TET2

Summary

TET2 (tet methylcytosine dioxygenase 2, HGNC:25941) is a protein-coding gene on chromosome 4q24, encoding Methylcytosine dioxygenase TET2 (Q6N021). Dioxygenase that catalyzes the conversion of the modified genomic base 5-methylcytosine (5mC) into 5-hydroxymethylcytosine (5hmC) and plays a key role in active DNA demethylation.

The protein encoded by this gene is a methylcytosine dioxygenase that catalyzes the conversion of methylcytosine to 5-hydroxymethylcytosine. The encoded protein is involved in myelopoiesis, and defects in this gene have been associated with several myeloproliferative disorders. Two variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 54790 — RefSeq curated summary.

At a glance

• Gene–disease (curated): immunodeficiency 75 (Strong, GenCC) — +1 more curated relationship
• GWAS associations: 94
• Clinical variants (ClinVar): 1,910 total — 154 pathogenic, 22 likely-pathogenic
• Phenotypes (HPO): 135
• Druggable target: yes — 3 molecules with ChEMBL bioactivity
• Cancer driver (intOGen): loss-of-function (tumor-suppressor-like) across 7 cancer types
• MANE Select transcript: NM_001127208

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25941
Approved symbol	TET2
Name	tet methylcytosine dioxygenase 2
Location	4q24
Locus type	gene with protein product
Status	Approved
Aliases	FLJ20032
Ensembl gene	ENSG00000168769
Ensembl biotype	protein_coding
OMIM	612839
Entrez	54790

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 7 protein_coding, 1 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000265149, ENST00000305737, ENST00000380013, ENST00000413648, ENST00000504042, ENST00000505801, ENST00000513237, ENST00000514870, ENST00000540549, ENST00000950395

RefSeq mRNA: 2 — MANE Select: NM_001127208 NM_001127208, NM_017628

CCDS: CCDS3666, CCDS47120

Canonical transcript exons

ENST00000380013 — 11 exons

Exon	Start	End
ENSE00001372902	105190360	105190505
ENSE00001682685	105241339	105241429
ENSE00003521446	105275048	105279803
ENSE00003579219	105272564	105272918
ENSE00003643496	105243570	105243778
ENSE00003645006	105233897	105237351
ENSE00003648713	105269610	105269747
ENSE00003649981	105242834	105242927
ENSE00003651882	105259619	105259769
ENSE00003690667	105261759	105261848
ENSE00003909145	105146876	105146979

Expression profiles

Bgee: expression breadth ubiquitous, 249 present calls, max score 94.14.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 26.5783 / max 1332.2474, expressed in 1772 samples.

FANTOM5 promoters (11 alternative TSS)

Promoter ID	TPM avg	Samples expressed
49126	19.2170	1659
49125	4.2468	1534
49133	0.7494	386
49130	0.6078	297
49134	0.5001	195
49123	0.2730	77
49132	0.2592	67
49122	0.2441	69
49131	0.2144	77
49124	0.1895	54

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
palpebral conjunctiva	UBERON:0001812	94.14	gold quality
amniotic fluid	UBERON:0000173	93.29	gold quality
epithelium of nasopharynx	UBERON:0001951	92.76	gold quality
germinal epithelium of ovary	UBERON:0001304	91.90	gold quality
bone marrow cell	CL:0002092	91.71	gold quality
gingival epithelium	UBERON:0001949	91.49	gold quality
esophagus squamous epithelium	UBERON:0006920	91.18	gold quality
ileal mucosa	UBERON:0000331	90.62	gold quality
nasal cavity epithelium	UBERON:0005384	90.55	gold quality
monocyte	CL:0000576	90.52	gold quality
leukocyte	CL:0000738	90.07	gold quality
visceral pleura	UBERON:0002401	89.90	gold quality
bone marrow	UBERON:0002371	89.88	gold quality
tibia	UBERON:0000979	89.79	gold quality
upper arm skin	UBERON:0004263	89.72	gold quality
epithelial cell of pancreas	CL:0000083	89.56	gold quality
gingiva	UBERON:0001828	89.53	gold quality
blood	UBERON:0000178	89.34	gold quality
cardiac muscle of right atrium	UBERON:0003379	89.24	silver quality
oral cavity	UBERON:0000167	89.10	gold quality
parietal pleura	UBERON:0002400	88.79	gold quality
jejunal mucosa	UBERON:0000399	88.75	gold quality
mucosa of paranasal sinus	UBERON:0005030	88.63	gold quality
upper leg skin	UBERON:0004262	88.59	gold quality
skin of hip	UBERON:0001554	88.51	gold quality
calcaneal tendon	UBERON:0003701	88.00	gold quality
colonic epithelium	UBERON:0000397	87.69	gold quality
left ventricle myocardium	UBERON:0006566	87.25	silver quality
tendon	UBERON:0000043	87.22	gold quality
tendon of biceps brachii	UBERON:0008188	87.09	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

1 targets.

Target	Regulation
FOXP3

Upstream regulators (CollecTRI, top): ASXL2, EBF1, GATA3, POU5F1, PRDM4, TET1

miRNA regulators (miRDB)

279 targeting TET2, 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-4795-3P	100.00	74.62	4024
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-6748-5P	100.00	65.81	1057
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-4510	100.00	66.60	2050
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-6127	100.00	66.76	2188
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-3064-3P	100.00	70.09	1254
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997

Literature-anchored findings (GeneRIF, showing 40)

• Loss-of-function mutations in TET2 occur at a high frequency in systemic mastocytosis, and are associated with KITD816V mutations. (PMID:19262599)
• TET2 mutations occur in both JAK2V617F-positive and -negative myeloproliferative neoplasms. (PMID:19262601)
• looked for the presence of TET2 mutations in myeloid malignancies other than MPN, including chronic myelomonocytic leukemia (CMML), myelodysplastic syndrome (MDS), ‘MDS/MPN’ and acute myeloid leukemia (AML) (PMID:19295549)
• TET2 mutations were found in patients with MDS/MPN including CMML or sAML evolved from MDS/MPN and typical MDS, suggesting they may play a ubiquitous role in malignant evolution. (PMID:19372255)
• Sequencing of TET2 in 408 paired tumor/normal samples distinguished between 68 somatic mutations and 6 novel single nucleotide polymorphisms and identified TET2 mutations in MPN (7.6%), CMML (42%), AML (12%), and M7 AML (3.6%) samples. (PMID:19420352)
• Somatic mutations in TET2 occur in about 15% of patients with various myeloid cancers. (PMID:19474426)
• TET2 is the most frequently mutated gene in Myelodysplastic syndromes known so far. (PMID:19483684)
• Novel TET2 mutations associated with UPD4q24 in myelodysplastic syndrome. (PMID:19528370)
• TET2 mutations were mainly observed (10 of 12) in patients with primary myelofibrosis or patients with polycythemia vera or essential thrombocythemia who secondarily evolved toward myelofibrosis or acute myeloid leukemia. (PMID:19564637)
• TET2 mutation is an independent favorable prognostic factor in myelodysplastic syndromes (PMID:19666869)
• TET2 mutations are not observed in all cases of JAK2V617F-negative acute myeloblastic leukemia (AML) that develops from myeloproliferative neoplasms (MPN). (PMID:19710701)
• Data show that TET2 gene alterations are more frequent in chronic myelomonocytic leukemia than in other subgroups of hematopoietic diseases studied so far and could negatively affect the patients’ outcome. (PMID:19797729)
• Mutated in myeloid cancers and other myeloproliferative disorders. (PMID:19849974)
• High frequency of TET2 mutations are associated with refractory anemia with ring sideroblasts and thrombocytosis. (PMID:19903679)
• TET family influences DNA methylation in hematopoietic malignancy (PMID:19923888)
• TET2(tet oncogene family member 2) mutations do not affect initial or subsequent cytogenetic findings in myeloproliferative neoplasms (PMID:19957346)
• Mutations of an E3 ubiquitin ligase c-Cbl but not TET2 mutations are pathogenic in juvenile myelomonocytic leukemia. (PMID:20008299)
• The lack of a strict temporal order of occurrence makes it unlikely that mutations in TET2 represent a predisposing event for acquiring mutations in JAK2. (PMID:20061559)
• TET2 mutations were associated with idic(X)-positive myeloid malignancies. (PMID:20093295)
• the occurrence of TET2 mutations may represent an early event in the pathogenesis of the myeloproliferative neoplasms and splanchnic vein thrombosis (PMID:20156304)
• JAK2 and TET2 mutations in myelodysplastic syndromes [review] (PMID:20171768)
• Mutations of the TET2 and CBL genes: novel molecular markers in myeloid malignancies. (PMID:20195608)
• TET2 mutations are associated with refractory anemia with ring sideroblasts and thrombocytosis. (PMID:20334914)
• TET2 point mutations are associated with acute myeloid leukemia. (PMID:20489055)
• TET2 is not deleted in CMML patients, although it is mutated in a high proportion of cases (PMID:20595094)
• TET2 mutations are not associated with transformed myeloproliferative neoplasms. (PMID:20629097)
• methylation of TET2, CBL and CEBPA is infrequent in myeloproliferative neoplasms at diagnosis. (PMID:20671051)
• Mutations in TET2 occurred with similar frequency in myelodysplastic syndromes and acute myeloid leukemias and associated equally with either ASXL1 or NPM1 mutations. (PMID:20678218)
• Seventy-one TET2 mutations, with a relative mutation abundance (RMA) >/= 10%, were identified in 39 of 320 (12%) myelodysplastic syndrome and 16 of 35 (46%) chronic myelomonocytic leukemia patients (P < .001). (PMID:20693430)
• novel TET2 mutations in 3.8% of pediatric AML. (PMID:21042320)
• disruption of TET2 enzymatic activity favours myeloid tumorigenesis (PMID:21057493)
• TET2 deletions are associated with chronic myelomonocytic leukemia. (PMID:21087791)
• Leukemic IDH1 and IDH2 mutations result in a hypermethylation phenotype, disrupt TET2 function, and impair hematopoietic differentiation. (PMID:21130701)
• JAK2 GGCC haplotype and germline mutations in the TET2 gene in patients with familial myeloproliferative neoplasms may cause an increase in overall carcinogenesis. (PMID:21173100)
• The oncometabolite 2-hydroxyglutarate is a competitive inhibitor of multiple alpha-ketoglutarate-dependent dioxygenases, including histone demethylases, prolyl hydroxylases, and the TET family of 5-methlycytosine hydroxylases. (PMID:21251613)
• Data showed that in vitro the concomitant presence of JAK2(V617F) and TET2 mutations favors clonal polycythemia vera erythroid progenitors in contrast with non-TET2 mutated progenitors. (PMID:21273266)
• determination of TET2 mutational status in blastic plasmacytoid dendritic cell neoplasms(BPDCN); BPDCN belongs to the wide spectrum of haematological neoplasms that display TET2 mutations; relevance of TET2 mutation remains undetermined in this disease (PMID:21275969)
• Studies indicate that additional mutations in genes which appear to affect the epigenome of MPN patients have been discovered including mutations in TET2, IDH1/ 2, EZH2, and ASXL1. (PMID:21307773)
• Loss of the TET2 hydroxylase activity in cells homozygous for TET2 mutations does not appear to increase their competitive advantage, suggesting that the TET2 hydroxylase activity is tightly regulated. (PMID:21310937)
• Mutations in the TET2 gene is associated with chronic myelomonocytic leukemia. (PMID:21339759)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	tet2	ENSDARG00000076928
mus_musculus	Tet2	ENSMUSG00000040943
rattus_norvegicus	Tet2	ENSRNOG00000023579

