TRIM16

Summary

TRIM16 (tripartite motif containing 16, HGNC:17241) is a protein-coding gene on chromosome 17p12, encoding Tripartite motif-containing protein 16 (O95361). E3 ubiquitin ligase that plays an essential role in the organization of autophagic response and ubiquitination upon lysosomal and phagosomal damages.

The protein encoded by this gene is a tripartite motif (TRIM) family member that contains two B box domains and a coiled-coiled region that are characteristic of the B box zinc finger protein family. While it lacks a RING domain found in other TRIM proteins, the encoded protein can homodimerize or heterodimerize with other TRIM proteins and has E3 ubiquitin ligase activity. This gene is also a tumor suppressor and is involved in secretory autophagy.

Source: NCBI Gene 10626 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 104 total
• MANE Select transcript: NM_001348119

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17241
Approved symbol	TRIM16
Name	tripartite motif containing 16
Location	17p12
Locus type	gene with protein product
Status	Approved
Aliases	EBBP
Ensembl gene	ENSG00000221926
Ensembl biotype	protein_coding
OMIM	609505
Entrez	10626

Gene structure

Transcript identifiers

Ensembl transcripts: 43 — 28 protein_coding, 12 protein_coding_CDS_not_defined, 2 retained_intron, 1 nonsense_mediated_decay

ENST00000336708, ENST00000416464, ENST00000460728, ENST00000473368, ENST00000473540, ENST00000473659, ENST00000494759, ENST00000577326, ENST00000577372, ENST00000577446, ENST00000577886, ENST00000578237, ENST00000578744, ENST00000579219, ENST00000579272, ENST00000579535, ENST00000579630, ENST00000579843, ENST00000580110, ENST00000580388, ENST00000581200, ENST00000581224, ENST00000582182, ENST00000582708, ENST00000584142, ENST00000649191, ENST00000852769, ENST00000932631, ENST00000932632, ENST00000932633, ENST00000932634, ENST00000967546, ENST00000967547, ENST00000967548, ENST00000967549, ENST00000967550, ENST00000967551, ENST00000967552, ENST00000967553, ENST00000967554, ENST00000967555, ENST00000967556, ENST00000967557

RefSeq mRNA: 8 — MANE Select: NM_001348119 NM_001348119, NM_001348120, NM_001348121, NM_001348122, NM_001348124, NM_001348125, NM_001348126, NM_006470

CCDS: CCDS11171, CCDS86578, CCDS86579

Canonical transcript exons

ENST00000649191 — 12 exons

Exon	Start	End
ENSE00000855518	15651091	15651946
ENSE00001425069	15677176	15677280
ENSE00002407341	15682854	15682951
ENSE00003485799	15636036	15636269
ENSE00003528052	15677575	15677721
ENSE00003544880	15632509	15632674
ENSE00003570594	15683036	15683157
ENSE00003609122	15642721	15642816
ENSE00003611319	15680865	15680953
ENSE00003613662	15631619	15631714
ENSE00003835465	15627966	15629198
ENSE00003901874	15684196	15684311

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 98.20.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 14.5949 / max 279.2969, expressed in 1746 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
164695	10.0162	1417
164702	2.6432	1302
164699	0.8799	440
164693	0.2740	138
164697	0.2693	134
164694	0.2216	110
164701	0.1699	54
164700	0.0891	21
164698	0.0317	7

