TRIM59

Summary

TRIM59 (tripartite motif containing 59, HGNC:30834) is a protein-coding gene on chromosome 3q25.33, encoding Tripartite motif-containing protein 59 (Q8IWR1). E3 ubiquitin ligase involved in different processes such as development and immune response.

Predicted to enable ubiquitin protein ligase activity. Acts upstream of or within negative regulation of canonical NF-kappaB signal transduction. Predicted to be located in endoplasmic reticulum.

Source: NCBI Gene 286827 — RefSeq curated summary.

At a glance

• GWAS associations: 11
• Clinical variants (ClinVar): 55 total
• Druggable target: yes
• MANE Select transcript: NM_173084

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30834
Approved symbol	TRIM59
Name	tripartite motif containing 59
Location	3q25.33
Locus type	gene with protein product
Status	Approved
Aliases	TSBF1, Mrf1, RNF104
Ensembl gene	ENSG00000213186
Ensembl biotype	protein_coding
OMIM	616148
Entrez	286827

Gene structure

Transcript identifiers

Ensembl transcripts: 18 — 18 protein_coding

ENST00000309784, ENST00000468542, ENST00000471155, ENST00000471396, ENST00000479460, ENST00000494486, ENST00000496222, ENST00000543469, ENST00000870881, ENST00000870882, ENST00000870883, ENST00000916991, ENST00000916992, ENST00000916993, ENST00000916994, ENST00000916995, ENST00000916996, ENST00000916997

RefSeq mRNA: 1 — MANE Select: NM_173084 NM_173084

CCDS: CCDS3190

Canonical transcript exons

ENST00000309784 — 3 exons

Exon	Start	End
ENSE00001192323	160435503	160439186
ENSE00003560821	160448726	160448795
ENSE00003565234	160449717	160449786

Expression profiles

Bgee: expression breadth ubiquitous, 224 present calls, max score 97.94.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 15.3733 / max 330.1147, expressed in 1642 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
45357	12.8223	1606
45354	1.6472	826
45356	0.4966	282
45358	0.2430	111
45355	0.1641	55

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
oocyte	CL:0000023	97.94	gold quality
secondary oocyte	CL:0000655	96.68	gold quality
ventricular zone	UBERON:0003053	94.58	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	91.65	gold quality
embryo	UBERON:0000922	90.01	gold quality
ganglionic eminence	UBERON:0004023	90.01	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	89.83	gold quality
corpus callosum	UBERON:0002336	88.28	gold quality
trabecular bone tissue	UBERON:0002483	84.28	gold quality
bone marrow	UBERON:0002371	82.40	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	80.88	gold quality
stromal cell of endometrium	CL:0002255	79.93	gold quality
spinal cord	UBERON:0002240	79.45	gold quality
adrenal tissue	UBERON:0018303	78.87	gold quality
palpebral conjunctiva	UBERON:0001812	78.81	gold quality
thymus	UBERON:0002370	78.67	gold quality
lower esophagus mucosa	UBERON:0035834	77.89	gold quality
lymph node	UBERON:0000029	77.76	gold quality
Brodmann (1909) area 46	UBERON:0006483	77.69	gold quality
epithelium of nasopharynx	UBERON:0001951	77.59	gold quality
nasopharynx	UBERON:0001728	77.58	gold quality
bone marrow cell	CL:0002092	77.21	gold quality
substantia nigra	UBERON:0002038	76.55	gold quality
inferior vagus X ganglion	UBERON:0005363	76.38	gold quality
esophagus squamous epithelium	UBERON:0006920	75.95	gold quality
gingival epithelium	UBERON:0001949	75.65	gold quality
testis	UBERON:0000473	75.62	gold quality
midbrain	UBERON:0001891	75.55	gold quality
endothelial cell	CL:0000115	75.31	gold quality
ileal mucosa	UBERON:0000331	75.25	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-MTAB-7051	yes	3330.65
E-MTAB-7052	yes	657.53
E-MTAB-6678	yes	7.84
E-ANND-3	yes	7.51

