Rxivist logo

Rxivist combines preprints from bioRxiv with data from Twitter to help you find the papers being discussed in your field. Currently indexing 62,232 bioRxiv papers from 276,305 authors.

Genetic variants that inactivate protein-coding genes are a powerful source of information about the phenotypic consequences of gene disruption: genes critical for an organism’s function will be depleted for such variants in natural populations, while non-essential genes will tolerate their accumulation. However, predicted loss-of-function (pLoF) variants are enriched for annotation errors, and tend to be found at extremely low frequencies, so their analysis requires careful variant annotation and very large sample sizes. Here, we describe the aggregation of 125,748 exomes and 15,708 genomes from human sequencing studies into the Genome Aggregation Database (gnomAD). We identify 443,769 high-confidence pLoF variants in this cohort after filtering for sequencing and annotation artifacts. Using an improved human mutation rate model, we classify human protein-coding genes along a spectrum representing tolerance to inactivation, validate this classification using data from model organisms and engineered human cells, and show that it can be used to improve gene discovery power for both common and rare diseases.

Download data

  • Downloaded 12,643 times
  • Download rankings, all-time:
    • Site-wide: 69 out of 62,232
    • In genomics: 20 out of 4,277
  • Year to date:
    • Site-wide: 9 out of 62,232
  • Since beginning of last month:
    • Site-wide: 21 out of 62,232

Altmetric data


Downloads over time

Distribution of downloads per paper, site-wide


Sign up for the Rxivist weekly newsletter! (Click here for more details.)


News