TRIM2

Summary

TRIM2 (tripartite motif containing 2, HGNC:15974) is a protein-coding gene on chromosome 4q31.3, encoding Tripartite motif-containing protein 2 (Q9C040). UBE2D1-dependent E3 ubiquitin-protein ligase that mediates the ubiquitination of NEFL and of phosphorylated BCL2L11.

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 filaments. It plays a neuroprotective role and functions as an E3-ubiquitin ligase in proteasome-mediated degradation of target proteins. Mutations in this gene can cause early-onset axonal neuropathy. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 23321 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Charcot-Marie-Tooth disease type 2R (Strong, GenCC)
• GWAS associations: 32
• Clinical variants (ClinVar): 562 total — 3 pathogenic, 3 likely-pathogenic
• Phenotypes (HPO): 20
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity no evidence
• MANE Select transcript: NM_015271

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:15974
Approved symbol	TRIM2
Name	tripartite motif containing 2
Location	4q31.3
Locus type	gene with protein product
Status	Approved
Aliases	KIAA0517, RNF86, CMT2R
Ensembl gene	ENSG00000109654
Ensembl biotype	protein_coding
OMIM	614141
Entrez	23321

Gene structure

Transcript identifiers

Ensembl transcripts: 93 — 56 protein_coding, 24 nonsense_mediated_decay, 11 retained_intron, 2 protein_coding_CDS_not_defined

ENST00000338700, ENST00000433687, ENST00000437508, ENST00000441616, ENST00000460908, ENST00000479711, ENST00000482578, ENST00000491446, ENST00000494872, ENST00000502281, ENST00000632856, ENST00000674718, ENST00000674726, ENST00000674730, ENST00000674769, ENST00000674786, ENST00000674787, ENST00000674832, ENST00000674847, ENST00000674872, ENST00000674874, ENST00000674876, ENST00000674896, ENST00000674935, ENST00000674976, ENST00000675019, ENST00000675049, ENST00000675054, ENST00000675063, ENST00000675136, ENST00000675146, ENST00000675159, ENST00000675170, ENST00000675210, ENST00000675239, ENST00000675293, ENST00000675312, ENST00000675315, ENST00000675340, ENST00000675343, ENST00000675348, ENST00000675363, ENST00000675384, ENST00000675411, ENST00000675412, ENST00000675425, ENST00000675456, ENST00000675462, ENST00000675492, ENST00000675567, ENST00000675611, ENST00000675623, ENST00000675627, ENST00000675673, ENST00000675710, ENST00000675738, ENST00000675744, ENST00000675745, ENST00000675780, ENST00000675782, ENST00000675783, ENST00000675804, ENST00000675835, ENST00000675862, ENST00000675871, ENST00000675899, ENST00000675977, ENST00000676015, ENST00000676029, ENST00000676033, ENST00000676057, ENST00000676158, ENST00000676167, ENST00000676169, ENST00000676172, ENST00000676191, ENST00000676196, ENST00000676202, ENST00000676220, ENST00000676224, ENST00000676252, ENST00000676264, ENST00000676291, ENST00000676305, ENST00000676335, ENST00000676348, ENST00000676374, ENST00000676408, ENST00000676423, ENST00000676458, ENST00000894199, ENST00000894200, ENST00000928353

RefSeq mRNA: 24 — MANE Select: NM_015271 NM_001130067, NM_001302692, NM_001302693, NM_001302694, NM_001351054, NM_001351055, NM_001351056, NM_001351057, NM_001375488, NM_001375489, NM_001375490, NM_001375491, NM_001375512, NM_001375513, NM_001375514, NM_001375515, NM_001375516, NM_001375517, NM_001375519, NM_001375520, NM_001375522, NM_001375523, NM_001375525, NM_015271

CCDS: CCDS3781, CCDS47147, CCDS93653, CCDS93654, CCDS93655, CCDS93656, CCDS93657

Canonical transcript exons

ENST00000338700 — 12 exons

Exon	Start	End
ENSE00000740017	153324078	153324148
ENSE00000740018	153322648	153322816
ENSE00000821091	153315832	153315999
ENSE00000821092	153315485	153315588
ENSE00001790597	153328530	153328670
ENSE00001925312	153334814	153339317
ENSE00001947404	153204443	153204560
ENSE00003490864	153294305	153294485
ENSE00003521018	153295313	153296036
ENSE00003526156	153270335	153270519
ENSE00003600484	153275893	153276130
ENSE00003615398	153292982	153293133

Expression profiles

Bgee: expression breadth ubiquitous, 284 present calls, max score 99.63.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 31.3353 / max 976.9348, expressed in 1474 samples.

