TRIM14

Summary

TRIM14 (tripartite motif containing 14, HGNC:16283) is a protein-coding gene on chromosome 9q22.33, encoding Tripartite motif-containing protein 14 (Q14142). Plays an essential role in the innate immune defense against viruses and bacteria.

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 and its function has not been determined. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 9830 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 83 total — 1 pathogenic
• MANE Select transcript: NM_014788

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16283
Approved symbol	TRIM14
Name	tripartite motif containing 14
Location	9q22.33
Locus type	gene with protein product
Status	Approved
Aliases	KIAA0129
Ensembl gene	ENSG00000106785
Ensembl biotype	protein_coding
OMIM	606556
Entrez	9830

Gene structure

Transcript identifiers

Ensembl transcripts: 20 — 17 protein_coding, 2 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000341469, ENST00000342043, ENST00000375098, ENST00000475147, ENST00000478401, ENST00000478530, ENST00000869642, ENST00000869643, ENST00000869644, ENST00000869645, ENST00000869646, ENST00000869647, ENST00000869648, ENST00000869649, ENST00000869650, ENST00000869651, ENST00000869652, ENST00000869653, ENST00000956697, ENST00000956698

RefSeq mRNA: 2 — MANE Select: NM_014788 NM_014788, NM_033219

CCDS: CCDS6734

Canonical transcript exons

ENST00000341469 — 6 exons

Exon	Start	End
ENSE00001381055	98084353	98088005
ENSE00003464229	98094867	98095029
ENSE00003515864	98091909	98092001
ENSE00003630699	98109889	98109984
ENSE00003637353	98099931	98100164
ENSE00003843408	98118982	98119222

Expression profiles

Bgee: expression breadth ubiquitous, 265 present calls, max score 96.65.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 9.8635 / max 372.2685, expressed in 1544 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
101666	7.2503	1467
101667	1.8644	652
101668	0.3197	129
101669	0.2039	79
101664	0.1494	24
101663	0.0700	39
101665	0.0058	4

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
palpebral conjunctiva	UBERON:0001812	96.65	gold quality
jejunal mucosa	UBERON:0000399	94.65	gold quality
pancreatic ductal cell	CL:0002079	94.36	gold quality
cervix squamous epithelium	UBERON:0006922	94.14	gold quality
esophagus squamous epithelium	UBERON:0006920	93.14	gold quality
amniotic fluid	UBERON:0000173	92.85	gold quality
squamous epithelium	UBERON:0006914	92.28	gold quality
epithelium of esophagus	UBERON:0001976	92.12	gold quality
duodenum	UBERON:0002114	92.11	gold quality
epithelium of nasopharynx	UBERON:0001951	91.51	gold quality
granulocyte	CL:0000094	91.16	gold quality
colonic mucosa	UBERON:0000317	90.98	gold quality
gingival epithelium	UBERON:0001949	90.94	gold quality
ileal mucosa	UBERON:0000331	90.91	gold quality
decidua	UBERON:0002450	90.90	gold quality
leukocyte	CL:0000738	90.89	gold quality
monocyte	CL:0000576	90.88	gold quality
mononuclear cell	CL:0000842	90.84	gold quality
mucosa of sigmoid colon	UBERON:0004993	90.28	gold quality
gingiva	UBERON:0001828	90.07	gold quality
endothelial cell	CL:0000115	89.71	gold quality
nephron tubule	UBERON:0001231	89.43	gold quality
lymph node	UBERON:0000029	89.41	gold quality
spleen	UBERON:0002106	89.35	gold quality
thymus	UBERON:0002370	88.88	gold quality
blood	UBERON:0000178	88.71	gold quality
germinal epithelium of ovary	UBERON:0001304	88.66	gold quality
visceral pleura	UBERON:0002401	88.24	gold quality
renal glomerulus	UBERON:0000074	88.21	gold quality
mucosa of transverse colon	UBERON:0004991	88.02	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.75
E-GEOD-93593	yes	3.96

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

1 targets.

