TRIM17

Summary

TRIM17 (tripartite motif containing 17, HGNC:13430) is a protein-coding gene on chromosome 1q42.13, encoding E3 ubiquitin-protein ligase TRIM17 (Q9Y577). E3 ubiquitin ligase that plays important roles in the regulation of neuronal apoptosis, selective autophagy or cell proliferation.

The protein encoded by this gene 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. The protein localizes to cytoplasmic bodies. The protein is expressed almost exclusively in the testis, but its function is unknown. Multiple alternatively spliced transcript variants have been found for this gene.

Source: NCBI Gene 51127 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 90 total
• MANE Select transcript: NM_016102

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:13430
Approved symbol	TRIM17
Name	tripartite motif containing 17
Location	1q42.13
Locus type	gene with protein product
Status	Approved
Aliases	terf, RBCC
Ensembl gene	ENSG00000162931
Ensembl biotype	protein_coding
OMIM	606123
Entrez	51127

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 10 protein_coding

ENST00000295033, ENST00000355586, ENST00000366697, ENST00000366698, ENST00000456946, ENST00000457345, ENST00000479800, ENST00000520264, ENST00000882179, ENST00000882180

RefSeq mRNA: 3 — MANE Select: NM_016102 NM_001024940, NM_001134855, NM_016102

CCDS: CCDS1571, CCDS44327

Canonical transcript exons

ENST00000366698 — 7 exons

Exon	Start	End
ENSE00001069942	228409389	228409411
ENSE00001069944	228413797	228413892
ENSE00001069945	228410946	228411176
ENSE00001413601	228416539	228416861
ENSE00001416217	228414644	228415113
ENSE00003789613	228409172	228409275
ENSE00003841324	228407935	228408751

Expression profiles

Bgee: expression breadth ubiquitous, 133 present calls, max score 92.09.

FANTOM5 (CAGE): breadth broad, TPM avg 1.6471 / max 91.5525, expressed in 465 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
17836	0.4278	232
17839	0.4218	214
17837	0.2545	115
17840	0.2487	119
17834	0.1177	58
17838	0.0758	29
17833	0.0433	28
17835	0.0385	14
17832	0.0190	5

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right hemisphere of cerebellum	UBERON:0014890	92.09	gold quality
cerebellar hemisphere	UBERON:0002245	91.92	gold quality
cerebellar cortex	UBERON:0002129	91.86	gold quality
cerebellum	UBERON:0002037	91.82	gold quality
left testis	UBERON:0004533	88.96	gold quality
right testis	UBERON:0004534	88.73	gold quality
testis	UBERON:0000473	88.29	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	87.02	gold quality
nucleus accumbens	UBERON:0001882	85.94	gold quality
caudate nucleus	UBERON:0001873	83.83	gold quality
right frontal lobe	UBERON:0002810	83.35	gold quality
putamen	UBERON:0001874	82.58	gold quality
superior frontal gyrus	UBERON:0002661	81.29	gold quality
Brodmann (1909) area 9	UBERON:0013540	81.02	gold quality
frontal cortex	UBERON:0001870	80.19	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	79.71	gold quality
cerebral cortex	UBERON:0000956	78.47	gold quality
brain	UBERON:0000955	78.17	gold quality
prefrontal cortex	UBERON:0000451	77.94	gold quality
anterior cingulate cortex	UBERON:0009835	77.27	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	77.08	gold quality
primary visual cortex	UBERON:0002436	76.99	gold quality
right uterine tube	UBERON:0001302	76.72	gold quality
Ammon’s horn	UBERON:0001954	76.46	gold quality
temporal lobe	UBERON:0001871	73.06	gold quality
spleen	UBERON:0002106	72.95	gold quality
amygdala	UBERON:0001876	72.86	gold quality
hypothalamus	UBERON:0001898	72.30	gold quality
granulocyte	CL:0000094	71.20	gold quality
right ovary	UBERON:0002118	70.92	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.22

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): NKX3-1

miRNA regulators (miRDB)