FANTOM5 promoters (17 alternative TSS)

Promoter ID	TPM avg	Samples expressed
50050	13.0131	701
50059	7.3850	453
50055	4.8926	1216
50056	2.5448	976
50044	0.8488	309
50067	0.5738	207
50046	0.3925	187
50045	0.3722	207
50052	0.2711	121
50051	0.2699	97

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
inferior olivary complex	UBERON:0002127	99.63	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	99.60	gold quality
corpus callosum	UBERON:0002336	99.57	gold quality
lateral globus pallidus	UBERON:0002476	99.48	gold quality
substantia nigra pars reticulata	UBERON:0001966	99.41	gold quality
inferior vagus X ganglion	UBERON:0005363	99.41	gold quality
subthalamic nucleus	UBERON:0001906	99.39	gold quality
medulla oblongata	UBERON:0001896	99.36	gold quality
pons	UBERON:0000988	99.35	gold quality
superior vestibular nucleus	UBERON:0007227	99.32	gold quality
substantia nigra pars compacta	UBERON:0001965	99.30	gold quality
lateral nuclear group of thalamus	UBERON:0002736	99.27	gold quality
middle temporal gyrus	UBERON:0002771	99.23	gold quality
globus pallidus	UBERON:0001875	99.22	gold quality
parietal lobe	UBERON:0001872	99.19	gold quality
postcentral gyrus	UBERON:0002581	99.19	gold quality
medial globus pallidus	UBERON:0002477	99.15	gold quality
paraflocculus	UBERON:0005351	99.04	gold quality
CA1 field of hippocampus	UBERON:0003881	99.02	gold quality
Brodmann (1909) area 10	UBERON:0013541	99.01	gold quality
middle frontal gyrus	UBERON:0002702	99.00	gold quality
dorsal plus ventral thalamus	UBERON:0001897	98.98	gold quality
Brodmann (1909) area 23	UBERON:0013554	98.98	gold quality
entorhinal cortex	UBERON:0002728	98.96	gold quality
ventral tegmental area	UBERON:0002691	98.93	gold quality
frontal pole	UBERON:0002795	98.90	gold quality
cortical plate	UBERON:0005343	98.77	gold quality
occipital lobe	UBERON:0002021	98.47	gold quality
ventricular zone	UBERON:0003053	98.30	gold quality
primary visual cortex	UBERON:0002436	98.22	gold quality

Single-cell (SCXA)

Detected in 6 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-GEOD-75688	yes	676.44
E-ANND-3	yes	13.11
E-GEOD-84465	yes	9.98
E-CURD-135	no	710.00
E-GEOD-36552	no	200.56
E-GEOD-83139	no	3.44

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

288 targeting TRIM2, 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-5011-5P	100.00	83.46	5820
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-485-3P	99.98	70.68	1585
HSA-MIR-539-3P	99.98	70.74	1616
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-4482-3P	99.98	72.50	3147

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 15)

