TRIM16

Chr 17

tripartite motif containing 16

Also known as: EBBP

NCBI Gene: 10626ENSG00000221926UniProt: O95361

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. [provided by RefSeq, Jan 2017]

117
ClinVar variants
19
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— TRIM16
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
19 Pathogenic / Likely Pathogenic· 87 VUS of 117 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
1.13LOEUF
pLI 0.000
Z-score 1.10
OE 0.74 (0.50–1.13)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.34Z-score
OE missense 0.95 (0.86–1.04)
300 obs / 316.8 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.74 (0.50–1.13)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.95 (0.86–1.04)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.88
0≤1.21.6
LoF obs/exp: 16 / 21.5Missense obs/exp: 300 / 316.8Syn Z: 1.10

ClinVar Variant Classifications

117 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic19
VUS87
Likely Benign10
Benign1
19
Pathogenic
87
VUS
10
Likely Benign
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
19
0
19
Likely Pathogenic
0
0
0
0
0
VUS
0
85
2
0
87
Likely Benign
0
7
1
2
10
Benign
0
1
0
0
1
Total093222117

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

TRIM16 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Autophagy in age-related macular degeneration.
Kaarniranta K et al.·Autophagy
2023Review
Periplocin suppresses the growth of colorectal cancer cells by triggering LGALS3 (galectin 3)-mediated lysophagy.
Wang K et al.·Autophagy
2023
TRIM16 E121D variant affects the risk and prognosis of hepatocellular carcinoma by modulating the Wnt/β-catenin pathway.
Li S et al.·Mol Carcinog
2023
NPRL2 promotes TRIM16-mediated ubiquitination degradation of Galectin-3 to prevent CD8(+)T lymphocyte cuproptosis in glioma.
Wang F et al.·Cell Mol Life Sci
2024
TRIM3 and TRIM16 as potential tumor suppressors in breast cancer patients.
Roshanazadeh MR et al.·BMC Res Notes
2022Cohort
AKT2-mediated lysosomal dysfunction promotes secretory autophagy in retinal pigment epithelium (RPE) cells.
Ghosh S et al.·Autophagy
2024
TRIM16 overexpression inhibits the metastasis of colorectal cancer through mediating Snail degradation.
Ruan L et al.·Exp Cell Res
2021
NFKBIZ regulates NFκB signaling pathway to mediate tumorigenesis and metastasis of hepatocellular carcinoma by direct interaction with TRIM16.
Guo D et al.·Cell Mol Life Sci
2024
Sanggenol L Enhances Temozolomide Drug Sensitivity by Inhibiting Mitophagy and Inducing Apoptosis Through the Regulation of the TRIM16-OPTN Axis in Glioblastoma.
Chang H et al.·Adv Sci (Weinh)
2025
TRIM16 inhibits proliferation and migration through regulation of interferon beta 1 in melanoma cells.
Sutton SK et al.·Oncotarget
2014
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools