TRIM3

Summary

TRIM3 (tripartite motif containing 3, HGNC:10064) is a protein-coding gene on chromosome 11p15.4, encoding Tripartite motif-containing protein 3 (O75382). E3 ubiquitin ligase that plays essential roles in neuronal functions such as regulation of neuronal plasticity, learning, and memory.

The protein encoded by this gene is a member of the tripartite motif (TRIM) family, also called the ‘RING-B-box-coiled-coil’ (RBCC) subgroup of RING finger proteins. 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. This protein localizes to cytoplasmic filaments. It is similar to a rat protein which is a specific partner for the tail domain of myosin V, a class of myosins which are involved in the targeted transport of organelles. The rat protein can also interact with alpha-actinin-4. Thus it is suggested that this human protein may play a role in myosin V-mediated cargo transport. Alternatively spliced transcript variants encoding the same isoform have been identified.

Source: NCBI Gene 10612 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 84 total
• Phenotypes (HPO): 1
• MANE Select transcript: NM_033278

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10064
Approved symbol	TRIM3
Name	tripartite motif containing 3
Location	11p15.4
Locus type	gene with protein product
Status	Approved
Aliases	HAC1, BERP, RNF97
Ensembl gene	ENSG00000110171
Ensembl biotype	protein_coding
OMIM	605493
Entrez	10612

Gene structure

Transcript identifiers

Ensembl transcripts: 14 — 6 protein_coding, 5 protein_coding_CDS_not_defined, 3 retained_intron

ENST00000345851, ENST00000359518, ENST00000525074, ENST00000526845, ENST00000527237, ENST00000528227, ENST00000528932, ENST00000529058, ENST00000529529, ENST00000530724, ENST00000532542, ENST00000533064, ENST00000533309, ENST00000536344

RefSeq mRNA: 4 — MANE Select: NM_033278 NM_001248006, NM_001248007, NM_006458, NM_033278

CCDS: CCDS58115, CCDS7764

Canonical transcript exons

ENST00000345851 — 12 exons

Exon	Start	End
ENSE00000695067	6451271	6451438
ENSE00000821301	6458065	6458296
ENSE00001102068	6456297	6457029
ENSE00001129806	6456072	6456175
ENSE00001383683	6465565	6465732
ENSE00001945581	6448613	6449180
ENSE00003511167	6449306	6449446
ENSE00003571782	6450892	6451060
ENSE00003617967	6457696	6457847
ENSE00003635661	6450551	6450621
ENSE00003682327	6457296	6457476
ENSE00003842861	6473791	6473941

Expression profiles

Bgee: expression breadth ubiquitous, 238 present calls, max score 98.40.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 3.2931 / max 52.7371, expressed in 1551 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
118430	3.0600	1513
118429	0.2331	87

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cerebellar hemisphere	UBERON:0002245	98.40	gold quality
right hemisphere of cerebellum	UBERON:0014890	98.39	gold quality
cerebellar cortex	UBERON:0002129	98.32	gold quality
cerebellum	UBERON:0002037	96.65	gold quality
cortical plate	UBERON:0005343	94.26	gold quality
mucosa of transverse colon	UBERON:0004991	94.10	gold quality
right frontal lobe	UBERON:0002810	93.49	gold quality
paraflocculus	UBERON:0005351	93.42	gold quality
small intestine Peyer’s patch	UBERON:0003454	92.78	gold quality
tibial nerve	UBERON:0001323	92.57	gold quality
transverse colon	UBERON:0001157	92.34	gold quality
body of uterus	UBERON:0009853	91.90	gold quality
right coronary artery	UBERON:0001625	91.81	gold quality
popliteal artery	UBERON:0002250	91.76	gold quality
tibial artery	UBERON:0007610	91.75	gold quality
ascending aorta	UBERON:0001496	91.71	gold quality
muscle layer of sigmoid colon	UBERON:0035805	91.65	gold quality
thoracic aorta	UBERON:0001515	91.62	gold quality
aorta	UBERON:0000947	91.57	gold quality
descending thoracic aorta	UBERON:0002345	91.31	gold quality
prefrontal cortex	UBERON:0000451	90.97	gold quality
anterior cingulate cortex	UBERON:0009835	90.92	gold quality
endocervix	UBERON:0000458	90.91	gold quality
cingulate cortex	UBERON:0003027	90.87	gold quality
small intestine	UBERON:0002108	90.86	gold quality
ganglionic eminence	UBERON:0004023	90.76	gold quality
Brodmann (1909) area 10	UBERON:0013541	90.75	gold quality
left uterine tube	UBERON:0001303	90.74	gold quality
left coronary artery	UBERON:0001626	90.70	gold quality
right lung	UBERON:0002167	90.59	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	4.19

