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50 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
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FMR1
fragile X messenger ribonucleoprotein 1
Chromosome X Β· Xq27.3
NCBI Gene: 2332Ensembl: ENSG00000102081.17HGNC: HGNC:3775UniProt: Q06787
923PubMed Papers
23Diseases
0Drugs
27Pathogenic Variants
FUNCTIONAL ROLE
DNA RepairHub GeneTransporter
RESEARCH IMPACT
Highly Studied
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
membraneless organelle assemblysiRNA bindingpositive regulation of intracellular transport of viral materialmiRNA bindingfragile X syndromefragile X-associated tremor/ataxia syndromepremature ovarian failure 1Intellectual disability
✦AI Summary

FMR1 encodes FMRP (Fragile X Mental Retardation Protein), an RNA-binding protein that regulates multiple cellular processes including translation, synaptic plasticity, and RNA metabolism 1. The protein contains motifs characteristic of RNA-binding proteins and shuttles between cytoplasm and nucleus via a functional nuclear localization signal 1. FMRP plays critical roles in nuclear function including chrX dynamics and non-canonical nucleic acid structure formation 2. The FMR1 gene contains polymorphic CGG repeats in its 5' UTR that are essential for normal neuronal function, regulating mRNA localization, cellular stress responses, and glucocorticoid receptor signaling 3. CGG repeat expansions cause distinct disease phenotypes: full mutations (>200 repeats) lead to gene silencing and Fragile X syndrome, while smaller expansions result in aberrant splicing producing the FMR1-217 isoform and premutation-associated disorders 4. FMRP absence impairs synaptic maturation and causes neuronal hyperexcitability 1. Emerging evidence suggests FMR1 also regulates cellular metabolism with potential implications for cancer biology 5. Clinically, FMR1 mutations cause a spectrum of disorders including intellectual disability, autism-like features, premature ovarian failure, and late-onset tremor/ataxia syndrome 16.

Sources cited
1
FMRP is an RNA-binding protein with nuclear localization signal that shuttles between cytoplasm and nucleus, and its absence impairs synaptic maturation
PMID: 11180223
2
CGG repeats in FMR1 5' UTR regulate mRNA localization, cellular stress responses, and glucocorticoid receptor signaling in neurons
PMID: 38865241
3
CGG expansions cause aberrant splicing producing FMR1-217 isoform in fragile X syndrome tissues
PMID: 37364131
4
FMRP plays important roles in nuclear function including chromatin dynamics and non-canonical nucleic acid structure formation
PMID: 39796070
5
Emerging evidence suggests FMR1 involvement in regulating cellular metabolism with implications for cancer biology
PMID: 40563420
6
FMR1 mutations are associated with premature ovarian failure and reproductive health outcomes
PMID: 27432256
Disease Associationsβ“˜23
fragile X syndromeOpen Targets
0.81Strong
fragile X-associated tremor/ataxia syndromeOpen Targets
0.70Strong
premature ovarian failure 1Open Targets
0.65Moderate
Intellectual disabilityOpen Targets
0.51Moderate
primary ovarian insufficiencyOpen Targets
0.48Moderate
genetic disorderOpen Targets
0.47Moderate
type 2 diabetes mellitusOpen Targets
0.33Weak
Autistic behaviorOpen Targets
0.27Weak
adolescent idiopathic scoliosisOpen Targets
0.18Weak
femur fractureOpen Targets
0.17Weak
Neurodevelopmental abnormalityOpen Targets
0.11Weak
autismOpen Targets
0.11Weak
neoplasmOpen Targets
0.11Weak
attention deficit hyperactivity disorderOpen Targets
0.10Weak
colorectal carcinomaOpen Targets
0.10Suggestive
breast cancerOpen Targets
0.09Suggestive
Alzheimer diseaseOpen Targets
0.09Suggestive
schizophreniaOpen Targets
0.09Suggestive
