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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
ZNF670 ENST00000366503 87.15 90.37 91.60 0.23 0.25 0.14 0.38 0.37 0.18
ZNF671 ENST00000317398 97.08 90.57 96.62 0.10 0.25 0.08 0.11 0.37 0.08
ZNF672 ENST00000306562 76.89 27.06 51.05 0.33 1.23 0.66 0.73 1.11 1.89
ZNF674 ENST00000523374 79.05 71.71 78.64 0.32 0.51 0.38 0.64 1.07 0.55
ZNF675 ENST00000359788 82.50 62.68 75.55 0.30 0.51 0.37 0.56 1.31 0.64
ZNF676 ENST00000397121 97.16 82.41 92.51 0.10 0.34 0.14 0.11 0.52 0.15
ZNF677 ENST00000333952 82.14 59.33 73.52 0.30 0.51 0.40 0.57 1.41 0.74
ZNF678 ENST00000343776 88.93 95.50 94.96 0.19 0.23 0.09 0.32 0.21 0.10
ZNF679 ENST00000421025 94.53 62.52 81.89 0.10 0.53 0.37 0.11 1.31 0.46
ZNF680 ENST00000309683 86.37 47.85 69.24 0.27 0.59 0.44 0.42 1.98 0.97
ZNF681 ENST00000402377 94.42 82.36 91.29 0.10 0.34 0.15 0.11 0.52 0.18
ZNF682 ENST00000397165 95.30 80.18 90.81 0.10 0.37 0.15 0.11 0.59 0.20
ZNF683 ENST00000374204 75.75 74.13 78.19 0.35 0.53 0.39 0.76 1.03 0.55
ZNF684 ENST00000372699 47.74 78.75 64.60 0.53 0.42 0.51 1.80 0.73 1.32
ZNF687 ENST00000324048 24.42 11.19 15.64 1.33 2.09 1.75 1.12 0.54 0.67
ZNF688 ENST00000223459 95.32 85.02 92.92 0.10 0.25 0.14 0.11 0.45 0.15
ZNF689 ENST00000287461 20.10 24.48 20.34 1.53 1.32 1.48 1.00 1.01 0.88
ZNF69 ENST00000340180 98.35 91.25 97.40 0.10 0.23 0.08 0.10 0.34 0.07
ZNF691 ENST00000397044 51.27 23.75 35.65 0.59 1.39 0.85 1.85 0.93 1.76
ZNF692 ENST00000451251 59.98 64.85 63.63 0.62 0.48 0.49 1.40 1.24 1.39
ZNF695 ENST00000339986 98.70 91.29 97.60 0.10 0.23 0.09 0.11 0.34 0.06
ZNF696 ENST00000330143 89.64 38.00 65.34 0.16 0.77 0.53 0.29 1.71 1.32
ZNF697 ENST00000421812 88.31 49.72 71.55 0.20 0.66 0.44 0.35 2.02 0.83
ZNF699 ENST00000591998 75.97 46.37 61.92 0.34 0.73 0.48 0.76 2.04 1.45
ZNF7 ENST00000528372 58.12 47.51 52.04 0.56 0.62 0.62 1.54 2.01 1.94

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