• TRIM2 is repressed by miR-9 and -181c, either alone or in combination. (PMID:21720722)
• The functional role of the C-terminal NHL domain was characterized in TRIM2. (PMID:24817735)
• TRIM2 homozygous missense mutation (c.2000A>C; p.D667A) in a patient with peripheral neuropathy and bilateral vocal cord paralysis (PMID:25893792)
• Studies indicate most-studied TRIpartite Motif (TRIM)-NHL proteins TRIM2, TRIM3, TRIM32 and TRIM71, and their mutations have been linked to diseases. (PMID:26514622)
• TRIM2 is associated with clinical fibrotic phenotypes of eosinophilic esophagitis. (PMID:29628359)
• We found that CREBRF and TRIM2 mRNA were significantly upregulated by rHDL, particularly in response to its phospholipid component 1-palmitoyl-2-linoleoyl-phosphatidylcholine, however, protein expression was not significantly altered. (PMID:29958463)
• Study revealed that TRIM2 performs important functions in regulating the development and metastasis of osteosarcoma. (PMID:30066883)
• TRIM2, a novel member of the antiviral family, limits New World arenavirus entry. (PMID:30726215)
• TRIM2 expression was significantly higher in colorectal cancer tissues than in non-cancerous tissues and was significantly associated with some clinicopathological factors. The results indicate that TRIM2 is a novel promoter of human colorectal cancer. (PMID:30916596)
• Oncogenic function of TRIM2 in pancreatic cancer by activating ROS-related NRF2/ITGB7/FAK axis. (PMID:32929153)
• Long non-coding RNA NR2F1-AS1 promoted neuroblastoma progression through miR-493-5p/TRIM2 axis. (PMID:33378023)
• Knockdown of long noncoding RNA DLEU2 suppresses idiopathic pulmonary fibrosis by regulating the microRNA3693p/TRIM2 axis. (PMID:33760118)
• Expression and Role of TRIM2 in Human Diseases. (PMID:36051486)
• Divergent self-association properties of paralogous proteins TRIM2 and TRIM3 regulate their E3 ligase activity. (PMID:36481767)
• Hsa_circ_0001361 facilitates cell progression and glycolytic metabolism in neuroblastoma via interacting with mir-490-5p to induce TRIM2 upregulation. (PMID:36920626)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	trim2a	ENSDARG00000031817
danio_rerio	trim2b	ENSDARG00000076174
mus_musculus	Trim2	ENSMUSG00000027993
rattus_norvegicus	Trim2	ENSRNOG00000010124

Paralogs (80): MID2 (ENSG00000080561), TRIM9 (ENSG00000100505), MID1 (ENSG00000101871), MEFV (ENSG00000103313), TRIM35 (ENSG00000104228), TRIM14 (ENSG00000106785), TRIM37 (ENSG00000108395), 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), TRIM63 (ENSG00000158022)

Protein

Protein identifiers

Tripartite motif-containing protein 2 — Q9C040 (reviewed: Q9C040)

Alternative names: E3 ubiquitin-protein ligase TRIM2, RING finger protein 86, RING-type E3 ubiquitin transferase TRIM2

All UniProt accessions (39): Q9C040, A0A0J9YW02, A0A0J9YW70, A0A0J9YX34, A0A6Q8PEY7, A0A6Q8PEY9, A0A6Q8PF63, A0A6Q8PF74, A0A6Q8PF82, A0A6Q8PFB0, A0A6Q8PFD3, A0A6Q8PFE3, A0A6Q8PFI4, A0A6Q8PFM2, A0A6Q8PFP1, A0A6Q8PFS5, A0A6Q8PFV0, A0A6Q8PFX3, A0A6Q8PG16, A0A6Q8PG79, A0A6Q8PG80, A0A6Q8PG97, A0A6Q8PGE9, A0A6Q8PGF3, A0A6Q8PGG4, A0A6Q8PGK8, A0A6Q8PGL5, A0A6Q8PGM7, A0A6Q8PGR7, A0A6Q8PGS7, A0A6Q8PGW9, A0A6Q8PGZ0, A0A6Q8PH39, A0A6Q8PHB2, A0A6Q8PHE9, A0A6Q8PHG3, A0A6Q8PHP4, A0A6Q8PHR6, C9J084

UniProt curated annotations — full annotation on UniProt →

Function. UBE2D1-dependent E3 ubiquitin-protein ligase that mediates the ubiquitination of NEFL and of phosphorylated BCL2L11. Plays a neuroprotective function. May play a role in neuronal rapid ischemic tolerance. Plays a role in antiviral immunity and limits New World arenavirus infection independently of its ubiquitin ligase activity.

Subunit / interactions. Forms homooligomers. Interacts with TRIM3; this interaction reduces TRIM2 activity. Interacts with myosin V; myosin V may not be a substrate for ubiquitination. Interacts with NEFL. Interacts with phosphorylated BCL2L11. Interacts with SIRPA.

Subcellular location. Cytoplasm.

Post-translational modifications. RING-type zinc finger-dependent and UBE2D1-dependent autoubiquitination.

