TRIM8

Chr 10

tripartite motif containing 8

Also known as: FSGSNEDS, GERP, RNF27

The protein functions as an E3 ubiquitin-protein ligase that regulates innate immune signaling pathways, including interferon-gamma, TNF-alpha, and IL-1beta responses, by targeting specific proteins for ubiquitination and degradation. Mutations cause focal segmental glomerulosclerosis and neurodevelopmental syndrome with autosomal dominant inheritance, affecting both kidney and neurological development. The gene is highly constrained against loss-of-function variants (pLI 0.99, LOEUF 0.26), indicating that most protein-truncating variants are likely pathogenic.

ResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismLOEUF 0.26
Clinical SummaryTRIM8
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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.
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.26LOEUF
pLI 0.994
Z-score 4.18
OE 0.08 (0.030.26)
Highly constrained

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

Missense Constraint
2.74Z-score
OE missense 0.58 (0.520.66)
198 obs / 340.3 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.08 (0.030.26)
00.351.4
Missense OE0.58 (0.520.66)
00.61.4
Synonymous OE0.86
01.21.6
LoF obs/exp: 2 / 24.2Missense obs/exp: 198 / 340.3Syn Z: 1.42

ClinVar Variant Classifications

0 submitted variants 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.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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