AFF2

AFF2
Identifiers
Aliases	AFF2 , FMR2, FMR2P, FRAXE, MRX2, OX19, AF4/FMR2 family member 2, XLID109
External IDs	OMIM: 300806; MGI: 1202294; HomoloGene: 136314; GeneCards: AFF2; OMA:AFF2 - orthologs
Gene location (Human) Chr. X chromosome (human) [1] Band Xq28 Start 148,500,617 bp [1] End 149,000,663 bp [1]
Gene location (Mouse) Chr. X chromosome (mouse) [2] Band X|X A7.1- A7.2 Start 68,403,900 bp [2] End 68,911,643 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in ganglionic eminence Achilles tendon ventricular zone bone marrow cells Brodmann area 23 periodontal fiber cerebellar cortex cerebellar hemisphere right lung middle temporal gyrus Top expressed in genital tubercle granulocyte lumbar subsegment of spinal cord tail of embryo dentate gyrus of hippocampal formation granule cell ganglionic eminence superior frontal gyrus embryo ventricular zone primary visual cortex More reference expression data BioGPS More reference expression data
Gene ontology Molecular function G-quadruplex RNA binding RNA binding double-stranded DNA binding DNA-binding transcription factor activity Cellular component nuclear speck nucleus transcription elongation factor complex super elongation complex Biological process mRNA 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-templated Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 2334 14266 Ensembl ENSG00000155966 ENSMUSG00000031189 UniProt P51816 O55112 RefSeq (mRNA) NM_002025 NM_001169122 NM_001169123 NM_001169124 NM_001169125 NM_001170628 NM_008032 RefSeq (protein) NP_001162593 NP_001162594 NP_001162595 NP_001162596 NP_001164099 NP_002016 NP_032058 Location (UCSC) Chr X: 148.5 – 149 Mb Chr X: 68.4 – 68.91 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

AF4/FMR2 family member 2 is a protein that in humans is encoded by the AFF2 gene. ^[5] Mutations in AFF2 are implicated in cases of breast cancer. ^[6]

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. ^[7]

Genomics

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. ^[8] 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

1. GRCh38: Ensembl release 89: ENSG00000155966 – Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000031189 – Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. "Entrez Gene: AFF2 AF4/FMR2 family, member 2".
6. 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.
7. 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.
8. 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

• 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. 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.
• 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. 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, 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. PMC   1934615 . PMID   17196195.

External links

• Human AFF2 genome location and AFF2 gene details page in the UCSC Genome Browser .