INT229794

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Context Info
Confidence 0.65
First Reported 2008
Last Reported 2010
Negated 0
Speculated 1
Reported most in Body
Documents 2
Total Number 25
Disease Relevance 11.68
Pain Relevance 1.31

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

Golgi apparatus (RAB7A) GTPase activity (RAB7A) lysosome (RAB7A)
Anatomy Link Frequency
nucleus 1
vesicle 1
RAB7A (Homo sapiens)
RAB7A - Q67L (1)
Pain Link Frequency Relevance Heat
Hsan 94 96.96 Very High Very High Very High
imagery 122 95.56 Very High Very High Very High
Peripheral nervous system 24 72.96 Quite High
Pain 76 48.52 Quite Low
Demyelination 25 42.48 Quite Low
Congenital analgesia 24 5.00 Very Low Very Low Very Low
Nerve growth factor 24 5.00 Very Low Very Low Very Low
unmyelinated 2 5.00 Very Low Very Low Very Low
Spinal cord 1 5.00 Very Low Very Low Very Low
lancinating pain 1 5.00 Very Low Very Low Very Low
Disease Link Frequency Relevance Heat
Disease 1848 99.98 Very High Very High Very High
Hereditary Sensory And Autonomic Neuropathies 101 96.96 Very High Very High Very High
Necrosis 5 88.48 High High
Infection 6 88.00 High High
Neuropathic Pain 37 77.68 Quite High
Charcot Marie Tooth Disease 150 70.40 Quite High
Mouth Disease 48 69.28 Quite High
Peripheral Neuropathy 25 64.56 Quite High
Muscle Weakness 27 58.36 Quite High
Frailty 1 54.00 Quite High

Sentences Mentioned In

Key: Protein Mutation Event Anatomy Negation Speculation Pain term Disease term
In addition, fusion of autophagic vacuoles with lysosomes requires Rab7 activity (11,12).
Positive_regulation (requires) of Rab7
1) Confidence 0.65 Published 2010 Journal Human Molecular Genetics Section Body Doc Link PMC2830827 Disease Relevance 0.27 Pain Relevance 0.04
Unregulated Rab7 cycling and accumulation of activated Rab7
Positive_regulation (activated) of Rab7
2) Confidence 0.65 Published 2010 Journal Human Molecular Genetics Section Body Doc Link PMC2830827 Disease Relevance 0.48 Pain Relevance 0
However, we show that the increased activation of mutant Rab7 is counterbalanced by unregulated, GTP hydrolysis-independent membrane cycling.
Positive_regulation (activation) of Rab7
3) Confidence 0.65 Published 2010 Journal Human Molecular Genetics Section Abstract Doc Link PMC2830827 Disease Relevance 0.47 Pain Relevance 0.05
To account for this, we documented that unregulated activation of Rab7 disease mutants is mitigated by unregulated inactivation.
Positive_regulation (activation) of Rab7 associated with disease
4) Confidence 0.65 Published 2010 Journal Human Molecular Genetics Section Body Doc Link PMC2830827 Disease Relevance 0.48 Pain Relevance 0
We report that misregulation of Rab7 activation results in an increase in the active fraction of Rab7 and abnormal retention on target membranes.
Positive_regulation (increase) of Rab7
5) Confidence 0.65 Published 2010 Journal Human Molecular Genetics Section Body Doc Link PMC2830827 Disease Relevance 0.46 Pain Relevance 0
Unregulated Rab7 cycling and accumulation of activated Rab7
Positive_regulation (accumulation) of Rab7
6) Confidence 0.65 Published 2010 Journal Human Molecular Genetics Section Body Doc Link PMC2830827 Disease Relevance 0.48 Pain Relevance 0
We showed that disease mutations result in an increase in the active fraction of Rab7 and a corresponding increase in binding to a subset of effector proteins.
Positive_regulation (increase) of Rab7 associated with disease
7) Confidence 0.65 Published 2010 Journal Human Molecular Genetics Section Body Doc Link PMC2830827 Disease Relevance 0.46 Pain Relevance 0
Specifically, we demonstrate significantly increased interaction of both Rab7 disease mutants with ORP1L, a well-characterized effector of active Rab7 that facilitates retrograde trafficking of late endosomes (36), and Vps13C, which also shows increased binding to the Q67L mutant and is likely a mediator of active Rab7 function.
Positive_regulation (mediator) of Rab7 associated with disease
8) Confidence 0.65 Published 2010 Journal Human Molecular Genetics Section Body Doc Link PMC2830827 Disease Relevance 0.34 Pain Relevance 0
Furthermore, the increased interaction with Vps13C and the GTP-dependent interactor ORP1L seen in disease mutants and in the Q67L mutant provides additional support for an increase in the active fraction of mutant Rab7.