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
lower esophagus mucosa	UBERON:0035834	98.20	gold quality
esophagus mucosa	UBERON:0002469	97.34	gold quality
placenta	UBERON:0001987	93.46	gold quality
cortical plate	UBERON:0005343	92.88	gold quality
right adrenal gland cortex	UBERON:0035827	92.50	gold quality
right adrenal gland	UBERON:0001233	92.26	gold quality
esophagus	UBERON:0001043	92.24	gold quality
skin of leg	UBERON:0001511	91.99	gold quality
zone of skin	UBERON:0000014	91.95	gold quality
skin of abdomen	UBERON:0001416	91.85	gold quality
adrenal tissue	UBERON:0018303	91.83	gold quality
vagina	UBERON:0000996	91.53	gold quality
left adrenal gland	UBERON:0001234	91.36	gold quality
adrenal gland	UBERON:0002369	90.95	gold quality
urinary bladder	UBERON:0001255	90.92	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	90.91	gold quality
left adrenal gland cortex	UBERON:0035825	90.58	gold quality
ganglionic eminence	UBERON:0004023	89.54	gold quality
tonsil	UBERON:0002372	89.49	gold quality
minor salivary gland	UBERON:0001830	89.42	gold quality
apex of heart	UBERON:0002098	89.22	gold quality
duodenum	UBERON:0002114	88.99	gold quality
saliva-secreting gland	UBERON:0001044	88.82	gold quality
skeletal muscle tissue	UBERON:0001134	88.39	gold quality
heart left ventricle	UBERON:0002084	87.75	gold quality
right lobe of thyroid gland	UBERON:0001119	87.71	gold quality
body of stomach	UBERON:0001161	87.57	gold quality
gall bladder	UBERON:0002110	87.37	gold quality
corpus callosum	UBERON:0002336	87.35	gold quality
muscle tissue	UBERON:0002385	87.30	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-GEOD-110499	yes	92.70
E-MTAB-10137	no	4.85
E-ANND-3	no	0.00

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

3 targets.

Target	Regulation
DES	Repression
E2F1	Repression
VIM	Repression

Upstream regulators (CollecTRI, top): ESR1, RARB, TCF3

miRNA regulators (miRDB)

46 targeting TRIM16, 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-4510	100.00	66.60	2050
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-3613-3P	100.00	76.36	7965
HSA-MIR-4455	100.00	65.48	1587
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-767-5P	99.95	70.85	993
HSA-MIR-4302	99.89	67.94	1187
HSA-MIR-3065-3P	99.87	70.25	1407
HSA-MIR-7856-5P	99.75	69.99	2901
HSA-MIR-1827	99.63	68.57	3265
HSA-MIR-940	99.37	66.14	2064
HSA-MIR-6808-5P	99.31	66.23	2150
HSA-MIR-6893-5P	99.31	66.25	2119
HSA-MIR-4784	99.15	67.41	1733
HSA-MIR-6506-5P	99.04	65.66	1386
HSA-MIR-1843	98.97	66.07	838
HSA-MIR-4802-5P	98.97	66.26	833
HSA-MIR-3150B-3P	98.81	67.21	1728
HSA-MIR-7977	98.65	66.18	2590
HSA-MIR-3135B	98.61	65.33	1470
HSA-MIR-619-5P	98.57	64.97	1988
HSA-MIR-4766-3P	98.48	67.94	1347
HSA-MIR-3187-5P	98.36	65.74	1776
HSA-MIR-4684-5P	98.29	67.99	1650
HSA-MIR-4768-3P	98.16	66.02	2330

Literature-anchored findings (GeneRIF, showing 28)

