FMR1

Chr XXLDX-linked

fragile X messenger ribonucleoprotein 1

Also known as: FMRP, FRAXA, POF, POF1

NCBI Gene: 2332ENSG00000102081UniProt: Q06787

The protein encoded by this gene binds RNA and is associated with polysomes. The encoded protein may be involved in mRNA trafficking from the nucleus to the cytoplasm. A trinucleotide repeat (CGG) in the 5' UTR is normally found at 6-53 copies, but an expansion to 55-230 repeats is the cause of fragile X syndrome. Expansion of the trinucleotide repeat may also cause one form of premature ovarian failure (POF1). Multiple alternatively spliced transcript variants that encode different protein isoforms and which are located in different cellular locations have been described for this gene. [provided by RefSeq, May 2010]

Primary Disease Associations & Inheritance

Fragile X syndromeMIM #300624
XLD
Fragile X tremor/ataxia syndromeMIM #300623
XLD
Premature ovarian failure 1MIM #311360
X-linked
611
ClinVar variants
96
Pathogenic / LP
0.65
pLI score
7
Active trials
Clinical Summary— FMR1
⚡
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.65) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
96 Pathogenic / Likely Pathogenic· 48 VUS of 611 total submissions
💊
Clinical Trials
7 active or recruiting trials — potential therapeutic options may be available
Some data sources returned errors (1)

pubmed: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esummary.fcgi

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
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?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
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?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.20 (0.10–0.42)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.47 (0.41–0.55)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.80
0≤1.21.6
LoF obs/exp: 5 / 25.2Missense obs/exp: 118 / 250.4Syn Z: 1.40

ClinVar Variant Classifications

611 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic86
Likely Pathogenic10
VUS48
Likely Benign18
Benign59
Conflicting4
86
Pathogenic
10
Likely Pathogenic
48
VUS
18
Likely Benign
59
Benign
4
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
1
0
85
0
86
Likely Pathogenic
2
3
5
0
10
VUS
0
36
11
1
48
Likely Benign
0
7
3
8
18
Benign
0
0
58
1
59
Conflicting
—4
Total34616210225

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in 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.

Gene2Phenotype Curations

FMR1-related fragile X syndrome

definitive
Monoallelic X HemizygousLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

FMR1-related fragile X tremor/ataxia syndrome

definitive
Monoallelic X HemizygousGain Of FunctionAltered Gene Product Structure
Dev. Disorders
G2P ↗

FMR1-related premature ovarian failure syndrome

definitive
Monoallelic X HeterozygousUndeterminedUncertain
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Fragile X syndrome

MIM #300624

Molecular basis of disorder known

X-linked dominant

Fragile X tremor/ataxia syndrome

MIM #300623

Molecular basis of disorder known

X-linked dominant

Premature ovarian failure 1

MIM #311360

Molecular basis of disorder known

X-linked
Clinical Literature
Landmark / reviewRecent case evidence
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
A new mechanism regulating microglial NLRP3 inflammasome: FMR1 mediates NLRP3 mRNA stability.
Deng Q et al.·PLoS One
2026🔓 Open AccessFunctional
T2-FLAIR hyperintensities in the inferior cerebellar peduncles and their association with clinical symptoms, molecular and MRI markers in male FMR1 premutation carriers.
Elias-Mas A et al.·Front Mol Neurosci
2026🔓 Open Access
A human electrophysiological signature of Fragile X pathophysiology is shared in V1 of Fmr1-/y mice.
Kornfeld-Sylla SS et al.·Nat Commun
2026🔓 Open Access
Cognitive dysfunction in women with the FMR1 premutation during midlife: The LASSI-L reveals curvilinear CGG-dependent risk buffered by college education.
Klusek J et al.·J Alzheimers Dis
2026🔓 Open Access
FMR1 RNA interaction with DNMT1 blocks DNA methylation at the FMR1 locus.
Nobile V et al.·NAR Mol Med
2026🔓 Open Access
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
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 Syndrome (FXS)Creatine Transporter Deficiency

Optical Imaging in X-linked Disorders.

NOT YET RECRUITING
NCT06868979Phase NAHospices Civils de LyonStarted 2025-03
Clinical assessmentParental questionnairesCognitive assessment
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
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
Primary Ovarian Insufficiency

Investigation of Copy Number Variations and Genetic Variants in POI

RECRUITING
NCT05327283Ospedale Policlinico San MartinoStarted 2012-01-31

External Resources

Links to major genomics databases and tools