Alt. symbols: ZIBRA | FLJ10111 | FLJ23501 | HOIP | Paul

Approved name: ring finger protein 31
Alt. names: HOIL-1-interacting protein

Location: 14q12: 24146683 - 24160660 (+)
Gene type: protein_coding, 36 transcripts.

Scores: LoFtool: 0.427000 | pLI: 0.99971869 | LOEUF: 0.190

HGNC: 16031

NCBI: 55072, RefSeq: NG_042234.1

Ensembl: ENSG00000092098.18

LRG_1315 | Status: public

OMIM: 612487

Expression | ProteinAtlas

LUBAC is a heterotrimeric E3 ligase complex (HOIP, HOIL-1 and SHARPIN) responsible for adding linear polyubiquitin chains to target proteins after receptor engagement and activation to stabilize various receptor signaling complexes associated with TNFR1, TLRs, IL-1R and CD40 (PMID: 21455181, 23104095, 28469620). LUBAC has been shown to be important for CD40-dependent activation of B cells in both humans and mice (PMID: 20614026, 21829693, 23942237, 23104095). Moreover, as a component of the NF-κB cascade, it targets key proteins such as NEMO and RIPK1 to play a key role in IKK complex activation. HOIP is the catalytically active component of LUBAC, but HOIL1 is required for LUBAC assembly, stability, and retention in the TNFR1 signaling complex to prevent aberrant cell death.

Germline mutations in all three LUBAC subunits (HOIP, HOIL1, SHARPIN) have been identified and its disruption results in dysregulated immune responses, featuring both an inability to properly upregulate NF-kB activity in non-immune cells and hyperresponsiveness to IL-1b, along with excessive pro-inflammatory cytokine production, in immune cells such as monocytes (PMID: 32107482). Thus far, two patients have been reported with biallelic mutations in RNF31, the gene encoding HOIP, the catalytic co mponent of LUBAC. Both had a history of severe recurrent bacterial and viral infections with suboptimal vaccine responses and showed signs of systemic autoinflammation at an early age, but the second patient showed no evidence of lymphangiectasia, amylopectinosis, IgG deficiency or T cell lymphopenia (PMID: 26008899, 30936877). Interestingly, not only did this patient’s PBMCs show upregulation of type I IFN and TNF-mediated inflammatory gene expression signatures, her asymptomatic heterozygous carrier mother’s did as well (PMID: 30936877). [Load More]