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): TP53

miRNA regulators (miRDB)

72 targeting TRIM3, 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-6825-5P	99.96	69.81	3431
HSA-MIR-454-3P	99.91	74.01	1925
HSA-MIR-106A-5P	99.90	73.94	2683
HSA-MIR-130A-3P	99.90	73.31	1861
HSA-MIR-130B-3P	99.90	73.27	1850
HSA-MIR-301A-3P	99.90	73.15	1839
HSA-MIR-301B-3P	99.90	73.19	1836
HSA-MIR-3666	99.90	73.24	1833
HSA-MIR-4295	99.90	73.11	1838
HSA-MIR-4302	99.89	67.94	1187
HSA-MIR-17-5P	99.89	73.83	2665
HSA-MIR-4697-3P	99.89	67.09	1123
HSA-MIR-106B-5P	99.88	74.72	2795
HSA-MIR-20A-5P	99.88	74.76	2769
HSA-MIR-20B-5P	99.88	74.01	2621
HSA-MIR-519D-3P	99.88	73.97	2607
HSA-MIR-526B-3P	99.88	74.06	2587
HSA-MIR-93-5P	99.88	73.98	2606
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-1321	99.84	65.30	1811
HSA-MIR-4739	99.84	65.25	1832
HSA-MIR-4756-5P	99.84	64.98	1809
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-7110-5P	99.80	67.84	1712
HSA-MIR-6842-5P	99.80	67.54	1587
HSA-MIR-3150A-3P	99.76	64.44	1640
HSA-MIR-6763-5P	99.76	64.68	1767
HSA-MIR-92A-2-5P	99.75	67.01	2164
HSA-MIR-3617-5P	99.75	69.41	1968
HSA-MIR-641	99.75	69.35	1975

Literature-anchored findings (GeneRIF, showing 27)

