TRIM24

Summary

TRIM24 (tripartite motif containing 24, HGNC:11812) is a protein-coding gene on chromosome 7q33-q34, encoding Transcription intermediary factor 1-alpha (O15164). Transcriptional coactivator that interacts with numerous nuclear receptors and coactivators and modulates the transcription of target genes.

The protein encoded by this gene mediates transcriptional control by interaction with the activation function 2 (AF2) region of several nuclear receptors, including the estrogen, retinoic acid, and vitamin D3 receptors. The protein localizes to nuclear bodies and is thought to associate with chromatin and heterochromatin-associated factors. The protein is a member of the tripartite motif (TRIM) family. The TRIM motif includes three zinc-binding domains - a RING, a B-box type 1 and a B-box type 2 - and a coiled-coil region. Two alternatively spliced transcript variants encoding different isoforms have been described for this gene.

Source: NCBI Gene 8805 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 107 total — 1 likely-pathogenic
• Druggable target: yes
• Cancer driver (intOGen): activating (oncogene-like) across 1 cancer types
• MANE Select transcript: NM_015905

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11812
Approved symbol	TRIM24
Name	tripartite motif containing 24
Location	7q33-q34
Locus type	gene with protein product
Status	Approved
Aliases	hTIF1, Tif1a, RNF82, TIF1A
Ensembl gene	ENSG00000122779
Ensembl biotype	protein_coding
OMIM	603406
Entrez	8805

Gene structure

Transcript identifiers

Ensembl transcripts: 22 — 18 protein_coding, 4 protein_coding_CDS_not_defined

ENST00000343526, ENST00000415680, ENST00000464210, ENST00000485318, ENST00000493595, ENST00000497516, ENST00000883777, ENST00000883778, ENST00000883779, ENST00000883780, ENST00000883781, ENST00000883782, ENST00000883783, ENST00000883784, ENST00000921873, ENST00000921874, ENST00000921875, ENST00000921876, ENST00000921877, ENST00000921878, ENST00000921879, ENST00000970296

RefSeq mRNA: 2 — MANE Select: NM_015905 NM_003852, NM_015905

CCDS: CCDS47720, CCDS5847

Canonical transcript exons

ENST00000343526 — 19 exons

Exon	Start	End
ENSE00000725518	138576373	138576445
ENSE00000725524	138577420	138577588
ENSE00000725530	138579204	138579532
ENSE00000725535	138580562	138580694
ENSE00000725539	138581697	138581771
ENSE00001209905	138583850	138583999
ENSE00001209956	138460259	138460912
ENSE00001958225	138584742	138589996
ENSE00003382534	138554698	138554966
ENSE00003469942	138504290	138504408
ENSE00003587885	138538657	138538803
ENSE00003603463	138570830	138571003
ENSE00003627025	138551063	138551180
ENSE00003638626	138515212	138515359
ENSE00003657001	138567481	138567654
ENSE00003663115	138519189	138519321
ENSE00003678589	138525241	138525357
ENSE00003683843	138573507	138573642
ENSE00003684323	138529116	138529230

Expression profiles

Bgee: expression breadth ubiquitous, 291 present calls, max score 97.48.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 27.0596 / max 624.6226, expressed in 1805 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
81407	11.8083	1768
81404	9.6876	1228
81406	4.3446	1478
81405	0.7207	335
81408	0.1980	62
81409	0.1916	77
81403	0.0706	20
81416	0.0383	7

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sperm	CL:0000019	97.48	gold quality
male germ cell	CL:0000015	96.60	gold quality
adrenal tissue	UBERON:0018303	94.98	gold quality
ganglionic eminence	UBERON:0004023	94.55	gold quality
ventricular zone	UBERON:0003053	94.46	gold quality
cortical plate	UBERON:0005343	94.06	gold quality
embryo	UBERON:0000922	93.81	gold quality
right adrenal gland cortex	UBERON:0035827	91.12	gold quality
right adrenal gland	UBERON:0001233	90.68	gold quality
cervix squamous epithelium	UBERON:0006922	90.64	gold quality
parotid gland	UBERON:0001831	90.41	gold quality
adrenal gland	UBERON:0002369	90.05	gold quality
left adrenal gland	UBERON:0001234	90.00	gold quality
adrenal cortex	UBERON:0001235	89.86	gold quality
endothelial cell	CL:0000115	89.75	gold quality
left adrenal gland cortex	UBERON:0035825	89.49	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	89.07	gold quality
esophagus squamous epithelium	UBERON:0006920	87.94	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	87.70	gold quality
squamous epithelium	UBERON:0006914	87.57	gold quality
epithelial cell of pancreas	CL:0000083	87.25	gold quality
jejunum	UBERON:0002115	87.18	gold quality
mucosa of paranasal sinus	UBERON:0005030	87.15	gold quality
biceps brachii	UBERON:0001507	86.85	gold quality
epithelium of esophagus	UBERON:0001976	86.40	gold quality
visceral pleura	UBERON:0002401	86.36	gold quality
jejunal mucosa	UBERON:0000399	86.31	gold quality
liver	UBERON:0002107	86.21	gold quality
oviduct epithelium	UBERON:0004804	86.02	gold quality
choroid plexus epithelium	UBERON:0003911	85.96	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	9.25
E-MTAB-6524	no	198.40

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

1 targets.

Target	Regulation
STAT1	Repression

miRNA regulators (miRDB)

43 targeting TRIM24, 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-3613-3P	100.00	76.36	7965
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-101-3P	99.94	75.03	2230
HSA-MIR-144-3P	99.94	73.98	2698
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-4760-3P	99.93	70.50	2385
HSA-MIR-6835-3P	99.93	70.49	2904
HSA-MIR-1305	99.91	71.43	3443
HSA-MIR-8062	99.88	68.43	995
HSA-MIR-5003-3P	99.85	69.29	2517
HSA-MIR-4307	99.82	70.45	3374
HSA-MIR-6875-3P	99.82	70.26	2983
HSA-MIR-4659A-3P	99.80	72.62	4248
HSA-MIR-4659B-3P	99.80	72.62	4248
HSA-MIR-374C-5P	99.80	72.06	2910
HSA-MIR-655-3P	99.80	72.19	2909
HSA-MIR-139-5P	99.80	69.50	1399
HSA-MIR-320A-3P	99.77	69.73	2107
HSA-MIR-320B	99.77	69.73	2107
HSA-MIR-320C	99.77	69.73	2107
HSA-MIR-320D	99.77	69.73	2107
HSA-MIR-4429	99.77	69.62	2111
HSA-MIR-4756-3P	99.62	66.30	1319
HSA-MIR-6073	99.60	70.36	793
HSA-MIR-888-3P	99.53	69.77	1057
HSA-MIR-302B-5P	99.50	69.49	1857
HSA-MIR-302D-5P	99.50	69.34	1863
HSA-MIR-12132	99.47	68.90	1341

Literature-anchored findings (GeneRIF, showing 40)

