TRIM22

Summary

TRIM22 (tripartite motif containing 22, HGNC:16379) is a protein-coding gene on chromosome 11p15.4, encoding E3 ubiquitin-protein ligase TRIM22 (Q8IYM9). Interferon-induced E3 ubiquitin ligase that plays important roles in innate and adaptive immunity.

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. This protein localizes to the cytoplasm and its expression is induced by interferon. The protein is involved in innate immunity against different DNA and RNA viruses.

Source: NCBI Gene 10346 — RefSeq curated summary.

At a glance

• Gene–disease (curated): inborn error of immunity (Strong, GenCC) — +1 more curated relationship
• GWAS associations: 6
• Clinical variants (ClinVar): 109 total
• MANE Select transcript: NM_006074

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16379
Approved symbol	TRIM22
Name	tripartite motif containing 22
Location	11p15.4
Locus type	gene with protein product
Status	Approved
Aliases	STAF50, GPSTAF50, RNF94
Ensembl gene	ENSG00000132274
Ensembl biotype	protein_coding
OMIM	606559
Entrez	10346

Gene structure

Transcript identifiers

Ensembl transcripts: 24 — 14 protein_coding, 8 retained_intron, 2 nonsense_mediated_decay

ENST00000379965, ENST00000414641, ENST00000414897, ENST00000425490, ENST00000429063, ENST00000444844, ENST00000450670, ENST00000454828, ENST00000460454, ENST00000480395, ENST00000493494, ENST00000699052, ENST00000699053, ENST00000699054, ENST00000699055, ENST00000699056, ENST00000699057, ENST00000699058, ENST00000901728, ENST00000932828, ENST00000932829, ENST00000932830, ENST00000957657, ENST00000957658

RefSeq mRNA: 2 — MANE Select: NM_006074 NM_001199573, NM_006074

CCDS: CCDS41612

Canonical transcript exons

ENST00000379965 — 8 exons

Exon	Start	End
ENSE00000903265	5696167	5696655
ENSE00001432184	5698315	5698545
ENSE00001483256	5689790	5689899
ENSE00001647173	5697248	5697343
ENSE00001900762	5709053	5710863
ENSE00003617789	5708577	5708603
ENSE00003667544	5708173	5708273
ENSE00003684220	5706594	5706616

Expression profiles

Bgee: expression breadth ubiquitous, 285 present calls, max score 98.65.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 48.0091 / max 1063.4058, expressed in 1492 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
112829	37.9259	1446
112824	4.6794	940
112828	3.2028	1034
112825	0.6820	381
112826	0.5052	298
112827	0.5041	289
112823	0.3606	227
112830	0.1493	54

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
monocyte	CL:0000576	98.65	gold quality
mononuclear cell	CL:0000842	98.65	gold quality
leukocyte	CL:0000738	98.63	gold quality
spleen	UBERON:0002106	98.56	gold quality
lymph node	UBERON:0000029	98.47	gold quality
calcaneal tendon	UBERON:0003701	98.44	gold quality
granulocyte	CL:0000094	98.26	gold quality
gall bladder	UBERON:0002110	98.24	gold quality
palpebral conjunctiva	UBERON:0001812	98.14	gold quality
vermiform appendix	UBERON:0001154	98.06	gold quality
right uterine tube	UBERON:0001302	97.96	gold quality
blood	UBERON:0000178	97.84	gold quality
epithelium of nasopharynx	UBERON:0001951	97.58	gold quality
upper lobe of left lung	UBERON:0008952	97.29	gold quality
superficial temporal artery	UBERON:0001614	97.18	gold quality
upper lobe of lung	UBERON:0008948	97.17	gold quality
descending thoracic aorta	UBERON:0002345	97.05	gold quality
caput epididymis	UBERON:0004358	97.00	gold quality
cauda epididymis	UBERON:0004360	96.98	gold quality
corpus epididymis	UBERON:0004359	96.93	gold quality
sural nerve	UBERON:0015488	96.89	gold quality
lower lobe of lung	UBERON:0008949	96.65	gold quality
tibial nerve	UBERON:0001323	96.54	gold quality
skin of hip	UBERON:0001554	96.52	gold quality
right lung	UBERON:0002167	96.40	gold quality
tonsil	UBERON:0002372	96.30	gold quality
caecum	UBERON:0001153	96.16	gold quality
left ovary	UBERON:0002119	96.11	gold quality
nasal cavity epithelium	UBERON:0005384	96.11	gold quality
right ovary	UBERON:0002118	96.08	gold quality

Single-cell (SCXA)

Detected in 6 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-MTAB-7381	yes	453.69
E-HCAD-13	yes	22.82
E-MTAB-9801	yes	7.74
E-MTAB-6379	no	372.04
E-MTAB-10137	no	164.69
E-ANND-3	no	0.00

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

3 targets.

