TRIM56

Summary

TRIM56 (tripartite motif containing 56, HGNC:19028) is a protein-coding gene on chromosome 7q22.1, encoding E3 ubiquitin-protein ligase TRIM56 (Q9BRZ2). E3 ubiquitin-protein ligase that plays a key role in innate antiviral immunity by mediating ubiquitination of CGAS and STING1.

Enables ubiquitin protein ligase activity. Involved in defense response to virus; positive regulation of signal transduction; and protein monoubiquitination. Predicted to be located in cytoplasm. Predicted to be active in nucleoplasm.

Source: NCBI Gene 81844 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 139 total
• MANE Select transcript: NM_030961

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:19028
Approved symbol	TRIM56
Name	tripartite motif containing 56
Location	7q22.1
Locus type	gene with protein product
Status	Approved
Aliases	RNF109
Ensembl gene	ENSG00000169871
Ensembl biotype	protein_coding
OMIM	616996
Entrez	81844

Gene structure

Transcript identifiers

Ensembl transcripts: 18 — 17 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000306085, ENST00000412507, ENST00000467847, ENST00000487252, ENST00000877458, ENST00000877459, ENST00000877460, ENST00000877461, ENST00000877462, ENST00000877463, ENST00000877464, ENST00000877465, ENST00000877466, ENST00000877467, ENST00000877468, ENST00000877469, ENST00000971054, ENST00000971055

RefSeq mRNA: 1 — MANE Select: NM_030961 NM_030961

CCDS: CCDS43625

Canonical transcript exons

ENST00000306085 — 3 exons

Exon	Start	End
ENSE00001125895	101087006	101087168
ENSE00001125901	101085481	101085571
ENSE00002609296	101087312	101097967

Expression profiles

Bgee: expression breadth ubiquitous, 276 present calls, max score 96.19.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 10.2426 / max 228.4067, expressed in 1781 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
80107	9.0154	1746
80106	1.2272	752

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
tendon of biceps brachii	UBERON:0008188	96.19	gold quality
nipple	UBERON:0002030	94.48	gold quality
buccal mucosa cell	CL:0002336	94.25	gold quality
pylorus	UBERON:0001166	93.62	gold quality
palpebral conjunctiva	UBERON:0001812	93.05	gold quality
cardia of stomach	UBERON:0001162	92.01	gold quality
urethra	UBERON:0000057	91.87	gold quality
bronchial epithelial cell	CL:0002328	91.51	gold quality
mucosa of paranasal sinus	UBERON:0005030	91.41	gold quality
seminal vesicle	UBERON:0000998	91.22	gold quality
epithelium of nasopharynx	UBERON:0001951	91.11	gold quality
nasopharynx	UBERON:0001728	91.10	gold quality
renal medulla	UBERON:0000362	91.04	gold quality
bronchus	UBERON:0002185	91.04	gold quality
epithelium of bronchus	UBERON:0002031	91.02	gold quality
pericardium	UBERON:0002407	90.73	gold quality
nasal cavity epithelium	UBERON:0005384	90.49	gold quality
parotid gland	UBERON:0001831	89.97	gold quality
parietal pleura	UBERON:0002400	89.97	gold quality
trachea	UBERON:0003126	89.55	gold quality
amniotic fluid	UBERON:0000173	89.31	gold quality
cervix squamous epithelium	UBERON:0006922	89.28	silver quality
visceral pleura	UBERON:0002401	88.91	gold quality
vena cava	UBERON:0004087	88.78	silver quality
decidua	UBERON:0002450	88.61	gold quality
germinal epithelium of ovary	UBERON:0001304	88.46	gold quality
lower lobe of lung	UBERON:0008949	88.32	gold quality
medial globus pallidus	UBERON:0002477	88.10	gold quality
penis	UBERON:0000989	88.09	gold quality
pleura	UBERON:0000977	87.79	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-MTAB-8142	yes	12.38
E-ANND-3	yes	8.73
E-CURD-135	no	2441.55
E-HCAD-6	no	617.98