• role in regulating keratinocyte differentiation (PMID:11919186)
• These results provide evidence for a role of EBBP in innate immunity by enhancing the alternative secretion pathway of IL-1beta. (PMID:16575408)
• EBBP increased betaRARE-transactivating function through its coiled-coil domain (PMID:16636064)
• The estrogen-responsive B box protein (EBBP) restores retinoid sensitivity in retinoid-resistant cancer cells via effects on histone acetylation. (PMID:19147277)
• TRIM16 acts as a tumour suppressor, affecting neuritic differentiation, cell migration and replication through interactions with cytoplasmic vimentin and nuclear E2F1 in neuroblastoma cells. (PMID:20729920)
• via its unique structure, TRIM16 possesses both heterodimerization function with other TRIM proteins and also has E3 ubiquitin ligase activity. (PMID:22629402)
• TRIM16 can promote apoptosis by directly modulating caspase-2 activity in cancer cells. (PMID:23404198)
• data suggest that TRIM16 acts as a novel regulator of both neuroblastoma G 1/S progression and cell differentiation (PMID:23422002)
• Chromatin immunoprecipitation assays revealed TRIM16 directly bound the IFNbeta1 gene promoter. Low level TRIM16 expression in 91 melanoma patient samples, strongly correlated with lymph node metastasis, and, predicted poor patient prognosis. (PMID:25333256)
• results suggest that TRIM16 is a potential pharmacologic target for the treatment of NSCLC and promotion TRIM16 expression might represent a novel strategy to NSCLC metastasis (PMID:25843803)
• Expression of SDMGC and TRIM16 was upregulated in the distant metastasis tissues (PMID:25866896)
• Data suggest that TRIM16 and TDP43 are both good prognosis indicators; data shows that TRIM16 inhibits cancer cell viability by a novel mechanism involving interaction and stabilisation of TDP43 with consequent effects on E2F1 and pRb proteins. (PMID:26902425)
• The cooperation between TRIM16 and Galectin-3 in targeting and activation of selective autophagy protects cells from lysosomal damage and Mycobacterium tuberculosis invasion. (PMID:27693506)
• TRIM16 inhibits the migration and invasion via suppressing the Sonic hedgehog signaling pathway in ovarian cancer cells. (PMID:27737724)
• TRIM16 acts as a scaffold protein and, by interacting with p62, ULK1, ATG16L1, and LC3B, facilitates autophagic degradation of protein aggregates. (PMID:30143514)
• Papillary thyroid carcinoma was characterized by high expression of ESR2 and AR, which was associated with expression and content of nuclear factors Brn-3A and TRIM16. (PMID:30488195)
• Galectin-3 and TRIM16 coregulate osteogenic differentiation of human bone marrow-derived mesenchymal stem cells at least partly via enhancing autophagy. (PMID:31521826)
• The results indicate that the RASSF6-TRIM16 axis is a key effector in ESCC progression and that RASSF6 serves as a potential target for the treatment of ESCC. (PMID:31812473)
• AKT-induced lncRNA VAL promotes EMT-independent metastasis through diminishing Trim16-dependent Vimentin degradation. (PMID:33046716)
• A thermosensitive, reactive oxygen species-responsive, MR409-encapsulated hydrogel ameliorates disc degeneration in rats by inhibiting the secretory autophagy pathway. (PMID:33391467)
• Impaired TRIM16-Mediated Lysophagy in Chronic Obstructive Pulmonary Disease Pathogenesis. (PMID:34135057)
• TRIM16 overexpression inhibits the metastasis of colorectal cancer through mediating Snail degradation. (PMID:34265287)
• Prognostic Significance of Tripartite Motif Containing 16 Expression in Patients with Gastric Cancer. (PMID:34452557)
• Changes in the Expression of Long Non-Coding RNA SDMGC and Its Target Gene, TRIM16, in Patients with Gastric Cancer. (PMID:34978663)
• CircPTK2 inhibits cell cisplatin (CDDP) resistance by targeting miR-942/TRIM16 axis in non-small cell lung cancer (NSCLC). (PMID:35230201)
• TRIM3 and TRIM16 as potential tumor suppressors in breast cancer patients. (PMID:36180926)
• TRIM16 E121D variant affects the risk and prognosis of hepatocellular carcinoma by modulating the Wnt/beta-catenin pathway. (PMID:37477507)
• NFKBIZ regulates NFkappaB signaling pathway to mediate tumorigenesis and metastasis of hepatocellular carcinoma by direct interaction with TRIM16. (PMID:38581570)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
danio_rerio	trim16	ENSDARG00000010673
mus_musculus	Trim16	ENSMUSG00000047821

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

Tripartite motif-containing protein 16 — O95361 (reviewed: O95361)

Alternative names: E3 ubiquitin-protein ligase TRIM16, Estrogen-responsive B box protein

All UniProt accessions (9): B3KP96, O95361, J3QKY5, J3QL38, J3QLP0, J3QR69, K7EJH2, K7EL43, K7ENN8