Target	Regulation
JUN	Activation

miRNA regulators (miRDB)

108 targeting TRIM14, 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-4776-3P	100.00	68.73	1340
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-3689D	100.00	66.14	1181
HSA-MIR-6851-5P	100.00	65.63	1294
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-223-3P	99.99	70.14	1140
HSA-MIR-8075	99.97	67.20	962
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-23C	99.95	73.92	3192
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-7845-5P	99.88	64.88	771
HSA-MIR-221-5P	99.86	65.45	1052
HSA-MIR-8073	99.86	65.21	1118
HSA-MIR-4307	99.82	70.45	3374
HSA-MIR-4668-5P	99.79	70.58	3782
HSA-MIR-4319	99.76	69.83	2586
HSA-MIR-7856-5P	99.75	69.99	2901
HSA-MIR-4766-5P	99.75	69.23	2662
HSA-MIR-92A-2-5P	99.75	67.01	2164
HSA-MIR-6745	99.74	65.33	1321
HSA-MIR-4306	99.72	70.50	3630

Literature-anchored findings (GeneRIF, showing 30)

• Upon virus infection, TRIM14 recruits NF-kappaB essential modulator (NEMO) to the MAVS complex via ubiquitin chains. (PMID:24379373)
• stable enhanced expression of trim14 gene in cells activates the transcription of many immunity genes and suppresses Sindbis virus reproduction, but Sindbis virus infection of HEK-trim14 cells promotes inhibition of some genes involved in innate immunity. (PMID:25948474)
• Data suggest that tripartite motif containing 14 protein (TRIM14) might play an important role in the malignant progression of tongue squamous cells carcinoma (TSCC) and in regulation of the NF_Kappa B (NF-kappaB) signaling pathway. (PMID:26799420)
• In searching for mechanisms how TRIM14 exerts its antiviral function we found that TRIM14 interacted with HCV encoded non-structural protein NS5A and could strongly induce its degradation dependent on the NS5A1 subdomain. Interestingly extensive domain mapping analyses revealed that NS5A degradation was mediated by the highly conserved SPRY domain of TRIM14, which might involve the K48 ubiquitination pathway (PMID:27578425)
• Study shows that tripartite Motif 14 (TRIM14) is a putative tumor suppressor and regulator of innate immune response in non-small cell lung cancer. The functional data establishes a novel tumor suppressive role for TRIM14 in non-small cell lung cancer progression. (PMID:28059079)
• Our findings collectively suggest that TRIM14 functions as an oncogene by upregulating the AKT signaling pathway in osteosarcoma cells, supporting its potential utility as a therapeutic target for this disease. (PMID:28205534)
• MiR-15b degrades TRIM14 in oral tongue squamous cell cancer.TRIM14 role in oral tongue squamous cell cancer resistance to cisplatin. (PMID:28350138)
• study identifies new gene-type zinc finger protein 125 (RNF125) as a negative regulator of TRIM14 in the innate antiviral immune response (PMID:28476934)
• survival of xenograft mice was prolonged by BsAbBmi/TRIM treatment compared to either AbBmi-1 or AbTRIM-14 treatment. In conclusion, these results provided new evidence that BsAbBmi/TRIM inhibited the progression of osteosarcoma, which suggest that BsAbBmi/TRIM may be a novel anti-cancer agent for osteosarcoma therapy (PMID:28631557)
• findings define the WHIP-TRIM14-PPP6C mitochondrial signalosome required for RIG-I-mediated innate antiviral immunity. (PMID:29053956)
• we identify the tripartite motif-containing protein (TRIM14) as a target of miR-195-5p. Therefore, we reason that the tumor suppressor role of miR-195-5p in oral squamous cell carcinoma is dependent on the interaction with TRIM14. (PMID:29204446)
• TRIM14 was upregulated in both tissues and cell lines of human breast cancer. Knockdown of TRIM14 inhibited cell proliferation but increased cell apoptosis. (PMID:29562956)
• TRIM14 promotes chemoresistance in gliomas by activating Wnt/beta-catenin signaling via stabilizing Dvl2 (PMID:29867201)
• this study demonstrates that TRIM14 is a STAT1-dependent IFN-stimulated gene, and that the IFN-I-TRIM14-HBx axis shows an alternative way to understand the mechanism by which IFN-I inhibits virus replication (PMID:30150992)
• Results showed that TRIM14 is increased in gastric cancer (GC) tissues and cell lines and associated with malignant features and unfavorable prognosis. Gain and lossoffunctional data confirmed that TRIM14 promotes migration, invasion and EMT progression by activating AKT signaling. TRIM14 was found to function as an oncogene in regulating EMT and metastasis of GC via AKT signaling, which was regulated by miR195. (PMID:30272351)
• The crystal structure of the TRIM14 PRYSPRY domain was solved, and found a positively charged surface that may mediate its partner specificity. TRIM14 PRYSPRY domain binds to acidic peptides, and the analysis of the reported partners of TRIM14 is consistent with this assumption. (PMID:30973643)
• Knockdown of IRF-1 reduces the stimulation of TRIM14 transcription by IFN-alpha, suggesting that IRF-1 is involved in the activation of TRIM14 by IFN-I. IRF-2 has little effect on IFN-alpha-induced TRIM14 transcription but is essential for the basal transcription of TRIM14. (PMID:31150153)
• the function of TRIM14 and NF-kappaB signalling and might (PMID:31322007)
• TRIM14 may be a prognostic factor and oncogene in papillary thyroid carcinoma (PMID:31668806)
• Trim14 promotes autophagy and chemotherapy resistance of gastric cancer cells by regulating AMPK/mTOR pathway. (PMID:32096264)
• Human TRIM14 protects transgenic mice from influenza A viral infection without activation of other innate immunity pathways. (PMID:33864033)
• TRIM14 regulates melanoma malignancy via PTEN/PI3K/AKT and STAT3 pathways. (PMID:33982666)
• miR-4443 targets TRIM14 to suppress metastasis and energy metabolism of papillary thyroid carcinoma (PTC) in vitro. (PMID:34051007)
• miR-671-5p repressed progression of papillary thyroid carcinoma via TRIM14. (PMID:34292652)
• Human mesenchymal stem cells derived exosomes inhibit the growth of acute myeloid leukemia cells via regulating miR-23b-5p/TRIM14 pathway. (PMID:34656078)
• Circular RNA circ_0048764 promotes the development of breast cancer by regulating microRNA-1296-5p/tripartite motif containing 14 axis. (PMID:34787066)
• TRIM14 Overexpression Induces Chemoresistance and Malignant Behaviors of Hepatocellular Carcinoma Cells by Activating the STAT3/HIF-1alpha Pathway. (PMID:37628777)
• TRIM14 suppressed the progression of NSCLC via hexosamine biosynthesis pathway. (PMID:38267812)
• Trim14-IkappaBalpha Signaling Regulates Chronic Inflammatory Pain in Rats and Osteoarthritis Patients. (PMID:38697463)
• Circ_RPPH1 facilitates progression of breast cancer via miR-1296-5p/TRIM14 axis. (PMID:38816350)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Trim14	ENSMUSG00000039853
rattus_norvegicus	Trim14	ENSRNOG00000008922

