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AFF2 gene
URL of this page: https://medlineplus.gov/genetics/gene/aff2/

AFF2 gene

ALF transcription elongation factor 2

Normal Function

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 6 to about 30.

Health Conditions Related to Genetic Changes

Fragile XE syndrome

Variants (also called 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 variant 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.

More About This Health Condition

Other Names for This Gene

  • AFF2_HUMAN
  • FMR2
  • FMR2P
  • FRAXE
  • MRX2

Additional Information & Resources

Tests Listed in the Genetic Testing Registry

Scientific Articles on PubMed

Catalog of Genes and Diseases from OMIM

Gene and Variant Databases

References

  • 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. Citation on PubMed or Free article on PubMed Central
  • 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. doi: 10.1038/ng0596-105. Citation on PubMed
  • Gecz 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. doi: 10.1093/hmg/6.3.435. Citation on PubMed
  • 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. doi: 10.1017/S0003480000007983. Citation on PubMed
  • 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. doi: 10.1007/s100380170074. Citation on PubMed
  • 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. doi: 10.1016/0092-8674(93)90300-f. Citation on PubMed
  • 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. Citation on PubMed
  • 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. Citation on PubMed
  • Stettner GM, Shoukier M, Hoger 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. Citation on PubMed

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