CUL4B

Summary

CUL4B (cullin 4B, HGNC:2555) is a protein-coding gene on chromosome Xq24, encoding Cullin-4B (Q13620). Core component of multiple cullin-RING-based E3 ubiquitin-protein ligase complexes which mediate the ubiquitination and subsequent proteasomal degradation of target proteins. It is haploinsufficient (ClinGen: sufficient evidence).

This gene is a member of the cullin family. The encoded protein forms a complex that functions as an E3 ubiquitin ligase and catalyzes the polyubiquitination of specific protein substrates in the cell. The protein interacts with a ring finger protein, and is required for the proteolysis of several regulators of DNA replication including chromatin licensing and DNA replication factor 1 and cyclin E. Multiple transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 8450 — RefSeq curated summary.

At a glance

• Gene–disease (curated): X-linked intellectual disability, Cabezas type (Definitive, ClinGen)
• Clinical variants (ClinVar): 572 total — 35 pathogenic, 26 likely-pathogenic
• Phenotypes (HPO): 82
• Druggable target: yes
• Dosage sensitivity (ClinGen): haploinsufficiency sufficient evidence, triplosensitivity no evidence
• MANE Select transcript: NM_001079872

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2555
Approved symbol	CUL4B
Name	cullin 4B
Location	Xq24
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000158290
Ensembl biotype	protein_coding
OMIM	300304
Entrez	8450

Gene structure

Transcript identifiers

Ensembl transcripts: 42 — 17 protein_coding, 12 retained_intron, 9 nonsense_mediated_decay, 3 protein_coding_CDS_not_defined, 1 non_stop_decay

ENST00000336592, ENST00000371322, ENST00000371323, ENST00000404115, ENST00000467641, ENST00000486604, ENST00000497616, ENST00000673919, ENST00000674073, ENST00000674137, ENST00000679405, ENST00000679432, ENST00000679844, ENST00000679927, ENST00000679965, ENST00000680165, ENST00000680324, ENST00000680457, ENST00000680474, ENST00000680577, ENST00000680673, ENST00000680918, ENST00000680988, ENST00000681080, ENST00000681090, ENST00000681148, ENST00000681189, ENST00000681206, ENST00000681224, ENST00000681236, ENST00000681253, ENST00000681263, ENST00000681333, ENST00000681487, ENST00000681652, ENST00000681681, ENST00000681706, ENST00000681864, ENST00000681869, ENST00000681908, ENST00000890508, ENST00000890509

RefSeq mRNA: 4 — MANE Select: NM_001079872 NM_001079872, NM_001330624, NM_001369145, NM_003588

CCDS: CCDS35379, CCDS43987, CCDS83487, CCDS94662

Canonical transcript exons

ENST00000371322 — 20 exons

Exon	Start	End
ENSE00001097655	120532422	120532594
ENSE00001097668	120543727	120543809
ENSE00001097669	120557924	120558039
ENSE00001170280	120538660	120538770
ENSE00001170284	120539268	120539372
ENSE00001170293	120541602	120541720
ENSE00001170312	120544481	120544643
ENSE00001245121	120544114	120544203
ENSE00001322740	120545444	120545517
ENSE00001356012	120538124	120538209
ENSE00001388844	120540370	120540562
ENSE00001454952	120546547	120546616
ENSE00001454953	120547136	120547239
ENSE00001595928	120530102	120530254
ENSE00001729403	120542966	120543033
ENSE00003513087	120534481	120534586
ENSE00003601382	120536927	120537034
ENSE00003609753	120535830	120535943
ENSE00003896707	120560083	120560962
ENSE00003898822	120523858	120526856

Expression profiles

Bgee: expression breadth ubiquitous, 291 present calls, max score 97.56.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 54.7739 / max 1010.2018, expressed in 1821 samples.

FANTOM5 promoters (25 alternative TSS)

Promoter ID	TPM avg	Samples expressed
200366	16.2666	1794
200360	8.4106	1523
200361	7.4890	1570
200372	3.9219	1575
200369	3.5416	1488
200356	3.3007	979
200353	2.0415	763
200367	1.3501	919
200365	1.1786	733
200362	0.8949	528

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sperm	CL:0000019	97.56	gold quality
male germ cell	CL:0000015	97.21	gold quality
corpus epididymis	UBERON:0004359	97.14	gold quality
tendon of biceps brachii	UBERON:0008188	96.98	gold quality
cauda epididymis	UBERON:0004360	96.78	gold quality
caput epididymis	UBERON:0004358	96.00	gold quality
tendon	UBERON:0000043	95.08	gold quality
calcaneal tendon	UBERON:0003701	94.93	gold quality
ganglionic eminence	UBERON:0004023	94.50	gold quality
cortical plate	UBERON:0005343	94.49	gold quality
stromal cell of endometrium	CL:0002255	94.00	gold quality
ventricular zone	UBERON:0003053	93.99	gold quality
superficial temporal artery	UBERON:0001614	93.94	gold quality
adenohypophysis	UBERON:0002196	93.85	gold quality
seminal vesicle	UBERON:0000998	93.84	gold quality
buccal mucosa cell	CL:0002336	93.82	gold quality
tibia	UBERON:0000979	93.67	gold quality
pituitary gland	UBERON:0000007	93.62	gold quality
descending thoracic aorta	UBERON:0002345	93.62	gold quality
endocervix	UBERON:0000458	93.45	gold quality
right coronary artery	UBERON:0001625	93.26	gold quality
embryo	UBERON:0000922	93.19	gold quality
popliteal artery	UBERON:0002250	93.15	gold quality
tibial artery	UBERON:0007610	93.15	gold quality
ovary	UBERON:0000992	93.09	gold quality
adrenal tissue	UBERON:0018303	93.07	gold quality
lower esophagus mucosa	UBERON:0035834	93.05	gold quality
parietal pleura	UBERON:0002400	92.94	gold quality
left coronary artery	UBERON:0001626	92.82	gold quality
ectocervix	UBERON:0012249	92.82	gold quality