UniProt curated annotations — full annotation on UniProt →

Function. E3 ubiquitin ligase that plays an essential role in the organization of autophagic response and ubiquitination upon lysosomal and phagosomal damages. Plays a role in the stress-induced biogenesis and degradation of protein aggresomes by regulating the p62-KEAP1-NRF2 signaling and particularly by modulating the ubiquitination levels and thus stability of NRF2. Acts as a scaffold protein and facilitates autophagic degradation of protein aggregates by interacting with p62/SQSTM, ATG16L1 and LC3B/MAP1LC3B. In turn, protects the cell against oxidative stress-induced cell death as a consequence of endomembrane damage.

Subunit / interactions. Homodimerizes via its coiled-coil domain. Heterodimerizes with MID1, TRIM24 and PML. Interacts with Galectin-3/LGALS3 in a ULK1-dependent manner; this interaction mediates autophagy of damage endomembranes. Interacts with BECN1. Interacts with ATG16L1. Interacts with p62/SQSTM and LC3B/MAP1LC3B.

Subcellular location. Cytoplasm.

Tissue specificity. Highest levels found in testis, ovary, small intestine, colon, placenta, heart, skeletal muscle and mammary gland. More highly expressed in the fetus than in the corresponding adult tissues. Expressed in basal keratinocytes.

Post-translational modifications. Phosphorylated by ULK1. Auto-ubiquitinates via its B-Boxes.

Similarity. Belongs to the TRIM/RBCC family.

Isoforms (2)

UniProt ID	Names	Canonical?
O95361-1	1, Alpha	yes
O95361-2	2, Beta

RefSeq proteins (8): NP_001335048, NP_001335049, NP_001335050, NP_001335051, NP_001335053, NP_001335054, NP_001335055, NP_006461 (=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
IPR051051	E3_ubiq-ligase_TRIM/RNF	Family
IPR058030	TRIM8/14/16/25/29/45/65_CC	Domain

Pfam: PF00622, PF00643, PF13765, PF25600

UniProt features (46 total): strand 14, sequence conflict 5, binding site 4, sequence variant 3, helix 3, turn 3, coiled-coil region 3, modified residue 2, mutagenesis site 2, zinc finger region 2, chain 1, domain 1, splice variant 1, region of interest 1, compositionally biased region 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
7QS3	X-RAY DIFFRACTION	1.75

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O95361-F1	80.63	0.41

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): 134; 153; 157; 131

Post-translational modifications (2): 116, 203

Mutagenesis-validated functional residues (2):

Position	Phenotype
116	loss of protection from cell death during oxidative stress; when associated with a-203.
203	loss of protection from cell death during oxidative stress; when associated with a-116.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 157 (showing top): VALK_AML_WITH_FLT3_ITD, GOBP_POSITIVE_REGULATION_OF_EPITHELIAL_CELL_DIFFERENTIATION, chr17p12, SHEPARD_BMYB_MORPHOLINO_UP, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_EPITHELIUM_DEVELOPMENT, YAGI_AML_WITH_INV_16_TRANSLOCATION, GOBP_POSITIVE_REGULATION_OF_KERATINOCYTE_DIFFERENTIATION, GOBP_REGULATION_OF_EPIDERMIS_DEVELOPMENT, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, GOBP_REGULATION_OF_RETINOIC_ACID_RECEPTOR_SIGNALING_PATHWAY, GOBP_POSITIVE_REGULATION_OF_CYTOKINE_PRODUCTION, MODULE_16, GOBP_INTERLEUKIN_1_PRODUCTION

GO Biological Process (7): response to retinoic acid (GO:0032526), positive regulation of interleukin-1 beta production (GO:0032731), positive regulation of keratinocyte differentiation (GO:0045618), positive regulation of DNA-templated transcription (GO:0045893), positive regulation of retinoic acid receptor signaling pathway (GO:0048386), response to growth hormone (GO:0060416), regulation of DNA-templated transcription (GO:0006355)