Target	Regulation
JUN	Activation
NFKB1	Unknown
RELA	Unknown

Upstream regulators (CollecTRI, top): CREBBP, EP300, IRF1, TP53

miRNA regulators (miRDB)

82 targeting TRIM22, 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-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-3617-3P	99.98	67.86	918
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-3910	99.95	71.13	2227
HSA-MIR-4760-3P	99.93	70.50	2385
HSA-MIR-589-3P	99.91	69.62	2088
HSA-MIR-7845-5P	99.88	64.88	771
HSA-MIR-30A-3P	99.87	69.74	2928
HSA-MIR-30D-3P	99.87	69.92	2917
HSA-MIR-30E-3P	99.87	69.68	2942
HSA-MIR-6844	99.82	70.69	2423
HSA-MIR-6739-5P	99.80	67.87	2806
HSA-MIR-323A-3P	99.79	70.30	1739
HSA-MIR-577	99.78	69.13	2479
HSA-MIR-6733-5P	99.74	67.94	2759
HSA-MIR-12129	99.72	67.45	1311
HSA-MIR-33A-3P	99.70	70.27	3362
HSA-MIR-12124	99.68	69.17	2700
HSA-MIR-6512-3P	99.65	66.07	1468
HSA-MIR-6720-5P	99.65	66.22	1459
HSA-MIR-1251-3P	99.64	67.21	1408
HSA-MIR-6848-3P	99.64	66.49	885

Literature-anchored findings (GeneRIF, showing 40)

• May be involved in proliferation and/or differentiation of leukemic cells. (PMID:15064739)
• Overexpression of Staf50 inhibited the HIV-1 infection between 50% and 90% in 293 T CD4/CCR5 as well as in monocyte-derived macrophages. (PMID:16926043)
• These data suggest a more complex role for TRIM22 during T lymphocyte activation than merely as an antiproliferative factor. (PMID:17970695)
• TRIM22 inhibits HIV-1 particle production by interfering with the trafficking of Gag to the plasma membrane and is a key player in the antiviral activity of the Type I interferon response to HIV-1. (PMID:18389079)
• A novel property of TRIM22, E3 ubiquitin ligase activity, was demonstrated. (PMID:18656448)
• Study shows that human and rhesus TRIM22 localise to different subcellular compartments and that this difference can be assigned to the positively selected B30.2 domain. (PMID:19212762)
• TRIM22 is an E3 Ubiquitin ligase whose expression leads to antiviral effects towards Encephalomyocarditis virus infections in HeLa cells. [TRIM22] (PMID:19218198)
• Deletion of putative nuclear localization signal abolished TRIM22 localization and nuclear body (NB) formation, the B30.2/SplA and ryanodine receptor (SPRY) domain, and residues 491-494 specifically are essential for nuclear localization and NB formation. (PMID:19481078)
• TRIM22-mediated anti-hepatitis B virus activity dependent on the nuclear-located RING domain (PMID:19585648)
• REVIEW: current knowledge on the anti-retroviral effects of TRIM5 alpha and TRIM22 (PMID:19943174)
• Specific polymorphisms in tripartite motif22 (TRIM22) genes were significantly associated with rubella vaccine humoral immunity (PMID:20001730)
• endogenous TRIM22 is localized to both nucleus and cytosol in primary human mononuclear cells, as well as in the human osteosarcoma cell line U2OS (PMID:20006605)
• These data suggest concordance between type 1 IFN and TRIM22 in PBMCs and that TRIM22 likely acts as an antiviral effector in HIV-1 infection. (PMID:20980524)
• Nuclear TRIM22 significantly impairs HIV-1 replication, likely by interfering with Tat- and NF-kappaB-independent long-terminal-repeat-driven transcription. (PMID:21345949)
• These data suggested that TRIM22 was a positive regulator of NF-kappaB-mediated transcription. (PMID:21651891)
• BRG1-mediated chromatin remodeling is critical for the IFN-gamma-inducibility of TRIM22 gene. (PMID:21683060)
• TRIM22 to repress protein translation preferably of some specific mRNAs. TRIM22 represses translation by inhibiting the binding of eIF4E to eIF4G, suggesting a mechanism for regulation of protein translation (PMID:22509910)
• Restriction of influenza A virus replication was accounted for by the interaction between TRIM22 and the viral nucleoprotein (NP), resulting in its polyubiquitination and degradation in a proteasome-dependent manner (PMID:23408607)
• p300 contributed to both IFN-gamma- and IRF-1-mediated TRIM22 transcription independent of its histone acetyltransferase activity, however, it was required for the recruitment of RNA polymerase II to TRIM22 promoter region. (PMID:23670564)
• These data indicate that overexpression of TRIM22 may negatively regulate the TRAF6-stimulated NF-kappaB pathway by interacting with and degrading TAB2. (PMID:23818111)
• TRIM22 genetic diversity affects HIV-1 replication in vitro and it is a potentially novel determinant of HIV-1 disease severity (PMID:23921607)
• Data report that markers in two TRIMs, TRIM5 and TRIM22 and a marker in BST2, associated statistically with the risk of getting MS. (PMID:24066097)
• this study shows that TRIM22 is greatly under-expressed in breast cancer. p53 dysfunction may be one of the mechanisms for TRIM22 down-regulation. (PMID:24183724)
• TRIM5alpha and TRIM22 have differential transcriptional regulation and distinct anti-HIV roles according to infection phase. (PMID:24478420)
• our data characterize the extensive genetic variation in TRIM22 and identify rs1063303:G>C as a highly prevalent SNP that influences its function. (PMID:24863734)
• Upregulation of TRIM22 may be associated with responsiveness to Peg-IFNalpha-2a/RBV combination therapy in hepatitis C. (PMID:24889558)
• A number of putative structural and functional residues, including several sites that undergo post-translational modification, were also identified in TRIM22. (PMID:24983760)
• TRIM22 could interact with IkappaB kinase (IKK)alpha but not IKKbeta and could increase the level and phosphorylation of IKKalpha through its really interesting new gene (RING) and spla-ryanodine receptor (SPRY) domains. (PMID:25510414)
• Interferon-alpha-induced TRIM22 interrupts hepatitis c virus replication by ubiquitinating NS5A. (PMID:25683609)
• regulation of FoxO4 protein expression and cell survival by TRIM22 controls TLR3-mediated IFN type I gene induction, preventing excessive antiviral response through dsRNA-induced apoptosis. (PMID:26237181)
• Data show that capsid protein p24-DsRed-Monomer was co-localized with tripartite motif containing 22 (TRIM22)-EGFP in HEK293T cells. (PMID:26271984)
• propose that TRIM22 is a direct target gene of PR and that it can mediate progesterone actions in uterine cells (PMID:26316153)
• Demonstrated that TRIM22 acts as a negative regulator of HIV-1 replication via inhibition of basal Sp1-driven proviral transcription. (PMID:26683615)
• Infant with severe IBD characterized by granulomatous colitis and severe perianal disease, we identified a homozygous variant of TRIM22 that affects the ability of its product to regulate NOD2. (PMID:26836588)
• TRIM5 and TRIM22 single nucleotide polymorphisms are associated to increased odds of significant liver fibrosis and sustained virological response after pegIFNalpha/RBV therapy in human immunodeficiency virus/hepatitis C virus coinfected patients. (PMID:27590274)
• Wthis study identified a genetic variation (rs7935564 G allele) in TRIM22 gene, which encodes TRIM22 protein acting like a HIV restriction factor, as being associated with good response to dendritic cell-based immunotherapy (PMID:27704462)
• Upregulation of TRIM22 triggers the expression and oligomerization of Bak and subsequently leads to cytochrome c release in a caspase-9- and caspase-3-dependent manner. Both the RING domain and the SPRY domain of the TRIM22 molecule are associated with its pro-apoptotic function. (PMID:28079123)
• Suppression of interferon-mediated anti-HBV response by single CpG methylation in the 5’-UTR of TRIM22. (PMID:28341749)
• trim22 is a broad and multifunctional host anti-viral factor induced by interferons. (PMID:28782753)
• TRIM22 may act as epigenetic inhibitor of HIV-1 transcription by preventing the binding of the host cell transcription factor Sp1 to the viral promoter. (PMID:29650252)