Single-cell (SCXA)

Detected in 6 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-MTAB-6678	yes	1485.50
E-ANND-3	yes	4.23
E-MTAB-7249	no	45006.94
E-GEOD-124858	no	1106.48
E-MTAB-7606	no	137.04
E-CURD-112	no	2.25

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

156 targeting CUL4B, 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-3646	100.00	73.56	5283
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-4776-3P	100.00	68.73	1340
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-3617-3P	99.98	67.86	918
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-146A-5P	99.96	68.93	988
HSA-MIR-146B-5P	99.96	69.13	977
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-101-3P	99.94	75.03	2230
HSA-MIR-7153-5P	99.94	68.89	1006
HSA-MIR-381-3P	99.93	71.87	2854

Functional genomics

ClinGen dosage: haploinsufficiency 3 (sufficient evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• human CUL4B and cyclin E proteins interact with each other and the CUL4B complexes can polyubiquitinate the CUL4B-associated cyclin E (PMID:16322693)
• Cul4B, PCNA, and DDB1 are involved in the degradation of Cdt1 after ultraviolet radiation (PMID:16407252)
• The relatively high frequency of CUL4B mutations in this series indicates that it is one of the most commonly mutated genes underlying XLMR and suggests that its introduction into clinical diagnostics should be a high priority. (PMID:17236139)
• Mutation in CUL4B causes X-linked mental retardation (PMID:17273978)
• a fat-soluble ligand-dependent ubiquitin ligase complex in human cell lines, in which dioxin receptor (AhR) is integrated as a component of a novel cullin 4B ubiquitin ligase complex, CUL4B(AhR) (PMID:17392787)
• CUL4-DDB1 ubiquitin ligase interacts with Raptor and regulates the mTORC1-mediated signaling pathway through ubiquitin-dependent proteolysis. (PMID:18235224)
• 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)
• CUL4A and CUL4B are therefore components of a conserved Wnt-induced proteasome targeting (WIPT) complex that regulates p27(KIP1) levels and cell cycle progression in mammalian cells. (PMID:19056892)
• Cells depleted of Dda1 spontaneously accumulated double-stranded DNA breaks in a similar way to Cul4A-, Cul4B- or Wdr23-depleted cells, indicating that Dda1 interacts physically and functionally with cullin-RING E3 ligases complexes. (PMID:19295130)
• Data show that that RNA interference of CUL4B led to an inhibition of cell proliferation and a prolonged S phase, due to the overaccumulation of cyclin E. (PMID:19801544)
• Studies indicate that CUL4 uses a large beta-propeller protein, DDB1, as a linker to interact with a subset of WD40 proteins. (PMID:19818632)
• The CUL4B gene is associated with X-linked mental retardation syndrome. (PMID:20002452)
• CUL4B is over-expressed in placenta in intra-uterine growth restriction. (PMID:20005570)
• the interplay between CUL4A and CUL4B in pathogenesis of CUL4B-deficiency in humans (PMID:20064923)
• This study identifies CRL4-Cdt2 ubiquitin ligase to promote the ubiquitin-dependent proteolysis of the histone H4 methyltransferase Set8 during S-phase of the cell cycle and after UV-irradiation in a reaction that is dependent on PCNA. (PMID:20932471)
• Increased PRMT5 activity mediates key events associated with cyclin D1-dependent neoplastic growth, including CUL4 repression, CDT1 overexpression, and DNA rereplication. (PMID:20951943)
• the unexpected association of defective CUL4B with syndromal X-linked mental retardation in humans (PMID:21352845)
• Cullin 4B protein ubiquitin ligase targets peroxiredoxin III for degradation. (PMID:21795677)
• CUL4B targets WDR5 for ubiquitylation and degradation in the nucleus. (PMID:21816345)
• The data suggest that unneddylated Cul4B isoforms specifically inhibits beta-catenin degradation during mitosis. (PMID:22992378)
• Cullin4B-Ring E3 ligase complex (CRL4B) is physically associated with PRC2. CRL4B possesses an intrinsic transcription repressive activity by promoting H2AK119 monoubiquitination. CUL4B promotes cancer cell proliferation, invasion, and tumorigenesis in vitro and in vivo. (PMID:23238014)
• Our results suggest that XLID CUL4B mutants are defective in promoting TSC2 degradation and positively regulating mTOR signaling in neocortical neurons (PMID:23348097)
• Studies indicate Jun activation domain-binding protein Jab1 as a substrate for CUL4B E3 ligase. (PMID:23357576)
• the up-regulation of CDK2 by CUL4B is achieved via the repression of miR-372 and miR-373, which target CDK2. (PMID:23479742)
• Investigated CUL4B expression pattern in patients with colon cancer; immunohistochemistry and PCR study showed that high CUL4B expression was significantly associated with colon cancer progression and pathogenesis. (PMID:23649548)
• CRL4B promotes tumorigenesis by coordinating with SUV39H1/HP1/DNMT3A in DNA methylation-based epigenetic silencing (PMID:24292684)
• these observations establish an important negative regulatory role of CUL4B on p53 stability. (PMID:24452595)
• HIV-1 Vpr can trigger G2 cell cycle arrest in the absence of either CUL4A or CUL4B. (PMID:24719410)
• The intellectual disability phenotype is caused by aberrant splicing and removal of intron 7 from CUL4B gene primary transcript. (PMID:24898194)
• Results demonstrated that CUL4B promotes cell proliferation and inhibits the apoptosis of osteosarcoma cells. (PMID:25189186)
• Data show that CUL4B variants are associated with a wide range of cerebral malformations and suggest an important role in brain through its interaction with WDR62, a protein in which variants were identified in patients with cerebral malformations. (PMID:25385192)
• CUL4B can up-regulate Wnt/beta-catenin signalling in human HCC through transcriptionally repressing Wnt antagonists and thus contributes to the malignancy of HCC. (PMID:25430888)
• results established a critical role of CUL4B in negatively regulating the p53-ROS positive feedback loop that drives cellular senescence (PMID:25464270)
• Results show that CUL4A- and CUL4B-mediated polyubiquitination of gamma-tubulin for its degradation. (PMID:25542213)
• FBXO44-mediated degradation of RGS2 protein uniquely depends on a Cul4B/DDB1 complex. (PMID:25970626)
• Our data are consistent with the idea that the CUL4A/B-DDB1-CRBN complex catalyses the polyubiquitination and thus controls the degradation of CLC-1 channels. (PMID:26021757)
• these results showed that knockdown of CUL4B inhibit proliferation and promotes apoptosis of colorectal cancer cells through suppressing the Wnt/beta-catenin signaling pathway (PMID:26617747)
• these results suggest that knockdown of CUL4B inhibited the proliferation and invasion through suppressing the Wnt/beta-catenin signaling pathway in NSCLC cells. Therefore, CUL4B may represent a novel therapeutic target for the treatment of NSCLC. (PMID:27656838)
• CUL4B protein levels in human subcutaneous adipose tissue is negatively correlated with body mass index. (PMID:27899484)
• findings revealed that CUL4A and CUL4B are differentially associated with etiologic factors for pulmonary malignancies and are independent prognostic markers for the survival of distinct lung cancer subtypes (PMID:27974468)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	cul4b	ENSDARG00000060510
mus_musculus	Cul4b	ENSMUSG00000031095
rattus_norvegicus	Cul4b	ENSRNOG00000002585
drosophila_melanogaster	Cul5	FBGN0288875
caenorhabditis_elegans		WBGENE00000840

