INT37351

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Context Info
Confidence 0.58
First Reported 1986
Last Reported 2010
Negated 0
Speculated 1
Reported most in Body
Documents 16
Total Number 19
Disease Relevance 9.60
Pain Relevance 0.56

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signal transduction (IKBKAP) nucleolus (IKBKAP) nucleus (IKBKAP)
protein complex assembly (IKBKAP) DNA binding (IKBKAP) cytoplasm (IKBKAP)
Anatomy Link Frequency
neuronal 1
neuron 1
peripheral nervous system 1
IKBKAP (Homo sapiens)
Pain Link Frequency Relevance Heat
Enkephalin 1 100.00 Very High Very High Very High
Peripheral nervous system 13 98.62 Very High Very High Very High
Inflammation 1 88.76 High High
Pain management 1 77.52 Quite High
cINOD 1 68.00 Quite High
Pain 24 64.60 Quite High
imagery 27 63.48 Quite High
Hsan 8 62.40 Quite High
unmyelinated 6 18.92 Low Low
Potency 16 5.00 Very Low Very Low Very Low
Disease Link Frequency Relevance Heat
Familial Dysautonomia 1828 100.00 Very High Very High Very High
Disease 158 98.40 Very High Very High Very High
Cognitive Disorder 21 96.08 Very High Very High Very High
INFLAMMATION 2 88.76 High High
Cancer 3 87.60 High High
Neuropathic Pain 21 87.04 High High
Rare Diseases 27 83.44 Quite High
Rheumatoid Arthritis 13 80.64 Quite High
Pain 24 77.52 Quite High
Gastric Motility Disorder 16 73.68 Quite High

Sentences Mentioned In

Key: Protein Mutation Event Anatomy Negation Speculation Pain term Disease term
In one of the past studies, IKBKAP expression level can be downregulated by RNAi in control cells [10], where there is no production of MU transcripts.
Negative_regulation (downregulated) of IKBKAP
1) Confidence 0.58 Published 2010 Journal PLoS ONE Section Body Doc Link PMC3004942 Disease Relevance 0.27 Pain Relevance 0
FD sphere cells display a strongly reduced IKBKAP exon 20 skipping
Negative_regulation (reduced) of IKBKAP exon 20 associated with familial dysautonomia
2) Confidence 0.51 Published 2010 Journal PLoS ONE Section Body Doc Link PMC3004942 Disease Relevance 0.38 Pain Relevance 0
The skipped isoform has a frameshift relative to the wild-type mRNA that results in a premature stop codon, leading to considerably reduced IKAP expression [9], [10].
Negative_regulation (reduced) of IKAP
3) Confidence 0.43 Published 2010 Journal PLoS ONE Section Body Doc Link PMC3012102 Disease Relevance 0.46 Pain Relevance 0.06
We found that in FD cell lines PS significantly raises IKAP mRNA and protein levels.
Negative_regulation (raises) of IKAP mRNA associated with familial dysautonomia
4) Confidence 0.43 Published 2010 Journal PLoS ONE Section Body Doc Link PMC3012102 Disease Relevance 0.63 Pain Relevance 0
We tested whether this drug could also modify the splicing defect of IKBKAP in FD hOE-MSC cells.
Negative_regulation (defect) of IKBKAP associated with familial dysautonomia
5) Confidence 0.43 Published 2010 Journal PLoS ONE Section Body Doc Link PMC3004942 Disease Relevance 0.56 Pain Relevance 0
Moreover, we showed that kinetin improved exon 20 inclusion and restores a normal level of IKAP/hELP1 in FD hOE-MSCs.
Negative_regulation (level) of IKAP/hELP1 associated with familial dysautonomia
6) Confidence 0.43 Published 2010 Journal PLoS ONE Section Abstract Doc Link PMC3004942 Disease Relevance 0.88 Pain Relevance 0
In order to establish a direct link between low levels of IKBKAP WT transcripts and decreased neuronal populations in FD patients, several groups have investigated transcriptome variations resulting from a reduced level of IKBKAP transcripts using microarray technology [10], [22], [34], [40], [53].
Negative_regulation (reduced) of IKBKAP in neuronal associated with familial dysautonomia
7) Confidence 0.43 Published 2010 Journal PLoS ONE Section Body Doc Link PMC3004942 Disease Relevance 0.15 Pain Relevance 0
This mutation leads to variable, tissue-specific skipping of exon 20 of IKBKAP mRNA, with the central and peripheral nervous system more prone to complete skipping than others tissues, which leads to reduced IKAP/hELP1 protein levels [8].
Negative_regulation (reduced) of IKAP/hELP1 in peripheral nervous system associated with peripheral nervous system
8) Confidence 0.42 Published 2010 Journal PLoS ONE Section Body Doc Link PMC3004942 Disease Relevance 0.61 Pain Relevance 0.11
This may mean that the IKAP protein is directly or indirectly involved in cell cycle checkpoint regulation, and the reduced levels of IKAP in FD cells results in abnormal growth of cells.
Negative_regulation (reduced) of IKAP associated with familial dysautonomia
9) Confidence 0.38 Published 2010 Journal PLoS ONE Section Body Doc Link PMC3012102 Disease Relevance 0.81 Pain Relevance 0
Thus, these results confirmed a decreased level of IKBKAP transcripts (WT+MU) in FD cells.
Negative_regulation (level) of IKBKAP associated with familial dysautonomia
10) Confidence 0.37 Published 2010 Journal PLoS ONE Section Body Doc Link PMC3004942 Disease Relevance 0.36 Pain Relevance 0
Second, a potential source of variability among transcriptome analyses derives from the technical manipulations employed to downregulate IKBKAP (presence of the FD mutation in its original context compared to WT IKBKAP knockdown using different interfering RNAs), resulting in differential residual IKBKAP/IKAP expression.
Negative_regulation (downregulate) of IKBKAP associated with familial dysautonomia
11) Confidence 0.37 Published 2010 Journal PLoS ONE Section Body Doc Link PMC3004942 Disease Relevance 0.32 Pain Relevance 0
The specificity of neuron loss in FD is poorly understood due to the lack of an appropriate model system.
Negative_regulation (loss) of FD in neuron associated with familial dysautonomia
12) Confidence 0.37 Published 2010 Journal PLoS ONE Section Abstract Doc Link PMC3004942 Disease Relevance 0.64 Pain Relevance 0
Thus, these results confirmed a decreased level of IKBKAP transcripts (WT+MU) in FD cells.
Negative_regulation (decreased) of IKBKAP associated with familial dysautonomia
13) Confidence 0.37 Published 2010 Journal PLoS ONE Section Body Doc Link PMC3004942 Disease Relevance 0.36 Pain Relevance 0
After comparing the migration pattern of 3 control and 3 FD hOE-MSCs in serum medium and serum-free medium (ITS), we determined that FD cells invasion is significantly reduced compared to control cells both in serum and in ITS medium (Figure 5).