Cross-species orthologs

1 orthologs

Organism	Symbol	Gene ID
mus_musculus	Trim75	ENSMUSG00000071089

Paralogs (80): MID2 (ENSG00000080561), TRIM9 (ENSG00000100505), MID1 (ENSG00000101871), MEFV (ENSG00000103313), TRIM35 (ENSG00000104228), TRIM14 (ENSG00000106785), TRIM37 (ENSG00000108395), TRIM2 (ENSG00000109654), TRIM3 (ENSG00000110171), TRIM38 (ENSG00000112343), TRIM62 (ENSG00000116525), TRIM67 (ENSG00000119283), TRIM32 (ENSG00000119401), BSPRY (ENSG00000119411), TRIM25 (ENSG00000121060), TRIM6 (ENSG00000121236), TRIM24 (ENSG00000122779), TRIM51 (ENSG00000124900), TRIM28 (ENSG00000130726), TRIM21 (ENSG00000132109), TRIM5 (ENSG00000132256), 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 TRIM22 — Q8IYM9 (reviewed: Q8IYM9)

Alternative names: 50 kDa-stimulated trans-acting factor, RING finger protein 94, RING-type E3 ubiquitin transferase TRIM22, Staf-50, Tripartite motif-containing protein 22

All UniProt accessions (10): Q8IYM9, A0A8V8TN39, A0A8V8TP25, C9J060, C9JIU5, C9JWC5, H7BZD3, H7C262, H7C2K0, H7C376

