TRIM32

Summary

TRIM32 (tripartite motif containing 32, HGNC:16380) is a protein-coding gene on chromosome 9q33.1, encoding E3 ubiquitin-protein ligase TRIM32 (Q13049). E3 ubiquitin ligase that plays a role in various biological processes including neural stem cell differentiation, innate immunity, inflammatory resonse and autophagy.

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 bodies. The protein has also been localized to the nucleus, where it interacts with the activation domain of the HIV-1 Tat protein. The Tat protein activates transcription of HIV-1 genes.

Source: NCBI Gene 22954 — RefSeq curated summary.

At a glance

• Gene–disease (curated): autosomal recessive limb-girdle muscular dystrophy (Definitive, ClinGen) — +3 more curated relationships
• GWAS associations: 2
• Clinical variants (ClinVar): 45 total — 4 pathogenic, 6 likely-pathogenic
• Phenotypes (HPO): 130
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity no evidence
• MANE Select transcript: NM_012210

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16380
Approved symbol	TRIM32
Name	tripartite motif containing 32
Location	9q33.1
Locus type	gene with protein product
Status	Approved
Aliases	HT2A, TATIP, BBS11
Ensembl gene	ENSG00000119401
Ensembl biotype	protein_coding
OMIM	602290
Entrez	22954

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 12 protein_coding

ENST00000373983, ENST00000411410, ENST00000450136, ENST00000882855, ENST00000882856, ENST00000882857, ENST00000882858, ENST00000882859, ENST00000882860, ENST00000929584, ENST00000929585, ENST00000929586

RefSeq mRNA: 5 — MANE Select: NM_012210 NM_001099679, NM_001379048, NM_001379049, NM_001379050, NM_012210

CCDS: CCDS6817

Canonical transcript exons

ENST00000450136 — 2 exons

Exon	Start	End
ENSE00001667250	116687305	116687381
ENSE00001733281	116697662	116701299

Expression profiles

Bgee: expression breadth ubiquitous, 252 present calls, max score 86.22.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 7.7239 / max 64.6557, expressed in 1672 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
98283	7.7239	1672

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
stromal cell of endometrium	CL:0002255	86.22	gold quality
tibialis anterior	UBERON:0001385	85.21	silver quality
gastrocnemius	UBERON:0001388	84.91	gold quality
muscle of leg	UBERON:0001383	84.74	gold quality
secondary oocyte	CL:0000655	84.56	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	83.83	gold quality
hindlimb stylopod muscle	UBERON:0004252	83.71	gold quality
muscle organ	UBERON:0001630	83.45	gold quality
cortical plate	UBERON:0005343	83.27	gold quality
deltoid	UBERON:0001476	83.21	silver quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	83.20	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	82.76	gold quality
bronchial epithelial cell	CL:0002328	82.17	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	81.93	gold quality
epithelium of bronchus	UBERON:0002031	81.81	gold quality
skeletal muscle tissue	UBERON:0001134	81.50	gold quality
biceps brachii	UBERON:0001507	81.27	gold quality
bronchus	UBERON:0002185	81.20	gold quality
islet of Langerhans	UBERON:0000006	80.85	gold quality
cerebellar cortex	UBERON:0002129	80.78	gold quality
cerebellum	UBERON:0002037	80.74	gold quality
cerebellar hemisphere	UBERON:0002245	80.72	gold quality
descending thoracic aorta	UBERON:0002345	80.63	gold quality
decidua	UBERON:0002450	80.42	gold quality
smooth muscle tissue	UBERON:0001135	80.29	gold quality
ganglionic eminence	UBERON:0004023	80.04	gold quality
muscle tissue	UBERON:0002385	79.89	gold quality
skin of hip	UBERON:0001554	79.84	gold quality
quadriceps femoris	UBERON:0001377	79.81	silver quality
ventricular zone	UBERON:0003053	79.55	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.52

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

1 targets.

Target	Regulation
JUN	Activation

Upstream regulators (CollecTRI, top): TP73

miRNA regulators (miRDB)

99 targeting TRIM32, 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-4533	100.00	69.48	2758
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-3617-3P	99.98	67.86	918
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-9-3P	99.96	70.88	2068
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-9718	99.94	68.91	918
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-4496	99.88	68.89	2236
HSA-MIR-3681-3P	99.88	70.46	2254
HSA-MIR-548D-3P	99.87	70.67	4362
HSA-MIR-548BB-3P	99.86	70.58	4354
HSA-MIR-548AC	99.84	70.77	4351
HSA-MIR-548H-3P	99.84	70.80	4349
HSA-MIR-548Z	99.84	70.80	4349

Functional genomics

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

Literature-anchored findings (GeneRIF, showing 40)

