Lrrc9, a member of a novel predicted ADP-ribosyltransferase-like family, has a unique structure with an ART domain between flanking leucine-rich repeat (LRR) domains. It may be involved in an ancient defense mechanism, potentially coupling pathogen detection to ADP-ribosyltransfer or other signalling mechanisms [2].

In a study on major depressive disorder (MDD) subtypes, Lrrc9 was among the genes investigated for tissue-specific expression. It was found to be expressed at low levels in brain tissues among those related to non-atypical-like features MDD, early-onset MDD, MDD with suicidal thoughts, or postpartum depression, suggesting its possible role in the pathogenesis of these MDD subtypes [1].

In another study, exposure of Xenopus tropicalis embryos to the retinoid X receptor antagonist UVI3003 led to differential regulation of Lrrc9, indicating its involvement in processes related to galactose metabolism and PPAR signalling pathways which may account for the observed malformations [3].

In summary, Lrrc9 is potentially involved in an ancient defence-related mechanism. Its low-level expression in certain brain tissues in MDD subtypes and its differential regulation in Xenopus embryos exposed to UVI3003 suggest its roles in MDD pathogenesis and in processes related to embryo development and associated metabolic and signalling pathways. However, no KO/CKO mouse model-based findings were presented in the references, so the full understanding of its function in these contexts from a mammalian in-vivo perspective remains to be explored.

References:

1. Torii, Kaai, Ohi, Kazutaka, Fujikane, Daisuke, Sugiyama, Shunsuke, Shioiri, Toshiki. 2024. Tissue-specific gene expression of genome-wide significant loci associated with major depressive disorder subtypes. In Progress in neuro-psychopharmacology & biological psychiatry, 133, 111019. doi:10.1016/j.pnpbp.2024.111019. https://pubmed.ncbi.nlm.nih.gov/38663672/

2. Wyżewski, Zbigniew, Gradowski, Marcin, Krysińska, Marianna, Dudkiewicz, Małgorzata, Pawłowski, Krzysztof. 2021. A novel predicted ADP-ribosyltransferase-like family conserved in eukaryotic evolution. In PeerJ, 9, e11051. doi:10.7717/peerj.11051. https://pubmed.ncbi.nlm.nih.gov/33854844/

3. Zhu, Jingmin, Shi, Huahong, Zhu, Pan, Yang, Yi, Rotchell, Jeanette M. 2014. Effects of antagonist of retinoid X receptor (UVI3003) on morphology and gene profile of Xenopus tropicalis embryos. In Environmental toxicology and pharmacology, 38, 153-62. doi:10.1016/j.etap.2014.05.010. https://pubmed.ncbi.nlm.nih.gov/24950139/