{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T10:12:49Z","timestamp":1780567969102,"version":"3.54.1"},"reference-count":48,"publisher":"Oxford University Press (OUP)","issue":"19","license":[{"start":{"date-parts":[[2025,7,18]],"date-time":"2025-07-18T00:00:00Z","timestamp":1752796800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82471751"],"award-info":[{"award-number":["82471751"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2022YFC2703200"],"award-info":[{"award-number":["2022YFC2703200"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2024YFC3406300"],"award-info":[{"award-number":["2024YFC3406300"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2024YFC2706700"],"award-info":[{"award-number":["2024YFC2706700"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Key Research and Development Program of Shandong Province, China","award":["2023CXPT010"],"award-info":[{"award-number":["2023CXPT010"]}]},{"name":"Guangxi Key Research and Development Plan Project","award":["AB22035080"],"award-info":[{"award-number":["AB22035080"]}]},{"name":"Guangxi Science and Technology Base and Talent Project","award":["AC22080002"],"award-info":[{"award-number":["AC22080002"]}]},{"name":"Innovation Platform for Academicians of Hainan Province","award":["YSPTZX202310"],"award-info":[{"award-number":["YSPTZX202310"]}]},{"name":"ShanDong Provincial Medical Association","award":["YXH2024YS028"],"award-info":[{"award-number":["YXH2024YS028"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,9,19]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background &amp; Aims<\/jats:title>\n                  <jats:p>Infant liver failure syndrome type 2 (ILFS2), a rare autosomal recessive disorder manifesting as recurrent acute liver failure (ALF) triggered by febrile illness, is associated with neuroblastoma amplified sequence (NBAS) mutations. This study employs molecular dynamics simulation (MDS) to investigate how missense variants in the Sec39 domain influence protein conformation and thermostability.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Approach &amp; Results<\/jats:title>\n                  <jats:p>We identified novel compound heterozygous variants in the NBAS gene, c.2231\u00a0T\u2009&amp;gt;\u2009C (p.Leu744Pro) and c.2266C\u2009&amp;gt;\u2009T (p.Arg756Cys), in two Chinese siblings diagnosed with ILFS2. According to ACMG guideline, both variants were initially classified as variants of uncertain significance. To elucidate the potential functional impact, MDS was performed to compare structural dynamics between wild-type (WT) and mutant (MUT) NBASs at physiological temperature (37\u00b0C) and under thermal stress (42\u00b0C). The results revealed distinct thermal responses. WT demonstrated robust thermotolerance, with comparable trajectory patterns and curve parameters across two temperatures. In contrast, specific variants induced localized conformational perturbations and secondary structural reorganization. Notably, while MUT exhibited kinetic profiles similar to WT at 37\u00b0C, it showed pronounced fluctuations in flexible regions under thermal stress, with disrupted hydrogen-bonding networks and significant conformational changes, indicating compromised thermostability.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>The diagnosis of ILFS2 primarily relies on clinical presentation and genetic confirmation. Although the exact pathogenesis remains unclear, our findings suggest that temperature-sensitive structural destabilization induced by missense mutations within the Sec39 domain of NBAS probably underlies the fever-associated ALF. This provides critical guidance for subsequent protein structural elucidation and mechanism research, and regions exhibiting significantly reduced thermostability represent promising therapeutic targets.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/hmg\/ddaf120","type":"journal-article","created":{"date-parts":[[2025,7,18]],"date-time":"2025-07-18T18:12:10Z","timestamp":1752862330000},"page":"1610-1620","source":"Crossref","is-referenced-by-count":1,"title":["Novel compound heterozygous variants in <i>NBAS<\/i> underlying fever-dependent infantile liver failure syndrome type 2: potential implications of protein thermostability"],"prefix":"10.1093","volume":"34","author":[{"given":"Jiexin","family":"Tang","sequence":"first","affiliation":[{"name":"State Key Laboratory of Reproductive Medicine and Offspring Health, Center for Reproductive Medicine, Institute of Women, Children and Reproductive Health, Shandong University , 44 Wenhuaxi Road, Lixia District, Jinan, Shandong, 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(No. 2021RU001) , 44 Wenhuaxi Road, Lixia District, Jinan, Shandong, 250012 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoru","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Shandong Provincial Hospital Affiliated to Shandong First Medical University, 324 Jingwu Weiqi Road, Huaiyin District , Jinan, Shandong, 250001 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongmei","family":"Qiu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Reproductive Medicine and Offspring Health, Center for Reproductive Medicine, Institute of Women, Children and Reproductive Health, Shandong University , 44 Wenhuaxi Road, Lixia District, Jinan, Shandong, 250012 ,","place":["China"]},{"name":"National Research Center for Assisted Reproductive Technology and Reproductive Genetics, Shandong University , 44 Wenhuaxi Road, Lixia District, Jinan, Shandong, 250012 ,","place":["China"]},{"name":"Key Laboratory of Reproductive Endocrinology, (Shandong University), Ministry of Education , 44 Wenhuaxi Road, Lixia District, Jinan, Shandong, 250012 ,","place":["China"]},{"name":"Shandong Technology Innovation Center for Reproductive Health , 44 Wenhuaxi Road, Lixia District, Jinan, Shandong, 250012 ,","place":["China"]},{"name":"Shandong Provincial Clinical Research Center for Reproductive Health , 44 Wenhuaxi Road, Lixia District, Jinan, Shandong, 250012 ,","place":["China"]},{"name":"Shandong Key Laboratory of Reproductive Research and Birth Defect Prevention , 44 Wenhuaxi Road, Lixia District, Jinan, Shandong, 250012 ,","place":["China"]},{"name":"Research Unit of Gametogenesis and Health of ART-Offspring, Chinese Academy of Medical Sciences (No. 2021RU001) , 44 Wenhuaxi Road, Lixia District, Jinan, Shandong, 250012 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Wei","sequence":"additional","affiliation":[{"name":"Department of liver transplantation, Beijing Friendship Hospital, Capital Medical University , 95 Yong'an Road, Xicheng District, Beijing, 100050 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7644-2994","authenticated-orcid":false,"given":"Yuan","family":"Gao","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Reproductive Medicine and Offspring Health, Center for Reproductive Medicine, Institute of Women, Children and Reproductive Health, Shandong University , 44 Wenhuaxi Road, Lixia District, Jinan, Shandong, 250012 ,","place":["China"]},{"name":"National Research Center for Assisted Reproductive Technology and Reproductive Genetics, Shandong University , 44 Wenhuaxi Road, Lixia District, Jinan, Shandong, 250012 ,","place":["China"]},{"name":"Key Laboratory of Reproductive Endocrinology, (Shandong University), Ministry of Education , 44 Wenhuaxi Road, Lixia District, Jinan, Shandong, 250012 ,","place":["China"]},{"name":"Shandong Technology Innovation Center for Reproductive Health , 44 Wenhuaxi Road, Lixia District, Jinan, Shandong, 250012 ,","place":["China"]},{"name":"Shandong Provincial Clinical Research Center for Reproductive Health , 44 Wenhuaxi Road, Lixia District, Jinan, Shandong, 250012 ,","place":["China"]},{"name":"Shandong Key Laboratory of Reproductive Research and Birth Defect Prevention , 44 Wenhuaxi Road, Lixia District, Jinan, Shandong, 250012 ,","place":["China"]},{"name":"Research Unit of Gametogenesis and Health of ART-Offspring, Chinese Academy of Medical Sciences (No. 2021RU001) , 44 Wenhuaxi Road, Lixia District, Jinan, Shandong, 250012 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