AFF2

Chr XXLR

ALF transcription elongation factor 2

Also known as: FMR2, FMR2P, FRAXE, MRX2, OX19, XLID109

NCBI Gene: 2334 ENSG00000155966 UniProt: P51816 OMIM: 300806

This RNA-binding protein is involved in alternative splicing regulation and is highly constrained against loss-of-function variants (pLI 0.996, LOEUF 0.275). Mutations cause X-linked intellectual developmental disorder 109 (Fragile X E syndrome), a form of nonsyndromic cognitive disability resulting from expansion of GCC repeats in the gene that leads to gene silencing. The condition follows X-linked recessive inheritance.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a putative transcriptional activator that is a member of the AF4\FMR2 gene family. This gene is associated with the folate-sensitive fragile X E locus on chromosome X. A repeat polymorphism in the fragile X E locus results in silencing of this gene causing Fragile X E syndrome. Fragile X E syndrome is a form of nonsyndromic X-linked cognitive disability. In addition, this gene contains 6-25 GCC repeats that are expanded to >200 repeats in the disease state. Alternate splicing results in multiple transcript variants.[provided by RefSeq, Jul 2016]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Intellectual developmental disorder, X-linked 109MIM #309548

XLR

Clinical highlights

Gene-disease validity (ClinGen)

non-syndromic X-linked intellectual disability · XLDefinitivesufficient evidence for diagnostic panels

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

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P/LP submissions

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P/LP missense

0.28

LOEUF· LoF intol.

LOF

Mechanism· predicted