TET3

Summary

TET3 (tet methylcytosine dioxygenase 3, HGNC:28313) is a protein-coding gene on chromosome 2p13.1, encoding Methylcytosine dioxygenase TET3 (O43151). Dioxygenase that catalyzes the conversion of the modified genomic base 5-methylcytosine (5mC) into 5-hydroxymethylcytosine (5hmC) and plays a key role in epigenetic chromatin reprogramming in the zygote following fertilization.

Enables RNA polymerase II cis-regulatory region sequence-specific DNA binding activity; methyl-CpG binding activity; and zinc ion binding activity. Involved in positive regulation of transcription by RNA polymerase II and protein O-linked glycosylation. Predicted to be located in cytoplasm and male pronucleus. Predicted to be active in nucleus. Biomarker of esophagus squamous cell carcinoma.

Source: NCBI Gene 200424 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Beck-Fahrner syndrome (Definitive, ClinGen)
• GWAS associations: 10
• Clinical variants (ClinVar): 491 total — 12 pathogenic, 37 likely-pathogenic
• Phenotypes (HPO): 40
• Druggable target: yes — 2 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_001287491

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28313
Approved symbol	TET3
Name	tet methylcytosine dioxygenase 3
Location	2p13.1
Locus type	gene with protein product
Status	Approved
Aliases	MGC22014, hCG_40738
Ensembl gene	ENSG00000187605
Ensembl biotype	protein_coding
OMIM	613555
Entrez	200424

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 3 protein_coding, 1 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000305799, ENST00000409262, ENST00000475405, ENST00000496886, ENST00000718303

RefSeq mRNA: 2 — MANE Select: NM_001287491 NM_001287491, NM_001366022

CCDS: CCDS46339, CCDS92780

Canonical transcript exons

ENST00000409262 — 12 exons

Exon	Start	End
ENSE00001121638	74093529	74093666
ENSE00001121647	74092902	74092991
ENSE00001121655	74089897	74090047
ENSE00001121666	74087830	74088038
ENSE00001121677	74080498	74080591
ENSE00001168240	74099276	74099612
ENSE00001576575	74100393	74108176
ENSE00001581317	74003110	74003166
ENSE00001588201	74046278	74048411
ENSE00001793533	74073549	74073639
ENSE00003753249	73985980	73986706
ENSE00003912414	73984910	73985157

Expression profiles

Bgee: expression breadth ubiquitous, 259 present calls, max score 97.78.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 8.1224 / max 475.9939, expressed in 1615 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
21001	4.0640	1113
20998	2.3440	994
20999	1.7144	623

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
oocyte	CL:0000023	97.78	gold quality
secondary oocyte	CL:0000655	96.59	gold quality
type B pancreatic cell	CL:0000169	94.77	gold quality
olfactory bulb	UBERON:0002264	94.66	gold quality
upper leg skin	UBERON:0004262	94.57	gold quality
gingival epithelium	UBERON:0001949	91.65	gold quality
gingiva	UBERON:0001828	90.73	gold quality
upper arm skin	UBERON:0004263	90.14	gold quality
trabecular bone tissue	UBERON:0002483	90.08	gold quality
penis	UBERON:0000989	89.92	gold quality
skin of hip	UBERON:0001554	89.45	gold quality
diaphragm	UBERON:0001103	89.25	gold quality
bone marrow	UBERON:0002371	88.40	gold quality
oral cavity	UBERON:0000167	87.92	gold quality
bone element	UBERON:0001474	87.92	gold quality
cartilage tissue	UBERON:0002418	87.84	gold quality
bone marrow cell	CL:0002092	87.04	gold quality
mononuclear cell	CL:0000842	86.86	gold quality
monocyte	CL:0000576	86.83	gold quality
esophagus squamous epithelium	UBERON:0006920	86.67	gold quality
mammalian vulva	UBERON:0000997	86.52	gold quality
leukocyte	CL:0000738	86.50	gold quality
squamous epithelium	UBERON:0006914	86.41	gold quality
epithelium of esophagus	UBERON:0001976	86.31	gold quality
amniotic fluid	UBERON:0000173	86.22	gold quality
tongue squamous epithelium	UBERON:0006919	85.67	silver quality
cortical plate	UBERON:0005343	85.50	gold quality
epithelium of nasopharynx	UBERON:0001951	85.16	gold quality
jejunal mucosa	UBERON:0000399	84.87	gold quality
epithelium of bronchus	UBERON:0002031	84.69	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.62

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): PRDM4, TET1

miRNA regulators (miRDB)

416 targeting TET3, 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-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-6127	100.00	66.76	2188
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-188-3P	100.00	68.76	1240
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-3667-3P	99.99	67.17	1636
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-513B-5P	99.99	69.96	2150

Literature-anchored findings (GeneRIF, showing 40)

