Entry Name Spinocerebellar ataxia - Homo sapiens (human)
Description The autosomal dominant spinocerebellar ataxias (SCAs) are a group of progressive neurodegenerative diseases characterised by loss of balance and motor coordination due to the primary dysfunction of the cerebellum. Compelling evidence points to major aetiological roles for transcriptional dysregulation, protein aggregation and clearance, autophagy, the ubiquitin-proteasome system, alterations of calcium homeostasis, mitochondria defects, toxic RNA gain-of-function mechanisms and eventual cell death with apoptotic features of neurons during SCA disease progression.
Class Human Diseases; Neurodegenerative diseaseBRITE hierarchy
Pathway map Ortholog table Network Element N00954 Mutation-activated GRM1 to mGluR1-TRPC3 signaling pathway
N00955 Mutation-inactivated PRKCG to mGluR1-TRPC3 signaling pathway
N00956 Mutation-activated PRKCG to mGluR1-TRPC3 signaling pathway
N00957 Mutation-caused abberant ATXN2/3 to mGluR5-Ca2+ -apoptotic pathway
N00958 Mutation-activated ITPR1 to mGluR1-TRPC3 signaling pathway
N00959 ITPR1-reduced expression to mGluR1-TRPC3 signaling pathway
N00960 Mutation-caused aberrant SPTBN2 to mGluR1-TRPC3 signaling pathway
N00961 Mutation-activated TRPC3 to mGluR1-TRPC3 signaling pathway
N00962 Mutation-inactivated ATXN3 to autophagy-vesicle nucleation
N00964 DAB1-overexpression to RELN-VLDLR-PI3K signaling pathway
N00966 Mutation-caused aberrant ATXN1 to RORA-mediated transcription
N00968 Mutation-activated CACNA1A to VGCC-Ca2+ -apoptotic pathway
N00969 Mutation-inactivated CACNA1A to VGCC-Ca2- -apoptotic pathway
N00971 Mutation-caused aberrant PDYN to transport of calcium
N00973 Mutation-inactivated KCNC3 to transport of potassium
N00975 Mutation-inactivated KCND3 to transport of potassium
Disease H00063 Spinocerebellar ataxia (SCA)
Organism Homo sapiens (human) [GN:
hsa ]
Gene 7222 TRPC3; transient receptor potential cation channel subfamily C member 3 [KO:K04966 ]
2911 GRM1; glutamate metabotropic receptor 1 [KO:K04603 ]
2890 GRIA1; glutamate ionotropic receptor AMPA type subunit 1 [KO:K05197 ]
2891 GRIA2; glutamate ionotropic receptor AMPA type subunit 2 [KO:K05198 ]
2892 GRIA3; glutamate ionotropic receptor AMPA type subunit 3 [KO:K05199 ]
773 CACNA1A; calcium voltage-gated channel subunit alpha1 A [KO:K04344 ]
3708 ITPR1; inositol 1,4,5-trisphosphate receptor type 1 [KO:K04958 ]
3709 ITPR2; inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959 ]
3710 ITPR3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960 ]
2902 GRIN1; glutamate ionotropic receptor NMDA type subunit 1 [KO:K05208 ]
2903 GRIN2A; glutamate ionotropic receptor NMDA type subunit 2A [KO:K05209 ]
2904 GRIN2B; glutamate ionotropic receptor NMDA type subunit 2B [KO:K05210 ]
2905 GRIN2C; glutamate ionotropic receptor NMDA type subunit 2C [KO:K05211 ]
2906 GRIN2D; glutamate ionotropic receptor NMDA type subunit 2D [KO:K05212 ]
116443 GRIN3A; glutamate ionotropic receptor NMDA type subunit 3A [KO:K05213 ]
116444 GRIN3B; glutamate ionotropic receptor NMDA type subunit 3B [KO:K05214 ]
7416 VDAC1; voltage dependent anion channel 1 [KO:K05862 ]
