AFF2

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]

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

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.