CCG repeat expansions in this gene are associated with X-linked intellectual disability and specifically a syndrome known as Fragile XE mental retardation (FRAXE). FRAXE is one of the most common forms of non-syndromic X-linked intellectual disability. The gene is also known as FMR2 (Fragile Mental Retardation 2) after this condition.[5]
This gene is located on the long arm of chromosome X (Xq27.3-Xq28) It has 22 exons spanning at least 500 kb. Alternative splicing may occur and involve exons 2, 3, 5, 7 and 21. The normal encoded protein is 1311 codons in length. It is expressed as an 8.7 kilobase transcript in the placenta and adult brain.[citation needed]
The normal 5' untranslated region has 10-35 CCG repeats and more frequently 15–20. Pathogenic expansions have typically over 200 repeats and are methylated.[citation needed]
This gene belongs to the AFF family of genes which currently has four members: AFF1/AF4, AFF2/FMR2, AFF3/LAF4 and AFF4/AF5q31.[6] All AFF proteins are localized in the nucleus and have a role as transcriptional activators with a positive action on RNA elongation. AFF2/FMR2, AFF3/LAF4 and AFF4/AF5q31 localize in nuclear speckles (subnuclear structures considered to be storage/modification sites of pre-mRNA splicing factors) and are able to bind RNA with a high apparent affinity for the G-quadruplex structure. They appear to modulate alternative splicing via the interaction with the G-quadruplex RNA-forming structure.
The other members of this family have been reported to form fusion genes as a consequence of chromosome translocations and are involved in the pathogenesis of myeloid/lymphoid or mixed lineage leukemia.
Referencesedit
^ abcGRCh38: Ensembl release 89: ENSG00000155966 - Ensembl, May 2017
^"Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^The Cancer Genome Atlas Network (October 2012). "Comprehensive molecular portraits of human breast tumours". Nature. 490 (7418): 61–70. Bibcode:2012Natur.490...61T. doi:10.1038/nature11412. PMC3465532. PMID 23000897.
^Stettner GM, Shoukier M, Höger C, Brockmann K, Auber B (August 2011). "Familial intellectual disability and autistic behavior caused by a small FMR2 gene deletion". American Journal of Medical Genetics. Part A. 155A (8): 2003–7. doi:10.1002/ajmg.a.34122. PMID 21739600. S2CID 9568277.
^Melko M, Douguet D, Bensaid M, Zongaro S, Verheggen C, Gecz J, Bardoni B (May 2011). "Functional characterization of the AFF (AF4/FMR2) family of RNA-binding proteins: insights into the molecular pathology of FRAXE intellectual disability". Human Molecular Genetics. 20 (10): 1873–85. doi:10.1093/hmg/ddr069. PMID 21330300.
Further readingedit
Mulley JC, Yu S, Loesch DZ, Hay DA, Donnelly A, Gedeon AK, Carbonell P, López I, Glover G, Gabarrón I (March 1995). "FRAXE and mental retardation". Journal of Medical Genetics. 32 (3): 162–9. doi:10.1136/jmg.32.3.162. PMC1050310. PMID 7783162.
Gecz J, Gedeon AK, Sutherland GR, Mulley JC (May 1996). "Identification of the gene FMR2, associated with FRAXE mental retardation". Nature Genetics. 13 (1): 105–8. doi:10.1038/ng0596-105. PMID 8673085. S2CID 40161014.
Gu Y, Shen Y, Gibbs RA, Nelson DL (May 1996). "Identification of FMR2, a novel gene associated with the FRAXE CCG repeat and CpG island". Nature Genetics. 13 (1): 109–13. doi:10.1038/ng0596-109. PMID 8673086. S2CID 6781698.
Chakrabarti L, Knight SJ, Flannery AV, Davies KE (February 1996). "A candidate gene for mild mental handicap at the FRAXE fragile site". Human Molecular Genetics. 5 (2): 275–82. doi:10.1093/hmg/5.2.275. PMID 8824884.
Gécz J, Oostra BA, Hockey A, Carbonell P, Turner G, Haan EA, Sutherland GR, Mulley JC (March 1997). "FMR2 expression in families with FRAXE mental retardation". Human Molecular Genetics. 6 (3): 435–41. doi:10.1093/hmg/6.3.435. PMID 9147647.
Gecz J, Bielby S, Sutherland GR, Mulley JC (September 1997). "Gene structure and subcellular localization of FMR2, a member of a new family of putative transcription activators". Genomics. 44 (2): 201–13. doi:10.1006/geno.1997.4867. PMID 9299237.