7417 VDAC2; voltage dependent anion channel 2 [KO:K15040 ]
7419 VDAC3; voltage dependent anion channel 3 [KO:K15041 ]
291 SLC25A4; solute carrier family 25 member 4 [KO:K05863 ]
292 SLC25A5; solute carrier family 25 member 5 [KO:K05863 ]
293 SLC25A6; solute carrier family 25 member 6 [KO:K05863 ]
83447 SLC25A31; solute carrier family 25 member 31 [KO:K05863 ]
10939 AFG3L2; AFG3 like matrix AAA peptidase subunit 2 [KO:K08956 ] [EC:3.4.24.-]
115209 OMA1; OMA1 zinc metallopeptidase [KO:K23010 ] [EC:3.4.24.-]
2259 FGF14; fibroblast growth factor 14 [KO:K23920 ]
6712 SPTBN2; spectrin beta, non-erythrocytic 2 [KO:K23932 ]
5701 PSMC2; proteasome 26S subunit, ATPase 2 [KO:K03061 ]
5700 PSMC1; proteasome 26S subunit, ATPase 1 [KO:K03062 ]
5704 PSMC4; proteasome 26S subunit, ATPase 4 [KO:K03063 ]
5706 PSMC6; proteasome 26S subunit, ATPase 6 [KO:K03064 ]
5702 PSMC3; proteasome 26S subunit, ATPase 3 [KO:K03065 ]
5705 PSMC5; proteasome 26S subunit, ATPase 5 [KO:K03066 ]
5708 PSMD2; proteasome 26S subunit ubiquitin receptor, non-ATPase 2 [KO:K03028 ]
5707 PSMD1; proteasome 26S subunit, non-ATPase 1 [KO:K03032 ]
5709 PSMD3; proteasome 26S subunit, non-ATPase 3 [KO:K03033 ]
5715 PSMD9; proteasome 26S subunit, non-ATPase 9 [KO:K06693 ]
5718 PSMD12; proteasome 26S subunit, non-ATPase 12 [KO:K03035 ]
5717 PSMD11; proteasome 26S subunit, non-ATPase 11 [KO:K03036 ]
9861 PSMD6; proteasome 26S subunit, non-ATPase 6 [KO:K03037 ]
5713 PSMD7; proteasome 26S subunit, non-ATPase 7 [KO:K03038 ]
5719 PSMD13; proteasome 26S subunit, non-ATPase 13 [KO:K03039 ]
5710 PSMD4; proteasome 26S subunit ubiquitin receptor, non-ATPase 4 [KO:K03029 ]
10213 PSMD14; proteasome 26S subunit, non-ATPase 14 [KO:K03030 ]
5714 PSMD8; proteasome 26S subunit, non-ATPase 8 [KO:K03031 ]
11047 ADRM1; ADRM1 26S proteasome ubiquitin receptor [KO:K06691 ]
7979 SEM1; SEM1 26S proteasome subunit [KO:K10881 ]
2081 ERN1; endoplasmic reticulum to nucleus signaling 1 [KO:K08852 ] [EC:2.7.11.1 3.1.26.-]
6095 RORA; RAR related orphan receptor A [KO:K08532 ]
487 ATP2A1; ATPase sarcoplasmic/endoplasmic reticulum Ca2+ transporting 1 [KO:K05853 ] [EC:7.2.2.10 ]
489 ATP2A3; ATPase sarcoplasmic/endoplasmic reticulum Ca2+ transporting 3 [KO:K05853 ] [EC:7.2.2.10 ]
488 ATP2A2; ATPase sarcoplasmic/endoplasmic reticulum Ca2+ transporting 2 [KO:K05853 ] [EC:7.2.2.10 ]
6511 SLC1A6; solute carrier family 1 member 6 [KO:K05617 ]
23152 CIC; capicua transcriptional repressor [KO:K20225 ]
23369 PUM2; pumilio RNA binding family member 2 [KO:K17943 ]
9698 PUM1; pumilio RNA binding family member 1 [KO:K17943 ]
9519 TBPL1; TATA-box binding protein like 1 [KO:K03120 ]
11317 RBPJL; recombination signal binding protein for immunoglobulin kappa J region like [KO:K06053 ]
3516 RBPJ; recombination signal binding protein for immunoglobulin kappa J region [KO:K06053 ]
2959 GTF2B; general transcription factor IIB [KO:K03124 ]
4800 NFYA; nuclear transcription factor Y subunit alpha [KO:K08064 ]
4654 MYOD1; myogenic differentiation 1 [KO:K09064 ]
9821 RB1CC1; RB1 inducible coiled-coil 1 [KO:K17589 ]
55626 AMBRA1; autophagy and beclin 1 regulator 1 [KO:K17985 ]
29982 NRBF2; nuclear receptor binding factor 2 [KO:K21246 ]