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

39 targeting TRIM56, 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-5193	100.00	67.26	1744
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-8082	99.95	67.27	1170
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-6892-3P	99.68	66.40	1178
HSA-MIR-10393-5P	99.65	68.01	1368
HSA-MIR-642A-5P	99.51	65.10	1152
HSA-MIR-6727-3P	99.49	65.92	1333
HSA-MIR-4251	99.40	69.19	3363
HSA-MIR-4722-3P	99.35	65.22	1099
HSA-MIR-4652-3P	99.33	70.02	2742
HSA-MIR-504-3P	99.30	67.18	1745
HSA-MIR-4292	99.16	65.57	1767
HSA-MIR-6791-5P	99.16	65.92	1844
HSA-MIR-7151-3P	99.04	69.72	2370
HSA-MIR-2355-5P	98.83	65.51	1589
HSA-MIR-4716-5P	98.82	68.57	1168
HSA-MIR-6761-5P	98.71	68.03	1504
HSA-MIR-3130-5P	98.14	66.00	711
HSA-MIR-4303	98.01	68.13	2304
HSA-MIR-4438	97.96	63.70	947
HSA-MIR-3620-3P	97.78	64.88	772
HSA-MIR-6747-3P	97.73	64.84	1596
HSA-MIR-6782-3P	97.60	67.75	931
HSA-MIR-6890-3P	97.50	65.71	997
HSA-MIR-6791-3P	97.45	64.31	1123
HSA-MIR-6829-3P	97.45	64.31	1137
HSA-MIR-3173-5P	97.35	65.82	1282
HSA-MIR-6799-3P	97.35	65.60	1302

Literature-anchored findings (GeneRIF, showing 23)

• TRIM56 is an interferon-inducible E3 ubiquitin ligase that modulates STING to confer double-stranded DNA-mediated innate immune responses. (PMID:21074459)
• These data demonstrate that TRIM56 is a novel antiviral host factor that restricts pestivirus infection. (PMID:21289118)
• TRIM56 is a target gene of the BACH1 transcription factor according to ChIP-seq analysis in HEK 293 cells. (PMID:21555518)
• TRIM56 is an essential component of the TLR3 antiviral signaling pathway and reveal a novel role for TRIM56 in innate antiviral immunity. (PMID:22948160)
• Altogether, TRIM56 is a versatile antiviral host factor that confers resistance to yellow fever virus, dengue virus serotype 2, and human coronavirus OC43 through overlapping and distinct molecular determinants (PMID:25253338)
• The C-Terminal Tail of TRIM56 Dictates Antiviral Restriction of Influenza A and B Viruses by Impeding Viral RNA Synthesis (PMID:26889027)
• SopA inhibits TRIM56 E3 ligase activity by occluding the E2-interacting surface of TRIM56. (PMID:28084320)
• TRIM56 is the ubiquitin ligase that is degrading vimentin in ovarian cancer cells, regulation cell migration and neoplasm invasiveness. (PMID:28771721)
• TRIM56 may act as a tumor suppressor in multiple myeloma through activation of TLR3/TRIF signaling pathway. (PMID:29214775)
• TRIM56 E3 ligase-induced monoubiquitination of cGAS is important for cytosolic DNA sensing and IFNalphabeta production to induce anti-DNA viral immunity. (PMID:29426904)
• PCBP1 regulates post-transcriptional expression of TRIM56 in ovarian cancer. (PMID:30281912)
• Suppression of the SAP18/HDAC1 complex by targeting TRIM56 and Nanog is essential for oncogenic viral FLICE-inhibitory protein-induced acetylation of p65/RelA, NF-kappaB activation, and promotion of cell invasion and angiogenesis. (PMID:30670829)
• Altogether, this study reveals TRIM56 is an RNA binding protein that acts as a Zika virus restriction factor and provides new insights into the antiviral mechanism by which this E3 ligase tackles flavivirus infections. (PMID:31251739)
• TRIM56 suppresses the malignant development of hepatocellular carcinoma via targeting RBM24 and inactivating the Wnt signaling. (PMID:33577026)
• Impaired Antiviral Responses to Extracellular Double-Stranded RNA and Cytosolic DNA, but Not to Interferon-alpha Stimulation, in TRIM56-Deficient Cells. (PMID:35062293)
• TRIM56 impairs HBV infection and replication by inhibiting HBV core promoter activity. (PMID:36084850)
• Exosomal circZNF451 restrains anti-PD1 treatment in lung adenocarcinoma via polarizing macrophages by complexing with TRIM56 and FXR1. (PMID:36209117)
• TRIM56 promotes malignant progression of glioblastoma by stabilizing cIAP1 protein. (PMID:36471347)
• The Functions of TRIM56 in Antiviral Innate Immunity and Tumorigenesis. (PMID:36902478)
• TRIM56: a promising prognostic immune biomarker for glioma revealed by pan-cancer and single-cell analysis. (PMID:38348047)
• Key roles for phosphorylation and the Coiled-coil domain in TRIM56-mediated positive regulation of TLR3-TRIF-dependent innate immunity. (PMID:38556084)
• PGRMC1 promotes NSCLC stemness phenotypes by disrupting TRIM56-mediated ubiquitination of AHR. (PMID:39059592)
• TRIM56 restricts Coxsackievirus B infection by mediating the ubiquitination of viral RNA-dependent RNA polymerase 3D. (PMID:39348396)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Trim56	ENSMUSG00000043279
rattus_norvegicus	Trim56	ENSRNOG00000071001