Disease relevance. Charcot-Marie-Tooth disease, axonal, type 2R (CMT2R) [MIM:615490] An axonal form of Charcot-Marie-Tooth disease, a disorder of the peripheral nervous system, characterized by progressive weakness and atrophy, initially of the peroneal muscles and later of the distal muscles of the arms. Charcot-Marie-Tooth disease is classified in two main groups on the basis of electrophysiologic properties and histopathology: primary peripheral demyelinating neuropathies (designated CMT1 when they are dominantly inherited) and primary peripheral axonal neuropathies (CMT2). Neuropathies of the CMT2 group are characterized by signs of axonal degeneration in the absence of obvious myelin alterations, normal or slightly reduced nerve conduction velocities, and progressive distal muscle weakness and atrophy. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. The interaction with myosin V is dependent upon its NHL repeats, which form a beta-propeller (NHL) domain containing six blades.

Pathway. Protein modification; protein ubiquitination.

Similarity. Belongs to the TRIM/RBCC family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9C040-1	1	yes
Q9C040-2	2

RefSeq proteins (24): NP_001123539, NP_001289621, NP_001289622, NP_001289623, NP_001337983, NP_001337984, NP_001337985, NP_001337986, NP_001362417, NP_001362418, NP_001362419, NP_001362420, NP_001362441, NP_001362442, NP_001362443, NP_001362444, NP_001362445, NP_001362446, NP_001362448, NP_001362449, NP_001362451, NP_001362452, NP_001362454, NP_056086* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000315	Znf_B-box	Domain
IPR001258	NHL_repeat	Repeat
IPR001298	Filamin/ABP280_rpt	Repeat
IPR001841	Znf_RING	Domain
IPR003649	Bbox_C	Domain
IPR011042	6-blade_b-propeller_TolB-like	Homologous_superfamily
IPR013083	Znf_RING/FYVE/PHD	Homologous_superfamily
IPR013783	Ig-like_fold	Homologous_superfamily
IPR014756	Ig_E-set	Homologous_superfamily
IPR017868	Filamin/ABP280_rpt-like	Repeat
IPR017907	Znf_RING_CS	Conserved_site
IPR027370	Znf-RING_euk	Domain
IPR050952	TRIM-NHL_E3_ligases	Family
IPR057750	TRIM2/3_C	Domain

Pfam: PF00630, PF00643, PF01436, PF13445

UniProt features (69 total): strand 33, repeat 7, turn 7, helix 6, modified residue 5, binding site 4, zinc finger region 2, chain 1, region of interest 1, splice variant 1, sequence variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

6 structures.

PDB	Method	Resolution (Å)
7QRV	X-RAY DIFFRACTION	1.45
7B2R	X-RAY DIFFRACTION	1.6
7B96	X-RAY DIFFRACTION	1.8
8A38	X-RAY DIFFRACTION	2.2
8AMS	X-RAY DIFFRACTION	2.4
7ZJ3	X-RAY DIFFRACTION	2.53

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9C040-F1	84.91	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): 118; 121; 141; 146

Post-translational modifications (5): 10, 371, 375, 424, 428

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-877300	Interferon gamma signaling

MSigDB gene sets: 359 (showing top): GGGACCA_MIR133A_MIR133B, GCACCTT_MIR18A_MIR18B, GNF2_RTN1, KOBAYASHI_EGFR_SIGNALING_24HR_UP, BROWNE_HCMV_INFECTION_6HR_DN, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, GOBP_RESPONSE_TO_PEPTIDE, GOZGIT_ESR1_TARGETS_DN, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GAUSSMANN_MLL_AF4_FUSION_TARGETS_A_UP, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, MONNIER_POSTRADIATION_TUMOR_ESCAPE_UP, MODULE_66, LI_WILMS_TUMOR_VS_FETAL_KIDNEY_1_UP

GO Biological Process (5): protein polyubiquitination (GO:0000209), proteasome-mediated ubiquitin-dependent protein catabolic process (GO:0043161), regulation of neuron apoptotic process (GO:0043523), cellular response to leukemia inhibitory factor (GO:1990830), protein ubiquitination (GO:0016567)

GO Molecular Function (6): ubiquitin-protein transferase activity (GO:0004842), 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 (1): cytoplasm (GO:0005737)

