Locus SCA EP400

A provisional form of spinocerebellar ataxia. Progressive gait ataxia is present in all reported cases, ranging from juvenile-onset (age 15, rapidly progressive with bulbar and respiratory involvement) to adult-onset (40s, slowly progressive over decades). Other features vary by family and include cerebellar dysarthria, abnormal eye movements, dysphagia, and limb incoordination¹. This locus has not yet been assigned an SCA number and is not yet listed in OMIM, GeneReviews, MONDO, or other clinical genetics databases.

Prevalence

Age of Onset

HPO Terms

–

Association

Mendelian

Locus

hg19 chr12:132547069-132547156

hg38 chr12:132062524-132062611

t2t chr12:132111361-132111451

Details

56 to 75 pure CAGs have been observed in affected individuals¹, however differences in locus definitions make defining the pathogenic range challenging. STRchive is using the broad locus definition of hg38 chr12:132062524-132062611, where the reference locus structure is (CAG)6(CAA)2(CAG)14(CAA)1(CAG)4(CAA)(CAG). All allele size ranges in STRchive are based on this definition and report the total length of the allele including CAA interruptions. A narrower locus definition of hg38 chr12:132062548-132062611 has also been used to describe this locus and results in a differently described pathogenic range¹. Disease link was proposed by Danzi et al¹. Family 1 (father and daughter) had a longest pure tract of 56-58 repeats with the structure (CAG)6(CAA)2(CAG)46-58(CAA)1(CAG)4(CAA)(CAG), while the son in Family 2 (mother ungenotyped) had 75 pure CAG repeats with the structure (CAG)75(CAA)(CAG), i.e. loss of several CAA interruptions.

Mechanism

Unknown

Detection

Long-read sequencing with targeted sanger confirmation has detected expansions in this locus¹.

Year

2026

Location in Gene

Exon 47

Gene Strand

Alleles

Ref. Motif

CAG

Ranges

Benign (ref.)

–

Benign (gene)

–

Pathogenic (ref.)

CAG

Pathogen. (gene)

CAG

Unknown (ref.)

–

Unknown (gene)

–

Interruption (ref.)

CAA

Interrup. (gene)

CAA

References

Direct supporting references for info on this page.

Population-scale variability at short tandem repeat loci reveals pathogenicity signature

Matt C.,Danzi, Isaac R. L.,Xu, Sarah,Fazal, Egor,Dolzhenko, David,Pellerin, Ben,Weisburd, Liedewei,Van de Vondel, Chloe,Reuter, Jacinda B.,Sampson, Chiara,Folland, Carolin K.,Scriba, Gavin,Monahan, Phillipa J.,Lamont, Julie,Wertz, Adriana,Rebelo, Sophia B.,Gibson, Daniel G.,Calame, Haloom,Rafehi, Penny,Snell, Kate,Kotschet, Kayli C.,Davies, Igor,Stevanovski, Ira W.,Deveson, Danny E.,Miller, Chia-Lin,Wei, Jane,Grimwood, Donna M.,Muzny, Niall,Lennon, Melanie,Bahlo, Paul J.,Lockhart, Matthew,Wheeler, Anne,O’Donnell-Luria, Stefan,Wuchty, Gianina,Ravenscroft, Michael A.,Eberle, Kiran V.,Garimella, Fritz J.,Sedlazeck, Michael E.,Talkowski, Michael C.,Schatz, Evan E.,Eichler, Stephan,Zuchner

openRxiv · 2025-01-07

doi:10.1101/2025.01.06.631535

Additional Literature

Additional literature related to this locus.

Identifying unstable CNG repeat loci in the human genome: a heuristic approach and implications for neurological disorders.

Varun,Suroliya, Bharathram,Uppili, Manish,Kumar, Vineet,Jha, Achal K,Srivastava, Mohammed,Faruq

Human genome variation · 2024-06-13

pmid:38871700

The landscape of genetic diseases in Saudi Arabia based on the first 1000 diagnostic panels and exomes.

