AFF2
Homo sapiens
Gene Name: AF4/FMR2 family, member 2
Aliases: FMR2, FMR2P, FRAXE, MRX2, OX19
Chromosome No: X
Chromosome Band: Xq28
Genetic Category: Syndromic-Rare Single Gene variant
Associated Syndrome(s): Fragile X syndrome
Aliases: FMR2, FMR2P, FRAXE, MRX2, OX19
Chromosome No: X
Chromosome Band: Xq28
Genetic Category: Syndromic-Rare Single Gene variant
Associated Syndrome(s): Fragile X syndrome
Summary Statistics:
ASD Reports: 21
Recent Reports: 1
Annotated variants: 46
Associated CNVs: 12
Evidence score: 3
ASD Reports: 21
Recent Reports: 1
Annotated variants: 46
Associated CNVs: 12
Evidence score: 3
| Associated Disorders: |
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Relevance to Autism
Rare mutations in the AFF2 gene have been identified with autism and ADHD (Abrams et al., 1997) as well as with X-linked intellectual disability (XLID) (Stettner et al., 2011) and developmental and speech delay (Sahoo et al., 2011). In addition, this gene has been associated with syndromic autism, where a subpopulation of individuals with a given syndrome develop autism. In particular, a rare mutation in the AFF2 gene has been identified with fragile X syndrome (Moore et al., 1999).
Molecular Function
This gene encodes a putative transcriptional activator that is a member of the AF4FMR2 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 mental retardation. Alternate splicing results in multiple transcript variants.
External Links
References
Type
Title
Type of Disorder
Associated Disorders
Author, Year
Primary
Cognitive, behavioral, and neuroanatomical assessment of two unrelated male children expressing FRAXE.
ASD
ADHD
Support
Clinical Targeted Panel Sequencing Analysis in Clinical Evaluation of Children with Autism Spectrum Disorder in China
ASD
Support
Whole-exome sequencing and homozygosity analysis implicate depolarization-regulated neuronal genes in autism.
ASD
Support
AFF2 Is Associated With X-Linked Partial (Focal) Epilepsy With Antecedent Febrile Seizures
Epilepsy/seizures
Support
Microdeletion of Xq28 involving the AFF2 (FMR2) gene in two unrelated males with developmental delay.
DD
Support
Detection of clinically relevant genetic variants in autism spectrum disorder by whole-genome sequencing.
ASD
Support
Autism spectrum disorder and comorbid neurodevelopmental disorders (ASD-NDDs): Clinical and genetic profile of a pediatric cohort
ASD
DD, ID
Support
Familial intellectual disability and autistic behavior caused by a small FMR2 gene deletion.
XLID
Support
Using whole-exome sequencing to identify inherited causes of autism.
ASD
Support
Functional relationships between recessive inherited genes and genes with de novo variants in autism spectrum disorder
ASD
Support
Fragile X syndrome with FMR1 and FMR2 deletion.
Fragile X syndrome
MR, Epilepsy
Support
Rare complete knockouts in humans: population distribution and significant role in autism spectrum disorders.
ASD
Support
Genetic Diagnostic Evaluation of Trio-Based Whole Exome Sequencing Among Children With Diagnosed or Suspected Autism Spectrum Disorder.
ASD
DD/ID
Support
Analysis of the chromosome X exome in patients with autism spectrum disorders identified novel candidate genes, including TMLHE.
ASD
ID
Support
Whole genome sequencing resource identifies 18 new candidate genes for autism spectrum disorder
ASD
Support
Range of genetic mutations associated with severe non-syndromic sporadic intellectual disability: an exome sequencing study.
ID
Epilepsy, ASD
Support
Gene Mutation Analysis in 253 Chinese Children with Unexplained Epilepsy and Intellectual/Developmental Disabilities.
DD, ID, epilepsy/seizures
Recent Recommendation
Excess variants in AFF2 detected by massively parallel sequencing of males with autism spectrum disorder.
ASD
Rare
Variant ID
Variant Type
Allele Change
Residue Change
Inheritance Pattern
Inheritance Association
Family Type
Author, Year
GEN289R001
trinucleotide_repeat_microsatellite_feature
c.-460_-458GCC(6_25)
Familial
Maternal
Simplex
GEN289R002
trinucleotide_repeat_microsatellite_feature
c.-460_-458GCC(6_25)
Familial
Maternal
Simplex
GEN289R007
missense_variant
c.2539C>G
p.Pro847Ala
Familial
Maternal
Multiplex
GEN289R008
missense_variant
c.2140G>A
p.Asp714Asn
Familial
Maternal
Multiplex
GEN289R009
missense_variant
c.2780G>A
p.Arg927His
Familial
Maternal
Multiplex
GEN289R028
missense_variant
c.3634G>A
p.Val1212Ile
Familial
Maternal
Multi-generational
GEN289R029
trinucleotide_repeat_microsatellite_feature
c.-460_-458GCC(6_25)
Familial
Maternal
Simplex
GEN289R032a
frameshift_variant
c.511dup
p.Ser171LysfsTer28
Familial
Maternal
Simplex
GEN289R032b
frameshift_variant
c.527_528del
p.Gly176AlafsTer26
Familial
Maternal
Simplex
GEN289R034
frameshift_variant
c.2483dup
p.Glu829ArgfsTer5
Familial
Maternal
Simplex
Common
Variant ID
Polymorphism
SNP ID
Allele Change
Residue Change
Population Origin
Population Stage
Author, Year
GEN289C001
intron_variant
rs193241784
c.1074+4388T>A;c.1086+4388T>A;c.96+4388T>A
202 ASD cases from AGRE and SSC; controls from NIMH and EVS.
Discovery