Paralogs (7): CUL3 (ENSG00000036257), CUL1 (ENSG00000055130), CUL2 (ENSG00000108094), CUL4A (ENSG00000139842), CACUL1 (ENSG00000151893), CUL5 (ENSG00000166266), ANAPC2 (ENSG00000176248)

Protein

Protein identifiers

Cullin-4B — Q13620 (reviewed: Q13620)

All UniProt accessions (21): Q13620, A0A669KAU9, A0A669KAX4, A0A669KBG9, A0A7P0T809, A0A7P0T894, A0A7P0T8P8, A0A7P0T8W4, A0A7P0T954, A0A7P0T9C8, A0A7P0T9D0, A0A7P0T9L3, A0A7P0T9P5, A0A7P0T9R8, A0A7P0TAF9, A0A7P0TAQ3, A0A7P0Z439, A0A7P0Z4E4, A0A7P0Z4G9, A0A804CL36, K4DI93

UniProt curated annotations — full annotation on UniProt →

Function. Core component of multiple cullin-RING-based E3 ubiquitin-protein ligase complexes which mediate the ubiquitination and subsequent proteasomal degradation of target proteins. The functional specificity of the E3 ubiquitin-protein ligase complex depends on the variable substrate recognition subunit. CUL4B may act within the complex as a scaffold protein, contributing to catalysis through positioning of the substrate and the ubiquitin-conjugating enzyme. Plays a role as part of the E3 ubiquitin-protein ligase complex in polyubiquitination of CDT1, histone H2A, histone H3 and histone H4 in response to radiation-induced DNA damage. Targeted to UV damaged chromatin by DDB2 and may be important for DNA repair and DNA replication. A number of DCX complexes (containing either TRPC4AP or DCAF12 as substrate-recognition component) are part of the DesCEND (destruction via C-end degrons) pathway, which recognizes a C-degron located at the extreme C terminus of target proteins, leading to their ubiquitination and degradation. The DCX(AMBRA1) complex is a master regulator of the transition from G1 to S cell phase by mediating ubiquitination of phosphorylated cyclin-D (CCND1, CCND2 and CCND3). The DCX(AMBRA1) complex also acts as a regulator of Cul5-RING (CRL5) E3 ubiquitin-protein ligase complexes by mediating ubiquitination and degradation of Elongin-C (ELOC) component of CRL5 complexes. Required for ubiquitination of cyclin E (CCNE1 or CCNE2), and consequently, normal G1 cell cycle progression. Regulates the mammalian target-of-rapamycin (mTOR) pathway involved in control of cell growth, size and metabolism. Specific CUL4B regulation of the mTORC1-mediated pathway is dependent upon 26S proteasome function and requires interaction between CUL4B and MLST8. With CUL4A, contributes to ribosome biogenesis.

Subunit / interactions. Component of multiple DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complexes that seem to be formed of DDB1, CUL4A or CUL4B, RBX1 and a variable substrate recognition component which seems to belong to a protein family described as DCAF (Ddb1- and Cul4-associated factor) or CDW (CUL4-DDB1-associated WD40-repeat) proteins. Component of the DCX(DTL) complex with the putative substrate recognition component DTL. Component of the DCX(DDB2) complex with the putative substrate recognition component DDB2. Component of DCX complexes part of the DesCEND (destruction via C-end degrons) pathway, which contain either TRPC4AP or DCAF12 as substrate-recognition component. Component of the DCX(AMBRA1) complex with the substrate recognition component AMBRA1. Part of a complex with RBX1 and TIP120A/CAND1. Interacts with RBX1, GRWD1, MLST8, SMU1, TLE2, TLE3, DCAF1, DDA1, DCAF6, DCAF17, DDB2, DCAF8, TIP120A/CAND1 and TMEM113. Interacts with cyclin E (CCNE1 or CCNE2) and with importins alpha-1 (KPNA2), alpha-3 (KPNA4), alpha-5 (KPNA1) and beta-1 (KPNB1). May interact with WDR26, WDR51B, SNRNP40, WDR61, WDR76 and WDR5. Interacts (unneddylated form) with DCUN1D1, DCUN1D2, DCUN1D3, DCUN1D4 and DCUN1D5; these interactions promote the cullin neddylation. Interacts with FBOX44.