Dorota,Monies, Mohamed,Abouelhoda, Moeenaldeen,AlSayed, Zuhair,Alhassnan, Maha,Alotaibi, Husam,Kayyali, Mohammed,Al-Owain, Ayaz,Shah, Zuhair,Rahbeeni, Mohammad A,Al-Muhaizea, Hamad I,Alzaidan, Edward,Cupler, Saeed,Bohlega, Eissa,Faqeih, Maha,Faden, Banan,Alyounes, Dyala,Jaroudi, Ewa,Goljan, Hadeel,Elbardisy, Asma,Akilan, Renad,Albar, Hesham,Aldhalaan, Shamshad,Gulab, Aziza,Chedrawi, Bandar K,Al Saud, Wesam,Kurdi, Nawal,Makhseed, Tahani,Alqasim, Heba Y,El Khashab, Hamoud,Al-Mousa, Amal,Alhashem, Imaduddin,Kanaan, Talal,Algoufi, Khalid,Alsaleem, Talal A,Basha, Fathiya,Al-Murshedi, Sameena,Khan, Adila,Al-Kindy, Maha,Alnemer, Sami,Al-Hajjar, Suad,Alyamani, Hasan,Aldhekri, Ali,Al-Mehaidib, Rand,Arnaout, Omar,Dabbagh, Mohammad,Shagrani, Dieter,Broering, Maha,Tulbah, Amal,Alqassmi, Maisoon,Almugbel, Mohammed,AlQuaiz, Abdulaziz,Alsaman, Khalid,Al-Thihli, Raashda A,Sulaiman, Wajeeh,Al-Dekhail, Abeer,Alsaegh, Fahad A,Bashiri, Alya,Qari, Suzan,Alhomadi, Hisham,Alkuraya, Mohammed,Alsebayel, Muddathir H,Hamad, Laszlo,Szonyi, Faisal,Abaalkhail, Sulaiman M,Al-Mayouf, Hamad,Almojalli, Khalid S,Alqadi, Hussien,Elsiesy, Taghreed M,Shuaib, Mohammed Zain,Seidahmed, Ibraheem,Abosoudah, Hana,Akleh, Abdulaziz,AlGhonaium, Turki M,Alkharfy, Fuad,Al Mutairi, Wafa,Eyaid, Abdullah,Alshanbary, Farrukh R,Sheikh, Fahad I,Alsohaibani, Abdullah,Alsonbul, Saeed,Al Tala, Soher,Balkhy, Randa,Bassiouni, Ahmed S,Alenizi, Maged H,Hussein, Saeed,Hassan, Mohamed,Khalil, Brahim,Tabarki, Saad,Alshahwan, Amira,Oshi, Yasser,Sabr, Saad,Alsaadoun, Mustafa A,Salih, Sarar,Mohamed, Habiba,Sultana, Abdullah,Tamim, Moayad,El-Haj, Saif,Alshahrani, Dalal K,Bubshait, Majid,Alfadhel, Tariq,Faquih, Mohamed,El-Kalioby, Shazia,Subhani, Zeeshan,Shah, Nabil,Moghrabi, Brian F,Meyer, Fowzan S,Alkuraya

Human genetics · 2017-06-09

pmid:28600779

Variants in EP400, encoding a chromatin remodeler, cause epilepsy with neurodevelopmental disorders.

Sheng,Luo, Peng-Yu,Wang, Peng,Zhou, Wen-Jun,Zhang, Yu-Jie,Gu, Xiao-Yu,Liang, Jing-Wen,Zhang, Jun-Xia,Luo, Hong-Wei,Zhang, Song,Lan, Ting-Ting,Zhang, Jie-Hua,Yang, Su-Zhen,Sun, Xiang-Yang,Guo, Ju-Li,Wang, Lin-Fan,Deng, Ze-Hai,Xu, Liang,Jin, Yun-Yan,He, Zi-Long,Ye, Wei-Yue,Gu, Bing-Mei,Li, Yi-Wu,Shi, Xiao-Rong,Liu, Hong-Jun,Yan, Yong-Hong,Yi, Yu-Wu,Jiang, Xiao,Mao, Wen-Ling,Li, Heng,Meng, Wei-Ping,Liao

American journal of human genetics · 2024-12-20

pmid:39708813

Chromatin remodeler Ep400 ensures oligodendrocyte survival and is required for myelination in the vertebrate central nervous system.

Olga,Elsesser, Franziska,Fröb, Melanie,Küspert, Ernst R,Tamm, Toshihiro,Fujii, Rikiro,Fukunaga, Michael,Wegner

Nucleic acids research · 2019-07-09

pmid:31081019

A unique missense variant in the E1A-binding protein P400 gene is implicated in schizophrenia by whole-exome sequencing and mutant mouse models.

Yoshiro,Morimoto, Shinji,Ono, Shintaro,Yoshida, Hiroyuki,Mishima, Akira,Kinoshita, Takeshi,Tanaka, Yoshihiro,Komohara, Naohiro,Kurotaki, Tatsuya,Kishino, Yuji,Okazaki, Hiroki,Ozawa, Koh-Ichiro,Yoshiura, Akira,Imamura

Translational psychiatry · 2021-02-18

pmid:33602898