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
protein ubiquitination	1
ubiquitin-dependent protein catabolic process	1
proteasomal protein catabolic process	1
regulation of apoptotic process	1
neuron apoptotic process	1
cellular response to cytokine stimulus	1
response to leukemia inhibitory factor	1
protein modification by small protein conjugation	1
ubiquitin-like protein transferase activity	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
cellular anatomical structure	1

Protein interactions and networks

STRING

982 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TRIM2	NEFL	P07196	682
TRIM2	TRAT1	Q6PIZ9	582
TRIM2	TRIM44	Q96DX7	573
TRIM2	BTBD3	Q9Y2F9	524
TRIM2	LRSAM1	Q6UWE0	449
TRIM2	BBOX1	O75936	447
TRIM2	TSNARE1	Q96NA8	431
TRIM2	MYC	P01106	431
TRIM2	AKR1C8	Q5T2L2	422
TRIM2	SH3TC2	Q8TF17	421
TRIM2	CFH	P08603	415
TRIM2	NUMB	P49757	414
TRIM2	NUMBL	Q9Y6R0	410
TRIM2	IGHMBP2	P38935	403
TRIM2	GDAP1	Q8TB36	400

IntAct

99 interactions, top by confidence:

A	B	Type	Score
UBAC1	TRIM2	psi-mi:“MI:0915”(physical association)	0.780
TRIM2	TRIM3	psi-mi:“MI:0915”(physical association)	0.770
TRIM3	TRIM2	psi-mi:“MI:0915”(physical association)	0.770
TRIM2	TRIM3	psi-mi:“MI:0914”(association)	0.770
LRRC8E	TRIM2	psi-mi:“MI:0915”(physical association)	0.740
TRIM2	LRRC8E	psi-mi:“MI:0915”(physical association)	0.740
TRIM2	CIB3	psi-mi:“MI:0915”(physical association)	0.720
CIB3	TRIM2	psi-mi:“MI:0915”(physical association)	0.720
rep	TRIM2	psi-mi:“MI:0915”(physical association)	0.600
	TRIM2	psi-mi:“MI:0915”(physical association)	0.560
TRIM2		psi-mi:“MI:0915”(physical association)	0.560
TRIM2	UBC1	psi-mi:“MI:0915”(physical association)	0.560
HAT1	TRIM2	psi-mi:“MI:0915”(physical association)	0.560
UBC1	TRIM2	psi-mi:“MI:0915”(physical association)	0.560
CDK20	TRIM2	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (194): TRIM2 (Two-hybrid), CIB3 (Two-hybrid), SIRPA (Two-hybrid), TRIM2 (Affinity Capture-MS), SIRPA (Two-hybrid), PDHA1 (Co-fractionation), TRIM2 (Proximity Label-MS), TRIM2 (Two-hybrid), LRRC8E (Two-hybrid), TRIM3 (Affinity Capture-MS), TRIM2 (Affinity Capture-MS), TRIM2 (Two-hybrid), TRIM2 (Two-hybrid), TRIM2 (Two-hybrid), TRIM2 (Affinity Capture-RNA)

ESM2 similar proteins: A0A3L7I2I8, A4IF63, A4II46, A6QQZ7, A8KBF6, D2GXS7, D3ZQG6, D3ZVM4, E1BJS7, E7FAM5, F6QEU4, F7H9X2, O60733, O70277, O75382, P23727, P26450, P27986, P42694, P49754, P79987, P97570, P97819, Q15139, Q1LY10, Q1PRL4, Q1PSW8, Q28C55, Q2Q1W2, Q2T9K6, Q59H18, Q5GIG6, Q5R685, Q5RF15, Q5T2T1, Q5U2Y3, Q63787, Q7TQP6, Q8AVG0, Q8BVD5

Diamond homologs: A4IF63, A5D7F8, A5D8S5, D2GXS7, D3ZHA0, D3ZQG6, F7H9X2, O70277, O75369, O75382, P13466, P21333, Q14315, Q1XHU0, Q28E95, Q3UIW8, Q5RBR0, Q60953, Q69ZI1, Q6NRD3, Q71F54, Q7Z6J0, Q80X90, Q80XJ2, Q8BTM8, Q8C120, Q8TEJ3, Q8VHX6, Q9C040, Q9ESN6, Q9HCM9, Q9R1R2, Q9VEN1, A0JNB0, A1CEK6, A1DFN5, A1Y2K1, A2QW93, A4RF61, A6QLK6

