FREM1

Summary

Gene Symbol: FREM1
Description: FRAS1 related extracellular matrix 1
Alias: BNAR, C9orf143, C9orf145, C9orf154, MOTA, TILRR, TRIGNO2, FRAS1-related extracellular matrix protein 1, extracellular matrix protein QBRICK
Species: human

Top Publications

  1. pmc Heterozygous mutations of FREM1 are associated with an increased risk of isolated metopic craniosynostosis in humans and mice
    Lisenka E L M Vissers
    Department of Human Genetics, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
    PLoS Genet 7:e1002278. 2011
  2. doi Manitoba-oculo-tricho-anal (MOTA) syndrome is caused by mutations in FREM1
    Anne M Slavotinek
    Department of Pediatrics, Division of Genetics, University of California, 533 Parnassus Street, Room U585P, San Francisco, CA 94143 0748, USA
    J Med Genet 48:375-82. 2011
  3. pmc The extracellular matrix gene Frem1 is essential for the normal adhesion of the embryonic epidermis
    Ian Smyth
    Medical Research Council Human Genetics Unit, Crewe Road, Edinburgh EH4 2XU, Scotland, United Kingdom
    Proc Natl Acad Sci U S A 101:13560-5. 2004
  4. pmc FREM1 mutations cause bifid nose, renal agenesis, and anorectal malformations syndrome
    Anas M Alazami
    Developmental Genetics Unit, Department of Genetics, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia
    Am J Hum Genet 85:414-8. 2009
  5. pmc Novel FREM1 mutations expand the phenotypic spectrum associated with Manitoba-oculo-tricho-anal (MOTA) syndrome and bifid nose renal agenesis anorectal malformations (BNAR) syndrome
    Jared Nathanson
    Division of Genetics, Department of Pediatrics, University of California, San Francisco, California 94143 0748, USA
    Am J Med Genet A 161:473-8. 2013
  6. pmc Regulation of PDGFC signalling and extracellular matrix composition by FREM1 in mice
    Fenny Wiradjaja
    Department of Biochemistry and Molecular Biology, Monash University, Wellington Road, Clayton, Victoria 3800, Australia
    Dis Model Mech 6:1426-33. 2013
  7. doi NF-κB and STAT3 cooperatively induce IL6 in starved cancer cells
    S Yoon
    Department of Microbiology, Ajou University School of Medicine, Suwon, Gyeonggi Do, Korea
    Oncogene 31:3467-81. 2012
  8. pmc Distinct control of MyD88 adapter-dependent and Akt kinase-regulated responses by the interleukin (IL)-1RI co-receptor, TILRR
    Xiao Zhang
    Cell Biology Group, University of Sheffield, Sheffield S10 2RX, United Kingdom
    J Biol Chem 287:12348-52. 2012
  9. doi Cytogenomic characterization of an unexpected 17.6 Mb 9p deletion associated to a 14.8 Mb 20p duplication in a dysmorphic patient with multiple congenital anomalies presenting a normal G-banding karyotype
    Vera de Freitas Ayres Meloni
    Department of Morphology and Genetics, Universidade Federal de Sao Paulo, Sao Paulo, Brazil
    Gene 496:59-62. 2012
  10. pmc Basement membrane assembly of the integrin α8β1 ligand nephronectin requires Fraser syndrome-associated proteins
    Daiji Kiyozumi
    Laboratory of Extracellular Matrix Biochemistry, Institute for Protein Research, Osaka University, Suita, Osaka 565 0871, Japan
    J Cell Biol 197:677-89. 2012

