type: gene_score
filename: ExAC.csv
scores:
  - id: pLI
    desc: Probability of Loss-of-Function Intolerance
    small_values_desc: "less likely to be Loss-of-function intolerant"
    large_values_desc: "more likely to be Loss-of-function intolerant"
    histogram:
      type: number
      number_of_bins: 126
      view_range:
        min: 0
        max: 1
      x_min_log: 0.00001
      x_log_scale: false
      y_log_scale: true
  - id: pLI_rank
    desc: Gene rank after sorting by pLI intolerance score
    small_values_desc: "more likely to be Loss-of-function intolerant"
    large_values_desc: "less likely to be Loss-of-function intolerant"
    histogram:
      type: number
      number_of_bins: 150
      view_range:
        min: 1
        max: 18225
      x_log_scale: false
      y_log_scale: false


meta:
  summary: |
    Probability of Loss-of-Function Intolerance

  description: |
    The probability of loss-of-function intolerance (pLI) score reflects a gene's sensitivity to LoF mutations, with higher scores indicating greater intolerance. It's calculated by comparing observed versus expected protein-truncating variants (PTVs), where a pLI near 1 suggests LoF mutations are likely deleterious. Genes with pLI >= 0.9 are strongly considered LoF-intolerant, often associated with haploinsufficiency and dominant genetic diseases. pLI calculations utilize human genetic diversity data from large-scale databases, including the Exome Aggregation Consortium (ExAC) and gnomAD.


    [Lek et al., Analysis of protein-coding genetic variation in 60,706 humans, Nature 2016](https://www.nature.com/articles/nature19057)