TRIM61

Summary

TRIM61 (tripartite motif containing 61, HGNC:24339) is a protein-coding gene on chromosome 4q32.3, encoding Putative tripartite motif-containing protein 61 (Q5EBN2). It is a selective cancer dependency (DepMap: 17.5% of cell lines).

Predicted to enable ubiquitin protein ligase activity. Predicted to be involved in innate immune response and regulation of gene expression. Predicted to be active in cytoplasm.

Source: NCBI Gene 391712 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 41 total
• Cancer dependency (DepMap): dependent in 17.5% of screened cell lines
• MANE Select transcript: NM_001414904

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24339
Approved symbol	TRIM61
Name	tripartite motif containing 61
Location	4q32.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000183439
Ensembl biotype	protein_coding
OMIM	619417
Entrez	391712

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 12 protein_coding

ENST00000329314, ENST00000508856, ENST00000710271, ENST00000902449, ENST00000902450, ENST00000915834, ENST00000915835, ENST00000915836, ENST00000915837, ENST00000915838, ENST00000915839, ENST00000962683

RefSeq mRNA: 2 — MANE Select: NM_001414904 NM_001012414, NM_001414904

CCDS: CCDS34093

Canonical transcript exons

ENST00000710271 — 3 exons

Exon	Start	End
ENSE00001516459	164976688	164976825
ENSE00002020609	164968281	164970339
ENSE00003895351	164977531	164977657

Expression profiles

Bgee: expression breadth ubiquitous, 180 present calls, max score 97.67.

FANTOM5 (CAGE): breadth broad, TPM avg 1.7072 / max 65.0649, expressed in 745 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
54702	1.5716	719
54703	0.0893	22
54701	0.0463	12

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	97.67	gold quality
oocyte	CL:0000023	91.94	gold quality
buccal mucosa cell	CL:0002336	90.82	gold quality
pancreatic ductal cell	CL:0002079	85.84	silver quality
adrenal tissue	UBERON:0018303	85.30	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	82.05	gold quality
tendon of biceps brachii	UBERON:0008188	78.33	gold quality
sperm	CL:0000019	77.21	gold quality
islet of Langerhans	UBERON:0000006	74.66	gold quality
germinal epithelium of ovary	UBERON:0001304	74.19	gold quality
testis	UBERON:0000473	73.99	gold quality
left testis	UBERON:0004533	73.68	gold quality
right testis	UBERON:0004534	73.17	gold quality
right adrenal gland cortex	UBERON:0035827	72.84	gold quality
cortical plate	UBERON:0005343	72.74	gold quality
tibialis anterior	UBERON:0001385	72.62	silver quality
oviduct epithelium	UBERON:0004804	72.59	gold quality
left adrenal gland	UBERON:0001234	72.58	gold quality
ventricular zone	UBERON:0003053	72.58	gold quality
adrenal gland	UBERON:0002369	72.47	gold quality
right adrenal gland	UBERON:0001233	72.39	gold quality
left adrenal gland cortex	UBERON:0035825	72.30	gold quality
parotid gland	UBERON:0001831	72.15	gold quality
adrenal cortex	UBERON:0001235	71.87	gold quality
ganglionic eminence	UBERON:0004023	71.71	gold quality
smooth muscle tissue	UBERON:0001135	70.20	gold quality
pigmented layer of retina	UBERON:0001782	70.06	gold quality
upper arm skin	UBERON:0004263	69.83	gold quality
ovary	UBERON:0000992	69.62	gold quality
deltoid	UBERON:0001476	69.31	silver quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-6819	yes	441.28
E-ANND-3	no	3.76

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

31 targeting TRIM61, 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-190A-3P	100.00	80.35	5520
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-4282	99.99	75.36	6408
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-552-5P	99.93	68.56	1583
HSA-MIR-380-3P	99.89	70.18	1978
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-MIR-1273H-5P	99.77	66.32	2471
HSA-MIR-30B-3P	99.70	65.76	2325
HSA-MIR-3689A-3P	99.70	65.73	2306
HSA-MIR-3689B-3P	99.70	65.71	2311
HSA-MIR-3689C	99.70	65.71	2311
HSA-MIR-6779-5P	99.70	65.76	2363
HSA-MIR-4677-5P	99.70	70.09	1940
HSA-MIR-5580-3P	99.70	69.41	2052
HSA-MIR-4328	99.57	71.06	4094
HSA-MIR-4643	99.49	67.63	1791
HSA-MIR-578	99.46	68.36	1787
HSA-MIR-940	99.37	66.14	2064
HSA-MIR-6808-5P	99.31	66.23	2150
HSA-MIR-6893-5P	99.31	66.25	2119
HSA-MIR-6799-5P	99.14	65.72	2093
HSA-MIR-7977	98.65	66.18	2590
HSA-MIR-10395-3P	98.10	66.70	1726

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 17.5% of screened cell lines.

