A novel alteration in metaxin 1, F202L, is associated with N370S in Gaucher disease

LaMarca, Mary E.; Goldstein, Mona; Tayebi, Nahid; Arcos‐Burgos, Mauricio; Martin, Brian M.; Sidransky, Ellen

doi:10.1007/s10038-004-0134-7

Cited by 7 publications

(3 citation statements)

References 12 publications

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“…identified a p.F202L mutation in the MTX1 gene in some patients with GD, most commonly found in association with the p.N409S mutation. The authors extrapolated that this MTX1 mutation could dampen the burden of disease in patients with the p.N409S mutation (LaMarca et al., ). Moreover, Gan‐Or et al.…”

Section: Modifiers Of Gaucher Disease: Results Of Candidate Gene Studiesmentioning

confidence: 99%

Exploring genetic modifiers of Gaucher disease: The next horizon

et al. 2018

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Gaucher disease is an autosomal recessive lysosomal storage disorder resulting from mutations in the gene GBA1 that lead to a deficiency in the enzyme glucocerebrosidase. Accumulation of the enzyme's substrates, glucosylceramide and glucosylsphingosine, results in symptoms ranging from skeletal and visceral involvement to neurological manifestations. Nonetheless, there is significant variability in clinical presentations amongst patients, with limited correlation between genotype and phenotype. Contributing to this clinical variation are genetic modifiers that influence the phenotypic outcome of the disorder. In this review, we explore the role of genetic modifiers in Mendelian disorders and describe methods to facilitate their discovery. In addition, we provide examples of candidate modifiers of Gaucher disease, explore their relevance in the development of potential therapeutics, and discuss the impact of GBA1 and modifying mutations on other more common diseases like Parkinson disease. Identifying these important modulators of Gaucher phenotype may ultimately unravel the complex relationship between genotype and phenotype and lead to improved counseling and treatments.

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Section: Modifiers Of Gaucher Disease: Results Of Candidate Gene Studiesmentioning

confidence: 99%

Exploring genetic modifiers of Gaucher disease: The next horizon

et al. 2018

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“…MTX1 has an essential role in embryonic development, and GBA encodes glucocerebrosidase, an enzyme mediating glycolipid metabolism 19 . Both are known as causal genes in Gaucher disease 19 , a lysosomal storage disease, although kidney function decline has not been implicated in pathogenesis. PAX8 is a member of the PAX gene family and is widely expressed in renal tissues 20 .…”

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confidence: 99%

Meta-analysis identifies multiple loci associated with kidney function–related traits in east Asian populations

Okada¹,

Sim²,

Go³

et al. 2012

Nat Genet

276

280

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Chronic kidney disease (CKD), impairment of kidney function, is a serious public health problem, and the assessment of genetic factors influencing kidney function has substantial clinical relevance. Here, we report a meta-analysis of genome-wide association studies for kidney function–related traits, including 71,149 east Asian individuals from 18 studies in 11 population-, hospital- or family-based cohorts, conducted as part of the Asian Genetic Epidemiology Network (AGEN). Our meta-analysis identified 17 loci newly associated with kidney function–related traits, including the concentrations of blood urea nitrogen, uric acid and serum creatinine and estimated glomerular filtration rate based on serum creatinine levels (eGFRcrea) (P < 5.0 × 10−8). We further examined these loci with in silico replication in individuals of European ancestry from the KidneyGen, CKDGen and GUGC consortia, including a combined total of ~110,347 individuals. We identify pleiotropic associations among these loci with kidney function–related traits and risk of CKD. These findings provide new insights into the genetics of kidney function.

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“…The gene order is GBA1-psMTX1-psGBA1-MTX1-THBS3. In humans, a deficiency of the glucocerebrosidase enzyme as a result of mutations in GBA1 can cause Gaucher disease (Mistry et al, 2017;Tayebi et al, 2003;LaMarca et al, 2004). An increased genetic risk for the development of Parkinson's disease is also associated with GBA1 mutations (Do et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

Invertebrate Metaxins 1 and 2: Widely Distributed Proteins Homologous to Vertebrate Metaxins Implicated in Protein Import into Mitochondria

Adolph

2020

Preprint

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Metaxin 1 and 2 genes, previously investigated in vertebrates, are shown to be widely distributed among invertebrates. But metaxin 3 is absent. The predicted proteins of the invertebrate metaxins were initially identified by homology with human metaxin 1 and 2 proteins, and by the presence of characteristic GST_Metaxin protein domains. Invertebrate metaxins were revealed for a variety of phyla, including Echinodermata, Cnidaria, Porifera, Chordata, Arthropoda, Mollusca, Brachiopoda, Placozoa, and Nematoda. Metaxins were also found in insects (Arthropoda) of different taxonomic orders: Diptera, Coleoptera, Lepidoptera, Hymenoptera, and Blattodea. Invertebrate and human metaxin 1 proteins have about 41% identical amino acids, while metaxin 2 proteins have about 49% identities. Invertebrate and vertebrate metaxins share the same characteristic protein domains, further strengthening the identification of the invertebrate proteins as metaxins. The domains are, for metaxin 1, GST_N_Metaxin1_like, GST_C_Metaxin1_3, and Tom37. For metaxin 2, they are GST_N_Metaxin2, GST_C_Metaxin2, and Tom37. Phylogenetic trees show that invertebrate metaxin 1 and metaxin 2 proteins are related, but form separate groups. The invertebrate proteins are also closely related to vertebrate metaxins, though forming separate clusters. These phylogenetic results indicate that all metaxins likely arose from a common ancestral sequence. The neighboring genes of the invertebrate metaxin 1 and 2 genes are largely different for different invertebrate species. This is unlike the situation with vertebrate metaxin genes, where, for example, the metaxin 1 gene is adjacent to the thrombospondin 3 gene. The dominant secondary structures predicted for the invertebrate metaxins are alpha-helical segments, with little beta-strand. The conserved pattern of helical segments is the same as that found for vertebrate metaxins 1, 2, and 3.

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A novel alteration in metaxin 1, F202L, is associated with N370S in Gaucher disease

Cited by 7 publications

References 12 publications

Exploring genetic modifiers of Gaucher disease: The next horizon

Exploring genetic modifiers of Gaucher disease: The next horizon

Meta-analysis identifies multiple loci associated with kidney function–related traits in east Asian populations

Invertebrate Metaxins 1 and 2: Widely Distributed Proteins Homologous to Vertebrate Metaxins Implicated in Protein Import into Mitochondria

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