• Preferential expression of the HTIF1alpha gene in acute myeloid leukemia and MDS-related AML. Could play a role in myeloid differentiation, being distinctly regulated in hematopoietic lineages. (PMID:11986951)
• TIF1alpha interacts with TIF1gamma and the coiled-coil region of TIF1gamma is necessary for this interaction. (PMID:12096914)
• We propose that ZCCHC11 is a unique TLR signal regulator, which interacts with TIFA after LPS treatment and suppresses the TRAF6-dependent activation of NF-kappaB. (PMID:16643855)
• We identified a novel interaction between E4 ORF3 and TIF1alpha (PMID:17287283)
• TRIM24 regulates AR-mediated transcription in collaboration with TIP60 and BRD7. (PMID:19909775)
• Aberrant expression of TRIM24 negatively correlates with survival of breast cancer patients. (PMID:21164480)
• overexpression of the TRIM24/TIF-1alpha gene in breast cancer is associated with poor prognosis and worse surviva (PMID:21435435)
• These results suggest that E4-ORF3 targets proteins for relocalization through a loosely homologous sequence dependent on accessibility. (PMID:22123502)
• TRIM24 plays an important role in NSCLC progression (PMID:22666376)
• Upon TRIM24 silencing, the proliferation of HNSCC cells was notably inhibited due to the induction of apoptosis. (PMID:23717505)
• Overexpression of TRIM24 is associated with the onset and progress of human hepatocellular carcinoma. (PMID:24409330)
• Our results suggest that TRIM24 might serve as a potential prognostic marker and therapeutic target for the management of malignant gliomas. (PMID:24469053)
• Study shows that TRIM24 is destabilized by ATM-mediated phosphorylation of TRIM24S768 in response to DNA damage, which disrupts TRIM24-p53 interactions and promotes the degradation of TRIM24. (PMID:24820418)
• A role for TRIM24 in breast tumorigenesis through reprogramming of glucose metabolism in human mammary epithelial cells, further supporting TRIM24 as a viable therapeutic target in breast cancer. (PMID:25065590)
• functions as an oncogene in colorectal carcinogenesis (PMID:25700357)
• our study shows that TRIM24 is overexpressed in human gastric cancer and accelerates cell growth as well as induce chemoresistance (PMID:25724180)
• TRIM24 is overexpressed in human bladder cancer and facilitates bladder cancer growth and invasion, possibly through NF-kappaB and AKT signaling pathways. (PMID:25846736)
• TRIM24 regulate resistance to Gefitinib via Akt pathway in non-small cell lung cancer cells. (PMID:26805734)
• hypothesis of “synergistic modification induced recognition” is then proposed to link histone modification and TRIM24 binding (PMID:27079666)
• Report provides evidence for an oncogenic role for TRIM24 as a transcriptional activator and mediator of hormone-refractory prostate cancer cell growth in SPOP mutant and castration-resistant prostate cells. (PMID:27238081)
• TRIM24 expression is positively correlated with Acetylated H3 lysine 23 levels, and high levels of both TRIM24 and Acetylated H3 lysine 23 predict shorter overall survival of breast cancer patients. (PMID:27638829)
• This study concluded that reduced TRIM24 protein is associated with poor survival in esophageal squamous cell cancer (ESCC) patients, suggesting TRIM24 protein is a potential prognostic biomarker for ESCC. (PMID:27689360)
• we identified altered glucose metabolism in the progression of head and neck squamous cell carcinoma and showed that it could be partially attributed to the novel link between GLUT4 and TRIM24 (PMID:28061796)
• Study showed that TRIM24 was upregulated during gastric carcinogenesis and demonstrated that TRIM24 was a functional target gene of miR-511, and miR-511 inactivated PI3K/AKT and Wnt/beta-catenin pathways by suppressing TRIM24. (PMID:28114950)
• Data suggest that, in cardiomyocytes, TRIM32 attenuates activation of SRF signaling and hypertrophy due to dysbindin; TRIM24 promotes these effects. TRIM32 promotes dysbindin degradation; TRIM24 protects dysbindin from degradation. (TRIM = tripartite motif-containing protein; SRF = serum response factor) (PMID:28465353)
• TRIM24 expression was increased in human colorectal cancer and might be a novel prognostic biomarker. (PMID:28916426)
• Overexpression of KAT6A or TRIM24 promoted PIK3CA expression, AKT phosphorylation, and cell proliferation. (PMID:29021135)
• Results suggest that TRIM24 is a novel coactivator of the CAR that is involved in cell- and/or promoter- selective transactivation. (PMID:29101097)
• The findings identify TRIM24 as an oncogenic transcriptional co-activator in epidermal growth factor receptor-driven glioblastoma and also demonstrate a previously unknown signal relay by which H3K23ac/TRIM24 mediates epidermal growth factor receptor stimulation of STAT3 activation, thereby enhancing the oncogenic activity of the epidermal growth factor receptor/STAT3 pathway in human cancers. (PMID:29129908)
• findings establish a new link between histone H3 acetylation and SUMOylation of the reader protein TRIM24, a functional connection that may bear on TRIM24’s oncogenic function and may inform future studies of PTM cross-talk between histones and epigenetic regulators (PMID:29523690)
• in response to RA, TRIM24 serves as an adapter linking RARalpha to the proteasome for its degradation. In addition, TRIM24 and the proteasome are recruited with RARalpha to the promoters of target genes and thus are inherently linked to RARalpha transcriptional activity. (PMID:29543331)
• TRIM24 appears to promote liver tumor development via AMPK signaling (PMID:29627320)
• these results suggested that TRIM24 has an important role in the growth of Nasopharyngeal carcinoma (NPC). Additionally, silenced TRIM24 may lead to inhibited cell proliferation and induced cell apoptosis in NPC cells. (PMID:29749443)
• demonstrate that the transcription co-factor and oncoprotein TRIM24 (tripartite motif-containing protein 24) is SUMOylated upon association with a specific histone modification signature, which regulates the transcription of genes involved in cell adhesion (PMID:29752422)
• TRIM24 is upregulated in HNSCC and promotes HNSCC cell growth and invasion through modulation of cell cycle, glucose metabolism, and GLUT3, making TRIM24 a potential oncoprotein in HNSCC. (PMID:29862279)
• TRIM24 and AR coactivated gene signature of SPOP-mutant prostate cancer (PCa) is similarly activated in human PCa with high TRIM28 expression. (PMID:30479348)
• the prognostic significance of Trim 24 in patients with solid carcinomas (PMID:31211611)
• NCK1-AS1 Increases Drug Resistance of Glioma Cells to Temozolomide by Modulating miR-137/TRIM24. (PMID:31750728)
• TRIM24 aggravates the progression of ovarian cancer through negatively regulating FOXM1 level. (PMID:31858531)
• Tripartite motif-containing 24 protein (TRIM24) promotes clear cell renal cell carcinoma (ccRCC) progression through the Wnt/beta-catenin pathway. Nuclear factor erythroid 2-related factor 2 (Nrf2) promotes the transcription of TRIM24 in ccRCC. BMP8A/Nrf2/TRIM24-induced reactive oxygen species imbalance and Wnt pathway activation correlates with As2O3 resistance. (PMID:32128917)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	trim24	ENSDARG00000103350
mus_musculus	Trim24	ENSMUSG00000029833
rattus_norvegicus	Trim24	ENSRNOG00000013251

Paralogs (80): MID2 (ENSG00000080561), TRIM9 (ENSG00000100505), MID1 (ENSG00000101871), MEFV (ENSG00000103313), TRIM35 (ENSG00000104228), TRIM14 (ENSG00000106785), TRIM37 (ENSG00000108395), TRIM2 (ENSG00000109654), TRIM3 (ENSG00000110171), TRIM38 (ENSG00000112343), TRIM62 (ENSG00000116525), TRIM67 (ENSG00000119283), TRIM32 (ENSG00000119401), BSPRY (ENSG00000119411), TRIM25 (ENSG00000121060), TRIM6 (ENSG00000121236), TRIM51 (ENSG00000124900), TRIM28 (ENSG00000130726), TRIM21 (ENSG00000132109), TRIM5 (ENSG00000132256), TRIM22 (ENSG00000132274), TRIM47 (ENSG00000132481), TRIM45 (ENSG00000134253), TRIM29 (ENSG00000137699), TRIM54 (ENSG00000138100), PML (ENSG00000140464), TRIM65 (ENSG00000141569), TRIM43B (ENSG00000144010), TRIM43 (ENSG00000144015), TRIM7 (ENSG00000146054), TRIM41 (ENSG00000146063), TRIM50 (ENSG00000146755), TRIM4 (ENSG00000146833), TRIM55 (ENSG00000147573), TRIM48 (ENSG00000150244), TRIM36 (ENSG00000152503), TRIM11 (ENSG00000154370), TRIM74 (ENSG00000155428), TRIM42 (ENSG00000155890), TRIM63 (ENSG00000158022)

Protein

Protein identifiers

Transcription intermediary factor 1-alpha — O15164 (reviewed: O15164)

Alternative names: E3 ubiquitin-protein ligase TRIM24, RING finger protein 82, RING-type E3 ubiquitin transferase TIF1-alpha, Tripartite motif-containing protein 24

All UniProt accessions (1): O15164

UniProt curated annotations — full annotation on UniProt →

Function. Transcriptional coactivator that interacts with numerous nuclear receptors and coactivators and modulates the transcription of target genes. Interacts with chromatin depending on histone H3 modifications, having the highest affinity for histone H3 that is both unmodified at ‘Lys-4’ (H3K4me0) and acetylated at ‘Lys-23’ (H3K23ac). Has E3 protein-ubiquitin ligase activity. During the DNA damage response, participates in an autoregulatory feedback loop with TP53. Early in response to DNA damage, ATM kinase phosphorylates TRIM24 leading to its ubiquitination and degradation. After sufficient DNA repair has occurred, TP53 activates TRIM24 transcription, ultimately leading to TRIM24-mediated TP53 ubiquitination and degradation. Plays a role in the regulation of cell proliferation and apoptosis, at least in part via its effects on p53/TP53 levels. Up-regulates ligand-dependent transcription activation by AR, GCR/NR3C1, thyroid hormone receptor (TR) and ESR1. Modulates transcription activation by retinoic acid (RA) receptors, including RARA. Plays a role in regulating retinoic acid-dependent proliferation of hepatocytes. Also participates in innate immunity by mediating the specific ‘Lys-63’-linked ubiquitination of TRAF3 leading to activation of downstream signal transduction of the type I IFN pathway. Additionally, negatively regulates NLRP3/CASP1/IL-1beta-mediated pyroptosis and cell migration probably by ubiquitinating NLRP3.