Subcellular location. Cytoplasm. Nucleus.

Post-translational modifications. Neddylated. Deneddylated via its interaction with the COP9 signalosome (CSN) complex.

Disease relevance. Intellectual developmental disorder, X-linked, syndromic, Cabezas type (MRXSC) [MIM:300354] A syndromic form of X-linked intellectual disability characterized by severe intellectual deficit associated with short stature, craniofacial dysmorphism, small testes, muscle wasting in lower legs, kyphosis, joint hyperextensibility, pes cavus, small feet, and abnormalities of the toes. Additional neurologic manifestations include speech delay and impairment, tremor, seizures, gait ataxia, hyperactivity and decreased attention span. The disease is caused by variants affecting the gene represented in this entry.

Pathway. Protein modification; protein ubiquitination.

Similarity. Belongs to the cullin family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q13620-2	1	yes
Q13620-1	2
Q13620-3	3

RefSeq proteins (4): NP_001073341, NP_001317553, NP_001356074, NP_003579 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001373	Cullin_N	Domain
IPR016157	Cullin_CS	Conserved_site
IPR016158	Cullin_homology	Domain
IPR016159	Cullin_repeat-like_dom_sf	Homologous_superfamily
IPR019559	Cullin_neddylation_domain	Domain
IPR036317	Cullin_homology_sf	Homologous_superfamily
IPR036388	WH-like_DNA-bd_sf	Homologous_superfamily
IPR036390	WH_DNA-bd_sf	Homologous_superfamily
IPR045093	Cullin	Family
IPR059120	Cullin-like_AB	Domain

Pfam: PF00888, PF10557, PF26557

UniProt features (70 total): helix 24, modified residue 9, sequence conflict 9, mutagenesis site 5, strand 5, sequence variant 4, splice variant 3, compositionally biased region 3, cross-link 2, turn 2, chain 1, domain 1, region of interest 1, short sequence motif 1

Structure

Experimental structures (PDB)

5 structures.

PDB	Method	Resolution (Å)
4A64	X-RAY DIFFRACTION	2.57
8EI1	X-RAY DIFFRACTION	2.89
4A0C	X-RAY DIFFRACTION	3.8
4A0L	X-RAY DIFFRACTION	7.4
2DO7	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q13620-F1	80.02	0.61

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 (11): 146, 148, 193, 190, 859, 1, 8, 10, 49, 53, 100

Mutagenesis-validated functional residues (5):

Position	Phenotype
55–58	distributed in cytoplasm. fails to promote cell proliferation. no binding to kpna2, kpna4 and kpna1.
55	no impairment in nuclear localization.
56	disrupts nuclear localization and does not bind kpna2, kpna4, kpna1; when associated with a-57. disrupts nuclear localiz
57	disrupts nuclear localization and does not bind kpna2, kpna4, kpna1; when associated with a-56. disrupts nuclear localiz
58	no impairment in nuclear localization.

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: 496 (showing top): GOBP_DNA_TEMPLATED_DNA_REPLICATION_MAINTENANCE_OF_FIDELITY, REACTOME_FORMATION_OF_INCISION_COMPLEX_IN_GG_NER, GOBP_MITOTIC_CYTOKINESIS, GOBP_REGULATION_OF_CELL_ACTIVATION, GOBP_RIBOSOME_BIOGENESIS, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, GOBP_REGULATION_OF_AUTOPHAGY, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, GOBP_REGULATION_OF_DNA_TEMPLATED_DNA_REPLICATION, GOBP_CELLULAR_RESPONSE_TO_UV, GOBP_CELLULAR_RESPONSE_TO_LIGHT_STIMULUS, WANG_RECURRENT_LIVER_CANCER_UP, GOBP_CELL_CYCLE_PHASE_TRANSITION, GOBP_POSITIVE_REGULATION_OF_MITOTIC_CELL_CYCLE, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN

GO Biological Process (15): G1/S transition of mitotic cell cycle (GO:0000082), protein polyubiquitination (GO:0000209), ubiquitin-dependent protein catabolic process (GO:0006511), DNA damage response (GO:0006974), gene expression (GO:0010467), proteasomal protein catabolic process (GO:0010498), protein ubiquitination (GO:0016567), cellular response to UV (GO:0034644), ribosome biogenesis (GO:0042254), positive regulation of protein catabolic process (GO:0045732), astrocyte differentiation (GO:0048708), UV-damage excision repair (GO:0070914), positive regulation of G1/S transition of mitotic cell cycle (GO:1900087), DNA repair (GO:0006281), protein import (GO:0017038)

GO Molecular Function (3): ubiquitin protein ligase binding (GO:0031625), damaged DNA binding (GO:0003684), protein binding (GO:0005515)

GO Cellular Component (11): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytosol (GO:0005829), Cul4A-RING E3 ubiquitin ligase complex (GO:0031464), Cul4B-RING E3 ubiquitin ligase complex (GO:0031465), protein-containing complex (GO:0032991), extracellular exosome (GO:0070062), Cul4-RING E3 ubiquitin ligase complex (GO:0080008), cytoplasm (GO:0005737), membrane (GO:0016020), cullin-RING ubiquitin ligase complex (GO:0031461)