6 targeting TRIM17, 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-33A-3P	99.70	70.27	3362
HSA-MIR-3059-5P	99.70	69.93	2491
HSA-MIR-1246	98.54	66.21	959
HSA-MIR-4277	98.34	67.17	1323
HSA-MIR-3650	97.88	64.89	693
HSA-MIR-7848-3P	95.69	65.00	363

Literature-anchored findings (GeneRIF, showing 9)

• terf interacts with TRIM44;TRIM44 inhibited ubiquitination of terf, and thus stabilized the protein. (PMID:19358823)
• the E3 ubiquitin ligase terf causes protein degradation of ZWINT and negatively regulates cell proliferation (PMID:22023800)
• NFATc3 interacted in a SUMO-dependent manner with Trim17, an E3 ubiquitin ligase necessary for neuronal apoptosis (PMID:25215946)
• TRIM17 promoted the removal of midbodies, remnants of the cell division machinery that are known autophagy targets. (PMID:27562068)
• overexpression of TRIM28 or knock-out of TRIM17 reduced BCLA1 protein levels and restored sensitivity of melanoma cells to BRAF-targeted therapy. Therefore, our data describe a molecular rheostat in which two proteins of the TRIM family antagonistically regulate BCL2A1 stability and modulate cell death. (PMID:30042493)
• deregulation of the TRIM17/TRIM41/ZSCAN21 pathway may be involved in the pathogenesis of Parkinson’s disease. (PMID:30485814)
• data suggest LSD1 largely plays a tumor suppressor role in luminal breast cancer and the oncogenic program associated with LSD1-inhibition may be suppressed via TRIM37-inhibition (PMID:31409898)
• MiR-1246 is responsible for lung cancer cells-derived exosomes-mediated promoting effects on lung cancer stemness via targeting TRIM17. (PMID:35894553)
• TRIM17-mediated ubiquitination and degradation of RBM38 promotes cisplatin resistance in non-small cell lung cancer. (PMID:37219768)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Trim17	ENSMUSG00000036964
rattus_norvegicus	Trim17	ENSRNOG00000022983

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), TRIM24 (ENSG00000122779), 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)

Protein

Protein identifiers

E3 ubiquitin-protein ligase TRIM17 — Q9Y577 (reviewed: Q9Y577)

Alternative names: RING finger protein 16, RING-type E3 ubiquitin transferase TRIM17, Testis RING finger protein, Tripartite motif-containing protein 17

All UniProt accessions (5): E5RI62, E5RJW6, Q9Y577, J3KNZ3, J3KQG0

UniProt curated annotations — full annotation on UniProt →

Function. E3 ubiquitin ligase that plays important roles in the regulation of neuronal apoptosis, selective autophagy or cell proliferation. Stimulates the degradation of kinetochore ZW10 interacting protein ZWINT in a proteasome-dependent manner, leading to negative regulation of cell proliferation. Inhibits autophagic degradation of diverse known targets while contributing to autophagy of midbodies. Autophagy-inhibitory activity involves MCL1, which TRIM17 assembles into complexes with the key autophagy regulator BECN1. Controls neuronal apoptosis by mediating ubiquitination and degradation of MCL1 to initiate neuronal death. In addition, regulates NFAT transcription factors NFATC3 and NFATC4 activities by preventing their nuclear localization, thus inhibiting their transcriptional activities. Decreases TRIM41-mediated degradation of ZSCAN2 thereby stimulating alpha-synuclein/SNCA transcription in neuronal cells. Prevents the E3 ubiquitin-ligase activity of TRIM28 and its interaction with anti-apoptotic BCL2A1, blocking TRIM28 from ubiquitinating BCL2A1.

Subunit / interactions. Interacts (via coiled coil) with TRIM44 (via coiled coil). Interacts with TRIM28; this interaction prevents TRIM28 activity on BCL2A1. Interacts with TRIM41; this interaction prevents TRIM41 activity on ZSCAN2. Interacts with BECN1. Interacts with NFATC3 and NFATC4; these interactions prevent NFATC3 and NFATC4 nuclear localization.

Subcellular location. Cytoplasm. Lysosome.

Tissue specificity. Almost exclusively in the testis.

Post-translational modifications. Auto-ubiquitinated.

Pathway. Protein modification; protein ubiquitination.

Similarity. Belongs to the TRIM/RBCC family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9Y577-1	1	yes
Q9Y577-2	2

RefSeq proteins (3): NP_001020111, NP_001128327, NP_057186* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000315	Znf_B-box	Domain
IPR001841	Znf_RING	Domain
IPR001870	B30.2/SPRY	Domain
IPR003877	SPRY_dom	Domain
IPR003879	Butyrophylin_SPRY	Domain
IPR006574	PRY	Domain
IPR013083	Znf_RING/FYVE/PHD	Homologous_superfamily
IPR013320	ConA-like_dom_sf	Homologous_superfamily
IPR017907	Znf_RING_CS	Conserved_site
IPR027370	Znf-RING_euk	Domain
IPR035687	TRIM17_PRY/SPRY	Domain
IPR043136	B30.2/SPRY_sf	Homologous_superfamily
IPR050143	TRIM/RBCC	Family

Pfam: PF00622, PF00643, PF13445

UniProt features (11 total): binding site 4, splice variant 2, zinc finger region 2, chain 1, domain 1, coiled-coil region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9Y577-F1	86.17	0.55

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): 99; 102; 121; 127

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-877300	Interferon gamma signaling

MSigDB gene sets: 45 (showing top): REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GOBP_DEFENSE_RESPONSE_TO_OTHER_ORGANISM, GOBP_PROTEIN_AUTOUBIQUITINATION, SCHAEFFER_PROSTATE_DEVELOPMENT_6HR_DN, GOBP_POST_TRANSLATIONAL_PROTEIN_MODIFICATION, MARSON_BOUND_BY_FOXP3_STIMULATED, GOMF_ACYLTRANSFERASE_ACTIVITY, GOMF_AMINOACYLTRANSFERASE_ACTIVITY, GOMF_UBIQUITIN_LIKE_PROTEIN_LIGASE_ACTIVITY, CHYLA_CBFA2T3_TARGETS_DN, GOBP_PROCESS_UTILIZING_AUTOPHAGIC_MECHANISM, DELACROIX_RAR_BOUND_ES, ALK_DN.V1_DN, NRL_DN.V1_DN

GO Biological Process (6): autophagy (GO:0006914), regulation of gene expression (GO:0010468), regulation of protein localization (GO:0032880), innate immune response (GO:0045087), protein autoubiquitination (GO:0051865), protein ubiquitination (GO:0016567)

GO Molecular Function (7): ubiquitin-protein transferase activity (GO:0004842), zinc ion binding (GO:0008270), protein-macromolecule adaptor activity (GO:0030674), ubiquitin protein ligase activity (GO:0061630), protein binding (GO:0005515), transferase activity (GO:0016740), metal ion binding (GO:0046872)

GO Cellular Component (2): cytoplasm (GO:0005737), lysosome (GO:0005764)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Interferon Signaling	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
catabolic process	1
transmembrane transport	1
process utilizing autophagic mechanism	1
gene expression	1
regulation of macromolecule biosynthetic process	1
intracellular protein localization	1
regulation of localization	1
immune response	1
defense response to symbiont	1
protein ubiquitination	1
protein modification by small protein conjugation	1
ubiquitin-like protein transferase activity	1
transition metal ion binding	1
protein binding	1
molecular adaptor activity	1
ubiquitin-protein transferase activity	1
ubiquitin-like protein ligase activity	1
binding	1
catalytic activity	1
cation binding	1
intracellular anatomical structure	1
cellular anatomical structure	1
lytic vacuole	1