26100 WIPI2; WD repeat domain, phosphoinositide interacting 2 [KO:K17908 ]
55062 WIPI1; WD repeat domain, phosphoinositide interacting 1 [KO:K17908 ]
3748 KCNC3; potassium voltage-gated channel subfamily C member 3 [KO:K04889 ]
3752 KCND3; potassium voltage-gated channel subfamily D member 3 [KO:K04893 ]
7436 VLDLR; very low density lipoprotein receptor [KO:K20053 ]
5290 PIK3CA; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha [KO:K00922 ] [EC:2.7.1.153 ]
5293 PIK3CD; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta [KO:K00922 ] [EC:2.7.1.153 ]
5291 PIK3CB; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta [KO:K00922 ] [EC:2.7.1.153 ]
5295 PIK3R1; phosphoinositide-3-kinase regulatory subunit 1 [KO:K02649 ]
5296 PIK3R2; phosphoinositide-3-kinase regulatory subunit 2 [KO:K02649 ]
8503 PIK3R3; phosphoinositide-3-kinase regulatory subunit 3 [KO:K02649 ]
6315 ATXN8OS; ATXN8 opposite strand lncRNA [KO:K23933 ]
146227 BEAN1; brain expressed associated with NEDD4 1 [KO:K19324 ]
Compound C01245 D-myo-Inositol 1,4,5-trisphosphate
C04549 1-Phosphatidyl-1D-myo-inositol 3-phosphate
Reference Authors Matilla-Duenas A, Sanchez I, Corral-Juan M, Davalos A, Alvarez R, Latorre P
Title Cellular and molecular pathways triggering neurodegeneration in the spinocerebellar ataxias.
Journal Reference Authors Duenas AM, Goold R, Giunti P
Title Molecular pathogenesis of spinocerebellar ataxias.
Journal Reference Authors Mark MD, Schwitalla JC, Groemmke M, Herlitze S
Title Keeping Our Calcium in Balance to Maintain Our Balance.
Journal Reference Authors Egorova PA, Bezprozvanny IB
Title Inositol 1,4,5-trisphosphate receptors and neurodegenerative disorders.
Journal Reference Authors Shimobayashi E, Kapfhammer JP
Title Calcium Signaling, PKC Gamma, IP3R1 and CAR8 Link Spinocerebellar Ataxias and Purkinje Cell Dendritic Development.
Journal Reference Authors Kasumu A, Bezprozvanny I
Title Deranged calcium signaling in Purkinje cells and pathogenesis in spinocerebellar ataxia 2 (SCA2) and other ataxias.
Journal Reference Authors Egorova P, Popugaeva E, Bezprozvanny I
Title Disturbed calcium signaling in spinocerebellar ataxias and Alzheimer's disease.
Journal Reference Authors Hisatsune C, Hamada K, Mikoshiba K
Title Ca(2+) signaling and spinocerebellar ataxia.
Journal Reference Authors Takada SH, Ikebara JM, de Sousa E, Cardoso DS, Resende RR, Ulrich H, Ruckl M, Rudiger S, Kihara AH
Title Determining the Roles of Inositol Trisphosphate Receptors in Neurodegeneration: Interdisciplinary Perspectives on a Complex Topic.
Journal Reference Authors Brown SA, Loew LM
Title Integration of modeling with experimental and clinical findings synthesizes and refines the central role of inositol 1,4,5-trisphosphate receptor 1 in spinocerebellar ataxia.
Journal Reference Authors Inoue T
Title Dynamics of calcium and its roles in the dendrite of the cerebellar Purkinje cell.
Journal Reference Authors Adachi N, Kobayashi T, Takahashi H, Kawasaki T, Shirai Y, Ueyama T, Matsuda T, Seki T, Sakai N, Saito N
Title Enzymological analysis of mutant protein kinase Cgamma causing spinocerebellar ataxia type 14 and dysfunction in Ca2+ homeostasis.