Chakrabarti L, Bristulf J, Foss GS, Davies KE (March 1998). "Expression of the murine homologue of FMR2 in mouse brain and during development". Human Molecular Genetics. 7 (3): 441–8. doi:10.1093/hmg/7.3.441. PMID 9467002.
Gecz J, Mulley JC (1999). "Characterisation and expression of a large, 13.7 kb FMR2 isoform". European Journal of Human Genetics. 7 (2): 157–62. doi:10.1038/sj.ejhg.5200279. PMID 10196698.
Murray A, Webb J, Dennis N, Conway G, Morton N (October 1999). "Microdeletions in FMR2 may be a significant cause of premature ovarian failure". Journal of Medical Genetics. 36 (10): 767–70. doi:10.1136/jmg.36.10.767. PMC1734234. PMID 10528856.
Dias Neto E, Correa RG, Verjovski-Almeida S, Briones MR, Nagai MA, da Silva W, Zago MA, Bordin S, Costa FF, Goldman GH, Carvalho AF, Matsukuma A, Baia GS, Simpson DH, Brunstein A, de Oliveira PS, Bucher P, Jongeneel CV, O'Hare MJ, Soares F, Brentani RR, Reis LF, de Souza SJ, Simpson AJ (March 2000). "Shotgun sequencing of the human transcriptome with ORF expressed sequence tags". Proceedings of the National Academy of Sciences of the United States of America. 97 (7): 3491–6. Bibcode:2000PNAS...97.3491D. doi:10.1073/pnas.97.7.3491. PMC16267. PMID 10737800.
Lo Nigro C, Faravelli F, Cavani S, Perroni L, Novello P, Vitali M, Bricarelli FD, Grasso M (March 2000). "FRAXE mutation in a mentally retarded subject and in his phenotypically normal twin brother". European Journal of Human Genetics. 8 (3): 157–62. doi:10.1038/sj.ejhg.5200425. PMID 10780779.
Tzeng CC, Tzeng PY, Sun HS, Chen RM, Lin SJ (June 2000). "Implication of screening for FMR1 and FMR2 gene mutation in individuals with nonspecific mental retardation in Taiwan". Diagnostic Molecular Pathology. 9 (2): 75–80. doi:10.1097/00019606-200006000-00002. PMID 10850542.
Musumeci SA, Scuderi C, Ferri R, Anello G, Salluzzo R, Bosco P, Elia M (September 2000). "Does a peculiar EEG pattern exist also for FRAXE mental retardation?". Clinical Neurophysiology. 111 (9): 1632–6. doi:10.1016/S1388-2457(00)00367-9. PMID 10964075. S2CID 42912350.
Hillman MA, Gecz J (2001). "Fragile XE-associated familial mental retardation protein 2 (FMR2) acts as a potent transcription activator". Journal of Human Genetics. 46 (5): 251–9. doi:10.1007/s100380170074. PMID 11355014.
Kitano T, Schwarz C, Nickel B, Pääbo S (August 2003). "Gene diversity patterns at 10 X-chromosomal loci in humans and chimpanzees". Molecular Biology and Evolution. 20 (8): 1281–9. doi:10.1093/molbev/msg134. PMID 12777533.
Brylawski BP, Chastain PD, Cohen SM, Cordeiro-Stone M, Kaufman DG (April 2007). "Mapping of an origin of DNA replication in the promoter of fragile X gene FMR1". Experimental and Molecular Pathology. 82 (2): 190–6. doi:10.1016/j.yexmp.2006.10.004. PMC1934615. PMID 17196195.
External linksedit
Human AFF2 genome location and AFF2 gene details page in the UCSC Genome Browser.
This article on a gene on the human X chromosome and/or its associated protein is a stub. You can help Wikipedia by expanding it.