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

Protein

Protein identifiers

Tripartite motif-containing protein 14 — Q14142 (reviewed: Q14142)

All UniProt accessions (2): Q14142, F2Z2M2

UniProt curated annotations — full annotation on UniProt →

Function. Plays an essential role in the innate immune defense against viruses and bacteria. Promotes the ‘Lys-48’-linked ubiquitination and subsequent degradation of hepatitis C virus NS5A leading to the inhibition of viral replication. Also plays a role in the inhibition of ebolavirus infection by enhancing IFN-beta and NF-kappa-B activation after binding to the viral protein NP. Facilitates the type I IFN response by interacting with MAVS at the outer mitochondria membrane and thereby recruiting NF-kappa-B essential modulator IKBKG/NEMO to the MAVS signalosome, leading to the activation of both the IFN regulatory factor 3/IRF3 and NF-kappa-B pathways. Positively regulates the CGAS-induced type I interferon signaling pathway by stabilizing CGAS and inhibiting its autophagic degradation. Acts as a scaffold between TBK1 and STAT3 to promote phosphorylation of STAT3 and resolve interferon-stimulated gene (ISG) expression. Inhibits the transcriptional activity of SPI1 in a dose-dependent manner. Also inhibits OPTN-mediated selective autophagic degradation of KDM4D and thereby negatively regulates H3K9me2 and H3K9me3. Mechanistically, recruits USP14 to remove the ‘Lys-63’-linked ubiquitination of KDM4D, preventing its recognition by OPTN and subsequent degradation.

