nonane-2,4-dione	KD	4 nM	US-11623929: Spirocyclic compounds
N-methyl-1-(2-oxo-3,3a-dihydroimidazo[4,5-b]pyridin-6-yl)-2-propan-2-ylbenzimidazole-5-carboxamide	KD	4 nM	US-11787802: Dihydrobenzimidazolones for medical treatment
N-methyl-3-[1-(2-oxo-3,3a-dihydrobenzimidazol-5-yl)benzimidazol-2-yl]propanamide	KD	4 nM	US-11787802: Dihydrobenzimidazolones for medical treatment
N-(1-acetylpiperidin-4-yl)-N-methyl-2-oxo-3,5-dihydrobenzimidazole-5-carboxamide	KD	4 nM	US-11787802: Dihydrobenzimidazolones for medical treatment
N-(2-oxo-1,3,3a,4,5,6,7,7a-octahydroimidazo[4,5-b]pyridin-6-yl)-2,3-dihydroindole-1-carboxamide	KD	4 nM	US-11787802: Dihydrobenzimidazolones for medical treatment
N-(1-benzylpiperidin-4-yl)-2-oxo-1,3,3a,4,5,6,7,7a-octahydrobenzimidazole-5-carboxamide	KD	4 nM	US-11787802: Dihydrobenzimidazolones for medical treatment
(1R)-N-(2,6-dioxopiperidin-3-yl)-1,2,3,4-tetrahydronaphthalene-1-carboxamide	KD	4 nM	US-11802131: Glutarimides for medical treatment
N-[(3S)-2,6-dioxopiperidin-3-yl]-3,4-dihydro-2H-quinoline-1-carboxamide	KD	4 nM	US-11802131: Glutarimides for medical treatment
N-[(3S)-2,6-dioxopiperidin-3-yl]-3,4-dihydro-2H-1,8-naphthyridine-1-carboxamide	KD	4 nM	US-11802131: Glutarimides for medical treatment
(1R)-N-[(3R)-2,6-dioxopiperidin-3-yl]-1,2,3,4-tetrahydronaphthalene-1-carboxamide	KD	4 nM	US-11802131: Glutarimides for medical treatment
N-[(3S)-2,6-dioxopiperidin-3-yl]imidazo[1,5-a]pyridine-3-carboxamide	KD	4 nM	US-11802131: Glutarimides for medical treatment
tert-butyl 3-[[(3S)-2,6-dioxopiperidin-3-yl]carbamoyl]-1-methyl-6,7-dihydro-4H-pyrazolo[4,3-c]pyridine-5-carboxylate	KD	4 nM	US-11802131: Glutarimides for medical treatment
6-(2-methyl-1,3-thiazol-5-yl)-1,6-dihydrobenzimidazol-2-one	KD	5 nM	US-11787802: Dihydrobenzimidazolones for medical treatment
1-acetyl-N-(2-oxobenzimidazol-5-yl)piperidine-4-carboxamide	KD	5 nM	US-11787802: Dihydrobenzimidazolones for medical treatment
N-[(3S)-2,6-dioxopiperidin-3-yl]-3,4-dihydro-2H-chromene-4-carboxamide	KD	5 nM	US-11802131: Glutarimides for medical treatment
N-[(3S)-2,6-dioxopiperidin-3-yl]-1-methyl-3,4-dihydro-2H-quinoline-4-carboxamide	KD	5 nM	US-11802131: Glutarimides for medical treatment
N-(1-Acetyl-4-piperidyl)-2-oxo-3H-1,3-benzoxazole-6-carboxamide	KD	6 nM	US-12528797: Heterocyclic compounds for medical treatment