UniProt curated annotations — full annotation on UniProt →

Function. Interferon-induced E3 ubiquitin ligase that plays important roles in innate and adaptive immunity. Restricts the replication of many viruses including HIV-1, encephalomyocarditis virus (EMCV), hepatitis B virus (HBV), hepatitis C virus (HCV) or Zika virus (ZIKV). Mechanistically, negatively regulates HCV replication by promoting ubiquitination and subsequent degradation of viral NS5A. Also acts by promoting the degradation of Zika virus NS1 and NS3 proteins through proteasomal degradation. Acts as a suppressor of basal HIV-1 LTR-driven transcription by preventing Sp1 binding to the HIV-1 promoter. Also plays a role in antiviral immunity by co-regulating together with NT5C2 the RIGI/NF-kappa-B pathway by promoting ‘Lys-63’-linked ubiquitination of RIGI, while NT5C2 is responsible for ‘Lys-48’-linked ubiquitination of RIGI. Participates in adaptive immunity by suppressing the amount of MHC class II protein in a negative feedback manner in order to limit the extent of MHC class II induction.

Subunit / interactions. Homotrimer. (Microbial infection) Interacts with HIV-1 Gag polyprotein; this interaction seems to reduce gag production or virus budding. (Microbial infection) Interacts with EMCV protease 3C; this interaction leads to viral protease ubiquitination.

Subcellular location. Cytoplasm. Nucleus. Nucleus speckle. Cajal body.

Tissue specificity. Strongly expressed in peripheral blood leukocytes, spleen, thymus, and ovary. Expressed at basal levels in other tissues.

Post-translational modifications. Auto-ubiquitinated.

Domain organisation. The C-terminal SPRY domain is required for the transcriptional suppressor activity, probably by mediating correct nuclear localization. Residues 491-494 are essential for nuclear localization and nuclear bodies formation. The RING domain is essential for antiviral activity and for TRIM22 nuclear bodies (NB) formation but is not necessary for nuclear localization.

Induction. By interferons alpha and beta. Up-regulated by p53/TP53. Dramatically induced by progesterone in MDA-MB-231-derived ABC28 cells and T47D cells. By interferon gamma. Expression is also modulated in response to several viruses and viral antigens.

Pathway. Protein modification; protein ubiquitination.

Similarity. Belongs to the TRIM/RBCC family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q8IYM9-1	1	yes
Q8IYM9-2	2

RefSeq proteins (2): NP_001186502, NP_006065* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000315	Znf_B-box	Domain
IPR001841	Znf_RING	Domain
IPR001870	B30.2/SPRY	Domain
IPR003877	SPRY_dom	Domain
IPR003879	Butyrophylin_SPRY	Domain
IPR013083	Znf_RING/FYVE/PHD	Homologous_superfamily
IPR013320	ConA-like_dom_sf	Homologous_superfamily
IPR017907	Znf_RING_CS	Conserved_site
IPR027370	Znf-RING_euk	Domain
IPR035827	PRY/SPRY_TRIM22	Domain
IPR043136	B30.2/SPRY_sf	Homologous_superfamily
IPR050143	TRIM/RBCC	Family

Pfam: PF00622, PF00643, PF13445

Enzyme classification (BRENDA):

• EC 2.3.2.27 — RING-type E3 ubiquitin transferase (BRENDA: 28 organisms, 138 substrates, 10 inhibitors, 1 Km, 1 kcat entries)

Substrate kinetics (BRENDA)

1 substrates with measured Km, best-characterized 1. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
[UBE2W]-S-UBIQUITINYL-L-CYSTEINE	0.3014	1

UniProt features (19 total): sequence variant 4, binding site 4, mutagenesis site 3, zinc finger region 2, chain 1, domain 1, splice variant 1, sequence conflict 1, coiled-coil region 1, short sequence motif 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8IYM9-F1	85.38	0.54

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): 97; 100; 119; 125

Mutagenesis-validated functional residues (3):

Position	Phenotype
15	loss of e3 ubiquitin-protein ligase activity, reduces auto-ubiquitination and not affect nuclear bodies formation. loss
18	loss of antiviral activity and not affect nuclear bodies formation; when associated with a-15.
493–494	reduces formation of regular nuclear bodies.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-877300	Interferon gamma signaling

MSigDB gene sets: 290 (showing top): LEE_NEURAL_CREST_STEM_CELL_DN, GOBP_REGULATION_OF_AUTOPHAGY, IIZUKA_LIVER_CANCER_EARLY_RECURRENCE, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, GOBP_REGULATION_OF_DEFENSE_RESPONSE_TO_VIRUS, HOFMANN_CELL_LYMPHOMA_UP, MODULE_45, GOBP_CANONICAL_NF_KAPPAB_SIGNAL_TRANSDUCTION, WIELAND_UP_BY_HBV_INFECTION, BILD_HRAS_ONCOGENIC_SIGNATURE, CHANG_IMMORTALIZED_BY_HPV31_DN, CAIRO_HEPATOBLASTOMA_CLASSES_DN, ONKEN_UVEAL_MELANOMA_UP, GOBP_DEFENSE_RESPONSE_TO_OTHER_ORGANISM, DEURIG_T_CELL_PROLYMPHOCYTIC_LEUKEMIA_DN

