Huntington's Disease Pathway

Preferred Label : Huntington's Disease Pathway;

NCIt synonyms : Huntingtons Disease Pathway;

NCIt related terms : Huntington's Disease;

Alternative definition : KEGG: Huntington disease (HD) is an autosomal-dominant neurodegenerative disorder that primarily affects medium spiny striatal neurons (MSN). HD is caused by a CAG repeat expansion in the IT15 gene, which results in a long stretch of polyglutamine close to the amino-terminus of the HD protein huntingtin (Htt). Mutant Htt (mHtt) has effects both in the cytoplasm and in the nucleus. In the cytoplasm, full-length mHtt can interfere with BDNF vesicular transport on microtubules. This mutant protein also may lead to abnormal endocytosis and secretion in neurons, because normal Htt form a complex with the proteins Hip1, clathrin and AP2 that are involved in endocytosis. In addition, mHtt affects Ca2 signaling by sensitizing InsP3R1 to activation by InsP3, stimulating NR2B/NR1 NMDAR activity, and destabilizing mitochondrial Ca2 handling. As a result, stimulation of glutamate receptors leads to supranormal Ca2 responses in HD MSN and mitochondrial Ca2 overload. The mHtt translocates to the nucleus, where it forms intranuclear inclusions, though they are not primarily responsible for toxicity. Nuclear toxicity is believed to be caused by interference with gene transcription, leading to loss of transcription of neuroprotective molecules such as BDNF. While mHtt binds to p53 and upregulates levels of nuclear p53 as well as p53 transcriptional activity. Augmented p53 mediates mitochondrial dysfunction.;

NCIt note : This pathway originally was KEGG_ID hsa05040.;

KEGG ID : hsa05016;

Details

Origin ID

C38825;

UMLS CUI

C2919056;

