Reviewed January 2014
What is the official name of the AFF2 gene?
The official name of this gene is “AF4/FMR2 family member 2.”
AFF2 is the gene's official symbol. The AFF2 gene is also known by other names, listed below.
What is the normal function of the AFF2 gene?
The AFF2 gene provides instructions for making a protein that is found in the nucleus of cells but whose function is not well understood. Some studies suggest that it acts as a transcription factor, which means that it attaches (binds) to specific regions of DNA and helps control the activity of other genes, although the identity of these genes is unknown. Other studies show that the protein can attach to specific regions of messenger RNA (mRNA), which is a chemical cousin of DNA that serves as the genetic blueprint for protein production. It is thought that the AFF2 protein helps control the process by which the mRNA blueprint is cut and rearranged to produce different versions of proteins (alternative splicing).
One region of the AFF2 gene contains a particular DNA segment known as a CCG trinucleotide repeat, so called because this segment of three DNA building blocks (nucleotides) is repeated multiple times within the gene. In most people, the number of CCG repeats ranges from 4 to about 40.
How are changes in the AFF2 gene related to health conditions?
- fragile XE syndrome - caused by mutations in the AFF2 gene
Mutations in the AFF2 gene cause fragile XE syndrome, a condition characterized by mild intellectual disability and learning difficulties. Nearly all cases are caused by a mutation called a CCG trinucleotide repeat expansion, in which the CCG trinucleotide is abnormally repeated more than 200 times, which makes this region of the gene unstable. As a result, the AFF2 gene is turned off (silenced), and no protein is produced from it. It is unclear how a shortage of this protein leads to problems with intellectual functioning.
Rarely, small deletions of genetic material from the AFF2 gene are associated with fragile XE syndrome, although how these deletions affect the protein and lead to intellectual disability is unknown.
Where is the AFF2 gene located?
Cytogenetic Location: Xq28
Molecular Location on the X chromosome: base pairs 148,500,619 to 149,000,663
(Homo sapiens Annotation Release 107, GRCh38.p2) (NCBI (http://www.ncbi.nlm.nih.gov/gene/2334))
The AFF2 gene is located on the long (q) arm of the X chromosome at position 28.
More precisely, the AFF2 gene is located from base pair 148,500,619 to base pair 149,000,663 on the X chromosome.
See How do geneticists indicate the location of a gene? (http://ghr.nlm.nih.gov/handbook/howgeneswork/genelocation) in the Handbook.
Where can I find additional information about AFF2?
You and your healthcare professional may find the following resources about AFF2 helpful.
You may also be interested in these resources, which are designed for genetics professionals and researchers.
- PubMed - Recent literature (http://www.ncbi.nlm.nih.gov/pubmed?term=%28AFF2%5BTIAB%5D%29%20OR%20%28%28FMR2%5BTIAB%5D%29%20OR%20%28FMR2P%5BTIAB%5D%29%20OR%20%28fragile%20X%20mental%20retardation%202%20protein%5BTIAB%5D%29%20OR%20%28FRAXE%5BTIAB%5D%29%29%20AND%20%28%28Genes%5BMH%5D%29%20OR%20%28Genetic%20Phenomena%5BMH%5D%29%29%20AND%20english%5Bla%5D%20AND%20human%5Bmh%5D%20AND%20%22last%201080%20days%22%5Bdp%5D)
- OMIM - Genetic disorder catalog (http://omim.org/entry/300806)
Research Resources - Tools for researchers
- HGNC Gene Family: AF4/FMR2 family (http://www.genenames.org/cgi-bin/genefamilies/set/1145)
- HGNC Gene Symbol Report (http://www.genenames.org/cgi-bin/gene_symbol_report?q=data/hgnc_data.php&hgnc_id=3776)
- NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/2334)
What other names do people use for the AFF2 gene or gene products?
- AF4/FMR2 family, member 2
- fragile X E mental retardation syndrome protein
- fragile X mental retardation 2 protein
- protein FMR-2
See How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.