GO Biological Process (16): positive regulation of defense response to virus by host (GO:0002230), regulation of DNA-templated transcription (GO:0006355), immune response (GO:0006955), response to virus (GO:0009615), regulation of gene expression (GO:0010468), positive regulation of autophagy (GO:0010508), regulation of protein localization (GO:0032880), positive regulation of canonical NF-kappaB signal transduction (GO:0043123), innate immune response (GO:0045087), defense response to virus (GO:0051607), protein K63-linked ubiquitination (GO:0070534), protein ubiquitination (GO:0016567), negative regulation of DNA-templated transcription (GO:0045892), positive regulation of DNA-templated transcription (GO:0045893), regulation of primary metabolic process (GO:0080090), antiviral innate immune response (GO:0140374)

GO Molecular Function (10): transcription coactivator activity (GO:0003713), transcription corepressor activity (GO:0003714), zinc ion binding (GO:0008270), protein kinase binding (GO:0019901), protein-macromolecule adaptor activity (GO:0030674), identical protein binding (GO:0042802), 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), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), Golgi apparatus (GO:0005794), cytosol (GO:0005829), Cajal body (GO:0015030), nuclear body (GO:0016604), nuclear speck (GO:0016607)

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
DNA-templated transcription	3
cellular anatomical structure	3
regulation of DNA-templated transcription	2
transcription coregulator activity	2
protein binding	2
intracellular membrane-bounded organelle	2
cytoplasm	2
nuclear ribonucleoprotein granule	2
regulation of defense response to virus by host	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
immune system process	1
response to stimulus	1
response to other organism	1
gene expression	1
regulation of macromolecule biosynthetic process	1
autophagy	1
positive regulation of catabolic process	1
regulation of autophagy	1
intracellular protein localization	1
regulation of localization	1
canonical NF-kappaB signal transduction	1
regulation of canonical NF-kappaB signal transduction	1
positive regulation of intracellular signal transduction	1
immune response	1
defense response to symbiont	1
defense response	1
response to virus	1
protein polyubiquitination	1
protein modification by small protein conjugation	1
negative regulation of RNA biosynthetic process	1
positive regulation of RNA biosynthetic process	1
regulation of metabolic process	1
primary metabolic process	1
innate immune response	1
defense response to virus	1
positive regulation of DNA-templated transcription	1
negative regulation of DNA-templated transcription	1
transition metal ion binding	1
kinase binding	1

Protein interactions and networks

STRING

1390 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TRIM22	TRAT1	Q6PIZ9	964
TRIM22	BBOX1	O75936	798
TRIM22	IFIT3	O14879	676
TRIM22	IFI44L	Q53G44	674
TRIM22	EIF2AK2	P19525	661
TRIM22	IFITM3	Q01628	631
TRIM22	IFI44	Q8TCB0	628
TRIM22	IRF1	P10914	596
TRIM22	PML	P29590	591
TRIM22	TRIM56	Q9BRZ2	590
TRIM22	BST2	Q10589	581
TRIM22	XAF1	Q6GPH4	579
TRIM22	PARP9	Q8IXQ6	563
TRIM22	HELZ2	Q9BYK8	543
TRIM22	BECN1	Q14457	533

IntAct

25 interactions, top by confidence:

A	B	Type	Score
TRIM22	NOD2	psi-mi:“MI:0915”(physical association)	0.590
NOD2	TRIM22	psi-mi:“MI:0915”(physical association)	0.590
TRIM22	NOD2	psi-mi:“MI:0403”(colocalization)	0.590
TRIM22	PLEKHF2	psi-mi:“MI:0915”(physical association)	0.560
TRIM22	MFHAS1	psi-mi:“MI:0407”(direct interaction)	0.440
TRIM22		psi-mi:“MI:0915”(physical association)	0.370
CREB1	TRIM22	psi-mi:“MI:0915”(physical association)	0.370
TAF7	TRIM22	psi-mi:“MI:0915”(physical association)	0.370
TRIM22	ZZZ3	psi-mi:“MI:0915”(physical association)	0.370
CASK	TRIM22	psi-mi:“MI:0915”(physical association)	0.370
STAT3	MRPL33	psi-mi:“MI:0914”(association)	0.350
TP53BP1	PSMD14	psi-mi:“MI:2364”(proximity)	0.270
PLEKHF2	TRIM22	psi-mi:“MI:0915”(physical association)	0.000
rpoB	TRIM22	psi-mi:“MI:0915”(physical association)	0.000
TRIM22	rho	psi-mi:“MI:0915”(physical association)	0.000
TRIM22		psi-mi:“MI:0915”(physical association)	0.000
	TRIM22	psi-mi:“MI:0915”(physical association)	0.000
TRIM22	CIC	psi-mi:“MI:0915”(physical association)	0.000
TRIM22	RERE	psi-mi:“MI:0915”(physical association)	0.000
USP7	TRIM22	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (100): EIF4E (Affinity Capture-Western), TRIM22 (Affinity Capture-Western), CHUK (Affinity Capture-Western), TRIM22 (Reconstituted Complex), TRIM22 (Reconstituted Complex), CIITA (Affinity Capture-Western), CIITA (Co-localization), PML (Co-localization), CCNT1 (Co-localization), TRIM22 (PCA), TRIM22 (Reconstituted Complex), TRIM22 (Proximity Label-MS), PLEKHF2 (Two-hybrid), NFKBIA (Biochemical Activity), UBE2D1 (Reconstituted Complex)

