TRIM8

Chr 10AD

tripartite motif containing 8

Also known as: FSGSNEDS, GERP, RNF27

NCBI Gene: 81603ENSG00000171206UniProt: Q9BZR9

This gene encodes a member of the tripartite motif (TRIM) protein family. Based on similarities to other proteins, the encoded protein is suspected to be an E3 ubiquitin-protein ligase. Regulation of this gene may be altered in some cancers. Mutations resulting in a truncated protein product have been observed in early-onset epileptic encephalopathy (EOEE). [provided by RefSeq, Sep 2016]

Primary Disease Associations & Inheritance

Focal segmental glomerulosclerosis and neurodevelopmental syndromeMIM #619428
AD
468
ClinVar variants
39
Pathogenic / LP
0.99
pLI score· haploinsufficient
0
Active trials
Clinical Summary— TRIM8
🧬
Gene-Disease Validity (ClinGen)
focal segmental glomerulosclerosis and neurodevelopmental syndrome · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.99). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
39 Pathogenic / Likely Pathogenic· 188 VUS of 468 total submissions
Some data sources returned errors (1)

clinvar: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esearch.fcgi

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
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.
0.26LOEUF
pLI 0.994
Z-score 4.18
OE 0.08 (0.03–0.26)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

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.
2.74Z-score
OE missense 0.58 (0.52–0.66)
198 obs / 340.3 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

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.0.08 (0.03–0.26)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.58 (0.52–0.66)
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.0.86
0≤1.21.6
LoF obs/exp: 2 / 24.2Missense obs/exp: 198 / 340.3Syn Z: 1.42

ClinVar Variant Classifications

468 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic28
Likely Pathogenic11
VUS188
Likely Benign210
Benign16
Conflicting15
28
Pathogenic
11
Likely Pathogenic
188
VUS
210
Likely Benign
16
Benign
15
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
1
0
27
0
28
Likely Pathogenic
4
0
7
0
11
VUS
6
169
12
1
188
Likely Benign
0
43
30
137
210
Benign
0
5
6
5
16
Conflicting
—15
Total1121782143468

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

View in ClinVar →

Protein Context — Lollipop Plot

TRIM8 · protein map & ClinVar variants

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

Gene2Phenotype Curations

TRIM8-related neurodevelopmental disorder

definitive
ADLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Focal segmental glomerulosclerosis and neurodevelopmental syndrome

MIM #619428

Molecular basis of disorder known

Autosomal dominant
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
TRIB3-TRIM8 complex drives NAFLD progression by regulating HNF4α stability.
Xiao MC et al.·J Hepatol
2024
m6A Modification Promotes EMT and Metastasis of Castration-Resistant Prostate Cancer by Upregulating NFIB.
Shu F et al.·Cancer Res
2024
De novo TRIM8 variants impair its protein localization to nuclear bodies and cause developmental delay, epilepsy, and focal segmental glomerulosclerosis.
Weng PL et al.·Am J Hum Genet
2021
TRIM8: a double-edged sword in glioblastoma with the power to heal or hurt.
Hosseinalizadeh H et al.·Cell Mol Biol Lett
2023Review
De novo truncating variants of TRIM8 and atypical neuro-renal syndrome: a case report and literature review.
Li W et al.·Ital J Pediatr
2023Review
ITLN1 exacerbates Crohn's colitis by driving ZBP1-dependent PANoptosis in intestinal epithelial cells through antagonizing TRIM8-mediated CAPN2 ubiquitination.
Zhao J et al.·Int J Biol Sci
2025
TNFAIP3 Interacting Protein 3 Overexpression Suppresses Nonalcoholic Steatohepatitis by Blocking TAK1 Activation.
Liu D et al.·Cell Metab
2020
Mutual regulation between TRIM21 and TRIM8 via K48-linked ubiquitination.
Wang L et al.·Oncogene
2023
Dissecting genetics of spectrum of epilepsies with eyelid myoclonia by exome sequencing.
Coppola A et al.·Epilepsia
2024
TRIM8 regulates stemness in glioblastoma through PIAS3-STAT3.
Zhang C et al.·Mol Oncol
2017
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