Research Grants

Scientific Experts

  • Chih Ping Chen
  • Ma Luo
  • Ian Smyth
  • Thomas J Carney
  • A M Slavotinek
  • Daiji Kiyozumi
  • Petros Petrou
  • Georges Chalepakis
  • Kiyotoshi Sekiguchi
  • Evangelos Pavlakis
  • Tyler F Beck
  • Xiao Zhang
  • Rena Chiotaki
  • Yannis Dalezios
  • Fenny Wiradjaja
  • Apostolos K Makrygiannis
  • Itsuko Nakano
  • Jolanta E Pitera
  • Nagisa Sugimoto
  • Zhiyin Yu
  • David W Stockton
  • Hitisha P Zaveri
  • Oleg A Shchelochkov
  • Monica J Justice
  • Daryl A Scott
  • Bum Jun Kim
  • Jared Nathanson
  • Vera de Freitas Ayres Meloni
  • Robertino Karlo Mateo
  • S Yoon
  • Endre Kiss-Toth
  • Eva E Qwarnstrom
  • Freya Shephard
  • Lisenka E L M Vissers
  • Jae Jung Kim
  • Anas M Alazami
  • Peter J Scambler
  • Adrian S Woolf
  • E Pavlakis
  • Shalini Jadeja
  • Yolande van Bever
  • Jane Hurst
  • Paul A Overbeek
  • Dick Tibboel
  • Amihood Singer
  • Brendan Lee
  • Terry K Bertin
  • Wendy Jones
  • Danielle Veenma
  • Pragna I Patel
  • Hannie Douben
  • Elaine Zackai
  • Evgenia Kalogeraki
  • Andres Hernandez-Garcia
  • Annelies de Klein
  • Sunju Choi
  • Amy Chinn
  • Lynelle Jones
  • Denny L Cottle
  • Mochi Liu
  • COLIN BISHOP
  • Nahla Khalek
  • Daniel T Swarr
  • Gemma Montagut Pino
  • Royce Johnson
  • Decio Brunoni
  • Makiko Takeichi
  • Sylvia Satomi Takeno
  • J H Kang
  • S Park
  • K Kim
  • Leslie Domenici Kulikowski
  • Ordan J Lehmann
  • H S Gwak
  • Maria de Fátima de Faria Soares
  • Yuya Sato
  • Maria Isabel Melaragno
  • Flavia Balbo Piazzon
  • H J Shin
  • S U Woo
  • Tomohiko Fukuda
  • M Albert Basson
  • Y J Chwae
  • Denise Maria Christofolini
  • Joris A Veltman
  • Michael L Cunningham
  • Jia Liu
  • Simeon A Boyadjiev
  • Garima Yagnik
  • Hans van Bokhoven