Paralogs (2): TET1 (ENSG00000138336), TET3 (ENSG00000187605)

Protein

Protein identifiers

Methylcytosine dioxygenase TET2 — Q6N021 (reviewed: Q6N021)

All UniProt accessions (5): A0A158SIU0, D6RE87, E7EPB1, E7EQS8, Q6N021

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 active DNA demethylation. Has a preference for 5-hydroxymethylcytosine in CpG motifs. 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. Methylation at the C5 position of cytosine bases is an epigenetic modification of the mammalian genome which plays an important role in transcriptional regulation. 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.

Subunit / interactions. Interacts with HCFC1. Interacts with OGT. Interacts with PROSER1; this interaction mediates TET2 O-GlcNAcylation and stability by promoting the interaction between OGT and TET2. Directly interacts (via C-terminus) with the DCAF1 component of the CRL4(VprBP) E3 ubiquitin-protein ligase complex.

Subcellular location. Nucleus. Chromosome.

Tissue specificity. Broadly expressed. Highly expressed in hematopoietic cells; highest expression observed in granulocytes. Expression is reduced in granulocytes from peripheral blood of patients affected by myelodysplastic syndromes.

Post-translational modifications. May be glycosylated. It is unclear whether interaction with OGT leads to GlcNAcylation. According to a report, it is not GlcNAcylated by OGT. In contrast, another group reports GlcNAcylation by OGT in mouse ortholog. Monoubiquitinated at Lys-1299 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. Acetylated. Deacetylase HDAC6 acts as a valine sensor by binding to valine through its primate-specific SE14 repeat region and deacetylates TET2 following valine deprivation which promotes TET2-dependent DNA demethylation.

Disease relevance. TET2 is frequently mutated in myeloproliferative disorders (MPD). These constitute a heterogeneous group of disorders, also known as myeloproliferative diseases or myeloproliferative neoplasms (MPN), characterized by cellular proliferation of one or more hematologic cell lines in the peripheral blood, distinct from acute leukemia. Included diseases are: essential thrombocythemia, polycythemia vera, primary myelofibrosis (chronic idiopathic myelofibrosis). Bone marrow samples from patients display uniformly low levels of hmC in genomic DNA compared to bone marrow samples from healthy controls as well as hypomethylation relative to controls at the majority of differentially methylated CpG sites. Polycythemia vera (PV) [MIM:263300] A myeloproliferative disorder characterized by abnormal proliferation of all hematopoietic bone marrow elements, erythroid hyperplasia, an absolute increase in total blood volume, but also by myeloid leukocytosis, thrombocytosis and splenomegaly. The disease is caused by variants affecting the gene represented in this entry. TET2 is frequently mutated in systemic mastocytosis; also known as systemic mast cell disease. A condition with features in common with myeloproliferative diseases. It is a clonal disorder of the mast cell and its precursor cells. The clinical symptoms and signs of systemic mastocytosis are due to accumulation of clonally derived mast cells in different tissues, including bone marrow, skin, the gastrointestinal tract, the liver, and the spleen. Myelodysplastic syndrome (MDS) [MIM:614286] A heterogeneous group of closely related clonal hematopoietic disorders. All are characterized by a hypercellular or hypocellular bone marrow with impaired morphology and maturation, dysplasia of the myeloid, megakaryocytic and/or erythroid lineages, and peripheral blood cytopenias resulting from ineffective blood cell production. Included diseases are: refractory anemia (RA), refractory anemia with ringed sideroblasts (RARS), refractory anemia with excess blasts (RAEB), refractory cytopenia with multilineage dysplasia and ringed sideroblasts (RCMD-RS); chronic myelomonocytic leukemia (CMML) is a myelodysplastic/myeloproliferative disease. MDS is considered a premalignant condition in a subgroup of patients that often progresses to acute myeloid leukemia (AML). The disease is caused by variants affecting the gene represented in this entry. Bone marrow samples from patients display uniformly low levels of hmC in genomic DNA compared to bone marrow samples from healthy controls as well as hypomethylation relative to controls at the majority of differentially methylated CpG sites. Immunodeficiency 75 with lymphoproliferation (IMD75) [MIM:619126] An autosomal recessive immunologic disorder characterized by recurrent infections, mainly viral and affecting the respiratory tract, immunodeficieny, immune dysregulation, and the development of lymphoproliferative disorders, including lymphoma. The disease is caused by variants affecting the gene represented in this entry.

Cofactor. Binds 1 Fe(2+) ion per subunit. Binds 3 zinc ions per subunit. The zinc ions have a structural role.

Miscellaneous. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.

Similarity. Belongs to the TET family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q6N021-1	1	yes
Q6N021-2	2
Q6N021-3	3

RefSeq proteins (2): NP_001120680, NP_060098 (=MANE)

Domains & families (InterPro)

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

Pfam: 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 (195 total): sequence variant 75, strand 22, binding site 21, compositionally biased region 16, mutagenesis site 16, helix 13, region of interest 12, modified residue 6, turn 5, splice variant 4, sequence conflict 3, chain 1, cross-link 1

Structure

Experimental structures (PDB)

6 structures.