Subunit / interactions. Interacts with MAVS. Interacts with WRNIP1 and PPP6C; these interactions positively regulate the RIGI signaling pathway. Interacts with CGAS; this interaction stabilizes CGAS and promotes type I interferon production. Interacts with USP14; this interaction mediates the cleavage of ‘Lys-48’-linked ubiquitination of CGAS. Interacts with TBK1. Interacts with SPI1. Interacts with KDM4D and USP14. (Microbial infection) Interacts with hepatitis B virus HBX; this interaction inhibits formation of the HBX-DDB1 complex, thus inhibiting viral replication. (Microbial infection) Interacts with hepatitis C virus protein NS5A; this interaction promotes NS5A degradation, thus inhibiting viral replication. (Microbial infection) Interacts with ebolavirus protein NP.

Subcellular location. Mitochondrion outer membrane. Cytoplasmic vesicle. Phagosome. Nucleus.

Tissue specificity. Highest expression in liver; undetectable in skeletal muscle.

Post-translational modifications. Ubiquitinated. Undergoes ‘Lys-63’-linked polyubiquitination; this modification allows IKBKG/NEMO recruitment to MAVS. Undergoes ‘Lys-48’-linked polyubiquitination by RNF125; this modification mediates its degradation via the ubiquitin-proteasome pathway.

Domain organisation. The B-box zinc finger is responsible for inhibition of SPI1-mediated transcriptional activation.

Induction. By interferons alpha and gamma in a STAT1-dependent way.

Similarity. Belongs to the TRIM/RBCC family.

Isoforms (4)

UniProt ID	Names	Canonical?
Q14142-1	Alpha	yes
Q14142-2	Beta
Q14142-3	3
Q14142-4	4

RefSeq proteins (2): NP_055603, NP_150088 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000315	Znf_B-box	Domain
IPR001870	B30.2/SPRY	Domain
IPR003877	SPRY_dom	Domain
IPR003879	Butyrophylin_SPRY	Domain
IPR006574	PRY	Domain
IPR013320	ConA-like_dom_sf	Homologous_superfamily
IPR043136	B30.2/SPRY_sf	Homologous_superfamily
IPR044116	SPRY_PRY_TRIM14	Domain
IPR051051	E3_ubiq-ligase_TRIM/RNF	Family
IPR058030	TRIM8/14/16/25/29/45/65_CC	Domain

Pfam: PF00622, PF00643, PF13765, PF25600

UniProt features (37 total): strand 14, splice variant 5, turn 4, binding site 4, helix 2, coiled-coil region 2, chain 1, domain 1, sequence variant 1, mutagenesis site 1, zinc finger region 1, sequence conflict 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
6JBM	X-RAY DIFFRACTION	2.1

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q14142-F1	86.70	0.64

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): 24; 27; 47; 53

Mutagenesis-validated functional residues (1):

Position	Phenotype
365	more than 50% loss of interaction with mavs. however it has equal potency in inhibiting hcv replication that the wild ty

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-877300	Interferon gamma signaling

MSigDB gene sets: 239 (showing top): BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, MODULE_255, GOBP_INFLAMMATORY_RESPONSE, GOBP_NEGATIVE_REGULATION_OF_VIRAL_PROCESS, MODULE_317, GOBP_DEFENSE_RESPONSE_TO_OTHER_ORGANISM, BLALOCK_ALZHEIMERS_DISEASE_UP, DER_IFN_BETA_RESPONSE_UP, GOCC_MITOCHONDRIAL_ENVELOPE, DAUER_STAT3_TARGETS_DN, GOBP_REGULATION_OF_VIRAL_TRANSCRIPTION, TIEN_INTESTINE_PROBIOTICS_24HR_UP, chr9q22, GOBP_NEGATIVE_REGULATION_OF_VIRAL_TRANSCRIPTION

GO Biological Process (6): inflammatory response (GO:0006954), negative regulation of viral transcription (GO:0032897), innate immune response (GO:0045087), immune system process (GO:0002376), positive regulation of DNA-templated transcription (GO:0045893), protein K48-linked deubiquitination (GO:0071108)

