FMR1 Gene: Fragile X Messenger Ribonucleoprotein 1
Genetic insights into FMR1-related disorders, including fragile X syndrome, FXTAS, and FXPOI.
Gene Information Card
| Symbol | FMR1 |
|---|---|
| Full Name | Fragile X Messenger Ribonucleoprotein 1 |
| Gene Type | Protein coding |
| Chromosomal Location | Xq27.3 |
| NCBI Gene ID | 2332 ncbi.nlm.nih.gov/gene/2332 |
| Ensembl ID | ENSG00000102081 |
| UniProt ID | Q06787 |
| OMIM ID | 309550 |
| HGNC ID | 3775 |
| Aliases | FMRP, FRAXA, POF, POF1, FMR1P |
Description
The FMR1 gene encodes the fragile X messenger ribonucleoprotein 1 (FMRP), an RNA-binding protein that regulates translation of specific mRNAs, playing a critical role in synaptic plasticity and neuronal development. Expansion of a CGG trinucleotide repeat in the 5' UTR of FMR1 leads to fragile X syndrome (full mutation >200 repeats) via promoter hypermethylation and gene silencing. Premutation alleles (55-200 repeats) cause fragile X-associated tremor/ataxia syndrome (FXTAS) and fragile X-associated primary ovarian insufficiency (FXPOI) through toxic RNA gain-of-function mechanisms.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Fragile X syndrome | Full CGG repeat expansion (>200) leading to promoter hypermethylation and transcriptional silencing, resulting in loss of FMRP function. | OMIM #300624; ClinVar; NCBI Gene |
| Fragile X-associated tremor/ataxia syndrome (FXTAS) | Premutation alleles (55-200 CGG repeats) produce elevated FMR1 mRNA with expanded CGG repeats, sequestering RNA-binding proteins and causing neuronal toxicity. | OMIM #300623; ClinVar; NCBI Gene |
| Fragile X-associated primary ovarian insufficiency (FXPOI) | Premutation alleles (55-200 CGG repeats) lead to altered FMR1 mRNA levels and repeat-associated non-AUG (RAN) translation, affecting ovarian function. | OMIM #311360; ClinVar; NCBI Gene |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | High |
| Testis | 8.2 | Medium |
| Ovary | 6.1 | Medium |
| Heart | 4.3 | Low |
| Liver | 2.0 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 15.3 | High expression; used in neuronal studies |
| HeLa (cervical carcinoma) | 7.8 | Moderate expression |
| HEK293 (embryonic kidney) | 5.4 | Low expression |
| MCF7 (breast cancer) | 3.2 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| CGG repeat expansion (full mutation >200) | Repeat expansion | ~1 in 4000 males; ~1 in 8000 females | Loss of FMRP expression; fragile X syndrome |
| CGG repeat expansion (premutation 55-200) | Repeat expansion | ~1 in 130-250 females; ~1 in 250-800 males | Elevated mRNA; FXTAS and FXPOI risk |
| Missense variants (e.g., p.Ile304Asn) | Missense | Rare | Impaired FMRP RNA-binding; intellectual disability |
| Deletions (partial or whole gene) | Deletion | Rare | Loss of FMRP; fragile X syndrome phenotype |
Mutation functional classification
Loss of Function (LOF)
Full CGG repeat expansions cause gene silencing and loss of FMRP, leading to fragile X syndrome. Missense mutations that disrupt RNA-binding or protein stability also result in loss of function.
Gain of Function (GOF)
Premutation alleles produce toxic gain-of-function via elevated FMR1 mRNA with expanded CGG repeats, leading to FXTAS and FXPOI through RNA toxicity and RAN translation.
Dominant Negative (DN)
Not well established; FMR1 is X-linked, and most pathogenic variants act via loss of function or gain of function rather than dominant-negative effects.
View complete mutation data：
Gene Ontology (GO)
| • RNA binding | • mRNA binding |
| • translation regulator activity | • poly(A) RNA binding |
| • ribosome binding | • cytoplasm |
| • dendrite | • synapse |
| • regulation of translation | • mRNA transport |
Pathways
• FMRP regulation of translation
• mRNA surveillance
• Synaptic signaling
• RNA transport
Protein Summary
FMRP is a 71 kDa RNA-binding protein that shuttles between nucleus and cytoplasm, associating with polyribosomes and regulating translation of target mRNAs. It contains two KH domains and an RGG box, which mediate RNA binding. FMRP is essential for synaptic plasticity, dendritic mRNA localization, and neuronal development. Loss of FMRP leads to altered synaptic protein synthesis, contributing to fragile X syndrome pathophysiology.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| FMR1 Knockout HEK293T Cell Line | EDJ-KQ215 | Human | 2332 | Details Get a Quote |
| FMR1 Knockout HEK293 Cell Line | EDJ-KQ3472 | Human | 2332 | Details Get a Quote |
| FMR1 Knockout A-549 Cell Line | EDJ-KQ25232 | Human | 2332 | Details Get a Quote |
| FMR1 Knockout HCT 116 Cell Line | EDJ-KQ25233 | Human | 2332 | Details Get a Quote |
| FMR1 Knockout HeLa Cell Line | EDJ-KQ25234 | Human | 2332 | Details Get a Quote |
| FMR1NB Knockout HEK293 Cell Line | EDJ-KQ52092 | Human | 158521 | Details Get a Quote |
| FMR1NB Knockout HeLa Cell Line | EDJ-KQ58787 | Human | 158521 | Details Get a Quote |
| FMR1NB Knockout A-549 Cell Line | EDJ-KQ67270 | Human | 158521 | Details Get a Quote |
| FMR1NB Knockout HCT 116 Cell Line | EDJ-KQ75670 | Human | 158521 | Details Get a Quote |
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