Systematically testing human HMBS missense variants to reveal mechanism and pathogenic variation.


Journal

bioRxiv : the preprint server for biology
Titre abrégé: bioRxiv
Pays: United States
ID NLM: 101680187

Informations de publication

Date de publication:
06 Feb 2023
Historique:
entrez: 17 2 2023
pubmed: 18 2 2023
medline: 18 2 2023
Statut: epublish

Résumé

Defects in hydroxymethylbilane synthase (HMBS) can cause Acute Intermittent Porphyria (AIP), an acute neurological disease. Although sequencing-based diagnosis can be definitive, ~⅓ of clinical HMBS variants are missense variants, and most clinically-reported HMBS missense variants are designated as "variants of uncertain significance" (VUS). Using saturation mutagenesis,

Identifiants

pubmed: 36798224
doi: 10.1101/2023.02.06.527353
pmc: PMC9934555
pii:
doi:

Types de publication

Preprint

Langues

eng

Subventions

Organisme : NHGRI NIH HHS
ID : RM1 HG010461
Pays : United States
Organisme : NHGRI NIH HHS
ID : UM1 HG011989
Pays : United States

Commentaires et corrections

Type : UpdateIn

Références

Mol Syst Biol. 2017 Dec 21;13(12):957
pubmed: 29269382
Am J Hum Genet. 2021 Jan 7;108(1):163-175
pubmed: 33357406
iScience. 2021 Feb 06;24(3):102152
pubmed: 33665570
J Biol Chem. 1958 Aug;233(2):501-9
pubmed: 13563528
Biol Direct. 2017 Jan 17;12(1):1
pubmed: 28095902
PLoS One. 2015 Aug 19;10(8):e0135896
pubmed: 26287972
Hum Mol Genet. 2018 Apr 1;27(7):1164-1173
pubmed: 29360981
Genetics. 2015 Jun;200(2):413-22
pubmed: 25823446
Nat Genet. 2018 Jun;50(6):874-882
pubmed: 29785012
N Engl J Med. 2017 Aug 31;377(9):862-872
pubmed: 28854095
Elife. 2017 Jun 29;6:
pubmed: 28661399
Genome Med. 2020 Jan 30;12(1):13
pubmed: 32000841
BMC Bioinformatics. 2019 Jul 3;20(Suppl 14):335
pubmed: 31266447
Am J Hum Genet. 2021 Dec 2;108(12):2248-2258
pubmed: 34793697
Am J Hum Genet. 2022 Dec 1;109(12):2163-2177
pubmed: 36413997
Patient. 2018 Oct;11(5):527-537
pubmed: 29915990
J Biol Chem. 1980 Mar 10;255(5):1993-9
pubmed: 7354069
Biochem J. 2009 Apr 28;420(1):17-25
pubmed: 19207107
Mol Biol Evol. 2021 Jul 29;38(8):3235-3246
pubmed: 33779753
Phys Rev B Condens Matter. 1988 Jan 15;37(2):785-789
pubmed: 9944570
J Chem Theory Comput. 2015 Aug 11;11(8):3696-713
pubmed: 26574453
Am J Hum Genet. 2018 May 3;102(5):943-955
pubmed: 29706350
Genet Med. 2018 Sep;20(9):1054-1060
pubmed: 29300386
Biochem J. 2021 Mar 12;478(5):1023-1042
pubmed: 33600566
Hum Genet. 2000 Sep;107(3):243-8
pubmed: 11071386
Cell Rep. 2022 Jan 11;38(2):110207
pubmed: 35021073
FEBS Open Bio. 2022 Dec;12(12):2136-2146
pubmed: 36115019
Eur J Biochem. 1987 Jan 2;162(1):105-10
pubmed: 3816774
Annu Rev Genet. 2022 Nov 30;56:441-465
pubmed: 36055970
Nucleic Acids Res. 2012 Jul;40(Web Server issue):W452-7
pubmed: 22689647
Nat Methods. 2011 Jun 26;8(8):659-61
pubmed: 21706014
J Chem Theory Comput. 2013 Jul 9;9(7):3084-95
pubmed: 26583988
Genet Med. 2015 May;17(5):405-24
pubmed: 25741868
J Inherit Metab Dis. 2013 Sep;36(5):849-57
pubmed: 23114748
Front Pharmacol. 2019 Sep 13;10:1018
pubmed: 31572191
PLoS One. 2012;7(10):e46688
pubmed: 23056405
Mol Genet Metab. 2020 May;130(1):87-99
pubmed: 32067921
Am J Hum Genet. 2021 Dec 2;108(12):2389
pubmed: 34861178
Am J Hum Genet. 2021 Oct 7;108(10):1891-1906
pubmed: 34551312
PeerJ. 2017 Jul 31;5:e3657
pubmed: 28785526
J Hepatol. 2022 Oct;77(4):1038-1046
pubmed: 35636578
Biochemistry. 2022 Nov 1;61(21):2409-2416
pubmed: 36241173
Bioinformatics. 2001 Jun;17(6):509-19
pubmed: 11395427
J Inherit Metab Dis. 2019 Jan;42(1):186-194
pubmed: 30740734
Mol Biol Evol. 2014 Aug;31(8):1956-78
pubmed: 24859245
Nucleic Acids Res. 2012 Jul;40(Web Server issue):W537-41
pubmed: 22570416
Nat Genet. 2018 Oct;50(10):1381-1387
pubmed: 30224644
Nucleic Acids Res. 2014 Jan;42(Database issue):D980-5
pubmed: 24234437
Proc Natl Acad Sci U S A. 1988 Jan;85(1):6-10
pubmed: 3422427
Biochim Biophys Acta Gen Subj. 2018 Sep;1862(9):1948-1955
pubmed: 29908816
Genome Res. 2016 May;26(5):670-80
pubmed: 26975778
Am J Hum Genet. 2021 Jul 1;108(7):1283-1300
pubmed: 34214447
Proc Natl Acad Sci U S A. 2018 Apr 24;115(17):E4071-E4080
pubmed: 29632172
Hum Mutat. 2016 Nov;37(11):1215-1222
pubmed: 27539938
Biochem J. 1988 Sep 1;254(2):427-35
pubmed: 3052434
Br J Haematol. 2017 Feb;176(4):527-538
pubmed: 27982422
Genome Biol. 2019 Nov 4;20(1):223
pubmed: 31679514