Protein interactions and networks

STRING

792 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TRIM17	BBOX1	O75936	977
TRIM17	RBCK1	Q9BYM8	959
TRIM17	TRAT1	Q6PIZ9	924
TRIM17	TRIM28	Q13263	858
TRIM17	TRIM24	O15164	804
TRIM17	TRIM9	Q9C026	793
TRIM17	TRIM66	O15016	786
TRIM17	TINF2	Q9BSI4	780
TRIM17	TRIM67	Q6ZTA4	755
TRIM17	PML	P29590	741
TRIM17	TRIM33	Q9UPN9	731
TRIM17	TMLHE	Q9NVH6	715
TRIM17	PRY	O14603	694
TRIM17	KCNRG	Q8N5I3	573
TRIM17	TRIM32	Q13049	571

IntAct

42 interactions, top by confidence:

A	B	Type	Score
TRIM39	TRIM17	psi-mi:“MI:0915”(physical association)	0.860
TRIM17	TRIM39	psi-mi:“MI:0915”(physical association)	0.860
HGS	TRIM17	psi-mi:“MI:0915”(physical association)	0.720
TRIM41	TRIM17	psi-mi:“MI:0915”(physical association)	0.670
MEOX2	TRIM17	psi-mi:“MI:0915”(physical association)	0.560
TRIM17	HSP90AB1	psi-mi:“MI:0915”(physical association)	0.400
MLF1	TRIM17	psi-mi:“MI:0915”(physical association)	0.400
HSP90AB1	TRIM17	psi-mi:“MI:0915”(physical association)	0.400
	TRIM17	psi-mi:“MI:0915”(physical association)	0.400
NUDC	TRIM17	psi-mi:“MI:0915”(physical association)	0.400
NUDCD3	TRIM17	psi-mi:“MI:0915”(physical association)	0.400
TRIM17	CACYBP	psi-mi:“MI:0915”(physical association)	0.400
TRIM17	AARSD1	psi-mi:“MI:0915”(physical association)	0.400
TRIM17	UBE2W	psi-mi:“MI:0915”(physical association)	0.370
UBE2D1	TRIM17	psi-mi:“MI:0915”(physical association)	0.370
TRIM17	UBE2D2	psi-mi:“MI:0915”(physical association)	0.370
TRIM17	UBE2D3	psi-mi:“MI:0915”(physical association)	0.370
UBE2H	TRIM17	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (107): TRIM39 (Two-hybrid), TRIM39 (Two-hybrid), TRIM44 (Affinity Capture-MS), SNX2 (Affinity Capture-MS), TRIM17 (Reconstituted Complex), TRIM17 (Reconstituted Complex), TRIM17 (Two-hybrid), BCL2A1 (Affinity Capture-Western), TRIM17 (Affinity Capture-Western), TRIM28 (Affinity Capture-Western), TRIM28 (Co-localization), TRIM17 (Co-fractionation), TRIM17 (Affinity Capture-RNA), TRIM39 (Two-hybrid), TRIM17 (Two-hybrid)

ESM2 similar proteins: A0JN74, A6NCK2, A6NGJ6, A6NI03, B1H278, K7N6K2, O00478, O00481, P14373, P19474, Q13410, Q1ACD5, Q1ACD6, Q1ACD7, Q1ACD8, Q1XHU0, Q2YEM8, Q2YEM9, Q3ZEE5, Q587N6, Q5C8T6, Q5C8T8, Q5C8U1, Q5D7I9, Q5D7J0, Q5D7J1, Q5NCC9, Q5R996, Q62158, Q6MFZ5, Q7YR33, Q7YRV4, Q80V85, Q8BGE7, Q8NG06, Q923T7, Q96BQ3, Q96F44, Q99PP6, Q99PQ2

Diamond homologs: A0JN74, A6NCK2, A6NDI0, A6NGJ6, A6NI03, A6NK02, A6NLI5, B1H278, C9J1S8, K7N6K2, O00635, O15553, O19085, O77666, P0CI25, P0CI26, P14373, P15533, P18892, P19474, Q02084, Q0PF16, Q12899, Q13410, Q1ACD5, Q1ACD6, Q1ACD7, Q1ACD8, Q1XHU0, Q2T9Z0, Q2YEM8, Q2YEM9, Q2YEN0, Q2YEN2, Q3UWZ0, Q3ZEE5, Q495X7, Q587N6, Q587N7, Q58DK8

