TRIML2

Summary

TRIML2 (tripartite motif family like 2, HGNC:26378) is a protein-coding gene on chromosome 4q35.2, encoding Probable E3 ubiquitin-protein ligase TRIML2 (Q8N7C3).

This gene encodes a member of the tri-partite motif (TRIM) family of proteins. This protein may be regulated by the tumor suppressor p53 and may regulate p53 through the enhancement of p53 SUMOylation. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 205860 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 70 total — 1 pathogenic
• MANE Select transcript: NM_173553

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26378
Approved symbol	TRIML2
Name	tripartite motif family like 2
Location	4q35.2
Locus type	gene with protein product
Status	Approved
Aliases	FLJ25801, SPRYD6
Ensembl gene	ENSG00000179046
Ensembl biotype	protein_coding
OMIM	620480
Entrez	205860

Gene structure

Transcript identifiers

Ensembl transcripts: 13 — 8 protein_coding, 2 protein_coding_CDS_not_defined, 2 nonsense_mediated_decay, 1 retained_intron

ENST00000326754, ENST00000394461, ENST00000502707, ENST00000503141, ENST00000503475, ENST00000511771, ENST00000512729, ENST00000682553, ENST00000913513, ENST00000913514, ENST00000913515, ENST00000913516, ENST00000913517

RefSeq mRNA: 2 — MANE Select: NM_173553 NM_001303419, NM_173553

CCDS: CCDS3850

Canonical transcript exons

ENST00000682553 — 8 exons

Exon	Start	End
ENSE00001269257	188097324	188097346
ENSE00001269263	188099035	188099175
ENSE00002083623	188109243	188109603
ENSE00003527571	188097061	188097161
ENSE00003561786	188104837	188104932
ENSE00003636658	188101056	188101250
ENSE00003916489	188091272	188091941
ENSE00003920679	188105180	188105590

Expression profiles

Bgee: expression breadth ubiquitous, 111 present calls, max score 83.65.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.2590 / max 68.7233, expressed in 86 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
55403	0.2298	80
55402	0.0231	10
55401	0.0061	1

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	83.65	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	83.46	gold quality
right testis	UBERON:0004534	70.12	gold quality
parotid gland	UBERON:0001831	70.10	gold quality
trabecular bone tissue	UBERON:0002483	68.58	gold quality
left testis	UBERON:0004533	68.28	gold quality
testis	UBERON:0000473	67.53	gold quality
vena cava	UBERON:0004087	61.28	silver quality
placenta	UBERON:0001987	58.61	gold quality
nasal cavity epithelium	UBERON:0005384	58.54	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	58.37	gold quality
decidua	UBERON:0002450	57.14	gold quality
myocardium	UBERON:0002349	54.45	gold quality
heart right ventricle	UBERON:0002080	54.22	gold quality
stromal cell of endometrium	CL:0002255	53.32	silver quality
putamen	UBERON:0001874	53.05	gold quality
buccal mucosa cell	CL:0002336	52.88	gold quality
blood	UBERON:0000178	52.61	gold quality
nucleus accumbens	UBERON:0001882	52.52	gold quality
lower lobe of lung	UBERON:0008949	52.29	silver quality
caudate nucleus	UBERON:0001873	51.94	gold quality
monocyte	CL:0000576	51.32	gold quality
mucosa of transverse colon	UBERON:0004991	51.29	gold quality
leukocyte	CL:0000738	50.61	gold quality
medial globus pallidus	UBERON:0002477	49.71	gold quality
Brodmann (1909) area 9	UBERON:0013540	48.50	gold quality
globus pallidus	UBERON:0001875	47.57	gold quality
biceps brachii	UBERON:0001507	47.43	gold quality
adrenal tissue	UBERON:0018303	47.37	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	47.30	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-9388	yes	131.73
E-ANND-3	yes	4.25

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

4 targeting TRIML2, 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-515-5P	99.92	69.82	2343
HSA-MIR-519E-5P	99.92	69.62	2358
HSA-MIR-7978	99.86	66.90	856
HSA-MIR-1290	99.59	69.90	2079

Literature-anchored findings (GeneRIF, showing 4)