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

97 targeting TRIM59, 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-5011-5P	100.00	83.46	5820
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-499A-5P	99.98	70.79	1323
HSA-MIR-103A-3P	99.98	69.14	1595
HSA-MIR-107	99.98	69.14	1595
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-507	99.97	70.11	1915
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-557	99.96	70.01	1640
HSA-MIR-205-3P	99.92	69.92	3165
HSA-MIR-450B-5P	99.92	71.48	3175
HSA-MIR-374A-5P	99.90	71.34	2923
HSA-MIR-374B-5P	99.90	69.98	2734
HSA-MIR-8087	99.90	69.55	1351
HSA-MIR-345-3P	99.89	70.23	1421
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-MIR-5582-3P	99.86	72.48	4221
HSA-MIR-5003-3P	99.85	69.29	2517
HSA-MIR-548AR-3P	99.85	71.26	3889
HSA-MIR-383-3P	99.85	65.84	1359
HSA-MIR-369-3P	99.85	70.52	2264

Literature-anchored findings (GeneRIF, showing 40)

• PMID:12095697 pertains to mouse Mrf1 gene which appears to be the homolog of human TSBF1. (PMID:12095697)
• These findings indicate that TRIM59 may serve as a multifunctional regulator for innate immune signaling pathways. (PMID:22588174)
• TRIM59 interacts with P53, promoting its ubiquitination and degradation, and TRIM59 might promote gastric carcinogenesis via this mechanism. (PMID:25046164)
• we knocked down TRIM59 and found that p53 protein expression levels did not upregulate, so we proposed that TRIM59 may promote NSCLC cell growth through other pathways but not the p53 signaling pathway (PMID:26599082)
• These data suggest the oncogenic abilities of TRIM59 in osteosarcoma, which promote osteosarcoma cell proliferation, migration and invasion (PMID:27121462)
• The expression of TRIM59 was significantly elevated in cervical cancers. (PMID:27662486)
• our results suggest that rs1141023 polymorphism contributes to increased predisposition to gastric cancer (PMID:28009992)
• TRIM59 overexpression is associated with colorectal cancer metastasis. (PMID:28534983)
• Knockdown of TRIM59 may be a promising strategy concerning the early detection and treatment of Renal cell carcinoma. (PMID:28719348)
• The level of TRIM59 is correlated with malignant features of colorectal carcinoma (CRC)and may serve as potential therapeutic and preventive strategies for CRC (PMID:28849218)
• Silencing TRIM59 suppresses cell proliferation, migration, and orthotopic xenograft brain tumor formation of glioblastoma cells and glioma stem cells. (PMID:29386185)
• TRIM59 expression is upregulated in hepatocellular carcinoma (HCC) cells; TRIM59 promotes cell proliferation, migration and invasion in HCC cells (PMID:29442042)
• The modified methylation of TRIM59 and KLF14 in top athletes may be accounted for by the biological roles played by these genes. Their known anti-tumour and anti-inflammatory activities suggests that intense physical training has a complex influence on aging and potentially launches signalling networks that contribute to the observed lower risk of elite athletes to develop cardiovascular disease and cancer. (PMID:29466246)
• Study demonstrated that TRIM59 was upregulated in breast cancer tissues and associated with poor prognosis. TRIM59 overexpression promotes breast cancer cell proliferation, invasion, migration, cell cycle, and chemoresistance, possibly through regulation of AKT pathway. (PMID:30175868)
• Novel dual roles for TRIM59 in autophagy regulation by affecting both the transcription and the ubiquitination of BECN1. (PMID:30231667)
• TRIM59 was up-regulated in neuroblastoma.TRIM59 regulates cell proliferation and apoptosis through Wnt/beta-catenin signaling in neuroblastoma. (PMID:30389710)