• limb-girdle muscular dystrophy type 2H associated with mutation in TRIM32, a putative E3-ubiquitin-ligase gene (PMID:11822024)
• TRIM32 mutation found in the sarcotubular myopathy patients is identical to the causative mutation for LGMD2H (D487N) (PMID:15786463)
• Mutation analysis of TRIM32 shows it is a Bardet-Biedl syndrome gene. (PMID:16606853)
• by controlling Piasy stability, Trim32 regulates UVB-induced keratinocyte apoptosis through induction of NFkappaB (PMID:16816390)
• The interplay between Trim32 and Pias3 is positively regulated by nitric oxide. (PMID:17987106)
• The mutations here reported may cause muscular dystrophy by affecting the interaction properties of TRIM32. (PMID:17994549)
• TRIM32 is a novel oncogene that promotes tumor growth, metastasis, and resistance to anticancer drugs via degradation of Abl-interactor 2 (PMID:18632609)
• Together with two recently reported mutations, this novel mutation confirms that integrity of the C-terminal domain of TRIM32 is necessary for muscle maintenance. (PMID:19303295)
• TRIM32 is a widely expressed ubiquitin ligase and binds and ubiquitinates dysbindin. (PMID:19349376)
• Intragenic deletion of TRIM32 in compound heterozygotes with sarcotubular myopathy/LGMD2H (PMID:19492423)
• As CCL20 is activated by Th17 cytokines, the upregulation of CCL20 production by Trim32 provides a positive feedback loop of CCL20 and Th17 activation in the self-perpetuating cycle of psoriasis (PMID:20054338)
• It is likely that C-terminal mutations in TRIM32 affect the ability of muscle proteins to be degraded by the ubiquitin-proteasome pathway.[review] (PMID:21496629)
• TRIM32 sensitizes TNFalpha-induced apoptosis by antagonizing XIAP (PMID:21628460)
• Malin is related to TRIM32 at both the phylogenetic and functional level. (PMID:21798009)
• promotes neural differentiation through retinoic acid receptor-mediated transcription (PMID:21984809)
• These findings suggest that TRIM32 functions as one of the coactivators for RARalpha-mediated transcription in acute promyelogenous leukemia cells. (PMID:22182411)
• TRIM32 protein modulates type I interferon induction and cellular antiviral response by targeting MITA/STING protein for K63-linked ubiquitination (PMID:22745133)
• TRIM32 assembles polyubiquitin chains as a Ubc5-linked thioester intermediate. (PMID:23408431)
• a novel connection between ubiquitylation and phosphorylation pathways, which could modulate a variety of cell events by stimulating the formation of the 14-3-3-TRIM32 signaling complex. (PMID:23444366)
• Deletions near the 3’ terminus of ASTN2, a subset of these deletions also includes TRIM32, are significantly enriched in neurodevelopmental disorder subjects. (PMID:24381304)
• BBS11 promotes accumulation of NPHP7, changing the properties of NPHP7. TRIM32 Modulates the Transcriptional Activities of Glis2 (PMID:24500717)
• Trim32 is a positive regulator of ACD that acts against MYCN and should be considered as a tumor-suppressor candidate (PMID:25100564)
• Identification of TRIM32 as a novel p53 target and as a novel negative regulator for p53. (PMID:25146927)
• Data indicate that variants in tripartite motif-containing 32 protein (TRIM32) in two patients presenting nonspecific limb-girdle muscular dystrophy type 2H (LGMD2H) were identified by using high-throughput variants screening techniques. (PMID:25351777)
• TRIM32, an E3 ubiquitin ligase, promotes HIV reactivation from latency by directly modifying IkappaBalpha (PMID:25873391)
• TRIM32 represents a model of intrinsic immunity, in which a host protein directly senses and counters viral infection in a species specific fashion by directly limiting viral replication (PMID:26057645)
• Results suggest that Salmonella effector SseK3 binding to host tripartite motif-containing 32 protein (TRIM32) in the inhibition of nuclear factor kappa B (NF-kappaB) activation: [SseK3] (PMID:26394407)
• Studies indicate most-studied TRIpartite Motif (TRIM)-NHL proteins TRIM2, TRIM3, TRIM32 and TRIM71, and their mutations have been linked to diseases. (PMID:26514622)
• results show a novel molecular cascade involving miR-155 and TRIM32 leading to HIV-1 Tat-induced attenuated proliferation of neural precursor cells; study also uncovered an unidentified role for miR-155 in modulating human neural stem cell proliferation, helping in better understanding of neural precursor cells and diseased brain (PMID:26586575)
• that TRIM32 plays a protective role in aortic banding-induced pathological cardiac remodelling by blocking Akt-dependent signalling (PMID:26884348)
• we provide a detailed characterization of the TRIM ligases TRIM25 and TRIM32 and show how their oligomeric state is linked to catalytic activity (PMID:27154206)
• Duchenne muscular dystrophy muscles showed a selective up-regulation of the ubiquitin ligase tripartite motif-containing protein 32 (TRIM32). The induction of TRIM32 was due to a transcriptional effect and it correlated with disease severity. (PMID:27295345)
• these findings suggest that TRIM32 might play important roles in the hepatocarcinogenesis. (PMID:27573002)
• HSP70-TRIM32 complex is biochemically distinct from the previously characterized 14-3-3-TRIM32 phospho-complex. (PMID:28052117)
• Data suggest that, in cardiomyocytes, TRIM32 attenuates activation of SRF signaling and hypertrophy due to dysbindin; TRIM24 promotes these effects. TRIM32 promotes dysbindin degradation; TRIM24 protects dysbindin from degradation. (TRIM = tripartite motif-containing protein; SRF = serum response factor) (PMID:28465353)
• TRIM32 as a crucial positive regulator of Herpes Simplex Virus type 1 (HSV-1) induced IFN-beta production in corneal epithelial cells, and it played a predominant role in clearing HSV-1 from the cornea. (PMID:28954259)
• In a cohort of non-Hutterite TRIM32 myopathy patients, several pathogenic variants are identified. (PMID:29921608)
• we found that the mechanism behind the TRIM32-promoted GC progression was related to the b-catenin signalling pathway. Collectively, these data suggest that TRIM32 promotes GC cell proliferation, migration, and invasion by activating the b-catenin signalling pathway. (PMID:30079558)
• TRIM32 may regulate lung cancer cell proliferation, apoptosis, and motility. (PMID:30378152)
• A mutation in TRIM32 causes muscle dystrophy and reduced levels of TRIM32 was observed in all patient muscle studied. (PMID:30823891)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
		ENSDARG00000102505
mus_musculus	Trim32	ENSMUSG00000051675
rattus_norvegicus	Trim32	ENSRNOG00000010303