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	4
protein ubiquitination	2
protein catabolic process	2
Cul4-RING E3 ubiquitin ligase complex	2
mitotic cell cycle	1
mitotic cell cycle phase transition	1
cell cycle G1/S phase transition	1
modification-dependent protein catabolic process	1
cellular response to stress	1
macromolecule biosynthetic process	1
protein modification by small protein conjugation	1
response to UV	1
cellular response to light stimulus	1
ribonucleoprotein complex biogenesis	1
positive regulation of catabolic process	1
regulation of protein catabolic process	1
positive regulation of protein metabolic process	1
central nervous system development	1
glial cell differentiation	1
DNA repair	1
cellular response to UV	1
G1/S transition of mitotic cell cycle	1
positive regulation of mitotic cell cycle phase transition	1
positive regulation of cell cycle G1/S phase transition	1
regulation of G1/S transition of mitotic cell cycle	1
DNA metabolic process	1
DNA damage response	1
protein transport	1
ubiquitin-like protein ligase binding	1
DNA binding	1
binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
cytoplasm	1
cellular_component	1
extracellular vesicle	1
cullin-RING ubiquitin ligase complex	1
intracellular anatomical structure	1
ubiquitin ligase complex	1

Protein interactions and networks

STRING

2740 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CUL4B	DDB1	Q16531	999
CUL4B	RBX1	P62877	997
CUL4B	CRBN	Q96SW2	992
CUL4B	DCAF1	Q9Y4B6	985
CUL4B	DTL	Q9NZJ0	982
CUL4B	CUL4A	Q13619	967
CUL4B	CUL1	Q13616	962
CUL4B	RNF7	Q9UBF6	937
CUL4B	DET1	Q7L5Y6	926
CUL4B	CUL2	Q13617	920
CUL4B	CUL3	Q13618	914
CUL4B	CDT1	Q9H211	910
CUL4B	CUL7	Q14999	904
CUL4B	DDB2	Q92466	846
CUL4B	CUL5	Q93034	845

IntAct

251 interactions, top by confidence:

A	B	Type	Score
CAND1	CUL1	psi-mi:“MI:0914”(association)	0.960
CUL4B	DDB1	psi-mi:“MI:0914”(association)	0.940
CUL2	VHL	psi-mi:“MI:0914”(association)	0.940
NEDD8	UBE2M	psi-mi:“MI:0914”(association)	0.940
DDB1	CUL4B	psi-mi:“MI:0915”(physical association)	0.940
COPS8	COPS2	psi-mi:“MI:0914”(association)	0.850
CAND1	CUL4B	psi-mi:“MI:0407”(direct interaction)	0.840
CAND1	CUL4B	psi-mi:“MI:0915”(physical association)	0.840
CUL4B	RBX1	psi-mi:“MI:0914”(association)	0.820
CUL4B	COPS2	psi-mi:“MI:0914”(association)	0.790
STK11	HSP90AA1	psi-mi:“MI:0914”(association)	0.740
CUL4B	CUL4A	psi-mi:“MI:0914”(association)	0.730
DTL	CUL4B	psi-mi:“MI:0914”(association)	0.730
COPS6	RHOBTB1	psi-mi:“MI:0914”(association)	0.730

BioGRID (1351): 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), CUL4B (Affinity Capture-Western), CUL4B (Affinity Capture-Western), CUL4B (Affinity Capture-Western), CUL4B (Affinity Capture-Western), CUL4B (Affinity Capture-Western), CUL4B (Affinity Capture-Western), CUL4B (Affinity Capture-Western)

ESM2 similar proteins: A2A432, A6H5Z3, A9X1D0, B0VX69, B1MTJ4, B2KI88, B5FW36, C1FXW2, E2R766, E2RBS6, F1LSG8, O43242, O54923, O55047, O70133, P60762, Q13098, Q13619, Q13620, Q29425, Q2KJ46, Q3TCH7, Q4V860, Q5NVP9, Q5R5J4, Q5RAN1, Q5RB36, Q5VIR6, Q5ZKV9, Q5ZLD7, Q5ZML9, Q6AYU1, Q6NRT5, Q6NZH6, Q86TU7, Q8CCB4, Q8CI71, Q8K4Q0, Q8N122, Q8R3S6

Diamond homologs: A2A432, A4IHP4, B5DF89, O13790, O14122, O60999, P0CH31, Q09760, Q13616, Q13618, Q13619, Q13620, Q17391, Q17392, Q24311, Q3TCH7, Q54CS2, Q54NZ5, Q54XF7, Q5R4G6, Q5ZC88, Q6DE95, Q6GPF3, Q8LGH4, Q94AH6, Q9C9L0, Q9JLV5, Q9SRZ0, Q9WTX6, Q9ZVH4, Q12018, Q13617, Q17389, Q17390, Q21346, Q5RCF3, Q9D4H8, Q9SZ75, Q9XZJ3, Q9XIE8

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
NAE	“up-regulates activity”	CUL4B	neddylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 155 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	10	25.5×	1e-09
Recognition of DNA damage by PCNA-containing replication complex	6	20.4×	4e-05
Downregulation of ERBB2 signaling	6	20.4×	4e-05
Formation of TC-NER Pre-Incision Complex	9	17.0×	5e-07
HSF1 activation	5	17.0×	5e-04
Neddylation	39	16.5×	9e-35
Transcriptional Regulation by E2F6	5	13.1×	2e-03
NOTCH1 Intracellular Domain Regulates Transcription	6	12.8×	5e-04

GO biological processes:

GO term	Partners	Fold	FDR
protein neddylation	11	57.2×	6e-15
regulation of protein neddylation	7	48.5×	2e-08
SCF-dependent proteasomal ubiquitin-dependent protein catabolic process	6	16.6×	2e-04
intrinsic apoptotic signaling pathway	6	15.9×	2e-04
cellular response to UV	6	13.1×	6e-04
protein monoubiquitination	5	12.7×	3e-03
rhythmic process	6	11.2×	1e-03
protein ubiquitination	35	10.7×	2e-23

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	35
Likely pathogenic	26
Uncertain significance	168
Likely benign	131
Benign	42

