{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Moulton MJ"],"funding":["University of Texas Southwestern Medical Center","NIA NIH HHS","NIH Office of the Director","NIA","NHGRI","NHGRI NIH HHS","Baylor College of Medicine","NINDS NIH HHS","National Institutes of Health","NIH HHS","NINDS"],"pagination":["101174"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12358889"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["26(9)"],"pubmed_abstract":["<h4>Purpose</h4>We identified 2 individuals with de novo variants in SREBF2 that disrupt a conserved site 1 protease (S1P) cleavage motif required for processing SREBP2 into its mature transcription factor. These individuals exhibit complex phenotypic manifestations that partially overlap with sterol regulatory element binding proteins (SREBP) pathway-related disease phenotypes, but SREBF2-related disease has not been previously reported. Thus, we set out to assess the effects of SREBF2 variants on SREBP pathway activation.<h4>Methods</h4>We undertook ultrastructure and gene expression analyses using fibroblasts from an affected individual and utilized a fly model of lipid droplet (LD) formation to investigate the consequences of SREBF2 variants on SREBP pathway function.<h4>Results</h4>We"],"journal":["Genetics in medicine : official journal of the American College of Medical Genetics"],"pubmed_title":["Dominant missense variants in SREBF2 are associated with complex dermatological, neurological, and skeletal abnormalities."],"pmcid":["PMC12358889"],"funding_grant_id":["U01 NS134354","R01 AG073260","OD R24 OD022005","T32 NS043124-19","U01 HG007703","U01 NS13454","U54D083092","U01 AG072439","T32 NS043124","R24 OD022005","U54 NS093793","U01 HG010215"],"pubmed_authors":["Douglas J","Dasari S","Cole FS","Undiagnosed Diseases Network","Emrick LT","Rios J","Wener M","Novacic D","Taylor H","Malicdan MCV","Worley K","Sutton S","Cunningham M","Jobanputra V","Walker M","Butte MJ","Stoler JM","Ezell K","Jean-Marie O","Bonner D","Gropman A","Loo SK","Seto E","Coakley TR","Pallais JC","Fieg EL","Atala K","Papp JC","Bellen HJ","Acosta MT","Posey JE","Lanza IR","Rebelo A","Silverman EK","Miller D","Dayal JG","Jarvik GP","Vogel TP","Adams DR","Krakow D","Kratz L","Byers P","Martin MG","Shelkowitz E","Fisher PG","Bale J","Fogel BL","Mahoney R","Renteria G","Sinsheimer JS","Lanpher BC","Scott DA","Izumi K","Smith CA","McCray AT","Whitlock J","Phillips JA","Petcharet L","Sweetser DA","Alvey J","Tran AA","Macnamara EF","Cobban LA","Raper A","Davis J","Wegner DJ","Tarakad A","Marth G","Cogan JD","Maghiro ASC","Bivona S","Tabor HK","Wenger T","Gonzalez JM","Pusey Swerdzewski BN","Bejerano G","Jarvik J","Craigen WJ","Might M","Wangler MF","Pak S","Zuchner S","Hisama FM","Bayrak-Toydemir P","Martin BA","Longo N","Hayes N","Ketkar S","Rosenfeld JA","Mao R","Liu P","Sullivan K","Mamounas LA","Wambach J","Lalani SR","Alvarez RL","Dutta D","Dorrani N","Parker NH","Wise CA","Blue E","Wambach JA","Orengo JP","Thorson W","Wheeler MT","Hing A","Horike-Pyne M","Martinez-Agosto JA","Kilich G","Bennett J","Bamshad M","Corona R","Zhang Z","Tekin M","Eng CM","D'Souza P","Hom J","Kravets E","Peart L","Hanchard N","Nelson SF","Halley MC","Smith KS","Sheppeard S","Sybert V","Latchman K","Delgado M","Krasnewich DM","Introne W","Urv TK","Bohnsack J","Tifft CJ","Wan J","Baldridge D","Lewis RA","Holm IA","Solomon B","Solnica-Krezel L","Clark GD","Zheng Y","Rodan LH","Afzali B","Kohane IS","Byrd WE","Nieves-Rodriguez S","Beck A","Khanshour A","Potocki L","Moretti P","Oxendine I","Crouse AB","Glass I","Mikati M","Wegner D","Doss AL","Hutchison S","Rives L","Coggins M","Lin WW","Andrews A","Kiley D","Kohler JN","Shashi V","Behrens E","Tan ALM","Botto L","Ashley EA","Bacino CA","Chanprasert S","Eckstein DJ","Barbouth D","Briere LC","Quinlan A","Ruzhnikov M","Wood H","Beggs AH","Marwaha S","Nakano-Okuno M","Huang Y","Hamid R","Fu J","Reuter CM","Dai H","Spillmann RC","Goddard PC","Sisco K","Duker AL","Vanderver A","Glanton E","Balasubramanyam A","Burrage LC","Morimoto M","Shin J","Schoch K","Marom R","Ungar RA","Manolio TA","Toro C","Pace L","Lee BH","Chao HT","Cassini T","Oglesbee D","Huang A","Grange DK","Velinder M","McConkie-Rosell A","Stergachis A","Morava E","Maduro VV","Yamamoto S","Bober MB","Moulton MJ","Viskochil D","Carey J","Sampson JB","Bademci G","Falk M","High F","Bernstein JA","Berry GT","Burke EA","Bican A","Kobren SN","LeBlanc K","Walley NM","Rossignol F","Lam C","Robertson AK","Hassey K","Ward PA","Earl D","McGee E","Hubshman MW","MacRae CA","Kaitryn E","Rosenthal E","Chinn I","Doherty D","Mirzaa G","Corner B","Allworth A","Maas RL","Loscalzo J","Colley HA","Mulvihill JJ","Gahl WA","Schedl T","Rao DA","Jayadev S","Kanca O","Dipple K","Neumann S","Wolfe LA","Korrick S","Raskind W","Dell'Angelica EC","Borja N","Tan QK","Westerfield M","Wahl CE","Sabaii M","Douine ED"],"additional_accession":[]},"is_claimable":false,"name":"Dominant missense variants in SREBF2 are associated with complex dermatological, neurological, and skeletal abnormalities.","description":"<h4>Purpose</h4>We identified 2 individuals with de novo variants in SREBF2 that disrupt a conserved site 1 protease (S1P) cleavage motif required for processing SREBP2 into its mature transcription factor. These individuals exhibit complex phenotypic manifestations that partially overlap with sterol regulatory element binding proteins (SREBP) pathway-related disease phenotypes, but SREBF2-related disease has not been previously reported. Thus, we set out to assess the effects of SREBF2 variants on SREBP pathway activation.<h4>Methods</h4>We undertook ultrastructure and gene expression analyses using fibroblasts from an affected individual and utilized a fly model of lipid droplet (LD) formation to investigate the consequences of SREBF2 variants on SREBP pathway function.<h4>Results</h4>We","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Sep","modification":"2026-05-29T17:08:53.635Z","creation":"2026-04-08T05:28:23.759Z"},"accession":"S-EPMC12358889","cross_references":{"pubmed":["38847193"],"doi":["10.1016/j.gim.2024.101174"]}}