Ptosis, external ophthalmoplegia, facial weakness, and pharyngeal and distal limb weakness¹; Slowly progressive distal weakness, ophthalmoplegia, facial and bulbar weakness². Two probands presented with ataxia and mild cognitive impairment³.

Prevalence

Population dependent; presumed rare. Predominantly found in individuals of East Asian ancestry¹.

Age of Onset

Typical: 20-34⁴; Range: 2³- 70⁵.

HPO Terms

–

Association

Mendelian

Locus

hg19 chr19:14606853-14606887

hg38 chr19:14496041-14496075

t2t chr19:14622655-14622692

Details

Benign repeats range from absent⁶to 32⁷, while pathogenic alleles range from 73-164 repeats^1,7. Findings suggest that alternative initiation sites and an upstream CTG codon serve as the initiation site for RAN translation⁸. Intermediate alleles have undetermined significance but may represent a phenotypic spectrum⁴. Interruptions documented: CGA⁹. Interruptions proposed but not confirmed in primary literature: TCG/CCT/TTG¹⁰. One proband with ataxia and repeat size 11/112 had an asymptomatic father with 650 repeats and higher methylation³.

Mechanism

LoF/GoF?

Findings suggest that the mechanism is likely not LoF, but the mechanism is otherwise unknown⁸. This expansion appears to be predominantly RAN translated into a toxic protein⁸. This protein has been reported to impair cell proliferation, induce cytotoxicity and apoptosis in multiple cell lines, and caused phenotypic defects in a zebrafish model⁸.

Detection

Short-read WGS or exome sequencing have been reported to be inaccurate in detecting these expansions [@pmid:32413282]. RP-PCR has detected most repeats, while long-read sequencing accurately resolved size and structure [@pmid:32413282].

Year

2020⁴

Location in Gene

5' UTR

Gene Strand

Alleles

Ref. Motif

CCG

Ranges

Benign (ref.)

–

Benign (gene)

–

Pathogenic (ref.)

CCG

Pathogenic (gene)

CGG

Unknown (ref.)

–

Unknown (gene)

–

Interruption (ref.)

–

Interruption (gene)

–

gnomAD

References

Direct supporting references for info on this page.

Neurological disorders caused by novel non-coding repeat expansions: clinical features and differential diagnosis.

Elisa,Vegezzi, Hiroyuki,Ishiura, D Cristopher,Bragg, David,Pellerin, Francesca,Magrinelli, Riccardo,Currò, Stefano,Facchini, Arianna,Tucci, John,Hardy, Nutan,Sharma, Matt C,Danzi, Stephan,Zuchner, Bernard,Brais, Mary M,Reilly, Shoji,Tsuji, Henry,Houlden, Andrea,Cortese

The Lancet. Neurology · 2024-07-01

pmid:38876750

Repeat expansion disorders.

Zhongbo,Chen, Huw R,Morris, James,Polke, Nicholas W,Wood, Sonia,Gandhi, Mina,Ryten, Henry,Houlden, Arianna,Tucci

Practical neurology · 2025-05-15

pmid:39349043

CGG Repeat Expansion in GIPC1 is Associated with Childhood-Onset Hereditary Ataxia.

Ying,Wu, Taoyun,Ji, Quanzhen,Tan, Xingzhi,Chang, Shirang,Pan, Jing,An, Enrui,Chen, Yuwu,Jiang, Jianwen,Deng, Cuijie,Wei

Movement disorders : official journal of the Movement Disorder Society · 2026-04-13

pmid:41975469

Expansion of GGC Repeat in GIPC1 Is Associated with Oculopharyngodistal Myopathy.

Jianwen,Deng, Jiaxi,Yu, Pidong,Li, Xinghua,Luan, Li,Cao, Juan,Zhao, Meng,Yu, Wei,Zhang, He,Lv, Zhiying,Xie, LingChao,Meng, Yiming,Zheng, Yawen,Zhao, Qiang,Gang, Qingqing,Wang, Jing,Liu, Min,Zhu, Xueyu,Guo, Yanan,Su, Yu,Liang, Fan,Liang, Tomohiro,Hayashi, Meiko Hashimoto,Maeda, Tatsuro,Sato, Shigehisa,Ura, Yasushi,Oya, Masashi,Ogasawara, Aritoshi,Iida, Ichizo,Nishino, Chang,Zhou, Chuanzhu,Yan, Yun,Yuan, Daojun,Hong, Zhaoxia,Wang

American journal of human genetics · 2020-05-14

pmid:32413282

5' UTR CGG repeat expansion in GIPC1 is associated with oculopharyngodistal myopathy.

Jianying,Xi, Xilu,Wang, Dongyue,Yue, Tonghai,Dou, Qunfeng,Wu, Jun,Lu, Yiqi,Liu, Wenbo,Yu, Kai,Qiao, Jie,Lin, Sushan,Luo, Jing,Li, Ailian,Du, Jihong,Dong, Yan,Chen, Lijun,Luo, Jie,Yang, Zhenmin,Niu, Zonghui,Liang, Chongbo,Zhao, Jiahong,Lu, Wenhua,Zhu, Yan,Zhou

Brain : a journal of neurology · 2021-03-03

pmid:33374016

gnomAD

gnomad:GIPC1

Resources for Genetics Professionals — Genetic Disorders Caused by Nucleotide Repeat Expansions and Contractions

Stephanie E.,Wallace, Lora JH,Bean

GeneReviews® [Internet] · 2022-10-20

genereviews:NBK535148

Translation of GGC repeats into a toxic polyglycine protein in oculopharyngodistal myopathy type 2.