Paralogs (80): MID2 (ENSG00000080561), TRIM9 (ENSG00000100505), MID1 (ENSG00000101871), MEFV (ENSG00000103313), TRIM35 (ENSG00000104228), TRIM14 (ENSG00000106785), TRIM37 (ENSG00000108395), TRIM2 (ENSG00000109654), TRIM3 (ENSG00000110171), TRIM38 (ENSG00000112343), TRIM62 (ENSG00000116525), TRIM67 (ENSG00000119283), TRIM32 (ENSG00000119401), BSPRY (ENSG00000119411), TRIM25 (ENSG00000121060), TRIM6 (ENSG00000121236), TRIM24 (ENSG00000122779), TRIM51 (ENSG00000124900), TRIM28 (ENSG00000130726), TRIM21 (ENSG00000132109), TRIM5 (ENSG00000132256), TRIM22 (ENSG00000132274), TRIM47 (ENSG00000132481), TRIM45 (ENSG00000134253), TRIM29 (ENSG00000137699), TRIM54 (ENSG00000138100), PML (ENSG00000140464), TRIM65 (ENSG00000141569), TRIM43B (ENSG00000144010), TRIM43 (ENSG00000144015), TRIM7 (ENSG00000146054), TRIM41 (ENSG00000146063), TRIM50 (ENSG00000146755), TRIM4 (ENSG00000146833), TRIM55 (ENSG00000147573), TRIM48 (ENSG00000150244), TRIM36 (ENSG00000152503), TRIM11 (ENSG00000154370), TRIM74 (ENSG00000155428), TRIM42 (ENSG00000155890)

Protein

Protein identifiers

E3 ubiquitin-protein ligase TRIM56 — Q9BRZ2 (reviewed: Q9BRZ2)

Alternative names: RING finger protein 109, Tripartite motif-containing protein 56

All UniProt accessions (3): Q9BRZ2, A0A0D9SF19, C9JI91

UniProt curated annotations — full annotation on UniProt →

Function. E3 ubiquitin-protein ligase that plays a key role in innate antiviral immunity by mediating ubiquitination of CGAS and STING1. In response to pathogen- and host-derived double-stranded DNA (dsDNA), targets STING1 to ‘Lys-63’-linked ubiquitination, thereby promoting its homodimerization, a step required for the production of type I interferon IFN-beta. Also mediate monoubiquitination of CGAS, thereby promoting CGAS oligomerization and subsequent activation. Promotes also TNFalpha-induced NF-kappa-B signaling by mediating ‘Lys-63’-linked ubiquitination TAK1, leading to enhanced interaction between TAK1 and CHUK/IKKalpha. Independently of its E3 ubiquitin ligase activity, positive regulator of TLR3 signaling. Potentiates extracellular double stranded RNA (dsRNA)-induced expression of IFNB1 and interferon-stimulated genes ISG15, IFIT1/ISG56, CXCL10, OASL and CCL5/RANTES. Promotes establishment of an antiviral state by TLR3 ligand and TLR3-mediated chemokine induction following infection by hepatitis C virus. Acts as a restriction factor of Zika virus through direct interaction with the viral RNA via its C-terminal region.

Subunit / interactions. Homooligomer. Interacts with STING1. Interacts with TICAM1.

Subcellular location. Cytoplasm.

Tissue specificity. Widely expressed (at protein level).

Post-translational modifications. (Microbial infection) Preferentially ubiquitinated with ‘Lys-48’ and ‘Lys-11’-linked ubiquitin chains by Salmonella effector SopA leading to proteasomal targeting and degradation. Autoubiquitinated.