Journal Reference Authors Smeets CJ, Jezierska J, Watanabe H, Duarri A, Fokkens MR, Meijer M, Zhou Q, Yakovleva T, Boddeke E, den Dunnen W, van Deursen J, Bakalkin G, Kampinga HH, van de Sluis B, Verbeek DS
Title Elevated mutant dynorphin A causes Purkinje cell loss and motor dysfunction in spinocerebellar ataxia type 23.
Journal Reference Authors Tulli S, Del Bondio A, Baderna V, Mazza D, Codazzi F, Pierson TM, Ambrosi A, Nolte D, Goizet C, Toro C, Baets J, Deconinck T, DeJonghe P, Mandich P, Casari G, Maltecca F
Title Pathogenic variants in the AFG3L2 proteolytic domain cause SCA28 through haploinsufficiency and proteostatic stress-driven OMA1 activation.
Journal Reference Authors Mancini C, Hoxha E, Iommarini L, Brussino A, Richter U, Montarolo F, Cagnoli C, Parolisi R, Gondor Morosini DI, Nicolo V, Maltecca F, Muratori L, Ronchi G, Geuna S, Arnaboldi F, Donetti E, Giorgio E, Cavalieri S, Di Gregorio E, Pozzi E, Ferrero M, Riberi E, Casari G, Altruda F, Turco E, Gasparre G, Battersby BJ, Porcelli AM, Ferrero E, Brusco A, Tempia F
Title Mice harbouring a SCA28 patient mutation in AFG3L2 develop late-onset ataxia associated with enhanced mitochondrial proteotoxicity.
Journal Reference Authors Becker EBE
Title From Mice to Men: TRPC3 in Cerebellar Ataxia.
Journal Reference Authors Hoxha E, Tempia F, Lippiello P, Miniaci MC
Title Modulation, Plasticity and Pathophysiology of the Parallel Fiber-Purkinje Cell Synapse.
Journal Reference Authors Yan H, Pablo JL, Pitt GS
Title FGF14 regulates presynaptic Ca2+ channels and synaptic transmission.
Journal Reference Authors Tada M, Nishizawa M, Onodera O
Title Roles of inositol 1,4,5-trisphosphate receptors in spinocerebellar ataxias.
Journal Reference Authors Pietrobon D
Title CaV2.1 channelopathies.
Journal Reference Authors Matsuyama Z, Yanagisawa NK, Aoki Y, Black JL 3rd, Lennon VA, Mori Y, Imoto K, Inuzuka T
Title Polyglutamine repeats of spinocerebellar ataxia 6 impair the cell-death-preventing effect of CaV2.1 Ca2+ channel--loss-of-function cellular model of SCA6.
Journal Reference Authors Nishitoh H, Matsuzawa A, Tobiume K, Saegusa K, Takeda K, Inoue K, Hori S, Kakizuka A, Ichijo H
Title ASK1 is essential for endoplasmic reticulum stress-induced neuronal cell death triggered by expanded polyglutamine repeats.
Journal Reference Authors Evers MM, Toonen LJ, van Roon-Mom WM
Title Ataxin-3 protein and RNA toxicity in spinocerebellar ataxia type 3: current insights and emerging therapeutic strategies.
Journal Reference Authors Ashkenazi A, Bento CF, Ricketts T, Vicinanza M, Siddiqi F, Pavel M, Squitieri F, Hardenberg MC, Imarisio S, Menzies FM, Rubinsztein DC
Title Polyglutamine tracts regulate autophagy.
Journal Reference Authors Chen RH, Chen YH, Huang TY
Title Ubiquitin-mediated regulation of autophagy.
Journal Reference Authors Serra HG, Duvick L, Zu T, Carlson K, Stevens S, Jorgensen N, Lysholm A, Burright E, Zoghbi HY, Clark HB, Andresen JM, Orr HT
Title RORalpha-mediated Purkinje cell development determines disease severity in adult SCA1 mice.