• these data provide evidence that TRIM59 is involved in lung carcinoma growth and progression possibly through the induction of CDK6 expression and epithelial-to-mesenchymal transition (EMT) process by activation of ERK pathway. (PMID:30515965)
• TRIM59 Is a Novel Marker of Poor Prognosis and Promotes Malignant Progression of Ovarian Cancer by Inducing Annexin A2 Expression (PMID:30585270)
• Study revealed that TRIM59 is up-regulated in CCA tissues and cell lines and promoted CCA cell proliferation, possibly by affecting the PI3K/AKT/mTOR signalling pathway. (PMID:30822475)
• High TRIM59 expression is associated with gefitinib-resistant EGFR mutant lung adenocarcinoma. (PMID:30902544)
• Silencing TRIM59 significantly suppressed EOC cell proliferation, migration, and invasion. In terms of molecular mechanism, silencing TRIM59 inhibited the FAK/AKT/MMP pathway. (PMID:31062766)
• CDK5-dependent phosphorylation and nuclear translocation of TRIM59 promotes macroH2A1 ubiquitination and tumorigenicity. (PMID:31488827)
• TRIM59 predicts poor prognosis and promotes pancreatic cancer progression via the PI3K/AKT/mTOR-glycolysis signaling axis. (PMID:31693252)
• TRIM59 promotes tumor growth in hepatocellular carcinoma and regulates the cell cycle by degradation of protein phosphatase 1B. (PMID:31875525)
• Expression of TRIM59 in Non-small Cell Lung Cancer and Its Correlation with Prognosis (PMID:31948534)
• TRIM59, amplified in ovarian cancer, promotes tumorigenesis through the MKP3/ERK pathway. (PMID:31951023)
• miR-4698-Trim59 axis plays a suppressive role in hepatocellular carcinoma. (PMID:32114426)
• Tripartite motif containing 59 (TRIM59) promotes esophageal cancer progression via promoting MST4 expression and ERK pathway. (PMID:32340525)
• TRIM59 inhibits PPM1A through ubiquitination and activates TGF-beta/Smad signaling to promote the invasion of ectopic endometrial stromal cells in endometriosis. (PMID:32348176)
• TRIM59 attenuates IL-1beta-driven cartilage matrix degradation in osteoarthritis via direct suppression of NF-kappaB and JAK2/STAT3 signaling pathway. (PMID:32560815)
• TRIM59 Promotes Retinoblastoma Progression by Activating the p38-MAPK Signaling Pathway. (PMID:32744597)
• Cancer-derived exosomal TRIM59 regulates macrophage NLRP3 inflammasome activation to promote lung cancer progression. (PMID:32867817)
• Effects of TRIM59 on RAW264.7 macrophage gene expression and function. (PMID:34252840)
• [TRIM59 regulates invasion and migration of nasopharyngeal carcinoma cells by targeted modulation of PPM1B]. (PMID:34308852)
• TRIM59 promotes osteosarcoma progression via activation of STAT3. (PMID:34625908)
• Evaluation of tripartite motif 59 and its diagnostic utility in benign bowel diseases and colorectal cancer. (PMID:35377964)
• [Down-regulation of tripartite motif containing 59 (TRIM59) blocks the NF-kappaB signaling pathway and inhibits the invasion and migration of nasopharyngeal carcinoma cells]. (PMID:35603650)
• The role of Tripartite motif containing 59 (TRIM59) in the proliferation and prognosis of intrahepatic cholangiocarcinoma. (PMID:35753134)
• Regulations of LINC0196/miR-584-5p/miR-34a-5p/TRIM59 on Progression of Pediatric Neuroblastoma. (PMID:36227666)
• TRIM59 guards ER proteostasis and prevents Bortezomib-mediated colorectal cancer (CRC) cells’ killing. (PMID:36306030)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
mus_musculus	Trim59	ENSMUSG00000034317
rattus_norvegicus	Trim59	ENSRNOG00000010515
drosophila_melanogaster	Oseg5	FBGN0032891
caenorhabditis_elegans		WBGENE00000484

Paralogs (1): IFT80 (ENSG00000068885)

Protein

Protein identifiers

Tripartite motif-containing protein 59 — Q8IWR1 (reviewed: Q8IWR1)

