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Genes Fold Enrichment Color Codes
  • Gene Name, Canonical Transcript - gene identifiers from gnomAD database (Build 37)
  • GeVIR % - gene rank measured in percentiles based on Gene Variation Intolerance Ranking (GeVIR) (low values indicate more variation intolerant genes, which is also true for "LOEUF %" and "VIRLoF %"). GeVIR is a method which we developed and applied on a list of 19,361 genes to sort them based on number, length and evolutionary conservation of regions without functional variants (i.e. between two missense, loss-of-function, insertion or delition variants) in gnomAD database (version 2.0.1). Only canonical transcripts were analysed.
  • LOEUF % - gene rank measured in percentiles based gnomAD loss-of-function observed/expected upper bound fraction (LOEUF) (see Figure 1). For more information about this metric, please read "Constraint" section of MacArthur Lab blog post. If you use this metric please cite gnomAD flagship paper and use most up-to-date values from gnomAD website.

    LoF observed/expected (o/e) upper Confidence Interval (CI)

    Figure 1. Screenshot of ELN gene constraint metrics from gnomAD browser

  • VIRLoF % - gene rank measured in percentiles based on both GeVIR and gnomAD LOEUF (shows the best overall performance, see Figure 2). If you use this metric please cite both GeVIR and gnomAD flagship paper.
  • GeVIR AD, LOEUF AD, VIRLoF AD, GeVIR AR, LOEUF AR, VIRLoF AR - to help users interpret gene ranks, we calculated fold enrichment of Autosomal Dominant (AD) and Autosomal Recessive (AR) genes with known molecular basis of disorder in OMIM in a range of +-5% of gene X (see Figure 2). Statistical significant fold enrichements (Fisher Exact Test p-value < 1e-5) are shown in bold in the table. For example CDK19 gene's GeVIR % is 2.37, so examined range is from 0 (2.37-5, rounded to minimal percentile) to 7.37% (2.37+5). Genes in this range are ~4 times more often (4.05 fold enrichement) associated with AD diseases and ~4 times less often (0.25 fold enrichement) associated with AR diseases. Both enrichment of AD genes and deficiency of AR genes is statistical significant. Thus GeVIR metric adds supportive evidence that CDK19 is more likely to be associated with AD than AR disease.

    Gene Percentiles AD AR Fold Enrichment

    Figure 2. Fold Enrichment of known Autosomal Dominant (AD) and Autosomal Recessive (AR) genes of each gene in the ranked lists (GeVIR, LOEUF, VIRLoF. AD genes are enriched among top ranked genes (lowest percentiles), whereas AR genes are enriched among middle ranked genes (approximetly 35-65 percentiles). Combined metric (VIRLoF, purple) shows the best perfornance, i.e. high ranked genes are more often associated with AD than AR diseases, low ranked genes are less often associated with both AD and AR diseases.
Gene Name Canonical Transcript GeVIR % LOEUF % VIRLoF % GeVIR AD LOEUF AD VIRLoF AD GeVIR AR LOEUF AR VIRLoF AR
ZNF727 ENST00000550760 89.56 89.43 92.16 0.16 0.27 0.14 0.30 0.37 0.16
ZNF728 ENST00000594710 97.06 88.33 95.46 0.10 0.23 0.08 0.11 0.37 0.11
ZNF729 ENST00000601693 94.90 52.15 76.62 0.10 0.62 0.37 0.12 1.85 0.61
ZNF730 ENST00000597761 94.39 90.40 95.13 0.10 0.25 0.09 0.11 0.37 0.10
ZNF732 ENST00000419098 89.51 69.95 83.10 0.16 0.53 0.30 0.30 1.14 0.40
ZNF736 ENST00000423484 91.30 91.78 94.44 0.15 0.23 0.10 0.20 0.32 0.12
ZNF737 ENST00000427401 87.23 85.73 89.62 0.23 0.27 0.18 0.38 0.44 0.23
ZNF738 ENST00000311015 73.09 64.59 71.31 0.33 0.48 0.43 0.78 1.22 0.87
ZNF74 ENST00000400451 77.27 47.25 63.42 0.34 0.66 0.49 0.70 2.00 1.37
ZNF740 ENST00000416904 50.22 23.19 34.88 0.57 1.44 0.90 1.80 0.91 1.75
ZNF746 ENST00000458143 26.81 19.53 21.25 1.30 1.43 1.40 1.36 0.74 0.90
ZNF747 ENST00000252799 95.60 77.84 89.82 0.11 0.42 0.18 0.11 0.79 0.23
ZNF749 ENST00000334181 98.66 85.46 94.78 0.10 0.25 0.09 0.11 0.45 0.11
ZNF750 ENST00000269394 74.67 18.87 45.48 0.38 1.53 0.70 0.78 0.75 1.98
ZNF75A ENST00000574298 41.58 53.61 46.26 0.81 0.62 0.67 1.71 1.71 1.92
ZNF75D ENST00000370766 69.27 54.68 63.01 0.54 0.58 0.51 0.98 1.65 1.39
ZNF76 ENST00000373953 42.83 72.95 57.92 0.78 0.51 0.48 1.77 1.03 1.66
ZNF763 ENST00000343949 97.48 79.79 91.51 0.10 0.35 0.15 0.11 0.62 0.18
ZNF763 ENST00000590798 97.67 76.99 90.37 0.10 0.43 0.15 0.10 0.79 0.21
ZNF764 ENST00000252797 89.57 65.91 81.09 0.16 0.54 0.39 0.30 1.23 0.49
ZNF765 ENST00000396408 97.30 96.74 98.98 0.10 0.23 0.11 0.11 0.19 0.04
ZNF766 ENST00000439461 97.74 90.02 96.67 0.10 0.25 0.08 0.10 0.37 0.08
ZNF768 ENST00000380412 21.07 24.66 21.00 1.53 1.29 1.43 1.02 1.05 0.88
ZNF77 ENST00000314531 96.11 80.86 91.39 0.11 0.35 0.15 0.11 0.57 0.18
ZNF770 ENST00000356321 20.76 10.20 13.04 1.57 2.29 2.09 1.00 0.49 0.52

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