Negative_regulation (reduced) of FD associated with familial dysautonomia
14) Confidence 0.37 Published 2010 Journal PLoS ONE Section Body Doc Link PMC3004942 Disease Relevance 0.74 Pain Relevance 0
Previous studies have shown that i) IKBKAP exon 20 is poorly defined in a “healthy” context, due to the presence of a weak 3?
Negative_regulation (defined) of IKBKAP exon 20
15) Confidence 0.37 Published 2010 Journal PLoS ONE Section Body Doc Link PMC3004942 Disease Relevance 0.51 Pain Relevance 0
Thus, to investigate the involvement of candidate disease mechanisms in FD and to test whether differences in gene expression are stably imprinted in FD compared to control hOE-MSCs, we explored the transcriptome of these cells at very early (P1, P2) and later (P5, P9) cell passages with the same samples used to quantify IKBKAP transcripts.
Spec (whether) Negative_regulation (imprinted) of FD associated with familial dysautonomia and disease
16) Confidence 0.37 Published 2010 Journal PLoS ONE Section Body Doc Link PMC3004942 Disease Relevance 0.59 Pain Relevance 0.03
Recently, RNA interference studies have shown that depletion of IKAP, and thus Elongator, results in reduced transcriptional elongation of several target genes via histone H3 hypoacetylation.
Negative_regulation (depletion) of IKAP
17) Confidence 0.20 Published 2007 Journal Orphanet J Rare Dis Section Body Doc Link PMC2098750 Disease Relevance 0.78 Pain Relevance 0.06
These compounds are effective inhibitors of human enkephalin degrading aminopeptidase, microsomal leucine aminopeptidase (EC 3.4.11.2), and cytosolic leucine aminopeptidase (EC 3.4.11.1) at micro- to nanomolar concentrations.
Negative_regulation (inhibitors) of EC 3.4.11.2 associated with enkephalin
18) Confidence 0.15 Published 1986 Journal Biochemistry Section Abstract Doc Link 3516217 Disease Relevance 0 Pain Relevance 0.10
Aminopeptidase-N/CD13 (EC 3.4.11.2) inhibitors: chemistry, biological evaluations, and therapeutic prospects.
Negative_regulation (inhibitors) of EC 3.4.11.2
19) Confidence 0.11 Published 2006 Journal Med Res Rev Section Title Doc Link 16216010 Disease Relevance 0.56 Pain Relevance 0.19

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