# Affinity-optimizing enhancer variants disrupt development

*PRI Rank #16 · Topics and Trends in Most Cited Genomics and Chromatin Dynamics Papers, Class of 2026*

*Canonical URL: https://pri.pepkio.com/top-papers/genomics-and-chromatin-dynamics/2026/rank-16*

| Field | Value |
| --- | --- |
| Rank | #16 |
| 18m citations | 61 |
| Journal | Nature |
| Year | 2024 |
| DOI | 10.1038/s41586-023-06922-8 |
| Corresponding authors | Fabian Lim, Joe J Solvason, Genevieve E Ryan |
| Institution | University of California San Diego, United States |

**Ranking page:** [Topics and Trends in Most Cited Genomics and Chromatin Dynamics Papers, Class of 2026](https://pri.pepkio.com/top-papers/genomics-and-chromatin-dynamics/2026)

**Paper link:** [10.1038/s41586-023-06922-8](https://doi.org/10.1038/s41586-023-06922-8)

## Topics

ZRS enhancer · Shh expression · limb development · polydactyly · ETS binding sites · ETS-A site · low-affinity binding sites · affinity-optimizing variants · single-nucleotide variants (SNVs) · gain-of-function gene expression · IRF sites · HOX sites · AP-1 sites · enhanceropathies · penetrance · suboptimal binding affinity · tissue-specific enhancer activity · Transcription factor binding affinity · pathogenic variants in enhancers

## Cite this ranking

```
Pepkio Research Index (PRI). Topics and Trends in Most Cited Genomics and Chromatin Dynamics Papers, Class of 2026. https://pri.pepkio.com/top-papers/genomics-and-chromatin-dynamics/2026. Accessed 2026-10-28.

Zheng Su, Tinsley Li, Thematic Shifts in Early-High-Impact Cancer Genomics and Diagnostics Research: A Bibliometric and Semantic Analysis. bioRxiv 2026.07.04.736459; doi: https://doi.org/10.64898/2026.07.04.736459
```