TRIM48

Summary

TRIM48 (tripartite motif containing 48, HGNC:19021) is a protein-coding gene on chromosome 11q11, encoding E3 ubiquitin-protein ligase TRIM48 (Q8IWZ4). E3 ubiquitin-protein ligase which promotes K48-linked polyubiquitination of protein methyltransferase PRMT1, leading to PRMT1 degradation.

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

Source: NCBI Gene 79097 — RefSeq curated summary.

At a glance

• GWAS associations: 11
• Clinical variants (ClinVar): 54 total
• MANE Select transcript: NM_024114

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:19021
Approved symbol	TRIM48
Name	tripartite motif containing 48
Location	11q11
Locus type	gene with protein product
Status	Approved
Aliases	RNF101
Ensembl gene	ENSG00000150244
Ensembl biotype	protein_coding
Entrez	79097

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000417545

RefSeq mRNA: 1 — MANE Select: NM_024114 NM_024114

CCDS: CCDS7947

Canonical transcript exons

ENST00000417545 — 6 exons

Exon	Start	End
ENSE00002210606	55262155	55262311
ENSE00002439381	55264900	55265314
ENSE00002458459	55268350	55268372
ENSE00002467148	55269242	55269339
ENSE00002490598	55270437	55271114
ENSE00002513438	55265600	55265695

Expression profiles

Bgee: expression breadth tissue_specific, 3 present calls, max score 37.20.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0139 / max 18.1310, expressed in 3 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
114246	0.0139	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
colonic epithelium	UBERON:0000397	37.20	gold quality
sural nerve	UBERON:0015488	36.58	gold quality
ventricular zone	UBERON:0003053	36.48	gold quality
cortical plate	UBERON:0005343	36.47	gold quality
apex of heart	UBERON:0002098	36.26	gold quality
bone marrow cell	CL:0002092	36.16	gold quality
ganglionic eminence	UBERON:0004023	35.49	gold quality
skeletal muscle tissue	UBERON:0001134	33.38	gold quality
muscle tissue	UBERON:0002385	32.41	gold quality
hindlimb stylopod muscle	UBERON:0004252	32.15	gold quality
bone marrow	UBERON:0002371	31.74	gold quality
stromal cell of endometrium	CL:0002255	29.87	gold quality
prefrontal cortex	UBERON:0000451	29.21	gold quality
skin of leg	UBERON:0001511	28.73	gold quality
smooth muscle tissue	UBERON:0001135	28.60	silver quality
duodenum	UBERON:0002114	28.14	gold quality
liver	UBERON:0002107	28.04	gold quality
urinary bladder	UBERON:0001255	27.70	gold quality
lymph node	UBERON:0000029	27.57	gold quality
tonsil	UBERON:0002372	27.05	gold quality
islet of Langerhans	UBERON:0000006	26.55	gold quality
vermiform appendix	UBERON:0001154	26.42	gold quality
leukocyte	CL:0000738	26.15	gold quality
monocyte	CL:0000576	26.00	gold quality
blood	UBERON:0000178	26.00	gold quality
gall bladder	UBERON:0002110	25.98	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	25.89	gold quality
placenta	UBERON:0001987	25.81	gold quality
zone of skin	UBERON:0000014	25.79	gold quality
muscle of leg	UBERON:0001383	25.12	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.28

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

52 targeting TRIM48, 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-188-3P	100.00	68.76	1240
HSA-MIR-4776-3P	100.00	68.73	1340
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-6499-3P	99.90	66.38	1212
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-6875-3P	99.82	70.26	2983
HSA-MIR-204-5P	99.79	71.62	2439
HSA-MIR-211-5P	99.79	71.65	2440
HSA-MIR-3150A-3P	99.76	64.44	1640
HSA-MIR-6763-5P	99.76	64.68	1767
HSA-MIR-10393-3P	99.72	66.56	961
HSA-MIR-6801-5P	99.72	66.50	981
HSA-MIR-802	99.61	67.70	1254
HSA-MIR-6861-3P	99.60	68.46	444
HSA-MIR-4762-5P	99.57	68.54	1424
HSA-MIR-1252-3P	99.55	67.71	2862
HSA-MIR-105-5P	99.54	69.24	2060
HSA-MIR-7853-5P	99.54	69.30	2055
HSA-MIR-122B-5P	99.46	70.81	1457
HSA-MIR-4762-3P	99.43	69.72	2363
HSA-MIR-3678-3P	99.31	67.10	1432
HSA-MIR-593-3P	99.22	67.28	1327
HSA-MIR-361-3P	99.19	66.45	1381
HSA-MIR-10399-5P	99.17	69.87	2610
HSA-MIR-6504-3P	99.17	69.31	2891
HSA-MIR-4784	99.15	67.41	1733
HSA-MIR-323B-3P	99.14	68.89	725
HSA-MIR-7854-3P	99.08	66.26	1117

Literature-anchored findings (GeneRIF, showing 1)