• mutational status of TET1, TET2, and TET3 in myeloproliferative neoplasms (MPNs), chronic myelomonocytic leukemia (CMML), and acute myeloid leukemia (AML) (PMID:19420352)
• TET family influences DNA methylation in hematopoietic malignancy (PMID:19923888)
• variable association with CXXC modules may contribute to context specific functions of Tet proteins (PMID:23690950)
• Studies indicate that the TET-family enzymes are Fe(II), 2-oxoglutarate-dependent oxygenases and catalyze demethylation of 5-methylcytosine (5mC) by iterative oxidation reactions. (PMID:23727577)
• MiR-29a mimics decrease the levels of Tet1, Tet2, and Tet3; miR-29a inhibition increases all three Tets in human dermal fibroblasts. (PMID:23820384)
• TET3 enhanced its localization to chromatin through the stabilization of OGT protein. (PMID:24304661)
• OGT catalyzes the O-GlcNAcylation of TET3, promotes TET3 nuclear export, and, consequently, inhibits the formation of 5-hydroxymethylcytosine catalyzed by TET3. (PMID:24394411)
• TET1 depletion yields widespread reduction of 5hmC, while depletion of TET2 and TET3 reduces 5hmC at a subset of TET1 targets suggesting functional co-dependence. (PMID:24958354)
• GABRA3 also carries a microRNA (miR-767) with predicted target sites in TET1 and TET3, two members of the ten-eleven-translocation family of tumor suppressor genes, involved in the conversion of 5-methylcytosines to 5-hydroxymethylcytosines in DNA. (PMID:25089631)
• In hepatic stellate cells, cell proliferation rise significantly and cell apoptosis reduce obviously after knockdown of TET3. (PMID:25550811)
• TET1, TET2, and TET3 are highly phosphorylated. (PMID:25568311)
• levels of TET3 and TDG mRNAs were independent prognostic factors for early breast cancer patients who received anthracycline chemotherapy (PMID:26207381)
• Hypoxia deregulates TET3. TET1/3 levels were associated with tumor hypoxia, tumor malignancy, and poor prognosis in breast cancer patients. Coordinate functions of TET1 and TET3 were needed to activate TNFalpha-p38-MAPK signaling in hypoxia. (PMID:26294212)
• these data show that hypoxia-inducible genes are regulated in a multilayered manner that includes epigenetic regulation via TETs and 5-hmC levels in addition to HIF stabilization. (PMID:26703470)
• TET3 expression inhibits glioblastoma tumorigenesis and self-renewal in glioblastoma stem cells. (PMID:26838672)
• TET1, TET2, and TET3 genes are downregulated in endometriosis. (PMID:26917261)
• Results revealed that TET3 acted as a suppressor of ovarian cancer by demethylating miR-30d precursor gene promoter to block TGF-beta1-induced epithelial-mesenchymal transition. (PMID:27141829)
• TET3-5-hydroxymethylcytosine was upregulated in the femoral head tissues of SAON patients and MLO-Y4 cells with dexamethasone (Dex) treatment. (PMID:27627619)
• Here we report that retinoic acid (RA) or retinol (vitamin A) and ascorbate (vitamin C) act as modulators of TET levels and activity. RA or retinol enhances 5hmC production in naive embryonic stem cells by activation of TET2 and TET3 transcription, whereas ascorbate potentiates TET activity and 5hmC production through enhanced Fe(2+) recycling, and not as a cofactor as reported previously (PMID:27729528)
• DNMT3A senses the TGF-beta signal and silences TET2 and TET3 promoters to induce the epithelial-mesenchymal transition-like process and metastasis in melanoma. (PMID:27852070)
• High mRNA levels of TET3 is independent predictor of poor outcome in Renal Cell Carcinoma patients. (PMID:28069330)
• findings have identified distinct roles for TET2 and TET3 in human erythropoiesis, and provide new insights into their role in regulating human erythroid differentiation at distinct stages of development. (PMID:28167661)
• Because the DNA hypomethylation might be a result of TET dioxygenase activity, the study examined expression of TET1-3 enzymes and the level of their product, 5-hydroxymethylcytosine (5hmC), in a panel of histologically characterized seminomas and non-seminomatous germ cell tumors. The study found highly increased expression of TET1 dioxygenase in most seminomas and strong TET1 staining in seminoma cells. (PMID:28218476)
• We found that TET1 and TET2 messenger RNA expression was lower and TET3 was higher in cancers compared to normal tissues. Positive correlation between 5-hmC and the relative expression of TET1 and TET2 was found, but no correlation was observed in the case of TET3. (PMID:28349832)
• Patients with mutations 6 showed higher rate of achieving major molecular response than those<6 (P=0.0381). Mutations in epigenetic regulator, ASXL1, TET2, TET3, KDM1A and MSH6 were found in 25% of patients. TET2 or TET3, AKT1 and RUNX1 were mutated in one patient each. ASXL1 was mutated within exon 12 in three cases (PMID:28452984)
• TET3 interacts with different members of the thyroid hormone nuclear receptors superfamily and also enhances their association to chromatin. (PMID:28716910)
• Overexpression of the wild-type TET1/2/3 3’UTR caused a significant increase in EZH2 expression and tumor growth, whereas the mutation in miR-26-binding sites abolished this effect. (PMID:28923852)
• Infrequent occurrence of TET1, TET3, and ASXL2 mutations in myelodysplastic/myeloproliferative neoplasms (PMID:29531217)
• The expression of TET1, TET2, and TET3 was lower in the villi in early pregnancy loss group than in normal pregnancy group (PMID:30074219)
• abnormal expression in eutopic endometrium from infertile women with endometriosis (PMID:30130982)
• We report a comparison of the specificities of the human MLL1 and TET3 CXXC domains bound to dsDNA containing either cytosine, 5mC, or an enzymatically oxidized 5mC derivatives, in CpG or non-CpG context. With respect to CXXC domain specificity towards non-modified DNA, our work extends a recent analysis, but accounts more carefully for possible confounding influences of cytosine bases away from the site of interest. (PMID:30352306)
• Study data, for the first time, demonstrated an association of the expression levels of TET3 in endothelial progenitor cells (EPCs) with the development of peripheral artery disease (PAD) in diabetic patients. The expression pattern of TET3 mRNA and TET3 protein in EPCs may be a biomarker of angiopathy in diabetic patients. (PMID:30574144)
• miR-150 target that regulates monocyte subsets (PMID:30575719)
• Results indicate that TET3 expression regulated cell proliferation, which is associated with 5hmC in HepG2 cells. (PMID:30836118)
• Hyperglycemia appeared to promote the mRNA expression of SIRT6, TET2 and TE3, which in turn might cause the dynamic changes of 5mC and 5hmC in white blood cells from type 2 diabetes mellitus patients. (PMID:30987683)
• Epigenetic drugs increased expression of TET3 in glioblastoma cells and ectopic overexpression of TET3 impaired in vitro cell growth and markedly reduced tumor formation in immunodeficient mice models. Elevated TET3 mRNA levels were correlated with better prognosis in glioma samples. Results suggest that epigenetic repression of TET3 might promote glioblastoma tumorigenesis through the genome-wide alteration of 5hmC. (PMID:31211412)
• TET3 is a direct target gene of miR-27a-5p, and induces hypomethylation of CpG sites causing overexpression of Synaptophysin (SYP). The miR-27a-5p - TET3 - SYP signaling pathway may regulate proliferation and cortisol secretion in H295R cells and thus play a key role in the development of cortisol-producing adenoma. (PMID:31352437)
• elevated expression of TET3 is associated with poor clinic-pathological functions, poor prognosis, wherein TET3, which presents epigenetic changes or methylation changes, might be served as a diagnostic marker or therapeutic target for ovarian cancer. (PMID:31656201)
• Integrin alpha6 signaling induces STAT3-TET3-mediated hydroxymethylation of genes critical for maintenance of glioma stem cells. (PMID:31819166)
• Somatic mutation and loss of expression of a candidate tumor suppressor gene TET3 in gastric and colorectal cancers. (PMID:31859118)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	tet3	ENSDARG00000062646
mus_musculus	Tet3	ENSMUSG00000034832
rattus_norvegicus	Tet3	ENSRNOG00000011387

Paralogs (2): TET1 (ENSG00000138336), TET2 (ENSG00000168769)

Protein

Protein identifiers

Methylcytosine dioxygenase TET3 — O43151 (reviewed: O43151)

All UniProt accessions (2): A0A5H1ZRP3, O43151

UniProt curated annotations — full annotation on UniProt →

Function. Dioxygenase that catalyzes the conversion of the modified genomic base 5-methylcytosine (5mC) into 5-hydroxymethylcytosine (5hmC) and plays a key role in epigenetic chromatin reprogramming in the zygote following fertilization. Also mediates subsequent conversion of 5hmC into 5-formylcytosine (5fC), and conversion of 5fC to 5-carboxylcytosine (5caC). Conversion of 5mC into 5hmC, 5fC and 5caC probably constitutes the first step in cytosine demethylation. Selectively binds to the promoter region of target genes and contributes to regulate the expression of numerous developmental genes. In zygotes, DNA demethylation occurs selectively in the paternal pronucleus before the first cell division, while the adjacent maternal pronucleus and certain paternally-imprinted loci are protected from this process. Participates in DNA demethylation in the paternal pronucleus by mediating conversion of 5mC into 5hmC, 5fC and 5caC. Does not mediate DNA demethylation of maternal pronucleus because of the presence of DPPA3/PGC7 on maternal chromatin that prevents TET3-binding to chromatin. In addition to its role in DNA demethylation, also involved in the recruitment of the O-GlcNAc transferase OGT to CpG-rich transcription start sites of active genes, thereby promoting histone H2B GlcNAcylation by OGT. Binds preferentially to DNA containing cytidine-phosphate-guanosine (CpG) dinucleotides over CpH (H=A, T, and C), hemimethylated-CpG and hemimethylated-hydroxymethyl-CpG.

Subunit / interactions. Interacts with HCFC1. Interacts with OGT. Directly interacts (via C-terminus) with the DCAF1 component of the CRL4(VprBP) E3 ubiquitin-protein ligase complex.

Subcellular location. Nucleus. Cytoplasm. Chromosome.

Tissue specificity. Expressed in colon, muscle, adrenal gland and peripheral blood lymphocytes.

Post-translational modifications. Monoubiquitinated at Lys-994 by the DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complex called CRL4(VprBP) or CUL4A-RBX1-DDB1-DCAF1/VPRBP complex; this modification promotes binding to DNA.

Disease relevance. Beck-Fahrner syndrome (BEFAHRS) [MIM:618798] A developmental disorder characterized by mild to severe intellectual disability, global developmental delay, hypotonia, autistic traits, movement disorders, growth abnormalities including overgrowth or poor growth, and facial dysmorphism. Both autosomal dominant and autosomal recessive inheritance has been reported. The disease is caused by variants affecting the gene represented in this entry.

Cofactor. Binds 1 Fe(2+) ion per subunit. The zinc ions have a structural role.

Domain organisation. The CXXC zinc finger mediates binding to CpG-DNA. It mediates binding to DNA sequences containing unmethylated cytosine or 5-carboxylcytosine in 5’-CCG-3’ DNA sequence motifs.

Similarity. Belongs to the TET family.

Isoforms (3)

UniProt ID	Names	Canonical?
O43151-1	4	yes
O43151-2	2
O43151-3	3

RefSeq proteins (2): NP_001274420, NP_001352951 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002857	Znf_CXXC	Domain
IPR024779	2OGFeDO_JBP1/TET_oxygenase_dom	Domain
IPR040175	TET1/2/3	Family
IPR046942	TET_oxygenase	Domain

Pfam: PF02008, PF12851

Catalyzed reactions (Rhea), 3 shown:

• a 5-methyl-2’-deoxycytidine in DNA + 2-oxoglutarate + O2 = a 5-hydroxymethyl-2’-deoxycytidine in DNA + succinate + CO2 (RHEA:52636)
• a 5-hydroxymethyl-2’-deoxycytidine in DNA + 2-oxoglutarate + O2 = a 5-formyl-2’-deoxycytidine in DNA + succinate + CO2 + H2O (RHEA:53828)
• a 5-formyl-2’-deoxycytidine in DNA + 2-oxoglutarate + O2 = a 5-carboxyl-2’-deoxycytidine in DNA + succinate + CO2 + H(+) (RHEA:53832)

UniProt features (69 total): binding site 29, region of interest 9, sequence variant 9, cross-link 6, compositionally biased region 5, helix 3, splice variant 2, turn 2, chain 1, zinc finger region 1, mutagenesis site 1, strand 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
4Z3C	X-RAY DIFFRACTION	1.57
8U2Y	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O43151-F1	52.49	0.20

Functional residue map

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

Ligand- & substrate-binding residues (29): 57; 60; 63; 69; 72; 75; 84; 89; 828; 830; 888; 914 …

Post-translational modifications (6): 491, 994, 1188, 1219, 1397, 1561

Mutagenesis-validated functional residues (1):

Position	Phenotype
1077–1079	abolishes methylcytosine dioxygenase activity.