• the endosome-associated protein hrs is a subunit of a protein complex containing actinin-4, BERP, and myosin V that is necessary for efficient TfR recycling but not for EGFR degradation (PMID:15772161)
• Using shotgun mass spectrometry, we found this protein differentially expressed in the dorsolateral prefrontal cortex from patients with schizophrenia. (PMID:19165527)
• Loss of heterozygosity of chromosome segment 11p15.5 in malignant gliomas suggests TRIM3 as a candidate brain tumor suppressor gene. (PMID:19250537)
• TRIM63 is a candidate for genes mediating the glucocorticoid-induced promotion of osteoblastic differentiation. (PMID:20173306)
• brain-expressed RING finger protein (BERP) is a gene whose expression is up-regulated in a p53-dependent manner (PMID:20543135)
• Data indicate TRIM3 and p21 interact in cells. (PMID:23318451)
• TRIM3 acts as a tumor suppressor in GBM by restoring asymmetric cell division. (PMID:24947043)
• TRIM3 may play a significant role in hepatocellular carcinoma progression.TRIM3 is downregulated in hepatocellular carcinoma at both the mRNA and protein levels and that low TRIM3 expression is correlated with an unfavorable prognosis. (PMID:24994609)
• Studies indicate most-studied TRIpartite Motif (TRIM)-NHL proteins TRIM2, TRIM3, TRIM32 and TRIM71, and their mutations have been linked to diseases. (PMID:26514622)
• TRIM3 functions as a tumour suppressor in CRC progression. This tumour-suppressive function is exerted partially through regulation of p53 protein. (PMID:26691157)
• results support a novel role for Brat/TRIM3 in maintaining stem cell equilibrium and suppressing tumor growth by regulating NICD nuclear transport (PMID:26893479)
• TRIM3 exerted an anti-proliferation role in rheumatoid arthritis fibroblast-like synoviocytes via p38 signaling pathway. (PMID:28259936)
• TRIM3 plays a tumor-suppressing role in the regulation of liver cancer development by reducing cell proliferation through cell cycle arrest at the G0/G1 phase. (PMID:28950898)
• The results of quantitative real-time RT-PCR and western blotting showed that the TRIM3 expression was very low in five cervical cancer cell lines. The TRIM3 overexpression weakened cell viability, and promote apoptosis of C-33A and SiHa cells in vitro, and inhibit tumor growth in vivo, which suggested that TRIM3 could reduce proliferation of cervical cancer cells. (PMID:29524410)
• Exosomal TRIM3 may serve as a biomarker for gastric cancer diagnosis. (PMID:30031392)
• Tripartite motif-containing 3 (TRIM3) directly interacts with and induces E3 ligase-dependent proteasomal turnover of importin alpha3 and alpha-Actinin-4 (ACTN4). (PMID:30542119)
• Foxo3a exerted inhibitory effects on LPS-induced proliferation and inflammation through increasing TRIM3 transcription. (PMID:30980385)
• after silencing or overexpressing TRIM31 expression, the proliferation, invasion and migration of glioma cells could be downregulated or upregulated through Akt signaling pathway (PMID:31129970)
• miR-454-3p promotes proliferation and induces apoptosis in human cervical cancer cells by targeting TRIM3. (PMID:31270028)
• TRIM3 attenuates apoptosis in Parkinson’s disease via activating PI3K/AKT signal pathway. (PMID:33253119)
• Decreased expression of TRIM3 gene predicts a poor prognosis in gastric cancer. (PMID:33415720)
• TRIM3 Inhibits H2O2-Induced Apoptosis in Human Lens Epithelial Cells by Decreasing p53 via Ubiquitination. (PMID:35317686)
• TRIM3 facilitates estrogen signaling and modulates breast cancer cell progression. (PMID:35392925)
• Divergent self-association properties of paralogous proteins TRIM2 and TRIM3 regulate their E3 ligase activity. (PMID:36481767)
• TRIM3 facilitates ferroptosis in non-small cell lung cancer through promoting SLC7A11/xCT K11-linked ubiquitination and degradation. (PMID:37978273)
• Tripartite-motif 3 represses ovarian cancer progression by downregulating lactate dehydrogenase A and inhibiting AKT signaling. (PMID:38367118)
• Advances in the antitumor mechanisms of tripartite motif-containing protein 3. (PMID:38411731)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	trim3b	ENSDARG00000005397
danio_rerio	trim3a	ENSDARG00000063711
mus_musculus	Trim3	ENSMUSG00000036989
rattus_norvegicus	Trim3	ENSRNOG00000018356

Paralogs (80): MID2 (ENSG00000080561), TRIM9 (ENSG00000100505), MID1 (ENSG00000101871), MEFV (ENSG00000103313), TRIM35 (ENSG00000104228), TRIM14 (ENSG00000106785), TRIM37 (ENSG00000108395), TRIM2 (ENSG00000109654), 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 3 — O75382 (reviewed: O75382)

Alternative names: Brain-expressed RING finger protein, RING finger protein 22, RING finger protein 97

All UniProt accessions (3): O75382, E9PMK8, E9PMW5

UniProt curated annotations — full annotation on UniProt →

Function. E3 ubiquitin ligase that plays essential roles in neuronal functions such as regulation of neuronal plasticity, learning, and memory. In addition to its neuronal functions, participates in other biological processes such as innate immunity or cell cycle regulation. Component of the cytoskeleton-associated recycling or transport complex in neurons, polyubiquitinates gamma-actin, thus regulating neuronal plasticity, learning, and memory. Ubiquitinates postsynaptic scaffold GKAP, a neuronal substrate involved in synaptic remodeling and thereby modulates dendritic spine morphology. Positively regulates motility of microtubule-dependent motor protein KIF21B. Induces growth arrest via its RING-dependent E3 ligase activity and ubiquitinates CDKN1A. Positively regulates TLR3-mediated signaling by mediating ‘Lys-63’-linked polyubiquitination of TLR3. In turn, promotes the recognition and sorting of polyubiquitinated TLR3 by the ESCRT complexes.