aff2, fmr2, family, member, protein, that, humans, encoded, gene, mutations, implicated, cases, breast, cancer, identifiersaliases, fmr2, fmr2p, fraxe, mrx2, ox19, fmr2, family, member, xlid109external, idsomim, 300806, homologene, 136314, genecards, gene, loc. AF4 FMR2 family member 2 is a protein that in humans is encoded by the AFF2 gene 3 Mutations in AFF2 are implicated in cases of breast cancer 4 AFF2IdentifiersAliasesAFF2 FMR2 FMR2P FRAXE MRX2 OX19 AF4 FMR2 family member 2 XLID109External IDsOMIM 300806 HomoloGene 136314 GeneCards AFF2Gene location Human Chr X chromosome human 1 BandXq28Start148 500 617 bp 1 End149 000 663 bp 1 RNA expression patternBgeeHumanMouse ortholog Top expressed inganglionic eminenceAchilles tendonbone marrow cellsBrodmann area 23periodontal fibercerebellar cortexcerebellar hemisphereright lungmiddle temporal gyrustibialis anterior musclen aMore reference expression dataBioGPSMore reference expression dataGene ontologyMolecular functionG quadruplex RNA binding RNA binding double stranded DNA binding DNA binding transcription factor activityCellular componentnuclear speck nucleus transcription elongation factor complex super elongation complexBiological processmRNA processing regulation of RNA splicing brain development RNA splicing learning or memory regulation of gene expression negative regulation of gene expression nuclear speck organization regulation of transcription DNA templatedSources Amigo QuickGOOrthologsSpeciesHumanMouseEntrez2334n aEnsemblENSG00000155966n aUniProtP51816n aRefSeq mRNA NM 002025NM 001169122NM 001169123NM 001169124NM 001169125NM 001170628n aRefSeq protein NP 001162593NP 001162594NP 001162595NP 001162596NP 001164099NP 002016n aLocation UCSC Chr X 148 5 149 Mbn aPubMed search 2 n aWikidataView Edit HumanCCG repeat expansions in this gene are associated with X linked intellectual disability and specifically a syndrome known as Fragile XE mental retardation FRAXE FRAXE is one of the most common forms of non syndromic X linked intellectual disability The gene is also known as FMR2 Fragile Mental Retardation 2 after this condition 5 Contents 1 Genomics 2 References 3 Further reading 4 External linksGenomics editThis gene is located on the long arm of chromosome X Xq27 3 Xq28 It has 22 exons spanning at least 500 kb Alternative splicing may occur and involve exons 2 3 5 7 and 21 The normal encoded protein is 1311 codons in length It is expressed as an 8 7 kilobase transcript in the placenta and adult brain citation needed The normal 5 untranslated region has 10 35 CCG repeats and more frequently 15 20 Pathogenic expansions have typically over 200 repeats and are methylated citation needed This gene belongs to the AFF family of genes which currently has four members AFF1 AF4 AFF2 FMR2 AFF3 LAF4 and AFF4 AF5q31 6 All AFF proteins are localized in the nucleus and have a role as transcriptional activators with a positive action on RNA elongation AFF2 FMR2 AFF3 LAF4 and AFF4 AF5q31 localize in nuclear speckles subnuclear structures considered to be storage modification sites of pre mRNA splicing factors and are able to bind RNA with a high apparent affinity for the G quadruplex structure They appear to modulate alternative splicing via the interaction with the G quadruplex RNA forming structure The other members of this family have been reported to form fusion genes as a consequence of chromosome translocations and are involved in the pathogenesis of myeloid lymphoid or mixed lineage leukemia References edit a b c GRCh38 Ensembl release 89 ENSG00000155966 Ensembl May 2017 Human PubMed Reference National Center for Biotechnology Information U S National Library of Medicine Entrez Gene AFF2 AF4 FMR2 family member 2 The Cancer Genome Atlas Network October 2012 Comprehensive molecular portraits of human breast tumours Nature 490 7418 61 70 Bibcode 2012Natur 490 61T doi 10 1038 nature11412 PMC 3465532 PMID 23000897 Stettner GM Shoukier M Hoger C Brockmann K Auber B August 2011 Familial intellectual disability and autistic behavior caused by a small FMR2 gene deletion American Journal of Medical Genetics Part A 155A 8 2003 7 doi 10 1002 ajmg a 34122 PMID 21739600 S2CID 9568277 Melko M Douguet D Bensaid M Zongaro S Verheggen C Gecz J Bardoni B May 2011 Functional characterization of the AFF AF4 FMR2 family of RNA binding proteins insights into the