Automatic exact mappings (from CISMeF team)
- Huntington disease [PASCAL descriptor]
- Huntington disease [ORDO Disease]
- Huntington disease [OMIM Phenotype]
- Huntington's disease [ICD-10 category]
- Huntington's disease [DO Concept]
- Huntington's disease [MedDRA Preferred Term]
- huntington disease [MeSH concept]
- huntington disease [MeSH Descriptor]
- huntington's disease [MedlinePlus Topic]
See also inter- (CISMeF)
- Huntington disease [ICD-11 Sub-sub category]
Semantic type(s)
- Functional Concept [UMLS semantic type]
has_gene_product_element
- 1-Phosphatidylinositol 4,5-Bisphosphate Phosphodiesterase Beta-3 [NCIt concept]
- 1-Phosphatidylinositol 4,5-Bisphosphate Phosphodiesterase Beta-4 [NCIt concept]
- 26S Proteasome Non-ATPase Regulatory Subunit 3 [NCIt concept]
- 26S Proteasome Regulatory Subunit 6A [NCIt concept]
- ADP/ATP Translocase 1 [NCIt concept]
- ADP/ATP Translocase 2 [NCIt concept]
- ADP/ATP Translocase 3 [NCIt concept]
- AP-2 Complex Subunit Beta [NCIt concept]
- ATP Synthase Subunit Beta, Mitochondrial [NCIt concept]
- ATP Synthase Subunit Epsilon, Mitochondrial [NCIt concept]
- ATP Synthase Subunit a [NCIt concept]
- Activated Caspase-9 [NCIt concept]
- Activating Molecule In BECN1-Regulated Autophagy Protein 1 [NCIt concept]
- Apoptosis Regulator BAX [NCIt concept]
- Apoptotic Protease-Activating Factor 1 [NCIt concept]
- Bcl-2-Binding Component 3 [NCIt concept]
- Brain-Derived Neurotrophic Factor [NCIt concept]
- CREB-Binding Protein [NCIt concept]
- Calmodulin [NCIt concept]
- Caspase-3 [NCIt concept]
- Caspase-8 [NCIt concept]
- Caspase-9 [NCIt concept]
- Cellular Tumor Antigen p53 [NCIt concept]
- Clathrin Heavy Chain 1 [NCIt concept]
- Clathrin Heavy Chain 2 [NCIt concept]
- Cyclic AMP-Responsive Element-Binding Protein 1 [NCIt concept]
- Cyclic AMP-Responsive Element-Binding Protein 3 [NCIt concept]
- Cyclic AMP-Responsive Element-Binding Protein 3-Like Protein 1 [NCIt concept]
- Cyclic AMP-Responsive Element-Binding Protein 3-Like Protein 2 [NCIt concept]
- Cyclic AMP-Responsive Element-Binding Protein 3-Like Protein 3 [NCIt concept]
- Cyclic AMP-Responsive Element-Binding Protein 3-Like Protein 4 [NCIt concept]
- Cyclic AMP-Responsive Element-Binding Protein 5 [NCIt concept]
- Cytochrome C [NCIt concept]
- Cytochrome C Oxidase Subunit 1 [NCIt concept]
- Cytochrome C Oxidase Subunit 6A2, Mitochondrial [NCIt concept]
- Cytochrome C Oxidase Subunit 6C [NCIt concept]
- Cytochrome C Oxidase Subunit 7A-Related Protein, Mitochondrial [NCIt concept]
- Cytochrome b-c1 Complex Subunit 6, Mitochondrial [NCIt concept]
- DNA-Directed RNA Polymerase II Subunit RPB1 [NCIt concept]
- DNA-Directed RNA Polymerases I, II, and III Subunit RPABC5 [NCIt concept]
- Dynactin Subunit 1 [NCIt concept]
- Dynein Axonemal Heavy Chain 5 [NCIt concept]
- Dynein Axonemal Intermediate Chain 1 [NCIt concept]
- Dynein Heavy Chain 9, Axonemal [NCIt concept]
- Glutamate Receptor 1 [NCIt concept]
- Glutamate Receptor 2 [NCIt concept]
- Glutamate Receptor 3 [NCIt concept]
- Glutamate Receptor Ionotropic, NMDA 2B [NCIt concept]
- Glutamate Receptor Ionotropic, NMDA 2D [NCIt concept]
- Glutathione Peroxidase 1 [NCIt concept]
- Growth Factor Receptor-Bound Protein 2 [NCIt concept]
- Histone Acetyltransferase p300 [NCIt concept]
- Histone Deacetylase 1 [NCIt concept]
- Histone Deacetylase 2 [NCIt concept]
- Huntingtin [NCIt concept]
- Huntingtin-Interacting Protein 1 [NCIt concept]
- Inositol 1,4,5-Trisphosphate Receptor Type 1 [NCIt concept]
- Kinesin Heavy Chain Isoform 5A [NCIt concept]
- Kinesin-1 Heavy Chain [NCIt concept]
- Metabotropic Glutamate Receptor 5 [NCIt concept]
- Mitochondrial Brown Fat Uncoupling Protein 1 [NCIt concept]
- Peptidyl-Prolyl Cis-Trans Isomerase F, Mitochondrial [NCIt concept]
