TRIM43

Summary

TRIM43 (tripartite motif containing 43, HGNC:19015) is a protein-coding gene on chromosome 2q11.1, encoding Tripartite motif-containing protein 43 (Q96BQ3). E3 ligase that regulates nuclear lamina integrity and the association of viral chromatin with transcriptionally-active host chromatin. It is a selective cancer dependency (DepMap: 15.4% 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 located in centrosome. Predicted to be active in cytoplasm.

Source: NCBI Gene 129868 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 47 total
• Cancer dependency (DepMap): dependent in 15.4% of screened cell lines
• MANE Select transcript: NM_138800

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:19015
Approved symbol	TRIM43
Name	tripartite motif containing 43
Location	2q11.1
Locus type	gene with protein product
Status	Approved
Aliases	TRIM43A
Ensembl gene	ENSG00000144015
Ensembl biotype	protein_coding
Entrez	129868

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000272395

RefSeq mRNA: 1 — MANE Select: NM_138800 NM_138800

CCDS: CCDS2015

Canonical transcript exons

ENST00000272395 — 7 exons

Exon	Start	End
ENSE00001214615	95599092	95599778
ENSE00001804370	95592001	95592149
ENSE00002482910	95596202	95596432
ENSE00002486124	95597880	95597977
ENSE00002489517	95595050	95595145
ENSE00002509828	95594020	95594434
ENSE00002511532	95597329	95597351

Expression profiles

Bgee: expression breadth broad, 16 present calls, max score 82.63.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 1.5258 / max 182.2282, expressed in 44 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
21438	1.5258	44

Top tissues by expression

115 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	82.63	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	68.51	gold quality
lower esophagus mucosa	UBERON:0035834	44.11	silver quality
colonic epithelium	UBERON:0000397	37.20	gold quality
ventricular zone	UBERON:0003053	36.48	gold quality
cortical plate	UBERON:0005343	36.47	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
testis	UBERON:0000473	33.03	gold quality
muscle tissue	UBERON:0002385	32.26	gold quality
hindlimb stylopod muscle	UBERON:0004252	32.15	gold quality
tonsil	UBERON:0002372	32.12	gold quality
bone marrow	UBERON:0002371	31.74	gold quality
left testis	UBERON:0004533	31.70	silver quality
right testis	UBERON:0004534	31.29	silver quality
sural nerve	UBERON:0015488	30.93	gold quality
monocyte	CL:0000576	30.68	gold quality
nucleus accumbens	UBERON:0001882	30.51	gold quality
leukocyte	CL:0000738	30.40	gold quality
stromal cell of endometrium	CL:0002255	29.87	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	29.51	silver quality
right uterine tube	UBERON:0001302	29.25	gold quality
prefrontal cortex	UBERON:0000451	29.20	gold quality
gall bladder	UBERON:0002110	28.55	gold quality
duodenum	UBERON:0002114	28.14	gold quality
liver	UBERON:0002107	28.04	gold quality
smooth muscle tissue	UBERON:0001135	27.85	gold quality
lymph node	UBERON:0000029	27.57	gold quality
temporal lobe	UBERON:0001871	26.80	silver quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.30

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

19 targeting TRIM43, 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-3662	99.99	73.82	5684
HSA-MIR-6844	99.82	70.69	2423
HSA-MIR-8076	99.78	68.52	1170
HSA-MIR-548AV-5P	99.60	70.84	2107
HSA-MIR-548K	99.60	70.84	2107
HSA-MIR-3616-5P	99.55	67.02	989
HSA-MIR-573	99.55	67.44	955
HSA-MIR-8054	99.48	70.81	2084
HSA-MIR-4293	99.22	65.46	1263
HSA-MIR-6780B-3P	99.13	67.18	622
HSA-MIR-3117-5P	99.04	67.93	618
HSA-MIR-3908	98.75	67.31	1160
HSA-MIR-4780	98.57	64.75	611
HSA-MIR-4703-5P	98.53	70.13	1645
HSA-MIR-3942-5P	98.52	69.51	1517
HSA-MIR-4709-5P	98.51	67.25	1335
HSA-MIR-4766-3P	98.48	67.94	1347
HSA-MIR-10398-5P	97.12	64.94	1051
HSA-MIR-6514-5P	95.07	66.02	655