Subunit / interactions. Interacts with CARM1, NCOA2/GRIP1, PML, KAT5/TIP60, BRD7, CBX1, CBX3 and CBX5. Part of a coactivator complex containing TRIM24, NCOA2 and CARM1. Interacts with NR3C2/MCR. Interacts with the ligand-binding domain of estrogen receptors (in vitro). Interaction with DNA-bound estrogen receptors requires the presence of estradiol. Interacts with AR and p53/TP53. Interacts (via bromo domain) with histone H3 (via N-terminus), provided that it is not methylated at ‘Lys-4’ (H3K4me0). Does not interact with histone H3 that is methylated at ‘Lys-4’ (H3K4me1, H3K4me2 or H3K4me3). Interacts (via bromo domain) with histone H3 (via N-terminus) that is acetylated at ‘Lys-23’ (H3K23ac). Has the highest affinity for histone H3 that is both unmodified at ‘Lys-4’ (H3K4me0) and acetylated at ‘Lys-23’ (H3K23ac). Has very low affinity for histone H3 that is methylated at ‘Lys-9’ (H3K9me), or acetylated at both ‘Lys-9’ (H3K9ac) and ‘Lys-14’ (H3K14ac), or acetylated at ‘Lys-27’ (H3K27ac) (in vitro). Interacts with TRIM16.

Subcellular location. Nucleus. Cytoplasm. Mitochondrion.

Post-translational modifications. Phosphorylated at Ser-768 by ATM kinase induces ubiquitination and degradation during DNA damage. Sumoylated. Undergoes ubiquitination-mediated degradation in response to DNA damage.

Disease relevance. A chromosomal aberration involving TRIM24/TIF1 is found in papillary thyroid carcinomas (PTCs). Translocation t(7;10)(q32;q11) with RET. The translocation generates the TRIM24/RET (PTC6) oncogene.

Induction. Up-regulated in some cases of breast cancer. Expression is induced by damage-activated TP53.

Pathway. Protein modification; protein ubiquitination.

Isoforms (2)

UniProt ID	Names	Canonical?
O15164-1	Long	yes
O15164-2	Short

RefSeq proteins (2): NP_003843, NP_056989* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000315	Znf_B-box	Domain
IPR001487	Bromodomain	Domain
IPR001841	Znf_RING	Domain
IPR001965	Znf_PHD	Domain
IPR003649	Bbox_C	Domain
IPR011011	Znf_FYVE_PHD	Homologous_superfamily
IPR013083	Znf_RING/FYVE/PHD	Homologous_superfamily
IPR017907	Znf_RING_CS	Conserved_site
IPR018359	Bromodomain_CS	Conserved_site
IPR019786	Zinc_finger_PHD-type_CS	Conserved_site
IPR019787	Znf_PHD-finger	Domain
IPR036427	Bromodomain-like_sf	Homologous_superfamily

Pfam: PF00439, PF00628, PF00643

UniProt features (107 total): cross-link 18, modified residue 15, region of interest 10, compositionally biased region 10, helix 8, binding site 8, sequence conflict 7, strand 6, turn 5, sequence variant 5, zinc finger region 4, mutagenesis site 4, site 2, chain 1, domain 1, coiled-coil region 1, short sequence motif 1, splice variant 1

Structure

Experimental structures (PDB)

22 structures.

PDB	Method	Resolution (Å)
4YBM	X-RAY DIFFRACTION	1.46
9GDG	X-RAY DIFFRACTION	1.46
9R9C	X-RAY DIFFRACTION	1.59
9GD5	X-RAY DIFFRACTION	1.68
3O36	X-RAY DIFFRACTION	1.7
4YAD	X-RAY DIFFRACTION	1.73
3O35	X-RAY DIFFRACTION	1.76
4ZQL	X-RAY DIFFRACTION	1.79
4YBT	X-RAY DIFFRACTION	1.82
4YC9	X-RAY DIFFRACTION	1.82
4YBS	X-RAY DIFFRACTION	1.83
3O34	X-RAY DIFFRACTION	1.9
4YAB	X-RAY DIFFRACTION	1.9
5H1U	X-RAY DIFFRACTION	1.9
5H1T	X-RAY DIFFRACTION	1.95
3O33	X-RAY DIFFRACTION	2
3O37	X-RAY DIFFRACTION	2
5H1V	X-RAY DIFFRACTION	2
4YAT	X-RAY DIFFRACTION	2.18
4YAX	X-RAY DIFFRACTION	2.25
2YYN	X-RAY DIFFRACTION	2.5
7B9X	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O15164-F1	63.84	0.26

Functional residue map

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

Catalytic / active sites (2): 476–477 (breakpoint for translocation to form trim24-ret oncogene); 827 (interaction with histone h3 that is not methylated at ’lys-4’ (h3k4me0))

Ligand- & substrate-binding residues (8): 163; 166; 187; 200; 223; 226; 246; 251

Post-translational modifications (33): 101, 110, 469, 654, 660, 667, 744, 768, 808, 811, 818, 1019, 1025, 1028, 1042, 7, 205, 276, 436, 458 …

Mutagenesis-validated functional residues (4):

Position	Phenotype
768	ubiquitination is significantly lower than wild-type.
827	strongly reduced affinity for histone h3 that is not methylated at ’lys-4’ (h3k4me0).
840	abolishes interaction with histone h3.
979–980	strongly reduced affinity for histone h3 that is acetylated at ’lys-23’ (h3k23ac).

Function

Pathways and Gene Ontology

Reactome pathways

8 pathways

ID	Pathway
R-HSA-1839117	Signaling by cytosolic FGFR1 fusion mutants
R-HSA-5655302	Signaling by FGFR1 in disease
R-HSA-6802952	Signaling by BRAF and RAF1 fusions
R-HSA-1226099	Signaling by FGFR in disease
R-HSA-1643685	Disease
R-HSA-1839124	FGFR1 mutant receptor activation
R-HSA-5663202	Diseases of signal transduction by growth factor receptors and second messengers
R-HSA-6802957	Oncogenic MAPK signaling

MSigDB gene sets: 242 (showing top): GOBP_RESPONSE_TO_NITROGEN_COMPOUND, LEE_NEURAL_CREST_STEM_CELL_DN, MORF_MSH3, GOBP_CELLULAR_RESPONSE_TO_LIPID, NKX25_02, MORF_BRCA1, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, AP2_Q3, MORF_ESR1, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, MORF_RAD51L3, PATIL_LIVER_CANCER, PUJANA_CHEK2_PCC_NETWORK, GOBP_HORMONE_MEDIATED_SIGNALING_PATHWAY, GOBP_CELLULAR_RESPONSE_TO_HORMONE_STIMULUS

GO Biological Process (16): transcription by RNA polymerase II (GO:0006366), positive regulation of gene expression (GO:0010628), protein ubiquitination (GO:0016567), protein catabolic process (GO:0030163), regulation of protein stability (GO:0031647), regulation of apoptotic process (GO:0042981), response to peptide hormone (GO:0043434), negative regulation of DNA-templated transcription (GO:0045892), epithelial cell proliferation (GO:0050673), negative regulation of epithelial cell proliferation (GO:0050680), calcium ion homeostasis (GO:0055074), regulation of vitamin D receptor signaling pathway (GO:0070562), cellular response to estrogen stimulus (GO:0071391), regulation of signal transduction by p53 class mediator (GO:1901796), chromatin organization (GO:0006325), positive regulation of DNA-templated transcription (GO:0045893)

GO Molecular Function (16): p53 binding (GO:0002039), chromatin binding (GO:0003682), transcription coactivator activity (GO:0003713), protein kinase activity (GO:0004672), signaling receptor binding (GO:0005102), zinc ion binding (GO:0008270), nuclear receptor binding (GO:0016922), estrogen response element binding (GO:0034056), ubiquitin protein ligase activity (GO:0061630), histone H3K23ac reader activity (GO:0140118), DNA binding (GO:0003677), ubiquitin-protein transferase activity (GO:0004842), protein binding (GO:0005515), transferase activity (GO:0016740), sequence-specific DNA binding (GO:0043565), metal ion binding (GO:0046872)

GO Cellular Component (10): chromatin (GO:0000785), euchromatin (GO:0000791), male germ cell nucleus (GO:0001673), nucleus (GO:0005634), nucleoplasm (GO:0005654), perichromatin fibrils (GO:0005726), mitochondrion (GO:0005739), cytosol (GO:0005829), cytoplasm (GO:0005737), nuclear lumen (GO:0031981)

Reactome top-level categories

Rollup of top-6 pathways:

