Please use this identifier to cite or link to this item: https://doi.org/10.1038/ncomms12353
Title: The severity of hereditary porphyria is modulated by the porphyrin exporter and Lan antigen ABCB6
Authors: Fukuda, Y
Cheong, P.L
Lynch, J
Brighton, C
Frase, S
Kargas, V
Rampersaud, E
Wang, Y
Sankaran, V.G
Yu, B
Ney, P.A
Weiss, M.J
Vogel, P
Bond, P.J 
Ford, R.C
Trent, R.J
Schuetz, J.D
Keywords: ABC transporter
CD11b antigen
CD4 antigen
CD45 antigen
CD8 antigen
cpox protein
fech protein
gamma interferon receptor 1
hmbs protein
lan antigen abcb6 protein
porphyrin
ppox protein
protein
ter119 protein
unclassified drug
ABC transporter
ABCB6 protein, human
Abcb6 protein, mouse
alloantigen
heme
LAN antigen
porphyrin
allele
antigen
blood
enzyme activity
gene expression
genetic analysis
membrane
mutation
phenotype
porphyrin
toxicity
abcb6 gene
adult
allele
animal cell
animal experiment
animal model
animal tissue
Article
cell membrane
clinical article
controlled study
disease exacerbation
experimental liver injury
female
gene
gene mutation
genetic code
genetic variability
hereditary porphyria
human
male
mouse
nonhuman
phenotype
porphyria
animal
Bagg albino mouse
biosynthesis
blood
cohort analysis
disease model
genetics
knockout mouse
metabolism
mutation
porphyria
sequence homology
severity of illness index
transport at the cellular level
urine
whole exome sequencing
Mus
Alleles
Animals
ATP-Binding Cassette Transporters
Biological Transport
Cell Membrane
Cohort Studies
Disease Models, Animal
Female
Heme
Humans
Isoantigens
Male
Mice
Mice, Inbred BALB C
Mice, Knockout
Mutation
Porphyrias
Porphyrins
Sequence Homology, Amino Acid
Severity of Illness Index
Whole Exome Sequencing
Issue Date: 2016
Publisher: Nature Publishing Group
Citation: Fukuda, Y, Cheong, P.L, Lynch, J, Brighton, C, Frase, S, Kargas, V, Rampersaud, E, Wang, Y, Sankaran, V.G, Yu, B, Ney, P.A, Weiss, M.J, Vogel, P, Bond, P.J, Ford, R.C, Trent, R.J, Schuetz, J.D (2016). The severity of hereditary porphyria is modulated by the porphyrin exporter and Lan antigen ABCB6. Nature Communications 7 : 12353. ScholarBank@NUS Repository. https://doi.org/10.1038/ncomms12353
Rights: Attribution 4.0 International
Abstract: Hereditary porphyrias are caused by mutations in genes that encode haem biosynthetic enzymes with resultant buildup of cytotoxic metabolic porphyrin intermediates. A long-standing open question is why the same causal porphyria mutations exhibit widely variable penetrance and expressivity in different individuals. Here we show that severely affected porphyria patients harbour variant alleles in the ABCB6 gene, also known as Lan, which encodes an ATP-binding cassette (ABC) transporter. Plasma membrane ABCB6 exports a variety of disease-related porphyrins. Functional studies show that most of these ABCB6 variants are expressed poorly and/or have impaired function. Accordingly, homozygous disruption of the Abcb6 gene in mice exacerbates porphyria phenotypes in the Fech m1Pas mouse model, as evidenced by increased porphyrin accumulation, and marked liver injury. Collectively, these studies support ABCB6 role as a genetic modifier of porphyria and suggest that porphyrin-inducing drugs may produce excessive toxicities in individuals with the rare Lan(-) blood type. © The Author(s)2016.
Source Title: Nature Communications
URI: https://scholarbank.nus.edu.sg/handle/10635/182438
ISSN: 2041-1723
DOI: 10.1038/ncomms12353
Rights: Attribution 4.0 International
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