- Peroxisome Proliferator-Activated Receptor Gamma [NCIt concept]
- Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-Alpha [NCIt concept]
- Protein-Glutamine Gamma-Glutamyltransferase 2 [NCIt concept]
- Serine/Threonine-Protein Kinase ULK2 [NCIt concept]
- Succinate Dehydrogenase Cytochrome b560 Subunit, Mitochondrial [NCIt concept]
- Succinate Dehydrogenase [Ubiquinone] Cytochrome B Small Subunit, Mitochondrial [NCIt concept]
- Succinate Dehydrogenase [Ubiquinone] Flavoprotein Subunit, Mitochondrial [NCIt concept]
- Succinate Dehydrogenase [Ubiquinone] Iron-Sulfur Subunit, Mitochondrial [NCIt concept]
- Superoxide Dismutase [Cu-Zn] [NCIt concept]
- Superoxide Dismutase [Mn], Mitochondrial [NCIt concept]
- Transcription Factor A, Mitochondrial [NCIt concept]
- Transcription Factor Sp1 [NCIt concept]
- Tubulin Beta-4A Chain [NCIt concept]
- Voltage-Dependent Anion-Selective Channel Protein 1 [NCIt concept]
- Voltage-Dependent Anion-Selective Channel Protein 2 [NCIt concept]
- Voltage-Dependent Anion-Selective Channel Protein 3 [NCIt concept]
pathway_has_gene_element
- AMBRA1 wt Allele [NCIt concept]
- AP2B1 wt Allele [NCIt concept]
- APAF1 wt Allele [NCIt concept]
- ATP5F1B wt Allele [NCIt concept]
- ATP5F1E wt Allele [NCIt concept]
- BAX wt Allele [NCIt concept]
- BBC3 wt Allele [NCIt concept]
- BDNF wt Allele [NCIt concept]
- CALM1 wt Allele [NCIt concept]
- CASP3 wt Allele [NCIt concept]
- CASP8 wt Allele [NCIt concept]
- CASP9 wt Allele [NCIt concept]
- CLTC wt Allele [NCIt concept]
- CLTCL1 wt Allele [NCIt concept]
- COX6A2 wt Allele [NCIt concept]
- COX6C wt Allele [NCIt concept]
- COX7A2L wt Allele [NCIt concept]
- CREB1 wt Allele [NCIt concept]
- CREB3 wt Allele [NCIt concept]
- CREB3L1 wt Allele [NCIt concept]
- CREB3L2 wt Allele [NCIt concept]
- CREB3L3 wt Allele [NCIt concept]
- CREB3L4 wt Allele [NCIt concept]
- CREB5 wt Allele [NCIt concept]
- CREBBP wt Allele [NCIt concept]
- CYCS wt Allele [NCIt concept]
- DCTN1 wt Allele [NCIt concept]
- DNAH5 wt Allele [NCIt concept]
- DNAH9 wt Allele [NCIt concept]
- DNAI1 wt Allele [NCIt concept]
- EP300 wt Allele [NCIt concept]
- GPX1 wt Allele [NCIt concept]
- GRB2 wt Allele [NCIt concept]
- GRIA1 wt Allele [NCIt concept]
- GRIA2 wt Allele [NCIt concept]
- GRIA3 wt Allele [NCIt concept]
- GRIN2B wt Allele [NCIt concept]
- GRIN2D wt Allele [NCIt concept]
- GRM5 wt Allele [NCIt concept]
- HDAC1 wt Allele [NCIt concept]
- HDAC2 wt Allele [NCIt concept]
- HIP1 wt Allele [NCIt concept]
- HTT wt Allele [NCIt concept]
- ITPR1 wt Allele [NCIt concept]
- KIF5A wt Allele [NCIt concept]
- KIF5B wt Allele [NCIt concept]
- MT-ATP6 wt Allele [NCIt concept]
- MT-CO1 wt Allele [NCIt concept]
- PLCB3 wt Allele [NCIt concept]
- PLCB4 wt Allele [NCIt concept]
- POLR2A wt Allele [NCIt concept]
- POLR2L wt Allele [NCIt concept]
- PPARG wt Allele [NCIt concept]
- PPARGC1A wt Allele [NCIt concept]
- PPIF wt Allele [NCIt concept]
- PSMC3 wt Allele [NCIt concept]
- PSMD3 wt Allele [NCIt concept]
- SDHA wt Allele [NCIt concept]
- SDHB wt Allele [NCIt concept]
- SDHC wt Allele [NCIt concept]
- SDHD wt Allele [NCIt concept]
- SLC25A4 wt Allele [NCIt concept]
- SLC25A5 wt Allele [NCIt concept]
- SLC25A6 wt Allele [NCIt concept]
- SOD1 wt Allele [NCIt concept]
- SOD2 wt Allele [NCIt concept]
- SP1 wt Allele [NCIt concept]
- TFAM wt Allele [NCIt concept]
- TGM2 wt Allele [NCIt concept]
- TP53 wt Allele [NCIt concept]
- TUBB4A wt Allele [NCIt concept]
- UCP1 wt Allele [NCIt concept]
- ULK2 wt Allele [NCIt concept]
- UQCRH wt Allele [NCIt concept]
- VDAC1 wt Allele [NCIt concept]
- VDAC2 wt Allele [NCIt concept]
- VDAC3 wt Allele [NCIt concept]

Keyword's position in hierarchy(ies) :

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