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), 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

E3 ubiquitin-protein ligase TRIM32 — Q13049 (reviewed: Q13049)

Alternative names: 72 kDa Tat-interacting protein, RING-type E3 ubiquitin transferase TRIM32, Tripartite motif-containing protein 32, Zinc finger protein HT2A

All UniProt accessions (2): Q13049, Q5JVY0

UniProt curated annotations — full annotation on UniProt →

Function. E3 ubiquitin ligase that plays a role in various biological processes including neural stem cell differentiation, innate immunity, inflammatory resonse and autophagy. Plays a role in virus-triggered induction of IFN-beta and TNF by mediating the ubiquitination of STING1. Mechanistically, targets STING1 for ‘Lys-63’-linked ubiquitination which promotes the interaction of STING1 with TBK1. Regulates bacterial clearance and promotes autophagy in Mycobacterium tuberculosis-infected macrophages. Negatively regulates TLR3/4-mediated innate immune and inflammatory response by triggering the autophagic degradation of TICAM1 in an E3 activity-independent manner. Plays an essential role in oxidative stress induced cell death by inducing loss of transmembrane potential and enhancing mitochondrial reactive oxygen species (ROS) production during oxidative stress conditions. Ubiquitinates XIAP and targets it for proteasomal degradation. Ubiquitinates DTNBP1 (dysbindin) and promotes its degradation. May ubiquitinate BBS2. Ubiquitinates PIAS4/PIASY and promotes its degradation in keratinocytes treated with UVB and TNF. Also acts as a regulator of autophagy by mediating formation of unanchored ‘Lys-63’-linked polyubiquitin chains that activate ULK1: interaction with AMBRA1 is required for ULK1 activation. Positively regulates dendritic branching by promoting ubiquitination and subsequent degradation of the epigenetic factor CDYL. Under metabolic stress and phosphorylation by CHK2, mediates ‘Lys-63’-linked ubiquitination of ATG7 at ‘Lys-45’ to initiate autophagy. (Microbial infection) May play a significant role in mediating the biological activity of the HIV-1 Tat protein in vivo. Binds specifically to the activation domain of HIV-1 Tat and can also interact with the HIV-2 and EIAV Tat proteins in vivo.

Subunit / interactions. It self-associates. Interacts with DTNBP1. Interacts with PIAS4/PIASY upon treatment with UVB and TNF. Interacts with AMBRA1; promoting activation of ULK1 through unanchored ‘Lys-63’-linked polyubiquitin chains. Interacts with TICAM1 and TAX1BP1; these interactions target TICAM1 to TAX1BP1-mediated selective autophagic degradation. (Microbial infection) Interacts with S.typhimurium protein SseK3; SseK3 does not glycosylate TRIM32.

Subcellular location. Cytoplasm. Mitochondrion. Endoplasmic reticulum.

Tissue specificity. Spleen, thymus, prostate, testis, ovary, intestine, colon and skeletal muscle.

Post-translational modifications. Ubiquitinated. Phosphorylation at Ser-55 by CHEK2 under oxidative stress, activates the E3 ligase activity and promotes ATG7 ubiquitination leading to positive regulation of the autophagosme assembly.