Subunit / interactions. Forms homooligomers. Interacts with TRIM2; this interaction reduces TRIM2 activity. Associates with myosin-Vb (MYO5B) and alpha-actinin-4 (ACTN4). Component of the CART complex, at least composed of ACTN4, HGS/HRS, MYO5B and TRIM3. Interacts with ZFYVE28/LST2. Interacts with KIF21B.

Subcellular location. Cytoplasm. Early endosome. Golgi apparatus. trans-Golgi network. Cell projection. Dendrite.

Tissue specificity. Expressed in brain, heart, uterus and testis.

Domain organisation. The interaction with MYO5B is dependent upon its NHL repeats, which form a beta-propeller (NHL) domain containing six blades.

Similarity. Belongs to the TRIM/RBCC family.

Isoforms (4)

UniProt ID	Names	Canonical?
O75382-1	Alpha	yes
O75382-2	Beta
O75382-3	Gamma
O75382-4	4

RefSeq proteins (4): NP_001234935, NP_001234936, NP_006449, NP_150594* (*=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
IPR018957	Znf_C3HC4_RING-type	Domain
IPR050952	TRIM-NHL_E3_ligases	Family
IPR057750	TRIM2/3_C	Domain

Pfam: PF00097, PF00630, PF00643, PF01436

UniProt features (80 total): strand 37, repeat 7, sequence conflict 7, turn 7, binding site 4, splice variant 4, modified residue 3, zinc finger region 2, region of interest 2, mutagenesis site 2, helix 2, initiator methionine 1, chain 1, sequence variant 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
7QRW	X-RAY DIFFRACTION	1.7
7O0B	X-RAY DIFFRACTION	2.13
8AMR	X-RAY DIFFRACTION	3.8

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O75382-F1	83.26	0.53

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): 115; 118; 138; 143

Post-translational modifications (3): 2, 7, 427

Mutagenesis-validated functional residues (2):

Position	Phenotype
22	strong loss of ubiquitin ligase activity; when associated with s-25.
25	strong loss of ubiquitin ligase activity; when associated with s-22.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-877300	Interferon gamma signaling

MSigDB gene sets: 172 (showing top): PAX4_01, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, TGCACTT_MIR519C_MIR519B_MIR519A, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, TAL1ALPHAE47_01, SRF_Q5_01, GOBP_NEURAL_PRECURSOR_CELL_PROLIFERATION, GOBP_POSITIVE_REGULATION_OF_RESPONSE_TO_EXTERNAL_STIMULUS, GOBP_REGULATION_OF_IMMUNE_RESPONSE, GOBP_DEFENSE_RESPONSE_TO_OTHER_ORGANISM, BILD_E2F3_ONCOGENIC_SIGNATURE, GATA1_01, GOBP_REGULATION_OF_RESPONSE_TO_STRESS, GOBP_POST_TRANSLATIONAL_PROTEIN_MODIFICATION, GOBP_PROTEIN_POLYUBIQUITINATION

GO Biological Process (9): protein polyubiquitination (GO:0000209), nervous system development (GO:0007399), protein transport (GO:0015031), positive regulation of toll-like receptor 3 signaling pathway (GO:0034141), proteasome-mediated ubiquitin-dependent protein catabolic process (GO:0043161), neural precursor cell proliferation (GO:0061351), protein K63-linked ubiquitination (GO:0070534), toll-like receptor signaling pathway (GO:0002224), protein ubiquitination (GO:0016567)

GO Molecular Function (7): zinc ion binding (GO:0008270), identical protein binding (GO:0042802), ubiquitin protein ligase activity (GO:0061630), ubiquitin-protein transferase activity (GO:0004842), protein binding (GO:0005515), transferase activity (GO:0016740), metal ion binding (GO:0046872)