GO Molecular Function (8): DNA binding (GO:0003677), zinc ion binding (GO:0008270), interleukin-1 binding (GO:0019966), NACHT domain binding (GO:0032089), ubiquitin protein ligase activity (GO:0061630), protein binding (GO:0005515), transferase activity (GO:0016740), metal ion binding (GO:0046872)

GO Cellular Component (4): cytoplasm (GO:0005737), cytosol (GO:0005829), plasma membrane (GO:0005886), PML body (GO:0016605)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
DNA-templated transcription	2
cellular anatomical structure	2
response to lipid	1
response to oxygen-containing compound	1
interleukin-1 beta production	1
regulation of interleukin-1 beta production	1
positive regulation of interleukin-1 production	1
keratinocyte differentiation	1
positive regulation of epidermal cell differentiation	1
regulation of keratinocyte differentiation	1
positive regulation of multicellular organismal process	1
regulation of DNA-templated transcription	1
positive regulation of RNA biosynthetic process	1
retinoic acid receptor signaling pathway	1
regulation of retinoic acid receptor signaling pathway	1
positive regulation of intracellular signal transduction	1
response to peptide hormone	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
nucleic acid binding	1
transition metal ion binding	1
growth factor binding	1
cytokine binding	1
protein domain specific binding	1
ubiquitin-protein transferase activity	1
ubiquitin-like protein ligase activity	1
binding	1
catalytic activity	1
cation binding	1
intracellular anatomical structure	1
cytoplasm	1
membrane	1
cell periphery	1
nuclear body	1

Protein interactions and networks

STRING

824 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TRIM16	LGALS3	P17931	992
TRIM16	SEC22B	O75396	937
TRIM16	ATG16L1	Q676U5	867
TRIM16	LGALS8	O00214	803
TRIM16	BBOX1	O75936	799
TRIM16	BECN1	Q14457	701
TRIM16	TRAT1	Q6PIZ9	694
TRIM16	IL1B	P01584	650
TRIM16	STX3	Q13277	631
TRIM16	PML	P29590	623
TRIM16	SNAP23	O00161	582
TRIM16	SQSTM1	Q13501	576
TRIM16	FGF7	P21781	556
TRIM16	KEAP1	Q14145	536
TRIM16	TARDBP	Q13148	508

IntAct

30 interactions, top by confidence:

A	B	Type	Score
CCDC22	VPS26C	psi-mi:“MI:0914”(association)	0.790
TRIM16	TRIM16L	psi-mi:“MI:0914”(association)	0.710
TRIM16	TRIM16L	psi-mi:“MI:0915”(physical association)	0.710
SLC39A4	TMEM120B	psi-mi:“MI:0914”(association)	0.530
TINF2	TRIM16	psi-mi:“MI:0915”(physical association)	0.510
TRIM16	VIM	psi-mi:“MI:0915”(physical association)	0.460
VIM	TRIM16	psi-mi:“MI:0915”(physical association)	0.460
TRIM16	VIM	psi-mi:“MI:0403”(colocalization)	0.460
TRIM16	E2F1	psi-mi:“MI:0915”(physical association)	0.400
E2F1	TRIM16	psi-mi:“MI:0915”(physical association)	0.400
USP38	TRIM16	psi-mi:“MI:0915”(physical association)	0.400
TERF1	TRIM16	psi-mi:“MI:0915”(physical association)	0.370
TRIM16	ACD	psi-mi:“MI:0915”(physical association)	0.370
TRIM16	POT1	psi-mi:“MI:0915”(physical association)	0.370
CFTR	TRIM16	psi-mi:“MI:0915”(physical association)	0.370
Rhoa	CLK2	psi-mi:“MI:0914”(association)	0.350
Sidt2	PRSS1	psi-mi:“MI:0914”(association)	0.350
Gnpnat1	SMCHD1	psi-mi:“MI:0914”(association)	0.350
	SHTN1	psi-mi:“MI:0914”(association)	0.350
CCR1	UBA6	psi-mi:“MI:0914”(association)	0.350
NUP62	RGPD3	psi-mi:“MI:0914”(association)	0.350
PINK1	A2ML1	psi-mi:“MI:0914”(association)	0.350
MBNL1	A2ML1	psi-mi:“MI:0914”(association)	0.350
NOL7	MAGEB2	psi-mi:“MI:0914”(association)	0.350
NUP62	MYO9A	psi-mi:“MI:0914”(association)	0.350
TRIM16L	IGLL5	psi-mi:“MI:0914”(association)	0.350
TINF2	TRIM16	psi-mi:“MI:0915”(physical association)	0.000
TRIM16	SETDB1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (76): TRIM16 (Affinity Capture-RNA), TRIM16 (Affinity Capture-RNA), TRIM16L (Affinity Capture-MS), TRIM16 (Affinity Capture-MS), TRIM16 (Affinity Capture-MS), TRIM16 (Affinity Capture-MS), TRIM16L (Affinity Capture-MS), OPTN (Affinity Capture-MS), TRIM16 (Affinity Capture-Western), TRIM16 (Affinity Capture-Western), LGALS3 (Affinity Capture-Western), TRIM16 (Biochemical Activity), ULK1 (Affinity Capture-Western), CUL4A (Affinity Capture-Western), BECN1 (Affinity Capture-Western)

