RNF168

Chr 3

ring finger protein 168

Also known as: RIDL, hRNF168

NCBI Gene: 165918 ENSG00000163961 UniProt: Q8IYW5

RNF168 encodes an E3 ubiquitin ligase that is required for accumulating DNA repair proteins at sites of double-strand breaks and interstrand cross-links, promoting histone ubiquitination to recruit key repair factors like TP53BP1 and BRCA1. Biallelic mutations cause RIDDLE syndrome, an autosomal recessive disorder characterized by radiosensitivity, immunodeficiency, dysmorphic features, and learning difficulties. The gene is not highly constrained against loss-of-function variants (pLI near zero), consistent with the recessive inheritance pattern where heterozygous carriers are typically unaffected.

ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes an E3 ubiquitin ligase protein that contains a RING finger, a motif present in a variety of functionally distinct proteins and known to be involved in protein-DNA and protein-protein interactions. The protein is involved in DNA double-strand break (DSB) repair. Mutations in this gene result in Riddle syndrome. [provided by RefSeq, Sep 2011]

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtRiddle syndrome

Clinical highlights

Gene-disease validity (ClinGen)

RIDDLE syndrome · ARDefinitivesufficient evidence for diagnostic panels

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

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P/LP submissions

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P/LP missense

1.20

LOEUF

LOF

Mechanism· G2P

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