GO Cellular Component (6): cytoplasm (GO:0005737), early endosome (GO:0005769), Golgi apparatus (GO:0005794), dendrite (GO:0030425), endosome (GO:0005768), cell projection (GO:0042995)

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
endomembrane system	2
protein ubiquitination	1
system development	1
transport	1
intracellular protein localization	1
establishment of protein localization	1
toll-like receptor 3 signaling pathway	1
regulation of toll-like receptor 3 signaling pathway	1
positive regulation of pattern recognition receptor signaling pathway	1
positive regulation of intracellular signal transduction	1
ubiquitin-dependent protein catabolic process	1
proteasomal protein catabolic process	1
cell population proliferation	1
protein polyubiquitination	1
pattern recognition receptor signaling pathway	1
protein modification by small protein conjugation	1
transition metal ion binding	1
protein binding	1
ubiquitin-protein transferase activity	1
ubiquitin-like protein ligase activity	1
ubiquitin-like protein transferase activity	1
binding	1
catalytic activity	1
cation binding	1
intracellular anatomical structure	1
endosome	1
cytoplasm	1
intracellular membrane-bounded organelle	1
neuron projection	1
dendritic tree	1
cytoplasmic vesicle	1

Protein interactions and networks

STRING

904 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TRIM3	ACTN4	O43707	879
TRIM3	BBOX1	O75936	721
TRIM3	MYO5A	Q9Y4I1	705
TRIM3	KIF21B	O75037	682
TRIM3	MLPH	Q9BV36	649
TRIM3	MAGI1	Q96QZ7	639
TRIM3	SYNPO	Q8N3V7	633
TRIM3	TRAT1	Q6PIZ9	621
TRIM3	FSCN1	Q16658	588
TRIM3	RAB27A	P51159	543
TRIM3	TRIM44	Q96DX7	542
TRIM3	TRIM8	Q9BZR9	483
TRIM3	ERN1	O75460	477
TRIM3	A0A2R8Y4M4	A0A2R8Y4M4	477
TRIM3	PADI1	Q9ULC6	471

IntAct

89 interactions, top by confidence:

A	B	Type	Score
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
rep	TRIM3	psi-mi:“MI:0915”(physical association)	0.670
EMC4	EMC8	psi-mi:“MI:0914”(association)	0.640
TRIM3	MYO5B	psi-mi:“MI:0915”(physical association)	0.560
TRIM3	LNX1	psi-mi:“MI:0915”(physical association)	0.560
TRIM3	KCTD7	psi-mi:“MI:0915”(physical association)	0.560
TRIM3	TRIM21	psi-mi:“MI:0915”(physical association)	0.560
TRIM3	UBE2E2	psi-mi:“MI:0915”(physical association)	0.560
TRIM3	LRRC8E	psi-mi:“MI:0915”(physical association)	0.560
TRIM3	CEP70	psi-mi:“MI:0915”(physical association)	0.560
TRIM3	UBE2D1	psi-mi:“MI:0915”(physical association)	0.560
TRIM3	CSNK1D	psi-mi:“MI:0915”(physical association)	0.560
TRIM3	TEAD1	psi-mi:“MI:0915”(physical association)	0.560
TRIM3	TRIM3	psi-mi:“MI:0915”(physical association)	0.560
TRIM3	TEAD2	psi-mi:“MI:0915”(physical association)	0.560
TRIM3	UBE2Z	psi-mi:“MI:0915”(physical association)	0.560
TRIM3	ROPN1	psi-mi:“MI:0915”(physical association)	0.560
TRIM3	UBE2I	psi-mi:“MI:0915”(physical association)	0.560
TRIM3	CSNK1E	psi-mi:“MI:0915”(physical association)	0.560
TRIM3	ASL	psi-mi:“MI:0915”(physical association)	0.560
TRIM3	USP32	psi-mi:“MI:0915”(physical association)	0.560
N	NOP56	psi-mi:“MI:0914”(association)	0.530
UBE2G2	TRIM3	psi-mi:“MI:0915”(physical association)	0.370
UBE2U	TRIM3	psi-mi:“MI:0915”(physical association)	0.370
TRIM3	DNMT1	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (171): PDHA1 (Co-fractionation), TRIM3 (Synthetic Lethality), TRIM3 (Affinity Capture-MS), TRIM3 (Affinity Capture-MS), TRIM3 (Affinity Capture-MS), CDKN1A (Biochemical Activity), UBE2D1 (Reconstituted Complex), UBE2D2 (Reconstituted Complex), UBE2E1 (Reconstituted Complex), TRIM3 (Affinity Capture-MS), TRIM3 (Affinity Capture-Western), KPNB1 (Affinity Capture-Western), NOTCH1 (Affinity Capture-Western), KPNA4 (Affinity Capture-Western), TRIM3 (PCA)

ESM2 similar proteins: A2AA28, A4FV42, A4FV98, A6NDG6, D3YWP0, D3ZVU9, O15315, O35719, O70277, O75382, O94759, P21964, P57775, P81799, Q2TBS1, Q3UGX3, Q4R3I0, Q5E9V4, Q5H879, Q5RJL2, Q5SUV1, Q6DC64, Q7Z624, Q86WI3, Q86XA0, Q8BNV1, Q8C436, Q8CIW5, Q8IZ69, Q8N8L6, Q8N9F0, Q8VCX6, Q8WXB1, Q96AZ1, Q96FB5, Q96RR1, Q9BQD7, Q9BRQ3, Q9BUU2, Q9CQL0

Diamond homologs: A0A7I2V3R4, D2H788, D3ZBM4, O70277, O75382, P0DH78, Q3SWY0, Q3UIW8, Q58EC8, Q68EV7, Q6INB3, Q8C432, Q8N6D2, Q8QZS5, Q96D59, Q9BRZ2, Q9R1R2, A4IF63, A5D7F8, A5D8S5, D2GXS7, D3ZHA0, D3ZQG6, F7H9X2, O75369, P13466, P21333, Q14315, Q1XHU0, Q28E95, Q5RBR0, Q60953, Q69ZI1, Q6NRD3, Q71F54, Q7Z6J0, Q80X90, Q80XJ2, Q8BTM8, Q8C120

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
Ub:E2	“up-regulates activity”	TRIM3	ubiquitination
TRIM3	“down-regulates quantity by destabilization”	GKAP1	polyubiquitination

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 50 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	8	8.3×	9e-04

GO biological processes:

GO term	Partners	Fold	FDR
protein polyubiquitination	5	13.4×	4e-03
ubiquitin-dependent protein catabolic process	6	10.4×	4e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	67
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1854 predictions. Top by Δscore:

Variant	Effect	Δscore
11:6449179:ACC:A	acceptor_loss	1.0000
11:6449181:C:G	acceptor_loss	1.0000
11:6449182:T:C	acceptor_loss	1.0000
11:6449192:G:GC	acceptor_gain	1.0000
11:6449300:A:AC	donor_gain	1.0000
11:6449301:C:CC	donor_gain	1.0000
11:6449301:CTCA:C	donor_gain	1.0000
11:6449303:CA:C	donor_loss	1.0000
11:6449304:A:AC	donor_gain	1.0000
11:6449304:AC:A	donor_gain	1.0000
11:6449305:C:CG	donor_loss	1.0000
11:6449305:C:CT	donor_gain	1.0000
11:6449305:CC:C	donor_gain	1.0000
11:6449305:CCTGG:C	donor_gain	1.0000
11:6451056:TTGGT:T	acceptor_gain	1.0000
11:6451059:GT:G	acceptor_gain	1.0000
11:6451060:TC:T	acceptor_loss	1.0000
11:6451061:C:CC	acceptor_gain	1.0000
11:6451061:CTG:C	acceptor_loss	1.0000
11:6451062:T:A	acceptor_loss	1.0000
11:6451266:CTCAC:C	donor_loss	1.0000
11:6451270:C:CT	donor_loss	1.0000
11:6451280:G:A	donor_gain	1.0000
11:6456067:CTTA:C	donor_loss	1.0000
11:6456068:TTACC:T	donor_loss	1.0000
11:6456069:TACCT:T	donor_loss	1.0000
11:6456070:A:AC	donor_gain	1.0000
11:6456071:C:CC	donor_gain	1.0000
11:6456172:CTGC:C	acceptor_gain	1.0000
11:6456173:TGC:T	acceptor_gain	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000103128 (11:6462882 C>T), RS1000505477 (11:6469264 G>A), RS1000531970 (11:6458405 A>G), RS1000665479 (11:6467277 G>A), RS1000736697 (11:6450499 G>A), RS1000750981 (11:6452396 T>C), RS1000782738 (11:6473841 G>A), RS1000837258 (11:6470173 G>A,T), RS1000996760 (11:6464383 C>T), RS1001052944 (11:6458096 C>T), RS1001111396 (11:6464060 C>A), RS1001184918 (11:6454431 GGACA>G), RS1001214871 (11:6463457 G>A,T), RS1001255719 (11:6460666 T>G), RS1001317251 (11:6456568 A>G)