What glossary definitions help with understanding AFF2?
alternative splicing ;
mental retardation ;
messenger RNA ;
transcription factor ;
You may find definitions for these and many other terms in the Genetics Home Reference
- OMIM: AF4/FMR2 FAMILY, MEMBER 2 (http://omim.org/entry/300806)
- Bensaid M, Melko M, Bechara EG, Davidovic L, Berretta A, Catania MV, Gecz J, Lalli E, Bardoni B. FRAXE-associated mental retardation protein (FMR2) is an RNA-binding protein with high affinity for G-quartet RNA forming structure. Nucleic Acids Res. 2009 Mar;37(4):1269-79. doi: 10.1093/nar/gkn1058. Epub 2009 Jan 9. (http://www.ncbi.nlm.nih.gov/pubmed/19136466?dopt=Abstract)
- Gecz J, Gedeon AK, Sutherland GR, Mulley JC. Identification of the gene FMR2, associated with FRAXE mental retardation. Nat Genet. 1996 May;13(1):105-8. (http://www.ncbi.nlm.nih.gov/pubmed/8673085?dopt=Abstract)
- Gécz J, Oostra BA, Hockey A, Carbonell P, Turner G, Haan EA, Sutherland GR, Mulley JC. FMR2 expression in families with FRAXE mental retardation. Hum Mol Genet. 1997 Mar;6(3):435-41. (http://www.ncbi.nlm.nih.gov/pubmed/9147647?dopt=Abstract)
- Gecz J. The FMR2 gene, FRAXE and non-specific X-linked mental retardation: clinical and molecular aspects. Ann Hum Genet. 2000 Mar;64(Pt 2):95-106. Review. (http://www.ncbi.nlm.nih.gov/pubmed/11246464?dopt=Abstract)
- Hillman MA, Gecz J. Fragile XE-associated familial mental retardation protein 2 (FMR2) acts as a potent transcription activator. J Hum Genet. 2001;46(5):251-9. (http://www.ncbi.nlm.nih.gov/pubmed/11355014?dopt=Abstract)
- Knight SJ, Flannery AV, Hirst MC, Campbell L, Christodoulou Z, Phelps SR, Pointon J, Middleton-Price HR, Barnicoat A, Pembrey ME, et al. Trinucleotide repeat amplification and hypermethylation of a CpG island in FRAXE mental retardation. Cell. 1993 Jul 16;74(1):127-34. (http://www.ncbi.nlm.nih.gov/pubmed/8334699?dopt=Abstract)
- Melko M, Bardoni B. The role of G-quadruplex in RNA metabolism: involvement of FMRP and FMR2P. Biochimie. 2010 Aug;92(8):919-26. doi: 10.1016/j.biochi.2010.05.018. Epub 2010 Jun 4. Review. (http://www.ncbi.nlm.nih.gov/pubmed/20570707?dopt=Abstract)
- Melko M, Douguet D, Bensaid M, Zongaro S, Verheggen C, Gecz J, Bardoni B. Functional characterization of the AFF (AF4/FMR2) family of RNA-binding proteins: insights into the molecular pathology of FRAXE intellectual disability. Hum Mol Genet. 2011 May 15;20(10):1873-85. doi: 10.1093/hmg/ddr069. Epub 2011 Feb 17. (http://www.ncbi.nlm.nih.gov/pubmed/21330300?dopt=Abstract)
- NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/2334)
- Stettner GM, Shoukier M, Höger C, Brockmann K, Auber B. Familial intellectual disability and autistic behavior caused by a small FMR2 gene deletion. Am J Med Genet A. 2011 Aug;155A(8):2003-7. doi: 10.1002/ajmg.a.34122. Epub 2011 Jul 7. (http://www.ncbi.nlm.nih.gov/pubmed/21739600?dopt=Abstract)
The resources on this site should not be used as a substitute for
professional medical care or advice. Users seeking information about
a personal genetic disease, syndrome, or condition should consult with a qualified
See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.