Detail Information

Publications33

  1. pmc Heterozygous mutations of FREM1 are associated with an increased risk of isolated metopic craniosynostosis in humans and mice
    Lisenka E L M Vissers
    Department of Human Genetics, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
    PLoS Genet 7:e1002278. 2011
    ..Five CNVs involving FREM1, all of which were de novo variants, were identified by array-based analyses...
  2. doi Manitoba-oculo-tricho-anal (MOTA) syndrome is caused by mutations in FREM1
    Anne M Slavotinek
    Department of Pediatrics, Division of Genetics, University of California, 533 Parnassus Street, Room U585P, San Francisco, CA 94143 0748, USA
    J Med Genet 48:375-82. 2011
    Manitoba-oculo-tricho-anal (MOTA) syndrome is a rare condition defined by eyelid colobomas, cryptophthalmos and anophthalmia/microphthalmia, an aberrant hairline, a bifid or broad nasal tip, and gastrointestinal anomalies such as ..
  3. pmc The extracellular matrix gene Frem1 is essential for the normal adhesion of the embryonic epidermis
    Ian Smyth
    Medical Research Council Human Genetics Unit, Crewe Road, Edinburgh EH4 2XU, Scotland, United Kingdom
    Proc Natl Acad Sci U S A 101:13560-5. 2004
    ..report the identification of mutations in an extracellular matrix gene Fras1-related extracellular matrix gene 1 (Frem1) in both the classic head blebs mutant and in an N-ethyl-N-nitrosourea-induced allele...
  4. pmc FREM1 mutations cause bifid nose, renal agenesis, and anorectal malformations syndrome
    Anas M Alazami
    Developmental Genetics Unit, Department of Genetics, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia
    Am J Hum Genet 85:414-8. 2009
    ..2-p23. Candidate-gene analysis revealed homozygous frameshift and missense mutations in FREM1, which encodes an extracellular matrix component of basement membranes...
  5. pmc Novel FREM1 mutations expand the phenotypic spectrum associated with Manitoba-oculo-tricho-anal (MOTA) syndrome and bifid nose renal agenesis anorectal malformations (BNAR) syndrome
    Jared Nathanson
    Division of Genetics, Department of Pediatrics, University of California, San Francisco, California 94143 0748, USA
    Am J Med Genet A 161:473-8. 2013
    Loss of function mutations in FREM1 have been demonstrated in Manitoba-oculo-tricho-anal (MOTA) syndrome and Bifid Nose Renal Agenesis and Anorectal malformations (BNAR) syndrome, but the wider phenotypic spectrum that is associated with ..
  6. pmc Regulation of PDGFC signalling and extracellular matrix composition by FREM1 in mice
    Fenny Wiradjaja
    Department of Biochemistry and Molecular Biology, Monash University, Wellington Road, Clayton, Victoria 3800, Australia
    Dis Model Mech 6:1426-33. 2013
    Fras1-related extracellular matrix protein 1 (FREM1) is required for epidermal adhesion during embryogenesis, and mice lacking the gene develop fetal skin blisters and a range of other developmental defects...
  7. doi NF-κB and STAT3 cooperatively induce IL6 in starved cancer cells
    S Yoon
    Department of Microbiology, Ajou University School of Medicine, Suwon, Gyeonggi Do, Korea
    Oncogene 31:3467-81. 2012
    ..from starved cancer cells contained various secretory factors, such as IL6, IL9, VWF (von Willebrand factor), FREM1 (FRAS1 related extracellular matrix 1), SAA1 (serum amyloid A1), SDK1 (sidekick homolog 1) and ADAM12 (ADAM ..
  8. pmc Distinct control of MyD88 adapter-dependent and Akt kinase-regulated responses by the interleukin (IL)-1RI co-receptor, TILRR
    Xiao Zhang
    Cell Biology Group, University of Sheffield, Sheffield S10 2RX, United Kingdom
    J Biol Chem 287:12348-52. 2012
    ..work demonstrates that the IL-1 receptor type 1 (IL-1RI) co-receptor, Toll-like and IL-1 receptor regulator (TILRR), amplifies IL-1 activation of NF-κB and inflammatory genes...
  9. doi Cytogenomic characterization of an unexpected 17.6 Mb 9p deletion associated to a 14.8 Mb 20p duplication in a dysmorphic patient with multiple congenital anomalies presenting a normal G-banding karyotype
    Vera de Freitas Ayres Meloni
    Department of Morphology and Genetics, Universidade Federal de Sao Paulo, Sao Paulo, Brazil
    Gene 496:59-62. 2012
    ..6Mb deletion of 9p associated to a 14.8 Mb duplication of 20p. The deleted 9p genes, especially CER1 and FREM1, seem to be more relevant to the phenotype than the duplicated 20p genes...
  10. pmc Basement membrane assembly of the integrin α8β1 ligand nephronectin requires Fraser syndrome-associated proteins
    Daiji Kiyozumi
    Laboratory of Extracellular Matrix Biochemistry, Institute for Protein Research, Osaka University, Suita, Osaka 565 0871, Japan
    J Cell Biol 197:677-89. 2012
    ....
  11. pmc Novel frem1-related mouse phenotypes and evidence of genetic interactions with gata4 and slit3
    Tyler F Beck
    Departments of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, United States of America
    PLoS ONE 8:e58830. 2013