• Data indicate that TRIML2 is part of a feed-forward loop that activates p53 in cells expressing the R72 variant, particularly after prolonged stress. (PMID:25256710)
• Findings indicate that the C allele of two single nucleotide polymorphisms in the tripartite motif family-like 2 (TRIML2) gene was associated with an increased risk of Alzheimer disease (AD). These results suggest that TRIML2 may contribute to AD susceptibility. (PMID:27471163)
• the degradation of STAT6 is induced and required for the lytic activation of human herpesviruses and is association with the increased ubiquitylated form of TRIML2 (PMID:30532138)
• Eutherian-Specific Gene TRIML2 Attenuates Inflammation in the Evolution of Placentation. (PMID:31633784)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Triml2	ENSMUSG00000091490
rattus_norvegicus	Triml2	ENSRNOG00000028299

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

Probable E3 ubiquitin-protein ligase TRIML2 — Q8N7C3 (reviewed: Q8N7C3)

Alternative names: RING-type E3 ubiquitin transferase TRIML2, SPRY domain-containing protein 6, Tripartite motif family-like protein 2

All UniProt accessions (4): Q8N7C3, A0A804HJA0, J3KNI5, Q6T5J5

UniProt curated annotations — full annotation on UniProt →

Pathway. Protein modification; protein ubiquitination.

Isoforms (2)

UniProt ID	Names	Canonical?
Q8N7C3-1	1	yes
Q8N7C3-2	2

RefSeq proteins (2): NP_001290348, NP_775824* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000315	Znf_B-box	Domain
IPR001870	B30.2/SPRY	Domain
IPR003877	SPRY_dom	Domain
IPR003879	Butyrophylin_SPRY	Domain
IPR006574	PRY	Domain
IPR013320	ConA-like_dom_sf	Homologous_superfamily
IPR043136	B30.2/SPRY_sf	Homologous_superfamily
IPR050143	TRIM/RBCC	Family

Pfam: PF00622, PF00643, PF13765

UniProt features (10 total): binding site 4, splice variant 2, chain 1, domain 1, zinc finger region 1, coiled-coil region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8N7C3-F1	86.66	0.67

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): 19; 22; 41; 47

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 32 (showing top): GOBP_DEFENSE_RESPONSE_TO_OTHER_ORGANISM, ROZANOV_MMP14_TARGETS_UP, chr4q35, GOBP_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, GOBP_POST_TRANSLATIONAL_PROTEIN_MODIFICATION, GOBP_RESPONSE_TO_LIPID, SENESE_HDAC1_TARGETS_UP, GOBP_RESPONSE_TO_RETINOIC_ACID, ACEVEDO_METHYLATED_IN_LIVER_CANCER_DN, GOMF_ACYLTRANSFERASE_ACTIVITY, GOMF_AMINOACYLTRANSFERASE_ACTIVITY, GOMF_UBIQUITIN_LIKE_PROTEIN_LIGASE_ACTIVITY, GSE13762_CTRL_VS_125_VITAMIND_DAY12_DC_UP, SENESE_HDAC1_AND_HDAC2_TARGETS_UP, ZWANG_TRANSIENTLY_UP_BY_2ND_EGF_PULSE_ONLY

GO Biological Process (3): protein ubiquitination (GO:0016567), response to retinoic acid (GO:0032526), innate immune response (GO:0045087)

GO Molecular Function (6): zinc ion binding (GO:0008270), identical protein binding (GO:0042802), ubiquitin protein ligase activity (GO:0061630), protein binding (GO:0005515), transferase activity (GO:0016740), 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
protein modification by small protein conjugation	1
response to lipid	1
response to oxygen-containing compound	1
immune response	1
defense response to symbiont	1
transition metal ion binding	1
protein binding	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

Protein interactions and networks

STRING

568 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TRIML2	FRG1	Q14331	513
TRIML2	ZFP42	Q96MM3	479
TRIML2	SWT1	Q5T5J6	476
TRIML2	BBOX1	O75936	475
TRIML2	PHTF1	Q9UMS5	457
TRIML2	DMRTB1	Q96MA1	443
TRIML2	FAM149A	A5PLN7	440
TRIML2	FMR1NB	Q8N0W7	432
TRIML2	TRIM69	Q86WT6	413
TRIML2	TRIM15	Q9C019	405
TRIML2	MAGEB17	A8MXT2	394
TRIML2	FRG2	Q64ET8	393
TRIML2	TRAT1	Q6PIZ9	392
TRIML2	TRIM7	Q9C029	379
TRIML2	MTNR1A	P48039	379

IntAct

157 interactions, top by confidence:

