Locus FRA2A AFF3

Disease ID
FRA2A
Gene ID
AFF3
Updated
Jun 15, 2026
v2.22.0
Other gene loci
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Disease

Name Intellectual disability associated with fragile site FRA2A
Inheritance
Description
These expansions are associated with intellectual disability and clinical phenotypes such as delayed motor development or delays in speech/language .
Prevalence
1/862 (1/654-1266) population prevalence of methylated AFF3 expansions (mild cognitive disability) . Disease cases observed in South Australia .
Age of Onset Age of Onset(Typical)Years1  70  0
Early childhood (small sample size) .
HPO Terms
Association
MendelianRisk

Locus

Details
Allele ranges established in study of 3 families; intermediate alleles likely premutations . Pathogenic threshold may be higher than 300 as this was the largest allele that could be accurately sized by the assay.
Mechanism
LoF/methylation
Silencing of the FMR2 gene as a consequence of a CCG expansion located upstream of this gene .
Detection
Standard PCR has detected small alleles, while RP-PCR and Southern blotting have detected large expansions. Short-read sequencing may underestimate the size of large expansions and exact sizing usually uses long-read sequencing [@pmid:24763282; @pmid:39313615].
Year
2014
Location in Gene
Intron 3
Gene Strand

Alleles

Ref. Motif
GCC
Ranges BenignIntermediatePathogenicUnits3  200  0300  300
Benign (ref.)
Benign (gene)
Pathogenic (ref.)
GCC
Pathogenic (gene)
CGG
Unknown (ref.)
Unknown (gene)
Interruption (ref.)
Interruption (gene)

References

Direct supporting references for info on this page.

1
FRA2A is a CGG repeat expansion associated with silencing of AFF3.
Sofie,Metsu, Liesbeth,Rooms, Jacqueline,Rainger, Martin S,Taylor, Hemant,Bengani, David I,Wilson, Chandra Sekhar Reddy,Chilamakuri, Harris,Morrison, Geert,Vandeweyer, Edwin,Reyniers, Evelyn,Douglas, Geoffrey,Thompson, Eric,Haan, Jozef,Gecz, David R,Fitzpatrick, R Frank,Kooy
PLoS genetics · 2014-04-24
pmid:24763282
2
A phenome-wide association study of methylated GC-rich repeats identifies a GCC repeat expansion in AFF3 associated with intellectual disability.
Bharati,Jadhav, Paras,Garg, Joke J F A,van Vugt, Kristina,Ibanez, Delia,Gagliardi, William,Lee, Mariya,Shadrina, Tom,Mokveld, Egor,Dolzhenko, Alejandro,Martin-Trujillo, Scott J,Gies, Gabrielle,Altman, Clarissa,Rocca, Mafalda,Barbosa, Miten,Jain, Nayana,Lahiri, Katherine,Lachlan, Henry,Houlden, Benedict,Paten, Jan,Veldink, Arianna,Tucci, Andrew J,Sharp
Nature genetics · 2024-09-23
pmid:39313615

Additional Literature

Additional literature related to this locus.

Raw PubMed search results
(All PubMed results returned by searching for this gene, tandem repeats, and disease, in medline format)

A genome-wide approach for the discovery of novel repeat expansion disorders in the Undiagnosed Diseases Network cohort.
Sarah,Fazal, Harriet,Dashnow, Maike F,Dohrn, Jacquelyn,Raposo, Laurel,Hiatt, Matt C,Danzi, Isaac R L,Xu, Camilo,Toro, David R,Adams, Karen,Usdin, Bruce,Hayward, Shilpa Nadimpalli,Kobren, Shamil R,Sunyaev, Rebecca C,Spillmann, Vandana,Shashi, Adriana,Rebelo, Guney,Bademci, Mustafa,Tekin, Aaron R,Quinlan, Stephan,Zuchner
Genetics in medicine : official journal of the American College of Medical Genetics · 2025-05-22
pmid:40417743
A phenome-wide association study of methylated GC-rich repeats identifies a GCC repeat expansion in
Bharati,Jadhav, Paras,Garg, Joke J F A,van Vugt, Kristina,Ibanez, Delia,Gagliardi, William,Lee, Mariya,Shadrina, Tom,Mokveld, Egor,Dolzhenko, Alejandro,Martin-Trujillo, Scott L,Gies, Clarissa,Rocca, Mafalda,Barbosa, Miten,Jain, Nayana,Lahiri, Katherine,Lachlan, Henry,Houlden, Benedict,Paten, Jan,Veldink, Arianna,Tucci, Andrew J,Sharp
medRxiv : the preprint server for health sciences · 2023-12-12
pmid:37205357