INT287580

Context Info Confidence 0.00 First Reported 2009 Last Reported 2009 Negated 0 Speculated 0 Reported most in Body Documents 1 Total Number 4 Disease Relevance 0.29 Pain Relevance 0

RNA binding (Mex3c) nucleus (Mex3c) biological_process (Mex3c) cytoplasm (Mex3c)

Mex3c (Mus musculus)

Pain Link Frequency Relevance Heat agonist 28 5.00 Glutamate receptor 8 5.00 Hippocampus 8 5.00 depression 4 5.00 Pain 4 5.00 nMDA receptor antagonist 4 5.00 alcohol 4 5.00 Immobilon 4 5.00 isoflurane 4 5.00 imagery 4 5.00

Disease Link Frequency Relevance Heat Fragile X Syndrome 84 78.88 Targeted Disruption 36 77.08 Disease 36 38.72 Liver Disease 20 10.88 Glycogen Storage Disease 8 8.48 Intellectual Impairment 36 5.00 Li-fraumeni Syndrome 20 5.00 Anxiety Disorder 20 5.00 Autism 16 5.00 Convulsion 16 5.00

Sentences Mentioned In

Key:

Protein

Mutation

Event

Anatomy

Negation

Speculation

Pain term

Disease term

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.

KH2 Binding (bind) of

1) Confidence 0.00 Published 2009 Journal PLoS Genetics Section Body Doc Link PMC2779495 Disease Relevance 0 Pain Relevance 0

RGG-domain RNA binding to RNA over 200nt is not evident in the I304N mouse, suggesting either that it plays a minor or dependent role to KH2 binding to large RNAs.

KH2 Binding (binding) of

2) Confidence 0.00 Published 2009 Journal PLoS Genetics Section Body Doc Link PMC2779495 Disease Relevance 0.14 Pain Relevance 0

This finding suggests that loss of FMRP activity, including but not necessarily limited to KH2 RNA binding, may play a critical role in leading to the synaptic defects evident in the mouse, and, presumably, in human patients.

KH2 Binding (binding) of

3) Confidence 0.00 Published 2009 Journal PLoS Genetics Section Body Doc Link PMC2779495 Disease Relevance 0 Pain Relevance 0

While other interpretations cannot be ruled out, including the loss of KH2-dependent interaction with a protein partner, taken together our data suggest that the resulting loss of polysome association and, presumably, proper regulation of translation of FMRP mRNA targets, is most likely to contribute to the phenotype of the Fmr1I304N mouse.

KH2 Binding (interaction) of

4) Confidence 0.00 Published 2009 Journal PLoS Genetics Section Body Doc Link PMC2779495 Disease Relevance 0.15 Pain Relevance 0

General Comments

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