PDB	Method	Resolution (Å)
5DEU	X-RAY DIFFRACTION	1.8
9HXV	X-RAY DIFFRACTION	1.9
5D9Y	X-RAY DIFFRACTION	1.97
4NM6	X-RAY DIFFRACTION	2.03
7NE3	X-RAY DIFFRACTION	2.26
7NE6	X-RAY DIFFRACTION	2.3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6N021-F1	47.31	0.19

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 (21): 1133; 1135; 1193; 1219; 1221; 1261; 1271; 1273; 1289; 1298; 1358; 1374 …

Post-translational modifications (7): 15, 75, 99, 1107, 1109, 1682, 1299

Mutagenesis-validated functional residues (16):

Position	Phenotype
1261	loss of enzyme activity.
1262	slightly reduces enzyme activity.
1290	reduces enzyme activity; when associated with a-1295.
1291–1296	loss of enzyme activity.
1292	no effect on interaction with dcaf1, monoubiquitination, nor on 5-methylcytosine demethylase activity in vivo, when test
1293–1294	strongly reduced enzyme activity. slightly decreased affinity for dna.
1295	reduces enzyme activity; when associated with a-1290.
1298	loss of monoubiquitination and of 5-methylcytosine demethylase activity in vivo. no effect on interaction with dcaf1, wh
1300	loss of interaction with dcaf1, monoubiquitination and of 5-methylcytosine demethylase activity in vivo, when tested in
1303	loss of enzyme activity; when associated with e-1299.
1382	loss of enzyme activity. still able to enhance histone h2b glcnacylation by ogt; when associated with a-1384. loss of en
1384	loss of enzyme activity. still able to enhance histone h2b glcnacylation by ogt; when associated with y-1382.
1384	loss of enzyme activity; when associated with y-1382.
1387	near loss of enzyme activity.
1902	loss of enzyme activity.
1904	loss of enzyme activity.

Function

Pathways and Gene Ontology

Reactome pathways

5 pathways

ID	Pathway
R-HSA-5221030	TET1,2,3 and TDG demethylate DNA
R-HSA-9827857	Specification of primordial germ cells
R-HSA-1474165	Reproduction
R-HSA-212165	Epigenetic regulation of gene expression
R-HSA-74160	Gene expression (Transcription)

MSigDB gene sets: 456 (showing top): GOBP_MYELOID_CELL_DIFFERENTIATION, RNGTGGGC_UNKNOWN, FREAC2_01, BENPORATH_ES_WITH_H3K27ME3, HNF3ALPHA_Q6, chr4q24, GOMF_OXIDOREDUCTASE_ACTIVITY_ACTING_ON_PAIRED_DONORS_WITH_INCORPORATION_OR_REDUCTION_OF_MOLECULAR_OXYGEN, YY1_Q6, GGCNKCCATNK_UNKNOWN, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, CREIGHTON_ENDOCRINE_THERAPY_RESISTANCE_1, FOSTER_TOLERANT_MACROPHAGE_UP, MYCMAX_01, YY1_02, GOBP_CARBOHYDRATE_DERIVATIVE_BIOSYNTHETIC_PROCESS

GO Biological Process (11): leukocyte differentiation (GO:0002521), protein O-linked glycosylation (GO:0006493), myeloid cell differentiation (GO:0030099), positive regulation of gene expression via chromosomal CpG island demethylation (GO:0044029), 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 (9): DNA binding (GO:0003677), ferrous iron binding (GO:0008198), zinc ion binding (GO:0008270), DNA 5-methylcytosine dioxygenase activity (GO:0070579), 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 (3): nucleus (GO:0005634), nucleoplasm (GO:0005654), chromosome (GO:0005694)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Epigenetic regulation of gene expression	1
Reproduction	1
Gene expression (Transcription)	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
hemopoiesis	2
cell differentiation	2
regulation of macromolecule biosynthetic process	2
glycoprotein biosynthetic process	1
transcription initiation-coupled chromatin remodeling	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
nucleic acid binding	1
iron ion binding	1
transition metal ion binding	1
2-oxoglutarate-dependent dioxygenase activity	1
catalytic activity, acting on DNA	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
nuclear lumen	1
cellular anatomical structure	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

2682 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TET2	HDAC2	Q92769	989
TET2	ASXL1	Q8IXJ9	976
TET2	EBF1	Q9UH73	968
TET2	NANOG	Q9H9S0	960
TET2	CXXC5	Q7LFL8	946
TET2	OGT	O15294	927
TET2	DNMT3A	Q9Y6K1	926
TET2	CXXC4	Q9H2H0	923
TET2	TET3	O43151	922
TET2	SPI1	P17947	918
TET2	IDH1	O75874	915
TET2	JAK2	O60674	906
TET2	DNMT3L	Q9UJW3	880
TET2	HDAC1	Q13547	875
TET2	EZH2	Q15910	874
TET2	DNMT1	P26358	874

IntAct

92 interactions, top by confidence:

A	B	Type	Score
NONO	SFPQ	psi-mi:“MI:0914”(association)	0.900
NFIC	NFIB	psi-mi:“MI:2364”(proximity)	0.690
TET2	OGT	psi-mi:“MI:0914”(association)	0.660
OGT	TET2	psi-mi:“MI:0915”(physical association)	0.660
TET2	OGT	psi-mi:“MI:0915”(physical association)	0.660
OGT	TET2	psi-mi:“MI:0407”(direct interaction)	0.660
YWHAG	BLTP3B	psi-mi:“MI:2364”(proximity)	0.640
WT1	TET2	psi-mi:“MI:0915”(physical association)	0.600
TET2	WT1	psi-mi:“MI:0915”(physical association)	0.600
TET2	WT1	psi-mi:“MI:0407”(direct interaction)	0.600
TET2	SEMG1	psi-mi:“MI:0915”(physical association)	0.590
YWHAH	BLTP3B	psi-mi:“MI:2364”(proximity)	0.570
TET2	FGFR3	psi-mi:“MI:0915”(physical association)	0.560
TET2	GSN	psi-mi:“MI:0915”(physical association)	0.560
YWHAZ	BLTP3B	psi-mi:“MI:0914”(association)	0.530
NONO	SERPINB7	psi-mi:“MI:0914”(association)	0.530
OGT	SETD1A	psi-mi:“MI:0914”(association)	0.530

BioGRID (191): TET2 (Two-hybrid), TET2 (Affinity Capture-Western), VPRBP (Affinity Capture-Western), DDB1 (Affinity Capture-Western), VPRBP (Reconstituted Complex), EBF1 (Affinity Capture-Western), TET2 (Affinity Capture-MS), SEMG1 (Affinity Capture-MS), TET2 (Affinity Capture-MS), TET2 (Affinity Capture-MS), TET2 (Affinity Capture-RNA), MYH9 (Affinity Capture-MS), VIM (Affinity Capture-MS), BCAR1 (Affinity Capture-MS), BCAR3 (Affinity Capture-MS)

ESM2 similar proteins: A0A1L8GSA2, A0A1L8H0H2, A0JP82, A0MS83, A2AWL7, A2RRX6, A2X0Q0, A6NCI8, A9ZPC9, F8VPJ6, K9JHZ4, O13186, O46567, O60284, O75362, P15822, P35547, P37275, P48552, P52551, P79269, Q03172, Q14207, Q28DZ0, Q2KHR2, Q3V0A6, Q3Y4E1, Q4JK59, Q4V7J0, Q5DTW7, Q5R782, Q5W1J6, Q5ZJK5, Q61624, Q62806, Q6N021, Q6YXZ4, Q7SZL5, Q80TY4, Q8BMA5

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

SIGNOR signaling

16 interactions.

A	Effect	B	Mechanism
TET2	up-regulates	OGT	binding
TET2	“up-regulates activity”	WT1	binding
TET2	down-regulates	Proliferation
2-oxoglutarate(2-)	“up-regulates activity”	TET2	binding
PRKAA1	“up-regulates quantity by stabilization”	TET2	phosphorylation
AMPK	“up-regulates quantity by stabilization”	TET2	phosphorylation
miR-29b	“down-regulates quantity by repression”	TET2	“post transcriptional regulation”
ASXL2	“up-regulates quantity by expression”	TET2	“transcriptional regulation”
AMPK	“up-regulates activity”	TET2	phosphorylation
(R)-2-hydroxyglutarate(2-)	“down-regulates activity”	TET2	“chemical inhibition”
miR-29c	“down-regulates quantity by repression”	TET2	“post transcriptional regulation”
FGFR3	“down-regulates quantity by destabilization”	TET2	phosphorylation
MAP2K1	“up-regulates quantity by stabilization”	TET2	phosphorylation
miR-29a	“down-regulates quantity by repression”	TET2	“post transcriptional regulation”
JAK2	“up-regulates activity”	TET2	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 82 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
Activation of BAD and translocation to mitochondria	8	99.8×	5e-13
SARS-CoV-1 targets host intracellular signalling and regulatory pathways	8	88.1×	1e-12
Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex	7	77.1×	1e-10
Activation of BH3-only proteins	8	65.1×	2e-11
FOXO-mediated transcription	7	38.5×	1e-08
Intrinsic Pathway for Apoptosis	8	38.4×	1e-09
RHO GTPases activate PKNs	7	36.4×	2e-08
SARS-CoV-1-host interactions	9	25.9×	3e-09

GO biological processes:

GO term	Partners	Fold	FDR
protein targeting	6	28.6×	3e-05
regulation of circadian rhythm	5	16.8×	3e-03
negative regulation of translation	5	12.7×	6e-03
intracellular protein localization	7	9.5×	3e-03
gene expression	7	7.3×	6e-03

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: loss-of-function (tumor-suppressor-like) across 7 cancer types — AML, MDS, MLYM, NHL, PCM, RCC, SOFT_TISSUE.