GO Molecular Function (6): transcription coactivator activity (GO:0003713), zinc ion binding (GO:0008270), molecular adaptor activity (GO:0060090), ubiquitin protein ligase activity (GO:0061630), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (7): nucleus (GO:0005634), cytoplasm (GO:0005737), mitochondrial outer membrane (GO:0005741), phagocytic vesicle (GO:0045335), mitochondrion (GO:0005739), membrane (GO:0016020), cytoplasmic vesicle (GO:0031410)

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
binding	2
intracellular membrane-bounded organelle	2
cellular anatomical structure	2
cytoplasm	2
defense response	1
viral transcription	1
regulation of viral transcription	1
negative regulation of viral process	1
immune response	1
defense response to symbiont	1
biological_process	1
DNA-templated transcription	1
regulation of DNA-templated transcription	1
positive regulation of RNA biosynthetic process	1
protein deubiquitination	1
transcription coregulator activity	1
positive regulation of DNA-templated transcription	1
transition metal ion binding	1
molecular_function	1
ubiquitin-protein transferase activity	1
ubiquitin-like protein ligase activity	1
cation binding	1
intracellular anatomical structure	1
mitochondrial membrane	1
organelle outer membrane	1
endocytic vesicle	1
intracellular vesicle	1

Protein interactions and networks

STRING

1663 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TRIM14	USP14	P54578	991
TRIM14	TRAT1	Q6PIZ9	918
TRIM14	PPP6C	O00743	846
TRIM14	BBOX1	O75936	829
TRIM14	MAVS	Q7Z434	804
TRIM14	TRIM44	Q96DX7	627
TRIM14	TRIM52	Q96A61	595
TRIM14	TRIM56	Q9BRZ2	570
TRIM14	TRIM31	Q9BZY9	541
TRIM14	USP15	Q9Y4E8	536
TRIM14	TRIM59	Q8IWR1	527
TRIM14	TRAF6	Q9Y4K3	517
TRIM14	CGAS	Q8N884	512
TRIM14	PLSCR1	O15162	509
TRIM14	TRIM32	Q13049	507

IntAct

110 interactions, top by confidence:

A	B	Type	Score
TRIM14	CARD9	psi-mi:“MI:0915”(physical association)	0.560
POLR1C	TRIM14	psi-mi:“MI:0915”(physical association)	0.560
TRIM14	KIFC3	psi-mi:“MI:0915”(physical association)	0.560
TRIM14	MAPRE3	psi-mi:“MI:0915”(physical association)	0.560
TRIM14	CIB3	psi-mi:“MI:0915”(physical association)	0.560
TRIM14	SLF2	psi-mi:“MI:0915”(physical association)	0.560
TRIM14	PRPF31	psi-mi:“MI:0915”(physical association)	0.560
TRIM14	CCDC125	psi-mi:“MI:0915”(physical association)	0.560
ADAMTS12	TRIM14	psi-mi:“MI:0915”(physical association)	0.560
HNRNPF	TRIM14	psi-mi:“MI:0915”(physical association)	0.560
GOLGA6L9	TRIM14	psi-mi:“MI:0915”(physical association)	0.560
VIM	TRIM14	psi-mi:“MI:0915”(physical association)	0.560
BYSL	TRIM14	psi-mi:“MI:0915”(physical association)	0.560
TRIM14	LNX1	psi-mi:“MI:0915”(physical association)	0.560
GOLGA2	TRIM14	psi-mi:“MI:0915”(physical association)	0.560
RAD51D	TRIM14	psi-mi:“MI:0915”(physical association)	0.560
TRIM14	CCDC57	psi-mi:“MI:0915”(physical association)	0.560
TRIM14	CCDC6	psi-mi:“MI:0915”(physical association)	0.560
PRKAB2	TRIM14	psi-mi:“MI:0915”(physical association)	0.560
TRIM14	ZGPAT	psi-mi:“MI:0915”(physical association)	0.560
ERCC3	TRIM14	psi-mi:“MI:0915”(physical association)	0.560
MYO15B	TRIM14	psi-mi:“MI:0915”(physical association)	0.560
TRIM14	EXOC8	psi-mi:“MI:0915”(physical association)	0.560
TRIM14	IHO1	psi-mi:“MI:0915”(physical association)	0.560
TRIM14	PTPN21	psi-mi:“MI:0915”(physical association)	0.560
TRAF2	TRIM14	psi-mi:“MI:0915”(physical association)	0.560
TRIM14	SPG21	psi-mi:“MI:0915”(physical association)	0.560
TRIM14	HEXIM2	psi-mi:“MI:0915”(physical association)	0.560
CKS1B	TRIM14	psi-mi:“MI:0915”(physical association)	0.560
TRIM14	PRDM6	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (409): TRIM14 (Affinity Capture-MS), TRIM14 (Affinity Capture-MS), TRIM14 (Affinity Capture-MS), TRIM14 (Affinity Capture-MS), TRIM14 (Affinity Capture-MS), MAVS (Affinity Capture-Western), TRIM14 (Affinity Capture-Western), MAVS (Co-fractionation), TRIM14 (Affinity Capture-Western), TRIM14 (Affinity Capture-Western), TRIM14 (Affinity Capture-Western), IKBKG (Reconstituted Complex), IKBKG (Affinity Capture-Western), TRIM14 (Affinity Capture-Western), TRIM14 (Biochemical Activity)