Category	Pathways
Diseases of signal transduction by growth factor receptors and second messengers	2
FGFR1 mutant receptor activation	1
Signaling by FGFR in disease	1
Oncogenic MAPK signaling	1
Signaling by FGFR1 in disease	1
Disease	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
DNA-templated transcription	3
regulation of DNA-templated transcription	2
regulation of intracellular signal transduction	2
protein binding	2
binding	2
chromatin	2
intracellular membrane-bounded organelle	2
cytoplasm	2
gene expression	1
regulation of gene expression	1
positive regulation of macromolecule biosynthetic process	1
protein modification by small protein conjugation	1
macromolecule catabolic process	1
protein metabolic process	1
regulation of biological quality	1
apoptotic process	1
regulation of programmed cell death	1
response to hormone	1
response to nitrogen compound	1
response to oxygen-containing compound	1
negative regulation of RNA biosynthetic process	1
cell population proliferation	1
negative regulation of cell population proliferation	1
epithelial cell proliferation	1
regulation of epithelial cell proliferation	1
monoatomic cation homeostasis	1
inorganic ion homeostasis	1
regulation of response to nutrient levels	1
vitamin D receptor signaling pathway	1
cellular response to hormone stimulus	1
response to estrogen	1
signal transduction by p53 class mediator	1
cellular component organization	1
positive regulation of RNA biosynthetic process	1
transcription coregulator activity	1
positive regulation of DNA-templated transcription	1
kinase activity	1
phosphotransferase activity, alcohol group as acceptor	1
catalytic activity, acting on a protein	1

Protein interactions and networks

STRING

2354 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TRIM24	TRIM28	Q13263	806
TRIM24	TRIM17	Q9Y577	804
TRIM24	RARA	P10276	802
TRIM24	BBOX1	O75936	800
TRIM24	H3-3A	P06351	795
TRIM24	H3C1	P02295	795
TRIM24	H3C14	Q71DI3	793
TRIM24	H3-5	Q6NXT2	793
TRIM24	H3-4	Q16695	793
TRIM24	H3-7	Q5TEC6	793
TRIM24	TRAT1	Q6PIZ9	779
TRIM24	ESR1	P03372	767
TRIM24	TRIM27	P14373	728
TRIM24	RARS1	P54136	723
TRIM24	MORC3	Q14149	713

IntAct

158 interactions, top by confidence:

A	B	Type	Score
TRIM33	TRIM24	psi-mi:“MI:0914”(association)	0.790
TRIM24	TRIM33	psi-mi:“MI:0915”(physical association)	0.790
TRIM24		psi-mi:“MI:0407”(direct interaction)	0.690
NFIC	NFIB	psi-mi:“MI:2364”(proximity)	0.690
TRIM24	ESR1	psi-mi:“MI:0915”(physical association)	0.640
ESR1	TRIM24	psi-mi:“MI:0914”(association)	0.640
QPRT	PIK3C2A	psi-mi:“MI:0914”(association)	0.640
TRIM28	TRIM24	psi-mi:“MI:0914”(association)	0.600
TRIM24		psi-mi:“MI:0407”(direct interaction)	0.560
TRIM28	ZNF316	psi-mi:“MI:0914”(association)	0.530
ZNF764	SH3PXD2B	psi-mi:“MI:0914”(association)	0.530
ZNF324B	ZNF316	psi-mi:“MI:0914”(association)	0.530
KXD1	HIP1	psi-mi:“MI:0914”(association)	0.530
ZNF331	USP9Y	psi-mi:“MI:0914”(association)	0.530
ZNF483	ZNF197	psi-mi:“MI:0914”(association)	0.530
NUP62	RGPD8	psi-mi:“MI:0914”(association)	0.530

BioGRID (540): TRIM24 (Protein-peptide), TRIM24 (Affinity Capture-MS), TRIM24 (Affinity Capture-MS), TRIM24 (Affinity Capture-MS), TRIM24 (Affinity Capture-MS), TRIM24 (Two-hybrid), TRIM24 (Affinity Capture-MS), TRIM24 (Synthetic Growth Defect), TRIM24 (Synthetic Growth Defect), TRIM24 (Affinity Capture-MS), TRIM24 (Affinity Capture-MS), TRIM24 (Affinity Capture-MS), TRIM24 (Proximity Label-MS), TRIM24 (Affinity Capture-MS), TRIM24 (Two-hybrid)

ESM2 similar proteins: A0A0R4IXF6, A1A5R8, A9ZLX4, D3YXJ0, E9PUQ8, G3UZ78, O00750, O15164, O54828, P30052, P40818, P48984, P52963, P59997, P97496, Q02225, Q08AX9, Q08BR4, Q08D35, Q16760, Q1LUC3, Q2I6J1, Q3UWM4, Q498F0, Q5JSH3, Q5JTW2, Q5RHD1, Q60665, Q64398, Q68FF0, Q6INA9, Q6NSI8, Q6NVE8, Q6PDG5, Q6ZMT4, Q7ZVP1, Q80U87, Q86XP1, Q8C5W4, Q8N7X0

Diamond homologs: A0A0R4IXF6, A0A7U2QYM2, A2AHJ4, A2AUY4, A2BIL7, B2RRD7, B7ZS37, D4A7T3, E9Q2Z1, F1QW93, F1R5H6, F7DRV9, G5E8P1, O15164, O60885, O74350, O88379, O88665, O95696, P13709, P21675, P25440, P35817, P51123, P53236, P54816, P55201, P87152, Q02206, Q03330, Q07442, Q08D75, Q09948, Q12830, Q15059, Q1LUC3, Q23590, Q32S26, Q338B9, Q4R8Y1

SIGNOR signaling

4 interactions.

A	Effect	B	Mechanism
TRIM24	down-regulates	TP53	ubiquitination
TRIM24	up-regulates	AR	binding
Ub:E2	“up-regulates activity”	TRIM24	ubiquitination
SPOP	“down-regulates quantity by destabilization”	TRIM24	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 163 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
Deactivation of the beta-catenin transactivating complex	6	11.8×	2e-03
Gastrulation	5	10.9×	7e-03
TCF dependent signaling in response to WNT	8	7.9×	2e-03
Signaling by WNT	8	7.5×	2e-03
Regulation of endogenous retroelements by KRAB-ZFP proteins	8	7.2×	2e-03

GO biological processes:

GO term	Partners	Fold	FDR
positive regulation of miRNA transcription	9	16.8×	7e-07
transcription by RNA polymerase II	15	6.8×	1e-06
positive regulation of gene expression	15	3.7×	1e-03

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: activating (oncogene-like) across 1 cancer types — PRAD.

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	69
Likely benign	1
Benign	4

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
2445349	NM_015905.3(TRIM24):c.2050C>T (p.Arg684Cys)	Likely pathogenic

SpliceAI

2898 predictions. Top by Δscore:

Variant	Effect	Δscore
7:138460911:AGGTG:A	donor_loss	1.0000
7:138460912:GGTG:G	donor_loss	1.0000
7:138460913:GTG:G	donor_loss	1.0000
7:138504288:A:AG	acceptor_gain	1.0000
7:138504288:AGTT:A	acceptor_gain	1.0000
7:138504289:G:GG	acceptor_gain	1.0000
7:138504289:GTTG:G	acceptor_gain	1.0000
7:138504406:CAGGT:C	donor_loss	1.0000
7:138504408:GGTA:G	donor_loss	1.0000
7:138504409:G:GG	donor_gain	1.0000
7:138504410:T:G	donor_loss	1.0000
7:138525236:TTCA:T	acceptor_loss	1.0000
7:138525237:TCA:T	acceptor_loss	1.0000
7:138525239:A:T	acceptor_loss	1.0000
7:138525354:ACAG:A	donor_loss	1.0000
7:138525356:AGGT:A	donor_loss	1.0000
7:138525357:GGT:G	donor_loss	1.0000
7:138525358:G:A	donor_loss	1.0000
7:138529114:A:AG	acceptor_gain	1.0000
7:138529115:G:GG	acceptor_gain	1.0000
7:138529115:GA:G	acceptor_gain	1.0000
7:138529228:GAGGT:G	donor_loss	1.0000
7:138529229:AGG:A	donor_loss	1.0000
7:138529231:G:GT	donor_loss	1.0000
7:138529232:T:TT	donor_loss	1.0000
7:138529233:AAGT:A	donor_loss	1.0000
7:138538648:T:A	acceptor_gain	1.0000
7:138538653:TCAGA:T	acceptor_gain	1.0000
7:138538654:CAGAG:C	acceptor_gain	1.0000
7:138538655:A:AC	acceptor_loss	1.0000