Cross-species orthologs

1 orthologs

Organism	Symbol	Gene ID
mus_musculus	Trim61	ENSMUSG00000109718

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

Putative tripartite motif-containing protein 61 — Q5EBN2 (reviewed: Q5EBN2)

Alternative names: RING finger protein 35

All UniProt accessions (2): A0A494C0U7, Q5EBN2

RefSeq proteins (2): NP_001012414, NP_001401833* (*=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
IPR050143	TRIM/RBCC	Family

Pfam: PF00643, PF15227

UniProt features (7 total): binding site 4, zinc finger region 2, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5EBN2-F1	85.52	0.68

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; 119; 125

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 19 (showing top): chr4q32, GOBP_DEFENSE_RESPONSE_TO_OTHER_ORGANISM, GOMF_ACYLTRANSFERASE_ACTIVITY, GOMF_AMINOACYLTRANSFERASE_ACTIVITY, GOMF_UBIQUITIN_LIKE_PROTEIN_LIGASE_ACTIVITY, ZWANG_TRANSIENTLY_UP_BY_2ND_EGF_PULSE_ONLY, MIR4328, MIR1185_1_3P_MIR1185_2_3P, LET_7F_2_3P, MIR552_5P, GSE11864_CSF1_VS_CSF1_PAM3CYS_IN_MAC_DN, MIR643, GOBP_BIOLOGICAL_PROCESS_INVOLVED_IN_INTERSPECIES_INTERACTION_BETWEEN_ORGANISMS, GSE18791_UNSTIM_VS_NEWCATSLE_VIRUS_DC_2H_UP, GSE2770_UNTREATED_VS_ACT_CD4_TCELL_48H_UP

GO Biological Process (2): regulation of gene expression (GO:0010468), innate immune response (GO:0045087)

GO Molecular Function (4): zinc ion binding (GO:0008270), ubiquitin protein ligase activity (GO:0061630), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (1): cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
gene expression	1
regulation of macromolecule biosynthetic process	1
immune response	1
defense response to symbiont	1
transition metal ion binding	1
ubiquitin-protein transferase activity	1
ubiquitin-like protein ligase activity	1
binding	1
cation binding	1
intracellular anatomical structure	1
cellular anatomical structure	1

Protein interactions and networks

STRING

312 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TRIM61	ZNF558	Q96NG5	644
TRIM61	ZNF701	Q9NV72	440
TRIM61	Q6GMV1	Q6GMV1	419
TRIM61	RNF207	Q6ZRF8	384
TRIM61	TRIM36	Q9NQ86	382
TRIM61	ANKRD7	Q92527	377
TRIM61	BBOX1	O75936	373
TRIM61	DQX1	Q8TE96	372
TRIM61	RFPL4A	A6NLU0	370
TRIM61	TRIM9	Q9C026	366
TRIM61	ZNF418	Q8TF45	354
TRIM61	OOSP1	A8MZH6	349
TRIM61	TRIM56	Q9BRZ2	348
TRIM61	TRIM44	Q96DX7	346
TRIM61	DCAF4L2	Q8NA75	323

IntAct

2 interactions, top by confidence:

A	B	Type	Score
TRIM61	VXN	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (1): C8orf46 (Affinity Capture-MS)

ESM2 similar proteins: A0A140LIF8, A1Z198, A6NK02, D4ABM4, F8VTS6, P15533, P59045, P59047, P62603, P86448, P86449, Q0GKD5, Q2LKU9, Q2LKV2, Q2LKV5, Q2LKW6, Q309B1, Q3TL54, Q3UWZ0, Q495X7, Q5BK82, Q5D7I6, Q5EBN2, Q5SZ99, Q66X01, Q66X03, Q66X05, Q66X22, Q6AYC2, Q6AZZ1, Q6B966, Q6ZWI9, Q80X56, Q86W25, Q86W28, Q86WT6, Q8BU40, Q8BVP1, Q8C6J9, Q8CCN1

