{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Recent studies have highlighted the potential importance of poorly characterized genes encoded on chromosome 4 in human disease. For instance, large‐scale gene expression profiling in rheumatoid arthritis revealed numerous differentially expressed transcripts – including several novel candidates – that may play roles in cellular structure and disease pathogenesis (see."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " Similarly, in a study of Epstein–Barr virus–associated intrahepatic cholangiocarcinoma, distinct mutational patterns and an altered tumor immune microenvironment were identified, underscoring the diverse functional implications of chromosomally encoded genes in modulating both tumor behavior and host immune responses."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Most notably, however, a candidate gene located on chromosome 4 – later designated FOPV – was identified in patients with obliterative portal venopathy."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " This gene, which corresponds to C4orf54, encodes a large protein of 1,793 amino acids that is predominantly expressed in intrahepatic portal veins. The identification of deleterious missense mutations in familial and non‐familial cases indicates that C4orf54 may be critical for maintaining portal venous integrity and proper vascular remodeling. Although its exact biological function remains to be fully deciphered, the collective evidence suggests that C4orf54 likely participates in the regulation of vascular structure and may have broader roles in disease contexts where altered gene expression or mutational profiles contribute to pathogenesis.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Alexander Platzer, Thomas Nussbaumer, Thomas Karonitsch, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Analysis of gene expression in rheumatoid arthritis and related conditions offers insights into sex-bias, gene biotypes and co-expression patterns."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0219698"}], "href": "https://doi.org/10.1371/journal.pone.0219698"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31344123"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31344123"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Yu-Hua Huang, Chris Zhi-Yi Zhang, Qun-Sheng Huang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Clinicopathologic features, tumor immune microenvironment and genomic landscape of Epstein-Barr virus-associated intrahepatic cholangiocarcinoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Hepatol (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.jhep.2020.10.037"}], "href": "https://doi.org/10.1016/j.jhep.2020.10.037"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33212090"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33212090"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Claude Besmond, Dominique Valla, Laurence Hubert, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mutations in the novel gene FOPV are associated with familial autosomal dominant and non-familial obliterative portal venopathy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Liver Int (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/liv.13547"}], "href": "https://doi.org/10.1111/liv.13547"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28792652"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28792652"}]}]}]}