Auteurs

Warren van Loggerenberg (W)

Donnelly Centre, University of Toronto, Toronto, Ontario, Canada.
Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada.
Lunenfeld-Tanenbaum Research Institute, Sinai Health, Toronto, Ontario, Canada.
Department of Computer Science, University of Toronto, Toronto, Ontario, Canada.

Shahin Sowlati-Hashjin (S)

Institute of Biomedical Engineering, University of Toronto, ON, Canada.
Institute of Biomaterials and Biomedical Engineering, University of Toronto, ON, Canada.

Jochen Weile (J)

Donnelly Centre, University of Toronto, Toronto, Ontario, Canada.
Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada.
Lunenfeld-Tanenbaum Research Institute, Sinai Health, Toronto, Ontario, Canada.
Department of Computer Science, University of Toronto, Toronto, Ontario, Canada.

Rayna Hamilton (R)

Advanced Academic Programs, Johns Hopkins University, Washington, DC, USA.

Aditya Chawla (A)

Donnelly Centre, University of Toronto, Toronto, Ontario, Canada.
Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada.
Lunenfeld-Tanenbaum Research Institute, Sinai Health, Toronto, Ontario, Canada.

Marinella Gebbia (M)

Donnelly Centre, University of Toronto, Toronto, Ontario, Canada.
Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada.
Lunenfeld-Tanenbaum Research Institute, Sinai Health, Toronto, Ontario, Canada.

Nishka Kishore (N)

Donnelly Centre, University of Toronto, Toronto, Ontario, Canada.
Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada.
Lunenfeld-Tanenbaum Research Institute, Sinai Health, Toronto, Ontario, Canada.

Laure Frésard (L)

Invitae Corp, San Francisco, CA 94103, USA.

Sami Mustajoki (S)

Research Program in Molecular Medicine, Biomedicum-Helsinki, University of Helsinki.

Elena Pischik (E)

Research Program in Molecular Medicine, Biomedicum-Helsinki, University of Helsinki.

Elena Di Pierro (E)

Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Unit of Medicine and Metabolic Diseases, Milan, Italy.

Michela Barbaro (M)

Porphyria Centre Sweden, Centre for Inherited Metabolic Diseases, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.

Ylva Floderus (Y)

Porphyria Centre Sweden, Centre for Inherited Metabolic Diseases, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.

Caroline Schmitt (C)

Centre Français des Porphyries, Hôpital Louis Mourier, Assistance Publique-Hôpitaux de Paris, Colombes and Centre de Recherche sur l'Inflammation, UMR1149 INSERM, Université Paris Cité, Paris, France.

Laurent Gouya (L)

Centre Français des Porphyries, Hôpital Louis Mourier, Assistance Publique-Hôpitaux de Paris, Colombes and Centre de Recherche sur l'Inflammation, UMR1149 INSERM, Université Paris Cité, Paris, France.

Alexandre Colavin (A)

Invitae Corp, San Francisco, CA 94103, USA.

Robert Nussbaum (R)

Invitae Corp, San Francisco, CA 94103, USA.

Edith C H Friesema (ECH)

Porphyria Expertcenter Rotterdam, Center for Lysosomal and Metabolic Diseases, Department of Internal Medicine, Erasmus MC, University Medical Center Rotterdam, the Netherlands.

Raili Kauppinen (R)

Research Program in Molecular Medicine, Biomedicum-Helsinki, University of Helsinki.

Jordi To-Figueras (J)

Biochemistry and Molecular Genetics Department, Hospital Clínic, IDIBAPS, University of Barcelona, Barcelona, Spain.

Aasne K Aarsand (AK)

Norwegian Porphyria Centre, Department of Medical Biochemistry and Pharmacology, Haukeland University Hospital, Bergen, Norway.

Robert J Desnick (RJ)

Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

Michael Garton (M)

Institute of Biomedical Engineering, University of Toronto, ON, Canada.
Institute of Biomaterials and Biomedical Engineering, University of Toronto, ON, Canada.

Frederick P Roth (FP)

Donnelly Centre, University of Toronto, Toronto, Ontario, Canada.
Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada.
Lunenfeld-Tanenbaum Research Institute, Sinai Health, Toronto, Ontario, Canada.
Department of Computer Science, University of Toronto, Toronto, Ontario, Canada.

Classifications MeSH