melanomaOpen Targets
0.09Suggestive
cancerOpen Targets
0.09Suggestive
Fragile X syndromeUniProt
Fragile X tremor/ataxia syndromeUniProt
Premature ovarian failure 1UniProt
Pathogenic Variants27
NM_002024.6(FMR1):c.1062dup (p.His355fs)Pathogenic
not provided|Intellectual disability
β˜…β˜…β˜†β˜†2024β†’ Residue 355
NM_002024.6(FMR1):c.271-1G>ALikely pathogenic
Inborn genetic diseases
β˜…β˜†β˜†β˜†2025
NM_002024.6(FMR1):c.210_211dup (p.Ala71fs)Pathogenic
Fragile X syndrome
β˜…β˜†β˜†β˜†2024β†’ Residue 71
NM_002024.6(FMR1):c.498_500del (p.Tyr166_Gln167delinsTer)Likely pathogenic
Fragile X syndrome
β˜…β˜†β˜†β˜†2024β†’ Residue 166
NM_002024.6(FMR1):c.1276-1202G>ALikely pathogenic
Fragile X syndrome
β˜…β˜†β˜†β˜†2023
NM_002024.6(FMR1):c.1375A>T (p.Lys459Ter)Pathogenic
Fragile X syndrome
β˜…β˜†β˜†β˜†2023β†’ Residue 459
NM_002024.6(FMR1):c.990+1G>TPathogenic
not provided
β˜…β˜†β˜†β˜†2022
NM_002024.6(FMR1):c.1268_1269del (p.Tyr423fs)Likely pathogenic
Fragile X syndrome
β˜…β˜†β˜†β˜†2022β†’ Residue 423
NM_002024.6(FMR1):c.1411C>T (p.Arg471Ter)Pathogenic
not provided
β˜…β˜†β˜†β˜†2022β†’ Residue 471
NM_002024.6(FMR1):c.866C>T (p.Pro289Leu)Likely pathogenic
See cases
β˜…β˜†β˜†β˜†2021β†’ Residue 289
NM_002024.6(FMR1):c.1184G>A (p.Trp395Ter)Likely pathogenic
Fragile X syndrome
β˜…β˜†β˜†β˜†2020β†’ Residue 395
NM_002024.6(FMR1):c.104+5G>CLikely pathogenic
not provided
β˜…β˜†β˜†β˜†2019
NM_002024.6(FMR1):c.797G>A (p.Gly266Glu)Likely pathogenic
Inborn genetic diseases
β˜…β˜†β˜†β˜†2019β†’ Residue 266
NM_002024.6(FMR1):c.-128GGC[55_200]Pathogenic
Premature ovarian failure 1|Fragile X-associated tremor/ataxia syndrome
β˜…β˜†β˜†β˜†2017
NM_002024.6(FMR1):c.990+1G>APathogenic
Intellectual disability|Nonpapillary renal cell carcinoma
β˜…β˜†β˜†β˜†2016
NM_002024.6(FMR1):c.420-8A>GPathogenic
Intellectual disability
β˜…β˜†β˜†β˜†2016
NM_002024.6(FMR1):c.1256A>G (p.Tyr419Cys)Likely pathogenic
not provided
β˜…β˜†β˜†β˜†2016β†’ Residue 419
NM_002024.6(FMR1):c.199-2A>GLikely pathogenic
Intellectual disability;Autistic behavior|Nonpapillary renal cell carcinoma
β˜…β˜†β˜†β˜†2015
GRCh38/hg38 Xq27.3(chrX:147933767-147951004)x0Pathogenic
See cases
β˜…β˜†β˜†β˜†2011
NM_002024.6(FMR1):c.1622_1636del (p.Gln541_Gly545del)Likely pathogenic
Fragile X-associated tremor/ataxia syndrome
β˜†β˜†β˜†β˜†2022β†’ Residue 541
View on ClinVar β†—
Related Genes
DICER1Protein interaction100%TNRC6AProtein interaction100%AGO1Protein interaction100%EIF4EProtein interaction100%HNRNPA2B1Protein interaction100%RNMTProtein interaction100%
Tissue Expression6 tissues
Bone Marrow
100%
Brain
96%
Liver
75%
Ovary
66%
Heart
63%
Lung
43%
Gene Interaction Network
Click a node to explore
FMR1DICER1TNRC6AAGO1EIF4EHNRNPA2B1RNMT
PROTEIN STRUCTURE
Preparing viewer…
PDB2QND Β· 1.90 Γ… Β· X-ray
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
0.41Moderately Constrained
pLIβ“˜
1.00Intolerant
Observed/Expected LoF0.26 [0.17–0.41]
RankingsWhere FMR1 stands among ~20K protein-coding genes
  • #188of 20,598
    Most Researched923 Β· top 1%
  • #1,880of 5,498
    Most Pathogenic Variants27
  • #2,086of 17,882
    Most Constrained (LOEUF)0.41 Β· top quartile
Genes detectedFMR1
Sources retrieved50 papers
Response timeβ€”
πŸ“„ Sources
50β–Ό
1
CGG repeats in the human FMR1 gene regulate mRNA localization and cellular stress in developing neurons.
PMID: 38865241
Cell Rep Β· 2024
1.00
2
FMR1 Premutation: Basic Mechanisms and Clinical Involvement.
PMID: 27338822
Cerebellum Β· 2016
0.92
3
Antisense oligonucleotide rescue of CGG expansion-dependent
PMID: 37364131
Proc Natl Acad Sci U S A Β· 2023
0.90
4
FMRP ribonucleoprotein complexes and RNA homeostasis.
PMID: 32560791
Adv Genet Β· 2020
0.84
5
Premature ovarian failure and the FMR1 gene.
PMID: 11299521
Semin Reprod Med Β· 2000
0.82