• TRIM48 Promotes ASK1 Activation and Cell Death through Ubiquitination-Dependent Degradation of the ASK1-Negative Regulator PRMT1 (PMID:29186683)

Cross-species orthologs

0 orthologs

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), TRIM36 (ENSG00000152503), TRIM11 (ENSG00000154370), TRIM74 (ENSG00000155428), TRIM42 (ENSG00000155890), TRIM63 (ENSG00000158022)

Protein

Protein identifiers

E3 ubiquitin-protein ligase TRIM48 — Q8IWZ4 (reviewed: Q8IWZ4)

Alternative names: RING finger protein 101, Tripartite motif-containing protein 48

All UniProt accessions (1): Q8IWZ4

UniProt curated annotations — full annotation on UniProt →

Function. E3 ubiquitin-protein ligase which promotes K48-linked polyubiquitination of protein methyltransferase PRMT1, leading to PRMT1 degradation. This suppresses methylation of the PRMT1 substrate MAP3K5/ASK1, promoting its activation and increasing MAP3K5-dependent cell death induced by oxidative stress. TRIM48-mediated ubiquitination of PRMT1 also suppresses methylation of FOXO1 by PRMT1, leading to inhibition of FOXO1 transcriptional activity. Additionally, it inhibits RIG-I-mediated antiviral signaling, functioning as an inducible negative feedback regulator of this pathway.

Subunit / interactions. Interacts with PRMT1; the interaction leads to ubiquitination of PRMT1 by TRIM48. Interacts with MAP3K5. Interacts with STRAP.

Subcellular location. Cytoplasm. Cytosol.

Induction. Upon RIG-I/DDX58 stimulation.

Similarity. Belongs to the TRIM/RBCC family.

RefSeq proteins (1): NP_077019* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000315	Znf_B-box	Domain
IPR001841	Znf_RING	Domain
IPR013083	Znf_RING/FYVE/PHD	Homologous_superfamily
IPR050143	TRIM/RBCC	Family

Pfam: PF00643, PF15227

UniProt features (8 total): binding site 4, zinc finger region 2, chain 1, mutagenesis site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8IWZ4-F1	81.33	0.37

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): 109; 112; 131; 137

Mutagenesis-validated functional residues (1):

Position	Phenotype
46	abolishes prmt1 ubiquitination and map3k5 activation.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-877300	Interferon gamma signaling

MSigDB gene sets: 50 (showing top): REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, MODULE_255, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, MODULE_317, IVANOVA_HEMATOPOIESIS_MATURE_CELL, GOBP_DEFENSE_RESPONSE_TO_OTHER_ORGANISM, GOBP_PROTEASOMAL_PROTEIN_CATABOLIC_PROCESS, GOBP_PROTEIN_CATABOLIC_PROCESS, MODULE_69, GOBP_PROTEOLYSIS, GOMF_ACYLTRANSFERASE_ACTIVITY, GOMF_AMINOACYLTRANSFERASE_ACTIVITY, GOMF_UBIQUITIN_LIKE_PROTEIN_LIGASE_ACTIVITY, MOREAUX_MULTIPLE_MYELOMA_BY_TACI_UP, KRAS.600_UP.V1_DN

GO Biological Process (3): regulation of gene expression (GO:0010468), proteasome-mediated ubiquitin-dependent protein catabolic process (GO:0043161), innate immune response (GO:0045087)

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 (2): cytoplasm (GO:0005737), cytosol (GO:0005829)

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
cellular anatomical structure	2
gene expression	1
regulation of macromolecule biosynthetic process	1
ubiquitin-dependent protein catabolic process	1
proteasomal protein catabolic 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
catalytic activity	1
cation binding	1
intracellular anatomical structure	1
cytoplasm	1

Protein interactions and networks

STRING

338 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TRIM48	PRAMEF13	Q5VWM6	505
TRIM48	OR8J3	Q8NGG0	505
TRIM48	PRAMEF1	O95521	480
TRIM48	PRAMEF11	O60813	480
TRIM48	KHDC1L	Q5JSQ8	479
TRIM48	OR5F1	O95221	476
TRIM48	RFPL2	O75678	471
TRIM48	OR5D16	Q8NGK9	469
TRIM48	OR4A15	Q8NGL6	448
TRIM48	OR8I2	Q8N0Y5	447
TRIM48	OR5T2	Q8NGG2	447
TRIM48	OR5D14	Q8NGL3	447
TRIM48	OR8H2	Q8N162	447
TRIM48	KBTBD3	Q8NAB2	445
TRIM48	OR5AS1	Q8N127	436

IntAct

4 interactions, top by confidence:

A	B	Type	Score
TRIM48	NME7	psi-mi:“MI:0915”(physical association)	0.560
NME7	TRIM48	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (5): PRMT1 (Affinity Capture-Western), PRMT1 (Biochemical Activity), TRIM48 (Two-hybrid), TRIM48 (Co-localization), TRIM48 (Affinity Capture-Western)