Induction. Up-regulated by IFN-alpha.

Pathway. Protein modification; protein ubiquitination.

Similarity. Belongs to the TRIM/RBCC family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q9BRZ2-1	1	yes
Q9BRZ2-2	2
Q9BRZ2-3	3

RefSeq proteins (1): NP_112223* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000315	Znf_B-box	Domain
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
IPR047153	TRIM45/56/19-like	Family

Pfam: PF00643, PF13445

UniProt features (27 total): binding site 4, splice variant 4, zinc finger region 3, modified residue 3, compositionally biased region 3, mutagenesis site 2, strand 2, chain 1, sequence conflict 1, turn 1, helix 1, region of interest 1, coiled-coil region 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
5JW7	X-RAY DIFFRACTION	2.85

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BRZ2-F1	76.60	0.33

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): 172; 192; 197; 169

Post-translational modifications (3): 418, 442, 475

Mutagenesis-validated functional residues (2):

Position	Phenotype
21	complete loss of autoubiquitination. complete loss of autoubiquitination, loss of antiviral activity against yellow feve
24	complete loss of autoubiquitination, loss of antiviral activity against yellow fever virus and human coronavirus virus o

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-3134975	Regulation of innate immune responses to cytosolic DNA

MSigDB gene sets: 133 (showing top): REACTOME_INNATE_IMMUNE_SYSTEM, GOBP_POSITIVE_REGULATION_OF_TYPE_I_INTERFERON_PRODUCTION, GOBP_RESPONSE_TO_PEPTIDE, GOBP_RESPONSE_TO_TYPE_I_INTERFERON, IVANOVA_HEMATOPOIESIS_MATURE_CELL, GOBP_POSITIVE_REGULATION_OF_CYTOKINE_PRODUCTION, GOBP_POSITIVE_REGULATION_OF_RESPONSE_TO_EXTERNAL_STIMULUS, GOBP_REGULATION_OF_IMMUNE_RESPONSE, GOBP_DEFENSE_RESPONSE_TO_OTHER_ORGANISM, GOBP_POSITIVE_REGULATION_OF_INTERFERON_BETA_PRODUCTION, GOBP_POSITIVE_REGULATION_OF_NON_CANONICAL_NF_KAPPAB_SIGNAL_TRANSDUCTION, GOBP_CYTOKINE_PRODUCTION, GOBP_REGULATION_OF_RESPONSE_TO_STRESS, GOBP_PROTEIN_MONOUBIQUITINATION, GOBP_REGULATION_OF_NON_CANONICAL_NF_KAPPAB_SIGNAL_TRANSDUCTION

GO Biological Process (13): protein monoubiquitination (GO:0006513), regulation of type I interferon production (GO:0032479), positive regulation of interferon-beta production (GO:0032728), response to type I interferon (GO:0034340), innate immune response (GO:0045087), positive regulation of innate immune response (GO:0045089), defense response to virus (GO:0051607), positive regulation of type I interferon-mediated signaling pathway (GO:0060340), protein K63-linked ubiquitination (GO:0070534), positive regulation of non-canonical NF-kappaB signal transduction (GO:1901224), immune system process (GO:0002376), protein ubiquitination (GO:0016567), cGAS/STING signaling pathway (GO:0140896)

GO Molecular Function (7): RNA binding (GO:0003723), ubiquitin-protein transferase activity (GO:0004842), zinc ion binding (GO:0008270), ubiquitin protein ligase activity (GO:0061630), protein binding (GO:0005515), transferase activity (GO:0016740), metal ion binding (GO:0046872)

