{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nRNPC3 encodes the U11/U12‐65K protein, a core and unique component of the minor spliceosome that is essential for the formation of the U11/U12 di‑snRNP complex and for the splicing of U12‑type introns found in a select subset of human genes. Disruption of RNPC3 function impairs accurate intron recognition and processing—defects that manifest in highly tissue‐restricted clinical phenotypes, most notably severe isolated growth hormone deficiency and pituitary hypoplasia."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nMechanistic studies have shown that pathogenic RNPC3 variants, particularly those affecting the C‑terminal RNA recognition motif, weaken binding to U12 and U6atac small nuclear RNAs. Such mutations compromise the assembly and stability of the U11/U12 di‑snRNP complex, leading to mis‐splicing of several U12‐type intron–containing transcripts—including candidates involved in hormonal processing and signaling. This molecular defect illustrates how a general impairment in minor intron splicing can provoke remarkably narrow, tissue‐specific outcomes."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nClinical reports further broaden the phenotypic spectrum of RNPC3-related disorders. In addition to isolated growth hormone deficiency, biallelic RNPC3 mutations have been associated with congenital hypopituitarism accompanied by central congenital hypothyroidism, congenital cataracts, developmental delay/intellectual disability, and primary ovarian insufficiency. These observations underscore the non-redundant function of RNPC3 within the minor spliceosome and highlight how even subtle defects in minor intron splicing can mediate complex, multisystem developmental abnormalities."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "5", "end_ref": "9"}]}, {"type": "t", "text": ""}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Jesús Argente, Raquel Flores, Armand Gutiérrez-Arumí, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "U6atac snRNA stem-loop interacts with U12 p65 RNA binding protein and is functionally interchangeable with the U12 apical stem-loop III."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Rep (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/srep31393"}], "href": "https://doi.org/10.1038/srep31393"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27510544"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27510544"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Antto J Norppa, Tuuli M Kauppala, Harri A Heikkinen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mutations in the U11/U12-65K protein associated with isolated growth hormone deficiency lead to structural destabilization and impaired binding of U12 snRNA."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "RNA (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1261/rna.062844.117"}], "href": "https://doi.org/10.1261/rna.062844.117"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29255062"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29255062"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Eline A Verberne, Sonja Faries, Marcel M A M Mannens, et al. 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