INT151543

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Context Info
Confidence 0.48
First Reported 2007
Last Reported 2010
Negated 2
Speculated 4
Reported most in Body
Documents 56
Total Number 60
Disease Relevance 19.40
Pain Relevance 1.65

This is a graph with borders and nodes. Maybe there is an Imagemap used so the nodes may be linking to some Pages.

transport (Fmr1) RNA binding (Fmr1) nucleus (Fmr1)
cytoplasm (Fmr1)
Anatomy Link Frequency
brain 15
dendrites 2
liver 1
cerebellum 1
hippocampus 1
Fmr1 (Mus musculus)
Fmr1 - I304N (17)
Pain Link Frequency Relevance Heat
Hippocampus 95 98.84 Very High Very High Very High
cerebral cortex 20 98.58 Very High Very High Very High
Lasting pain 1 97.48 Very High Very High Very High
gABA 3 97.36 Very High Very High Very High
Glutamate receptor 157 97.32 Very High Very High Very High
Glutamate 3 97.00 Very High Very High Very High
addiction 1 96.64 Very High Very High Very High
agonist 319 91.48 High High
Anterior cingulate cortex 5 84.24 Quite High
depression 41 27.20 Quite Low
Disease Link Frequency Relevance Heat
Intellectual Impairment 463 100.00 Very High Very High Very High
Disease 336 99.76 Very High Very High Very High
Autoimmune Disease 69 99.60 Very High Very High Very High
Syndrome 779 99.34 Very High Very High Very High
Repression 81 98.52 Very High Very High Very High
Congenital Anomalies 135 97.90 Very High Very High Very High
Liver Disease 186 97.64 Very High Very High Very High
Fragile X Syndrome 778 97.60 Very High Very High Very High
Pain 38 97.48 Very High Very High Very High
Targeted Disruption 1159 97.32 Very High Very High Very High

Sentences Mentioned In

Key: Protein Mutation Event Anatomy Negation Speculation Pain term Disease term
It has been reported that FMRP can bind a G-quartet motif in the coding sequence of its own mRNA, inhibiting its translation [65].
FMRP Binding (bind) of
1) Confidence 0.48 Published 2009 Journal PLoS Genetics Section Body Doc Link PMC2779495 Disease Relevance 0.19 Pain Relevance 0
We analyzed the ability of endogenous I304N-FMRP to heterodimerize in mouse brain by immunoprecipitating I304N protein and assaying for co-precipitating FXR1P and FXR2P by Western blot.
I304N-FMRP (I304N) Spec (analyzed) Binding (heterodimerize) of in brain
2) Confidence 0.48 Published 2009 Journal PLoS Genetics Section Body Doc Link PMC2779495 Disease Relevance 0 Pain Relevance 0
This suggests that FMRP must interact with polyribosomes or kissing-complex RNAs for normal mGluR-LTD regulation.
FMRP Binding (interact) of
3) Confidence 0.48 Published 2009 Journal PLoS Genetics Section Body Doc Link PMC2779495 Disease Relevance 0.17 Pain Relevance 0.04
A common theme associated with these diverse cellular roles is that a critical function of FMRP is binding to specific RNA targets.
FMRP Binding (binding) of
4) Confidence 0.48 Published 2009 Journal PLoS Genetics Section Body Doc Link PMC2779495 Disease Relevance 0.05 Pain Relevance 0
Several attempts have been made to assess the effect of the I304N mutation on FMRP RNA binding and function.
FMRP RNA Binding (binding) of
5) Confidence 0.48 Published 2009 Journal PLoS Genetics Section Body Doc Link PMC2779495 Disease Relevance 0 Pain Relevance 0
FMRP also binds to kissing complex sites [18], but APP mRNA lacks such a site.
FMRP Binding (binds) of
6) Confidence 0.47 Published 2007 Journal PLoS Biology Section Body Doc Link PMC1808499 Disease Relevance 0.06 Pain Relevance 0.03
In addition, FMRP binds to uridine-rich mRNAs [19,20].
FMRP Binding (binds) of
7) Confidence 0.47 Published 2007 Journal PLoS Biology Section Body Doc Link PMC1808499 Disease Relevance 0.21 Pain Relevance 0.04
Our data suggest that physical interactions between FMRP and APP mRNA underlie translational repression, with mGluR activation rapidly moderating these events.
FMRP Binding (interactions) of associated with repression
8) Confidence 0.47 Published 2007 Journal PLoS Biology Section Body Doc Link PMC1808499 Disease Relevance 0.16 Pain Relevance 0
Our data indicate that postsynaptic FMRP binds to and regulates the translation of APP mRNA through metabotropic glutamate receptor activation and suggests a possible link between Alzheimer disease and fragile X syndrome.