Disease associations

OMIM: gene MIM:605493 | disease phenotypes: MIM:209850

GenCC curated gene-disease

Mondo (1): autism (MONDO:0005260)

Orphanet (0):

HPO phenotypes

1 total (1 of 1 shown, HPO-id order):

HPO	Term
HP:0000717	Autism

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST010725_20	Malaria	4.000000e-69
GCST010725_33	Malaria	2.000000e-67
GCST010725_51	Malaria	1.000000e-55

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D001321	Autistic Disorder	F03.625.164.113.500

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

24 total (human), top 24 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
aristolochic acid I	increases expression	1
FR900359	increases phosphorylation	1
sodium arsenite	decreases expression	1
pentanal	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
nutlin 3	affects cotreatment, increases expression, increases secretion	1
2-methyl-2H-pyrazole-3-carboxylic acid (2-methyl-4-o-tolylazophenyl)amide	affects cotreatment, decreases expression	1
jinfukang	affects cotreatment, increases expression	1
Sunitinib	decreases expression	1
Leflunomide	decreases expression	1
Atrazine	increases expression	1
Camptothecin	increases expression	1
Cisplatin	affects cotreatment, increases expression	1
Dactinomycin	affects cotreatment, increases expression, increases secretion	1
Diazinon	increases methylation	1
Estradiol	affects expression	1
Hydrogen Peroxide	decreases expression	1
Ivermectin	decreases expression	1
Smoke	decreases expression	1
Tetrachlorodibenzodioxin	affects cotreatment, decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Urethane	increases expression	1
Gold Compounds	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_TU04	HAP1 TRIM3 (-) 1	Cancer cell line	Male
CVCL_TU05	HAP1 TRIM3 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00211796	PHASE4	COMPLETED	Divalproex Sodium ER in Adult Autism
NCT00391261	PHASE4	COMPLETED	An Open-label Trial of Metformin for Weight Control of Pediatric Patients on Antipsychotic Medications.
NCT00409747	PHASE4	COMPLETED	Minocycline to Treat Childhood Regressive Autism
NCT00576732	PHASE4	COMPLETED	A Study of the Effectiveness and Safety of Two Doses of Risperidone in the Treatment of Children and Adolescents With Autistic Disorder
NCT00844753	PHASE4	COMPLETED	Atomoxetine, Placebo and Parent Management Training in Autism
NCT01028820	PHASE4	COMPLETED	FMRI Brain Activation of Aripiprazole Treatment in Autism Spectrum Disorders
NCT01098383	PHASE4	UNKNOWN	Treatment With Acetyl-Choline Esterase Inhibitors in Children With Autism Spectrum Disorders
NCT01333865	PHASE4	COMPLETED	A Study of Memantine Hydrochloride (Namenda®) for Cognitive and Behavioral Impairment in Adults With Autism Spectrum Disorders
NCT01337700	PHASE4	COMPLETED	Milnacipran in Autism and the Functional Locus Coeruleus and Noradrenergic Model of Autism
NCT01695200	PHASE4	COMPLETED	Omega-3 Fatty Acids in Autism Spectrum Disorders
NCT02069977	PHASE4	UNKNOWN	Study to Evaluate the Efficacy and Safety of Aripiprazole
NCT02096952	PHASE4	COMPLETED	Methylphenidate ER Liquid Formulation in Adults With ASD and ADHD
