Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
Mol Med
2015 Feb 23;21:26-37. doi: 10.2119/molmed.2014.00219.
Show Gene links
Show Anatomy links
A Coding Variant of ANO10, Affecting Volume Regulation of Macrophages, Is Associated with Borrelia Seropositivity.
Hammer C
,
Wanitchakool P
,
Sirianant L
,
Papiol S
,
Monnheimer M
,
Faria D
,
Ousingsawat J
,
Schramek N
,
Schmitt C
,
Margos G
,
Michel A
,
Kraiczy P
,
Pawlita M
,
Schreiber R
,
Schulz TF
,
Fingerle V
,
Tumani H
,
Ehrenreich H
,
Kunzelmann K
.
???displayArticle.abstract???
In a first genome-wide association study (GWAS) approach to anti-Borrelia seropositivity, we identified two significant single nucleotide polymorphisms (SNPs) (rs17850869, P = 4.17E-09; rs41289586, P = 7.18E-08). Both markers, located on chromosomes 16 and 3, respectively, are within or close to genes previously connected to spinocerebellar ataxia. The risk SNP rs41289586 represents a missense variant (R263H) of anoctamin 10 (ANO10), a member of a protein family encoding Cl(-) channels and phospholipid scramblases. ANO10 augments volume-regulated Cl(-) currents (IHypo) in Xenopus oocytes, HEK293 cells, lymphocytes and macrophages and controls volume regulation by enhancing regulatory volume decrease (RVD). ANO10 supports migration of macrophages and phagocytosis of spirochetes. The R263H variant is inhibitory on IHypo, RVD and intracellular Ca(2+) signals, which may delay spirochete clearance, thereby sensitizing adaptive immunity. Our data demonstrate for the first time that ANO10 has a central role in innate immune defense against Borrelia infection.
???displayArticle.pubmedLink???
25730773
???displayArticle.pmcLink???PMC4461583 ???displayArticle.link???Mol Med
Abecasis,
An integrated map of genetic variation from 1,092 human genomes.
2012, Pubmed
Abecasis,
An integrated map of genetic variation from 1,092 human genomes.
2012,
Pubmed
Adzhubei,
A method and server for predicting damaging missense mutations.
2010,
Pubmed
Almaça,
TMEM16 proteins produce volume-regulated chloride currents that are reduced in mice lacking TMEM16A.
2009,
Pubmed
Arav-Boger,
Cerebellar ataxia as the presenting manifestation of Lyme disease.
2002,
Pubmed
Bartha,
A genome-to-genome analysis of associations between human genetic variation, HIV-1 sequence diversity, and viral control.
2013,
Pubmed
Begemann,
Modification of cognitive performance in schizophrenia by complexin 2 gene polymorphisms.
2010,
Pubmed
Berende,
Activation of innate host defense mechanisms by Borrelia.
2010,
Pubmed
Bowman,
Duplication of Atxn1l suppresses SCA1 neuropathology by decreasing incorporation of polyglutamine-expanded ataxin-1 into native complexes.
2007,
Pubmed
Brunner,
X-ray structure of a calcium-activated TMEM16 lipid scramblase.
2014,
Pubmed
Caputo,
TMEM16A, a membrane protein associated with calcium-dependent chloride channel activity.
2008,
Pubmed
Casjens,
Genome stability of Lyme disease spirochetes: comparative genomics of Borrelia burgdorferi plasmids.
2012,
Pubmed
Chamova,
ANO10 c.1150_1151del is a founder mutation causing autosomal recessive cerebellar ataxia in Roma/Gypsies.
2012,
Pubmed
Chapman,
Human genetic susceptibility to infectious disease.
2012,
Pubmed
Choi,
PROVEAN web server: a tool to predict the functional effect of amino acid substitutions and indels.
2015,
Pubmed
Dehnert,
Seropositivity of Lyme borreliosis and associated risk factors: a population-based study in Children and Adolescents in Germany (KiGGS).
2012,
Pubmed
Fallon,
Lyme disease: a neuropsychiatric illness.
1994,
Pubmed
Gosling,
Effects of arachidonic acid upon the volume-sensitive chloride current in rat osteoblast-like (ROS 17/2.8) cells.
