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Molecular findings were analyzed alongside patients\u2019 clinical characteristics and treatment histories. A rare missense mutation (c.79\u00a0C\u2009&gt;\u2009T, R27W) located in the JmjN domain was detected in a single patient with RA. In addition, a synonymous variant was identified in the PHD-type2 domain. The R27W variant is predicted by in silico analyses to impair protein homodimerization, while the synonymous change has been hypothesized to influence translational efficiency. Neither variant has previously been linked to RA.\n                    <jats:italic>KDM4C<\/jats:italic>\n                    mRNA expression was significantly reduced in patients with RA. This reduction was particularly evident in individuals with high CRP\/ESR levels, positive RF and anti-CCP status, and treatment resistance. Taken together, the molecular and clinical findings suggest a potential functional alteration of\n                    <jats:italic>KDM4C<\/jats:italic>\n                    activity. Specifically,\n                    <jats:italic>KDM4C<\/jats:italic>\n                    may have a reduced capacity to remove repressive methylation marks on histone H3, particularly H3K9me3. These findings suggest that\n                    <jats:italic>KDM4C<\/jats:italic>\n                    dysregulation may promote a closed chromatin conformation in immune cells. This state may lead to silencing of genes involved in immune regulation and increased expression of inflammatory genes, thereby contributing to the pathogenesis of RA.\n                    <jats:italic>KDM4C<\/jats:italic>\n                    appears to be an important epigenetic regulator in RA pathogenesis. The coexistence of structural variants and decreased expression underscores its potential as a diagnostic biomarker and therapeutic target. To our knowledge, this is the first study providing integrated clinical and genetic evidence linking\n                    <jats:italic>KDM4C<\/jats:italic>\n                    dysregulation to RA.\n                  <\/jats:p>","DOI":"10.1007\/s12026-026-09751-9","type":"journal-article","created":{"date-parts":[[2026,2,13]],"date-time":"2026-02-13T01:41:59Z","timestamp":1770946919000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Rare KDM4C variants and reduced expression underlie epigenetic dysregulation in rheumatoid arthritis"],"prefix":"10.1007","volume":"74","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9515-0073","authenticated-orcid":false,"given":"Deniz Aslar","family":"Oner","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hasan","family":"Toktas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Umit","family":"Dundar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sevda","family":"Adar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nuran","family":"Eyvaz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,2,13]]},"reference":[{"key":"9751_CR1","doi-asserted-by":"publisher","unstructured":"Adzhubei I, Jordan DM, Sunyaev SR. 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