NCT02199925	PHASE4	UNKNOWN	An Open-Label Study to Evaluate the Efficacy of High-Dose Gammaplex in Children on the Autism Spectrum
NCT02235467	PHASE4	COMPLETED	Multisite Study: Parental Training Using Video Modelling to Develop Social Skills in Children With Autism
NCT02255565	PHASE4	COMPLETED	Dose Response Effects of Quillivant XR in Children With ADHD and Autism: A Pilot Study
NCT02940574	PHASE4	COMPLETED	Neural and Behavioral Effects of Oxytocin in Autism Spectrum Disorders
NCT03333629	PHASE4	COMPLETED	Promoting Positive Outcomes for Individuals With ASD: Linking Early Detection, Treatment, and Long-term Outcomes
NCT03337646	PHASE4	COMPLETED	Evaluation of the Effect and Safety of Lisdexamfetamine in Children Aged 6-12 With ADHD and Autism
NCT03538431	PHASE4	COMPLETED	Improving Driving in Young People With Autism Spectrum Disorders
NCT03757585	PHASE4	COMPLETED	Natural Treatments for the Management of Emotional Dysregulation in Youth With Non-verbal Learning Disability (NVLD) and/or Autism Spectrum Disorders (ASD)
NCT04903353	PHASE4	COMPLETED	Pragmatic Trial Comparing Weight Gain in Children With Autism Taking Risperidone Versus Aripiprazole
NCT05063656	PHASE4	COMPLETED	Biomarker-Driven Pharmacological Treatment of Adolescents With Autism Spectrum Disorder With Gabapentin
NCT05146245	PHASE4	UNKNOWN	Safety and Pharmacokinetics of Antipsychotics in Children 2: Studying TDM in an RCT
NCT05916339	PHASE4	RECRUITING	AWARE: Management of ADHD in Autism Spectrum Disorder
NCT05954052	PHASE4	TERMINATED	A Study of Glutathione in Children With Autism Spectrum Disorder
NCT06853665	PHASE4	RECRUITING	The TEAM Study - Treatment Efficacy for Autism/Attention Using Mixed Amphetamine
NCT07054697	PHASE4	COMPLETED	Pilot-RCT With Individualized Homeopathic Treatment in the Children With Autism Spectrum Disorder
NCT07161804	PHASE4	COMPLETED	Pilot RCT Using Homeopathic Medicines in ASD
NCT07439042	PHASE4	NOT_YET_RECRUITING	Buspirone for Anxiety in Autistic Youth
NCT00036231	PHASE3	TERMINATED	Synthetic Human Secretin in Children With Autism and Gastrointestinal Dysfunction
NCT00036244	PHASE3	COMPLETED	Synthetic Human Secretin in Children With Autism
NCT00065884	PHASE3	UNKNOWN	Valproate Response in Aggressive Autistic Adolescents
NCT00065962	PHASE3	COMPLETED	Secretin for the Treatment of Autism
NCT00252603	PHASE3	COMPLETED	Galantamine Versus Placebo in Childhood Autism
NCT00346736	PHASE3	COMPLETED	Use of Acupuncture In Children With Autistic Spectrum Disorder
NCT00352248	PHASE3	COMPLETED	Randomized Controlled Trial of Acupuncture Versus Sham Acupuncture in Autistic Spectrum Disorder
NCT00352352	PHASE3	COMPLETED	Use of Acupuncture In Children With Autistic Spectrum Disorder
NCT00355329	PHASE3	COMPLETED	Randomized Control Trial of Using Tongue Acupuncture in Autistic Spectrum Disorder Using PET Scan for Clinical Correlation
NCT00498173	PHASE3	COMPLETED	Effectiveness of Atomoxetine in Treating ADHD Symptoms in Children and Adolescents With Autism
NCT00541346	PHASE3	COMPLETED	A Pilot Study of Daytrana TM in Children With Autism Co-Morbid for Attention Deficit Hyperactivity Disorder (ADHD) Symptoms