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
11338	NM_001079872.2(CUL4B):c.1660C>T (p.Arg554Cys)	Pathogenic
11339	NM_001079872.2(CUL4B):c.1108C>T (p.Arg370Ter)	Pathogenic
11340	NM_001079872.2(CUL4B):c.847-2A>G	Pathogenic
1174539	NM_001079872.2(CUL4B):c.784T>A (p.Leu262Met)	Pathogenic
1202879	NM_001079872.2(CUL4B):c.2158G>T (p.Glu720Ter)	Pathogenic
1342100	NM_001079872.2(CUL4B):c.2439+2T>C	Pathogenic
1803957	NM_001079872.2(CUL4B):c.2264_2265dup (p.Glu756Ter)	Pathogenic
1879772	NM_001079872.2(CUL4B):c.2176C>T (p.Gln726Ter)	Pathogenic
208796	NM_001079872.2(CUL4B):c.1852+1G>T	Pathogenic
235856	NM_001079872.2(CUL4B):c.757_758del (p.Gln253fs)	Pathogenic
265671	NM_001079872.2(CUL4B):c.2189_2190del (p.Phe730fs)	Pathogenic
3342601	NM_001079872.2(CUL4B):c.1246C>T (p.Gln416Ter)	Pathogenic
3364508	NM_001079872.2(CUL4B):c.2484_2487del (p.Arg828fs)	Pathogenic
3600671	NM_001079872.2(CUL4B):c.1349del (p.Asn450fs)	Pathogenic
3629995	NC_000023.10:g.(119681095_119691778)_(119694481_119708405)del	Pathogenic
3730851	NM_001079872.2(CUL4B):c.803dup (p.Leu268fs)	Pathogenic
375587	NM_001079872.2(CUL4B):c.1682_1683del (p.Thr561fs)	Pathogenic
3766067	NM_001079872.2(CUL4B):c.1945C>T (p.Gln649Ter)	Pathogenic
3773643	NM_001079872.2(CUL4B):c.1742-2A>G	Pathogenic
3895538	NM_001079872.2(CUL4B):c.1201_1204del (p.Lys401fs)	Pathogenic
4056404	NM_001079872.2(CUL4B):c.2069dup (p.Lys691fs)	Pathogenic
4075063	NM_001079872.2(CUL4B):c.2512C>T (p.Arg838Ter)	Pathogenic
426723	NM_001079872.2(CUL4B):c.953_957del (p.Ile318fs)	Pathogenic
432812	NM_001079872.2(CUL4B):c.869dup (p.Leu290fs)	Pathogenic
452754	NM_001079872.2(CUL4B):c.777-1G>A	Pathogenic
4530606	NM_001079872.2(CUL4B):c.1741_1741+8del	Pathogenic
4721795	NM_001079872.2(CUL4B):c.1079T>A (p.Leu360Ter)	Pathogenic
520903	NM_001079872.2(CUL4B):c.721C>T (p.Gln241Ter)	Pathogenic
521119	NM_001079872.2(CUL4B):c.1165G>T (p.Glu389Ter)	Pathogenic
523617	NM_001079872.2(CUL4B):c.1404_1405del (p.Val469fs)	Pathogenic

SpliceAI

2486 predictions. Top by Δscore:

Variant	Effect	Δscore
X:120526853:CAGG:C	acceptor_gain	1.0000
X:120526855:GG:G	acceptor_gain	1.0000
X:120526856:GC:G	acceptor_loss	1.0000
X:120526857:C:CA	acceptor_loss	1.0000
X:120526857:C:CC	acceptor_gain	1.0000
X:120526858:T:A	acceptor_loss	1.0000
X:120530100:A:AC	donor_gain	1.0000
X:120530100:ACC:A	donor_loss	1.0000
X:120530101:C:CC	donor_gain	1.0000
X:120530252:AACCT:A	acceptor_loss	1.0000
X:120532496:TGTC:T	donor_gain	1.0000
X:120532591:TCCT:T	acceptor_gain	1.0000
X:120532592:CCTC:C	acceptor_gain	1.0000
X:120532595:C:CC	acceptor_gain	1.0000
X:120534585:CC:C	acceptor_gain	1.0000
X:120534586:CC:C	acceptor_gain	1.0000
X:120534587:C:CA	acceptor_loss	1.0000
X:120534588:T:A	acceptor_loss	1.0000
X:120536920:CTCTT:C	donor_loss	1.0000
X:120536921:TCTTA:T	donor_loss	1.0000
X:120536922:CTTA:C	donor_loss	1.0000
X:120536923:TTACC:T	donor_loss	1.0000
X:120536924:TACCT:T	donor_loss	1.0000
X:120536925:A:AC	donor_gain	1.0000
X:120536925:A:AT	donor_loss	1.0000
X:120536926:C:CC	donor_gain	1.0000
X:120536926:CCT:C	donor_gain	1.0000
X:120536946:T:TA	donor_gain	1.0000
X:120537030:ATATA:A	acceptor_gain	1.0000
X:120537031:TATA:T	acceptor_gain	1.0000