ESM2 similar proteins: A0A3B3IT33, A6NCK2, A6NDI0, A6NGJ6, A6NI03, A6NLI5, C9J1S8, I1YAP6, K7N6K2, P0CI25, P0CI26, P15533, Q0PF16, Q1ACD5, Q1ACD6, Q1ACD7, Q1ACD8, Q2YEM8, Q2YEM9, Q2YEN0, Q2YEN2, Q3ZEE5, Q587N6, Q587N7, Q5BN31, Q5C8T6, Q5C8T8, Q5C8U1, Q5C8U3, Q5C8U4, Q5D7H7, Q5D7H8, Q5D7I0, Q5D7I1, Q5D7I2, Q5D7I3, Q5D7I5, Q5D7I6, Q5D7I9, Q5D7J0

Diamond homologs: A2XK56, A6NCK2, B8B5U8, P19474, Q0PF16, Q1ACD5, Q1ACD6, Q1ACD7, Q2YEM8, Q2YEM9, Q2YEN0, Q2YEN2, Q3U827, Q3ZEE5, Q587N6, Q587N7, Q5BN31, Q5C8T8, Q5C8U1, Q5C8U3, Q5D7H7, Q5D7H8, Q5D7I0, Q5D7I1, Q5D7I2, Q5D7I3, Q5D7I5, Q5D7I6, Q5D7I9, Q5D7J0, Q5D7J2, Q5RAK3, Q7XI73, Q7XZZ3, Q865W2, Q86T96, Q86XT4, Q8BGE7, Q8GW10, Q8IYM9

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
Ub:E2	“up-regulates activity”	TRIM22	ubiquitination
UBE2D2	“up-regulates activity”	TRIM22	binding
TRIM22	“down-regulates quantity by destabilization”	TRIM22	polyubiquitination

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	67
Likely benign	14
Benign	14

Top pathogenic / likely-pathogenic (0)

SpliceAI

1255 predictions. Top by Δscore:

Variant	Effect	Δscore
11:5697340:G:GT	donor_gain	1.0000
11:5697348:G:GT	donor_gain	1.0000
11:5697366:GGA:G	donor_gain	1.0000
11:5697367:G:T	donor_gain	1.0000
11:5697380:G:GT	donor_gain	1.0000
11:5698306:A:AG	acceptor_gain	1.0000
11:5698310:CCAA:C	acceptor_loss	1.0000
11:5698312:A:AG	acceptor_gain	1.0000
11:5698313:A:AG	acceptor_gain	1.0000
11:5698314:G:GG	acceptor_gain	1.0000
11:5698314:G:GT	acceptor_loss	1.0000
11:5698314:GA:G	acceptor_gain	1.0000
11:5698314:GAA:G	acceptor_gain	1.0000
11:5698314:GAAT:G	acceptor_gain	1.0000
11:5698314:GAATT:G	acceptor_gain	1.0000
11:5698544:AGGT:A	donor_loss	1.0000
11:5698546:G:A	donor_loss	1.0000
11:5709051:A:AG	acceptor_gain	1.0000
11:5709052:G:GG	acceptor_gain	1.0000
11:5689897:AAGGT:A	donor_loss	0.9900
11:5689901:T:G	donor_loss	0.9900
11:5695132:G:GT	donor_gain	0.9900
11:5696560:G:GT	donor_gain	0.9900
11:5697327:A:T	donor_gain	0.9900
11:5697341:A:T	donor_gain	0.9900
11:5697351:G:GT	donor_gain	0.9900
11:5697367:GA:G	donor_gain	0.9900
11:5697368:A:G	donor_gain	0.9900
11:5697381:A:T	donor_gain	0.9900
11:5698307:T:G	acceptor_gain	0.9900

AlphaMissense

3295 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:5709250:T:A	W367R	0.987
11:5709250:T:C	W367R	0.987
11:5709220:T:A	W357R	0.982
11:5709220:T:C	W357R	0.982
11:5709556:T:C	F469L	0.981
11:5709558:C:A	F469L	0.981
11:5709558:C:G	F469L	0.981
11:5709517:T:C	F456L	0.976
11:5709519:T:A	F456L	0.976
11:5709519:T:G	F456L	0.976
11:5709222:G:C	W357C	0.973
11:5709222:G:T	W357C	0.973
11:5709525:T:A	N458K	0.973
11:5709525:T:G	N458K	0.973
11:5709412:T:C	F421L	0.970
11:5709414:T:A	F421L	0.970
11:5709414:T:G	F421L	0.970
11:5709487:T:C	F446L	0.967
11:5709489:C:A	F446L	0.967
11:5709489:C:G	F446L	0.967
11:5709512:T:A	V454D	0.964
11:5698354:T:C	F187L	0.960
11:5698356:C:A	F187L	0.960
11:5698356:C:G	F187L	0.960
11:5709259:G:C	G370R	0.958
11:5709481:G:T	G444W	0.956
11:5696551:T:C	F107L	0.955
11:5696553:C:A	F107L	0.955
11:5696553:C:G	F107L	0.955
11:5696332:T:C	F34L	0.954