GO Cellular Component (3): nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Cytosolic sensors of pathogen-associated DNA	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
innate immune response	2
protein ubiquitination	1
regulation of cytokine production	1
type I interferon production	1
positive regulation of type I interferon production	1
interferon-beta production	1
regulation of interferon-beta production	1
response to cytokine	1
immune response	1
defense response to symbiont	1
positive regulation of response to biotic stimulus	1
positive regulation of defense response	1
positive regulation of response to external stimulus	1
regulation of innate immune response	1
positive regulation of immune response	1
defense response	1
response to virus	1
positive regulation of cytokine-mediated signaling pathway	1
positive regulation of innate immune response	1
type I interferon-mediated signaling pathway	1
regulation of type I interferon-mediated signaling pathway	1
protein polyubiquitination	1
non-canonical NF-kappaB signal transduction	1
regulation of non-canonical NF-kappaB signal transduction	1
positive regulation of intracellular signal transduction	1
biological_process	1
protein modification by small protein conjugation	1
cytoplasmic pattern recognition receptor signaling pathway	1
nucleic acid binding	1
ubiquitin-like protein transferase activity	1
transition metal ion binding	1
ubiquitin-protein transferase activity	1
ubiquitin-like protein ligase activity	1
binding	1
catalytic activity	1
cation binding	1
nuclear lumen	1
intracellular anatomical structure	1
cytoplasm	1

Protein interactions and networks

STRING

1242 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TRIM56	FAF2	Q96CS3	739
TRIM56	TRIM32	Q13049	736
TRIM56	TRIM23	P36406	684
TRIM56	TRIM38	O00635	679
TRIM56	TRAT1	Q6PIZ9	668
TRIM56	RNF26	Q9BY78	655
TRIM56	RNF5	Q99942	635
TRIM56	TRIM41	Q8WV44	610
TRIM56	CGAS	Q8N884	593
TRIM56	TRIM5	Q9C035	593
TRIM56	TBK1	Q9UHD2	591
TRIM56	IRF3	Q14653	590
TRIM56	TRIM22	Q8IYM9	590
TRIM56	AMFR	P26442	588
TRIM56	MUL1	Q969V5	582

IntAct

74 interactions, top by confidence:

A	B	Type	Score
SPC24	NDC80	psi-mi:“MI:0914”(association)	0.920
ING4	KAT7	psi-mi:“MI:0914”(association)	0.530
MAGEB2	GTPBP10	psi-mi:“MI:0914”(association)	0.530
ABT1	ZNF316	psi-mi:“MI:0914”(association)	0.530
ADARB1	SPTY2D1	psi-mi:“MI:0914”(association)	0.530
RPLP0	GTPBP10	psi-mi:“MI:0914”(association)	0.530
SRSF5	CBX6	psi-mi:“MI:0914”(association)	0.530
TICAM1	TRIM56	psi-mi:“MI:0915”(physical association)	0.400
TRIM56	HSP90AB1	psi-mi:“MI:0915”(physical association)	0.400
FKBP5	TRIM56	psi-mi:“MI:0915”(physical association)	0.400
HSP90AB1	TRIM56	psi-mi:“MI:0915”(physical association)	0.400
TRIM56		psi-mi:“MI:0915”(physical association)	0.400
HSP90AA1	TRIM56	psi-mi:“MI:0915”(physical association)	0.400
PTGES3	TRIM56	psi-mi:“MI:0915”(physical association)	0.400
TRIM56	UBE2H	psi-mi:“MI:0915”(physical association)	0.370
USP43	DKFZP586J0619	psi-mi:“MI:0914”(association)	0.350
Ccdc9	ACIN1	psi-mi:“MI:0914”(association)	0.350
Cep72	TBC1D31	psi-mi:“MI:0914”(association)	0.350
Espl1	BDP1	psi-mi:“MI:0914”(association)	0.350
MYH9	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
Sinhcaf	BRMS1	psi-mi:“MI:0914”(association)	0.350
ESR1	ESYT2	psi-mi:“MI:0914”(association)	0.350
CNBP	NOP56	psi-mi:“MI:0914”(association)	0.350
BMI1	MEIS3P1	psi-mi:“MI:0914”(association)	0.350
RYBP	FAM186A	psi-mi:“MI:0914”(association)	0.350
PPM1G	SRP14	psi-mi:“MI:0914”(association)	0.350
rl3_rl3l_human	MPHOSPH10	psi-mi:“MI:0914”(association)	0.350

BioGRID (181): TRIM56 (Affinity Capture-RNA), TRIM56 (Affinity Capture-MS), TRIM56 (Affinity Capture-MS), TRIM56 (Proximity Label-MS), TRIM56 (Affinity Capture-MS), TRIM56 (Affinity Capture-MS), TRIM56 (Affinity Capture-MS), TRIM56 (Affinity Capture-MS), TRIM56 (Affinity Capture-MS), TRIM56 (Affinity Capture-MS), TRIM56 (Affinity Capture-MS), TRIM56 (Affinity Capture-MS), TRIM56 (Affinity Capture-MS), TRIM56 (Affinity Capture-MS), TRIM56 (Affinity Capture-MS)