ESM2 similar proteins: A0JPQ4, E1BD59, O15197, P0C0K6, P62603, Q14142, Q1XH17, Q1XH18, Q3UWZ0, Q5BK82, Q5JZY3, Q5M929, Q5NCC3, Q5RBG2, Q5RKG6, Q5TM55, Q5W0U4, Q640S6, Q6P6S3, Q6PGR9, Q6PJ69, Q6ZMU5, Q7TPM3, Q7YR32, Q80VI1, Q80X56, Q80YW5, Q810I1, Q810I2, Q865W2, Q86UV6, Q86UV7, Q86XT4, Q8BFW4, Q8BVW3, Q8BYG9, Q8C006, Q8C0E3, Q8IUD6, Q8K243

Diamond homologs: A0A2P1BRP3, A0A2P1BRQ0, A0ZSK3, A0ZSK4, B1H278, O95361, Q14142, Q1LY10, Q1XHU0, Q309B1, Q5BK82, Q5R760, Q6MFZ5, Q6P6S3, Q6UXG8, Q80X56, Q80YW5, Q8BVW3, Q8WV44, Q8WVV5, Q91453, Q96F44, Q98989, Q98993, Q99PP9, Q99PQ2, Q9ESN2, Q9HCM9, Q14258, Q4FZT8, Q61510, Q8WW59, Q91WK1, A0JN74, A4QPC6, A6NK02, D3YY23, E7FAP1, F8RKW2, F8S122

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	59
Likely benign	7
Benign	2

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
235185	NM_018946.4(NANS):c.389dup (p.Lys131fs)	Pathogenic

SpliceAI

2206 predictions. Top by Δscore:

Variant	Effect	Δscore
9:98078345:TCG:T	donor_gain	1.0000
9:98078345:TCGG:T	donor_loss	1.0000
9:98078347:GGT:G	donor_loss	1.0000
9:98078348:G:C	donor_loss	1.0000
9:98078348:G:GG	donor_gain	1.0000
9:98078349:T:A	donor_loss	1.0000
9:98082844:A:AG	acceptor_gain	1.0000
9:98082844:AGCT:A	acceptor_gain	1.0000
9:98082844:AGCTG:A	acceptor_gain	1.0000
9:98082845:G:GG	acceptor_gain	1.0000
9:98082845:GCT:G	acceptor_gain	1.0000
9:98082845:GCTG:G	acceptor_gain	1.0000
9:98082845:GCTGG:G	acceptor_gain	1.0000
9:98094863:TTA:T	donor_loss	1.0000
9:98094864:TA:T	donor_loss	1.0000
9:98094865:A:AC	donor_gain	1.0000
9:98094865:AC:A	donor_loss	1.0000
9:98094865:ACTTT:A	donor_gain	1.0000
9:98094866:C:CT	donor_gain	1.0000
9:98094866:CT:C	donor_gain	1.0000
9:98094866:CTT:C	donor_gain	1.0000
9:98094866:CTTT:C	donor_gain	1.0000
9:98094866:CTTTC:C	donor_gain	1.0000
9:98094869:T:A	donor_gain	1.0000
9:98095032:G:GC	acceptor_gain	1.0000
9:98076915:TA:T	acceptor_loss	0.9900
9:98076916:A:AG	acceptor_gain	0.9900
9:98076917:G:GG	acceptor_gain	0.9900
9:98076917:G:GT	acceptor_loss	0.9900
9:98077014:AAAGG:A	donor_loss	0.9900

