Alt. symbols: KIAA2025 | roquin | RP5-1198E17.5 | RNF198

Approved name: ring finger and CCCH-type domains 1
Alt. names: ring finger and CCCH-type zinc finger domains 1 | KIAA2025 protein

Location: 1q25.1: 173931084 - 174022357 (-)
Gene type: protein_coding, 5 transcripts.

Scores: LoFtool: 0.305000 | pLI: 0.99953990 | LOEUF: 0.287

HGNC: 29434

NCBI: 149041, RefSeq: .0

Ensembl: ENSG00000135870.13

LRG_ | Status: none

OMIM: 609424

Expression | ProteinAtlas

RC3H1 encodes Roquin-1, a posttranscriptional repressor of immune-regulatory proteins such as ICOS, OX40 and TNF. Most Roquin targets are regulated by mRNA decay, but a small subset with more binding sites in their 3′-UTRs are also subject to translational inhibition (PMID: 30232334). Roquin can cleave translationally inactive mRNAs harboring a stem-loop in their 3'-UTRs, but can also interact with targets harboring linear sequence elements. Binding of multiple Roquin proteins to several stem–loops results in full posttranscriptional repression redundantly involving deadenylation, decapping, and translational inhibition. In Tfh cells, Roquin helps suppress ICOS and TNFRSF4/OX40 expression to prevent spontaneous Tfh cell differentiation and germinal center B-cell differentiation (PMID: 25594465). In macrophages, Roquin controls inflammation by initiating degradation of TNF-alpha mRNA to limit its production (PMID: 23663784). Roquin has also been shown to regulate microRNA homeostasis and may suppress ICOS mRNA expression via this mechanism as well (PMID: 25697406). Roquin may also act as a ubiquitin E3 ligase that can pair with a number of E2 complexes to produce short and long polyubiquitin chains (PMID: 26489670).

Homozygous nonsense RC3H1 mutations were identified in an 18-year-old male child of consanguineous parents with a relapsing hemophagocytic lymphohistiocytosis (HLH)-like presentation, as well as chronic hepatitis, dyslipidemia, dysmorphic features (short stature, webbed neck) and mild intellectual disability [OMIM: 618998] (PMID: 31636267, PMID: 31745085). Though his clinical course improved with resumption of Cyclosporin A (CSA), labs showed evidence of ongoing inflammation (elevated sIL-2R, LF Ts, ferritin, triglycerides) even under CSA treatment. Normal NK-cell cytotoxicity, expression of perforin and CD107a and normal iNKT cell numbers rendered fHLH less likely. Immunophenotyping found that IL-17A+ CD4 T cells, IFNγ+ CD8 T cells, and naive B cells were expanded while memory B cells were reduced. Serum cytokines were notable for increased proinflammatory cytokines TNF-α, IL-1β, IL-6, IL-17A, IL-18, IFN-γ, CXCL9, and regulatory mediators such as IL-1RA and IL-10 even under sustained CSA treatment. [Load More]