Alternative names: RING finger protein 104, Tumor suppressor TSBF-1

All UniProt accessions (8): C9IY67, C9IZE0, C9J614, C9J9F0, C9JE08, C9JNB9, Q8IWR1, F5GZP3

UniProt curated annotations — full annotation on UniProt →

Function. E3 ubiquitin ligase involved in different processes such as development and immune response. Serves as a negative regulator for innate immune signaling pathways by suppressing RLR-induced activation of IRF3/7 and NF-kappa-B via interaction with adapter ECSIT. Regulates autophagy through modulating both the transcription and the ubiquitination of BECN1. On the one hand, regulates the transcription of BECN1 through negatively modulating the NF-kappa-B pathway. On the other hand, regulates TRAF6-mediated ‘Lys-63’-linked ubiquitination of BECN1, thus affecting the formation of the BECN1-PIK3C3 complex. In addition, mediates ‘Lys-48’-linked ubiquitination of TRAF6 and thereby promotes TRAF6 proteasomal degradation. Also acts as a critical regulator for early embryo development from blastocyst stage to gastrula through modulating F-actin assembly and WASH1 ‘Lys-63’-linked ubiquitination.

Subunit / interactions. Interacts with ECSIT.

Subcellular location. Endoplasmic reticulum membrane.

Pathway. Protein modification; protein ubiquitination.

Similarity. Belongs to the TRIM/RBCC family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q8IWR1-1	1	yes
Q9P2H3-3	IFT80-L

RefSeq proteins (1): NP_775107* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000315	Znf_B-box	Domain
IPR001841	Znf_RING	Domain
IPR013083	Znf_RING/FYVE/PHD	Homologous_superfamily
IPR017907	Znf_RING_CS	Conserved_site
IPR027370	Znf-RING_euk	Domain

Pfam: PF00643, PF13445

UniProt features (9 total): binding site 4, zinc finger region 2, chain 1, transmembrane region 1, coiled-coil region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8IWR1-F1	84.52	0.56

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 (4): 97; 100; 120; 126

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 199 (showing top): STARK_PREFRONTAL_CORTEX_22Q11_DELETION_DN, GOBP_CANONICAL_NF_KAPPAB_SIGNAL_TRANSDUCTION, IVANOVA_HEMATOPOIESIS_MATURE_CELL, GOBP_MODULATION_OF_PROCESS_OF_ANOTHER_ORGANISM, GOBP_NEGATIVE_REGULATION_OF_INTRACELLULAR_SIGNAL_TRANSDUCTION, GOBP_DEFENSE_RESPONSE_TO_OTHER_ORGANISM, CREIGHTON_ENDOCRINE_THERAPY_RESISTANCE_1, LE_EGR2_TARGETS_UP, FISCHER_G2_M_CELL_CYCLE, GOBP_POST_TRANSLATIONAL_PROTEIN_MODIFICATION, GOBP_NEGATIVE_REGULATION_OF_CANONICAL_NF_KAPPAB_SIGNAL_TRANSDUCTION, GOBP_HOST_MEDIATED_SUPPRESSION_OF_SYMBIONT_INVASION, FISCHER_DREAM_TARGETS, ZHANG_BREAST_CANCER_PROGENITORS_UP, MARKEY_RB1_ACUTE_LOF_UP

GO Biological Process (4): protein ubiquitination (GO:0016567), negative regulation of canonical NF-kappaB signal transduction (GO:0043124), innate immune response (GO:0045087), host-mediated suppression of symbiont invasion (GO:0046597)

GO Molecular Function (5): zinc ion binding (GO:0008270), ubiquitin protein ligase activity (GO:0061630), protein binding (GO:0005515), transferase activity (GO:0016740), metal ion binding (GO:0046872)

GO Cellular Component (3): endoplasmic reticulum (GO:0005783), endoplasmic reticulum membrane (GO:0005789), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein modification by small protein conjugation	1
canonical NF-kappaB signal transduction	1
regulation of canonical NF-kappaB signal transduction	1
negative regulation of intracellular signal transduction	1
immune response	1
defense response to symbiont	1
innate immune response	1
host-mediated perturbation of symbiont process	1
transition metal ion binding	1
ubiquitin-protein transferase activity	1
ubiquitin-like protein ligase activity	1
binding	1
catalytic activity	1
cation binding	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
cellular anatomical structure	1

