Spinocerebellar ataxia type 36 (SCA36) is a subtype of autosomal dominant cerebellar ataxia type 1 (ADCA type 1) characterized by gait and limb ataxia, lower limb spasticity, dysarthria, muscle fasciculations, tongue atrophy and hyperreflexia¹. Some affected individuals may develop hearing loss^2,3.

Prevalence

Western Japan: 3.6% of all SCA; Costa da Morte region of Spain: 6.3% of all SCA⁴; US: 0.7% of large undiagnosed ataxia cohort⁵. Found across ancestries/ethnicities³.

Age of Onset

Typical: 40-60⁶; Range: 28⁷- 67⁴.

HPO Terms

HP:0000365 Hearing impairment HP:0000508 Ptosis HP:0000511 Vertical supranuclear gaze palsy HP:0000514 Slow saccadic eye movements HP:0000622 Blurred vision HP:0000639 Nystagmus HP:0000651 Diplopia HP:0001251 Ataxia HP:0001252 Hypotonia HP:0001260 Dysarthria HP:0001272 Cerebellar atrophy HP:0001276 Hypertonia HP:0001288 Gait disturbance HP:0001308 Tongue fasciculations HP:0001310 Dysmetria HP:0001324 Muscle weakness HP:0001347 Hyperreflexia HP:0002015 Dysphagia HP:0002066 Gait ataxia HP:0002070 Limb ataxia HP:0002076 Migraine HP:0002078 Truncal ataxia HP:0002080 Intention tremor HP:0002311 Incoordination HP:0002321 Vertigo HP:0002346 Head tremor HP:0002378 Hand tremor HP:0002380 Fasciculations HP:0002607 Bowel incontinence HP:0003202 Skeletal muscle atrophy HP:0003445 EMG: neuropathic changes HP:0003487 Babinski sign HP:0007001 Loss of Purkinje cells in the cerebellar vermis HP:0007018 Attention deficit hyperactivity disorder HP:0007772 Impaired smooth pursuit HP:0012473 Tongue atrophy HP:0045084 Limb myoclonus

Association

Mendelian

Locus

hg19 chr20:2633378-2633403

hg38 chr20:2652732-2652757

t2t chr20:2683189-2683230

Details

Benign alleles range from 3-14 repeats and pathogenic alleles (650+ repeats) appear fully penetrant; the significance of intermediate alleles has yet to be elucidated⁶. Interruptions documented: GGCTG, GGCCCTG, GGCCG, and GGCCTTG⁸.

Mechanism

GoF

Toxic RNA-mediated GoF: The expanded GGCCTG transcripts accumulate as nuclear RNA foci that sequester splicing factor SRSF2⁹. Additionally, toxic protein GoF through RAN translation has been implicated as an additional driver of pathogenicity^10,11.

Detection

RP-PCR with fragment analysis has been used to detect these expansions⁹. Long-read sequencing has accurately sized alleles⁸.

Year

2011⁹

Location in Gene

Intron 1

Gene Strand

Alleles

Ref. Motif

GGCCTG

Ranges

Benign (ref.)

–

Benign (gene)

–

Pathogenic (ref.)

CCTGGG

Pathogen. (gene)

CCTGGG

Unknown (ref.)

–

Unknown (gene)

–

Interruption (ref.)

CTGGG, CCCTGGG, CCGGG, CCTTGG

Interrup. (gene)

CTGGG, CCCTGGG, CCGGG, CCTTGG

gnomAD

References

Direct supporting references for info on this page.

Ontology Lookup Service (OLS)

mondo:0013594

Acoustic impairment is a distinguishable clinical feature of Asidan/SCA36.

Yoshio,Ikeda, Yasuyuki,Ohta, Tomoko,Kurata, Yoshihiko,Shiro, Yoshiki,Takao, Koji,Abe

Journal of the neurological sciences · 2012-11-07

pmid:23140984

3omim:614153

Spinocerebellar Ataxia 36 is a Frequent Cause of Hereditary Ataxia in Eastern Spain.

Raquel,Baviera-Muñoz, Lidón,Carretero-Vilarroig, Nuria,Muelas, Rafael,Sivera, Pablo,Sopena-Novales, Begoña,Martínez-Sanchis, Isabel,Sastre-Bataller, Marina,Campins-Romeu, Irene,Martínez-Torres, Jose Manuel,García-Verdugo, Jose M,Millán, Teresa,Jaijo, Elena,Aller, Luis,Bataller

Movement disorders clinical practice · 2023-05-05

pmid:37332636

Prevalence of spinocerebellar ataxia 36 in a US population.

