Book a test
On this page
⚠ Educational content only Not medical or genetic advice. Speak with a healthcare provider or genetic counsellor before acting on anything here.

FMR1

fragile X messenger ribonucleoprotein 1

The FMR1 gene provides instructions for producing the FMRP protein, which is vital for normal brain development, particularly in regulating synaptic plasticity, learning, and memory. The FMR1 gene is crucial for synthesising the fragile X messenger ribonucleoprotein (FMRP).

Chromosome Xq27.3 X-linked HGNC:3775 Tier C
FMR1 Xq27.3 p arm q arm X

FMR1 is located on the long (q) arm of chromosome X, at band Xq27.3. Arm ratio per GRCh38 - banding schematic.

Explore chromosome X in the library →

Available at Jeen Health

Clinical tests that include this

Carrier Screening panel
FMR1 is 1 of 1,008 genes on this panel
Expanded carrier screening for recessive and X-linked conditions

Overview

The FMR1 gene, or fragile X messenger ribonucleoprotein 1, encodes the FMRP protein. This protein is widely present across various tissues, including the brain, testes, and ovaries. In the brain, FMRP is particularly involved in the development of connections between nerve cells, known as synapses, which are essential for communication within the nervous system. FMRP's function is closely linked to regulating synaptic plasticity, a process allowing synapses to adapt and change over time, fundamental for learning and memory.

What the gene does

FMRP functions within cells as a shuttle for messenger RNA (mRNA) molecules, transporting them from the cell's nucleus to regions where proteins are assembled. It also helps control when the genetic instructions carried by these mRNA molecules are used to create proteins. Some of these proteins are important for the proper functioning of nerve cells, and potentially also for the testes and ovaries, although its precise role in these reproductive tissues is less understood. This regulatory role in protein synthesis and mRNA transport is crucial for normal cellular processes and development.

Video: Genetics 101

Chromosome location

The FMR1 gene is located on the long (q) arm of the X chromosome at position 27.3, specifically Xq27.3. This chromosomal location indicates its X-linked inheritance pattern.

Protein structure

The FMRP protein is 632 amino acids long and contains several distinct regions and domains crucial for its function. The N-terminal region from amino acids 1-184 is required for nuclear localisation and includes two Agenet-like domains: Agenet-like 1 (amino acids 4-50) and Agenet-like 2 (amino acids 63-115). A region from amino acids 172-211 is necessary for interaction with CYFIP1, CYFIP2, FXR1, and FXR2. Further along, there are two K-homology (KH) domains, KH 1 (amino acids 222-251) and KH 2 (amino acids 285-314). Disordered regions are present at amino acids 325-349 and 443-632. A region from amino acids 397-491 is required for nuclear export, containing a Nuclear export signal motif (amino acids 424-443). Interaction with RANBP9 occurs in the region spanning amino acids 419-632. Additionally, an RNA-binding RGG-box is found from amino acids 534-548, alongside two Nucleolar localisation signal motifs at amino acids 527-534 and 613-617.

Domain map · 632 amino acids
Agenet-like 1 (4–50)Agenet-like 2 (63–115)KH 1 (222–251)KH 2 (285–314)Interaction with RANBP9 (419–632)Nuclear export signal (424–443)Nucleolar localization signal 1 (527–534)Nucleolar localization signal 2 (613–617)Agenet-like 14–50Agenet-like 263–115Interaction with RANBP419–6321~316632
Domain - independent functional unit
Region - functional region
Motif - short conserved sequence
🧬 Explore 3D structure on AlphaFold
UniProt:Q06787Length:632 aaStructure:AlphaFold

Key variants

Genetic variations in the FMR1 gene typically involve an expansion of a CGG trinucleotide repeat sequence. The number of these repeats determines the clinical outcome. A normal range usually consists of fewer than 40 repeats. Expansions beyond this can lead to different clinical presentations, affecting protein production and function.

The table below shows the top 10 pathogenic or likely-pathogenic variants currently classified in ClinVar for FMR1.
View all on ClinVar →

Sample of pathogenic variants

10 pathogenic / likely-pathogenic variants from ClinVar, ranked by review status (expert-panel-reviewed first). This is a sample; recurrent founder variants in a specific population may not appear here - see the full ClinVar listing via the link above.

Variant (HGVS) Protein change Classification Evidence Associated condition
c.1062dup
Duplication
 p.His355fs Pathogenic/Likely pathogenic ★★☆☆ Intellectual disability
GRCh38/hg38 Xq27.3(chrX:147933767-147951004)x0
copy number loss
 - Pathogenic ★☆☆☆ See cases
g.(?_147030199)_(147046357_?)del
Deletion
 - Pathogenic ★☆☆☆ Intellectual disability
c.1375A>T
single nucleotide variant
 p.Lys459Ter Pathogenic ★☆☆☆ Fragile X syndrome
c.1411C>T
single nucleotide variant
 p.Arg471Ter Pathogenic ★☆☆☆ not provided
c.210_211dup
Microsatellite
 p.Ala71fs Pathogenic ★☆☆☆ Fragile X syndrome
c.420-8A>G
single nucleotide variant
 - Pathogenic ★☆☆☆ Intellectual disability
c.990+1G>A
single nucleotide variant
 - Pathogenic ★☆☆☆ Intellectual disability
c.990+1G>T
single nucleotide variant
 - Pathogenic ★☆☆☆ not provided
c.663del
Deletion
 p.Glu221fs Pathogenic - Intellectual disability

Evidence stars indicate ClinVar review status. Individual variant interpretation should always be performed by a qualified clinical laboratory - many variants remain classified as Variants of Uncertain Significance (VUS) pending more research.