Protein interactions and networks

STRING

783 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TRIM59	ECSIT	Q9BQ95	943
TRIM59	TRAT1	Q6PIZ9	691
TRIM59	TRIM47	Q96LD4	668
TRIM59	TRIM28	Q13263	632
TRIM59	KLF14	Q8TD94	620
TRIM59	ELOVL2	Q9NXB9	610
TRIM59	SP6	Q3SY56	582
TRIM59	ELOVL5	Q9NYP7	580
TRIM59	TP53	P04637	562
TRIM59	TRIM66	O15016	559
TRIM59	FHL2	Q14192	541
TRIM59	BBOX1	O75936	528
TRIM59	TRIM44	Q96DX7	528
TRIM59	TRIM14	Q14142	527
TRIM59	TRIM29	Q14134	521

IntAct

91 interactions, top by confidence:

A	B	Type	Score
ZDHHC22	TRIM59	psi-mi:“MI:0915”(physical association)	0.830
TRIM59	ZDHHC22	psi-mi:“MI:0915”(physical association)	0.830
TRIM59	NRM	psi-mi:“MI:0915”(physical association)	0.780
VTI1B	TRIM59	psi-mi:“MI:0915”(physical association)	0.780
NRM	TRIM59	psi-mi:“MI:0915”(physical association)	0.780
TRIM59	VTI1B	psi-mi:“MI:0915”(physical association)	0.780
	HMOX1	psi-mi:“MI:0914”(association)	0.740
TRIM59		psi-mi:“MI:0915”(physical association)	0.560
TRIM59	ANKRD33	psi-mi:“MI:0915”(physical association)	0.560
TRIM59	MEI4	psi-mi:“MI:0915”(physical association)	0.560
TRIM59	RASSF3	psi-mi:“MI:0915”(physical association)	0.560
TRIM59	KRTAP13-3	psi-mi:“MI:0915”(physical association)	0.560
TRIM59	BLZF1	psi-mi:“MI:0915”(physical association)	0.560
NECAB2	TRIM59	psi-mi:“MI:0915”(physical association)	0.560
TRIM59	SEC22A	psi-mi:“MI:0915”(physical association)	0.560
CLDN4	TRIM59	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (109): TRIM59 (Two-hybrid), TRIM59 (Two-hybrid), TRIM59 (Two-hybrid), TRIM59 (Affinity Capture-Western), TRIM59 (Reconstituted Complex), TRIM59 (Affinity Capture-MS), TRIM59 (Affinity Capture-MS), TRIM59 (Affinity Capture-MS), TRIM59 (Affinity Capture-RNA), STAT3 (Affinity Capture-Western), ANXA2 (Affinity Capture-Western), ANXA2 (Affinity Capture-MS), ANXA5 (Affinity Capture-MS), MDM2 (Affinity Capture-MS), RAD23B (Affinity Capture-MS)

ESM2 similar proteins: D3ZSP7, E9QHE3, F1M649, F1MHT9, F6ZQ54, O16616, O60858, O76064, O88196, O95361, P36406, P36407, Q07DV3, Q13075, Q13129, Q14258, Q309B1, Q32L60, Q38HM4, Q3UP24, Q4VSN4, Q4VSN5, Q503I2, Q5M7V1, Q5R4I2, Q5R760, Q5RB52, Q5ZMD4, Q61510, Q6NRG0, Q6XUX3, Q803C1, Q8BGX0, Q8IWR1, Q8IWZ5, Q8R2Q0, Q8TDY2, Q8WXH0, Q922Y2, Q969Q1

Diamond homologs: A0JPQ4, A6QQX5, D3YY23, D3Z8N2, F6ZQ54, F8S122, O00478, O00481, O60858, O75677, P18892, P82885, P83234, Q13410, Q14258, Q17RB8, Q1XH17, Q1XH18, Q27J48, Q2XXL4, Q32L60, Q503I2, Q5EBN2, Q5M7V1, Q5R846, Q5R996, Q5TA31, Q5ZMD4, Q61510, Q62556, Q640S6, Q6PGR9, Q6QA27, Q6UX41, Q6UXG8, Q6ZMU5, Q7SZN2, Q7T308, Q7TST0, Q810I1

SIGNOR signaling

7 interactions.