Disease relevance. Muscular dystrophy, limb-girdle, autosomal recessive 8 (LGMDR8) [MIM:254110] An autosomal recessive degenerative myopathy characterized by pelvic girdle, shoulder girdle and quadriceps muscle weakness. Clinical phenotype and severity are highly variable. Disease progression is slow and most patients remain ambulatory into the sixth decade of life. The disease is caused by variants affecting the gene represented in this entry. Bardet-Biedl syndrome 11 (BBS11) [MIM:615988] A syndrome characterized by usually severe pigmentary retinopathy, early-onset obesity, polydactyly, hypogenitalism, renal malformation and intellectual disability. Secondary features include diabetes mellitus, hypertension and congenital heart disease. Bardet-Biedl syndrome inheritance is autosomal recessive, but three mutated alleles (two at one locus, and a third at a second locus) may be required for clinical manifestation of some forms of the disease. The disease is caused by variants affecting the gene represented in this entry. It has been suggested that TRIM32 might be the E3 ubiquitin ligase for BBS2, a component of the BBSome complex involved in ciliogenesis, that is ubiquitinated and degraded by the proteasome.

Pathway. Protein modification; protein ubiquitination.

Similarity. Belongs to the TRIM/RBCC family.

RefSeq proteins (5): NP_001093149, NP_001365977, NP_001365978, NP_001365979, NP_036342* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000315	Znf_B-box	Domain
IPR001258	NHL_repeat	Repeat
IPR001841	Znf_RING	Domain
IPR011042	6-blade_b-propeller_TolB-like	Homologous_superfamily
IPR013083	Znf_RING/FYVE/PHD	Homologous_superfamily
IPR017907	Znf_RING_CS	Conserved_site
IPR027370	Znf-RING_euk	Domain
IPR047051	TRIM32_Bbox1_Znf	Domain

Pfam: PF01436, PF13445

UniProt features (40 total): sequence variant 7, modified residue 5, repeat 5, strand 5, binding site 4, mutagenesis site 3, helix 3, turn 2, zinc finger region 2, initiator methionine 1, chain 1, sequence conflict 1, coiled-coil region 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
5FEY	X-RAY DIFFRACTION	2.23
2CT2	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q13049-F1	78.19	0.30

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): 100; 103; 123; 128

Post-translational modifications (5): 2, 55, 328, 335, 339

Mutagenesis-validated functional residues (3):

Position	Phenotype
39	abolished e3 ubiquitin ligase activity and ability to activate ulk1. impairs atg7 ubiquitination.
55	increases the apoptotic cell death induced by glucose starvation.
55	decreases the apoptotic cell death induced by glucose starvation.

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-3134975	Regulation of innate immune responses to cytosolic DNA
R-HSA-983168	Antigen processing: Ubiquitination & Proteasome degradation

MSigDB gene sets: 603 (showing top): GSE45365_NK_CELL_VS_CD8_TCELL_UP, GOBP_REGULATION_OF_AUTOPHAGY, REACTOME_INNATE_IMMUNE_SYSTEM, GOBP_VACUOLE_ORGANIZATION, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, GOBP_RESPONSE_TO_PEPTIDE, REACTOME_CLASS_I_MHC_MEDIATED_ANTIGEN_PROCESSING_PRESENTATION, REACTOME_ANTIGEN_PROCESSING_UBIQUITINATION_PROTEASOME_DEGRADATION, GOBP_POSITIVE_REGULATION_OF_MUSCLE_CELL_DIFFERENTIATION, GOBP_POSITIVE_REGULATION_OF_VACUOLE_ORGANIZATION, GOBP_POSITIVE_REGULATION_OF_NEURON_DIFFERENTIATION, GOBP_NEGATIVE_REGULATION_OF_VIRAL_PROCESS, GOBP_CANONICAL_NF_KAPPAB_SIGNAL_TRANSDUCTION, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_UP

GO Biological Process (49): autophagosome assembly (GO:0000045), protein polyubiquitination (GO:0000209), tissue homeostasis (GO:0001894), ubiquitin-dependent protein catabolic process (GO:0006511), response to oxidative stress (GO:0006979), actin ubiquitination (GO:0007014), response to UV (GO:0009411), positive regulation of autophagy (GO:0010508), free ubiquitin chain polymerization (GO:0010994), protein ubiquitination (GO:0016567), positive regulation of cell growth (GO:0030307), positive regulation of cell migration (GO:0030335), negative regulation of viral transcription (GO:0032897), cellular response to stress (GO:0033554), negative regulation of toll-like receptor 4 signaling pathway (GO:0034144), cellular response to amino acid starvation (GO:0034198), response to tumor necrosis factor (GO:0034612), response to starvation (GO:0042594), positive regulation of canonical NF-kappaB signal transduction (GO:0043123), suppression of viral release by host (GO:0044790), innate immune response (GO:0045087), fat cell differentiation (GO:0045444), positive regulation of neuron differentiation (GO:0045666), positive regulation of protein catabolic process (GO:0045732), positive regulation of cell cycle (GO:0045787), positive regulation of proteolysis (GO:0045862), muscle cell cellular homeostasis (GO:0046716), negative regulation of fibroblast proliferation (GO:0048147), positive regulation of neurogenesis (GO:0050769), positive regulation of striated muscle cell differentiation (GO:0051155), axon development (GO:0061564), protein K63-linked ubiquitination (GO:0070534), negative regulation of cilium assembly (GO:1902018), negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage (GO:1902230), positive regulation of tumor necrosis factor-mediated signaling pathway (GO:1903265), positive regulation of interleukin-17-mediated signaling pathway (GO:1903883), positive regulation of chemokine (C-C motif) ligand 20 production (GO:1903886), positive regulation of cell motility (GO:2000147), positive regulation of autophagosome assembly (GO:2000786), positive regulation of catabolic process (GO:0009896)