dbSNP variants (sampled 300 via entrez): RS1000394056 (11:5701062 T>C), RS1000531907 (11:5691815 T>A), RS1000695921 (11:5697841 C>T), RS1000764078 (11:5692470 G>T), RS1001213271 (11:5696957 A>T), RS1001222552 (11:5701895 A>C), RS1001281199 (11:5702596 G>A,C), RS1001330729 (11:5701691 G>A), RS1001353754 (11:5689547 C>A,G,T), RS1001445722 (11:5707990 C>A,T), RS1001452357 (11:5695366 G>A), RS1001960564 (11:5707752 C>T), RS1001987408 (11:5704444 A>G), RS1002092561 (11:5704969 T>C), RS1002097268 (11:5698430 T>C)

Disease associations

OMIM: gene MIM:606559 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
inborn error of immunity	Strong	Autosomal recessive
inflammatory bowel disease	Limited	Autosomal recessive

Mondo (2): inflammatory bowel disease (MONDO:0005265), inborn error of immunity (MONDO:0003778)

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST005194_105	Coronary artery disease	2.000000e-12
GCST005195_51	Coronary artery disease	6.000000e-13
GCST005196_42	Coronary artery disease	2.000000e-12
GCST010725_20	Malaria	4.000000e-69
GCST010725_33	Malaria	2.000000e-67
GCST010725_51	Malaria	1.000000e-55

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D007153	Immunologic Deficiency Syndromes	C20.673
D015212	Inflammatory Bowel Diseases	C06.405.205.731; C06.405.469.432