Kexin,Jiao, Xinyu,Chen, Mengye,Cao, Jialong,Zhang, Xingyu,Xia, Xinyu,Gu, Xilu,Wang, Huahua,Zhong, Dongyue,Yue, Mingshi,Gao, Nachuan,Cheng, Sushan,Luo, Wenbo,Yu, Weijun,Pan, Chongbo,Zhao, Tao,Wang, Wenhua,Zhu, Jianying,Xi

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

pmid:41121761

Comprehensive genetic diagnosis of tandem repeat expansion disorders with programmable targeted nanopore sequencing.

Igor,Stevanovski, Sanjog R,Chintalaphani, Hasindu,Gamaarachchi, James M,Ferguson, Sandy S,Pineda, Carolin K,Scriba, Michel,Tchan, Victor,Fung, Karl,Ng, Andrea,Cortese, Henry,Houlden, Carol,Dobson-Stone, Lauren,Fitzpatrick, Glenda,Halliday, Gianina,Ravenscroft, Mark R,Davis, Nigel G,Laing, Avi,Fellner, Marina,Kennerson, Kishore R,Kumar, Ira W,Deveson

Science advances · 2022-03-04

pmid:35245110

Sequence composition changes in short tandem repeats: heterogeneity, detection, mechanisms and clinical implications.

Indhu-Shree,Rajan-Babu, Egor,Dolzhenko, Michael A,Eberle, Jan M,Friedman

Nature reviews. Genetics · 2024-03-11

pmid:38467784

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)

Neuronal and glial intranuclear inclusions in a patient with oculopharyngodistal myopathy associated with noncoding GGC repeat expansions in

Kaoru,Yagita, Hotake,Takizawa, Terunori,Sano, Yuji,Nakayma, Masashi,Ogasawara, Ichizo,Nishino, Yasushi,Ohya, Yuji,Takahashi, Masaki,Takao

Clinical neuropathology · 2026-04-30

pmid:42057638

Pathogenic CGG expansions in oculopharyngodistal myopathy exhibit distinct characteristics of each causative gene on the flanking sequences as well as methylation status.

Nobuyuki,Eura, Satoru,Noguchi, Megumu,Ogawa, Kyuto,Sonehara, Ai,Yamanaka, Takashi,Kurashige, Shinichiro,Hayashi, Yukinori,Okada, Kazuma,Sugie, Ichizo,Nishino

Genome medicine · 2026-03-27

pmid:41888971

Translation of expanded CGG repeats in LRP12 associated oculopharyngodistal myopathy.

Chengcheng,Li, Jil A,Daw, Sara K,Pittman, Connor J,Maltby, Hidetoshi,Sakurai, Peter K,Todd, Conrad C,Weihl

Acta neuropathologica communications · 2026-03-06

pmid:41792844

Economic evidence for expansion of HPV vaccination for the prevention of cervical cancer in LMICs: BIA framework construction and empirical analysis in China.

Yi,Li, Ran,Xin, Peipei,Chai, Bingjie,Liu, Liangru,Zhou, Xin,Zhang

BMC public health · 2026-01-19

pmid:41555317

CGG repeat expansions in Charcot-Marie-Tooth disease: insights from the 100 000 Genomes Project.

Alessandro,Bertini, Stefano,Facchini, Ilaria,Quartesan, Riccardo,Currò, Ricardo Parolin,Schnekenberg, Natalia,Dominik, Gustavo,Alves, Lucia,Ferullo, Arianna,Tucci, Henry,Houlden, Mary M,Reilly, Andrea,Cortese

Journal of neurology, neurosurgery, and psychiatry · 2026-05-14

pmid:40645757

A case report of oculopharyngodistal myopathy with 126 CGG repeat expansions in

Wenjing,Wang, Tielun,Yin, Xinyu,Zhang, Zhaoxia,Wang, Tianyun,Wang, Shuo,Zhang, Yingshuang,Zhang, Dongsheng,Fan

Frontiers in genetics · 2025-02-27

pmid:40084170

Heat-shock chaperone HSPB1 mitigates poly-glycine-induced neurodegeneration via restoration of autophagic flux.

Ning,Ding, Yijie,Song, Yuhang,Zhang, Wei,Yu, Xinnan,Li, Wei,Li, Lei,Li

Autophagy · 2025-02-25

pmid:39936620

dmTGS: Precise Targeted Enrichment Long-Read Sequencing Panel for Tandem Repeat Detection.

Kang,Yang, Yue,Liu, Ji,Zhang, Qian,Yu, Feng,Xu, Jiyuan,Liu, Yuting,Li, Xiaojie,Zhang, Zhiqiang,Wang, Ning,Wang, Yuezhen,Li, Yan,Shi, Wan-Jin,Chen

Clinical chemistry · 2025-02-03

pmid:39492694

Sequential development of parkinsonism in two patients with oculopharyngodistal type myopathy in GIPC1-related repeat expansion disorder.

Aki,Murayama, Utako,Nagaoka, Keizo,Sugaya, Rui,Shimazaki, Kazuhito,Miyamoto, Shiro,Matsubara, Masashi,Ogasawara, Aritoshi,Iida, Ichizo,Nishino, Kazushi,Takahashi

Neuromuscular disorders : NMD · 2024-09-27

pmid:39418922

Locus OPDM2 GIPC1

Disease

Locus

Alleles

gnomAD

References

Additional Literature