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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
ZNF841 ENST00000389534 97.35 75.68 89.64 0.10 0.44 0.18 0.11 0.89 0.23
ZNF843 ENST00000315678 92.59 99.10 97.53 0.15 0.15 0.08 0.18 0.14 0.07
ZNF844 ENST00000439326 95.27 89.91 95.32 0.10 0.25 0.08 0.11 0.37 0.10
ZNF845 ENST00000458035 98.97 94.39 98.74 0.10 0.23 0.10 0.11 0.24 0.05
ZNF846 ENST00000397902 96.86 95.66 98.47 0.09 0.23 0.10 0.11 0.20 0.05
ZNF85 ENST00000328178 89.34 93.20 94.03 0.16 0.28 0.09 0.32 0.30 0.12
ZNF850 ENST00000591344 99.56 38.33 71.46 0.12 0.75 0.46 0.13 1.72 0.86
ZNF852 ENST00000436261 76.01 67.08 74.46 0.34 0.54 0.40 0.76 1.23 0.69
ZNF853 ENST00000457543 96.23 23.45 60.32 0.12 1.42 0.47 0.11 0.93 1.59
ZNF860 ENST00000360311 86.91 99.73 95.70 0.24 0.17 0.07 0.39 0.11 0.11
ZNF862 ENST00000223210 64.22 46.41 54.86 0.57 0.73 0.51 1.19 2.04 1.74
ZNF865 ENST00000568956 90.62 3.81 46.09 0.16 3.30 0.68 0.24 0.31 1.97
ZNF878 ENST00000547628 98.33 75.53 90.01 0.09 0.44 0.18 0.10 0.90 0.22
ZNF879 ENST00000444149 87.21 51.54 71.98 0.23 0.63 0.42 0.38 1.87 0.81
ZNF880 ENST00000422689 95.05 86.31 93.42 0.10 0.25 0.11 0.12 0.43 0.15
ZNF891 ENST00000537226 81.13 63.76 75.36 0.33 0.49 0.37 0.59 1.22 0.66
ZNF90 ENST00000418063 96.22 86.18 94.00 0.12 0.27 0.09 0.11 0.42 0.11
ZNF91 ENST00000300619 96.43 45.60 73.80 0.10 0.75 0.42 0.11 1.99 0.71
ZNF92 ENST00000328747 80.99 90.34 88.76 0.32 0.25 0.19 0.60 0.38 0.28
ZNF93 ENST00000343769 99.90 89.98 97.55 0.10 0.25 0.08 0.14 0.37 0.07
ZNF98 ENST00000357774 88.63 83.54 89.18 0.20 0.27 0.19 0.34 0.47 0.25
ZNF99 ENST00000596209 96.27 75.14 88.81 0.12 0.51 0.19 0.11 0.91 0.28
ZNFX1 ENST00000396105 25.30 9.41 15.14 1.38 2.48 1.86 1.17 0.49 0.64
ZNHIT1 ENST00000305105 23.01 86.72 54.41 1.42 0.24 0.58 1.08 0.40 1.75
ZNHIT2 ENST00000310597 76.49 72.11 77.50 0.34 0.52 0.35 0.73 1.04 0.57

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