Clinical variants and AI predictions

ClinVar

1910 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	154
Likely pathogenic	22
Uncertain significance	1102
Likely benign	557
Benign	20

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1176035	NM_001127208.3(TET2):c.3589A>G (p.Lys1197Glu)	Pathogenic
1679818	NM_001127208.3(TET2):c.3562A>T (p.Lys1188Ter)	Pathogenic
1686257	NM_001127208.3(TET2):c.2029_2032del (p.Cys677fs)	Pathogenic
1899776	NM_001127208.3(TET2):c.4393C>T (p.Arg1465Ter)	Pathogenic
1936676	NM_001127208.3(TET2):c.822del (p.Asn275fs)	Pathogenic
1967918	NM_001127208.3(TET2):c.1630C>T (p.Arg544Ter)	Pathogenic
1998748	NM_001127208.3(TET2):c.2697T>G (p.Tyr899Ter)	Pathogenic
2012161	NM_001127208.3(TET2):c.294_295insCA (p.Ser99fs)	Pathogenic
2014909	NM_001127208.3(TET2):c.2290del (p.Gln764fs)	Pathogenic
2027208	NM_001127208.3(TET2):c.1513dup (p.Thr505fs)	Pathogenic
2028159	NM_001127208.3(TET2):c.3940del (p.Asp1314fs)	Pathogenic
2033736	NM_001127208.3(TET2):c.3765C>A (p.Tyr1255Ter)	Pathogenic
2036660	NM_001127208.3(TET2):c.2349del (p.Glu783fs)	Pathogenic
2092782	NM_001127208.3(TET2):c.4205dup (p.Asp1402fs)	Pathogenic
2110357	NM_001127208.3(TET2):c.3736_3746del (p.Ser1246fs)	Pathogenic
2111280	NM_001127208.3(TET2):c.1699_1703del (p.Leu567fs)	Pathogenic
2131122	NM_001127208.3(TET2):c.3061C>T (p.Gln1021Ter)	Pathogenic
2133052	NM_001127208.3(TET2):c.1061C>G (p.Ser354Ter)	Pathogenic
2190715	NM_001127208.3(TET2):c.4210C>T (p.Arg1404Ter)	Pathogenic
2429468	NM_001127208.3(TET2):c.3678del (p.Ile1226fs)	Pathogenic
2664682	NM_001127208.3(TET2):c.3893del (p.Cys1298fs)	Pathogenic
2681589	NM_001127208.3(TET2):c.3954+5G>A	Pathogenic
2681591	NM_001127208.3(TET2):c.1806del (p.Lys603fs)	Pathogenic
2681592	NM_001127208.3(TET2):c.5163del (p.Leu1721fs)	Pathogenic
2681593	NM_001127208.3(TET2):c.3917del (p.Pro1306fs)	Pathogenic
2681594	NM_001127208.3(TET2):c.340C>T (p.Gln114Ter)	Pathogenic
2681595	NM_001127208.3(TET2):c.3571C>T (p.Gln1191Ter)	Pathogenic
2681597	NM_001127208.3(TET2):c.2224C>T (p.Gln742Ter)	Pathogenic
2681598	NM_001127208.3(TET2):c.2227C>T (p.Gln743Ter)	Pathogenic
2681599	NM_001127208.3(TET2):c.2231del (p.Gln744fs)	Pathogenic

SpliceAI

1840 predictions. Top by Δscore:

Variant	Effect	Δscore
4:105190487:G:GG	donor_gain	1.0000
4:105155291:T:A	acceptor_gain	0.9900
4:105190479:G:GT	donor_gain	0.9900
4:105190484:GCA:G	donor_gain	0.9900
4:105190486:A:AG	donor_gain	0.9900
4:105238694:G:GT	donor_gain	0.9900
4:105190482:GAGCA:G	donor_gain	0.9800
4:105146061:G:GT	donor_gain	0.9700
4:105157590:GC:G	donor_gain	0.9700
4:105240536:CAATG:C	acceptor_gain	0.9700
4:105240537:A:AG	acceptor_gain	0.9700
4:105240537:AAT:A	acceptor_gain	0.9700
4:105240537:AATGA:A	acceptor_gain	0.9700
4:105146085:GG:G	donor_gain	0.9600
4:105146086:GG:G	donor_gain	0.9600
4:105192062:T:G	acceptor_gain	0.9600
4:105241954:C:CA	acceptor_gain	0.9600
4:105208611:A:AG	acceptor_gain	0.9500
4:105208612:G:GG	acceptor_gain	0.9500
4:105157591:C:G	donor_gain	0.9400
4:105190492:GGAC:G	donor_gain	0.9400
4:105190538:TC:T	donor_gain	0.9400
4:105190542:G:GG	donor_gain	0.9400
4:105146031:A:T	donor_gain	0.9300
4:105146036:A:T	donor_gain	0.9300
4:105148535:G:T	donor_gain	0.9300
4:105146891:G:GT	donor_gain	0.9200
4:105172471:CCTTG:C	acceptor_gain	0.9200
4:105241337:A:AG	acceptor_gain	0.9200
4:105241338:G:GG	acceptor_gain	0.9200

AlphaMissense

13260 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:105242910:T:C	C1193R	1.000
4:105242920:C:A	A1196D	1.000
4:105243718:T:C	L1248P	1.000
4:105243756:C:A	R1261S	1.000
4:105243762:T:C	C1263R	1.000
4:105243763:G:A	C1263Y	1.000
4:105243764:T:G	C1263W	1.000
4:105259626:T:C	C1271R	1.000
4:105259627:G:A	C1271Y	1.000
4:105259628:C:G	C1271W	1.000
4:105259632:T:C	C1273R	1.000
4:105259633:G:A	C1273Y	1.000
4:105259634:T:G	C1273W	1.000
4:105259677:G:C	G1288R	1.000
4:105259678:G:A	G1288D	1.000
4:105259680:T:C	C1289R	1.000
4:105259686:T:A	W1291R	1.000
4:105259686:T:C	W1291R	1.000
4:105259688:G:C	W1291C	1.000
4:105259688:G:T	W1291C	1.000
4:105259689:A:C	S1292R	1.000
4:105259691:C:A	S1292R	1.000
4:105259691:C:G	S1292R	1.000
4:105259705:G:A	G1297E	1.000
4:105259707:T:C	C1298R	1.000
4:105259708:G:A	C1298Y	1.000
4:105259709:T:G	C1298W	1.000
4:105259710:A:G	K1299E	1.000
4:105259713:T:C	F1300L	1.000
4:105259714:T:G	F1300C	1.000

dbSNP variants (sampled 300 via entrez): RS1000019578 (4:105204922 T>G), RS1000022513 (4:105249016 G>T), RS1000025284 (4:105159786 C>A,T), RS1000038854 (4:105160348 C>G,T), RS1000064666 (4:105249382 C>T), RS1000084990 (4:105203683 C>T), RS1000091592 (4:105151048 G>A), RS1000115132 (4:105249802 C>T), RS1000142474 (4:105150798 T>C), RS1000184182 (4:105194406 A>G), RS1000208579 (4:105229455 C>T), RS1000242804 (4:105201189 A>G), RS1000268152 (4:105153520 A>G), RS1000281413 (4:105222780 A>T), RS1000287731 (4:105182603 G>A,C)

Disease associations

OMIM: gene MIM:612839 | disease phenotypes: MIM:619126, MIM:614286, MIM:254500

GenCC curated gene-disease

Disease	Classification	Inheritance
immunodeficiency 75	Strong	Autosomal recessive
pulmonary arterial hypertension	Moderate	Autosomal dominant

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
pulmonary arterial hypertension	Moderate	AD

Mondo (10): immunodeficiency 75 (MONDO:0030858), myelodysplastic syndrome (MONDO:0018881), third-degree atrioventricular block (MONDO:0000468), angioimmunoblastic T-cell lymphoma (MONDO:0004977), atypical chronic myeloid leukemia, BCR-ABL1 negative (MONDO:0004653), clonal hematopoiesis (MONDO:0100542), squamous cell carcinoma (MONDO:0005096), Wilms tumor (MONDO:0006058), plasma cell myeloma (MONDO:0009693), pulmonary arterial hypertension (MONDO:0015924)