Juliana M,Valera, Tatyana,Diaz, Lauren E,Petty, Beatriz,Quintáns, Zuleima,Yáñez, Eric,Boerwinkle, Donna,Muzny, Dmitry,Akhmedov, Rebecca,Berdeaux, Maria J,Sobrido, Richard,Gibbs, James R,Lupski, Daniel H,Geschwind, Susan,Perlman, Jennifer E,Below, Brent L,Fogel

Neurology. Genetics · 2017-07-18

pmid:28761930

6pmid:25101480

Repeat expansions in

Tanya,Lam, Clarissa,Rocca, Kristina,Ibanez, Anupriya,Dalmia, Samuel,Tallman, Marios,Hadjivassiliou, Anke,Hensiek, Andrea,Nemeth, Stefano,Facchini, Nicholas,Wood, Andrea,Cortese, Henry,Houlden, Arianna,Tucci

Brain communications · 2023-09-14

pmid:37810464

A Chinese SCA36 pedigree analysis of

Jinlong,Zou, Fengyu,Wang, Zhenping,Gong, Runrun,Wang, Shuai,Chen, Haohan,Zhang, Ruihua,Sun, Chenhao,Gao, Wei,Li, Junkui,Shang, Jiewen,Zhang

Frontiers in genetics · 2023-03-27

pmid:37051597

Expansion of intronic GGCCTG hexanucleotide repeat in NOP56 causes SCA36, a type of spinocerebellar ataxia accompanied by motor neuron involvement.

Hatasu,Kobayashi, Koji,Abe, Tohru,Matsuura, Yoshio,Ikeda, Toshiaki,Hitomi, Yuji,Akechi, Toshiyuki,Habu, Wanyang,Liu, Hiroko,Okuda, Akio,Koizumi

American journal of human genetics · 2011-06-16

pmid:21683323

Hexanucleotide Repeat Expansions in c9FTD/ALS and SCA36 Confer Selective Patterns of Neurodegeneration In Vivo.

Tiffany W,Todd, Zachary T,McEachin, Jeannie,Chew, Alexander R,Burch, Karen,Jansen-West, Jimei,Tong, Mei,Yue, Yuping,Song, Monica,Castanedes-Casey, Aishe,Kurti, Judith H,Dunmore, John D,Fryer, Yong-Jie,Zhang, Beatriz,San Millan, Susana,Teijeira Bautista, Manuel,Arias, Dennis,Dickson, Tania F,Gendron, María-Jesús,Sobrido, Matthew D,Disney, Gary J,Bassell, Wilfried,Rossoll, Leonard,Petrucelli

Cell reports · 2020-05-05

pmid:32375043

Dissecting the mechanism of NOP56 GGCCUG repeat-associated non-AUG translation using cell-free translation systems.

Mayuka,Hasumi, Hayato,Ito, Kodai,Machida, Tatsuya,Niwa, Tomoya,Taminato, Yoshitaka,Nagai, Hiroaki,Imataka, Hideki,Taguchi

The Journal of biological chemistry · 2025-02-25

pmid:40015643

Additional Literature

Additional literature related to this locus.

Raw PubMed search results
(All PubMed results returned by searching for this gene, tandem repeats, and disease, in medline format)

Haplotype analysis of spinocerebellar ataxia type 36 suggests a shared permissive core haplotype across populations.

Katsuki,Eguchi, Satoko,Miyatake, Asako,Takei, Hiroaki,Yaguchi, Yuki,Iida, Shinsuke,Hamada, Yoshiko,Ito, Sanae,Honma, Fumio,Moriwaka, Taishi,Wada, Takashi,Jono, Misako,Kunii, Hiroyasu,Komiya, Hitaru,Kishida, Hiroshi,Doi, Fumiaki,Tanaka, Naomichi,Matsumoto, Ichiro,Yabe

Journal of human genetics · 2026-07-01

pmid:42387149

Detection of short tandem repeat expansions on a targeted neurological gene panel using STRipy improves the diagnostic rate for ataxias.

Carolin K,Scriba, Chiara,Folland, Michael,Black, Jessica,Baker, Daniel,Abromeit, Samantha,Saw, Mei-Ting,Chiew, Rebecca,Gooding, Nigel G,Laing, Mark R,Davis, Gianina,Ravenscroft

Brain communications · 2026-03-16

pmid:42038259

A fly model of SCA36 reveals combinatorial neurotoxicity of hexanucleotide and dipeptide repeats.