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	increases methylation, decreases methylation, increases expression	5
Valproic Acid	affects expression, decreases expression	5
methylmercuric chloride	increases expression, affects cotreatment	4
sodium arsenite	decreases expression, affects cotreatment, increases abundance, increases expression	4
Acetaminophen	decreases expression, increases expression	4
Aflatoxin B1	affects expression, increases expression	4
monomethylarsonous acid	decreases expression, increases expression	3
(+)-JQ1 compound	decreases expression, increases expression	3
Cisplatin	affects expression, affects cotreatment, increases expression	3
Tretinoin	increases expression, decreases expression	3
Cyclosporine	decreases expression, increases expression	3
bisphenol A	decreases reaction, increases expression	2
entinostat	increases expression, affects cotreatment	2
Decitabine	affects expression, increases expression	2
Air Pollutants	increases abundance, decreases expression	2
Arsenic	affects methylation, affects cotreatment, decreases expression, increases abundance	2
Doxorubicin	decreases expression, increases expression	2
Lipopolysaccharides	affects expression, increases expression, affects reaction, decreases reaction	2
Nickel	increases expression	2
Smoke	decreases expression, increases abundance	2
Tobacco Smoke Pollution	decreases expression, increases expression	2
Cadmium Chloride	decreases expression	2
OTX015	decreases expression	1
bisphenol F	increases expression	1
mivebresib	decreases expression	1
TAK-243	increases sumoylation	1
sotorasib	affects cotreatment, increases expression	1
tris(2-butoxyethyl) phosphate	affects expression	1
mono-(2-ethylhexyl)phthalate	decreases expression	1
sulforaphane	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_B2QV	Abcam A-549 TRIM22 KO	Cancer cell line	Male
CVCL_TT89	HAP1 TRIM22 (-) 1	Cancer cell line	Male
CVCL_TT90	HAP1 TRIM22 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00167882	PHASE4	COMPLETED	The Influence of 5-Aminosalicylates on Thiopurine Metabolite Levels
NCT00205062	PHASE4	TERMINATED	Positron Emission Tomography (PET)-Computed Tomography (CT) in Inflammatory Bowel Disease (IBD)
NCT00567593	PHASE4	COMPLETED	Gene Regulation by Thiazolidinediones
NCT00746395	PHASE4	COMPLETED	Randomized, Placebo-controlled Trial of Lubiprostone as a Preparation for Capsule Endoscopy
NCT01034358	PHASE4	COMPLETED	Immune Response to the Human Papillomavirus Vaccine in Young Women With Inflammatory Bowel Disease
NCT01056913	PHASE4	COMPLETED	NITI CAR27 (ColonRing) Compression Anastomosis in Colorectal Surgery
NCT01067547	PHASE4	COMPLETED	A Trial of Iron Replacement in Patients With Iron Deficiency.
NCT01341808	PHASE4	COMPLETED	Immunogenicity of Hepatitis A Vaccine in Inflammatory Bowel Disease (IBD) Patients
NCT01908283	PHASE4	COMPLETED	Induction of Immunity Against Streptococcus Pneumoniae in Adults With Inflammatory Bowel Disease
NCT01934088	PHASE4	COMPLETED	Satisfaction With Nurse Administered Propofol Sedation vs. Midazolam With Fentanyl Sedation for Endoscopy
NCT02162862	PHASE4	COMPLETED	Treating Disrupted Sleep in Individuals With Inflammatory Bowel Disease
NCT02248337	PHASE4	COMPLETED	Low Volume Colon Preparation for IBD
NCT02281799	PHASE4	WITHDRAWN	Thiopurine Induced Pancreatitis in IBD Patients
NCT02392286	PHASE4	TERMINATED	Corticosteroid Dosage for Crohn’s Disease Flare
NCT02437591	PHASE4	COMPLETED	Study to Evaluate the Pharmacokinetics of Fidaxomicin in Inflammatory Bowel Disease (IBD) Subjects With Clostridium Difficile Infection (CDI)
NCT02453776	PHASE4	COMPLETED	Precision Dosing of Infliximab Versus Conventional Dosing of Infliximab
NCT02461758	PHASE4	COMPLETED	Trial of High Dose vs. Standard Dose Influenza Vaccine in Inflammatory Bowel Disease Patients
NCT02566889	PHASE4	TERMINATED	An Efficacy and Safety Study of Infliximab Dose Escalation in Pediatric Participants With Inflammatory Bowel Disease
NCT02774057	PHASE4	UNKNOWN	Trial of Captafer® vs. Oral Iron Sulfate in the Treatment of Iron Deficiency Anemia in Patients With IBD
NCT02806206	PHASE4	UNKNOWN	Prucalopride Prior to Small Bowel Capsule Endoscopy
NCT02946203	PHASE4	COMPLETED	Comparison of VoLumen and Breeza Oral Contrast Agents in Pediatric Patients
NCT02994836	PHASE4	COMPLETED	GIS-SUSANTI-TNF-2015 (Anti-TNF Discontinuation )
NCT03220841	PHASE4	UNKNOWN	Stricture Definition and Treatment (STRIDENT) Drug Therapy Study
NCT03351972	PHASE4	COMPLETED	Differences in Preparation for Small Bowel Capsule Endoscopy
NCT03466983	PHASE4	COMPLETED	A Trial Comparing the Incidence of Hypophosphatemia in Relation to Treatment With Iron Isomaltoside and Ferric Carboxymaltose in Subjects With Iron Deficiency Anaemia Due to Inflammatory Bowel Disease
NCT03591770	PHASE4	TERMINATED	Shingrix Vaccine in Patients With Moderate to Severe Ulcerative Colitis on Tofacitinib
NCT03629379	PHASE4	COMPLETED	Response to Ustekinumab for Anti-tnf Induced Psoriasiform Skin Lesions
NCT03723447	PHASE4	COMPLETED	Intraoperative TAP Block With Bupivacaine/Dexamethasone Against Liposomal Bupivacaine (Exparel®)
NCT03798691	PHASE4	COMPLETED	Immunogenicity of Herpes Zoster Subunit Vaccine in Inflammatory Bowel Disease Patients Treated With Vedolizumab
NCT03860012	PHASE4	UNKNOWN	Folic Acid in Pediatric Inflammatory Bowel Disease
NCT03885713	PHASE4	COMPLETED	Identification of Predictive Biomarkers for Response to Biologic Therapies and Tofacitinib in Inflammatory Bowel Disease
NCT03917303	PHASE4	RECRUITING	Control Crohn Safe Trial
NCT04045782	PHASE4	COMPLETED	Evaluation of the Safety and Effectiveness of Switching From Humira® to Imraldi® in Flanders
NCT04304950	PHASE4	COMPLETED	Chronotherapy in Inflammatory Bowel Disease
NCT04626947	PHASE4	TERMINATED	Prevention of Recurrent Clostridium Difficile Infection (CDI) in Patients With Inflammatory Bowel Disease (IBD).
NCT04646187	PHASE4	ENROLLING_BY_INVITATION	De-escalation of Anti-TNF Therapy in Inflammatory Bowel Disease
NCT04835506	PHASE4	ACTIVE_NOT_RECRUITING	Proactive Infliximab Optimization Using a Pharmacokinetic Dashboard Versus Standard of Care in Patients With Inflammatory Bowel Disease: The OPTIMIZE Trial
NCT04982172	PHASE4	COMPLETED	Model-informed Dose De-escalation of Infliximab in Patients With Inflammatory Bowel Diseases
NCT05180175	PHASE4	COMPLETED	The Nordic IBD Treatment Strategy Trial
NCT05280405	PHASE4	UNKNOWN	Early Proactive Therapeutic Drug Monitoring of Infliximab in Children: EPIC Study