Orphanet (7): EBV-induced lymphoproliferative disease due to TET2 deficiency (Orphanet:664729), Myelodysplastic syndrome (Orphanet:52688), Angioimmunoblastic T-cell lymphoma (Orphanet:86886), Atypical chronic myeloid leukemia (Orphanet:98824), Nephroblastoma (Orphanet:654), Multiple myeloma (Orphanet:29073), AL amyloidosis (Orphanet:85443)

HPO phenotypes

135 total (30 of 135 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000505	Visual impairment
HP:0000939	Osteoporosis
HP:0000967	Petechiae
HP:0000978	Bruising susceptibility
HP:0000979	Purpura
HP:0000980	Pallor
HP:0000989	Pruritus
HP:0001025	Urticaria
HP:0001028	Hemangioma
HP:0001231	Abnormal fingernail morphology
HP:0001279	Syncope
HP:0001409	Portal hypertension
HP:0001410	Decreased liver function
HP:0001433	Hepatosplenomegaly
HP:0001442	Typified by somatic mosaicism
HP:0001541	Ascites
HP:0001635	Congestive heart failure
HP:0001649	Tachycardia
HP:0001658	Myocardial infarction
HP:0001744	Splenomegaly
HP:0001824	Weight loss
HP:0001871	Abnormality of blood and blood-forming tissues
HP:0001872	Abnormality of thrombocytes
HP:0001873	Thrombocytopenia
HP:0001875	Decreased total neutrophil count
HP:0001876	Pancytopenia
HP:0001880	Increased total eosinophil count
HP:0001892	Abnormal bleeding
HP:0001894	Thrombocytosis

GWAS associations

94 associations (top):

Study	Trait	p-value
GCST000488_9	Prostate cancer	3.000000e-14
GCST000817_143	Height	4.000000e-11
GCST001251_7	Pulmonary function	6.000000e-07
GCST001547_6	Immune response to anthrax vaccine	9.000000e-06
GCST001937_53	Breast cancer	4.000000e-08
GCST001956_84	Height	2.000000e-08
GCST002514_3	Melanoma	8.000000e-07
GCST002702_50	Height	6.000000e-09
GCST002890_15	Prostate cancer	4.000000e-09
GCST002937_10	Molybdenum levels	4.000000e-06
GCST003208_6	Colorectal or endometrial cancer	6.000000e-07
GCST003262_337	Post bronchodilator FEV1	5.000000e-06
GCST003264_197	Post bronchodilator FEV1/FVC ratio	3.000000e-06
GCST003995_10	Tonsillectomy	3.000000e-12
GCST004147_2	Chronic obstructive pulmonary disease	2.000000e-13
GCST004183_29	Lung function (FEV1)	9.000000e-09
GCST004185_52	Lung function (FEV1/FVC)	1.000000e-08
GCST004607_223	Plateletcrit	2.000000e-10
GCST004627_61	Lymphocyte count	3.000000e-14
GCST004632_110	Lymphocyte percentage of white cells	7.000000e-25
GCST004633_51	Neutrophil percentage of white cells	1.000000e-20
GCST004640_17	Western dietary pattern	7.000000e-06
GCST004988_219	Breast cancer	5.000000e-11
GCST005014_48	Tonsillectomy	3.000000e-12
GCST005141_50	Cognitive ability (MTAG)	5.000000e-12
GCST005142_54	Cognitive ability	1.000000e-08
GCST005316_608	Intelligence (MTAG)	3.000000e-08
GCST005316_609	Intelligence (MTAG)	2.000000e-15
GCST005316_614	Intelligence (MTAG)	5.000000e-15
GCST005316_615	Intelligence (MTAG)	1.000000e-10

EFO canonical traits (34, from GWAS)

EFO ID	Trait name
EFO:0003892	pulmonary function measurement
EFO:0004314	forced expiratory volume
EFO:0004645	response to vaccine
EFO:0004230	endometrial neoplasm
EFO:0004713	FEV/FVC ratio
EFO:0007924	tonsillectomy risk measurement
EFO:0007985	platelet crit
EFO:0004587	lymphocyte count
EFO:0007993	lymphocyte percentage of leukocytes
EFO:0007990	neutrophil percentage of leukocytes
EFO:0008111	diet measurement
EFO:0004337	intelligence
EFO:0004784	self reported educational attainment
EFO:0008579	risk-taking behaviour
EFO:0009592	social interaction measurement
EFO:0009270	heel bone mineral density
EFO:0003924	hair color
EFO:0009718	peak expiratory flow
EFO:0004344	birth weight
EFO:0005939	parental genotype effect measurement
EFO:0006781	coffee consumption measurement
EFO:0010538	taurocholate measurement
EFO:0009695	household income
EFO:0004614	apolipoprotein A 1 measurement
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0010091	tea consumption measurement
EFO:0009748	response to ketamine
EFO:0008039	BMI-adjusted hip circumference
EFO:0004980	appendicular lean mass
EFO:0004251	myeloproliferative disorder

MeSH disease descriptors (5)

Descriptor	Name	Tree numbers
D002294	Carcinoma, Squamous Cell	C04.557.470.200.400; C04.557.470.700.400
D007119	Immunoblastic Lymphadenopathy	C15.604.338.500; C15.604.515.509; C20.683.515.501
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
D000081029	Pulmonary Arterial Hypertension	C08.381.423.847
D009396	Wilms Tumor	C04.557.435.595; C04.588.945.947.535.585; C04.700.900; C12.050.351.937.820.535.585; C12.050.351.968.419.473.585; C12.200.758.820.750.585; C12.200.777.419.473.585; C12.900.820.535.585; C12.950.419.473.585; C12.950.983.535.585; C16.320.700.900

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4523344 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

3 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 37,950 (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
CHEMBL556	DEFEROXAMINE	4	25,751

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

PharmGKB clinical annotations

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs12505746	Efficacy	3	hydrochlorothiazide	Essential hypertension

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs12505746	TET2	3	0.00	1	hydrochlorothiazide

ChEMBL bioactivities

52 potent at pChembl≥5 of 90 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.91	IC50	123	nM	CHEMBL5527999
6.60	IC50	250	nM	CHEMBL5527999
6.60	IC50	250	nM	CHEMBL5565375
6.52	Kd	300	nM	CHEMBL4851104
6.45	IC50	354.8	nM	CHEMBL3785455
6.26	IC50	549.5	nM	CHEMBL1230640
6.21	Kd	610	nM	CHEMBL4855677
6.12	IC50	758.6	nM	CHEMBL1230640
6.08	IC50	831.8	nM	CHEMBL5561497
6.03	IC50	933.2	nM	CHEMBL5562105
5.95	IC50	1122	nM	CHEMBL5532540
5.92	IC50	1200	nM	CHEMBL4872206
5.89	IC50	1288	nM	CHEMBL5561920
5.81	IC50	1549	nM	CHEMBL1398529
5.69	Kd	2050	nM	CHEMBL4859276
5.68	IC50	2100	nM	CHEMBL5193408
5.66	IC50	2188	nM	CHEMBL5557587
5.66	IC50	2188	nM	CHEMBL5560200
5.64	IC50	2300	nM	CHEMBL5205660
5.64	IC50	2270	nM	CHEMBL1230640
5.61	IC50	2455	nM	CHEMBL5557957
5.60	IC50	2512	nM	CHEMBL5549950
5.59	IC50	2570	nM	CHEMBL5557957
5.55	IC50	2818	nM	CHEMBL5561920
5.54	IC50	2884	nM	CHEMBL5561497
5.52	IC50	3020	nM	CHEMBL1982368
5.52	IC50	3020	nM	CHEMBL5549844
5.52	IC50	3020	nM	CHEMBL5567655
5.52	IC50	3020	nM	CHEMBL5532540
5.51	IC50	3090	nM	CHEMBL5549844
5.50	IC50	3162	nM	CHEMBL5563232
5.49	IC50	3236	nM	CHEMBL5557793
5.47	Kd	3420	nM	CHEMBL4870693
5.47	IC50	3388	nM	CHEMBL5557587
5.44	IC50	3631	nM	CHEMBL5564980
5.42	IC50	3802	nM	PANOBINOSTAT
5.42	IC50	3800	nM	PANOBINOSTAT
5.41	IC50	3890	nM	CHEMBL5564944
5.40	IC50	3981	nM	CHEMBL5562105
5.39	IC50	4074	nM	CHEMBL4203498
5.31	IC50	4898	nM	CHEMBL1230640
5.30	IC50	5012	nM	VADADUSTAT
5.29	IC50	5129	nM	CHEMBL316034
5.27	IC50	5370	nM	CHEMBL5557372
5.26	IC50	5495	nM	CHEMBL4475458
5.19	IC50	6457	nM	CHEMBL5557793
5.16	EC50	6918	nM	CHEMBL1230640
5.16	EC50	6900	nM	CHEMBL1230640
5.11	IC50	7762	nM	CHEMBL5563232
5.05	IC50	8913	nM	N-OXALYLGLYCINE