AlphaMissense

6935 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:138460714:T:A	C56S	1.000
7:138460714:T:C	C56R	1.000
7:138460715:G:A	C56Y	1.000
7:138460715:G:C	C56S	1.000
7:138460716:C:G	C56W	1.000
7:138460723:T:A	C59S	1.000
7:138460723:T:C	C59R	1.000
7:138460724:G:A	C59Y	1.000
7:138460724:G:C	C59S	1.000
7:138460725:C:G	C59W	1.000
7:138460757:T:C	L70P	1.000
7:138460760:T:C	L71P	1.000
7:138460765:T:A	C73S	1.000
7:138460765:T:C	C73R	1.000
7:138460766:G:A	C73Y	1.000
7:138460766:G:C	C73S	1.000
7:138460767:C:G	C73W	1.000
7:138460769:T:C	L74P	1.000
7:138460771:C:G	H75D	1.000
7:138460780:T:A	C78S	1.000
7:138460780:T:C	C78R	1.000
7:138460781:G:A	C78Y	1.000
7:138460781:G:C	C78S	1.000
7:138460782:C:G	C78W	1.000
7:138460789:T:A	C81S	1.000
7:138460789:T:C	C81R	1.000
7:138460790:G:C	C81S	1.000
7:138460791:C:G	C81W	1.000
7:138504304:T:A	C127S	1.000
7:138504304:T:C	C127R	1.000

dbSNP variants (sampled 300 via entrez): RS1000000823 (7:138543345 C>A,T), RS1000019899 (7:138586685 A>G), RS1000023982 (7:138543305 T>C), RS1000038444 (7:138494309 G>A), RS1000072230 (7:138586684 C>T), RS1000072962 (7:138497336 A>G), RS1000094554 (7:138462790 G>A,C), RS1000124877 (7:138497551 T>C,G), RS1000166907 (7:138530513 A>G), RS1000168968 (7:138522802 A>G), RS1000236764 (7:138465071 T>G), RS1000266581 (7:138550244 T>A), RS1000268314 (7:138523263 G>A,T), RS1000297052 (7:138572535 T>G), RS1000326662 (7:138563307 T>G)

Disease associations

OMIM: gene MIM:603406 | disease phenotypes: MIM:167000

GenCC curated gene-disease

Mondo (1): ovarian cancer (MONDO:0008170)

Orphanet (1): Rare ovarian cancer (Orphanet:213500)

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST000337_5	Quantitative traits	9.000000e-06
GCST009144_32	Disease progression in age-related macular degeneration (adjusted for baseline)	4.000000e-06

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004338	body weight
EFO:0008336	disease progression measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D010051	Ovarian Neoplasms	C04.588.322.455; C12.050.351.500.056.630.705; C12.050.351.937.418.685; C12.100.250.056.630.705; C12.900.418.685; C19.344.410; C19.391.630.705

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL3108638 (SINGLE PROTEIN), CHEMBL5291690 (PROTEIN-PROTEIN INTERACTION)

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

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — TIF1 family

Most potent curated ligand interactions (2 total), top 2:

Ligand	Action	Affinity	Parameter
compound 34 [PMID: 25974391]	Binding	6.65	pKd
dTRIM24	Binding	6.47	pIC50

Binding affinities (BindingDB)

3 measured of 3 human assays (3 total across all organisms); most potent 3 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
4-cyano-N-(1,3-dimethyl-2-oxoquinolin-6-yl)-2-methoxybenzenesulfonamide	IC50	1010 nM
4-Bromo-N-(2,3-dihydro-6-methoxy-1,3-dimethyl-2-oxo-1H-benzimidazol-5-yl)-2-methyl-benzenesulfonamide	IC50	1200 nM
N-[2,3-Dihydro-1,3-dimethyl-2-oxo-6-(1-pyrrolidinyl)-1H-benzimidazol-5-yl]-2-methoxybenzamide	IC50	3520 nM

ChEMBL bioactivities

164 potent at pChembl≥5 of 215 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.89	Kd	1.3	nM	CHEMBL3774575
8.12	IC50	7.6	nM	CHEMBL3774575
8.12	IC50	7.6	nM	CHEMBL5715923
8.10	IC50	7.9	nM	CHEMBL3775251
8.10	IC50	8	nM	CHEMBL3774575
8.08	IC50	8.3	nM	CHEMBL3774933
8.00	IC50	10	nM	CHEMBL3775901
7.96	IC50	11	nM	CHEMBL3775348
7.96	IC50	11.07	nM	CHEMBL3774575
7.89	IC50	13	nM	CHEMBL3774542
7.89	IC50	13	nM	CHEMBL3774766
7.51	Kd	31	nM	CHEMBL3774575
7.51	Kd	31	nM	CHEMBL5715923
7.37	IC50	43	nM	CHEMBL3775853
7.30	EC50	50	nM	CHEMBL3774575
7.30	IC50	50	nM	CHEMBL5715923
7.28	IC50	53	nM	CHEMBL3775073
7.26	IC50	55	nM	CHEMBL5841247
7.26	IC50	55	nM	CHEMBL5275033
7.26	IC50	55	nM	CHEMBL5833163
7.24	IC50	57	nM	CHEMBL3774507
7.23	EC50	59	nM	CHEMBL3774933
7.22	IC50	60	nM	CHEMBL3774770
7.00	IC50	100	nM	CHEMBL3775689
6.96	EC50	110	nM	CHEMBL3775348
6.96	IC50	110	nM	CHEMBL3775132
6.92	EC50	120	nM	CHEMBL3774542
6.92	EC50	120	nM	CHEMBL3775251
6.89	IC50	130	nM	CHEMBL3774529
6.88	IC50	133.4	nM	CHEMBL4572394
6.87	IC50	135.8	nM	CYCLOPENTANONE
6.85	IC50	140	nM	CHEMBL3775263
6.82	IC50	150	nM	CHEMBL3774575
6.80	IC50	160	nM	CHEMBL3774638
6.80	IC50	160	nM	CHEMBL3774452
6.80	IC50	156.6	nM	CHEMBL4467793
6.79	IC50	162	nM	VANILLIN
6.78	IC50	166.3	nM	CYCLOOCTANONE
6.78	IC50	164.8	nM	CHEMBL4592980
6.77	EC50	170	nM	CHEMBL3774766
6.77	EC50	170	nM	CHEMBL3775901
6.75	IC50	180	nM	CHEMBL3774653
6.74	IC50	180.2	nM	CHEMBL2229659
6.66	IC50	220	nM	CHEMBL3775286
6.66	IC50	221.3	nM	SALICYLADEHYDE
6.66	IC50	219.7	nM	CHEMBL350966
6.66	IC50	217.8	nM	CHEMBL3775853
6.65	Kd	222	nM	CHEMBL3769965
6.65	IC50	225.2	nM	CHEMBL543846
6.57	IC50	270	nM	CHEMBL3774883