GO Molecular Function (14): transcription coactivator activity (GO:0003713), RNA binding (GO:0003723), ubiquitin-protein transferase activity (GO:0004842), zinc ion binding (GO:0008270), myosin binding (GO:0017022), protein-macromolecule adaptor activity (GO:0030674), Tat protein binding (GO:0030957), translation initiation factor binding (GO:0031369), identical protein binding (GO:0042802), ubiquitin binding (GO:0043130), ubiquitin protein ligase activity (GO:0061630), protein binding (GO:0005515), transferase activity (GO:0016740), metal ion binding (GO:0046872)

GO Cellular Component (8): nucleus (GO:0005634), cytoplasm (GO:0005737), mitochondrion (GO:0005739), autophagosome (GO:0005776), endoplasmic reticulum (GO:0005783), centrosome (GO:0005813), cytosol (GO:0005829), striated muscle myosin thick filament (GO:0005863)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Cytosolic sensors of pathogen-associated DNA	1
Class I MHC mediated antigen processing & presentation	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein ubiquitination	3
response to stress	3
protein binding	3
intracellular membrane-bounded organelle	3
cytoplasm	3
cellular anatomical structure	2
Atg12 activating enzyme activity	1
protein-phosphatidylethanolamide deconjugating activity	1
Atg12 conjugating enzyme activity	1
Atg12 ligase activity	1
organelle assembly	1
Atg1/ULK1 kinase complex assembly	1
autophagosome organization	1
multicellular organismal-level homeostasis	1
anatomical structure homeostasis	1
modification-dependent protein catabolic process	1
actin modification	1
response to light stimulus	1
autophagy	1
positive regulation of catabolic process	1
regulation of autophagy	1
ubiquitin recycling	1
protein polymerization	1
protein modification by small protein conjugation	1
regulation of cell growth	1
cell growth	1
positive regulation of growth	1
positive regulation of cellular process	1
cell migration	1
regulation of cell migration	1
positive regulation of cell motility	1
viral transcription	1
regulation of viral transcription	1
negative regulation of viral process	1
cellular response to stimulus	1
negative regulation of immune system process	1
negative regulation of signal transduction	1
toll-like receptor 4 signaling pathway	1
regulation of toll-like receptor 4 signaling pathway	1
cellular response to starvation	1

Protein interactions and networks

STRING

1664 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TRIM32	AGO1	Q9UL18	881
TRIM32	CAPN3	P20807	858
TRIM32	FKRP	Q9H9S5	852
TRIM32	BBS12	Q6ZW61	817
TRIM32	UBE2N	P61088	812
TRIM32	BBS10	Q8TAM1	805
TRIM32	WDPCP	O95876	802
TRIM32	MKS1	Q9NXB0	776
TRIM32	BBOX1	O75936	775
TRIM32	TRAT1	Q6PIZ9	765
TRIM32	TTC8	Q8TAM2	752
TRIM32	BBS5	Q8N3I7	749
TRIM32	BBS9	P78514	745
TRIM32	ANO5	Q75V66	738
TRIM32	BBS7	Q8IWZ6	737

IntAct

309 interactions, top by confidence:

A	B	Type	Score
PDE9A	TRIM32	psi-mi:“MI:0915”(physical association)	0.880
TRIM32	PDE9A	psi-mi:“MI:0915”(physical association)	0.880
TRIM32	SCGB1A1	psi-mi:“MI:0915”(physical association)	0.830
SCGB1A1	TRIM32	psi-mi:“MI:0915”(physical association)	0.830
TRIM32	RABAC1	psi-mi:“MI:0915”(physical association)	0.810
RABAC1	TRIM32	psi-mi:“MI:0915”(physical association)	0.810
TRIM32	PDE9A	psi-mi:“MI:0915”(physical association)	0.810
PDE9A	TRIM32	psi-mi:“MI:0915”(physical association)	0.810

BioGRID (349): TP53 (Affinity Capture-Western), TRIM32 (Affinity Capture-Western), TRIM32 (Biochemical Activity), UBE2E1 (Reconstituted Complex), UBE2D1 (Reconstituted Complex), PIAS4 (Biochemical Activity), TRIM32 (Two-hybrid), TRIM32 (Two-hybrid), TRIM32 (Two-hybrid), TRIM32 (Two-hybrid), TRIM32 (Two-hybrid), TRIM32 (Two-hybrid), TRIM32 (Two-hybrid), UBQLN1 (Two-hybrid), KCTD9 (Two-hybrid)