Function

Pathways and Gene Ontology

Reactome pathways

6 pathways

ID	Pathway
R-HSA-5221030	TET1,2,3 and TDG demethylate DNA
R-HSA-9821002	Chromatin modifications during the maternal to zygotic transition (MZT)
R-HSA-1266738	Developmental Biology
R-HSA-212165	Epigenetic regulation of gene expression
R-HSA-74160	Gene expression (Transcription)
R-HSA-9816359	Maternal to zygotic transition (MZT)

MSigDB gene sets: 333 (showing top): GOMF_OXIDOREDUCTASE_ACTIVITY_ACTING_ON_PAIRED_DONORS_WITH_INCORPORATION_OR_REDUCTION_OF_MOLECULAR_OXYGEN, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, GOBP_CARBOHYDRATE_DERIVATIVE_BIOSYNTHETIC_PROCESS, GOBP_DNA_TEMPLATED_TRANSCRIPTION_INITIATION, GOBP_TRANSCRIPTION_INITIATION_AT_RNA_POLYMERASE_II_PROMOTER, GOBP_CHROMATIN_REMODELING, GOBP_EPIGENETIC_REGULATION_OF_GENE_EXPRESSION, GOBP_PROTEIN_O_LINKED_GLYCOSYLATION, GOBP_GLYCOPROTEIN_METABOLIC_PROCESS, GOCC_PRONUCLEUS, ZHENG_BOUND_BY_FOXP3, SMID_BREAST_CANCER_LUMINAL_B_DN, GOMF_DIOXYGENASE_ACTIVITY, GOMF_METHYL_CPG_BINDING, GOMF_SEQUENCE_SPECIFIC_DNA_BINDING

GO Biological Process (10): protein O-linked glycosylation (GO:0006493), positive regulation of gene expression via chromosomal CpG island demethylation (GO:0044029), epigenetic programing of male pronucleus (GO:0044727), positive regulation of transcription by RNA polymerase II (GO:0045944), chromatin organization (GO:0006325), regulation of gene expression (GO:0010468), positive regulation of macromolecule biosynthetic process (GO:0010557), epigenetic regulation of gene expression (GO:0040029), chromosomal 5-methylcytosine DNA demethylation pathway (GO:0141166), chromosomal 5-methylcytosine DNA demethylation, oxidation pathway (GO:0141167)

GO Molecular Function (10): RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), zinc ion binding (GO:0008270), methyl-CpG binding (GO:0008327), DNA 5-methylcytosine dioxygenase activity (GO:0070579), DNA binding (GO:0003677), protein binding (GO:0005515), oxidoreductase activity (GO:0016491), 2-oxoglutarate-dependent dioxygenase activity (GO:0016706), metal ion binding (GO:0046872), dioxygenase activity (GO:0051213)

GO Cellular Component (5): female pronucleus (GO:0001939), male pronucleus (GO:0001940), nucleus (GO:0005634), chromosome (GO:0005694), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
Epigenetic regulation of gene expression	1
Maternal to zygotic transition (MZT)	1
Gene expression (Transcription)	1
Developmental Biology	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
regulation of macromolecule biosynthetic process	2
pronucleus	2
glycoprotein biosynthetic process	1
transcription initiation-coupled chromatin remodeling	1
epigenetic programming in the zygotic pronuclei	1
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
positive regulation of DNA-templated transcription	1
cellular component organization	1
gene expression	1
macromolecule biosynthetic process	1
positive regulation of biosynthetic process	1
positive regulation of macromolecule metabolic process	1
chromatin remodeling	1
regulation of gene expression	1
DNA metabolic process	1
positive regulation of gene expression, epigenetic	1
chromosomal 5-methylcytosine DNA demethylation pathway	1
RNA polymerase II transcription regulatory region sequence-specific DNA binding	1
cis-regulatory region sequence-specific DNA binding	1
transition metal ion binding	1
nucleotide binding	1
sequence-specific DNA binding	1
2-oxoglutarate-dependent dioxygenase activity	1
catalytic activity, acting on DNA	1
nucleic acid binding	1
binding	1
catalytic activity	1
oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen	1
dioxygenase activity	1
cation binding	1
oxidoreductase activity	1
intracellular membrane-bounded organelle	1
intracellular membraneless organelle	1
intracellular anatomical structure	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1364 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TET3	OGT	O15294	951
TET3	TET2	Q6N021	922
TET3	PRMT5	O14744	882
TET3	DNMT1	P26358	881
TET3	NANOG	Q9H9S0	876
TET3	TDG	Q13569	809
TET3	SIN3A	Q96ST3	809
TET3	DNMT3A	Q9Y6K1	801
TET3	DNMT3B	Q9UBC3	783
TET3	DNMT3L	Q9UJW3	657
TET3	UHRF1	Q96T88	635
TET3	DPPA3	Q6W0C5	623
TET3	MECP2	P51608	603
TET3	HCFC1	P51610	602
TET3	BDNF	P23560	584

IntAct

32 interactions, top by confidence:

A	B	Type	Score
OGT	TET3	psi-mi:“MI:0915”(physical association)	0.740
TET3	OGT	psi-mi:“MI:0915”(physical association)	0.740
TET3	OGT	psi-mi:“MI:0914”(association)	0.740
OGT	SETD1A	psi-mi:“MI:0914”(association)	0.530
TET3	RPL14	psi-mi:“MI:0915”(physical association)	0.400
TET3	RPL13A	psi-mi:“MI:0915”(physical association)	0.400
TET3	EXOSC4	psi-mi:“MI:0915”(physical association)	0.400
HCFC1	TET3	psi-mi:“MI:0915”(physical association)	0.400
TET3	MLF1	psi-mi:“MI:0915”(physical association)	0.400
TET3	MLF2	psi-mi:“MI:0915”(physical association)	0.400
HSP90AB1	TET3	psi-mi:“MI:0915”(physical association)	0.400
TET3	HSF2	psi-mi:“MI:0915”(physical association)	0.400
TET3	BAG4	psi-mi:“MI:0915”(physical association)	0.400
BAG2	TET3	psi-mi:“MI:0915”(physical association)	0.400
NUDCD3	TET3	psi-mi:“MI:0915”(physical association)	0.400
PSMD2	TET3	psi-mi:“MI:0915”(physical association)	0.400
SGTA	TET3	psi-mi:“MI:0915”(physical association)	0.400
	TET3	psi-mi:“MI:0915”(physical association)	0.400
STIP1	TET3	psi-mi:“MI:0915”(physical association)	0.400
TET3	STUB1	psi-mi:“MI:0915”(physical association)	0.400
TET3	CACYBP	psi-mi:“MI:0915”(physical association)	0.400
TET3	AARSD1	psi-mi:“MI:0915”(physical association)	0.400
PPP5C	TET3	psi-mi:“MI:0915”(physical association)	0.400
M		psi-mi:“MI:0914”(association)	0.350
NONO	TET3	psi-mi:“MI:0914”(association)	0.350
PSPC1	MCRIP1	psi-mi:“MI:0914”(association)	0.350
NUP62CL	WASH3P	psi-mi:“MI:0914”(association)	0.350

BioGRID (34): VPRBP (Affinity Capture-Western), DDB1 (Affinity Capture-Western), TET3 (Affinity Capture-MS), TET3 (Affinity Capture-MS), TET3 (Affinity Capture-MS), TET3 (Affinity Capture-RNA), TET3 (Affinity Capture-RNA), TET3 (Synthetic Lethality), TET3 (Affinity Capture-MS), EXOSC4 (Proximity Label-MS), RPL14 (Proximity Label-MS), RPL13A (Proximity Label-MS), TET3 (Affinity Capture-MS), VHL (Affinity Capture-Western), TET3 (Affinity Capture-Western)

ESM2 similar proteins: A0A1B0GTI1, A2BIL8, A5PKK9, C5DY61, E2QSX5, E7F555, O35147, O43151, P11805, P19416, P24940, P27579, Q06616, Q17QE3, Q1LZE2, Q1RMQ5, Q1T763, Q28CW2, Q2HR82, Q2TBN9, Q3B8E9, Q3ZBS1, Q567C6, Q5RDK8, Q62417, Q68FW2, Q6AY26, Q6DFB0, Q6P6I6, Q6PKN7, Q80U49, Q86YL5, Q8C3W1, Q8QVM1, Q8VEB3, Q8VI59, Q96FT9, Q96GV9, Q96GY3, Q99618

Diamond homologs: A0A1L8GSA2, A0JP82, K9JHZ4, M9NEY8, O43151, Q0VFP6, Q32LB3, Q4JK59, Q5R7N4, Q5XIQ3, Q6N021, Q6NXI8, Q7LFL8, Q800L6, Q8BG87, Q8NFU7, Q91WA4, Q9EQC9, Q9H2H0, Q3URK3

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
TET3	up-regulates	OGT	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 26 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.