PubChem BioAssay actives

52 with measured affinity, of 194 total; 34 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	2083784: Inhibition of N-terminal His-tagged recombinant human TET2 catalytic domain LCIdel mutant (D1129 to G1936 residues with Y1481 to N1843 replaced by 3 x GGGGS linker) expressed in Escherichia coli BL21 (DE3) using 5-methylcytosine as substrate preincubated for 10 mins followed by substrate and DNA-cofactor addition measured after 10 mins by Alphascreen assay	ic50	0.1230	uM
3-[(3R,6S,9S,12S,15S,18S,21S,24S,27S,30S,33S,36S,39S,42R)-3-[[N-[(4S)-4-amino-5-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-amino-5-carbamimidamido-1-oxopentan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-5-oxopentyl]carbamimidoyl]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	2083784: Inhibition of N-terminal His-tagged recombinant human TET2 catalytic domain LCIdel mutant (D1129 to G1936 residues with Y1481 to N1843 replaced by 3 x GGGGS linker) expressed in Escherichia coli BL21 (DE3) using 5-methylcytosine as substrate preincubated for 10 mins followed by substrate and DNA-cofactor addition measured after 10 mins by Alphascreen assay	ic50	0.2500	uM
2-hydroxy-4-methylidenepentanedioic acid	1763206: Binding affinity to human recombinant TET2 (1099 to 1936) catalytic domain assessed as dissociation constant by micro-scale thermophoresis analysis	kd	0.3000	uM
(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-amino-5-(diaminomethylideneamino)pentanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-5-(diaminomethylideneamino)pentanoic acid	2083784: Inhibition of N-terminal His-tagged recombinant human TET2 catalytic domain LCIdel mutant (D1129 to G1936 residues with Y1481 to N1843 replaced by 3 x GGGGS linker) expressed in Escherichia coli BL21 (DE3) using 5-methylcytosine as substrate preincubated for 10 mins followed by substrate and DNA-cofactor addition measured after 10 mins by Alphascreen assay	ic50	0.3548	uM
8-hydroxyquinoline-5-carboxylic acid	2083785: Inhibition of N-terminal His-tagged recombinant human TET2 catalytic domain LCIdel mutant (D1129 to G1936 residues with Y1481 to N1843 replaced by 3 x GGGGS linker) expressed in Escherichia coli BL21 (DE3) using 5-methylcytosine as substrate preincubated for 10 mins followed by substrate and DNA-cofactor addition measured after 12 mins by SPE-MS analysis	ic50	0.5495	uM
2-hydroxy-2-methyl-4-methylidenepentanedioic acid	1763206: Binding affinity to human recombinant TET2 (1099 to 1936) catalytic domain assessed as dissociation constant by micro-scale thermophoresis analysis	kd	0.6100	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	2083784: Inhibition of N-terminal His-tagged recombinant human TET2 catalytic domain LCIdel mutant (D1129 to G1936 residues with Y1481 to N1843 replaced by 3 x GGGGS linker) expressed in Escherichia coli BL21 (DE3) using 5-methylcytosine as substrate preincubated for 10 mins followed by substrate and DNA-cofactor addition measured after 10 mins by Alphascreen assay	ic50	0.8318	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	2083784: Inhibition of N-terminal His-tagged recombinant human TET2 catalytic domain LCIdel mutant (D1129 to G1936 residues with Y1481 to N1843 replaced by 3 x GGGGS linker) expressed in Escherichia coli BL21 (DE3) using 5-methylcytosine as substrate preincubated for 10 mins followed by substrate and DNA-cofactor addition measured after 10 mins by Alphascreen assay	ic50	0.9333	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	2083784: Inhibition of N-terminal His-tagged recombinant human TET2 catalytic domain LCIdel mutant (D1129 to G1936 residues with Y1481 to N1843 replaced by 3 x GGGGS linker) expressed in Escherichia coli BL21 (DE3) using 5-methylcytosine as substrate preincubated for 10 mins followed by substrate and DNA-cofactor addition measured after 10 mins by Alphascreen assay	ic50	1.1220	uM
[(2R,3R)-3-(3,4-dihydroxyphenyl)-6,8-dihydroxy-1,2,3,4-tetrahydronaphthalen-2-yl] (3S)-5-(3,4-dihydroxyphenyl)-3-hydroxypentanoate	1763193: Inhibition of TET2 (unknown origin)	ic50	1.2000	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	2083784: Inhibition of N-terminal His-tagged recombinant human TET2 catalytic domain LCIdel mutant (D1129 to G1936 residues with Y1481 to N1843 replaced by 3 x GGGGS linker) expressed in Escherichia coli BL21 (DE3) using 5-methylcytosine as substrate preincubated for 10 mins followed by substrate and DNA-cofactor addition measured after 10 mins by Alphascreen assay	ic50	1.2882	uM
N-[3-(dimethylamino)propyl]-4-(8-hydroxyquinolin-6-yl)benzamide	1984346: Inhibition of His10-FLAG tagged human TET2 catalytic domain (Q969 to I2002 residues) expressed in Sf9 cells using 5-methylcytosine as substrate preincubated for 10 mins followed by DNA-cofactor addition and measured after 10 mins by Alphascreen assay	ic50	1.5488	uM
2-hydroxy-4-methylidene-2-(trifluoromethyl)pentanedioic acid	1763206: Binding affinity to human recombinant TET2 (1099 to 1936) catalytic domain assessed as dissociation constant by micro-scale thermophoresis analysis	kd	2.0500	uM
8-fluoro-3-iodo-N-(5-methyl-1,2-oxazol-4-yl)quinoline-5-sulfonamide	1853071: Inhibition of N-terminal His6-tagged TET2 (unknown origin) expressed in Escherichia coli assessed as reduction in hmC and fC levels preincubated for 30 mins followed by Fe(II) addition and measured after 1 hrs using 5’-CACmCGGTG-3’ palindromic oligonucleotide as substrate by MALDI-TOF MS analysis	ic50	2.1000	uM
(3S,6R,12R,15S,18S,21S,24S,27S,30S,33S,36S,39S)-27-(2-amino-2-oxoethyl)-21-[(1R)-1-hydroxyethyl]-6,24,33-tris[(4-hydroxyphenyl)methyl]-15,18,30-tris(1H-indol-3-ylmethyl)-3-methyl-2,5,8,14,17,20,23,26,29,32,35,38-dodecaoxo-36-propan-2-yl-10-thia-1,4,7,13,16,19,22,25,28,31,34,37-dodecazabicyclo[37.3.0]dotetracontane-12-carboxamide	2083785: Inhibition of N-terminal His-tagged recombinant human TET2 catalytic domain LCIdel mutant (D1129 to G1936 residues with Y1481 to N1843 replaced by 3 x GGGGS linker) expressed in Escherichia coli BL21 (DE3) using 5-methylcytosine as substrate preincubated for 10 mins followed by substrate and DNA-cofactor addition measured after 12 mins by SPE-MS analysis	ic50	2.1878	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	2083784: Inhibition of N-terminal His-tagged recombinant human TET2 catalytic domain LCIdel mutant (D1129 to G1936 residues with Y1481 to N1843 replaced by 3 x GGGGS linker) expressed in Escherichia coli BL21 (DE3) using 5-methylcytosine as substrate preincubated for 10 mins followed by substrate and DNA-cofactor addition measured after 10 mins by Alphascreen assay	ic50	2.1878	uM
8-fluoro-3-iodoquinoline-5-sulfonic acid	1853071: Inhibition of N-terminal His6-tagged TET2 (unknown origin) expressed in Escherichia coli assessed as reduction in hmC and fC levels preincubated for 30 mins followed by Fe(II) addition and measured after 1 hrs using 5’-CACmCGGTG-3’ palindromic oligonucleotide as substrate by MALDI-TOF MS analysis	ic50	2.3000	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	2083785: Inhibition of N-terminal His-tagged recombinant human TET2 catalytic domain LCIdel mutant (D1129 to G1936 residues with Y1481 to N1843 replaced by 3 x GGGGS linker) expressed in Escherichia coli BL21 (DE3) using 5-methylcytosine as substrate preincubated for 10 mins followed by substrate and DNA-cofactor addition measured after 12 mins by SPE-MS analysis	ic50	2.4547	uM