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 15.4% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 1)

• TRIM43 ubiquitinates the centrosomal protein pericentrin, thereby targeting it for proteasomal degradation, which subsequently leads to alterations of the nuclear lamina that repress active viral chromatin states. (PMID:30420784)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
mus_musculus	Trim43c	ENSMUSG00000067399
mus_musculus	Trim43b	ENSMUSG00000079162
mus_musculus	Trim43a	ENSMUSG00000090693
rattus_norvegicus	Trim43a	ENSRNOG00000010699

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), TRIM7 (ENSG00000146054), TRIM41 (ENSG00000146063), TRIM50 (ENSG00000146755), TRIM4 (ENSG00000146833), TRIM55 (ENSG00000147573), TRIM48 (ENSG00000150244), TRIM36 (ENSG00000152503), TRIM11 (ENSG00000154370), TRIM74 (ENSG00000155428), TRIM42 (ENSG00000155890), TRIM63 (ENSG00000158022)

Protein

Protein identifiers

Tripartite motif-containing protein 43 — Q96BQ3 (reviewed: Q96BQ3)

All UniProt accessions (1): Q96BQ3

UniProt curated annotations — full annotation on UniProt →

Function. E3 ligase that regulates nuclear lamina integrity and the association of viral chromatin with transcriptionally-active host chromatin. Acts thereby as a herpesvirus-specific antiviral factor and mediates the ubiquitination-dependent proteasomal degradation of PCNT.

Subcellular location. Cytoplasm. Cytoskeleton. Microtubule organizing center. Centrosome.

Induction. By DUX4 during herpesvirus infection.

Similarity. Belongs to the TRIM/RBCC family.

RefSeq proteins (1): NP_620155* (*=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
IPR013083	Znf_RING/FYVE/PHD	Homologous_superfamily
IPR013320	ConA-like_dom_sf	Homologous_superfamily
IPR017907	Znf_RING_CS	Conserved_site
IPR043136	B30.2/SPRY_sf	Homologous_superfamily
IPR050143	TRIM/RBCC	Family

Pfam: PF00622, PF15227

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

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96BQ3-F1	88.47	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): 93; 96; 115; 121

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 18 (showing top): GOCC_MICROTUBULE_ORGANIZING_CENTER, GOBP_DEFENSE_RESPONSE_TO_OTHER_ORGANISM, GOCC_CENTROSOME, GOMF_ACYLTRANSFERASE_ACTIVITY, GOMF_AMINOACYLTRANSFERASE_ACTIVITY, GOMF_UBIQUITIN_LIKE_PROTEIN_LIGASE_ACTIVITY, chr2q11, BYSTRYKH_HEMATOPOIESIS_STEM_CELL_QTL_TRANS, MIR548AV_5P_MIR548K, MIR8054, MIR4703_5P, MIR3942_5P, MIR4766_3P, MIR3117_5P, MIR6780B_3P

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 (3): cytoplasm (GO:0005737), centrosome (GO:0005813), cytoskeleton (GO:0005856)

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
centriole	1
microtubule organizing center	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

430 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TRIM43	MBD3L2	Q8NHZ7	812
TRIM43	ZSCAN4	Q8NAM6	773
TRIM43	DUX4L2	P0CJ85	772
TRIM43	KHDC1L	Q5JSQ8	720
TRIM43	LEUTX	A8MZ59	718
TRIM43	KHDC1	Q4VXA5	697
TRIM43	PRAMEF2	O60811	694
TRIM43	PRAMEF1	O95521	692
TRIM43	SMCHD1	A6NHR9	584
TRIM43	MBD3L5	A6NJ08	580
TRIM43	WFDC3	Q8IUB2	511
TRIM43	MBD3L3	A6NE82	480
TRIM43	PRAMEF12	O95522	471
TRIM43	H3Y2	P0DPK5	454
TRIM43	PRAMEF11	O60813	446