GO biological processes:

GO term	Partners	Fold	FDR
protein stabilization	5	13.9×	4e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	12
Likely pathogenic	37
Uncertain significance	316
Likely benign	69
Benign	14

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1320151	NM_001287491.2(TET3):c.2161_2183dup (p.Ser729fs)	Pathogenic
1800783	NM_001287491.2(TET3):c.3448C>T (p.Arg1150Ter)	Pathogenic
1879477	NM_001287491.2(TET3):c.3234_3235delinsC (p.Lys1078fs)	Pathogenic
3247489	NC_000002.11:g.(?74307117)(74307868_?)del	Pathogenic
3342622	NM_001287491.2(TET3):c.5048G>A (p.Arg1683His)	Pathogenic
3376645	NM_001287491.2(TET3):c.1349G>A (p.Trp450Ter)	Pathogenic
3376875	NM_001287491.2(TET3):c.244C>T (p.Gln82Ter)	Pathogenic
3900457	NM_001287491.2(TET3):c.2818_2841del (p.Tyr940_Leu947del)	Pathogenic
4632995	NM_144993.1:c.658C>T	Pathogenic
4759489	NM_001287491.2(TET3):c.2212C>T (p.Gln738Ter)	Pathogenic
4818991	NM_001287491.2(TET3):c.1912C>T (p.Gln638Ter)	Pathogenic
985641	NM_001287491.2(TET3):c.2234_2235del (p.Pro745fs)	Pathogenic
1012945	NM_001287491.2(TET3):c.2731C>G (p.Arg911Gly)	Likely pathogenic
1298817	NM_001287491.2(TET3):c.2732G>A (p.Arg911Gln)	Likely pathogenic
1308639	NM_001287491.2(TET3):c.3878dup (p.Asn1293fs)	Likely pathogenic
1331623	NM_001287491.2(TET3):c.5062C>G (p.Arg1688Gly)	Likely pathogenic
1513490	NM_001287491.2(TET3):c.5121_5122dup (p.Leu1708fs)	Likely pathogenic
1676568	NM_001287491.2(TET3):c.3343C>G (p.Leu1115Val)	Likely pathogenic
1709508	NM_001287491.2(TET3):c.3272dup (p.Cys1091fs)	Likely pathogenic
1710272	NM_001287491.2(TET3):c.3223C>T (p.His1075Tyr)	Likely pathogenic
2292928	NM_001287491.2(TET3):c.2980A>C (p.Lys994Gln)	Likely pathogenic
2446221	NM_001287491.2(TET3):c.7C>T (p.Gln3Ter)	Likely pathogenic
2572535	NM_001287491.2(TET3):c.4851del (p.Ser1618fs)	Likely pathogenic
2629605	NM_001287491.2(TET3):c.5243del (p.Gly1748fs)	Likely pathogenic
2663463	NM_001287491.2(TET3):c.174dup (p.Thr59fs)	Likely pathogenic
3024527	NM_001287491.2(TET3):c.3000_3013del (p.Lys1003fs)	Likely pathogenic
3029821	NM_001287491.2(TET3):c.4525C>T (p.Arg1509Ter)	Likely pathogenic
3030995	NM_001287491.2(TET3):c.3565C>T (p.Gln1189Ter)	Likely pathogenic
3064113	NM_001287491.2(TET3):c.2684del (p.Ile895fs)	Likely pathogenic
3066311	NM_001287491.2(TET3):c.1310G>A (p.Trp437Ter)	Likely pathogenic

SpliceAI

2253 predictions. Top by Δscore:

Variant	Effect	Δscore
2:74073547:A:AG	acceptor_gain	1.0000
2:74073548:G:GG	acceptor_gain	1.0000
2:74073694:GATAT:G	donor_gain	1.0000
2:74080492:CTTCA:C	acceptor_loss	1.0000
2:74080493:TTCAG:T	acceptor_loss	1.0000
2:74080494:TCAG:T	acceptor_loss	1.0000
2:74080495:CAGG:C	acceptor_loss	1.0000
2:74080588:G:GG	donor_gain	1.0000
2:74087825:TGCA:T	acceptor_loss	1.0000
2:74087826:GCA:G	acceptor_loss	1.0000
2:74087827:CA:C	acceptor_loss	1.0000
2:74087828:AG:A	acceptor_gain	1.0000
2:74087828:AGGT:A	acceptor_gain	1.0000
2:74087829:GG:G	acceptor_gain	1.0000
2:74087829:GGTG:G	acceptor_gain	1.0000
2:74087829:GGTGA:G	acceptor_gain	1.0000
2:74087994:G:GT	donor_gain	1.0000
2:74087994:G:T	donor_gain	1.0000
2:74088034:GA:G	donor_gain	1.0000
2:74088034:GATGA:G	donor_gain	1.0000
2:74088035:A:AG	donor_gain	1.0000
2:74088035:A:G	donor_gain	1.0000
2:74088036:TGA:T	donor_gain	1.0000
2:74088037:GA:G	donor_gain	1.0000
2:74088037:GAG:G	donor_gain	1.0000
2:74088039:GTAT:G	donor_gain	1.0000
2:74089893:GCAGC:G	acceptor_loss	1.0000
2:74089894:CAGC:C	acceptor_loss	1.0000
2:74089895:A:AG	acceptor_gain	1.0000
2:74089895:AGCC:A	acceptor_gain	1.0000

AlphaMissense

11604 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:73986653:T:A	C84S	1.000
2:73986653:T:C	C84R	1.000
2:73986654:G:C	C84S	1.000
2:74046752:T:C	C279R	1.000
2:74046774:T:C	L286P	1.000
2:74046957:C:A	A347D	1.000
2:74046986:G:C	A357P	1.000
2:74046987:C:A	A357D	1.000
2:74046992:G:C	A359P	1.000
2:74047001:G:C	A362P	1.000
2:74047005:T:C	L363P	1.000
2:74048399:T:C	C828R	1.000
2:74048400:G:A	C828Y	1.000
2:74048401:C:G	C828W	1.000
2:74048405:T:C	C830R	1.000
2:74048406:G:A	C830Y	1.000
2:74048407:C:G	C830W	1.000
2:74073621:G:C	R856P	1.000
2:74080524:G:C	R871P	1.000
2:74080536:T:A	V875D	1.000
2:74080556:G:A	G882R	1.000
2:74080556:G:C	G882R	1.000
2:74080562:A:C	S884R	1.000
2:74080564:C:A	S884R	1.000
2:74080564:C:G	S884R	1.000
2:74080574:T:C	C888R	1.000
2:74080589:T:A	W893R	1.000
2:74080589:T:C	W893R	1.000
2:74087896:T:A	C916S	1.000
2:74087896:T:C	C916R	1.000

dbSNP variants (sampled 300 via entrez): RS1000015880 (2:74032868 T>C), RS1000044001 (2:74066796 G>GT), RS1000056749 (2:74122223 A>G), RS1000069249 (2:73997041 C>T), RS1000069980 (2:73992519 C>G,T), RS1000092062 (2:74122768 C>T), RS1000117342 (2:74014331 T>C), RS1000132853 (2:74131761 C>A,G), RS1000132906 (2:74032560 A>G), RS1000157381 (2:73997328 T>G), RS1000176155 (2:73990517 G>T), RS1000198012 (2:74009488 G>A), RS1000220586 (2:74014852 G>A), RS1000233899 (2:74079658 A>C,G,T), RS1000238173 (2:74117196 G>A)

Disease associations

OMIM: gene MIM:613555 | disease phenotypes: MIM:618798, MIM:181500, MIM:619522, MIM:254500, MIM:614299

GenCC curated gene-disease

Disease	Classification	Inheritance
Beck-Fahrner syndrome	Strong	Autosomal recessive