3-[(5R,8S,11S,14S,17S,20S,23S,26S,29S,32S,35S,38S,41S,44R)-41-(3-amino-3-oxopropyl)-38-[(2S)-butan-2-yl]-8-(3-carbamimidamidopropyl)-44-carbamoyl-26-[(1R)-1-hydroxyethyl]-5,14,23-tris[(4-hydroxyphenyl)methyl]-29,32-bis(1H-indol-3-ylmethyl)-17-methyl-20,35-bis(2-methylpropyl)-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]propanoic acid	2083785: Inhibition of N-terminal His-tagged recombinant human TET2 catalytic domain LCIdel mutant (D1129 to G1936 residues with Y1481 to N1843 replaced by 3 x GGGGS linker) expressed in Escherichia coli BL21 (DE3) using 5-methylcytosine as substrate preincubated for 10 mins followed by substrate and DNA-cofactor addition measured after 12 mins by SPE-MS analysis	ic50	2.5119	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	2083784: Inhibition of N-terminal His-tagged recombinant human TET2 catalytic domain LCIdel mutant (D1129 to G1936 residues with Y1481 to N1843 replaced by 3 x GGGGS linker) expressed in Escherichia coli BL21 (DE3) using 5-methylcytosine as substrate preincubated for 10 mins followed by substrate and DNA-cofactor addition measured after 10 mins by Alphascreen assay	ic50	3.0200	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	2083784: Inhibition of N-terminal His-tagged recombinant human TET2 catalytic domain LCIdel mutant (D1129 to G1936 residues with Y1481 to N1843 replaced by 3 x GGGGS linker) expressed in Escherichia coli BL21 (DE3) using 5-methylcytosine as substrate preincubated for 10 mins followed by substrate and DNA-cofactor addition measured after 10 mins by Alphascreen assay	ic50	3.0200	uM
5-chloro-N-[(E)-[phenyl(pyridin-2-yl)methylidene]amino]pyridin-2-amine	1984346: Inhibition of His10-FLAG tagged human TET2 catalytic domain (Q969 to I2002 residues) expressed in Sf9 cells using 5-methylcytosine as substrate preincubated for 10 mins followed by DNA-cofactor addition and measured after 10 mins by Alphascreen assay	ic50	3.0200	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	2083785: Inhibition of N-terminal His-tagged recombinant human TET2 catalytic domain LCIdel mutant (D1129 to G1936 residues with Y1481 to N1843 replaced by 3 x GGGGS linker) expressed in Escherichia coli BL21 (DE3) using 5-methylcytosine as substrate preincubated for 10 mins followed by substrate and DNA-cofactor addition measured after 12 mins by SPE-MS analysis	ic50	3.1623	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	2083784: Inhibition of N-terminal His-tagged recombinant human TET2 catalytic domain LCIdel mutant (D1129 to G1936 residues with Y1481 to N1843 replaced by 3 x GGGGS linker) expressed in Escherichia coli BL21 (DE3) using 5-methylcytosine as substrate preincubated for 10 mins followed by substrate and DNA-cofactor addition measured after 10 mins by Alphascreen assay	ic50	3.2359	uM
2-hydroxypentanedioic acid	1763206: Binding affinity to human recombinant TET2 (1099 to 1936) catalytic domain assessed as dissociation constant by micro-scale thermophoresis analysis	kd	3.4200	uM
3-[(3S,6S,9S,12S,15R,21R,24S,27S,30S,33S,36S,39S,42R,45S,48S,51S)-30-benzyl-3-[(2S)-butan-2-yl]-39-(3-carbamimidamidopropyl)-21-carbamoyl-24-[(1R)-1-hydroxyethyl]-6,9,15-tris[(4-hydroxyphenyl)methyl]-45,48-bis(1H-indol-3-ylmethyl)-36-methyl-2,5,8,11,14,17,23,26,29,32,35,38,41,44,47,50-hexadecaoxo-12,33-di(propan-2-yl)-42-(sulfanylmethyl)-19-thia-1,4,7,10,13,16,22,25,28,31,34,37,40,43,46,49-hexadecazabicyclo[49.3.0]tetrapentacontan-27-yl]propanoic acid	2083785: Inhibition of N-terminal His-tagged recombinant human TET2 catalytic domain LCIdel mutant (D1129 to G1936 residues with Y1481 to N1843 replaced by 3 x GGGGS linker) expressed in Escherichia coli BL21 (DE3) using 5-methylcytosine as substrate preincubated for 10 mins followed by substrate and DNA-cofactor addition measured after 12 mins by SPE-MS analysis	ic50	3.6308	uM
Panobinostat	1984346: Inhibition of His10-FLAG tagged human TET2 catalytic domain (Q969 to I2002 residues) expressed in Sf9 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
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	2083784: Inhibition of N-terminal His-tagged recombinant human TET2 catalytic domain LCIdel mutant (D1129 to G1936 residues with Y1481 to N1843 replaced by 3 x GGGGS linker) expressed in Escherichia coli BL21 (DE3) using 5-methylcytosine as substrate preincubated for 10 mins followed by substrate and DNA-cofactor addition measured after 10 mins by Alphascreen assay	ic50	3.8904	uM
(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-6-amino-2-[[(2S)-6-amino-2-[[(2S)-2-[[2-[[(2S)-2-amino-3-(4-hydroxyphenyl)propanoyl]amino]acetyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]hexanoyl]amino]hexanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-5-oxopentanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-5-(diaminomethylideneamino)pentanoic acid	2083784: Inhibition of N-terminal His-tagged recombinant human TET2 catalytic domain LCIdel mutant (D1129 to G1936 residues with Y1481 to N1843 replaced by 3 x GGGGS linker) expressed in Escherichia coli BL21 (DE3) using 5-methylcytosine as substrate preincubated for 10 mins followed by substrate and DNA-cofactor addition measured after 10 mins by Alphascreen assay	ic50	4.0738	uM
Vadadustat	1984346: Inhibition of His10-FLAG tagged human TET2 catalytic domain (Q969 to I2002 residues) expressed in Sf9 cells using 5-methylcytosine as substrate preincubated for 10 mins followed by DNA-cofactor addition and measured after 10 mins by Alphascreen assay	ic50	5.0119	uM
pyridine-2,4-dicarboxylic acid	1984346: Inhibition of His10-FLAG tagged human TET2 catalytic domain (Q969 to I2002 residues) expressed in Sf9 cells using 5-methylcytosine as substrate preincubated for 10 mins followed by DNA-cofactor addition and measured after 10 mins by Alphascreen assay	ic50	5.1286	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	2083785: Inhibition of N-terminal His-tagged recombinant human TET2 catalytic domain LCIdel mutant (D1129 to G1936 residues with Y1481 to N1843 replaced by 3 x GGGGS linker) expressed in Escherichia coli BL21 (DE3) using 5-methylcytosine as substrate preincubated for 10 mins followed by substrate and DNA-cofactor addition measured after 12 mins by SPE-MS analysis	ic50	5.3703	uM
4-oxo-1H-1,10-phenanthroline-3-carboxylic acid	1984346: Inhibition of His10-FLAG tagged human TET2 catalytic domain (Q969 to I2002 residues) expressed in Sf9 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
2-(carboxymethylamino)-2-oxoacetic acid	1984346: Inhibition of His10-FLAG tagged human TET2 catalytic domain (Q969 to I2002 residues) expressed in Sf9 cells using 5-methylcytosine as substrate preincubated for 10 mins followed by DNA-cofactor addition and measured after 10 mins by Alphascreen assay	ic50	8.9125	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects binding, increases reaction, increases abundance, decreases activity, decreases expression (+5 more)	4
sodium arsenite	affects binding, affects reaction, increases expression, increases methylation, decreases expression (+2 more)	4
Valproic Acid	affects expression, decreases expression	4
trichostatin A	affects cotreatment, decreases expression	3
bisphenol S	decreases activity, decreases abundance, affects binding, increases reaction, decreases expression (+5 more)	3
potassium chromate(VI)	affects cotreatment, decreases expression	2
perfluorooctane sulfonic acid	decreases expression	2
dorsomorphin	decreases expression, decreases reaction, affects cotreatment	2
Ascorbic Acid	decreases expression, decreases reaction, decreases stability	2
Hydrogen Peroxide	affects cotreatment, decreases expression, increases expression	2
Tetrachlorodibenzodioxin	affects expression, increases expression	2
aristolochic acid I	decreases expression	1
GSK-J4	increases expression	1
FR900359	affects phosphorylation	1
geldanamycin	increases expression	1
methylmercuric chloride	decreases expression	1
propionaldehyde	decreases expression	1
deoxynivalenol	increases expression	1
geniposide	affects cotreatment, decreases expression	1
5-hydroxymethylcytosine	decreases abundance, decreases reaction, increases abundance, increases reaction	1
arsenite	decreases reaction, affects binding	1
butyraldehyde	decreases expression	1
nickel chloride	increases abundance, increases expression	1
perfluorooctanoic acid	affects expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
pentanal	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
chromium hexavalent ion	decreases expression	1
entinostat	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1