ESM2 similar proteins: A0A3B3IT33, A6NCK2, A6NDI0, A6NGJ6, A6NI03, A6NLI5, C9J1S8, I1YAP6, K7N6K2, P0CI25, P0CI26, P86449, Q0PF16, Q1ACD5, Q1ACD6, Q1ACD7, Q1ACD8, Q2YEM8, Q2YEM9, Q2YEN0, Q2YEN2, Q3ZEE5, Q587N6, Q587N7, Q5BN31, Q5C8T6, Q5C8T8, Q5C8U1, Q5C8U3, Q5C8U4, Q5D7H7, Q5D7H8, Q5D7I0, Q5D7I1, Q5D7I2, Q5D7I3, Q5D7I5, Q5D7I6, Q5D7I9, Q5D7J0

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”	TRIM48	ubiquitination

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	51
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

710 predictions. Top by Δscore:

Variant	Effect	Δscore
11:55262308:AGCGG:A	donor_loss	1.0000
11:55262309:GCG:G	donor_gain	1.0000
11:55262310:CGGT:C	donor_loss	1.0000
11:55262312:G:GG	donor_gain	1.0000
11:55268344:TTACA:T	acceptor_loss	1.0000
11:55268345:TACA:T	acceptor_loss	1.0000
11:55268346:ACAGG:A	acceptor_loss	1.0000
11:55268347:CAGGC:C	acceptor_loss	1.0000
11:55268348:A:AC	acceptor_loss	1.0000
11:55268348:A:AG	acceptor_gain	1.0000
11:55268349:G:GA	acceptor_gain	1.0000
11:55268349:G:T	acceptor_loss	1.0000
11:55268373:G:GA	donor_loss	1.0000
11:55268373:G:GG	donor_gain	1.0000
11:55268374:T:A	donor_loss	1.0000
11:55269238:GCA:G	acceptor_loss	1.0000
11:55269240:A:AG	acceptor_gain	1.0000
11:55269240:A:AT	acceptor_loss	1.0000
11:55269241:G:GA	acceptor_gain	1.0000
11:55269241:GGA:G	acceptor_gain	1.0000
11:55269241:GGAGT:G	acceptor_gain	1.0000
11:55269336:TGAGG:T	donor_loss	1.0000
11:55269337:GAG:G	donor_gain	1.0000
11:55269338:AG:A	donor_gain	1.0000
11:55269338:AGG:A	donor_loss	1.0000
11:55269339:GG:G	donor_gain	1.0000
11:55269340:G:GG	donor_gain	1.0000
11:55269341:T:G	donor_loss	1.0000
11:55270435:A:AG	acceptor_gain	1.0000
11:55270435:AGT:A	acceptor_gain	1.0000

AlphaMissense

1499 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000011305 (11:55266266 A>C,G,T), RS1000131100 (11:55263435 T>C), RS1000160530 (11:55263576 C>T), RS1000334849 (11:55268410 C>G,T), RS1000487384 (11:55262857 A>T), RS1000612077 (11:55267653 T>A,C,G), RS1000687004 (11:55268650 G>A), RS1000767392 (11:55271487 T>A), RS1001291713 (11:55269689 T>C), RS1001742986 (11:55269463 A>G), RS1002903231 (11:55260827 C>G,T), RS1003500198 (11:55261682 C>T), RS1003506443 (11:55266000 TG>T), RS1003609812 (11:55265399 A>C,T), RS1003681643 (11:55270363 T>C,G)

Disease associations

OMIM: gene `` | 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
GCST005580_137	Intraocular pressure	7.000000e-13
GCST006624_128	Systolic blood pressure	1.000000e-16
GCST006947_12	Feeling fed-up	2.000000e-09
GCST008163_606	Height	8.000000e-06
GCST009733_166	Urinary metabolite levels in chronic kidney disease	1.000000e-73
GCST010241_199	Apolipoprotein A1 levels	4.000000e-25
GCST010242_531	HDL cholesterol levels	7.000000e-47
GCST010244_112	Triglyceride levels	8.000000e-09
GCST012020_180	Serum metabolite levels	7.000000e-55
GCST012020_208	Serum metabolite levels	2.000000e-50
GCST012021_105	Serum metabolite levels	7.000000e-55

EFO canonical traits (7, from GWAS)

EFO ID	Trait name
EFO:0004695	intraocular pressure measurement
EFO:0006335	systolic blood pressure
EFO:0009588	feeling “fed-up” measurement
EFO:0005116	urinary metabolite measurement
EFO:0004614	apolipoprotein A 1 measurement
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0004530	triglyceride measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

7 total (human), top 7 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases methylation, decreases expression	2
perfluorooctanoic acid	decreases expression	1
Acetaminophen	decreases expression	1
Calcitriol	increases expression, affects cotreatment	1
Malathion	decreases expression	1
Dihydrotestosterone	increases expression	1
Testosterone	affects cotreatment, increases expression	1

Clinical trials (associated diseases)

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