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
Ub:E2	“up-regulates activity”	TRIM2	ubiquitination
UBE2D1	“up-regulates activity”	TRIM2	binding
TRIM2	“down-regulates quantity by destabilization”	NEFL	ubiquitination

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 49 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
Synthesis of active ubiquitin: roles of E1 and E2 enzymes	7	71.6×	6e-10
E3 ubiquitin ligases ubiquitinate target proteins	5	26.9×	1e-04
Antigen processing: Ubiquitination & Proteasome degradation	13	13.4×	6e-10

GO biological processes:

GO term	Partners	Fold	FDR
protein K11-linked ubiquitination	6	53.4×	2e-07
protein monoubiquitination	5	39.1×	1e-05
protein K48-linked ubiquitination	9	34.5×	2e-09
protein K63-linked ubiquitination	5	30.4×	4e-05
protein polyubiquitination	9	23.6×	3e-08
ubiquitin-dependent protein catabolic process	8	13.5×	1e-05
DNA repair	6	8.7×	3e-03
proteasome-mediated ubiquitin-dependent protein catabolic process	7	8.3×	1e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	3
Likely pathogenic	3
Uncertain significance	273
Likely benign	246
Benign	24

Top pathogenic / likely-pathogenic (6)

Variant ID	HGVS	Classification
4734104	NM_015271.5(TRIM2):c.232_233dup (p.Pro79fs)	Pathogenic
83303	NM_015271.5(TRIM2):c.761A>T (p.Glu254Val)	Pathogenic
83304	NM_015271.5(TRIM2):c.1781del (p.Lys594fs)	Pathogenic
243075	NM_015271.5(TRIM2):c.2000A>C (p.Asp667Ala)	Likely pathogenic
4813761	NM_015271.5(TRIM2):c.1968dup (p.Val657fs)	Likely pathogenic
809695	NM_015271.5(TRIM2):c.2_5dup (p.Arg3fs)	Likely pathogenic

SpliceAI

3058 predictions. Top by Δscore:

Variant	Effect	Δscore
4:153153266:GAAAC:G	donor_gain	1.0000
4:153153267:AAACG:A	donor_loss	1.0000
4:153153268:AAC:A	donor_gain	1.0000
4:153153268:AACG:A	donor_loss	1.0000
4:153153269:AC:A	donor_gain	1.0000
4:153153269:ACGT:A	donor_loss	1.0000
4:153153270:CGTG:C	donor_loss	1.0000
4:153153271:G:GG	donor_gain	1.0000
4:153153272:T:A	donor_loss	1.0000
4:153275888:A:AG	acceptor_gain	1.0000
4:153275892:G:GT	acceptor_loss	1.0000
4:153276097:A:T	donor_gain	1.0000
4:153276126:GGAAT:G	donor_gain	1.0000
4:153276127:GAAT:G	donor_gain	1.0000
4:153276127:GAATG:G	donor_gain	1.0000
4:153276131:G:GG	donor_gain	1.0000
4:153291562:T:G	acceptor_gain	1.0000
4:153292977:CACA:C	acceptor_loss	1.0000
4:153292979:CAGGT:C	acceptor_loss	1.0000
4:153292980:A:AG	acceptor_gain	1.0000
4:153292980:AGGT:A	acceptor_gain	1.0000
4:153292981:G:GG	acceptor_gain	1.0000
4:153292981:GGT:G	acceptor_gain	1.0000
4:153292981:GGTG:G	acceptor_gain	1.0000
4:153293130:AAAGG:A	donor_loss	1.0000
4:153293131:AAG:A	donor_loss	1.0000
4:153293132:AGGT:A	donor_loss	1.0000
4:153293134:GTGG:G	donor_loss	1.0000
4:153294482:CAAA:C	donor_gain	1.0000
4:153294482:CAAAG:C	donor_loss	1.0000