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
Ub:E2	“up-regulates activity”	TRIM17	ubiquitination
TRIM17	“down-regulates quantity by destabilization”	MCL1	polyubiquitination

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 21 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
Antigen processing: Ubiquitination & Proteasome degradation	9	20.9×	1e-08

GO biological processes:

GO term	Partners	Fold	FDR
protein K48-linked ubiquitination	5	40.1×	1e-05
protein polyubiquitination	7	38.5×	6e-08
ubiquitin-dependent protein catabolic process	5	17.7×	3e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	66
Likely benign	10
Benign	5

Top pathogenic / likely-pathogenic (0)

SpliceAI

833 predictions. Top by Δscore:

Variant	Effect	Δscore
1:228410943:CA:C	donor_loss	1.0000
1:228410944:A:AC	donor_gain	1.0000
1:228410945:C:CC	donor_gain	1.0000
1:228410945:CCTG:C	donor_gain	1.0000
1:228411173:TGCC:T	acceptor_gain	1.0000
1:228411174:GCC:G	acceptor_gain	1.0000
1:228411175:CCC:C	acceptor_gain	1.0000
1:228411177:C:A	acceptor_loss	1.0000
1:228411177:C:CC	acceptor_gain	1.0000
1:228411178:T:C	acceptor_loss	1.0000
1:228411180:C:CT	acceptor_gain	1.0000
1:228411181:A:T	acceptor_gain	1.0000
1:228413792:CCCA:C	donor_loss	1.0000
1:228413793:CCAC:C	donor_loss	1.0000
1:228413794:CACC:C	donor_loss	1.0000
1:228413795:ACC:A	donor_loss	1.0000
1:228413796:CC:C	donor_loss	1.0000
1:228413889:TCAA:T	acceptor_gain	1.0000
1:228413890:CAA:C	acceptor_gain	1.0000
1:228413890:CAAC:C	acceptor_gain	1.0000
1:228413891:AAC:A	acceptor_loss	1.0000
1:228413892:AC:A	acceptor_loss	1.0000
1:228413893:C:CA	acceptor_loss	1.0000
1:228413893:C:CC	acceptor_gain	1.0000
1:228413894:T:A	acceptor_loss	1.0000
1:228414639:CCTAC:C	donor_loss	1.0000
1:228414641:TAC:T	donor_loss	1.0000
1:228414643:CCTTG:C	donor_loss	1.0000
1:228408411:CGGGG:C	acceptor_gain	0.9900
1:228408412:G:T	acceptor_gain	0.9900

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000351108 (1:228412539 T>C), RS1000457459 (1:228411845 C>G,T), RS1000890667 (1:228416903 G>A), RS1001100528 (1:228417410 G>A), RS1001595743 (1:228414446 A>G), RS1001752263 (1:228417944 A>T), RS1001974677 (1:228409855 C>G), RS1001996470 (1:228411651 G>A), RS1002025669 (1:228409490 G>A,C,T), RS1002137909 (1:228415576 CTT>C), RS1002490379 (1:228415797 A>T), RS1002609501 (1:228407680 G>C), RS1002723970 (1:228416418 G>A,C,T), RS1003076069 (1:228410191 G>A), RS1003633626 (1:228418813 A>T)

Disease associations

OMIM: gene MIM:606123 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST006276_1	Non-Richardson’s syndrome vs Richardson’s syndrome in progressive supranuclear palsy	2.000000e-09

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

13 total (human), top 13 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
GSK-J4	decreases expression	1
2-palmitoylglycerol	increases expression	1
rofecoxib	affects expression	1
jinfukang	affects cotreatment, increases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Air Pollutants	increases abundance, increases expression	1
Benzo(a)pyrene	affects methylation, decreases methylation	1
Cadmium	decreases expression	1
Cisplatin	affects cotreatment, increases expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Valproic Acid	increases methylation	1
Particulate Matter	increases abundance, increases expression	1

Clinical trials (associated diseases)

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