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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
ZNF70 ENST00000341976 68.58 43.06 55.48 0.56 0.61 0.51 0.95 1.90 1.73
ZNF700 ENST00000254321 88.94 85.63 90.34 0.19 0.27 0.15 0.32 0.44 0.21
ZNF701 ENST00000540331 97.44 95.78 98.69 0.10 0.22 0.10 0.11 0.20 0.05
ZNF703 ENST00000331569 92.06 38.78 67.43 0.15 0.70 0.52 0.20 1.66 1.14
ZNF704 ENST00000327835 13.25 7.94 7.96 1.68 2.53 2.59 0.65 0.44 0.36
ZNF705A ENST00000359286 96.98 82.92 92.71 0.09 0.32 0.14 0.11 0.49 0.15
ZNF705B ENST00000443676 91.79 91.68 95.68 0.14 0.24 0.07 0.20 0.32 0.11
ZNF705D ENST00000400085 90.70 98.06 97.77 0.16 0.20 0.09 0.24 0.16 0.04
ZNF705G ENST00000400156 88.90 95.49 94.94 0.19 0.23 0.09 0.32 0.21 0.11
ZNF706 ENST00000520347 0.29 38.24 17.11 4.45 0.76 1.64 0.17 1.70 0.73
ZNF707 ENST00000532205 96.11 61.64 82.25 0.11 0.54 0.35 0.11 1.39 0.44
ZNF708 ENST00000356929 81.73 85.18 86.64 0.32 0.25 0.30 0.60 0.45 0.33
ZNF709 ENST00000428311 86.68 91.63 91.91 0.24 0.23 0.14 0.40 0.32 0.17
ZNF709 ENST00000397732 86.68 91.11 91.72 0.24 0.25 0.14 0.40 0.35 0.18
ZNF71 ENST00000328070 84.64 67.50 79.37 0.29 0.54 0.39 0.47 1.20 0.53
ZNF710 ENST00000268154 15.10 10.57 10.42 1.57 2.15 2.18 0.74 0.51 0.43
ZNF711 ENST00000373165 10.60 7.72 6.50 1.99 2.53 3.05 0.57 0.43 0.32
ZNF713 ENST00000429591 54.33 52.96 53.07 0.65 0.63 0.62 1.73 1.78 1.87
ZNF714 ENST00000596143 97.19 87.65 95.15 0.10 0.24 0.09 0.11 0.36 0.10
ZNF716 ENST00000420713 82.59 90.09 89.46 0.30 0.25 0.18 0.56 0.37 0.24
ZNF717 ENST00000422325 93.41 95.55 96.16 0.13 0.23 0.07 0.15 0.21 0.10
ZNF720 ENST00000316491 83.93 49.22 68.58 0.29 0.66 0.47 0.48 2.02 1.05
ZNF721 ENST00000511833 97.24 93.13 97.76 0.10 0.28 0.09 0.11 0.30 0.04
ZNF724P ENST00000418100 89.04 69.43 82.66 0.19 0.54 0.32 0.32 1.13 0.43
ZNF726 ENST00000594466 88.17 93.37 93.54 0.20 0.28 0.13 0.35 0.28 0.15

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