Positive_regulation (increase) of Rab7 associated with disease
9) Confidence 0.57 Published 2010 Journal Human Molecular Genetics Section Body Doc Link PMC2830827 Disease Relevance 0.60 Pain Relevance 0
In contrast, the constitutively active Q67L mutant Rab7 colocalizes with LAMP2, but leads to prominent accumulation of enlarged vesicles that cluster adjacent to the nucleus (Fig. 5A, middle).
Positive_regulation (active) of Rab7 (Q67L) in nucleus
10) Confidence 0.47 Published 2010 Journal Human Molecular Genetics Section Body Doc Link PMC2830827 Disease Relevance 0.46 Pain Relevance 0
In activated regions of the cell, a majority of the activated Rab7 is membrane-bound and thus the fluorescence loss after photoactivation (FLAP) specifically measures the rate of extraction of Rab7 from its target vesicle membranes.
Positive_regulation (activated) of Rab7 in vesicle
11) Confidence 0.47 Published 2010 Journal Human Molecular Genetics Section Body Doc Link PMC2830827 Disease Relevance 0.28 Pain Relevance 0
The amount of Rab7 disease-causing mutants pulled down by GST-RILP was significantly increased compared with wild-type Rab7 (Fig. 3D and E).
Positive_regulation (increased) of Rab7 associated with disease
12) Confidence 0.47 Published 2010 Journal Human Molecular Genetics Section Body Doc Link PMC2830827 Disease Relevance 0.43 Pain Relevance 0
Mutant Rab7 undergoes GEF-independent nucleotide exchange and excessive activation
Positive_regulation (activation) of Rab7
13) Confidence 0.47 Published 2010 Journal Human Molecular Genetics Section Body Doc Link PMC2830827 Disease Relevance 0.31 Pain Relevance 0
Rab7 disease mutant localization is distinct from constitutively active Rab7
Positive_regulation (active) of Rab7 associated with disease
14) Confidence 0.47 Published 2010 Journal Human Molecular Genetics Section Body Doc Link PMC2830827 Disease Relevance 0.58 Pain Relevance 0
We also analyzed the V162M mutant to determine whether there are consistent biochemical alterations among different disease-causing Rab7 mutants.
Spec (whether) Positive_regulation (causing) of Rab7 associated with disease
15) Confidence 0.47 Published 2010 Journal Human Molecular Genetics Section Body Doc Link PMC2830827 Disease Relevance 0.22 Pain Relevance 0
Large families in which mutations in SPTLC1 and RAB7 are excluded can be used for genome wide linkage studies to detect a novel HSN I locus or to confirm linkage to the third known HSN I locus (i.e. the HSN IB locus).
Positive_regulation (mutations) of RAB7 associated with hsan
16) Confidence 0.47 Published 2008 Journal Orphanet J Rare Dis Section Body Doc Link PMC2311280 Disease Relevance 1.48 Pain Relevance 1.16
Together with our GTP exchange assays, our results indicate that Rab7 mutations lead to misregulation of both activation of Rab7 by nucleotide exchange and inactivation of Rab7 by GTP dissociation.
Positive_regulation (activation) of Rab7
17) Confidence 0.44 Published 2010 Journal Human Molecular Genetics Section Body Doc Link PMC2830827 Disease Relevance 0.32 Pain Relevance 0
These properties render Rabs, including Rab7, dependent on the positive and negative influences of regulatory GEF and GAP proteins.
Positive_regulation (dependent) of Rab7
18) Confidence 0.44 Published 2010 Journal Human Molecular Genetics Section Body Doc Link PMC2830827 Disease Relevance 0.46 Pain Relevance 0
We report that misregulation of Rab7 activation results in an increase in the active fraction of Rab7 and abnormal retention on target membranes.
Positive_regulation (activation) of Rab7
19) Confidence 0.44 Published 2010 Journal Human Molecular Genetics Section Body Doc Link PMC2830827 Disease Relevance 0.57 Pain Relevance 0
Indeed, overexpression of constitutively active Rab7 leads to developmental defects in Drosophila (33,34).
Positive_regulation (overexpression) of Rab7
20) Confidence 0.44 Published 2010 Journal Human Molecular Genetics Section Body Doc Link PMC2830827 Disease Relevance 0.61 Pain Relevance 0

General Comments

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