Journal Reference Authors Rousseaux MWC, Tschumperlin T, Lu HC, Lackey EP, Bondar VV, Wan YW, Tan Q, Adamski CJ, Friedrich J, Twaroski K, Chen W, Tolar J, Henzler C, Sharma A, Bajic A, Lin T, Duvick L, Liu Z, Sillitoe RV, Zoghbi HY, Orr HT
Title ATXN1-CIC Complex Is the Primary Driver of Cerebellar Pathology in Spinocerebellar Ataxia Type 1 through a Gain-of-Function Mechanism.
Journal Reference Authors Jimenez G, Shvartsman SY, Paroush Z
Title The Capicua repressor--a general sensor of RTK signaling in development and disease.
Journal Reference Authors Gennarino VA, Palmer EE, McDonell LM, Wang L, Adamski CJ, Koire A, See L, Chen CA, Schaaf CP, Rosenfeld JA, Panzer JA, Moog U, Hao S, Bye A, Kirk EP, Stankiewicz P, Breman AM, McBride A, Kandula T, Dubbs HA, Macintosh R, Cardamone M, Zhu Y, Ying K, Dias KR, Cho MT, Henderson LB, Baskin B, Morris P, Tao J, Cowley MJ, Dinger ME, Roscioli T, Caluseriu O, Suchowersky O, Sachdev RK, Lichtarge O, Tang J, Boycott KM, Holder JL Jr, Zoghbi HY
Title A Mild PUM1 Mutation Is Associated with Adult-Onset Ataxia, whereas Haploinsufficiency Causes Developmental Delay and Seizures.
Journal Reference Authors Irie T, Matsuzaki Y, Sekino Y, Hirai H
Title Kv3.3 channels harbouring a mutation of spinocerebellar ataxia type 13 alter excitability and induce cell death in cultured cerebellar Purkinje cells.
Journal Reference Authors Bushart DD, Murphy GG, Shakkottai VG
Title Precision medicine in spinocerebellar ataxias: treatment based on common mechanisms of disease.
Journal Reference Authors Hsiao CT, Fu SJ, Liu YT, Lu YH, Zhong CY, Tang CY, Soong BW, Jeng CJ
Title Novel SCA19/22-associated KCND3 mutations disrupt human KV 4.3 protein biosynthesis and channel gating.
Journal Reference Authors Duarri A, Lin MC, Fokkens MR, Meijer M, Smeets CJ, Nibbeling EA, Boddeke E, Sinke RJ, Kampinga HH, Papazian DM, Verbeek DS
Title Spinocerebellar ataxia type 19/22 mutations alter heterocomplex Kv4.3 channel function and gating in a dominant manner.
Journal Reference Authors Matilla-Duenas A, Volpini V
Title Spinocerebellar Ataxia Type 37
Journal GeneReviews (1993)
Reference Authors Corral-Juan M, Serrano-Munuera C, Rabano A, Cota-Gonzalez D, Segarra-Roca A, Ispierto L, Cano-Orgaz AT, Adarmes AD, Mendez-Del-Barrio C, Jesus S, Mir P, Volpini V, Alvarez-Ramo R, Sanchez I, Matilla-Duenas A
Title Clinical, genetic and neuropathological characterization of spinocerebellar ataxia type 37.
Journal Reference Authors Swinnen B, Robberecht W, Van Den Bosch L
Title RNA toxicity in non-coding repeat expansion disorders.
Journal Reference Authors Ishikawa K, Nagai Y
Title Molecular Mechanisms and Future Therapeutics for Spinocerebellar Ataxia Type 31 (SCA31).
Journal Reference Authors Niimi Y, Takahashi M, Sugawara E, Umeda S, Obayashi M, Sato N, Ishiguro T, Higashi M, Eishi Y, Mizusawa H, Ishikawa K
Title Abnormal RNA structures (RNA foci) containing a penta-nucleotide repeat (UGGAA)n in the Purkinje cell nucleus is associated with spinocerebellar ataxia type 31 pathogenesis.
Journal Reference Authors Kobayashi H, Abe K, Matsuura T, Ikeda Y, Hitomi T, Akechi Y, Habu T, Liu W, Okuda H, Koizumi A
Title Expansion of intronic GGCCTG hexanucleotide repeat in NOP56 causes SCA36, a type of spinocerebellar ataxia accompanied by motor neuron involvement.
Journal Related hsa04141 Protein processing in endoplasmic reticulum
KO pathway LinkDB All DBs