AlphaMissense

5106 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:153270452:T:A	C23S	1.000
4:153270452:T:C	C23R	1.000
4:153270453:G:A	C23Y	1.000
4:153270453:G:C	C23S	1.000
4:153270453:G:T	C23F	1.000
4:153270454:C:G	C23W	1.000
4:153270461:T:A	C26S	1.000
4:153270461:T:C	C26R	1.000
4:153270462:G:A	C26Y	1.000
4:153270462:G:C	C26S	1.000
4:153270463:C:G	C26W	1.000
4:153270483:C:A	P33H	1.000
4:153270492:T:A	L36H	1.000
4:153270492:T:C	L36P	1.000
4:153270497:T:A	C38S	1.000
4:153270497:T:C	C38R	1.000
4:153270498:G:A	C38Y	1.000
4:153270498:G:C	C38S	1.000
4:153270499:T:G	C38W	1.000
4:153270501:T:C	L39P	1.000
4:153270503:C:A	H40N	1.000
4:153270503:C:G	H40D	1.000
4:153270504:A:G	H40R	1.000
4:153270505:C:A	H40Q	1.000
4:153270505:C:G	H40Q	1.000
4:153270509:T:C	F42L	1.000
4:153270510:T:C	F42S	1.000
4:153270511:C:A	F42L	1.000
4:153270511:C:G	F42L	1.000
4:153270512:T:A	C43S	1.000

dbSNP variants (sampled 300 via entrez): RS1000023073 (4:153218716 T>C), RS1000038762 (4:153200640 A>G), RS1000061535 (4:153266130 A>T), RS1000078139 (4:153294153 A>G), RS1000092112 (4:153200929 G>A,C,T), RS1000093552 (4:153310326 A>G), RS1000101322 (4:153258227 C>T), RS10001079 (4:153324770 T>C,G), RS1000109555 (4:153225557 C>T), RS1000126415 (4:153225386 A>T), RS1000133509 (4:153265780 A>C,G), RS1000140183 (4:153266228 G>A,T), RS1000140608 (4:153159896 C>G), RS1000143802 (4:153224154 A>G), RS1000175720 (4:153248361 T>C)

Disease associations

OMIM: gene MIM:614141 | disease phenotypes: MIM:615490

GenCC curated gene-disease

Disease	Classification	Inheritance
Charcot-Marie-Tooth disease type 2R	Strong	Autosomal recessive

Mondo (2): Charcot-Marie-Tooth disease type 2R (MONDO:0014208), axonal neuropathy (MONDO:0004183)

Orphanet (1): Charcot-Marie-Tooth disease type 2R (Orphanet:397968)

HPO phenotypes

20 total (20 of 20 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0001252	Hypotonia
HP:0001284	Areflexia
HP:0001324	Muscle weakness
HP:0001605	Vocal cord paralysis
HP:0001761	Pes cavus
HP:0001762	Talipes equinovarus
HP:0002093	Respiratory insufficiency
HP:0002136	Broad-based gait
HP:0002540	Inability to walk
HP:0002779	Tracheomalacia
HP:0003199	Decreased muscle mass
HP:0003380	Decreased number of peripheral myelinated nerve fibers
HP:0003431	Decreased motor nerve conduction velocity
HP:0003477	Peripheral axonal neuropathy
HP:0003593	Infantile onset
HP:0006380	Knee flexion contracture
HP:0008954	Intrinsic hand muscle atrophy
HP:0031936	Delayed ability to walk
HP:0040078	Axonal degeneration

GWAS associations

32 associations (top):

