TRIM8

Chr 10

tripartite motif containing 8

Also known as: FSGSNEDS, GERP, RNF27

NCBI Gene: 81603 ENSG00000171206 UniProt: Q9BZR9

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

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]

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtFocal segmental glomerulosclerosis and neurodevelopmental syndrome

Clinical highlights

Gene-disease validity (ClinGen)

focal segmental glomerulosclerosis and neurodevelopmental syndrome · ADDefinitivesufficient evidence for diagnostic panels

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

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P/LP missense

0.26

LOEUF· LoF intol.

LOF

Mechanism· G2P

Some data sources returned errors (1)

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