ClinGen Gene-Disease Validity (2)

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

Disease	Classification	Inheritance
Beck-Fahrner syndrome	Limited	AR
Beck-Fahrner syndrome	Definitive	AD

Mondo (7): Beck-Fahrner syndrome (MONDO:0032922), neurodevelopmental disorder (MONDO:0700092), schizophrenia (MONDO:0005090), neurodevelopmental-craniofacial syndrome with variable renal and cardiac abnormalities (MONDO:0859190), plasma cell myeloma (MONDO:0009693), intellectual disability (MONDO:0001071), multiple mitochondrial dysfunctions syndrome 2 (MONDO:0013675)

Orphanet (6): Intellectual disability-facial dysmorphism-joint hypermobility-hearing loss syndrome (Orphanet:684216), Multiple myeloma (Orphanet:29073), AL amyloidosis (Orphanet:85443), Multiple mitochondrial dysfunctions syndrome type 2 (Orphanet:401874), NON RARE IN EUROPE: Schizophrenia (Orphanet:3140), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

40 total (30 of 40 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000194	Open mouth
HP:0000218	High palate
HP:0000248	Brachycephaly
HP:0000252	Microcephaly
HP:0000256	Macrocephaly
HP:0000276	Long face
HP:0000297	Facial hypotonia
HP:0000337	Broad forehead
HP:0000343	Long philtrum
HP:0000348	High forehead
HP:0000411	Protruding ear
HP:0000486	Strabismus
HP:0000508	Ptosis
HP:0000639	Nystagmus
HP:0000716	Depression
HP:0000729	Autistic behavior
HP:0000739	Anxiety
HP:0000750	Delayed speech and language development
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001263	Global developmental delay
HP:0001290	Generalized hypotonia
HP:0001382	Joint hypermobility
HP:0001385	Hip dysplasia
HP:0001629	Ventricular septal defect
HP:0001640	Cardiomegaly
HP:0001763	Pes planus
HP:0002119	Ventriculomegaly

GWAS associations

10 associations (top):

Study	Trait	p-value
GCST001066_14	Dialysis-related mortality	3.000000e-06
GCST001795_1	Systemic lupus erythematosus	7.000000e-17
GCST001795_2	Systemic lupus erythematosus	6.000000e-14
GCST003622_58	Systemic lupus erythematosus	3.000000e-08
GCST004899_10	Gestational age at birth (maternal effect)	2.000000e-07
GCST007325_255	General risk tolerance (MTAG)	2.000000e-09
GCST008522_15	Bitter alcoholic beverage consumption	2.000000e-07
GCST011956_66	Systemic lupus erythematosus	2.000000e-12
GCST90002381_32	Eosinophil count	1.000000e-10
GCST90002382_39	Eosinophil percentage of white cells	9.000000e-13

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0005112	gestational age
EFO:0005939	parental genotype effect measurement
EFO:0008579	risk-taking behaviour
EFO:0010092	bitter alcoholic beverage consumption measurement
EFO:0004842	eosinophil count
EFO:0007991	eosinophil percentage of leukocytes

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D009101	Multiple Myeloma	C04.557.595.500; C14.907.454.460; C15.378.147.780.650; C15.378.463.515.460; C20.683.515.845; C20.683.780.650
D065886	Neurodevelopmental Disorders	F03.625

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4879414 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

2 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 12,199 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL3646221	VADADUSTAT	4	533
CHEMBL483254	PANOBINOSTAT	4	11,666

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

ChEMBL bioactivities

34 potent at pChembl≥5 of 53 total, top 34 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.74	IC50	182	nM	CHEMBL5527999
6.30	IC50	501.2	nM	CHEMBL5561920
6.20	IC50	631	nM	CHEMBL5561497
6.16	IC50	691.8	nM	CHEMBL5562105
6.11	IC50	776.2	nM	CHEMBL316034
6.01	IC50	977.2	nM	CHEMBL1230640
5.99	IC50	1023	nM	CHEMBL5532540
5.92	EC50	1200	nM	CHEMBL1230640
5.91	EC50	1230	nM	CHEMBL1230640
5.90	IC50	1259	nM	CHEMBL1398529
5.86	IC50	1380	nM	CHEMBL5557587
5.64	IC50	2310	nM	CHEMBL4872206
5.62	IC50	2399	nM	CHEMBL5557793
5.62	IC50	2399	nM	CHEMBL5557957
5.57	IC50	2692	nM	CHEMBL1230640
5.57	IC50	2692	nM	CHEMBL5549844
5.56	IC50	2754	nM	CHEMBL5567655
5.51	IC50	3090	nM	CHEMBL5559263
5.45	IC50	3548	nM	CHEMBL5564944
5.42	IC50	3800	nM	PANOBINOSTAT
5.33	IC50	4677	nM	PANOBINOSTAT
5.29	IC50	5100	nM	CHEMBL5194845
5.28	IC50	5248	nM	CHEMBL5566835
5.26	IC50	5500	nM	CHEMBL5177921
5.26	IC50	5495	nM	VADADUSTAT
5.24	IC50	5800	nM	CHEMBL5189434
5.23	IC50	5888	nM	CHEMBL5557372
5.22	IC50	6026	nM	CHEMBL5563232
5.20	IC50	6310	nM	CHEMBL5556063
5.16	IC50	7000	nM	CHEMBL5181110
5.16	IC50	6918	nM	N-OXALYLGLYCINE
5.16	IC50	7000	nM	N-OXALYLGLYCINE
5.06	IC50	8800	nM	CHEMBL4851104
5.01	IC50	9772	nM	CHEMBL1982368

PubChem BioAssay actives

34 with measured affinity, of 111 total; 29 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
3-[(3S,6S,9S,12S,15S,18S,21S,24S,27S,30S,33S,36S,39S,42R)-3-[[(2S)-1-[[2-[[(2S)-1-[[(2S)-6-amino-1-[[(2S)-6-amino-1-[[(2S)-1-[[(2S)-1-[[(2S)-5-amino-1-[[(2S)-1-[[(2S)-1-amino-5-carbamimidamido-1-oxopentan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-1-oxohexan-2-yl]amino]-1-oxohexan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-2-oxoethyl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]carbamoyl]-36-[(2S)-butan-2-yl]-21-[(1R)-1-hydroxyethyl]-6-(hydroxymethyl)-24,27,33,42-tetrakis[(4-hydroxyphenyl)methyl]-9-(1H-imidazol-4-ylmethyl)-15,18-bis(1H-indol-3-ylmethyl)-30-methyl-39-(2-methylpropyl)-5,8,11,14,17,20,23,26,29,32,35,38,41,44-tetradecaoxo-1-thia-4,7,10,13,16,19,22,25,28,31,34,37,40,43-tetradecazacyclopentatetracont-12-yl]propanoic acid	2083786: Inhibition of recombinant human TET3 catalytic domain (E824 to I1795 residues) expressed in baculovirus infected Sf9 cells using 5-methylcytosine as substrate preincubated for 10 mins followed by substrate and DNA-cofactor addition measured after 10 mins by Alphascreen assay	ic50	0.1820	uM
(3R,6S,9S,12S,15S,18S,21S,24S,27S,30S,33S,36S,39S,42S,45S,48S,51R)-39-(4-aminobutyl)-27-(3-amino-3-oxopropyl)-24-[(2S)-butan-2-yl]-45-(3-carbamimidamidopropyl)-21,36-bis[(1R)-1-hydroxyethyl]-6-(hydroxymethyl)-12,18,33,48,51-pentakis[(4-hydroxyphenyl)methyl]-30-(1H-imidazol-4-ylmethyl)-5,8,11,14,17,20,23,26,29,32,35,38,41,44,47,50,53-heptadecaoxo-9,15,42-tri(propan-2-yl)-1-thia-4,7,10,13,16,19,22,25,28,31,34,37,40,43,46,49,52-heptadecazacyclotetrapentacontane-3-carboxamide	2083786: Inhibition of recombinant human TET3 catalytic domain (E824 to I1795 residues) expressed in baculovirus infected Sf9 cells using 5-methylcytosine as substrate preincubated for 10 mins followed by substrate and DNA-cofactor addition measured after 10 mins by Alphascreen assay	ic50	0.5012	uM
(3R,6S,9S,12S,15S,18S,21S,24S,27S,30S,33S,36R)-21-(2-amino-2-oxoethyl)-30,33-bis[(2S)-butan-2-yl]-6-(3-carbamimidamidopropyl)-15-[(1R)-1-hydroxyethyl]-18,27-bis[(4-hydroxyphenyl)methyl]-24-(1H-imidazol-4-ylmethyl)-9,12,36-tris(1H-indol-3-ylmethyl)-5,8,11,14,17,20,23,26,29,32,35,38-dodecaoxo-1-thia-4,7,10,13,16,19,22,25,28,31,34,37-dodecazacyclononatriacontane-3-carboxamide	2083786: Inhibition of recombinant human TET3 catalytic domain (E824 to I1795 residues) expressed in baculovirus infected Sf9 cells using 5-methylcytosine as substrate preincubated for 10 mins followed by substrate and DNA-cofactor addition measured after 10 mins by Alphascreen assay	ic50	0.6310	uM
(3R,6S,9S,12S,15S,18S,21S,24S,27S,30S,33S,36R)-33-(4-aminobutyl)-21-(2-amino-2-oxoethyl)-6-[(2S)-butan-2-yl]-15-[(1R)-1-hydroxyethyl]-18,24,27-tris[(4-hydroxyphenyl)methyl]-9,12,36-tris(1H-indol-3-ylmethyl)-30-(2-methylpropyl)-5,8,11,14,17,20,23,26,29,32,35,38-dodecaoxo-1-thia-4,7,10,13,16,19,22,25,28,31,34,37-dodecazacyclononatriacontane-3-carboxamide	2083786: Inhibition of recombinant human TET3 catalytic domain (E824 to I1795 residues) expressed in baculovirus infected Sf9 cells using 5-methylcytosine as substrate preincubated for 10 mins followed by substrate and DNA-cofactor addition measured after 10 mins by Alphascreen assay	ic50	0.6918	uM
pyridine-2,4-dicarboxylic acid	1984347: Inhibition of human TET3 catalytic domain (E824 to I1795 residues) expressed in mammalian cells using 5-methylcytosine as substrate preincubated for 10 mins followed by DNA-cofactor addition and measured after 10 mins by Alphascreen assay	ic50	0.7762	uM
8-hydroxyquinoline-5-carboxylic acid	2083786: Inhibition of recombinant human TET3 catalytic domain (E824 to I1795 residues) expressed in baculovirus infected Sf9 cells using 5-methylcytosine as substrate preincubated for 10 mins followed by substrate and DNA-cofactor addition measured after 10 mins by Alphascreen assay	ic50	0.9772	uM
(3S,6S,9R,12S,15R,21S,27S,30S,33S,36S,39S,42S,45S,48S,51S)-12-(4-aminobutyl)-9,30-dibenzyl-27-[(2S)-butan-2-yl]-39-(3-carbamimidamidopropyl)-6,15,33-tris[(4-hydroxyphenyl)methyl]-45,48-bis(1H-indol-3-ylmethyl)-42-methyl-36-(2-methylpropyl)-2,5,8,11,14,17,23,26,29,32,35,38,41,44,47,50-hexadecaoxo-3-propan-2-yl-19-thia-1,4,7,10,13,16,22,25,28,31,34,37,40,43,46,49-hexadecazabicyclo[49.3.0]tetrapentacontane-21-carboxamide	2083786: Inhibition of recombinant human TET3 catalytic domain (E824 to I1795 residues) expressed in baculovirus infected Sf9 cells using 5-methylcytosine as substrate preincubated for 10 mins followed by substrate and DNA-cofactor addition measured after 10 mins by Alphascreen assay	ic50	1.0233	uM
N-[3-(dimethylamino)propyl]-4-(8-hydroxyquinolin-6-yl)benzamide	1984347: Inhibition of human TET3 catalytic domain (E824 to I1795 residues) expressed in mammalian cells using 5-methylcytosine as substrate preincubated for 10 mins followed by DNA-cofactor addition and measured after 10 mins by Alphascreen assay	ic50	1.2589	uM
(3R,6S,9S,12S,15S,18S,21S,24S,27S,30S,33S,36R)-33-[(2S)-butan-2-yl]-6,24-bis(3-carbamimidamidopropyl)-15-[(1R)-1-hydroxyethyl]-18,21,27,36-tetrakis[(4-hydroxyphenyl)methyl]-9,12-bis(1H-indol-3-ylmethyl)-5,8,11,14,17,20,23,26,29,32,35,38-dodecaoxo-30-propan-2-yl-1-thia-4,7,10,13,16,19,22,25,28,31,34,37-dodecazacyclononatriacontane-3-carboxamide	2083786: Inhibition of recombinant human TET3 catalytic domain (E824 to I1795 residues) expressed in baculovirus infected Sf9 cells using 5-methylcytosine as substrate preincubated for 10 mins followed by substrate and DNA-cofactor addition measured after 10 mins by Alphascreen assay	ic50	1.3804	uM
[(2R,3R)-3-(3,4-dihydroxyphenyl)-6,8-dihydroxy-1,2,3,4-tetrahydronaphthalen-2-yl] (3S)-5-(3,4-dihydroxyphenyl)-3-hydroxypentanoate	1763194: Inhibition of TET3 (unknown origin)	ic50	2.3100	uM
(3R,6S,9S,12S,15S,18S,21S,24S,27S,30S,33S,36S,39S,42R)-12-(2-amino-2-oxoethyl)-27-benzyl-36-[(2S)-butan-2-yl]-39-(3-carbamimidamidopropyl)-21-[(1R)-1-hydroxyethyl]-6,24,33,42-tetrakis[(4-hydroxyphenyl)methyl]-15,18-bis(1H-indol-3-ylmethyl)-30-(2-methylpropyl)-5,8,11,14,17,20,23,26,29,32,35,38,41,44-tetradecaoxo-9-propan-2-yl-1-thia-4,7,10,13,16,19,22,25,28,31,34,37,40,43-tetradecazacyclopentatetracontane-3-carboxamide	2083786: Inhibition of recombinant human TET3 catalytic domain (E824 to I1795 residues) expressed in baculovirus infected Sf9 cells using 5-methylcytosine as substrate preincubated for 10 mins followed by substrate and DNA-cofactor addition measured after 10 mins by Alphascreen assay	ic50	2.3988	uM
(3S,6S,9S,12S,15S,21S,24S,27S,30R,36R,39S,42S,45S)-39-benzyl-6-(3-carbamimidamidopropyl)-12-(hydroxymethyl)-9,24,30-tris[(4-hydroxyphenyl)methyl]-27,42-bis(1H-indol-3-ylmethyl)-21-(2-methylpropyl)-2,5,8,11,14,20,23,26,29,32,38,41,44-tridecaoxo-3-propan-2-yl-34-thia-1,4,7,10,13,19,22,25,28,31,37,40,43-tridecazatricyclo[43.3.0.015,19]octatetracontane-36-carboxamide	2083786: Inhibition of recombinant human TET3 catalytic domain (E824 to I1795 residues) expressed in baculovirus infected Sf9 cells using 5-methylcytosine as substrate preincubated for 10 mins followed by substrate and DNA-cofactor addition measured after 10 mins by Alphascreen assay	ic50	2.3988	uM
(3R,6S,9S,12S,15S,18S,21S,24S,27S,30S,33S,36S,39S,42S,45S,48S,51R)-39-(4-aminobutyl)-27-(3-amino-3-oxopropyl)-24-[(2S)-butan-2-yl]-45-(3-carbamimidamidopropyl)-21,36-bis[(1R)-1-hydroxyethyl]-6-(hydroxymethyl)-12,18,30,33,48,51-hexakis[(4-hydroxyphenyl)methyl]-9-(2-methylpropyl)-5,8,11,14,17,20,23,26,29,32,35,38,41,44,47,50,53-heptadecaoxo-15,42-di(propan-2-yl)-1-thia-4,7,10,13,16,19,22,25,28,31,34,37,40,43,46,49,52-heptadecazacyclotetrapentacontane-3-carboxamide	2083786: Inhibition of recombinant human TET3 catalytic domain (E824 to I1795 residues) expressed in baculovirus infected Sf9 cells using 5-methylcytosine as substrate preincubated for 10 mins followed by substrate and DNA-cofactor addition measured after 10 mins by Alphascreen assay	ic50	2.6915	uM
(3R,6S,9S,12S,15S,18S,21S,24S,27S,30S,33S,36R)-24-benzyl-33-(3-carbamimidamidopropyl)-15-[(1R)-1-hydroxyethyl]-18,27,30,36-tetrakis[(4-hydroxyphenyl)methyl]-9,12-bis(1H-indol-3-ylmethyl)-6,21-dimethyl-5,8,11,14,17,20,23,26,29,32,35,38-dodecaoxo-1-thia-4,7,10,13,16,19,22,25,28,31,34,37-dodecazacyclononatriacontane-3-carboxamide	2083786: Inhibition of recombinant human TET3 catalytic domain (E824 to I1795 residues) expressed in baculovirus infected Sf9 cells using 5-methylcytosine as substrate preincubated for 10 mins followed by substrate and DNA-cofactor addition measured after 10 mins by Alphascreen assay	ic50	2.7542	uM