1996,
Pubmed
Hammer,
Neuropsychiatric disease relevance of circulating anti-NMDA receptor autoantibodies depends on blood-brain barrier integrity.
2014,
Pubmed
Hanincova,
Multilocus sequence typing of Borrelia burgdorferi suggests existence of lineages with differential pathogenic properties in humans.
2013,
Pubmed
Hess,
Borrelia burgdorferi central nervous system infection presenting as an organic schizophrenialike disorder.
1999,
Pubmed
Hoffmann,
Physiology of cell volume regulation in vertebrates.
2009,
Pubmed
Horne,
Common polymorphisms in the PKP3-SIGIRR-TMEM16J gene region are associated with susceptibility to tuberculosis.
2012,
Pubmed
Johnson,
SNAP: a web-based tool for identification and annotation of proxy SNPs using HapMap.
2008,
Pubmed
Juul,
Anoctamin 6 differs from VRAC and VSOAC but is involved in apoptosis and supports volume regulation in the presence of Ca2+.
2014,
Pubmed
Kumar,
Predicting the effects of coding non-synonymous variants on protein function using the SIFT algorithm.
2009,
Pubmed
Lemonnier,
Ca2+ modulation of volume-regulated anion channels: evidence for colocalization with store-operated channels.
2002,
Pubmed
Liveris,
Improving the yield of blood cultures from patients with early Lyme disease.
2011,
Pubmed
Malvezzi,
Ca2+-dependent phospholipid scrambling by a reconstituted TMEM16 ion channel.
2013,
Pubmed
Martins,
Anoctamin 6 is an essential component of the outwardly rectifying chloride channel.
2011,
Pubmed
Nilius,
Properties of volume-regulated anion channels in mammalian cells.
1997,
Pubmed
Ousingsawat,
Anoctamin 6 mediates effects essential for innate immunity downstream of P2X7 receptors in macrophages.
2015,
Pubmed
,
Xenbase
Pachner,
Borrelia burgdorferi in the nervous system: the new "great imitator".
1988,
Pubmed
Preston,
Appearance of water channels in Xenopus oocytes expressing red cell CHIP28 protein.
1992,
Pubmed
,
Xenbase
Purcell,
PLINK: a tool set for whole-genome association and population-based linkage analyses.
2007,
Pubmed
Qiu,
SWELL1, a plasma membrane protein, is an essential component of volume-regulated anion channel.
2014,
Pubmed
Ribbe,
The cross-sectional GRAS sample: a comprehensive phenotypical data collection of schizophrenic patients.
2010,
Pubmed
Schroeder,
Expression cloning of TMEM16A as a calcium-activated chloride channel subunit.
2008,
Pubmed
,
Xenbase
Schwab,
Role of ion channels and transporters in cell migration.
2012,
Pubmed
Shapiro,
Clinical practice. Lyme disease.
2014,
Pubmed
Stanek,
Lyme borreliosis.
2012,
Pubmed
Steere,
The emergence of Lyme disease.
2004,
Pubmed
Strange,
Cellular and molecular physiology of volume-sensitive anion channels.
1996,
Pubmed
Suzuki,
Calcium-dependent phospholipid scrambling by TMEM16F.
2010,
Pubmed
Vermeer,
Targeted next-generation sequencing of a 12.5 Mb homozygous region reveals ANO10 mutations in patients with autosomal-recessive cerebellar ataxia.
2010,
Pubmed
Voss,
Identification of LRRC8 heteromers as an essential component of the volume-regulated anion channel VRAC.
2014,
Pubmed
World Medical Association,
World Medical Association Declaration of Helsinki: ethical principles for medical research involving human subjects.
2013,
Pubmed
Wu,
Regulatory volume decrease by SV40-transformed rabbit corneal epithelial cells requires ryanodine-sensitive Ca2+-induced Ca2+ release.
1997,
Pubmed
Yang,
TMEM16A confers receptor-activated calcium-dependent chloride conductance.
2008,
Pubmed
,
Xenbase
Yang,
GCTA: a tool for genome-wide complex trait analysis.
2011,
Pubmed
Zoghbi,
Pathogenic mechanisms of a polyglutamine-mediated neurodegenerative disease, spinocerebellar ataxia type 1.
2009,
Pubmed