ESM2 similar proteins: A1L4K1, D4A7V9, E9QHE3, F1LW30, H0UZ81, O15344, O70583, O95361, P82457, P82458, P97573, Q14258, Q14596, Q28CB1, Q38HM4, Q3UMR0, Q3V3A7, Q58D15, Q5F479, Q5R760, Q5RC94, Q5REJ9, Q5REW9, Q5RF77, Q5XIH6, Q61510, Q6P549, Q6P6S3, Q6UXZ4, Q7T2L7, Q7TNH6, Q7Z494, Q80VK6, Q80WG7, Q8BZ52, Q8JZL1, Q8K1S2, Q8NFM7, Q91Z63, Q969Q1

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, A0JN74, O19085, P14373, P19474, Q02084, Q5R7W8, Q62158, Q62556, Q7KYR7, Q86WT6, Q8N7C3, Q91431

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	86
Likely benign	9
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

2257 predictions. Top by Δscore:

Variant	Effect	Δscore
17:15629194:CGCAT:C	acceptor_gain	1.0000
17:15629196:CAT:C	acceptor_gain	1.0000
17:15629199:C:CC	acceptor_gain	1.0000
17:15629208:C:CT	acceptor_gain	1.0000
17:15631617:A:AC	donor_gain	1.0000
17:15631618:C:CC	donor_gain	1.0000
17:15631618:CA:C	donor_gain	1.0000
17:15631710:CTCCT:C	acceptor_gain	1.0000
17:15631713:CT:C	acceptor_gain	1.0000
17:15631715:C:CC	acceptor_gain	1.0000
17:15632504:CTCA:C	donor_loss	1.0000
17:15632504:CTCAC:C	donor_loss	1.0000
17:15632505:TCACC:T	donor_loss	1.0000
17:15632506:CA:C	donor_loss	1.0000
17:15632507:A:C	donor_loss	1.0000
17:15632507:ACCTT:A	donor_gain	1.0000
17:15632508:CCTTC:C	donor_gain	1.0000
17:15632511:T:A	donor_gain	1.0000
17:15632511:T:TA	donor_gain	1.0000
17:15632672:CTC:C	acceptor_gain	1.0000
17:15632675:C:CC	acceptor_gain	1.0000
17:15632675:CT:C	acceptor_loss	1.0000
17:15632675:CTG:C	acceptor_loss	1.0000
17:15636030:CCATA:C	donor_loss	1.0000
17:15636031:CATA:C	donor_loss	1.0000
17:15636032:ATAC:A	donor_loss	1.0000
17:15636033:TA:T	donor_loss	1.0000
17:15636033:TACCT:T	donor_loss	1.0000
17:15636034:A:C	donor_loss	1.0000
17:15636035:C:G	donor_loss	1.0000