A	B	Type	Score
ZBTB33	TRIML2	psi-mi:“MI:0915”(physical association)	0.800
CCDC92	TRIML2	psi-mi:“MI:0915”(physical association)	0.740
BLOC1S2	TRIML2	psi-mi:“MI:0915”(physical association)	0.740
NECAB2	TRIML2	psi-mi:“MI:0915”(physical association)	0.600
TRIML2	FAM9C	psi-mi:“MI:0915”(physical association)	0.560
ZFHX3	TRIML2	psi-mi:“MI:0915”(physical association)	0.560
KRT34	TRIML2	psi-mi:“MI:0915”(physical association)	0.560
KRT75	TRIML2	psi-mi:“MI:0915”(physical association)	0.560
ZBED1	TRIML2	psi-mi:“MI:0915”(physical association)	0.560
CDR2	TRIML2	psi-mi:“MI:0915”(physical association)	0.560
TBC1D25	TRIML2	psi-mi:“MI:0915”(physical association)	0.560
TRIML2	TRIM54	psi-mi:“MI:0915”(physical association)	0.560
TRIML2	POLR1H	psi-mi:“MI:0915”(physical association)	0.560
KRT15	TRIML2	psi-mi:“MI:0915”(physical association)	0.560
MEOX1	TRIML2	psi-mi:“MI:0915”(physical association)	0.560
TRIML2	TFIP11	psi-mi:“MI:0915”(physical association)	0.560
KRT27	TRIML2	psi-mi:“MI:0915”(physical association)	0.560
TRIML2	STN1	psi-mi:“MI:0915”(physical association)	0.560
KRT38	TRIML2	psi-mi:“MI:0915”(physical association)	0.560
USHBP1	TRIML2	psi-mi:“MI:0915”(physical association)	0.560
KRT24	TRIML2	psi-mi:“MI:0915”(physical association)	0.560
TCF4	TRIML2	psi-mi:“MI:0915”(physical association)	0.560
POU6F2	TRIML2	psi-mi:“MI:0915”(physical association)	0.560
MEOX2	TRIML2	psi-mi:“MI:0915”(physical association)	0.560
EIF2B1	TRIML2	psi-mi:“MI:0915”(physical association)	0.560
HGS	TRIML2	psi-mi:“MI:0915”(physical association)	0.560
KRT31	TRIML2	psi-mi:“MI:0915”(physical association)	0.560
TRIML2	MBD3L2	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (81): TRIML2 (Reconstituted Complex), TRIML2 (Affinity Capture-MS), TRIML2 (Affinity Capture-MS), MTM1 (Affinity Capture-MS), CCDC92 (Affinity Capture-MS), LOH12CR1 (Affinity Capture-MS), ZBTB33 (Affinity Capture-MS), SPEN (Affinity Capture-MS), SRGAP2 (Affinity Capture-MS), KXD1 (Affinity Capture-MS), BLOC1S2 (Affinity Capture-MS), PML (Affinity Capture-MS), STIP1 (Affinity Capture-MS), SIKE1 (Affinity Capture-MS), DTNBP1 (Affinity Capture-MS)

ESM2 similar proteins: A0JPQ4, E1BD59, O15197, P0C0K6, P62603, Q14142, Q1XH17, Q1XH18, Q3UWZ0, Q5BK82, Q5JZY3, Q5M929, Q5NCC3, Q5RBG2, Q5RKG6, Q5TM55, Q5W0U4, Q640S6, Q6P6S3, Q6PGR9, Q6PJ69, Q6ZMU5, Q7TPM3, Q7YR32, Q80VI1, Q80X56, Q80YW5, Q810I1, Q810I2, Q865W2, Q86UV6, Q86UV7, Q86XT4, Q8BFW4, Q8BVW3, Q8BYG9, Q8C006, Q8C0E3, Q8IUD6, Q8K243

Diamond homologs: A0A2P1BRP3, A0A2P1BRQ0, A0JN74, A0ZSK3, A0ZSK4, B1H278, O19085, O95361, P14373, P19474, Q02084, Q1XHU0, Q309B1, Q5R760, Q5R7W8, Q62158, Q62556, Q7KYR7, Q86WT6, Q8N7C3, Q8WVV5, Q91431, Q91453, Q96F44, Q98989, Q98993, Q99PP9, Q99PQ2, Q9C029, Q9HCM9, Q9JLN5, A0A0E4BZH1, A4QPC6, A6NGJ6, A6NI03, A6NK02, A6NLU0, A7TZE6, A7TZF0, A7TZF3

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 54 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
Formation of the cornified envelope	7	18.1×	2e-05
Keratinization	7	11.5×	2e-04