A	Effect	B	Mechanism
TRIM59	“down-regulates activity”	ECSIT	binding
TRIM59	“down-regulates activity”	IRF3
TRIM59	“down-regulates activity”	IRF7
Ub:E2	“up-regulates activity”	TRIM59	ubiquitination
TRIM59	down-regulates	MACROH2A1	ubiquitination
CDK5	“up-regulates activity”	TRIM59	phosphorylation
TRIM59	“down-regulates quantity by destabilization”	MACROH2A1	polyubiquitination

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	50
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

922 predictions. Top by Δscore:

Variant	Effect	Δscore
3:160433024:A:AG	acceptor_gain	1.0000
3:160433025:G:GG	acceptor_gain	1.0000
3:160433025:GT:G	acceptor_gain	1.0000
3:160433210:G:GG	donor_gain	1.0000
3:160438216:T:TA	donor_gain	1.0000
3:160448724:A:AC	donor_gain	1.0000
3:160448725:C:CC	donor_gain	1.0000
3:160433021:TTCAG:T	acceptor_loss	0.9900
3:160433023:CAGTG:C	acceptor_loss	0.9900
3:160433024:AG:A	acceptor_loss	0.9900
3:160433025:GTGTT:G	acceptor_gain	0.9900
3:160433205:TATAT:T	donor_gain	0.9900
3:160433206:ATAT:A	donor_gain	0.9900
3:160433207:TAT:T	donor_gain	0.9900
3:160433208:ATGT:A	donor_loss	0.9900
3:160433209:TG:T	donor_loss	0.9900
3:160433210:G:GC	donor_loss	0.9900
3:160433211:TAAG:T	donor_loss	0.9900
3:160433212:AAG:A	donor_loss	0.9900
3:160433213:AGT:A	donor_loss	0.9900
3:160433651:CTTTA:C	acceptor_loss	0.9900
3:160433652:TTTA:T	acceptor_loss	0.9900
3:160433654:TA:T	acceptor_loss	0.9900
3:160433655:A:AC	acceptor_loss	0.9900
3:160433655:A:AG	acceptor_gain	0.9900
3:160433656:G:GG	acceptor_gain	0.9900
3:160438250:T:TA	donor_gain	0.9900
3:160449716:CCG:C	donor_gain	0.9900
3:160433024:AGT:A	acceptor_gain	0.9800
3:160433025:GTG:G	acceptor_gain	0.9800

AlphaMissense

2686 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:160439018:A:G	C56R	0.998
3:160439156:A:G	C10R	0.998
3:160438835:A:G	C117R	0.997
3:160438857:A:C	C109W	0.997
3:160438859:A:G	C109R	0.997
3:160438956:A:C	N76K	0.997
3:160438956:A:T	N76K	0.997
3:160439096:A:G	C30R	0.997
3:160439103:A:C	H27Q	0.997
3:160439103:A:T	H27Q	0.997
3:160439085:A:C	C33W	0.996
3:160439097:A:C	F29L	0.996
3:160439097:A:T	F29L	0.996
3:160439099:A:G	F29L	0.996
3:160439111:A:G	C25R	0.996
3:160439122:C:G	R21P	0.996
3:160438834:C:G	C117S	0.995
3:160438835:A:T	C117S	0.995
3:160439017:C:G	C56S	0.995
3:160439018:A:T	C56S	0.995
3:160439087:A:G	C33R	0.995
3:160439094:A:C	C30W	0.995
3:160439105:G:C	H27D	0.995
3:160439147:A:G	C13R	0.995
3:160438825:C:G	C120S	0.994
3:160438826:A:G	C120R	0.994
3:160438826:A:T	C120S	0.994
3:160438834:C:T	C117Y	0.994
3:160438895:A:G	C97R	0.994
3:160439095:C:G	C30S	0.994