IntAct

30 interactions, top by confidence:

A	B	Type	Score
ENOX1	TRIM43	psi-mi:“MI:0915”(physical association)	0.720
TRIM43	ENOX1	psi-mi:“MI:0915”(physical association)	0.720
GRB7	TRIM43	psi-mi:“MI:0915”(physical association)	0.560
TRIM43	UBE2K	psi-mi:“MI:0915”(physical association)	0.560
TRIM43	TGFBR2	psi-mi:“MI:0915”(physical association)	0.560
MLF1	TRIM43	psi-mi:“MI:0915”(physical association)	0.400
CACYBP	TRIM43	psi-mi:“MI:0915”(physical association)	0.400
TRIM43	UBE2G2	psi-mi:“MI:0915”(physical association)	0.370
TRIM43	UBE2D1	psi-mi:“MI:0915”(physical association)	0.370
UBE2D2	TRIM43	psi-mi:“MI:0915”(physical association)	0.370
UBE2D3	TRIM43	psi-mi:“MI:0915”(physical association)	0.370
TRIM43	UBE2D4	psi-mi:“MI:0915”(physical association)	0.370
TRIM43	HIP2	psi-mi:“MI:0915”(physical association)	0.370
TRIM43	MYOG	psi-mi:“MI:0915”(physical association)	0.370
TRIM27	TRIM43	psi-mi:“MI:0915”(physical association)	0.370
TRIM43	TRIM8	psi-mi:“MI:0915”(physical association)	0.370
TRIM43	CLPX	psi-mi:“MI:0914”(association)	0.350
TRIM43	VWA8	psi-mi:“MI:0914”(association)	0.350
TRIM43	ENOX1	psi-mi:“MI:0915”(physical association)	0.000
TRIM43	GRB7	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (60): TRIM43 (Two-hybrid), DHRS4 (Affinity Capture-MS), HSPD1 (Affinity Capture-MS), SIRT3 (Affinity Capture-MS), MIPEP (Affinity Capture-MS), MTIF2 (Affinity Capture-MS), CLPX (Affinity Capture-MS), CLPP (Affinity Capture-MS), PCNT (Affinity Capture-MS), TUBG1 (Affinity Capture-MS), SMC1A (Affinity Capture-MS), SMC3 (Affinity Capture-MS), RAD21 (Affinity Capture-MS), PCNT (Affinity Capture-Western), TRIM43 (Two-hybrid)

ESM2 similar proteins: A0A3B3IT33, A6NCK2, A6NDI0, A6NGJ6, A6NI03, A6NLI5, C9J1S8, I1YAP6, K7N6K2, P0CI25, P0CI26, P15533, 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”	TRIM43	ubiquitination

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 17 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	6	18.6×	7e-06

GO biological processes:

GO term	Partners	Fold	FDR
protein K48-linked ubiquitination	6	67.4×	3e-08
protein polyubiquitination	5	38.5×	6e-06
ubiquitin-dependent protein catabolic process	6	29.7×	2e-06

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	42
Likely benign	4
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

735 predictions. Top by Δscore:

