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Ectopic co-expression of canonical and LINE1 and THE1A-exonizing IL23R transcripts in sarcoid myopathy

Journal of Human Genetics (2026)Cite this article

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Abstract

Sarcoidosis is a heterogenous inflammatory disease with complex genetic susceptibilities. Multi-ethnic genome-wide association studies have validated the association of sarcoidosis susceptibilities with single nucleotide variants on interleukin 23 receptor gene (IL23R), which is highly expressed in adrenal gland and testis, but not in skeletal muscle. Here we report concomitant ectopic expression of a canonical IL23R transcript and alternative polyadenylation of intron 6 of IL23R, leading to novel aberrant transcripts containing two retrotransposons, LINE1 (L1PA16) and THE1A, in the 3’ untranslated region (IL23RL1-THE1A), in sarcoid myopathy (SM) compared with non-SM disease controls. RT-qPCR confirmed the expression of both transcripts in an additional sample set, including 14 SM and 29 non-SM. We also observed expression of both transcripts in T cells by single-nucleus RNA-sequencing. These findings should serve as an additional resource for investigating the role of IL23R transcript variants in the genetic background of sarcoidosis susceptibility and other inflammatory diseases.

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Data availability

The cDNA sequence of IL23RL1-THE1A has been deposited in DDBJ (accession numbers: LC880163).

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Acknowledgements

We wish to thank individuals and their families for their participation for this study. We also thank Drs. Y. Saito, J. Tanboon, FV De Los Reyes, S. Hayashi and all members of MGC, especially Mses. Y. Kanna and M. Uwai for their advice and technical assistance.

Funding

This study was supported by JSPS KAKENHI Grant Number 25H01048 (A.I. and I.N.) and an Intramural Research Grant for Neurological and Psychiatric Disorders of NCNP (5-6 to A.I. and I.N.).

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Author notes

  1. These authors contributed equally: Aritoshi Iida, Shunsuke Funaguma.

Authors and Affiliations

  1. Department of Genome Medicine Development, Medical Genome Center, National Center of Neurology and Psychiatry (NCNP), Kodaira, Tokyo, Japan

    Aritoshi Iida, Shunsuke Funaguma & Ichizo Nishino

  2. Department of Neuromuscular Research, Institute of Neuroscience, NCNP, Kodaira, Tokyo, Japan

    Ichizo Nishino

Authors
  1. Aritoshi Iida
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  2. Shunsuke Funaguma
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  3. Ichizo Nishino
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Contributions

A.I. conceived, designed, and directed the study. A.I. and S.F. conducted the transcriptomic, genomic and bioinformatic data analyses, data interpretation and visualization. I.N. managed all clinical, pathological and frozen muscle tissues from NCNP muscle repository. A.I. wrote the original draft of manuscript. All authors reviewed and edited the manuscript, and then approved the final version of manuscript. I.N. obtained funding.

Corresponding author

Correspondence to Aritoshi Iida.

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The authors declare no competing interests.

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Iida, A., Funaguma, S. & Nishino, I. Ectopic co-expression of canonical and LINE1 and THE1A-exonizing IL23R transcripts in sarcoid myopathy. J Hum Genet (2026). https://doi.org/10.1038/s10038-025-01451-w

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