ChEMBL screening assays

24 unique, capped per target: 24 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4334314	Binding	Inhibition of recombinant human C-terminal His/N-terminal FLAG-tagged TET2 (1129 to 2002 residues) expressed in baculovirus infected sf9 cells assessed as reduction in oxidation of methylated dsDNA at 100 uM after 2 hrs by chemiluminescence	Cytosine-Based TET Enzyme Inhibitors. — ACS Med Chem Lett

Cellosaurus cell lines

32 cell lines: 16 cancer cell line, 10 induced pluripotent stem cell, 3 spontaneously immortalized cell line, 3 telomerase immortalized cell line

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

Cellosaurus	Name	Category	Sex
CVCL_1149	CTB-1	Cancer cell line	Male
CVCL_1806	AMO1	Cancer cell line	Female
CVCL_A5IU	UKAi004-A	Induced pluripotent stem cell	Male
CVCL_A5IV	UKAi004-B	Induced pluripotent stem cell	Male
CVCL_A5IW	UKAi004-C	Induced pluripotent stem cell	Male
CVCL_A5IX	UKAi004-D	Induced pluripotent stem cell	Male
CVCL_A5IY	UKAi004-E	Induced pluripotent stem cell	Male
CVCL_A5MZ	UKAi007-A	Induced pluripotent stem cell	Male
CVCL_A5NA	UKAi007-B	Induced pluripotent stem cell	Male
CVCL_A5NB	UKAi008-A	Induced pluripotent stem cell	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00058929	PHASE4	COMPLETED	A Transition Study From Flolan® to Remodulin® in Patients With Pulmonary Arterial Hypertension
NCT00303459	PHASE4	COMPLETED	Effects of the Combination of Bosentan and Sildenafil Versus Sildenafil Monotherapy on Pulmonary Arterial Hypertension (PAH)
NCT00323297	PHASE4	COMPLETED	Assess the Efficacy and Safety of Sildenafil When Added to Bosentan in the Treatment of Pulmonary Arterial Hypertension
NCT00367770	PHASE4	COMPLETED	BREATHE 5-OL: Tracleer (Bosentan) in Patients With Pulmonary Arterial Hypertension Related to Eisenmenger Physiology
NCT00403650	PHASE4	COMPLETED	Inhaled Iloprost for Sarcoidosis-associated Pulmonary Hypertension
NCT00430716	PHASE4	TERMINATED	To Assess The Efficacy and Safety Of Oral Sildenafil in the Treatment of Pulmonary Arterial Hypertension.
NCT00433329	PHASE4	COMPLETED	Combination Therapy in Pulmonary Arterial Hypertension
NCT00439946	PHASE4	TERMINATED	Safety, Efficacy, and Treatment Satisfaction Switching From Flolan to Remodulin Using the Crono Five Ambulatory Pump in Patients With PAH
NCT00483626	PHASE4	UNKNOWN	Hemodynamic Response After Six Months of Sildenafil
NCT00494533	PHASE4	TERMINATED	Study of Intravenous Remodulin in Patients in India With Pulmonary Arterial Hypertension
NCT00617305	PHASE4	COMPLETED	Study of Add-on Ambrisentan Therapy to Background Phosphodiesterase Type-5 Inhibitor (PDE5i) Therapy in Pulmonary Arterial Hypertension (ATHENA-1)
NCT00625079	PHASE4	WITHDRAWN	Pulmonary Hypertension Secondary to Idiopathic Pulmonary Fibrosis And Treatment With Sildenafil
NCT00625469	PHASE4	WITHDRAWN	Pulmonary Arterial Hypertension Secondary to Idiopathic Pulmonary Fibrosis and Treatment With Bosentan
NCT00705588	PHASE4	UNKNOWN	Long Acting Phosphodiesterase 5 Inhibitors as Add-on Therapy for Patients With Pulmonary Hypertension Treated With Prostanoids.
NCT00741819	PHASE4	COMPLETED	Safety Evaluation of Inhaled Treprostinil Administration Following Transition From Inhaled Ventavis in Pulmonary Arterial Hypertension (PAH) Subjects
NCT01042158	PHASE4	COMPLETED	A Clinical Trial of Ambrisentan and Tadalafil in Pulmonary Arterial Hypertension Associated With Systemic Sclerosis
NCT01105091	PHASE4	COMPLETED	Epoprostenol for Injection in Pulmonary Arterial Hypertension
NCT01105117	PHASE4	COMPLETED	Epoprostenol for Injection in Pulmonary Arterial Hypertension - Extension of AC-066A401
NCT01268553	PHASE4	COMPLETED	Transition From Injectable Prostacyclin Medication to Inhaled Prostacyclin Medication
NCT01302444	PHASE4	TERMINATED	Treprostinil Combined With Tadalafil for Pulmonary Hypertension
NCT01330108	PHASE4	COMPLETED	Safely Change From Bosentan to Ambrisentan in Pulmonary Hypertension
NCT01433328	PHASE4	TERMINATED	Lidocaine Subcutaneous Infusion for Control of Treprostinil Related Site Pain
NCT01508780	PHASE4	WITHDRAWN	Combined Use of Angiography, Optical Coherence Tomography and Intravascular Ultrasound in Evaluation of Pulmonary Vascular Structure and Function in Patients With Pulmonary Arterial Hypertension Treated With Oral Bosentan
NCT01615627	PHASE4	WITHDRAWN	Hypotonic Treprostinil Subcutaneous Infusion for Control of Treprostinil Related Site Pain
NCT01642407	PHASE4	COMPLETED	Safety And Efficacy Of Sildenafil In Children With Pulmonary Arterial Hypertension
NCT01649739	PHASE4	UNKNOWN	Vardenafil as add-on Therapy for Patients With Pulmonary Hypertension Treated With Inhaled Iloprost
NCT02060487	PHASE4	TERMINATED	Effects of Oral Sildenafil on Mortality in Adults With PAH
NCT02253394	PHASE4	TERMINATED	The Combination Ambrisentan Plus Spironolactone in Pulmonary Arterial Hypertension Study
NCT02284737	PHASE4	TERMINATED	A Study to Investigate the Efficacy of PADN to Improved Functional Capacity and Hemodynamics in Patients With PAH
NCT02310672	PHASE4	COMPLETED	REPAIR: Right vEntricular Remodeling in Pulmonary ArterIal hypeRtension
NCT02847260	PHASE4	COMPLETED	Safety and Tolerability of Rapid Dose Titration of Subcutaneous Remodulin® Therapy in PAH Subjects (RAPID)
NCT02882126	PHASE4	WITHDRAWN	An Open Label Extension Study to Evaluate the Safety of Continued Therapy of Subcutanous Remodulin® in Pulmonary Arterial Hypertension
NCT02885012	PHASE4	TERMINATED	Crossover Study From Macitentan or Bosentan Over to Ambrisentan
NCT02891850	PHASE4	COMPLETED	Riociguat rEplacing PDE-5i Therapy evaLuated Against Continued PDE-5i thErapy
NCT02893995	PHASE4	WITHDRAWN	Safety, Tolerability, Pharmacokinetics and Efficacy of Two Different Rates of Subcutanous Remodulin® Dose Titration in Pulmonary Arterial Hypertension
NCT02968901	PHASE4	TERMINATED	Clinical Study Evaluating the Effects of First-line Oral cOmbination theraPy of maciTentan and tadalafIl in Patients With Newly Diagnosed pulMonary Arterial Hypertension (OPTIMA)
NCT03055221	PHASE4	COMPLETED	TRUST-2: Safety and Efficacy of Intravenous Remodulin® in Patients in India With Pulmonary Arterial Hypertension (PAH)
NCT03078907	PHASE4	COMPLETED	Effect of Selexipag on Daily Life Physical Activity of Patients With Pulmonary Arterial Hypertension.
NCT03236818	PHASE4	UNKNOWN	Goal Oriented Strategy to Preserve Ejection Fraction Trial
NCT03344159	PHASE4	COMPLETED	Spironolactone Therapy in Chronic Stable Right HF Trial