AlphaMissense

5977 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:120526772:A:C	Y911D	1.000
X:120526772:A:G	Y911H	1.000
X:120526778:A:C	Y909D	1.000
X:120526778:A:G	Y909H	1.000
X:120526800:T:A	R901S	1.000
X:120526800:T:G	R901S	1.000
X:120526801:C:A	R901I	1.000
X:120526801:C:G	R901T	1.000
X:120526811:A:C	Y898D	1.000
X:120526811:A:G	Y898H	1.000
X:120526816:C:G	R896P	1.000
X:120526824:T:A	L893F	1.000
X:120526824:T:G	L893F	1.000
X:120526825:A:G	L893S	1.000
X:120526829:A:G	S892P	1.000
X:120526834:A:C	I890R	1.000
X:120526834:A:T	I890K	1.000
X:120526836:T:A	R889S	1.000
X:120526836:T:G	R889S	1.000
X:120526837:C:G	R889T	1.000
X:120526842:C:A	K887N	1.000
X:120526842:C:G	K887N	1.000
X:120526844:T:C	K887E	1.000
X:120526846:A:G	L886P	1.000
X:120526846:A:T	L886H	1.000
X:120530111:A:C	F879L	1.000
X:120530111:A:T	F879L	1.000
X:120530113:A:G	F879L	1.000
X:120530118:A:C	L877W	1.000
X:120530139:A:T	V870D	1.000

dbSNP variants (sampled 300 via entrez): RS1000042031 (X:120548663 G>A), RS1000134960 (X:120526658 T>C,G), RS1000141793 (X:120576053 A>G), RS1000202122 (X:120557130 C>T), RS1000262373 (X:120567410 A>G), RS1000489179 (X:120525928 CTT>C), RS1000492628 (X:120576741 T>G), RS1000552650 (X:120557496 G>A), RS1000593369 (X:120564728 C>T), RS1000884348 (X:120541173 T>C), RS1000894946 (X:120550970 G>A,T), RS1000934560 (X:120541791 A>G), RS1000943093 (X:120555305 C>A), RS1001154505 (X:120539799 A>G), RS1001195873 (X:120541499 C>A)

Disease associations

OMIM: gene MIM:300304 | disease phenotypes: MIM:300354, MIM:300257, MIM:304340

GenCC curated gene-disease

Disease	Classification	Inheritance
X-linked intellectual disability, Cabezas type	Definitive	X-linked

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
X-linked intellectual disability, Cabezas type	Definitive	XL

Mondo (5): X-linked intellectual disability, Cabezas type (MONDO:0010306), intellectual disability (MONDO:0001071), oligospermia (MONDO:0001913), Danon disease (MONDO:0010281), syndromic X-linked intellectual disability 5 (MONDO:0010574)

Orphanet (7): X-linked intellectual disability, Vitale type (Orphanet:85289), X-linked intellectual disability, Cabezas type (Orphanet:85293), Danon disease (Orphanet:34587), X-linked intellectual disability-Dandy-Walker malformation-basal ganglia disease-seizures syndrome (Orphanet:1568), X-linked intellectual disability-hypotonia-facial dysmorphism-aggressive behavior syndrome (Orphanet:85329), Fried syndrome (Orphanet:85335), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

82 total (30 of 82 shown, HPO-id order):

HPO	Term
HP:0000023	Inguinal hernia
HP:0000028	Cryptorchidism
HP:0000047	Hypospadias
HP:0000054	Micropenis
HP:0000135	Hypogonadism
HP:0000154	Wide mouth
HP:0000158	Macroglossia
HP:0000179	Thick lower lip vermilion
HP:0000218	High palate
HP:0000252	Microcephaly
HP:0000256	Macrocephaly
HP:0000280	Coarse facial features
HP:0000286	Epicanthus
HP:0000303	Mandibular prognathia
HP:0000322	Short philtrum
HP:0000348	High forehead
HP:0000363	Abnormal earlobe morphology
HP:0000377	Abnormal pinna morphology
HP:0000414	Bulbous nose
HP:0000448	Prominent nose
HP:0000470	Short neck
HP:0000494	Downslanted palpebral fissures
HP:0000581	Blepharophimosis
HP:0000664	Synophrys
HP:0000712	Emotional lability
HP:0000718	Aggressive behavior
HP:0000750	Delayed speech and language development
HP:0000752	Hyperactivity
HP:0000771	Gynecomastia
HP:0000823	Delayed puberty

GWAS associations

0 associations (top):

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D052120	Glycogen Storage Disease Type IIb	C10.597.606.360.455.562; C14.280.238.458; C16.320.322.201; C16.320.565.202.449.510; C18.452.648.202.449.510
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D009845	Oligospermia	C12.100.500.430.508; C12.100.750.700.508; C12.200.294.430.508

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4523287 (SINGLE PROTEIN)

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

ChEMBL bioactivities

2 potent at pChembl≥5 of 2 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
5.75	Kd	1763	nM	CHEMBL3752910
5.75	ED50	1763	nM	CHEMBL3752910

PubChem BioAssay actives

1 with measured affinity, of 7 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148183: Binding affinity to human CUL4B incubated for 45 mins by Kinobead based pull down assay	kd	1.7633	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression, decreases methylation, increases expression, affects cotreatment	4
Valproic Acid	affects expression, decreases expression	4
trichostatin A	affects cotreatment, decreases expression	2
sodium arsenite	decreases expression, affects cotreatment, increases abundance	2
Benzo(a)pyrene	decreases expression	2
Dexamethasone	increases expression, affects cotreatment, decreases expression	2
Quercetin	decreases expression, increases expression	2
aristolochic acid I	decreases expression	1
FR900359	affects phosphorylation	1
bisphenol F	increases expression	1
2,4,6-tribromophenol	increases expression	1
methylmercuric chloride	decreases expression	1
decabromobiphenyl ether	increases expression	1
cobaltous chloride	decreases expression	1
tetrabromobisphenol A	increases expression	1
manganese chloride	affects cotreatment, decreases expression, increases abundance	1
cupric chloride	decreases expression	1
coumarin	increases phosphorylation	1
phenanthrene	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	decreases expression	1
CPG-oligonucleotide	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	decreases expression, affects cotreatment	1
ICG 001	increases expression	1
bisphenol B	increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	increases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
pentabrominated diphenyl ether 100	increases expression	1
hexabrominated diphenyl ether 153	increases expression	1
2-(1H-indazol-4-yl)-6-(4-methanesulfonylpiperazin-1-ylmethyl)-4-morpholin-4-ylthieno(3,2-d)pyrimidine	increases response to substance, increases expression	1