ESM2 similar proteins: A1E2V0, A5D8Q0, A9JTP3, A9ULZ2, B1B1A0, O08863, O62640, P33279, P36406, P36407, P42573, P51784, P98170, Q13049, Q13075, Q13489, Q13490, Q1L8G6, Q24307, Q4R8E0, Q5BKL8, Q60989, Q62210, Q63185, Q6P5D3, Q6ZPS6, Q6ZUJ8, Q7Z2W4, Q80Z32, Q8C7M3, Q8CH72, Q8JHV9, Q8K337, Q8N1W1, Q8R151, Q90660, Q95M71, Q95M72, Q96P09, Q9BQI3

Diamond homologs: A0A7I2V3R4, D2H6Z0, D4A723, E1C2W7, Q03601, Q13049, Q3SWY0, Q58EC8, Q68EV7, Q6GND7, Q6NRD3, Q8BG47, Q8CH72, Q8N8N0, Q8QZS5, Q96D59, Q9D241, A6NIN4, D2H788, D3ZBM4, O70277, O75382, Q3T0Y9, Q6IMG5, Q6INB3, Q8C432, Q8K0W3, Q8N6D2, Q9DCB3, Q9FY48, Q9H0X6, Q9NXI6, Q9R1R2, A6NCQ9, E7ERA6, M0QZC1, P0DH78, Q3UIW8, Q3UV31, Q8CEF8

SIGNOR signaling

8 interactions.

A	Effect	B	Mechanism
Ub:E2	“up-regulates activity”	TRIM32	ubiquitination
CHEK2	“up-regulates activity”	TRIM32	phosphorylation
TRIM32	“down-regulates quantity by destabilization”	POU5F1	ubiquitination
TRIM32	“down-regulates quantity by destabilization”	MYC	ubiquitination
TRIM32	“down-regulates quantity by destabilization”	PBRM1	ubiquitination
TRIM32	“down-regulates quantity”	DTNBP1	ubiquitination
TRIM32	“down-regulates quantity by destabilization”	DBNDD1	ubiquitination

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 78 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
Aggrephagy	5	24.8×	3e-04
HSP90 chaperone cycle for steroid hormone receptors (SHR) in the presence of ligand	5	19.4×	6e-04
Translocation of SLC2A4 (GLUT4) to the plasma membrane	6	18.5×	2e-04
ER to Golgi Anterograde Transport	5	13.3×	2e-03
Golgi-to-ER retrograde transport	5	13.3×	2e-03
COPI-mediated anterograde transport	5	11.0×	3e-03
Intra-Golgi and retrograde Golgi-to-ER traffic	5	10.5×	3e-03
Transport to the Golgi and subsequent modification	5	10.3×	3e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	4
Likely pathogenic	6
Uncertain significance	31
Likely benign	0
Benign	3

Top pathogenic / likely-pathogenic (10)

Variant ID	HGVS	Classification
1343785	NM_012210.4(TRIM32):c.1603del (p.Leu535fs)	Pathogenic
1878371	NC_000009.11:g.(?119449580)(119463580_?)del	Pathogenic
2504043	NC_000009.11:g.(119449661_119459940)(119463580?)del	Pathogenic
3384692	NM_012210.4(TRIM32):c.564T>A (p.Tyr188Ter)	Pathogenic
3596359	NM_012210.4(TRIM32):c.577_581del (p.Arg193fs)	Likely pathogenic
3596361	NM_012210.4(TRIM32):c.697_721dup (p.Tyr241delinsCysAlaGlyCysValSerLeuTer)	Likely pathogenic
3596372	NM_012210.4(TRIM32):c.1297_1298del (p.Val434fs)	Likely pathogenic
3596373	NM_012210.4(TRIM32):c.1448_1449dup (p.Val484fs)	Likely pathogenic
3596374	NM_012210.4(TRIM32):c.1481G>A (p.Trp494Ter)	Likely pathogenic
3897046	NM_012210.4(TRIM32):c.1569dup (p.Glu524Ter)	Likely pathogenic

SpliceAI

345 predictions. Top by Δscore:

Variant	Effect	Δscore
9:116695167:A:AC	donor_gain	1.0000
9:116695168:C:CC	donor_gain	1.0000
9:116697660:A:AG	acceptor_gain	1.0000
9:116697661:G:GG	acceptor_gain	1.0000
9:116687378:TCAG:T	donor_loss	0.9900
9:116687379:CAGG:C	donor_loss	0.9900
9:116687380:AGGTA:A	donor_loss	0.9900
9:116687381:GGTAG:G	donor_loss	0.9900
9:116687382:G:GA	donor_loss	0.9900
9:116687383:T:G	donor_loss	0.9900
9:116695162:T:C	donor_gain	0.9900
9:116695170:T:TA	donor_gain	0.9900
9:116697656:CTTTA:C	acceptor_loss	0.9900
9:116697657:TTTA:T	acceptor_loss	0.9900
9:116697658:TTAGC:T	acceptor_loss	0.9900
9:116697659:TAG:T	acceptor_loss	0.9900
9:116697660:AGCAG:A	acceptor_gain	0.9900
9:116697661:GCA:G	acceptor_gain	0.9900
9:116697661:GCAGG:G	acceptor_gain	0.9900
9:116697659:TAGCA:T	acceptor_gain	0.9800
9:116697661:GC:G	acceptor_gain	0.9800
9:116697663:AG:A	acceptor_gain	0.9800
9:116697664:GG:G	acceptor_gain	0.9800
9:116697664:GGA:G	acceptor_gain	0.9800
9:116687497:G:GT	donor_gain	0.9700
9:116697662:CA:C	acceptor_loss	0.9700
9:116697664:G:A	acceptor_loss	0.9700
9:116695164:TG:T	donor_gain	0.9500
9:116695169:T:C	donor_gain	0.9500
9:116687378:TC:T	donor_gain	0.9400