Cheng-Tsung,Hsiao, Ssu-Ju,Fu, Ting-Ni,Guo, Chia-Chi,Lin, Yu-Jung,Tsao, Wenying,Chang, Yi-Chu,Liao, Masayuki,Hashimoto, Shu-Yi,Huang, Yi-Chung,Lee, Chien-Hung,Yu, Chih-Chiang,Chan

PLoS genetics · 2025-12-03

pmid:41337098

Association of Non-Coding Repeat Expansions with Parkinson's Disease Risk: Evidence from a UK Biobank-Based Whole-Genome Sequencing Study.

Zhen,Hu, Qin-Qin,Yan, Jing-Jin,Wan, Yu,Fan, Jun,Liu

Movement disorders : official journal of the Movement Disorder Society · 2025-10-11

pmid:41074692

Repeat-associated ataxias in a German patient cohort analysed by targeted parallel long-read sequencing.

Hannes,Erdmann, Annalisa,Schaub, Morghan C,Lucas, Veronika,Scholz, Anna,Benet-Pagès, Kerstin,Becker, Christine,Dineiger, Veronika,Mayer, Inga,van Buren, Eva,Breithausen, Karl,Akbari, Isabell,Cordts, Mayra,Sauer, Christine,Schneider, Rosanna,Krakowsky, Franziska,Schnabel, Konstanze,Dunker, Lena,Fabritius, Johannes,Gerb, Denis,Grabova, Ken,Möhwald, Marius,Näher, Karoline,Steinmetz, Franziska,Thiessen, Alexander,Jäck, Christiane,Schneider-Gold, Simone,Zittel, Christina,Petersen, Isolde,Schreyer, Larissa,Mämecke, Sibylle,Wilfling, Gilbert,Wunderlich, David,Brenner, Yorck,Hellenbroich, Kirsten,Muhle, Tessa,Huchtemann, Inga,Claus, Thomas,Klopstock, Michael,Strupp, Johannes,Levin, Günter U,Höglinger, Doreen,Huppert, Sandra,Becker-Bense, Filipp,Filippopulos, Fabian,Kilpert, Elsa,Leitão, Sabine,Kaya, Christel,Depienne, Florian,Schöberl, Teresa,Neuhann, Elke,Holinski-Feder, Andreas,Zwergal, Angela,Abicht

Brain : a journal of neurology · 2026-03-05

pmid:40898875

Non-coding repeat analyses in patients with Parkinson's disease.

Makito,Hirano, Makoto,Samukawa, Satoko,Miyatake, Yuko,Yamagishi, Chiharu,Isono, Rino,Yoshikawa, Kazumasa,Saigoh, Atsushi,Terayama, Yuji,Higashimoto, Eriko,Koshimizu, Takeshi,Mizuguchi, Kanako,Fujii, Yoshiyuki,Mitsui, Naomichi,Matsumoto, Yoshitaka,Nagai

Frontiers in neurology · 2025-07-22

pmid:40765612

Diagnostic yield and limitations of whole-genome sequencing for hereditary cerebellar ataxia.

Wai Yan,Yau, Roisin,Sullivan, Emer,O'Connor, David,Pellerin, Michael H,Parkinson, Paola,Giunti, Marie-Josée,Dicaire, Matt C,Danzi, Stephan,Züchner, Bernard,Brais, Nicholas W,Wood, Henry,Houlden, Jana,Vandrovcova

Brain communications · 2025-05-17

pmid:40488180

Dissecting the mechanism of NOP56 GGCCUG repeat-associated non-AUG translation using cell-free translation systems.

Mayuka,Hasumi, Hayato,Ito, Kodai,Machida, Tatsuya,Niwa, Tomoya,Taminato, Yoshitaka,Nagai, Hiroaki,Imataka, Hideki,Taguchi

The Journal of biological chemistry · 2025-02-25

pmid:40015643

Analysis of Short Tandem Repeat Expansions in a Cohort of 12,496 Exomes from Patients with Neurological Diseases Reveals Variable Genotyping Rate Dependent on Exome Capture Kits.

Clarissa,Rocca, David,Murphy, Chris,Clarkson, Matteo,Zanovello, Delia,Gagliardi, Queen Square,Genomics, Rauan,Kaiyrzhanov, Javeria,Alvi, Reza,Maroofian, Stephanie,Efthymiou, Tipu,Sultan, Jana,Vandrovcova, James,Polke, Robyn,Labrum, Henry,Houlden, Arianna,Tucci

Genes · 2025-01-28

pmid:40004498

Locus SCA36 NOP56

Disease

Locus

Alleles

gnomAD

References

Additional Literature