ESM2 similar proteins: A0A061IR73, A0A1B0GUU1, A6H687, A8MYJ7, B1WC39, D3ZVB0, E1BD59, G3MY25, G3MZC5, O75064, P07199, P27790, P29597, P48988, P52333, P52824, Q08DF2, Q0VCE3, Q13608, Q1JPD6, Q2VPB7, Q3TAP4, Q3U1Y4, Q3ZBE0, Q499M4, Q53EQ6, Q5JZY3, Q62137, Q63272, Q6B0B8, Q6DI92, Q6ZPS2, Q6ZS72, Q7TM95, Q80VI1, Q86UT6, Q8BYG9, Q8N9M5, Q8R5G7, Q8TE96

Diamond homologs: A0A7I2V3R4, D2H788, D3ZBM4, O70277, O75382, P0DH78, Q3SWY0, Q3UIW8, Q58EC8, Q68EV7, Q6INB3, Q8C432, Q8N6D2, Q8QZS5, Q96D59, Q9BRZ2, Q9R1R2, E1BD59, E7ERA6, F6ZQ54, O60858, Q03601, Q0IIM1, Q32L60, Q503I2, Q5M7V1, Q5ZMD4, Q61510, Q7T308, Q80VI1, Q810I1, Q810I2, Q8BFW4, Q8IUD6, Q9CYB0, M0QZC1, Q3UV31, Q6IMG5, Q6VVB1, Q8BR37

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
Ub:E2	“up-regulates activity”	TRIM56	ubiquitination
TRIM56	“up-regulates activity”	STING1	ubiquitination

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 89 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
Peptide chain elongation	11	24.5×	4e-11
Viral mRNA Translation	11	24.5×	4e-11
PELO:HBS1L and ABCE1 dissociate a ribosome on a non-stop mRNA	11	24.2×	4e-11
Selenocysteine synthesis	11	23.2×	4e-11
Eukaryotic Translation Termination	11	23.2×	4e-11
Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC)	11	22.7×	4e-11
ZNF598 and the Ribosome-associated Quality Trigger (RQT) complex dissociate a ribosome stalled on a no-go mRNA	11	22.7×	4e-11
Formation of a pool of free 40S subunits	11	21.6×	7e-11

GO biological processes:

GO term	Partners	Fold	FDR
ribosomal large subunit biogenesis	5	29.2×	1e-04
cytoplasmic translation	11	26.8×	1e-10
ribosomal small subunit biogenesis	5	15.0×	1e-03
RNA processing	5	14.4×	1e-03
translation	10	13.5×	7e-07
rRNA processing	6	11.2×	1e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	126
Likely benign	9
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

650 predictions. Top by Δscore:

Variant	Effect	Δscore
7:101085568:C:G	donor_gain	1.0000
7:101087054:T:A	acceptor_gain	1.0000
7:101087310:AGCAT:A	acceptor_gain	1.0000
7:101087311:GCATG:G	acceptor_gain	1.0000
7:101085567:GC:G	donor_gain	0.9900
7:101085568:CTAG:C	donor_loss	0.9900
7:101085569:TAGGT:T	donor_loss	0.9900
7:101085571:GG:G	donor_loss	0.9900
7:101085572:GTAAG:G	donor_loss	0.9900
7:101085573:T:A	donor_loss	0.9900
7:101087055:G:A	acceptor_gain	0.9900
7:101087150:G:GT	donor_gain	0.9900
7:101087310:A:AG	acceptor_gain	0.9900
7:101087311:G:GG	acceptor_gain	0.9900
7:101087311:GC:G	acceptor_gain	0.9900
7:101087311:GCAT:G	acceptor_gain	0.9900
7:101087051:T:TA	acceptor_gain	0.9800
7:101087062:C:G	acceptor_gain	0.9800
7:101087066:C:CA	acceptor_gain	0.9800
7:101089577:T:G	donor_gain	0.9800
7:101089583:GGGC:G	donor_gain	0.9800
7:101085567:GCTAG:G	donor_gain	0.9700
7:101087065:AC:A	acceptor_gain	0.9700
7:101087311:GCA:G	acceptor_gain	0.9700
7:101085572:G:GG	donor_gain	0.9600
7:101087047:C:CA	acceptor_gain	0.9600
7:101087047:C:G	acceptor_gain	0.9600
7:101087061:A:AG	acceptor_gain	0.9600
7:101087063:ACAC:A	acceptor_gain	0.9600
7:101087309:CAG:C	acceptor_loss	0.9600