3-[(3R,6S,9S,12S,15S,18S,21S,24S,27S,30S,33S,36S,39S,42R)-36-[(2S)-butan-2-yl]-3-carbamoyl-21-[(1R)-1-hydroxyethyl]-6-(hydroxymethyl)-24,27,33,42-tetrakis[(4-hydroxyphenyl)methyl]-15,18-bis(1H-indol-3-ylmethyl)-9,30-dimethyl-39-(2-methylpropyl)-5,8,11,14,17,20,23,26,29,32,35,38,41,44-tetradecaoxo-1-thia-4,7,10,13,16,19,22,25,28,31,34,37,40,43-tetradecazacyclopentatetracont-12-yl]propanoic acid	2083786: Inhibition of recombinant human TET3 catalytic domain (E824 to I1795 residues) expressed in baculovirus infected Sf9 cells using 5-methylcytosine as substrate preincubated for 10 mins followed by substrate and DNA-cofactor addition measured after 10 mins by Alphascreen assay	ic50	3.0903	uM
2-[(5R,8S,11S,14S,17S,20S,23S,26S,29S,32S,35S,38S,41S,44R)-14-(4-aminobutyl)-44-carbamoyl-8,32-bis[(1R)-1-hydroxyethyl]-41-(hydroxymethyl)-17,20,29-tris[(4-hydroxyphenyl)methyl]-5,23,35,38-tetrakis(1H-indol-3-ylmethyl)-26-methyl-3,6,9,12,15,18,21,24,27,30,33,36,39,42-tetradecaoxo-1-thia-4,7,10,13,16,19,22,25,28,31,34,37,40,43-tetradecazacyclopentatetracont-11-yl]acetic acid	2083786: Inhibition of recombinant human TET3 catalytic domain (E824 to I1795 residues) expressed in baculovirus infected Sf9 cells using 5-methylcytosine as substrate preincubated for 10 mins followed by substrate and DNA-cofactor addition measured after 10 mins by Alphascreen assay	ic50	3.5481	uM
Panobinostat	1984347: Inhibition of human TET3 catalytic domain (E824 to I1795 residues) expressed in mammalian cells using 5-methylcytosine as substrate preincubated for 10 mins followed by DNA-cofactor addition and measured after 10 mins by Alphascreen assay	ic50	3.8000	uM
4-phenyl-1-prop-2-enoylpiperidine-4-carboxylic acid	1871099: Inhibition of GST-tagged human TET3 (49 to 68 residues) expressed in Escherichia coli BL21 cell incubated for 30 mins by fluorescence polarization assay	ic50	5.1000	uM
3-[(3R,6S,9S,12S,15S,18S,21S,24S,27S,30S,33S,36S,39S,42R)-36-[(2S)-butan-2-yl]-3-carbamoyl-6-(hydroxymethyl)-24,27,33,42-tetrakis[(4-hydroxyphenyl)methyl]-9-(1H-imidazol-4-ylmethyl)-15,18-bis(1H-indol-3-ylmethyl)-21,30-dimethyl-39-(2-methylpropyl)-5,8,11,14,17,20,23,26,29,32,35,38,41,44-tetradecaoxo-1-thia-4,7,10,13,16,19,22,25,28,31,34,37,40,43-tetradecazacyclopentatetracont-12-yl]propanoic acid	2083786: Inhibition of recombinant human TET3 catalytic domain (E824 to I1795 residues) expressed in baculovirus infected Sf9 cells using 5-methylcytosine as substrate preincubated for 10 mins followed by substrate and DNA-cofactor addition measured after 10 mins by Alphascreen assay	ic50	5.2481	uM
Vadadustat	1984347: Inhibition of human TET3 catalytic domain (E824 to I1795 residues) expressed in mammalian cells using 5-methylcytosine as substrate preincubated for 10 mins followed by DNA-cofactor addition and measured after 10 mins by Alphascreen assay	ic50	5.4954	uM
1-[4-phenyl-4-(2H-tetrazol-5-yl)piperidin-1-yl]prop-2-en-1-one	1871099: Inhibition of GST-tagged human TET3 (49 to 68 residues) expressed in Escherichia coli BL21 cell incubated for 30 mins by fluorescence polarization assay	ic50	5.5000	uM
4-(4-ethoxyphenyl)-1-prop-2-enoylpiperidine-4-carboxylic acid	1871099: Inhibition of GST-tagged human TET3 (49 to 68 residues) expressed in Escherichia coli BL21 cell incubated for 30 mins by fluorescence polarization assay	ic50	5.8000	uM
(3R,6S,9S,12S,15S,18S,21S,24S,27S,30S,33S,36S,39S,42R)-12-(3-amino-3-oxopropyl)-36-[(2S)-butan-2-yl]-21-[(1R)-1-hydroxyethyl]-6-(hydroxymethyl)-24,27,33,42-tetrakis[(4-hydroxyphenyl)methyl]-9-(1H-imidazol-4-ylmethyl)-15,18-bis(1H-indol-3-ylmethyl)-30-methyl-39-(2-methylpropyl)-5,8,11,14,17,20,23,26,29,32,35,38,41,44-tetradecaoxo-1-thia-4,7,10,13,16,19,22,25,28,31,34,37,40,43-tetradecazacyclopentatetracontane-3-carboxylic acid	2083786: Inhibition of recombinant human TET3 catalytic domain (E824 to I1795 residues) expressed in baculovirus infected Sf9 cells using 5-methylcytosine as substrate preincubated for 10 mins followed by substrate and DNA-cofactor addition measured after 10 mins by Alphascreen assay	ic50	5.8884	uM
(3R,6S,9S,12S,15S,18S,21S,24S,27S,30S,33S,36S,39S,42S,45S,48S,51R)-39-(4-aminobutyl)-27-(3-amino-3-oxopropyl)-24-[(2S)-butan-2-yl]-45-(3-carbamimidamidopropyl)-21,36-bis[(1R)-1-hydroxyethyl]-6-(hydroxymethyl)-12,18,30,33,48,51-hexakis[(4-hydroxyphenyl)methyl]-5,8,11,14,17,20,23,26,29,32,35,38,41,44,47,50,53-heptadecaoxo-9,15,42-tri(propan-2-yl)-1-thia-4,7,10,13,16,19,22,25,28,31,34,37,40,43,46,49,52-heptadecazacyclotetrapentacontane-3-carboxamide	2083786: Inhibition of recombinant human TET3 catalytic domain (E824 to I1795 residues) expressed in baculovirus infected Sf9 cells using 5-methylcytosine as substrate preincubated for 10 mins followed by substrate and DNA-cofactor addition measured after 10 mins by Alphascreen assay	ic50	6.0256	uM
3-[(3R,6S,9S,12S,15S,18S,21S,24S,27S,30S,33S,36S,39S,42R)-36-[(2S)-butan-2-yl]-3-carbamoyl-21-[(1R)-1-hydroxyethyl]-24,27,33,42-tetrakis[(4-hydroxyphenyl)methyl]-9-(1H-imidazol-4-ylmethyl)-15,18-bis(1H-indol-3-ylmethyl)-6,30-dimethyl-39-(2-methylpropyl)-5,8,11,14,17,20,23,26,29,32,35,38,41,44-tetradecaoxo-1-thia-4,7,10,13,16,19,22,25,28,31,34,37,40,43-tetradecazacyclopentatetracont-12-yl]propanoic acid	2083786: Inhibition of recombinant human TET3 catalytic domain (E824 to I1795 residues) expressed in baculovirus infected Sf9 cells using 5-methylcytosine as substrate preincubated for 10 mins followed by substrate and DNA-cofactor addition measured after 10 mins by Alphascreen assay	ic50	6.3096	uM
2-(carboxymethylamino)-2-oxoacetic acid	1984347: Inhibition of human TET3 catalytic domain (E824 to I1795 residues) expressed in mammalian cells using 5-methylcytosine as substrate preincubated for 10 mins followed by DNA-cofactor addition and measured after 10 mins by Alphascreen assay	ic50	6.9183	uM
1-[4-(3-ethoxyphenyl)-4-(2H-tetrazol-5-yl)piperidin-1-yl]prop-2-en-1-one	1871099: Inhibition of GST-tagged human TET3 (49 to 68 residues) expressed in Escherichia coli BL21 cell incubated for 30 mins by fluorescence polarization assay	ic50	7.0000	uM
2-hydroxy-4-methylidenepentanedioic acid	1763205: Inhibition of recombinant human N-terminal Flag-tagged C-terminal His-tagged TET3 (824 to 1795 residues) expressed in Baculovirus infected Sf9 cells assessed as reduction in 5hmc level incubated for 2 hrs by ELISA	ic50	8.8000	uM
5-chloro-N-[(E)-[phenyl(pyridin-2-yl)methylidene]amino]pyridin-2-amine	1984347: Inhibition of human TET3 catalytic domain (E824 to I1795 residues) expressed in mammalian cells using 5-methylcytosine as substrate preincubated for 10 mins followed by DNA-cofactor addition and measured after 10 mins by Alphascreen assay	ic50	9.7724	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
methylmercuric chloride	affects cotreatment, increases expression	2
bisphenol A	affects cotreatment, increases expression, decreases methylation	2
perfluorooctanoic acid	affects cotreatment, increases expression	2
bisphenol S	increases expression, decreases methylation, affects cotreatment	2
Air Pollutants	affects expression, increases abundance, decreases expression	2
Hydrogen Peroxide	increases expression	2
Valproic Acid	affects expression, increases methylation	2
Aflatoxin B1	decreases methylation	2
TAK-243	increases sumoylation	1
dicrotophos	increases expression	1
deoxynivalenol	increases expression	1
sodium arsenite	increases expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	increases expression, affects cotreatment	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
abrine	increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
jinfukang	affects cotreatment, decreases expression	1
(+)-JQ1 compound	decreases expression	1
Sunitinib	increases expression	1
Fulvestrant	affects cotreatment, decreases methylation	1
Vorinostat	decreases expression	1
Leflunomide	increases expression	1
Benzo(a)pyrene	increases expression	1
Cisplatin	decreases expression, affects cotreatment	1
Formaldehyde	decreases expression	1
Oleanolic Acid	decreases reaction, increases expression	1
Ozone	affects expression, increases abundance	1
Smoke	decreases expression, increases abundance	1
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	1

