Disease-associated protein states accessible to 8-oxoguanine transcriptional miscoding without genomic mutation
- 1Florida International University
Abstract
8-Oxoguanine (8-oxoG) is a common oxidative DNA lesion that can alter coding output during transcription without changing the underlying DNA sequence. When present on the template strand, 8-oxoG can direct RNA polymerase II to insert adenine, generating a transient coding-sense C>A error restricted by the genetic code to 18 directional amino-acid substitutions. Mapping these substitutions onto ClinVar identified 3,910 disease-associated protein states across 1,333 genes, representing 5.7% of evaluable pathogenic or likely pathogenic missense states. In 211 cases, transcriptional miscoding and the corresponding genomic disease variant affect different nucleotides within the same codon yet converge on the same amino acid substitution, allowing the disease-associated protein state to arise while the implicated genomic nucleotide remains wild type. Accessible states were enriched among genes with post-mitotic expression and neurological disease annotation, particularly in neuronal signaling pathways. Published oxidized-guanine maps supported 2,146 accessible genomic coordinates, while human proteogenomic data contained 78 exact codon-compatible protein states not explained by sample-specific transcript sequence. Together, these analyses define a chemically constrained set of disease-associated protein states accessible through 8-oxoG transcriptional miscoding without permanent genomic mutation.
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BibTeX
@misc{morenocaceres2026diseaseassociated,
title = {{Disease-associated protein states accessible to 8-oxoguanine transcriptional miscoding without genomic mutation}},
author = {S. Moreno-Caceres and A. M. Hayes and A. Delmas Eliason and D. P. Marciano},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.01.756037},
url = {https://www.biorxiv.org/content/10.64898/2026.10.01.756037v1},
note = {Public domain},
}
RIS
TY - UNPB
TI - Disease-associated protein states accessible to 8-oxoguanine transcriptional miscoding without genomic mutation
AU - S. Moreno-Caceres
AU - A. M. Hayes
AU - A. Delmas Eliason
AU - D. P. Marciano
PY - 2026
DA - 2026/10/01
PB - bioRxiv
DO - 10.64898/2026.10.01.756037
UR - https://www.biorxiv.org/content/10.64898/2026.10.01.756037v1
AB - 8-Oxoguanine (8-oxoG) is a common oxidative DNA lesion that can alter coding output during transcription without changing the underlying DNA sequence. When present on the template strand, 8-oxoG can direct RNA polymerase II to insert adenine, generating a transient coding-sense C>A error restricted by the genetic code to 18 directional amino-acid substitutions. Mapping these substitutions onto ClinVar identified 3,910 disease-associated protein states across 1,333 genes, representing 5.7% of evaluable pathogenic or likely pathogenic missense states. In 211 cases, transcriptional miscoding and the corresponding genomic disease variant affect different nucleotides within the same codon yet converge on the same amino acid substitution, allowing the disease-associated protein state to arise while the implicated genomic nucleotide remains wild type. Accessible states were enriched among genes with post-mitotic expression and neurological disease annotation, particularly in neuronal signaling pathways. Published oxidized-guanine maps supported 2,146 accessible genomic coordinates, while human proteogenomic data contained 78 exact codon-compatible protein states not explained by sample-specific transcript sequence. Together, these analyses define a chemically constrained set of disease-associated protein states accessible through 8-oxoG transcriptional miscoding without permanent genomic mutation.
ER -