AlphaMissense

4818 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:101087373:T:C	C21R	0.999
7:101087478:T:C	C56R	0.999
7:101087540:C:A	N76K	0.999
7:101087540:C:G	N76K	0.999
7:101088913:T:C	F534S	0.999
7:101089126:T:A	V605D	0.999
7:101087374:G:A	C21Y	0.998
7:101087418:T:C	C36R	0.998
7:101087670:T:C	C120R	0.998
7:101087694:T:C	C128R	0.998
7:101087715:C:G	H135D	0.998
7:101087717:C:A	H135Q	0.998
7:101087717:C:G	H135Q	0.998
7:101087817:T:C	C169R	0.998
7:101087853:T:C	C181R	0.998
7:101087877:T:C	C189R	0.998
7:101088877:T:C	L522P	0.998
7:101088885:G:C	D525H	0.998
7:101089128:A:C	S606R	0.998
7:101089130:C:A	S606R	0.998
7:101089130:C:G	S606R	0.998
7:101089227:T:C	F639L	0.998
7:101089229:T:A	F639L	0.998
7:101089229:T:G	F639L	0.998
7:101089264:C:G	S651W	0.998
7:101089486:C:A	P725H	0.998
7:101087373:T:A	C21S	0.997
7:101087374:G:C	C21S	0.997
7:101087375:T:G	C21W	0.997
7:101087426:T:A	H38Q	0.997

dbSNP variants (sampled 300 via entrez): RS1000151433 (7:101085532 C>A), RS1000904371 (7:101097497 G>A), RS1000937424 (7:101093120 A>G), RS1000990039 (7:101093259 C>T), RS1001272992 (7:101097798 G>T), RS1001662863 (7:101093064 G>C), RS1001697771 (7:101093648 G>A,C), RS1001748276 (7:101087227 G>A), RS1001821919 (7:101086917 G>A), RS1001841912 (7:101097753 C>A,T), RS1002158685 (7:101088183 A>C,G), RS1002301101 (7:101093298 T>A,C), RS1002431491 (7:101094685 G>T), RS1002898150 (7:101087058 T>TGTA), RS1003250839 (7:101096286 A>G)

Disease associations

OMIM: gene MIM:616996 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST007250_7	Nonunion in individuals with fractures	3.000000e-07
GCST007600_5	Alzheimer’s disease	5.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0009707	fractures, ununited

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects binding, increases reaction, affects cotreatment, increases abundance, increases expression (+1 more)	4
Calcitriol	affects cotreatment, increases expression	2
Valproic Acid	increases methylation, affects expression	2
Cadmium Chloride	increases expression	2
FR900359	increases phosphorylation	1
dicrotophos	increases expression	1
2,4,6-tribromophenol	decreases expression	1
methylmercuric chloride	increases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	decreases expression	1
decabromobiphenyl ether	increases expression	1
butyraldehyde	decreases expression	1
tetrabromobisphenol A	decreases expression	1
manganese chloride	affects cotreatment, increases abundance, increases expression	1
coumarin	decreases phosphorylation	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
hexabrominated diphenyl ether 153	decreases expression	1
Sunitinib	increases expression	1
Acetaminophen	increases expression	1
Arsenic	affects cotreatment, increases abundance, increases expression	1
Benzo(a)pyrene	increases methylation	1
Caffeine	affects phosphorylation	1
Doxorubicin	decreases expression	1
Manganese	affects cotreatment, increases abundance, increases expression	1
Potassium Dichromate	increases expression	1
Quercetin	increases phosphorylation	1
Ribonucleotides	affects binding	1
Testosterone	affects cotreatment, increases expression	1
Tobacco Smoke Pollution	increases expression	1
Tretinoin	increases 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_B1IE	Abcam A-549 TRIM56 KO 1	Cancer cell line	Male
CVCL_B2QY	Abcam A-549 TRIM56 KO 2	Cancer cell line	Male
CVCL_TU38	HAP1 TRIM56 (-)	Cancer cell line	Male

Clinical trials (associated diseases)

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