PubChem BioAssay actives

115 with measured affinity, of 385 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
N-[6-[3-[4-(dimethylamino)butoxy]-5-propoxyphenoxy]-1,3-dimethyl-2-oxobenzimidazol-5-yl]-3,4-dimethoxybenzenesulfonamide	1282162: Binding affinity to recombinant human TRIM24-PHD/bromodomain expressed in bacterial system by bromoscan assay	kd	0.0013	uM
N-[6-[3-(4-aminobutoxy)-5-propoxyphenoxy]-1,3-dimethyl-2-oxobenzimidazol-5-yl]-1-methylimidazole-4-sulfonamide	1282152: Inhibition of recombinant human His-tagged TRIM24-PHD/bromodomain expressed in Escherichia coli strains BL21 (DE3) cells using biotinylated H3K23ac (1 to 33 residues) peptide after 1 hr by AlphaScreen assay	ic50	0.0079	uM
N-[6-[3-(4-aminobutoxy)-5-propoxyphenoxy]-1,3-dimethyl-2-oxobenzimidazol-5-yl]-3,4-dimethoxybenzenesulfonamide	1282152: Inhibition of recombinant human His-tagged TRIM24-PHD/bromodomain expressed in Escherichia coli strains BL21 (DE3) cells using biotinylated H3K23ac (1 to 33 residues) peptide after 1 hr by AlphaScreen assay	ic50	0.0083	uM
N-[6-[3-(6-aminohexoxy)-5-propoxyphenoxy]-1,3-dimethyl-2-oxobenzimidazol-5-yl]-1-methylimidazole-4-sulfonamide	1282152: Inhibition of recombinant human His-tagged TRIM24-PHD/bromodomain expressed in Escherichia coli strains BL21 (DE3) cells using biotinylated H3K23ac (1 to 33 residues) peptide after 1 hr by AlphaScreen assay	ic50	0.0100	uM
N-[6-[3-(5-aminopentoxy)-5-propoxyphenoxy]-1,3-dimethyl-2-oxobenzimidazol-5-yl]-1-methylimidazole-4-sulfonamide	1282152: Inhibition of recombinant human His-tagged TRIM24-PHD/bromodomain expressed in Escherichia coli strains BL21 (DE3) cells using biotinylated H3K23ac (1 to 33 residues) peptide after 1 hr by AlphaScreen assay	ic50	0.0110	uM
N-[6-[3-(6-aminohexoxy)-5-propoxyphenoxy]-1,3-dimethyl-2-oxobenzimidazol-5-yl]-3,4-dimethoxybenzenesulfonamide	1282152: Inhibition of recombinant human His-tagged TRIM24-PHD/bromodomain expressed in Escherichia coli strains BL21 (DE3) cells using biotinylated H3K23ac (1 to 33 residues) peptide after 1 hr by AlphaScreen assay	ic50	0.0130	uM
N-[6-[3-(3-aminopropoxy)-5-propoxyphenoxy]-1,3-dimethyl-2-oxobenzimidazol-5-yl]-3,4-dimethoxybenzenesulfonamide	1282152: Inhibition of recombinant human His-tagged TRIM24-PHD/bromodomain expressed in Escherichia coli strains BL21 (DE3) cells using biotinylated H3K23ac (1 to 33 residues) peptide after 1 hr by AlphaScreen assay	ic50	0.0130	uM
N-[1,3-dimethyl-2-oxo-6-(3-propoxyphenoxy)benzimidazol-5-yl]-3,4-dimethoxybenzenesulfonamide	1282152: Inhibition of recombinant human His-tagged TRIM24-PHD/bromodomain expressed in Escherichia coli strains BL21 (DE3) cells using biotinylated H3K23ac (1 to 33 residues) peptide after 1 hr by AlphaScreen assay	ic50	0.0430	uM
N-[1,3-dimethyl-2-oxo-6-(3-propoxyphenoxy)benzimidazol-5-yl]-1,2-dimethylimidazole-4-sulfonamide	1282152: Inhibition of recombinant human His-tagged TRIM24-PHD/bromodomain expressed in Escherichia coli strains BL21 (DE3) cells using biotinylated H3K23ac (1 to 33 residues) peptide after 1 hr by AlphaScreen assay	ic50	0.0530	uM
N-[1,3-dimethyl-6-[3-(2-methylpropoxy)phenoxy]-2-oxobenzimidazol-5-yl]-1,2-dimethylimidazole-4-sulfonamide	1282152: Inhibition of recombinant human His-tagged TRIM24-PHD/bromodomain expressed in Escherichia coli strains BL21 (DE3) cells using biotinylated H3K23ac (1 to 33 residues) peptide after 1 hr by AlphaScreen assay	ic50	0.0570	uM
N-[6-[3-(6-hydroxyhexoxy)-5-propoxyphenoxy]-1,3-dimethyl-2-oxobenzimidazol-5-yl]-1-methylimidazole-4-sulfonamide	1282152: Inhibition of recombinant human His-tagged TRIM24-PHD/bromodomain expressed in Escherichia coli strains BL21 (DE3) cells using biotinylated H3K23ac (1 to 33 residues) peptide after 1 hr by AlphaScreen assay	ic50	0.0600	uM
N-[1,3-dimethyl-2-oxo-6-[3-(oxolan-3-ylmethoxy)phenoxy]benzimidazol-5-yl]-1-methylimidazole-4-sulfonamide	1282152: Inhibition of recombinant human His-tagged TRIM24-PHD/bromodomain expressed in Escherichia coli strains BL21 (DE3) cells using biotinylated H3K23ac (1 to 33 residues) peptide after 1 hr by AlphaScreen assay	ic50	0.1000	uM
N-[1,3-dimethyl-6-[3-(2-methylpropoxy)phenoxy]-2-oxobenzimidazol-5-yl]cyclopropanesulfonamide	1282152: Inhibition of recombinant human His-tagged TRIM24-PHD/bromodomain expressed in Escherichia coli strains BL21 (DE3) cells using biotinylated H3K23ac (1 to 33 residues) peptide after 1 hr by AlphaScreen assay	ic50	0.1100	uM
N-[6-[3-(3-methoxypropoxy)phenoxy]-1,3-dimethyl-2-oxobenzimidazol-5-yl]-1,2-dimethylimidazole-4-sulfonamide	1282152: Inhibition of recombinant human His-tagged TRIM24-PHD/bromodomain expressed in Escherichia coli strains BL21 (DE3) cells using biotinylated H3K23ac (1 to 33 residues) peptide after 1 hr by AlphaScreen assay	ic50	0.1300	uM
N-[1,3-dimethyl-2-oxo-6-(3-phenylmethoxyphenoxy)benzimidazol-5-yl]-3,4-dimethoxybenzenesulfonamide	1282152: Inhibition of recombinant human His-tagged TRIM24-PHD/bromodomain expressed in Escherichia coli strains BL21 (DE3) cells using biotinylated H3K23ac (1 to 33 residues) peptide after 1 hr by AlphaScreen assay	ic50	0.1400	uM
N-[6-(3-butoxyphenoxy)-1,3-dimethyl-2-oxobenzimidazol-5-yl]-1,2-dimethylimidazole-4-sulfonamide	1282152: Inhibition of recombinant human His-tagged TRIM24-PHD/bromodomain expressed in Escherichia coli strains BL21 (DE3) cells using biotinylated H3K23ac (1 to 33 residues) peptide after 1 hr by AlphaScreen assay	ic50	0.1600	uM
tert-butyl N-[6-[3-[1,3-dimethyl-6-[(1-methylimidazol-4-yl)sulfonylamino]-2-oxobenzimidazol-5-yl]oxy-5-propoxyphenoxy]hexyl]carbamate	1282152: Inhibition of recombinant human His-tagged TRIM24-PHD/bromodomain expressed in Escherichia coli strains BL21 (DE3) cells using biotinylated H3K23ac (1 to 33 residues) peptide after 1 hr by AlphaScreen assay	ic50	0.1600	uM
N-[6-(3-ethoxyphenoxy)-1,3-dimethyl-2-oxobenzimidazol-5-yl]-1,2-dimethylimidazole-4-sulfonamide	1282152: Inhibition of recombinant human His-tagged TRIM24-PHD/bromodomain expressed in Escherichia coli strains BL21 (DE3) cells using biotinylated H3K23ac (1 to 33 residues) peptide after 1 hr by AlphaScreen assay	ic50	0.1800	uM
N-[1,3-dimethyl-2-oxo-6-(3-phenylmethoxyphenoxy)benzimidazol-5-yl]-1-methylimidazole-4-sulfonamide	1282152: Inhibition of recombinant human His-tagged TRIM24-PHD/bromodomain expressed in Escherichia coli strains BL21 (DE3) cells using biotinylated H3K23ac (1 to 33 residues) peptide after 1 hr by AlphaScreen assay	ic50	0.2200	uM
3,4-dimethoxy-N-[6-(4-methoxyphenoxy)-1,3-dimethyl-2-oxobenzimidazol-5-yl]benzenesulfonamide	1279916: Binding affinity to N-terminal His6-SUMO-1-tagged recombinant human TRIM24 bromodomain expressed in Escherichia coli BL21(DE3)-R3-pRARE2 cells by isothermal titration calorimetry	kd	0.2220	uM
N-[1,3-dimethyl-2-oxo-6-(3-phenylmethoxyphenoxy)benzimidazol-5-yl]-1,2-dimethylimidazole-4-sulfonamide	1282152: Inhibition of recombinant human His-tagged TRIM24-PHD/bromodomain expressed in Escherichia coli strains BL21 (DE3) cells using biotinylated H3K23ac (1 to 33 residues) peptide after 1 hr by AlphaScreen assay	ic50	0.2700	uM
N-[6-[3-[4-(dimethylamino)butoxy]phenoxy]-1,3-dimethyl-2-oxobenzimidazol-5-yl]-3,4-dimethoxybenzenesulfonamide	1282152: Inhibition of recombinant human His-tagged TRIM24-PHD/bromodomain expressed in Escherichia coli strains BL21 (DE3) cells using biotinylated H3K23ac (1 to 33 residues) peptide after 1 hr by AlphaScreen assay	ic50	0.2700	uM
(2R,4S)-1-[(2R)-2-[[2-[2-[2-[2-[[3-[[1,3-dimethyl-2-oxo-6-(3-propoxyphenoxy)benzimidazol-5-yl]sulfamoyl]benzoyl]amino]ethoxy]ethoxy]ethoxy]acetyl]amino]-3,3-dimethylbutanoyl]-4-hydroxy-N-[[4-(4-methyl-1,3-thiazol-5-yl)phenyl]methyl]pyrrolidine-2-carboxamide	1921330: Inhibition of His-tagged TRIM24 (unknown origin) expressed in Escherichia coli BL21(DE3)pLysS competent cells using biotinylated-H3K23ac peptide as substrate incubated for 30 mins by Alphascreen assay	ic50	0.3377	uM