dbSNP variants (sampled 300 via entrez): RS1000184579 (3:160438498 C>G,T), RS1000240277 (3:160441072 C>T), RS1000532756 (3:160441613 G>T), RS1000847757 (3:160435849 C>G), RS1000947453 (3:160449828 C>A,T), RS1000949481 (3:160436613 A>G), RS1001001921 (3:160436893 G>GAAT), RS1001509022 (3:160442617 G>A), RS1001609336 (3:160446655 T>C), RS1001679508 (3:160435270 T>A), RS1001876684 (3:160447438 G>A), RS1002174819 (3:160440158 C>A,G), RS1002189457 (3:160441212 T>C,G), RS1002507973 (3:160444947 C>A,T), RS1002766371 (3:160450369 A>G)

Disease associations

OMIM: gene MIM:616148 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

11 associations (top):

Study	Trait	p-value
GCST005287_1	Intrinsic epigenetic age acceleration	2.000000e-09
GCST006716_3	Alcohol use disorder (total score)	2.000000e-08
GCST007267_260	Systolic blood pressure	7.000000e-13
GCST007269_91	Pulse pressure	2.000000e-08
GCST008103_105	Bipolar disorder	4.000000e-06
GCST010725_1	Malaria	3.000000e-09
GCST010725_57	Malaria	2.000000e-08
GCST010725_87	Malaria	3.000000e-09
GCST90002382_584	Eosinophil percentage of white cells	2.000000e-10
GCST90011898_155	Alanine aminotransferase levels	8.000000e-14
GCST90011899_119	Aspartate aminotransferase levels	2.000000e-09

EFO canonical traits (7, from GWAS)

EFO ID	Trait name
EFO:0000473	epigenetic status
EFO:0022597	aging
EFO:0009458	alcohol use disorder measurement
EFO:0006335	systolic blood pressure
EFO:0005763	pulse pressure measurement
EFO:0007991	eosinophil percentage of leukocytes
EFO:0004736	aspartate aminotransferase measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6067126 (SINGLE PROTEIN)

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

ChEMBL bioactivities

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

pChembl	Type	Value	Unit	Molecule
8.24	Kd	5.792	nM	CHEMBL5653589
8.23	ED50	5.847	nM	CHEMBL5653589

PubChem BioAssay actives

1 with measured affinity, of 2 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149658: Binding affinity to human TRIM59 incubated for 45 mins by Kinobead based pull down assay	kd	0.0058	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
trichostatin A	affects cotreatment, decreases expression	3
sodium arsenite	increases expression, decreases expression	2
potassium chromate(VI)	affects cotreatment, decreases expression, increases expression	2
Air Pollutants	affects expression, increases abundance, decreases expression	2
aristolochic acid I	decreases expression	1
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
GSK-J4	decreases expression	1
geldanamycin	increases expression	1
methylmercuric chloride	increases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	decreases expression	1
3,4-dichloroaniline	decreases expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, increases expression	1
cupric oxide	decreases expression	1
hydroquinone	decreases expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
di-n-butylphosphoric acid	affects expression	1
chromium hexavalent ion	affects expression	1
perfluorooctane sulfonic acid	decreases 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, decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Sunitinib	decreases expression	1
Vorinostat	decreases expression	1
Benzo(a)pyrene	decreases methylation	1
Calcitriol	affects cotreatment, decreases expression	1
Cannabidiol	decreases expression	1
Coumestrol	affects cotreatment, increases expression	1
Dichlorodiphenyl Dichloroethylene	increases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5652700	Binding	Binding affinity to human TRIM59 incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_TU41	HAP1 TRIM59 (-)	Cancer cell line	Male

Clinical trials (associated diseases)

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