AlphaMissense

4265 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:116697800:T:C	C20R	1.000
9:116697843:C:A	P34H	1.000
9:116697857:T:C	C39R	1.000
9:116697923:T:C	C61R	1.000
9:116697932:T:C	C64R	1.000
9:116698863:C:A	P374Q	1.000
9:116698863:C:G	P374R	1.000
9:116698902:T:A	V387D	1.000
9:116698923:G:C	R394P	1.000
9:116699289:C:A	P516H	1.000
9:116699298:T:A	V519D	1.000
9:116699637:T:A	V632D	1.000
9:116697800:T:A	C20S	0.999
9:116697801:G:C	C20S	0.999
9:116697802:C:G	C20W	0.999
9:116697809:T:A	C23S	0.999
9:116697809:T:C	C23R	0.999
9:116697810:G:A	C23Y	0.999
9:116697810:G:C	C23S	0.999
9:116697811:C:G	C23W	0.999
9:116697842:C:A	P34T	0.999
9:116697842:C:T	P34S	0.999
9:116697843:C:G	P34R	0.999
9:116697858:G:A	C39Y	0.999
9:116697859:T:G	C39W	0.999
9:116697863:C:G	H41D	0.999
9:116697865:T:A	H41Q	0.999
9:116697865:T:G	H41Q	0.999
9:116697872:T:C	C44R	0.999
9:116697873:G:A	C44Y	0.999

dbSNP variants (sampled 300 via entrez): RS1000223510 (9:116687295 G>A,C,T), RS1000239114 (9:116694934 G>A,C), RS1000579634 (9:116693060 G>A,C,T), RS1000762040 (9:116686249 C>T), RS1000775632 (9:116698883 A>C,G,T), RS1000826239 (9:116687413 G>T), RS1000966080 (9:116685942 G>T), RS1001023662 (9:116700630 C>A,G), RS1001047323 (9:116692731 C>T), RS1001385471 (9:116691110 G>A), RS1001557859 (9:116700365 G>T), RS1001841602 (9:116692135 CCAA>C), RS1001894063 (9:116699888 C>A,T), RS1002118104 (9:116692578 C>T), RS1002255184 (9:116691474 A>G)

Disease associations

OMIM: gene MIM:602290 | disease phenotypes: MIM:254110, MIM:253600, MIM:615988

GenCC curated gene-disease

Disease	Classification	Inheritance
autosomal recessive limb-girdle muscular dystrophy type 2H	Definitive	Autosomal recessive
Bardet-Biedl syndrome 11	Strong	Autosomal recessive
Bardet-Biedl syndrome	Supportive	Autosomal recessive

ClinGen Gene-Disease Validity (2)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
Bardet-Biedl syndrome 11	Limited	AR
autosomal recessive limb-girdle muscular dystrophy	Definitive	AR

Mondo (4): autosomal recessive limb-girdle muscular dystrophy type 2H (MONDO:0009683), autosomal recessive limb-girdle muscular dystrophy (MONDO:0015152), Bardet-Biedl syndrome 11 (MONDO:0014439), Bardet-Biedl syndrome (MONDO:0015229)

Orphanet (3): TRIM32-related limb-girdle muscular dystrophy R8 (Orphanet:1878), Autosomal recessive limb-girdle muscular dystrophy (Orphanet:102015), Bardet-Biedl syndrome (Orphanet:110)

HPO phenotypes

130 total (30 of 130 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000011	Neurogenic bladder
HP:0000028	Cryptorchidism
HP:0000076	Vesicoureteral reflux
HP:0000077	Abnormality of the kidney
HP:0000085	Horseshoe kidney
HP:0000098	Tall stature
HP:0000100	Nephrotic syndrome
HP:0000119	Abnormality of the genitourinary system
HP:0000126	Hydronephrosis
HP:0000135	Hypogonadism
HP:0000147	Polycystic ovaries
HP:0000163	Abnormal oral cavity morphology
HP:0000218	High palate
HP:0000278	Retrognathia
HP:0000298	Mask-like facies
HP:0000316	Hypertelorism
HP:0000343	Long philtrum
HP:0000358	Posteriorly rotated ears
HP:0000365	Hearing impairment
HP:0000388	Otitis media
HP:0000400	Macrotia
HP:0000426	Prominent nasal bridge
HP:0000470	Short neck
HP:0000483	Astigmatism
HP:0000486	Strabismus
HP:0000488	Retinopathy
HP:0000494	Downslanted palpebral fissures
HP:0000512	Abnormal electroretinogram
HP:0000518	Cataract