ChEMBL screening assays

5 unique, capped per target: 5 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4418845	Binding	Inhibition of CUL4B in human MCF7 cells assessed as reduction in 3-methylcholanthrene-induced androgen receptor degradation at 50 uM	Inhibitors of crl4 ubiquitin ligase and uses thereof

Cellosaurus cell lines

7 cell lines: 5 cancer cell line, 2 induced pluripotent stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_B7WX	Abcam Raji CUL4B KO	Cancer cell line	Male
CVCL_B9XH	Abcam THP-1 CUL4B KO	Cancer cell line	Male
CVCL_C6ZD	Abcam PC-3 CUL4B KO	Cancer cell line	Male
CVCL_E1UT	HAP1 CUL4B (-) 1	Cancer cell line	Male
CVCL_E1UU	HAP1 CUL4B (-) 2	Cancer cell line	Male
CVCL_YK76	SDQLCHi015-A	Induced pluripotent stem cell	Male
CVCL_YT39	SDUBMSi002-A	Induced pluripotent stem cell	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT05657860	PHASE4	COMPLETED	Guanfacine Extended Release for the Reduction of Aggression and Self-injurious Behavior Associated With Prader-Willi Syndrome
NCT05744479	PHASE4	RECRUITING	Metformin for Antipsychotic-induced Weight Gain in Adults With Intellectual Disability
NCT06107829	PHASE4	WITHDRAWN	Valbenazine Treatment of Tardive Dyskinesia in Adults With Intellectual/Developmental Disabilities
NCT06997198	PHASE4	NOT_YET_RECRUITING	Deutetrabenazine Treatment for Tardive Dyskinesia in Intellectual/Developmental Disabilities
NCT02270736	PHASE3	COMPLETED	Clinical Study to Investigate the Efficacy and Safety of NT 201 Compared to Placebo in the Treatment of Chronic Troublesome Drooling Associated With Neurological Disorders and/or Intellectual Disability
NCT02304302	PHASE2	COMPLETED	Down Syndrome Memantine Follow-up Study
NCT03862950	PHASE2	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome (Met)
NCT04529226	PHASE2	UNKNOWN	Study to Compare Clozapine vs Treatment as Usual in People With Intellectual Disability & Treatment-resistant Psychosis
NCT04821856	PHASE2	COMPLETED	Evaluation of the Effectiveness of Cannabidiol in Treating Severe Behavioural Problems in Children and Adolescents With Intellectual Disability
NCT05273320	PHASE1	COMPLETED	Clinical Trial of Nabilone for Aggression in Adults With Intellectual and Developmental Disabilities
NCT05301361	PHASE1	ENROLLING_BY_INVITATION	Sensitivity of the NIH Toolbox to Stimulant Treatment in Intellectual Disabilities
NCT06016764	PHASE1	COMPLETED	Use of MRI and cTBS for Catatonia in Autism
NCT06586827	PHASE1	COMPLETED	Impact of Competency-Based Training and Technical Assistance Employment Outcomes of Individuals With ID/DD
NCT07531940	PHASE1	NOT_YET_RECRUITING	Escalating Doses of Memantine in Down Syndrome (MEDS-123)
NCT03479476	PHASE2/PHASE3	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome
NCT02616796	PHASE1/PHASE2	COMPLETED	Effects of Social Gaze Training on Brain and Behavior in Fragile X Syndrome
NCT06860672	EARLY_PHASE1	RECRUITING	Clinical Trial of the Dual Vector Base Editor for the Treatment of the CHD3-R1025W Mutation
NCT00597948	Not specified	COMPLETED	Healthy Lifestyles for People With Intellectual Disabilities
NCT01087320	Not specified	RECRUITING	Genome Medical Sequencing for Gene Discovery
NCT01652963	Not specified	UNKNOWN	Picture-based Computerised Assessment and Training of Cognitive Behaviour Therapy Skills
NCT01695395	Not specified	COMPLETED	Mental Health Care Provision for Adults With Intellectual Disability and a Mental Disorder
NCT01867554	Not specified	COMPLETED	Research and Characterization of New Genes Involved in Intellectual Disability
NCT01915381	Not specified	COMPLETED	Improving Adherence Healthy Lifestyle With a Smartphone Application Based on Adults With Intellectual Disabilities
NCT01988623	Not specified	COMPLETED	Pivotal Response Treatment for Individuals With Intellectual Disabilities
NCT02099773	Not specified	COMPLETED	Support Staff-client Interactions With Augmentative and Alternative Communication
NCT02136849	Not specified	COMPLETED	Inter-regional Project of the Great Western Exploration Approach for Exome Molecular Causes Severe Intellectual Disability Isolated or Syndromic
NCT02225041	Not specified	COMPLETED	Sedation Strategy and Cognitive Outcome After Critical Illness in Early Childhood
NCT02414438	Not specified	COMPLETED	Establishing the Clinical Utility of First StepDx PLUS and NextStepDx PLUS Study
NCT02451761	Not specified	COMPLETED	Apparently Balanced Chromosomal Translocation/ Next-generation Sequencing/ Intellectual Disability
NCT02461420	Not specified	ACTIVE_NOT_RECRUITING	Mapping the Genotype, Phenotype, and Natural History of Phelan-McDermid Syndrome
NCT02461459	Not specified	ACTIVE_NOT_RECRUITING	Autism Spectrum Disorder (ASD) and Intellectual Disability (ID) Determinants in Tuberous Sclerosis Complex (TSC)
NCT02486081	Not specified	COMPLETED	Development and Application-Smart Football for Movement Evaluation and Training in the Special Education Population
NCT02504502	Not specified	COMPLETED	Enhancing Genomic Laboratory Reports to Enhance Communication and Empower Patients
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