AlphaMissense

2867 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:98087884:G:C	F305L	0.995
9:98087884:G:T	F305L	0.995
9:98087886:A:G	F305L	0.995
9:98087827:C:A	W324C	0.994
9:98087827:C:G	W324C	0.994
9:98087829:A:G	W324R	0.994
9:98087829:A:T	W324R	0.994
9:98087715:A:G	W362R	0.993
9:98087715:A:T	W362R	0.993
9:98087587:G:C	F404L	0.992
9:98087587:G:T	F404L	0.992
9:98087589:A:G	F404L	0.992
9:98087548:G:C	F417L	0.991
9:98087548:G:T	F417L	0.991
9:98087550:A:G	F417L	0.991
9:98087549:A:G	F417S	0.990
9:98087588:A:G	F404S	0.990
9:98087537:A:G	F421S	0.989
9:98087733:C:G	G356R	0.989
9:98119050:A:G	C47R	0.989
9:98119084:G:C	F35L	0.989
9:98119084:G:T	F35L	0.989
9:98119086:A:G	F35L	0.989
9:98087594:A:T	L402H	0.988
9:98087718:A:G	S361P	0.988
9:98087732:C:T	G356D	0.988
9:98087536:G:C	F421L	0.987
9:98087536:G:T	F421L	0.987
9:98087538:A:G	F421L	0.987
9:98087828:C:G	W324S	0.987

dbSNP variants (sampled 300 via entrez): RS1000036424 (9:98112089 A>G,T), RS1000067149 (9:98037891 G>A), RS1000154113 (9:98106734 A>C,G), RS1000195538 (9:98063679 C>T), RS1000203275 (9:98056627 C>A,G,T), RS1000260111 (9:98075092 G>C), RS1000300618 (9:98105337 C>T), RS1000340285 (9:98039278 G>A), RS1000351247 (9:98100334 G>A), RS1000356119 (9:98044967 G>T), RS1000371035 (9:98087897 G>C,T), RS1000377708 (9:98055818 A>G), RS1000412745 (9:98094097 A>G,T), RS1000429477 (9:98049680 G>A), RS1000509417 (9:98050850 T>C)

Disease associations

OMIM: gene MIM:606556 | disease phenotypes: MIM:610442

GenCC curated gene-disease

Mondo (1): spondyloepimetaphyseal dysplasia, Genevieve type (MONDO:0012495)

Orphanet (1): Spondyloepimetaphyseal dysplasia, Geneviève type (Orphanet:168454)

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST009597_110	Multiple sclerosis	1.000000e-10

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C535785	Spondyloepimetaphyseal dysplasia, Genevieve type (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression	5
trichostatin A	affects cotreatment, increases expression	3
Estradiol	increases expression, affects cotreatment	3
Tetrachlorodibenzodioxin	increases expression, decreases expression, affects cotreatment	3
sodium arsenite	increases abundance, increases expression, decreases expression, affects cotreatment	2
entinostat	increases expression, affects cotreatment	2
(+)-JQ1 compound	decreases expression	2
Vorinostat	affects cotreatment, increases expression	2
Panobinostat	affects cotreatment, increases expression	2
Acetaminophen	decreases expression	2
Nickel	increases expression	2
Phenylmercuric Acetate	decreases expression, affects cotreatment	2
Tretinoin	decreases expression, increases expression	2
Cadmium Chloride	decreases expression	2
dicrotophos	increases expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
methylselenic acid	decreases expression	1
cobaltous chloride	decreases expression	1
butyraldehyde	decreases expression	1
manganese chloride	increases abundance, increases expression, affects cotreatment	1
potassium chromate(VI)	increases expression	1
cupric oxide	decreases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
K 7174	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	decreases expression, affects cotreatment, increases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, increases expression, decreases expression	1

Cellosaurus cell lines

4 cell lines: 4 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B1IA	Abcam A-549 TRIM14 KO 2	Cancer cell line	Male
CVCL_B2QT	Abcam A-549 TRIM14 KO 1	Cancer cell line	Male
CVCL_TT82	HAP1 TRIM14 (-) 1	Cancer cell line	Male
CVCL_TT83	HAP1 TRIM14 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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