FRAXE AFF2

1-4/100,000 males²; 1/50-100,000 males, more than 50 families³. Found in populations around the globe, including in the UK, US, Canada, Taiwan, Germany, Greece, Cyprus, Spain, and Finland³.

Age of Onset Details

Typical: 2-10³. Range: 1-10; developmental delays without physical features can make onset difficult to detect until schooling⁴.

Locus

hg19

chrX:147582124-147582273

hg38

chrX:148500604-148500753

t2t

chrX:146765190-146765342

Details

Allele ranges (benign:4-39; pathogenic: >200) inferred from The Human Gene Mutation Database⁵. Intermediate alleles correspond to a premutation⁶. Non-canonical motifs include: CGG/CCT/GTG/CAG/CTG3^7,8.

Mechanism

LoF

Loss of function via transcriptional silencing^9,10.

Year

1993¹¹

Location in Gene

5' UTR

Gene Strand

Alleles

Ref. Motif

GCC

Pathogenic (ref.)

GCC

Pathogenic (gene)

CCG

gnomAD

Pathogenic genotype frequency data is not displayed for this locus because a substantial number of large alleles failed manual review by the gnomAD team.

References

Direct supporting references for info on this page.

Ontology Lookup Service (OLS)

mondo:0010659

Fragile XE syndrome: MedlinePlus Genetics

url:medlineplus.gov/genetics/condition/fragile-xe-syndrome

The FMR2 gene, FRAXE and non-specific X-linked mental retardation: clinical and molecular aspects.

J,Gecz

Annals of human genetics · 2000-03-01

pmid:11246464

omim:309548

Resources for Genetics Professionals — Genetic Disorders Caused by Nucleotide Repeat Expansions and Contractions

Stephanie E.,Wallace, Lora JH,Bean

GeneReviews® [Internet] · 2022-10-20

genereviews:NBK535148

Development and validation of a multiplex-PCR assay for X-linked intellectual disability.

Paula,Jorge, Bárbara,Oliveira, Isabel,Marques, Rosário,Santos

BMC medical genetics · 2013-08-05

pmid:23914978

Comprehensive genetic diagnosis of tandem repeat expansion disorders with programmable targeted nanopore sequencing.

Igor,Stevanovski, Sanjog R,Chintalaphani, Hasindu,Gamaarachchi, James M,Ferguson, Sandy S,Pineda, Carolin K,Scriba, Michel,Tchan, Victor,Fung, Karl,Ng, Andrea,Cortese, Henry,Houlden, Carol,Dobson-Stone, Lauren,Fitzpatrick, Glenda,Halliday, Gianina,Ravenscroft, Mark R,Davis, Nigel G,Laing, Avi,Fellner, Marina,Kennerson, Kishore R,Kumar, Ira W,Deveson

Science advances · 2022-03-04

pmid:35245110

Simultaneous Screening of the FRAXA and FRAXE Loci for Rapid Detection of FMR1 CGG and/or AFF2 CCG Repeat Expansions by Triplet-Primed PCR.

Timing,Liu, Furene S,Wang, Felicia S H,Cheah, Yanghong,Gu, Marie,Shaw, Hai-Yang,Law, Stacey K H,Tay, Caroline G,Lee, David L,Nelson, Jozef,Gecz, Samuel S,Chong

The Journal of molecular diagnostics : JMD · 2021-06-07

pmid:34111553

Diseases of unstable repeat expansion: mechanisms and common principles.

Jennifer R,Gatchel, Huda Y,Zoghbi

Nature reviews. Genetics · 2005-10-01

pmid:16205714

Clinical and neuroimaging review of triplet repeat diseases.

Ryo,Kurokawa, Mariko,Kurokawa, Akihiko,Mitsutake, Moto,Nakaya, Akira,Baba, Yasuhiro,Nakata, Toshio,Moritani, Osamu,Abe

Japanese journal of radiology · 2022-09-28

pmid:36169768

Trinucleotide repeat amplification and hypermethylation of a CpG island in FRAXE mental retardation.

S J,Knight, A V,Flannery, M C,Hirst, L,Campbell, Z,Christodoulou, S R,Phelps, J,Pointon, H R,Middleton-Price, A,Barnicoat, M E,Pembrey

Cell · 1993-07-16

pmid:8334699

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)

Association of Non-Coding Repeat Expansions with Parkinson's Disease Risk: Evidence from a UK Biobank-Based Whole-Genome Sequencing Study.

Zhen,Hu, Qin-Qin,Yan, Jing-Jin,Wan, Yu,Fan, Jun,Liu

Movement disorders : official journal of the Movement Disorder Society · 2025-10-11

pmid:41074692

Behavioural, psychiatric, and cognitive phenotypes associated with numbers of repeats of the FRAXE allele on the FMR2 gene.

Jean,Golding, Marcus E,Pembrey, Rosie,Clark, Yasmin,Iles-Caven, Steven,Gregory, Susan M,Ring, Sarah,Ennis, Matthew,Suderman

Wellcome open research · 2025-04-30

pmid:40708890

Dongfang,Zou, Bing,Qin, Jie,Wang, Yiwu,Shi, Peng,Zhou, Yonghong,Yi, Jianxiang,Liao, Xinguo,Lu

Frontiers in molecular neuroscience · 2022-03-30

pmid:35431806

Distribution of FMR1 and FMR2 Repeats in Argentinean Patients with Primary Ovarian Insufficiency.

Lucía Daniela,Espeche, Violeta,Chiauzzi, Ianina,Ferder, Mehrnoosh,Arrar, Andrea Paula,Solari, Carlos David,Bruque, Marisol,Delea, Susana,Belli, Cecilia Soledad,Fernández, Noemí Delia,Buzzalino, Eduardo Hernán,Charreau, Liliana Beatriz,Dain

Genes · 2017-08-16

pmid:28812997

Point mutation frequency in the FMR1 gene as revealed by fragile X syndrome screening.

Maximilian,Handt, Andrea,Epplen, Sabine,Hoffjan, Kemal,Mese, Jörg T,Epplen, Gabriele,Dekomien

Molecular and cellular probes · 2014-08-27

pmid:25171808

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

Crystallographic characterization of CCG repeats.

Agnieszka,Kiliszek, Ryszard,Kierzek, Wlodzimierz J,Krzyzosiak, Wojciech,Rypniewski

Nucleic acids research · 2012-06-19

pmid:22718980

Familial intellectual disability and autistic behavior caused by a small FMR2 gene deletion.

Georg M,Stettner, Moneef,Shoukier, Christoph,Höger, Knut,Brockmann, Bernd,Auber

American journal of medical genetics. Part A · 2011-07-07

pmid:21739600

Distribution of CGG/GCC repeats at the FMR1 and FMR2 genes in an Indian population with mental retardation of unknown etiology.

Lavanya,Katikala, Mallikarjuna R,Guruju, Sujatha,Madireddi, Omsairamesh,Vallamkonda, Nagaratna,Vallamkonda, Amarjyothi,Persha, Anandaraj M P J,Spurgeon

Genetic testing and molecular biomarkers · 2011-01-23

pmid:21254876