    The FRAS1-related extracellular matrix 1 (FREM1) gene encodes an extracellular matrix protein that plays a critical role in the development of multiple organ systems...
  12. ncbi Partial monosomy 9p (9p22.2-->pter) and partial trisomy 18q (18q21.32-->qter) in a female infant with anorectal malformations
    C P Chen
    Department of Obstetrics and Gynecology, Mackay Memorial Hospital, Taipei, Taiwan
    Genet Couns 23:201-6. 2012
    ..Array comparative genomic hybridization revealed a 16.93-Mb deletion at 9p24.3-p22.2 encompassing the FREM1 gene and a 20.43-Mb duplication at 18q21.32-q23 encompassing the PIGN gene...
  13. pmc A genetic polymorphism of FREM1 is associated with resistance against HIV infection in the Pumwani sex worker cohort
    Ma Luo
    Public Health Agency of Canada, National Microbiology Laboratory, Winnipeg, Manitoba, Canada
    J Virol 86:11899-905. 2012
    ..The SNP minor allele rs1552896, in an intron of FREM1, was significantly associated with the resistant phenotype (P = 1.68 × 10(-5); adjusted P = 2...
  14. pmc Sprouty1 haploinsufficiency prevents renal agenesis in a model of Fraser syndrome
    Jolanta E Pitera
    Molecular Medicine Unit, UCL Institute of Child Health, 30 Guilford Street, London WC1N 1EH, United Kingdom
    J Am Soc Nephrol 23:1790-6. 2012
    ..Whereas wild-type metanephroi expressed FRAS1 and the related proteins FREM1 and FREM2, FRAS1 was absent and the other proteins were downregulated in rescued kidneys, consistent with a ..
  15. pmc Deficiency of FRAS1-related extracellular matrix 1 (FREM1) causes congenital diaphragmatic hernia in humans and mice
    Tyler F Beck
    Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA
    Hum Mol Genet 22:1026-38. 2013
    ..Recessive mutations in the FRAS1-related extracellular matrix 1 (FREM1) gene have been shown to cause bifid nose with or without anorectal and renal anomalies (BNAR) syndrome and ..
  16. pmc Evidence for additional FREM1 heterogeneity in Manitoba oculotrichoanal syndrome
    Robertino Karlo Mateo
    Department of Medical Genetics, University of Alberta, Edmonton, Alberta, Canada
    Mol Vis 18:1301-11. 2012
    Manitoba Oculotrichoanal (MOTA) syndrome is an autosomal recessive disorder present in First Nations families that is characterized by ocular (cryptophthalmos), facial, and genital anomalies...
  17. doi Segmental and restricted localization pattern of Fras1 in the developing meningeal basement membrane in mouse
    Apostolos K Makrygiannis
    Department of Biology, University of Crete, Voutes University Campus, 700 13, Heraklion, Crete, Greece
    Histochem Cell Biol 140:595-601. 2013
    The Fras1/Frem family of extracellular matrix proteins consists of Fras1 and its structurally related proteins, Frem1 (Fras1-related extracellular matrix protein 1), Frem2 and Frem3...
  18. pmc Genetic analysis of fin development in zebrafish identifies furin and hemicentin1 as potential novel fraser syndrome disease genes
    Thomas J Carney
    Max Planck Institute of Immunobiology, Georges Koehler Laboratory, Freiburg, Germany
    PLoS Genet 6:e1000907. 2010
    ..Three of them are due to mutations in zebrafish orthologues of FRAS1, FREM1, or FREM2, large basement membrane protein encoding genes that are mutated in mouse bleb mutants and in human ..
  19. ncbi Identification of a new gene mutated in Fraser syndrome and mouse myelencephalic blebs
    Shalini Jadeja
    Molecular Medicine Unit, Institute of Child Health, University College London, London WC1N 1EH, UK
    Nat Genet 37:520-5. 2005
    ..The myelencephalic blebs (my) strain has a similar phenotype. We mapped my to Frem2, a gene related to Fras1 and Frem1, and showed that a Frem2 gene-trap mutation was allelic to my...
  20. ncbi Identification of a novel cell-adhesive protein spatiotemporally expressed in the basement membrane of mouse developing hair follicle
    Daiji Kiyozumi
    Sekiguchi Biomatrix Signaling Project, ERATO, Japan Science and Technology Agency JST, Aichi Medical University, 21 Karimata, Nagakute, Aichi 480 1195, Japan
    Exp Cell Res 306:9-23. 2005
    ..These results, together, indicate that QBRICK is an adhesive ligand of basement membrane distinctively recognized by cells in the embryonic skin and hair follicles through different types of integrins directed to the Arg-Gly-Asp motif...
  21. pmc Breakdown of the reciprocal stabilization of QBRICK/Frem1, Fras1, and Frem2 at the basement membrane provokes Fraser syndrome-like defects
    Daiji Kiyozumi
    Sekiguchi Biomatrix Signaling Project, Exploratory Research for Advanced Technology, Japan Science and Technology Agency, Aichi Medical University, Nagakute, Aichi 480 1195, Japan
    Proc Natl Acad Sci U S A 103:11981-6. 2006
    ..characterized by 12 consecutive CSPG repeats and the presence of Calx-beta motif(s) includes Fras1, QBRICK/Frem1, and Frem2...
  22. ncbi Overlapping and divergent localization of Frem1 and Fras1 and its functional implications during mouse embryonic development
    Petros Petrou