molecular pathology of FRAXE intellectual disability Human Molecular Genetics 20 10 1873 85 doi 10 1093 hmg ddr069 PMID 21330300 Further reading editMulley JC Yu S Loesch DZ Hay DA Donnelly A Gedeon AK Carbonell P Lopez I Glover G Gabarron I March 1995 FRAXE and mental retardation Journal of Medical Genetics 32 3 162 9 doi 10 1136 jmg 32 3 162 PMC 1050310 PMID 7783162 Gecz J Gedeon AK Sutherland GR Mulley JC May 1996 Identification of the gene FMR2 associated with FRAXE mental retardation Nature Genetics 13 1 105 8 doi 10 1038 ng0596 105 PMID 8673085 S2CID 40161014 Gu Y Shen Y Gibbs RA Nelson DL May 1996 Identification of FMR2 a novel gene associated with the FRAXE CCG repeat and CpG island Nature Genetics 13 1 109 13 doi 10 1038 ng0596 109 PMID 8673086 S2CID 6781698 Chakrabarti L Knight SJ Flannery AV Davies KE February 1996 A candidate gene for mild mental handicap at the FRAXE fragile site Human Molecular Genetics 5 2 275 82 doi 10 1093 hmg 5 2 275 PMID 8824884 Gecz J Oostra BA Hockey A Carbonell P Turner G Haan EA Sutherland GR Mulley JC March 1997 FMR2 expression in families with FRAXE mental retardation Human Molecular Genetics 6 3 435 41 doi 10 1093 hmg 6 3 435 PMID 9147647 Gecz J Bielby S Sutherland GR Mulley JC September 1997 Gene structure and subcellular localization of FMR2 a member of a new family of putative transcription activators Genomics 44 2 201 13 doi 10 1006 geno 1997 4867 PMID 9299237 Chakrabarti L Bristulf J Foss GS Davies KE March 1998 Expression of the murine homologue of FMR2 in mouse brain and during development Human Molecular Genetics 7 3 441 8 doi 10 1093 hmg 7 3 441 PMID 9467002 Gecz J Mulley JC 1999 Characterisation and expression of a large 13 7 kb FMR2 isoform European Journal of Human Genetics 7 2 157 62 doi 10 1038 sj ejhg 5200279 PMID 10196698 Murray A Webb J Dennis N Conway G Morton N October 1999 Microdeletions in FMR2 may be a significant cause of premature ovarian failure Journal of Medical Genetics 36 10 767 70 doi 10 1136 jmg 36 10 767 PMC 1734234 PMID 10528856 Dias Neto E Correa RG Verjovski Almeida S Briones MR Nagai MA da Silva W Zago MA Bordin S Costa FF Goldman GH Carvalho AF Matsukuma A Baia GS Simpson DH Brunstein A de Oliveira PS Bucher P Jongeneel CV O Hare MJ Soares F Brentani RR Reis LF de Souza SJ Simpson AJ March 2000 Shotgun sequencing of the human transcriptome with ORF expressed sequence tags Proceedings of the National Academy of Sciences of the United States of America 97 7 3491 6 Bibcode 2000PNAS 97 3491D doi 10 1073 pnas 97 7 3491 PMC 16267 PMID 10737800 Lo Nigro C Faravelli F Cavani S Perroni L Novello P Vitali M Bricarelli FD Grasso M March 2000 FRAXE mutation in a mentally retarded subject and in his phenotypically normal twin brother European Journal of Human Genetics 8 3 157 62 doi 10 1038 sj ejhg 5200425 PMID 10780779 Tzeng CC Tzeng PY Sun HS Chen RM Lin SJ June 2000 Implication of screening for FMR1 and FMR2 gene mutation in individuals with nonspecific mental retardation in Taiwan Diagnostic Molecular Pathology 9 2 75 80 doi 10 1097 00019606 200006000 00002 PMID 10850542 Musumeci SA Scuderi C Ferri R Anello G Salluzzo R Bosco P Elia M September 2000 Does a peculiar EEG pattern exist also for FRAXE mental retardation Clinical Neurophysiology 111 9 1632 6 doi 10 1016 S1388 2457 00 00367 9 PMID 10964075 S2CID 42912350 Hillman MA Gecz J 2001 Fragile XE associated familial mental retardation protein 2 FMR2 acts as a potent transcription activator Journal of Human Genetics 46 5 251 9 doi 10 1007 s100380170074 PMID 11355014 Kitano T Schwarz C Nickel B Paabo S August 2003 Gene diversity patterns at 10 X chromosomal loci in humans and chimpanzees Molecular Biology and Evolution 20 8 1281 9 doi 10 1093 molbev msg134 PMID 12777533 Brylawski BP Chastain PD Cohen SM Cordeiro Stone M Kaufman DG April 2007 Mapping of an origin of DNA replication in the promoter of fragile X gene FMR1 Experimental and Molecular Pathology 82 2 190 6 doi 10 1016 j yexmp 2006 10 004 PMC 1934615 PMID 17196195 External links editHuman AFF2 genome location and AFF2 gene details page in the UCSC Genome Browser nbsp This article on a gene on the human X chromosome and or its associated protein is a stub You can help Wikipedia by expanding it vte Retrieved from https en wikipedia org w index php title AFF2 amp oldid 1167716857, wikipedia, wiki, book, books, library,