AlphaMissense

3734 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:15629074:G:C	F412L	0.996
17:15629074:G:T	F412L	0.996
17:15629076:A:G	F412L	0.996
17:15651259:G:C	H117Q	0.995
17:15651259:G:T	H117Q	0.995
17:15651298:G:C	H104Q	0.995
17:15651298:G:T	H104Q	0.995
17:15651381:A:G	C77R	0.994
17:15651380:C:G	C77S	0.993
17:15651381:A:T	C77S	0.993
17:15651288:G:C	H108D	0.992
17:15651331:A:C	C93W	0.992
17:15651333:A:G	C93R	0.992
17:15651324:A:G	C96R	0.991
17:15651332:C:G	C93S	0.991
17:15651333:A:T	C93S	0.991
17:15629075:A:G	F412S	0.990
17:15651286:A:C	H108Q	0.990
17:15651286:A:T	H108Q	0.990
17:15651308:C:T	C101Y	0.990
17:15651380:C:T	C77Y	0.990
17:15651261:G:C	H117D	0.989
17:15651309:A:G	C101R	0.989
17:15651332:C:T	C93Y	0.989
17:15629153:A:G	L386P	0.988
17:15629153:A:T	L386H	0.988
17:15636200:C:G	A229P	0.988
17:15651187:G:C	F141L	0.988
17:15651187:G:T	F141L	0.988
17:15651189:A:G	F141L	0.988

dbSNP variants (sampled 300 via entrez): RS1000083719 (17:15651785 C>T), RS1000226461 (17:15673636 T>A), RS1000240327 (17:15645577 A>C,G), RS1000248219 (17:15651079 C>G), RS1000260610 (17:15673957 A>G), RS1000436259 (17:15679657 G>T), RS1000468644 (17:15638002 T>A), RS1000568768 (17:15675065 G>A,C), RS1000618669 (17:15630733 C>A), RS1000656890 (17:15674797 G>A), RS1000663234 (17:15655846 G>T), RS1000745247 (17:15679815 T>C), RS1000752738 (17:15639649 G>C), RS1000805053 (17:15640051 T>G), RS1000847209 (17:15649319 G>A)

Disease associations

OMIM: gene MIM:609505 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects cotreatment, increases abundance, increases expression, affects splicing	6
bisphenol A	increases expression, affects cotreatment, decreases methylation, decreases expression	5
Estradiol	affects cotreatment, decreases expression, decreases phosphorylation, increases expression	4
Cadmium Chloride	increases abundance, increases expression	3
lead acetate	increases expression	2
cinnamaldehyde	increases expression	2
Arsenic Trioxide	increases expression, decreases response to substance	2
Benzo(a)pyrene	decreases methylation, increases expression	2
Cadmium	increases abundance, increases expression	2
Tretinoin	affects localization, decreases expression, increases expression, increases phosphorylation, increases reaction	2
Trinitrobenzenesulfonic Acid	increases expression	2
aristolochic acid I	increases expression	1
2,4,6-tribromophenol	increases expression	1
testosterone enanthate	affects expression	1
sodium arsenate	increases expression	1
decabromobiphenyl ether	decreases expression	1
beta-lapachone	increases expression	1
sulforaphane	increases expression	1
cobaltous chloride	decreases expression	1
tetrabromobisphenol A	decreases expression	1
manganese chloride	affects cotreatment, increases abundance, increases expression	1
cupric chloride	increases expression	1
nickel sulfate	increases expression	1
isoeugenol	increases expression, affects cotreatment	1
S-(1,2-dichlorovinyl)cysteine	increases expression	1
di-n-butylphosphoric acid	affects expression	1
chromium hexavalent ion	decreases expression	1
perfluorooctane sulfonic acid	increases expression	1
vanillin	increases expression	1
monomethylarsonous acid	increases expression	1

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B2JM	Abcam HeLa TRIM16 KO	Cancer cell line	Female
CVCL_TT84	HAP1 TRIM16 (-)	Cancer cell line	Male

Clinical trials (associated diseases)

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