    Department of Biology, University of Crete, 71409 Heraklion, Crete, Greece
    Exp Cell Res 313:910-20. 2007
    b>Frem1 belongs to a family of structurally related extracellular matrix proteins of which Fras1 is the founding member...
  23. ncbi Spatiotemporal distribution of Fras1/Frem proteins during mouse embryonic development
    Rena Chiotaki
    Department of Biology, University of Crete, 71409 Heraklion, Crete, Greece
    Gene Expr Patterns 7:381-8. 2007
    ..Mutations in Fras1, Frem1 and Frem2 have been identified in different classes of mouse bleb mutants, while defects in the human orthologs ..
  24. ncbi Frem3, a member of the 12 CSPG repeats-containing extracellular matrix protein family, is a basement membrane protein with tissue distribution patterns distinct from those of Fras1, Frem2, and QBRICK/Frem1
    Daiji Kiyozumi
    Laboratory of Extracellular Matrix Biochemistry, Institute for Protein Research, Osaka University, Suita, Osaka, 565 0871, Japan
    Matrix Biol 26:456-62. 2007
    ..A novel protein family characterized by the presence of 12 CSPG repeats and Calx-beta domains includes Fras1, QBRICK/Frem1, Frem2 and Frem3...
  25. ncbi Ultrastructural localization of Fras1 in the sublamina densa of embryonic epithelial basement membranes
    Yannis Dalezios
    Department of Basic Sciences, Faculty of Medicine, University of Crete, PO Box 2208, 71003 Heraklion, Crete, Greece
    Arch Dermatol Res 299:337-43. 2007
    ..is the first identified member of a protein family comprising Fras1 and the related extracellular matrix proteins Frem1, Frem2 and Frem3...
  26. ncbi Basement membrane localization of Frem3 is independent of the Fras1/Frem1/Frem2 protein complex within the sublamina densa
    Petros Petrou
    Department of Biology, University of Crete, 71409 Heraklion, Crete, Greece
    Matrix Biol 26:652-8. 2007
    The Fraser syndrome protein Fras1 and the structurally related proteins Frem1, Frem2 and Frem3 comprise a novel family of extracellular matrix proteins implicated in the structural adhesion of the embryonic epidermis to the underlying ..
  27. doi Differential localization profile of Fras1/Frem proteins in epithelial basement membranes of newborn and adult mice
    E Pavlakis
    Department of Biology, University of Crete, 71409, Heraklion, Crete, Greece
    Histochem Cell Biol 130:785-93. 2008
    ..as deduced from the appearance of sub-epidermal blisters in mouse mutants compromising the function of Fras1, Frem1 and Frem2 proteins...
  28. doi The Fras1/Frem family of extracellular matrix proteins: structure, function, and association with Fraser syndrome and the mouse bleb phenotype
    Petros Petrou
    Department of Biological Sciences, University of Cyprus, Nicosia, Cyprus
    Connect Tissue Res 49:277-82. 2008
    Fras1 and the structurally related proteins Frem1, Frem2, and Frem3, comprise a novel family of extracellular matrix proteins, which localize in a similar fashion underneath the lamina densa of epithelial basement membranes...
  29. doi Identification of 15 loci influencing height in a Korean population
    Jae Jung Kim
    Asan Institute for Life Sciences, University of Ulsan College of Medicine, Seoul, Korea
    J Hum Genet 55:27-31. 2010
    ..Of these, eight loci were newly identified in Koreans (SUPT3H, EXT1, FREM1, PALM2-AKAP2, NUP37-PMCH, IGF1, KRT20 and ANKRD60). The 15 significant loci account for approximately 1...
  30. pmc TILRR, a novel IL-1RI co-receptor, potentiates MyD88 recruitment to control Ras-dependent amplification of NF-kappaB
    Xiao Zhang
    Units of Cell Biology, University of Sheffield, Sheffield S102RX, United Kingdom
    J Biol Chem 285:7222-32. 2010
    ..Here we identify a novel regulatory component, TILRR, which amplifies activation of IL-1RI and coordinates IL-1-induced control with mechanotransduction...
  31. doi Fused pulmonary lobes is a rat model of human Fraser syndrome
    Daiji Kiyozumi
    Laboratory of Extracellular Matrix Biochemistry, Institute for Protein Research, Osaka University, 3 2 Yamadaoka, Suita, Osaka 565 0871, Japan
    Biochem Biophys Res Commun 411:440-4. 2011
    ..Genomic DNA sequencing of the fpl/fpl mutant identified a nonsense mutation that introduced a stop codon at serine 2005 in Frem2. These findings indicate that the fpl mutant is a rat model of human Fraser syndrome...
  32. doi The role of Fras1/Frem proteins in the structure and function of basement membrane
    Evangelos Pavlakis
    Department of Biology, University of Crete, 71409 Heraklion, Crete, Greece
    Int J Biochem Cell Biol 43:487-95. 2011
    ..basement membrane proteins, Fras1 (Fraser syndrome protein (1) and the Fras1-related extracellular matrix proteins Frem1, Frem2 and Frem3, has emerged...

Research Grants3

  1. Genetic analysis of congenital diaphragmatic hernia
    Anne Slavotinek; Fiscal Year: 2006
    ..abstract_text> ..
  2. Molecular Genetic Analysis of Congenital Diaphragmatic Hernia
    Anne Slavotinek; Fiscal Year: 2007
    ....