ChEMBL screening assays

8 unique, capped per target: 8 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4822192	Binding	Inhibition of TET3 (unknown origin)	SAR insights into TET2 catalytic domain inhibition: Synthesis of 2-Hydroxy-4-Methylene-pentanedicarboxylates. — Bioorg Med Chem

Cellosaurus cell lines

6 cell lines: 6 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B8QP	Abcam HCT 116 TET3 KO	Cancer cell line	Male
CVCL_B9T5	Abcam A-549 TET3 KO	Cancer cell line	Male
CVCL_E0QP	Ubigene HeLa TET3 KO	Cancer cell line	Female
CVCL_TS10	HAP1 TET3 (-) 1	Cancer cell line	Male
CVCL_TS11	HAP1 TET3 (-) 2	Cancer cell line	Male
CVCL_TS12	HAP1 TET3 (-) 3	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04586348	PHASE4	UNKNOWN	Prenatal Iodine Supplementation and Early Childhood Neurodevelopment
NCT04873115	PHASE4	UNKNOWN	Double-blind, Placebo-controlled, Randomized Clinical Trial Comparing the Efficacy and Safety of Sialanar Plus orAl rehabiLitation Against Placebo Plus Oral Rehabilitation for chIldren and Adolescents With seVere Sialorrhoea and Neurodisabilties,
NCT00000374	PHASE4	COMPLETED	Treatment for First-Episode Schizophrenia
NCT00001656	PHASE4	COMPLETED	Comparison of Clozapine vs Olanzapine in Childhood-Onset Psychotic Disorders
NCT00007774	PHASE4	COMPLETED	To Determine if Olanzapine is More Cost Effective Than Haloperidol for the Treatment of Schizophrenia
NCT00014001	PHASE4	COMPLETED	CATIE- Schizophrenia Trial
NCT00018668	PHASE4	COMPLETED	Antipsychotic Response in Schizophrenia
NCT00034801	PHASE4	COMPLETED	Olanzapine Versus Active Comparator in the Treatment of Depression in Patients With Schizophrenia
NCT00034905	PHASE4	COMPLETED	A Comparison of Seroquel vs. Risperidone in Schizophrenia
NCT00036088	PHASE4	COMPLETED	Olanzapine Versus An Active Comparator in the Treatment of Schizophrenia
NCT00044187	PHASE4	COMPLETED	The Assessment of a Weight-Gain Agent for the Treatment of Olanzapine-Associated Anti-Obesity Agent in Patients With Schizophrenia, Schizophreniform Disorder, Schizoaffective Disorder, and Bipolar I Disorder
NCT00044655	PHASE4	COMPLETED	Switching Medication to Treat Schizophrenia
NCT00048828	PHASE4	COMPLETED	Treating Drug-Resistant Childhood Schizophrenia
NCT00053703	PHASE4	COMPLETED	Treatment of Early Onset Schizophrenia Spectrum Disorders (TEOSS)
NCT00056498	PHASE4	COMPLETED	Risperidone Treatment in Schizophrenia Patients Who Are Currently Taking Clozapine
NCT00061802	PHASE4	COMPLETED	Efficacy and Safety of Two Atypical Antipsychotics vs. Placebo in Patients With an Acute Exacerbation of Either Schizophrenia or Schizoaffective Disorder
NCT00080327	PHASE4	COMPLETED	Study of Three Doses of Aripiprazole in Patients With Acute Schizophrenia
NCT00088049	PHASE4	COMPLETED	Study of Olanzapine vs. Aripiprazole in the Treatment of Schizophrenia
NCT00090012	PHASE4	COMPLETED	Comparison of Continuing Olanzapine to Switching to Quetiapine in Overweight or Obese Patients With Schizophrenia and Schizoaffective Disorder
NCT00100776	PHASE4	COMPLETED	Efficacy of High Dose Olanzapine for the Treatment of Schizophrenia and Schizoaffective Disorder
NCT00103571	PHASE4	COMPLETED	Olanzapine Versus Aripiprazole in the Treatment of Acutely Ill Patients With Schizophrenia
NCT00108368	PHASE4	COMPLETED	The Effects of Risperidone and Olanzapine on Thinking
NCT00114595	PHASE4	COMPLETED	Ethyl-Eicosapentaenoic Acid and Tardive Dyskinesia
NCT00130923	PHASE4	COMPLETED	Risperidone Long-acting Versus Oral Risperidone in Patients With Schizophrenia and Alcohol Use Disorder
NCT00137020	PHASE4	COMPLETED	Clinical Effect Of Cross Titration Of Antipsychotics With Ziprasidone In Schizophrenia Or Schizoaffective Disorder
NCT00140166	PHASE4	COMPLETED	Treatment of Acute Schizophrenia With Vitamin Therapy
NCT00145847	PHASE4	COMPLETED	Naltrexone Treatment of Alcohol Abuse in Schizophrenia
NCT00148564	PHASE4	COMPLETED	Energy Homeostasis Under Treatment With Atypical Antipsychotics
NCT00156715	PHASE4	COMPLETED	Efficacy of Quetiapine in the Treatment of Patients With Schizophrenia and a Comorbid Substance Use Disorder
NCT00158223	PHASE4	COMPLETED	Effectiveness of Pimozide in Augmenting the Effects of Clozapine in the Treatment of Schizophrenia
NCT00159081	PHASE4	COMPLETED	One Year Drug Treatment in First-Episode Schizophrenia
NCT00159120	PHASE4	COMPLETED	Maintenance Treatment vs. Stepwise Drug Discontinuation in First-Episode Schizophrenia
NCT00159133	PHASE4	COMPLETED	Prodrome-Based Early Intervention With Antipsychotics vs. Benzodiazepines in First-Episode Schizophrenia
NCT00159757	PHASE4	TERMINATED	12 Week Open, Non-Comparative Switch Study Of Oral Ziprazidone In Previously Treated Schizophrenic Patients
NCT00167817	PHASE4	COMPLETED	Effect of Switch to Aripiprazole on Health and Smoking Parameters in Patients With Schizophrenia: A Pilot Study
NCT00169026	PHASE4	TERMINATED	Alcoholism and Schizophrenia: Effects of Clozapine
NCT00169039	PHASE4	TERMINATED	Clozapine Versus Chlorpromazine for Treatment-Unresponsive Schizophrenia
NCT00169065	PHASE4	COMPLETED	Effectiveness of Clozapine Versus Olanzapine for Treatment-resistant Schizophrenia
NCT00169091	PHASE4	TERMINATED	Clozapine Versus Haloperidol for Treating the First Episode of Schizophrenia
NCT00176423	PHASE4	COMPLETED	Efficacy Study of Galantamine for Cognitive Impairments in Schizophrenia