FMRP Binding (binds) of associated with syndrome, glutamate receptor and alzheimer's dementia
9) Confidence 0.47 Published 2007 Journal PLoS Biology Section Abstract Doc Link PMC1808499 Disease Relevance 1.61 Pain Relevance 0.13
Presumably, the loss of FMRP/APP mRNA interaction results in rapid, pulsatile protein expression in dendrites.


FMRP Binding (interaction) of in dendrites
10) Confidence 0.47 Published 2007 Journal PLoS Biology Section Body Doc Link PMC1808499 Disease Relevance 0.15 Pain Relevance 0
Taken together, our findings suggest that future studies should consider how autoimmunity in the mothers may interact with the FMR1 mutation to disrupt critical networks in the brain, particularly GABA and glutamate systems or perhaps through other mechanisms leading to clinical seizures, tics, and behavioral problems in their offspring with FXS.
FMR1 Binding (interact) of in brain associated with glutamate, gaba, tics, convulsion, autoimmune disease and syndrome
11) Confidence 0.46 Published 2010 Journal Hum Genet Section Body Doc Link PMC2955238 Disease Relevance 1.65 Pain Relevance 0.10
Generation of the Fmr1I304N mouse provides a new model for understanding molecular defects in the disease, for screening potential therapies, and heightens interest in identifying FMRP-RNA interactions in the brain.


FMRP Binding (interactions) of in brain associated with disease
12) Confidence 0.42 Published 2009 Journal PLoS Genetics Section Body Doc Link PMC2779495 Disease Relevance 0.19 Pain Relevance 0
The conclusion that I304N FMRP KH2 domain fails to bind RNA in vivo is consistent with structural studies of several RNA-binding proteins suggesting that this mutation should affect RNA binding.
I304N FMRP (I304N) Binding (bind) of
13) Confidence 0.42 Published 2009 Journal PLoS Genetics Section Body Doc Link PMC2779495 Disease Relevance 0 Pain Relevance 0
Recombinant I304N-FMRP produced in insect cells has been shown to bind to G-quartet RNA, but not the kissing complex RNA [51].
I304N-FMRP (I304N) Binding (bind) of
14) Confidence 0.42 Published 2009 Journal PLoS Genetics Section Body Doc Link PMC2779495 Disease Relevance 0 Pain Relevance 0
A Mouse Model of the Human Fragile X Syndrome I304N Mutation

The mental retardation, autistic features, and behavioral abnormalities characteristic of the Fragile X mental retardation syndrome result from the loss of function of the RNA┬ľbinding protein FMRP.

FMRP Binding (binding) of in Mouse associated with autism, intellectual impairment, syndrome, congenital anomalies and fragile x syndrome
15) Confidence 0.42 Published 2009 Journal PLoS Genetics Section Title Doc Link PMC2779495 Disease Relevance 0.96 Pain Relevance 0
This is consistent with our observation that I304N-FMRP in mouse brain fails to crosslink to kcRNA, but retains other activities, including the ability to crosslink to G-quartet RNA and to heterodimerize with FXR1P and FXR2P (Figure 7).
I304N-FMRP (I304N) Binding (crosslink) of in brain
16) Confidence 0.42 Published 2009 Journal PLoS Genetics Section Body Doc Link PMC2779495 Disease Relevance 0 Pain Relevance 0
Alterations in the association of FMRP with polyribosomes, small nontranslated RNAs, or other proteins have all been proposed [9,12,37,38].
FMRP Binding (association) of
17) Confidence 0.41 Published 2007 Journal PLoS Biology Section Body Doc Link PMC1808499 Disease Relevance 0.40 Pain Relevance 0.06
Therefore a major biochemical defect in the Fmr1I304N mouse is the loss of KH2-dependent RNA binding.
Fmr1I304N Binding (binding) of
18) Confidence 0.37 Published 2009 Journal PLoS Genetics Section Body Doc Link PMC2779495 Disease Relevance 0.15 Pain Relevance 0
The endogenous I304N-FMRP complex is abnormally small due to loss of RNA binding by mutant FMRP
I304N-FMRP (I304N) Binding (complex) of
19) Confidence 0.37 Published 2009 Journal PLoS Genetics Section Body Doc Link PMC2779495 Disease Relevance 0 Pain Relevance 0
I304N FMRP is defective in polyribosome association and RNA binding
I304N FMRP (I304N) Binding (binding) of
20) Confidence 0.37 Published 2009 Journal PLoS Genetics Section Body Doc Link PMC2779495 Disease Relevance 0 Pain Relevance 0

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