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

156 with measured affinity, of 390 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-[3-(difluoromethyl)-1-[4-[[4-[3-[1-[(3S)-2,6-dioxopiperidin-3-yl]-3-methyl-2-oxobenzimidazol-4-yl]prop-2-ynoxy]piperidin-1-yl]methyl]cyclohexyl]pyrazol-4-yl]-5-[(1R,4R)-2-oxa-5-azabicyclo[2.2.1]heptan-5-yl]pyrazolo[1,5-a]pyrimidine-3-carboxamide	2203528: Binding affinity to ZZ domain 6-His thrombin tagged CRBN (40 to 442 residues) (unknown origin)/DDB1 (1 to 1140 residues) (unknown origin) extracted from baculovirus expression system incubated for 60 mins in presence of Cy5-thalidomide probe by HTRF assay	ic50	0.0050	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
tert-butyl 6-[[3-(2,6-dioxopiperidin-3-yl)-1-methylindazol-6-yl]amino]-2-azaspiro[3.3]heptane-2-carboxylate	2251185: Binding affinity to 6-his tagged CRBN (1 to 442 residues)/ DDB1 (1 to 1140 residues) (unknown origin) incubated for 20 mins by time-resolved fluorescence probe displacement assay	ic50	0.0200	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
3-[1-methyl-6-(piperidin-4-ylamino)indazol-3-yl]piperidine-2,6-dione	2251185: Binding affinity to 6-his tagged CRBN (1 to 442 residues)/ DDB1 (1 to 1140 residues) (unknown origin) incubated for 20 mins by time-resolved fluorescence probe displacement assay	ic50	0.0300	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
tert-butyl 4-[[3-(2,6-dioxopiperidin-3-yl)-1-methylindazol-6-yl]amino]azepane-1-carboxylate	2251185: Binding affinity to 6-his tagged CRBN (1 to 442 residues)/ DDB1 (1 to 1140 residues) (unknown origin) incubated for 20 mins by time-resolved fluorescence probe displacement assay	ic50	0.0400	uM
2-[2-[[6-(hydroxymethyl)-2-pyridinyl]amino]-1,3-thiazol-4-yl]-N-(5-methyl-1,3-thiazol-2-yl)acetamide	1895603: Molecular glue activity at human CDK12/CCNK (11 to 267 residues)/human DDB1-CUL4-RBX1 expressed in baculovirus expression system in human 293 TA cells assessed as CCNK protein degradation	ec50	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-[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
3-[6-(1,4-dioxa-8-azaspiro[4.5]decan-8-yl)-1-methylindazol-3-yl]piperidine-2,6-dione	2251185: Binding affinity to 6-his tagged CRBN (1 to 442 residues)/ DDB1 (1 to 1140 residues) (unknown origin) incubated for 20 mins by time-resolved fluorescence probe displacement assay	ic50	0.0500	uM
tert-butyl (3S)-3-[[3-(2,6-dioxopiperidin-3-yl)-1-methylindazol-6-yl]amino]pyrrolidine-1-carboxylate	2251185: Binding affinity to 6-his tagged CRBN (1 to 442 residues)/ DDB1 (1 to 1140 residues) (unknown origin) incubated for 20 mins by time-resolved fluorescence probe displacement assay	ic50	0.0500	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
3-[6-(benzylamino)-1-methylindazol-3-yl]piperidine-2,6-dione	2251185: Binding affinity to 6-his tagged CRBN (1 to 442 residues)/ DDB1 (1 to 1140 residues) (unknown origin) incubated for 20 mins by time-resolved fluorescence probe displacement assay	ic50	0.0600	uM
tert-butyl 4-[[3-(2,6-dioxopiperidin-3-yl)-1-methylindazol-6-yl]amino]piperidine-1-carboxylate	2251185: Binding affinity to 6-his tagged CRBN (1 to 442 residues)/ DDB1 (1 to 1140 residues) (unknown origin) incubated for 20 mins by time-resolved fluorescence probe displacement assay	ic50	0.0700	uM
tert-butyl 4-[3-(2,6-dioxopiperidin-3-yl)-1-methylindazol-6-yl]piperazine-1-carboxylate	2251185: Binding affinity to 6-his tagged CRBN (1 to 442 residues)/ DDB1 (1 to 1140 residues) (unknown origin) incubated for 20 mins by time-resolved fluorescence probe displacement assay	ic50	0.0700	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Smoke	increases abundance, increases expression, decreases expression	3
Dronabinol	decreases expression, increases expression	3
Cadmium Chloride	decreases expression, increases abundance, increases expression	3
bisphenol A	increases methylation, decreases expression, affects cotreatment	2
Air Pollutants	increases abundance, increases expression, decreases expression	2
Doxorubicin	decreases expression, increases expression	2
Particulate Matter	increases abundance, increases expression, decreases expression	2
triphenyl phosphate	affects expression	1
pyrithione zinc	increases expression	1
beta-lapachone	increases expression, decreases 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
Arsenic	increases ubiquitination	1
Vehicle Emissions	increases abundance, increases expression	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

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)

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

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for DDB1 across ~30M SureChEMBL compounds — explore on Sugi Predict.