Study	Trait	p-value
GCST001096_3	Multiple sclerosis	4.000000e-06
GCST006611_19	HDL cholesterol	7.000000e-09
GCST006979_757	Heel bone mineral density	3.000000e-09
GCST008075_188	HDL cholesterol levels x alcohol consumption (regular vs non-regular drinkers) interaction (2df)	6.000000e-09
GCST008075_85	HDL cholesterol levels x alcohol consumption (regular vs non-regular drinkers) interaction (2df)	2.000000e-07
GCST008077_24	LDL cholesterol levels	2.000000e-06
GCST008077_81	LDL cholesterol levels	5.000000e-07
GCST008078_140	LDL cholesterol levels x alcohol consumption (regular vs non-regular drinkers) interaction (2df)	3.000000e-07
GCST008078_41	LDL cholesterol levels x alcohol consumption (regular vs non-regular drinkers) interaction (2df)	5.000000e-07
GCST008079_129	LDL cholesterol levels x alcohol consumption (drinkers vs non-drinkers) interaction (2df)	2.000000e-08
GCST008079_72	LDL cholesterol levels x alcohol consumption (drinkers vs non-drinkers) interaction (2df)	2.000000e-07
GCST008084_171	HDL cholesterol levels x alcohol consumption (drinkers vs non-drinkers) interaction (2df)	6.000000e-08
GCST008084_51	HDL cholesterol levels x alcohol consumption (drinkers vs non-drinkers) interaction (2df)	3.000000e-07
GCST008085_105	HDL cholesterol levels in current drinkers	2.000000e-06
GCST008085_170	HDL cholesterol levels in current drinkers	3.000000e-08
GCST008086_28	LDL cholesterol levels in current drinkers	5.000000e-07
GCST008086_4	LDL cholesterol levels in current drinkers	4.000000e-07
GCST010204_153	Low density lipoprotein cholesterol levels	6.000000e-10
GCST010241_252	Apolipoprotein A1 levels	4.000000e-08
GCST010796_1859	Electrocardiogram morphology (amplitude at temporal datapoints)	2.000000e-08
GCST010796_1860	Electrocardiogram morphology (amplitude at temporal datapoints)	3.000000e-09
GCST010796_1861	Electrocardiogram morphology (amplitude at temporal datapoints)	3.000000e-08
GCST010796_1862	Electrocardiogram morphology (amplitude at temporal datapoints)	3.000000e-08
GCST010796_1863	Electrocardiogram morphology (amplitude at temporal datapoints)	4.000000e-08
GCST010796_1864	Electrocardiogram morphology (amplitude at temporal datapoints)	2.000000e-08
GCST010796_1865	Electrocardiogram morphology (amplitude at temporal datapoints)	1.000000e-08
GCST010796_1866	Electrocardiogram morphology (amplitude at temporal datapoints)	1.000000e-08
GCST010796_1867	Electrocardiogram morphology (amplitude at temporal datapoints)	3.000000e-08
GCST010796_1868	Electrocardiogram morphology (amplitude at temporal datapoints)	2.000000e-09
GCST011932_3	Thyrotoxic periodic paralysis	2.000000e-09

EFO canonical traits (7, from GWAS)

EFO ID	Trait name
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0009270	heel bone mineral density
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0004329	alcohol drinking
EFO:0004614	apolipoprotein A 1 measurement
EFO:0004327	electrocardiography
EFO:0004533	alkaline phosphatase measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

61 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases expression	4
mercuric bromide	decreases expression, affects cotreatment	2
Phenylmercuric Acetate	decreases expression, affects cotreatment	2
Silicon Dioxide	decreases expression	2
Tobacco Smoke Pollution	increases expression, decreases expression	2
Valproic Acid	affects expression, increases expression	2
8-Bromo Cyclic Adenosine Monophosphate	increases expression, affects cotreatment	2
Cyclosporine	decreases expression, increases expression	2
Particulate Matter	affects expression, increases abundance, increases expression	2
3,19-(2-bromobenzylidene)andrographolide	decreases response to substance, increases expression	1
FR900359	increases phosphorylation	1
methylmercuric chloride	decreases expression	1
bisphenol A	increases expression	1
sodium arsenate	decreases expression	1
beta-lapachone	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
cobaltous chloride	increases expression	1
perfluorooctanoic acid	increases expression	1
zinc chromate	increases abundance, increases expression	1
coumarin	increases phosphorylation	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1
beta-methylcholine	affects expression	1
chromium hexavalent ion	increases expression, increases abundance	1
perfluorooctane sulfonic acid	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression, increases expression	1
torcetrapib	increases expression	1
abrine	decreases expression	1
dorsomorphin	decreases expression, increases expression, affects cotreatment	1
MRK 003	decreases expression	1
incobotulinumtoxinA	increases expression	1

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_TT85	HAP1 TRIM2 (-) 1	Cancer cell line	Male
CVCL_TT86	HAP1 TRIM2 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT05902351	Not specified	RECRUITING	Natural History Study for Charcot Marie Tooth Disease
NCT01847937	Not specified	COMPLETED	Magnetic Resonance Diagnostics of Diabetic Peripheral Neuropathy