N-(1,3-dimethyl-2-oxo-6-phenoxybenzimidazol-5-yl)-3,4-dimethoxybenzenesulfonamide	1279913: Inhibition of N-terminal His6-SUMO-1-tagged recombinant human TRIM24 bromodomain expressed in Escherichia coli BL21(DE3)-R3-pRARE2 cells by Alpha Screen assay	ic50	0.4800	uM
N-[6-(4-methoxyphenoxy)-1,3-dimethyl-2-oxobenzimidazol-5-yl]benzenesulfonamide	1279913: Inhibition of N-terminal His6-SUMO-1-tagged recombinant human TRIM24 bromodomain expressed in Escherichia coli BL21(DE3)-R3-pRARE2 cells by Alpha Screen assay	ic50	0.7300	uM
N-(1,3-dimethyl-2-oxo-6-phenoxybenzimidazol-5-yl)-4-methoxybenzenesulfonamide	1279913: Inhibition of N-terminal His6-SUMO-1-tagged recombinant human TRIM24 bromodomain expressed in Escherichia coli BL21(DE3)-R3-pRARE2 cells by Alpha Screen assay	ic50	0.7400	uM
4-methoxy-N-[6-(4-methoxyphenoxy)-1,3-dimethyl-2-oxobenzimidazol-5-yl]benzenesulfonamide	1279913: Inhibition of N-terminal His6-SUMO-1-tagged recombinant human TRIM24 bromodomain expressed in Escherichia coli BL21(DE3)-R3-pRARE2 cells by Alpha Screen assay	ic50	0.7700	uM
N,N-dimethyl-3-(6-methyl-7-oxo-1H-pyrrolo[2,3-c]pyridin-4-yl)benzamide	1625928: Binding affinity to human partial length TRIM24 expressed in bacterial expression system by BROMOscan assay	ic50	0.9100	uM
N-(1-acetyl-2,3-dihydroindol-5-yl)-5-cyclopropyl-2-methoxybenzenesulfonamide	1907138: Inhibition of TRIM24 (unknown origin) measured alphascreen assay	ic50	0.9800	uM
(1R)-7-[(1R)-1,2-dihydroxyethyl]-1,3-dimethyl-5-(1-methylpyrazol-4-yl)-1H-3-benzazepin-2-one	1918668: Binding affinity to human TRIM24 bromodomain by BROMOscan method	kd	1.2589	uM
N-(1,3-dimethyl-2-oxo-6-phenoxybenzimidazol-5-yl)-4-methylbenzenesulfonamide	1279913: Inhibition of N-terminal His6-SUMO-1-tagged recombinant human TRIM24 bromodomain expressed in Escherichia coli BL21(DE3)-R3-pRARE2 cells by Alpha Screen assay	ic50	1.2700	uM
N-(1-acetyl-2,3-dihydroindol-5-yl)-2-methoxy-5-propan-2-ylbenzenesulfonamide	1907138: Inhibition of TRIM24 (unknown origin) measured alphascreen assay	ic50	1.3600	uM
5-[8-[5-acetyl-1-(oxan-4-yl)-6,7-dihydro-4H-pyrazolo[4,3-c]pyridin-3-yl]isoquinolin-3-yl]-N-methylpyridine-2-carboxamide	1372273: Binding affinity to human partial length TRIM24 (G862 to E980 residues) expressed in bacterial expression system by BROMOscan assay	kd	1.4000	uM
N-[6-(4-methoxyphenoxy)-1,3-dimethyl-2-oxobenzimidazol-5-yl]-2-methylbenzenesulfonamide	1279913: Inhibition of N-terminal His6-SUMO-1-tagged recombinant human TRIM24 bromodomain expressed in Escherichia coli BL21(DE3)-R3-pRARE2 cells by Alpha Screen assay	ic50	1.4700	uM
4-chloro-N-(1,3-dimethyl-2-oxo-6-phenoxybenzimidazol-5-yl)benzenesulfonamide	1279913: Inhibition of N-terminal His6-SUMO-1-tagged recombinant human TRIM24 bromodomain expressed in Escherichia coli BL21(DE3)-R3-pRARE2 cells by Alpha Screen assay	ic50	1.5600	uM
4-cyano-N-(1,3-dimethyl-2-oxoquinolin-6-yl)-2-methoxybenzenesulfonamide	1475731: Inhibition of human TRIM24 bromodomain (790 to 977 residues) expressed in Escherichia coli BL21 after 1 hr by BROMOscan assay	ic50	1.6000	uM
4-cyclohexyl-N-(1,3-dimethyl-2-oxobenzimidazol-5-yl)benzenesulfonamide	1282152: Inhibition of recombinant human His-tagged TRIM24-PHD/bromodomain expressed in Escherichia coli strains BL21 (DE3) cells using biotinylated H3K23ac (1 to 33 residues) peptide after 1 hr by AlphaScreen assay	ic50	1.7000	uM
N-(1-acetyl-2,3-dihydroindol-5-yl)-5-(furan-2-yl)-2-methoxybenzenesulfonamide	1907138: Inhibition of TRIM24 (unknown origin) measured alphascreen assay	ic50	1.9800	uM
N-[1,3-dimethyl-2-oxo-6-(4-phenylmethoxyphenoxy)benzimidazol-5-yl]-1-methylimidazole-4-sulfonamide	1282152: Inhibition of recombinant human His-tagged TRIM24-PHD/bromodomain expressed in Escherichia coli strains BL21 (DE3) cells using biotinylated H3K23ac (1 to 33 residues) peptide after 1 hr by AlphaScreen assay	ic50	2.0000	uM
N-(1-acetyl-2,3-dihydroindol-5-yl)-5-bromo-2-methoxybenzenesulfonamide	1907138: Inhibition of TRIM24 (unknown origin) measured alphascreen assay	ic50	2.0000	uM
N-(1-acetyl-2,3-dihydroindol-5-yl)-2-methoxy-5-phenylbenzenesulfonamide	1907138: Inhibition of TRIM24 (unknown origin) measured alphascreen assay	ic50	2.0300	uM
N-(1-acetyl-2,3-dihydroindol-5-yl)-5-(cyclopenten-1-yl)-2-methoxybenzenesulfonamide	1907138: Inhibition of TRIM24 (unknown origin) measured alphascreen assay	ic50	2.1000	uM
N-(1-acetyl-2,3-dihydroindol-5-yl)-5-tert-butyl-2-methoxybenzenesulfonamide	1907138: Inhibition of TRIM24 (unknown origin) measured alphascreen assay	ic50	2.2800	uM
N-(1-acetyl-2,3-dihydroindol-5-yl)-2,5-dimethoxybenzenesulfonamide	1907138: Inhibition of TRIM24 (unknown origin) measured alphascreen assay	ic50	2.2900	uM
N-(1-acetyl-2,3-dihydroindol-5-yl)-3-methoxybenzenesulfonamide	1907138: Inhibition of TRIM24 (unknown origin) measured alphascreen assay	ic50	2.3600	uM
N-(1,3-dimethyl-2-oxo-6-phenoxybenzimidazol-5-yl)-3-methoxybenzenesulfonamide	1279913: Inhibition of N-terminal His6-SUMO-1-tagged recombinant human TRIM24 bromodomain expressed in Escherichia coli BL21(DE3)-R3-pRARE2 cells by Alpha Screen assay	ic50	2.3800	uM
1,3-dimethyl-5-[3-(2-methylpropoxy)phenoxy]benzimidazol-2-one	1282152: Inhibition of recombinant human His-tagged TRIM24-PHD/bromodomain expressed in Escherichia coli strains BL21 (DE3) cells using biotinylated H3K23ac (1 to 33 residues) peptide after 1 hr by AlphaScreen assay	ic50	2.4000	uM
N-(1-acetyl-2,3-dihydroindol-5-yl)-5-(cyclohexen-1-yl)-2-methoxybenzenesulfonamide	1907138: Inhibition of TRIM24 (unknown origin) measured alphascreen assay	ic50	2.4500	uM
4-chloro-N-(1,3-dimethyl-2-oxo-6-phenoxybenzimidazol-5-yl)-2-methylbenzenesulfonamide	1279913: Inhibition of N-terminal His6-SUMO-1-tagged recombinant human TRIM24 bromodomain expressed in Escherichia coli BL21(DE3)-R3-pRARE2 cells by Alpha Screen assay	ic50	2.4500	uM
2,4-dimethoxy-N-(1-methyl-2-oxo-3,4-dihydroquinolin-6-yl)benzenesulfonamide	1282152: Inhibition of recombinant human His-tagged TRIM24-PHD/bromodomain expressed in Escherichia coli strains BL21 (DE3) cells using biotinylated H3K23ac (1 to 33 residues) peptide after 1 hr by AlphaScreen assay	ic50	2.5000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases expression	5
Valproic Acid	decreases expression, affects expression, increases expression, affects cotreatment	5
bisphenol A	affects expression, affects binding, affects folding, increases reaction, decreases expression	4
Tetrachlorodibenzodioxin	decreases expression	3
potassium chromate(VI)	decreases expression, increases expression, affects cotreatment	2
entinostat	increases expression, affects cotreatment	2
Doxorubicin	decreases expression, increases expression	2
Smoke	increases abundance, increases expression, decreases expression	2
Aflatoxin B1	affects cotreatment, decreases expression, decreases methylation	2
aristolochic acid I	decreases expression	1
FR900359	affects phosphorylation	1
bisphenol F	affects cotreatment, increases expression	1
TAK-243	increases sumoylation	1
methylmercuric chloride	decreases expression	1
sodium arsenite	increases expression	1
ochratoxin A	decreases expression	1
4-hydroxy-2-nonenal	decreases expression	1
coumarin	increases phosphorylation	1
nivalenol	increases expression	1
testosterone-3-carboxymethyloxime-bovine serum albumin conjugate	affects expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
chromium hexavalent ion	affects expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression, decreases expression	1
ICG 001	increases expression	1
dorsomorphin	affects cotreatment, increases expression, decreases expression	1
bisphenol AF	affects binding, affects folding, increases reaction	1
Arsenic Trioxide	increases response to substance	1
Acetaminophen	increases expression	1
Air Pollutants	increases abundance, increases expression	1

