FMR1

Chr XXLDX-linked

fragile X messenger ribonucleoprotein 1

Also known as: FMRP, FRAXA, POF, POF1

NCBI Gene: 2332ENSG00000102081UniProt: Q06787OMIM: 309550

The protein binds RNA and regulates mRNA trafficking from the nucleus to the cytoplasm. Mutations causing CGG trinucleotide repeat expansions (>55 repeats) in the 5' UTR lead to fragile X syndrome, fragile X tremor/ataxia syndrome, and premature ovarian failure through loss of function, with X-linked inheritance. The mechanism involves loss of protein function when repeat expansions exceed the normal range of 6-53 copies.

OMIMResearchSummary from RefSeq, OMIM, UniProt, Mechanism
MultiplemechanismXLD/X-linkedLOEUF 0.423 OMIM phenotypes
Clinical Summary— FMR1
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Gene-Disease Validity (ClinGen)
fragile X syndrome · XLDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.65) — some intolerance to loss-of-function variants.
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Clinical Trials
7 active or recruiting trials — potential therapeutic options may be available
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint
0.42LOEUF
pLI 0.647
Z-score 3.73
OE 0.20 (0.10–0.42)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
2.97Z-score
OE missense 0.47 (0.41–0.55)
118 obs / 250.4 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.20 (0.10–0.42)
0≤0.351.4
Missense OE0.47 (0.41–0.55)
0≤0.61.4
Synonymous OE0.80
0≤1.21.6
LoF obs/exp: 5 / 25.2Missense obs/exp: 118 / 250.4Syn Z: 1.40
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveFMR1-related fragile X syndromeLOFXLR
definitiveFMR1-related fragile X tremor/ataxia syndromeGOFXLR
definitiveFMR1-related premature ovarian failure syndromeOTHERmonoallelic_X_heterozygous
DN
0.5081th %ile
GOF
0.4972th %ile
LOF
0.66top 25%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.42

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

FMR1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Fragile X Syndrome (FXS)Autism Spectrum Disorder

Group CBT in Adolescents With Fragile X Syndrome and in Adolescents With Autism Spectrum Disorder

RECRUITING
NCT06677866Phase NABambino Gesù Hospital and Research InstituteStarted 2022-09-01
Cognitive behavioral therapyWaiting List
Primary Ovarian Insufficiency

Investigation of Copy Number Variations and Genetic Variants in POI

RECRUITING
NCT05327283Ospedale Policlinico San MartinoStarted 2012-01-31
Fragile X Syndrome (FXS)Creatine Transporter Deficiency

Optical Imaging in X-linked Disorders.

RECRUITING
NCT06868979Phase NAHospices Civils de LyonStarted 2026-03-30
Clinical assessmentParental questionnairesCognitive assessment
Invasive PreNatal Diagnosis in a Context of Family History of Single-gene Disorders, IncludingSickle Cell DiseaseCystic Fibrosis

Development of Non-Invasive Prenatal Diagnosis for Single Gene Disorders

RECRUITING
NCT06147414Assistance Publique - Hôpitaux de ParisStarted 2024-10-23
Blood sample
FMR1 Gene Premutation

Assessment of Ovarian Reserve in Patients With Fragile X Premutation

RECRUITING
NCT07039734Assistance Publique - Hôpitaux de ParisStarted 2025-07-04
collection of data from medical records
Fragile X Syndrome

Effect of CANnabidiol on Anxiety and GABAergic Function in Individuals with Fragile-X Syndrome

NOT YET RECRUITING
NCT06261502Phase PHASE2Université de SherbrookeStarted 2025-05-01
CBD Oral SolutionPlacebo
Fragile X SyndromeAutism Spectrum DisorderAutistic Disorder

Alpha Auditory Entrainment for Cognitive Enhancement and Sensory Hypersensitivity in Youth With Developmental Disorders

RECRUITING
NCT06227780Phase NAChildren's Hospital Medical Center, CincinnatiStarted 2023-05-24
Alpha Auditory EntrainmentSham
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients