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AFF2

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AFF2
Identifiers
AliasesAFF2, FMR2, FMR2P, FRAXE, MRX2, OX19, AF4/FMR2 family member 2, XLID109
External IDsOMIM: 300806; MGI: 1202294; HomoloGene: 136314; GeneCards: AFF2; OMA:AFF2 - orthologs
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_008032

RefSeq (protein)

NP_032058

Location (UCSC)Chr X: 148.5 – 149 MbChr X: 68.4 – 68.91 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/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

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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

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  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000155966Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000031189Ensembl, 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

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