Associated conditions

Variations in the FMR1 gene are linked to a spectrum of conditions, primarily caused by the number of CGG repeats. These include Fragile X syndrome, which is the most common inherited cause of intellectual disability. Other related conditions are Fragile X-associated tremor/ataxia (FXTAS), characterised by neurological symptoms, and Fragile X-associated primary ovarian insufficiency (FXPOI), which affects ovarian function and can lead to Premature ovarian insufficiency (genetic).

Inheritance pattern

Conditions caused by pathogenic FMR1 variants typically follow x-linked inheritance.

♀ Carrier mother 1 altered X ♂ Unaffected father Typical Y Carrier daughter Unaffected daughter Affected son Unaffected son Affected Carrier Unaffected Circles = females · Squares = males

X-linked recessive: sons of a carrier mother have a 50% chance of being affected. Daughters have a 50% chance of being carriers.

Carrier frequency by population How common is heterozygous FMR1 carrier status across ancestry groups?

UK clinical status

The FMR1 gene is recognised in the UK by the NHS Genomic Medicine Service. It is listed on the 'DDG2P' panel for developmental disorders and the 'Intellectual disability' panel, both with a 'green' status, indicating that there is strong evidence for its association with human disease and it is routinely considered for testing.

Green-listed
High evidence · clinically actionable in NHS testing
Included in NHS GMS signed-off panels
DDG2P NHS GMS → Intellectual disability NHS GMS →
NHS Genomic Medicine Service Jeen carrier screening

Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory

Frequently asked questions

What is the FMR1 gene?

The FMR1 gene provides the genetic instructions for creating the FMRP protein. This protein is essential for normal brain development, particularly for synaptic function, learning, and memory.

What conditions are associated with changes in the FMR1 gene?

Changes in the FMR1 gene, particularly expansions of a CGG repeat, can lead to Fragile X syndrome, Fragile X-associated tremor/ataxia (FXTAS), and Fragile X-associated primary ovarian insufficiency (FXPOI).

How is Fragile X syndrome inherited?

Fragile X syndrome follows an X-linked inheritance pattern. This means the gene is located on the X chromosome, and its inheritance differs between males and females.

References

  1. Ma L, Herren AW, Espinal G. Composition of the Intranuclear Inclusions of Fragile X-associated Tremor/Ataxia Syndrome. Acta neuropathologica communications. 2019. PMID: 31481131
  2. Kim K, Hessl D, Randol JL. Association between IQ and FMR1 protein (FMRP) across the spectrum of CGG repeat expansions. PloS one. 2019. PMID: 31891607
  3. Hagerman RJ, Protic D, Rajaratnam A. Fragile X-Associated Neuropsychiatric Disorders (FXAND). Frontiers in psychiatry. 2018. PMID: 30483160
  4. Wang JY, Hessl D, Hagerman RJ. Abnormal trajectories in cerebellum and brainstem volumes in carriers of the fragile X premutation. Neurobiology of aging. 2017. PMID: 28391068
  5. Wheeler A, Raspa M, Hagerman R. Implications of the FMR1 Premutation for Children, Adolescents, Adults, and Their Families. Pediatrics. 2017. PMID: 28814538
  6. Hagerman RJ, Berry-Kravis E, Hazlett HC. Fragile X syndrome. Nature reviews. Disease primers. 2017. PMID: 28960184
  7. Todd PK, Oh SY, Krans A. CGG repeat-associated translation mediates neurodegeneration in fragile X tremor ataxia syndrome. Neuron. 2013. PMID: 23602499
  8. Hagerman R, Hagerman P. Advances in clinical and molecular understanding of the FMR1 premutation and fragile X-associated tremor/ataxia syndrome. The Lancet. Neurology. 2013. PMID: 23867198
  9. Li Y, Jin P. RNA-mediated neurodegeneration in fragile X-associated tremor/ataxia syndrome. Brain research. 2012. PMID: 22459047
  10. Hessl D, Wang JM, Schneider A. Decreased fragile X mental retardation protein expression underlies amygdala dysfunction in carriers of the fragile X premutation. Biological psychiatry. 2011. PMID: 21783174
  11. Hunsaker MR, Greco CM, Spath MA. Widespread non-central nervous system organ pathology in fragile X premutation carriers with fragile X-associated tremor/ataxia syndrome and CGG knock-in mice. Acta neuropathologica. 2011. PMID: 21785977
  12. Wittenberger MD, Hagerman RJ, Sherman SL. The FMR1 premutation and reproduction. Fertility and sterility. 2007. PMID: 17074338
  13. Tassone F, Beilina A, Carosi C. Elevated FMR1 mRNA in premutation carriers is due to increased transcription. RNA (New York, N.Y.). 2007. PMID: 17283214
  14. Bretherick KL, Fluker MR, Robinson WP. FMR1 repeat sizes in the gray zone and high end of the normal range are associated with premature ovarian failure. Human genetics. 2005. PMID: 16078053
  15. Jacquemont S, Hagerman RJ, Leehey MA. Penetrance of the fragile X-associated tremor/ataxia syndrome in a premutation carrier population. JAMA. 2004. PMID: 14747503
  16. Adam MP, Bick S, Mirzaa GM. FMR1 Disorders. 1993. PMID: 20301558
Educational content. This page is not medical or genetic advice, is not individually reviewed by a clinician for each reader, and should not replace a consultation with a qualified healthcare professional or genetic counsellor. If you are considering genetic testing or acting on a test result, book a consultation.
Data sources Last updated 13 September 2026. Content compiled from HGNC · MedlinePlus Genetics · ClinGen · Genomics England PanelApp · NHS National Genomic Test Directory · ClinVar · UniProt · AlphaFold .