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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
ZNF771 ENST00000319296 78.68 57.55 70.41 0.35 0.57 0.43 0.64 1.48 0.91
ZNF772 ENST00000343280 69.24 49.23 59.54 0.56 0.66 0.49 0.97 2.02 1.69
ZNF773 ENST00000282292 87.52 77.03 85.63 0.23 0.42 0.32 0.38 0.78 0.35
ZNF774 ENST00000354377 72.91 80.36 79.97 0.32 0.37 0.35 0.79 0.59 0.52
ZNF775 ENST00000329630 83.18 35.47 59.66 0.28 0.77 0.49 0.54 1.56 1.67
ZNF776 ENST00000317178 96.49 91.38 96.73 0.10 0.23 0.08 0.11 0.33 0.08
ZNF777 ENST00000247930 5.16 0.95 1.20 3.44 4.09 4.43 0.31 0.29 0.21
ZNF778 ENST00000433976 94.58 85.79 92.92 0.10 0.28 0.14 0.12 0.44 0.15
ZNF780A ENST00000455521 84.71 92.05 91.28 0.29 0.24 0.15 0.47 0.33 0.18
ZNF780B ENST00000434248 86.95 83.89 88.53 0.24 0.28 0.22 0.39 0.46 0.28
ZNF781 ENST00000358582 94.96 98.96 99.01 0.10 0.17 0.11 0.12 0.15 0.04
ZNF782 ENST00000481138 72.55 59.18 67.70 0.32 0.49 0.52 0.80 1.44 1.12
ZNF783 ENST00000434415 74.00 47.93 61.68 0.35 0.59 0.46 0.82 1.99 1.46
ZNF784 ENST00000325351 85.95 26.44 55.85 0.25 1.16 0.51 0.44 1.10 1.75
ZNF785 ENST00000395216 87.66 96.20 94.66 0.23 0.22 0.09 0.37 0.20 0.11
ZNF786 ENST00000491431 82.83 64.12 76.55 0.30 0.49 0.38 0.55 1.20 0.61
ZNF787 ENST00000270459 92.25 20.30 54.59 0.15 1.43 0.56 0.18 0.75 1.74
ZNF788 ENST00000596883 86.15 85.60 88.99 0.25 0.27 0.19 0.42 0.44 0.27
ZNF788 ENST00000339302 89.60 97.82 96.54 0.16 0.21 0.07 0.30 0.18 0.07
ZNF789 ENST00000331410 77.10 67.92 75.45 0.34 0.52 0.38 0.72 1.17 0.66
ZNF79 ENST00000342483 73.27 35.30 53.70 0.34 0.76 0.62 0.79 1.58 1.82
ZNF790 ENST00000356725 77.83 71.11 77.68 0.32 0.49 0.38 0.67 1.07 0.55
ZNF791 ENST00000343325 66.64 27.92 45.99 0.62 1.19 0.70 1.05 1.19 1.97
ZNF792 ENST00000404801 84.53 71.43 81.34 0.30 0.53 0.38 0.46 1.06 0.49
ZNF793 ENST00000445217 71.85 74.10 75.98 0.34 0.53 0.38 0.83 1.03 0.62

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