GO biological processes:

GO term	Partners	Fold	FDR
morphogenesis of an epithelium	6	43.0×	7e-07
intermediate filament organization	7	35.1×	3e-07
epithelial cell differentiation	6	21.9×	3e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	56
Likely benign	10
Benign	3

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
563016	GRCh37/hg19 4q35.2(chr4:188478516-190957473)x1	Pathogenic

SpliceAI

1330 predictions. Top by Δscore:

Variant	Effect	Δscore
4:188097060:CT:C	donor_gain	1.0000
4:188101258:A:C	acceptor_gain	1.0000
4:188101287:A:C	acceptor_gain	1.0000
4:188104831:A:AC	donor_gain	1.0000
4:188104832:C:CC	donor_gain	1.0000
4:188104832:CTGA:C	donor_gain	1.0000
4:188105178:AC:A	donor_gain	1.0000
4:188105179:CC:C	donor_gain	1.0000
4:188095873:C:CT	donor_gain	0.9900
4:188095873:CTA:C	donor_gain	0.9900
4:188095874:T:TT	donor_gain	0.9900
4:188095877:TGA:T	donor_gain	0.9900
4:188097059:A:AC	donor_gain	0.9900
4:188097060:C:CC	donor_gain	0.9900
4:188099174:CT:C	acceptor_gain	0.9900
4:188099176:C:CC	acceptor_gain	0.9900
4:188101254:CCTCA:C	acceptor_gain	0.9900
4:188101257:C:CT	acceptor_gain	0.9900
4:188101274:C:CC	acceptor_gain	0.9900
4:188104835:A:T	donor_loss	0.9900
4:188104836:CC:C	donor_loss	0.9900
4:188104930:CTT:C	acceptor_gain	0.9900
4:188105175:CTTA:C	donor_loss	0.9900
4:188105176:TTAC:T	donor_loss	0.9900
4:188105177:TACCC:T	donor_loss	0.9900
4:188105455:T:TA	donor_gain	0.9900
4:188095875:A:AC	donor_gain	0.9800
4:188095876:C:CC	donor_gain	0.9800
4:188095877:TGATA:T	donor_gain	0.9800
4:188101260:A:C	acceptor_gain	0.9800

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000222836 (4:188105260 G>A), RS1000283970 (4:188095240 CA>C), RS1000369986 (4:188100471 C>A), RS10004012 (4:188097459 A>G), RS10004783 (4:188096309 T>C), RS1000493878 (4:188095163 A>C), RS1000775055 (4:188100552 C>G), RS1000854579 (4:188105080 A>G), RS1000862299 (4:188110484 G>A), RS1000926120 (4:188104640 G>A,T), RS10009881 (4:188102843 T>A,C,G), RS1000997475 (4:188095502 T>C), RS10009988 (4:188103019 T>G), RS1001123875 (4:188100448 C>T), RS1001139602 (4:188109467 G>A,C)

Disease associations

OMIM: gene MIM:620480 | 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
GCST002741_2	Polycystic ovary syndrome	6.000000e-06
GCST009391_1296	Metabolite levels	3.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0010549	xanthosine measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

28 total (human), top 28 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases expression	2
entinostat	increases expression, affects cotreatment	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Cadmium Chloride	decreases expression, increases expression	2
perfluorooctane sulfonic acid	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
perfluorohexanesulfonic acid	increases expression	1
abrine	increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
(4-amino-1,4-dihydro-3-(2-pyridyl)-5-thioxo-1,2,4-triazole)copper(II)	increases expression	1
(+)-JQ1 compound	decreases expression	1
PCI 5002	affects cotreatment, increases expression	1
2,3,5-trichloro-6-phenyl-(1,4)benzoquinone	decreases expression	1
Bortezomib	increases expression, increases response to substance	1
Temozolomide	decreases expression	1
Air Pollutants	increases expression	1
Benzo(a)pyrene	decreases methylation	1
Cannabidiol	increases expression	1
Dichlorodiphenyl Dichloroethylene	decreases expression	1
Diethylhexyl Phthalate	increases expression	1
Estradiol	affects cotreatment, increases expression	1
Mustard Gas	increases expression	1
Silicon Dioxide	increases expression	1
Tobacco Smoke Pollution	increases expression	1
Triclosan	decreases expression	1
Zinc	affects cotreatment, increases expression	1
Aflatoxin B1	increases expression	1
Asbestos, Crocidolite	increases expression	1

Clinical trials (associated diseases)

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