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST007876_91	Estimated glomerular filtration rate	4.000000e-12
GCST012227_451	Hip circumference adjusted for BMI	4.000000e-09

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0008039	BMI-adjusted hip circumference

MeSH disease descriptors (4)

Descriptor	Name	Tree numbers
D020788	Bardet-Biedl Syndrome	C10.228.140.617.200; C11.270.684.624; C16.131.077.245.125; C16.320.184.125
C565920	Bardet-Biedl Syndrome 11 (supp.)
C538640	Limb-girdle muscular dystrophy autosomal recessive (supp.)
C535897	Limb-girdle muscular dystrophy type 2H (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases expression, increases methylation	3
sodium arsenite	increases abundance, decreases expression	2
Cisplatin	decreases expression, increases expression	2
Ethyl Methanesulfonate	decreases expression, increases expression	2
Formaldehyde	decreases expression, increases expression	2
Methyl Methanesulfonate	decreases expression, increases expression	2
aristolochic acid I	decreases expression	1
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
FR900359	affects phosphorylation	1
bisphenol F	affects cotreatment, increases expression	1
triphenyl phosphate	affects expression	1
arsenite	increases methylation	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
nickel sulfate	decreases expression	1
beta-methylcholine	affects expression	1
di-n-butylphosphoric acid	affects expression	1
perfluoro-n-nonanoic acid	decreases expression	1
Leflunomide	decreases expression	1
Acetaminophen	increases expression	1
Adenine	decreases expression	1
Air Pollutants, Occupational	affects expression	1
Arsenic	decreases expression, increases abundance	1
Caffeine	decreases phosphorylation	1
Colchicine	decreases expression	1
Dexamethasone	affects cotreatment, increases expression	1
Hydroxyurea	decreases expression	1
Indomethacin	affects cotreatment, increases expression	1
Ivermectin	decreases expression	1
Thiram	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_TU06	HAP1 TRIM32 (-) 1	Cancer cell line	Male
CVCL_TU07	HAP1 TRIM32 (-) 2	Cancer cell line	Male
CVCL_TU08	HAP1 TRIM32 (-) 3	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT03746522	PHASE3	COMPLETED	Setmelanotide (RM-493), Melanocortin-4 Receptor (MC4R) Agonist, in Bardet-Biedl Syndrome (BBS) and Alström Syndrome (AS) Participants With Moderate to Severe Obesity
NCT04966741	PHASE3	COMPLETED	Setmelanotide in Pediatric Participants With Rare Genetic Diseases of Obesity
NCT05194124	PHASE3	COMPLETED	Phase 3 Crossover Trial of Two Formulations of Setmelanotide in Participants With Specific Gene Defects in the MC4R Pathway
NCT03490019	PHASE2	WITHDRAWN	Treatment of Bardet-Biedl-Syndrome With Metformin for Evaluation of a Possible Visual Improvement
NCT00078091	Not specified	TERMINATED	Genetics and Clinical Characteristics of Bardet-Biedl Syndrome
NCT00213811	Not specified	COMPLETED	Bardet-Biedl Syndrome Study: Clinical and Genetic Epidemiology Study in Adults
NCT01401998	Not specified	RECRUITING	ARPKD Database Study
NCT02329210	Not specified	RECRUITING	Clinical Registry Investigating Bardet-Biedl Syndrome
NCT02435940	Not specified	RECRUITING	Inherited Retinal Degenerative Disease Registry
NCT04461444	Not specified	RECRUITING	COhort for Bardet-Bield Syndrome and Alström Syndrome for Translational Research Monocentric Interventional Study
NCT04463316	Not specified	RECRUITING	GROWing Up With Rare GENEtic Syndromes
NCT04874909	Not specified	COMPLETED	Classification, Functional Stratification and Biomarkers in Ciliopathy (CILLICORIRCM)
NCT05183802	Not specified	APPROVED_FOR_MARKETING	An Expanded Access Protocol for Setmelanotide for Treatment of Bardet-Biedl Syndrome (BBS)
NCT05400278	Not specified	COMPLETED	Characterizing the Genotype and Phenotype in Adults With Bardet-Biedl Syndrome
NCT06239064	Not specified	ACTIVE_NOT_RECRUITING	Early Genetic Identification of Obesity
NCT06615011	Not specified	NOT_YET_RECRUITING	Bardet Beidle Syndrome in a Syrian Adolescent : a Rare Case Report
NCT07602803	Not specified	COMPLETED	The Effect of GLP1 Agonists on Weight Loss in BBS Cohort in the UK