Variant	Effect	Δscore
2:95594431:CCGGG:C	donor_loss	1.0000
2:95594432:CGGG:C	donor_loss	1.0000
2:95594433:GG:G	donor_gain	1.0000
2:95594433:GGGT:G	donor_loss	1.0000
2:95594434:GG:G	donor_gain	1.0000
2:95594435:G:C	donor_loss	1.0000
2:95594436:T:G	donor_loss	1.0000
2:95595046:GCAG:G	acceptor_loss	1.0000
2:95595047:CA:C	acceptor_loss	1.0000
2:95595047:CAGG:C	acceptor_gain	1.0000
2:95595048:A:AC	acceptor_loss	1.0000
2:95595048:A:AG	acceptor_gain	1.0000
2:95595048:AG:A	acceptor_gain	1.0000
2:95595048:AGGA:A	acceptor_gain	1.0000
2:95595049:G:GA	acceptor_gain	1.0000
2:95595049:GG:G	acceptor_gain	1.0000
2:95595049:GGA:G	acceptor_gain	1.0000
2:95595049:GGAG:G	acceptor_gain	1.0000
2:95595049:GGAGA:G	acceptor_gain	1.0000
2:95595141:GGAGG:G	donor_gain	1.0000
2:95595142:GAGG:G	donor_gain	1.0000
2:95595142:GAGGG:G	donor_gain	1.0000
2:95595144:GG:G	donor_gain	1.0000
2:95595145:GG:G	donor_gain	1.0000
2:95595145:GGTA:G	donor_loss	1.0000
2:95595146:G:A	donor_loss	1.0000
2:95595146:G:GG	donor_gain	1.0000
2:95595147:T:A	donor_loss	1.0000
2:95597425:G:GG	donor_gain	1.0000
2:95597876:GCA:G	acceptor_loss	1.0000

AlphaMissense

3007 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:95599478:T:C	F416L	0.974
2:95599480:T:A	F416L	0.974
2:95599480:T:G	F416L	0.974
2:95599247:T:A	W339R	0.947
2:95599247:T:C	W339R	0.947
2:95594123:T:C	F34L	0.941
2:95594125:C:A	F34L	0.941
2:95594125:C:G	F34L	0.941
2:95599277:T:A	W349R	0.941
2:95599277:T:C	W349R	0.941
2:95599249:G:C	W339C	0.938
2:95599249:G:T	W339C	0.938
2:95599479:T:C	F416S	0.938
2:95597971:T:C	F285L	0.926
2:95597973:C:A	F285L	0.926
2:95597973:C:G	F285L	0.926
2:95599448:T:C	F406L	0.926
2:95599450:T:A	F406L	0.926
2:95599450:T:G	F406L	0.926
2:95599550:T:C	F440L	0.924
2:95599552:C:A	F440L	0.924
2:95599552:C:G	F440L	0.924
2:95594433:G:C	R137P	0.918
2:95594330:T:C	F103L	0.917
2:95594332:C:A	F103L	0.917
2:95594332:C:G	F103L	0.917
2:95599280:G:C	A350P	0.916
2:95599287:G:A	G352E	0.907
2:95594120:A:C	S33R	0.895
2:95594122:C:A	S33R	0.895

dbSNP variants (sampled 300 via entrez): RS1001153683 (2:95591370 C>A,T), RS1001993843 (2:95590765 C>T), RS1002764354 (2:95594053 G>A), RS1002798893 (2:95593828 G>A), RS1003774493 (2:95595465 T>C), RS1004002330 (2:95593477 T>C), RS1005034895 (2:95594647 A>G,T), RS1005384078 (2:95594962 A>G), RS1005593333 (2:95592504 A>T), RS1006081161 (2:95592171 T>A), RS1006802681 (2:95591777 A>G), RS1006879994 (2:95591446 G>A), RS1007844160 (2:95593097 C>T), RS1008474780 (2:95590314 C>A,G), RS1008502497 (2:95590072 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

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

15 total (human), top 15 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Genistein	decreases expression	2
propionaldehyde	increases expression	1
2-methyl-4-isothiazolin-3-one	increases expression	1
butyraldehyde	increases expression	1
CGP 52608	affects binding, increases reaction	1
2-palmitoylglycerol	increases expression	1
bisphenol S	decreases methylation	1
Decitabine	increases expression	1
Acetaminophen	decreases expression	1
Atrazine	increases expression	1
Estradiol	decreases expression	1
Folic Acid	increases expression	1
Plant Oils	increases expression	1
Tetrachlorodibenzodioxin	affects expression	1
Okadaic Acid	increases expression	1

Clinical trials (associated diseases)

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