Diamond homologs: A0A3B3IT33, A6NCK2, A6NDI0, A6NGJ6, A6NI03, A6NLI5, B0BLU1, C9J1S8, I1YAP6, O00478, O00481, O15344, O75677, O75678, O75679, O76064, P0CI25, P0CI26, P18892, P19474, P62603, P86448, P86449, Q13410, Q2HJ46, Q3C1V9, Q3TL54, Q4KLN8, Q5EBN2, Q5PQN2, Q5R4I2, Q5R996, Q61510, Q62556, Q6INS5, Q6MFY8, Q6UX41, Q6UXE8, Q6ZWI9, Q7T308

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
Ub:E2	“up-regulates activity”	TRIM61	ubiquitination

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	36
Likely benign	0
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

992 predictions. Top by Δscore:

Variant	Effect	Δscore
4:164976821:CTATG:C	acceptor_gain	1.0000
4:164957385:A:T	acceptor_gain	0.9900
4:164957384:C:CT	acceptor_gain	0.9800
4:164977525:GCTCA:G	donor_loss	0.9800
4:164977526:CTCAC:C	donor_loss	0.9800
4:164977527:TCA:T	donor_loss	0.9800
4:164977528:CACCT:C	donor_loss	0.9800
4:164977529:A:AG	donor_loss	0.9800
4:164977631:T:TA	donor_gain	0.9800
4:164976826:C:CC	acceptor_gain	0.9700
4:164976828:T:C	acceptor_gain	0.9700
4:164976823:ATGCT:A	acceptor_loss	0.9600
4:164976825:GCT:G	acceptor_loss	0.9600
4:164976826:C:A	acceptor_loss	0.9600
4:164976827:T:C	acceptor_gain	0.9600
4:164976827:T:G	acceptor_loss	0.9600
4:164976828:T:TC	acceptor_gain	0.9600
4:164957618:C:CT	donor_gain	0.9500
4:164957619:T:TT	donor_gain	0.9500
4:164976681:ATCTT:A	donor_loss	0.9500
4:164976682:TCTTA:T	donor_loss	0.9500
4:164976683:CTTAC:C	donor_loss	0.9500
4:164976684:TTACC:T	donor_loss	0.9500
4:164976685:T:TA	donor_loss	0.9500
4:164976686:A:G	donor_loss	0.9500
4:164976687:C:CA	donor_loss	0.9500
4:164976838:C:CT	acceptor_loss	0.9500
4:164976839:A:T	acceptor_loss	0.9500
4:164977484:T:TA	donor_gain	0.9500
4:164976822:TATG:T	acceptor_gain	0.9400

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000040597 (4:164967309 A>G), RS1000132797 (4:164955558 G>A,C,T), RS10001548 (4:164958229 T>C), RS1000251678 (4:164975542 T>C), RS1000256225 (4:164955829 C>T), RS1000311874 (4:164962065 ATTATC>A), RS1000411352 (4:164968720 G>A), RS10004751 (4:164968219 G>C), RS1000663813 (4:164962377 T>C), RS1000776480 (4:164955223 G>A), RS10007789 (4:164969225 C>G,T), RS1000821539 (4:164962058 T>C), RS1000914836 (4:164976371 G>C), RS1001320540 (4:164973541 A>G), RS1001375441 (4:164967808 T>C)

Disease associations

OMIM: gene MIM:619417 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST007830_1	Anti-thyroid peroxidase (TPOAb) levels in Hashimoto’s thyroiditis	5.000000e-07
GCST007851_1	Anti-thyroid peroxidase (TPOAb) and anti-thyroglobulin (TgAb) levels in Hashimoto’s thyroiditis	7.000000e-07

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

9 total (human), top 9 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases methylation, affects cotreatment, decreases expression	2
jinfukang	affects cotreatment, decreases expression	1
Amiodarone	increases expression	1
Benzo(a)pyrene	decreases methylation	1
Cisplatin	affects cotreatment, decreases expression	1
Hydralazine	affects cotreatment, decreases expression	1
Methyl Methanesulfonate	increases expression	1
Tunicamycin	increases expression	1
Okadaic Acid	decreases expression	1

Clinical trials (associated diseases)

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