ChEMBL screening assays

115 unique, capped per target: 113 binding, 2 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3111123	Binding	Displacement of H3K14(Ac) peptide from TIF1alpha bromodomain (unknown origin) at 50 uM by AlphaScreen assay relative to control	[1,2,4]triazolo[4,3-a]phthalazines: inhibitors of diverse bromodomains. — J Med Chem
CHEMBL5723150	Functional	Affinity Biochemical interaction: (AlphaScreen) EUB0002253aAD TRIM24	Affinity Biochemical Literature for EUbOPEN Chemogenomic Library

Cellosaurus cell lines

5 cell lines: 5 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B2JN	Abcam HeLa TRIM24 KO	Cancer cell line	Female
CVCL_B8RC	Abcam HCT 116 TRIM24 KO	Cancer cell line	Male
CVCL_B9TR	Abcam A-549 TRIM24 KO	Cancer cell line	Male
CVCL_TT93	HAP1 TRIM24 (-) 1	Cancer cell line	Male
CVCL_TT94	HAP1 TRIM24 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00190697	PHASE4	COMPLETED	A Study of LY353381 (Arzoxifene) for Patients Who Benefitted From This Drug in Other Oncology Trials and Wished to Continue Treatment
NCT00277160	PHASE4	COMPLETED	A Study of Primary Prophylaxis With Neulasta (Pegfilgrastim) Versus Secondary Prophylaxis After Chemotherapy in Elderly Subjects (>/= 65 Years Old) With Cancer
NCT00727961	PHASE4	COMPLETED	A Study to Evaluate Efficacy and Tolerance of Caelyx in Patients With Epithelial Ovarian Cancer. (Study P04072)(COMPLETED)
NCT00740116	PHASE4	COMPLETED	Tranexamic Acid in Surgery of Advanced Ovarian Cancer
NCT00817479	PHASE4	COMPLETED	Tumor Gene Expression in Women With Ovarian Cancer
NCT01432015	PHASE4	COMPLETED	Fosaprepitant Versus Aprepitant in the Prevention of Chemotherapy Induced Nausea and Vomiting
NCT01706120	PHASE4	UNKNOWN	Study of Clinical and Biological Prognostic Factors in Patients With Ovarian Cancer Receiving Carboplatin +Paclitaxel With Bevacizumab
NCT01932125	PHASE4	COMPLETED	An Interventional Study of Avastin (Bevacizumab) in Patients With Advanced/Metastatic Epithelial Ovarian Cancer, Fallopian Tube Cancer or Primary Peritoneal Cancer
NCT01953107	PHASE4	COMPLETED	Oral Iron vs. Placebo in Newly Diagnosed Gynecologic Oncology Patients Who Are Surgical Candidates.
NCT02035345	PHASE4	TERMINATED	Slowed Carboplatin Infusion for Ovarian Cancer Patients Receiving Carboplatin Re-Treatment
NCT02243059	PHASE4	WITHDRAWN	Magnetic Resonance Imaging for Lymph Node Staging in Ovarian Cancer
NCT03164980	PHASE4	TERMINATED	QoL-Comparison Between Trabectedin/PLD and Pt-based Therapy in Patients With Pt-sensitive Recurrent Ovarian Cancer
NCT03384511	PHASE4	COMPLETED	The Use of 18F-ALF-NOTA-PRGD2 PET/CT Scan to Predict the Efficacy and Adverse Events of Apatinib in Malignancies.
NCT03543462	PHASE4	COMPLETED	Diaphragmatic Resection And Gynecological Ovarian Neoplasm
NCT03752216	PHASE4	COMPLETED	NIraparib and Quality of LifE is a Longitudinal Study Evaluating in Real Life the Tolerability of Niraparib.
NCT03858166	PHASE4	TERMINATED	Efficacy and Safety of PEG-rhG-CSF Secondary Prophylaxis vs. Therapeutic Administration in Patients With Ovarian Cancer
NCT04024254	PHASE4	COMPLETED	A Study of Serum Folate Levels in Patients Treated With Olaparib
NCT04330040	PHASE4	COMPLETED	Prospective Multicentre Phase-IV Clinical Trial of Olaparib in Indian Patients With Ovarian and Metastatic Breast Cancer
NCT04352439	PHASE4	COMPLETED	Aspirin for Prevention of Venous Thromboembolism Among Ovarian Cancer Patients Receiving Neoadjuvant Chemotherapy
NCT05187208	PHASE4	UNKNOWN	PARP Inhibitor Oral Maintenance in Low-Risk Ovarian Cancer
NCT05606692	PHASE4	RECRUITING	Influences of Propofol and Sevoflurane Anesthesia in Ovarian Cancer (Anesthetics)
NCT05926336	PHASE4	RECRUITING	The Effects of Using Different Anesthetics on the Prognosis of Primary Tumors and Its Mechanism of Action
NCT06412120	PHASE4	RECRUITING	Study Evaluating Safety, Tolerability, and Metabolism of Niraparib
NCT06871787	PHASE4	NOT_YET_RECRUITING	Near-Infrared Fluorescence Imaging With Indocyanine Green to Evaluate Bowel Anastomoses in Gynecologic Oncology Surgery
NCT06887933	PHASE4	NOT_YET_RECRUITING	A Trial to Evaluate the Safety of Niraparib Tablets in Adult Female Participants With Advanced or Relapsed Epithelial Ovarian Cancer
NCT07469202	PHASE4	NOT_YET_RECRUITING	CYTALUX Dose Extension Study
NCT00001806	PHASE3	COMPLETED	Methods in Education for Breast Cancer Genetics
NCT00002477	PHASE3	UNKNOWN	Adjuvant Chemotherapy Compared With Observation in Treating Patients With Resected Early Stage Ovarian Epithelial Cancer
NCT00002568	PHASE3	COMPLETED	Combination Chemotherapy With or Without Surgery in Treating Patients With Stage III Ovarian Epithelial Cancer
NCT00002641	PHASE3	COMPLETED	Surgery With or Without Chemotherapy in Treating Patients With Soft Tissue Sarcoma
NCT00002717	PHASE3	COMPLETED	Paclitaxel and Cisplatin in Treating Patients With Stage III or Stage IV Ovarian Cancer or Primary Peritoneal Cancer
NCT00002764	PHASE3	COMPLETED	Surgery With or Without Combination Chemotherapy in Treating Patients With Lung Metastases From Soft Tissue Sarcoma
NCT00002819	PHASE3	TERMINATED	Chemotherapy With or Without Peripheral Stem Cell Transplantation in Treating Patients With Persistent Ovarian Epithelial Cancer
NCT00002894	PHASE3	COMPLETED	Platinum-based Chemotherapy With or Without Paclitaxel in Treating Patients With Relapsed Ovarian Cancer
NCT00002895	PHASE3	COMPLETED	Early Chemotherapy Based on CA 125 Level Alone Compared With Delayed Chemotherapy in Treating Patients With Recurrent Ovarian Epithelial , Fallopian Tube, or Primary Peritoneal Cancer
NCT00003120	PHASE3	COMPLETED	S9701 Paclitaxel in Treating Patients With Advanced Ovarian, Fallopian Tube, or Primary Peritoneal Cancer in Remission
NCT00003214	PHASE3	COMPLETED	Chemosensitivity Testing to Assign Treatment for Patients With Stage III or Stage IV Ovarian Cancer
NCT00003322	PHASE3	COMPLETED	Combination Chemotherapy in Treating Patients With Primary Peritoneal or Stage III Epithelial Ovarian Cancer
NCT00003636	PHASE3	COMPLETED	Chemotherapy Plus Surgery in Treating Patients With Stage III or Stage IV Ovarian, Peritoneal, or Fallopian Tube Cancer
NCT00003644	PHASE3	COMPLETED	Carboplatin Plus Paclitaxel With or Without Continued Low-Dose Paclitaxel in Treating Patients With Early-Stage Ovarian Cancer