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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
ZNF571 ENST00000328550 86.69 72.42 82.91 0.24 0.51 0.32 0.40 1.03 0.40
ZNF572 ENST00000319286 58.78 37.23 46.70 0.56 0.77 0.66 1.48 1.66 1.86
ZNF573 ENST00000590414 77.88 69.39 76.73 0.32 0.56 0.34 0.67 1.14 0.60
ZNF574 ENST00000600245 30.55 24.50 25.62 0.99 1.32 1.06 1.63 1.01 1.20
ZNF575 ENST00000314228 64.91 66.71 67.65 0.54 0.56 0.51 1.18 1.21 1.13
ZNF576 ENST00000336564 33.82 90.59 63.32 0.92 0.25 0.48 1.73 0.37 1.36
ZNF577 ENST00000301399 84.08 58.47 74.11 0.30 0.54 0.39 0.48 1.39 0.69
ZNF578 ENST00000421239 96.66 93.53 97.68 0.11 0.28 0.09 0.11 0.28 0.06
ZNF579 ENST00000325421 91.72 23.68 57.97 0.14 1.39 0.47 0.20 0.93 1.68
ZNF580 ENST00000543039 91.38 69.96 83.29 0.15 0.53 0.32 0.20 1.14 0.40
ZNF581 ENST00000587252 75.55 70.28 75.94 0.35 0.52 0.38 0.75 1.10 0.62
ZNF582 ENST00000301310 98.73 86.78 95.51 0.10 0.24 0.08 0.11 0.40 0.11
ZNF583 ENST00000333201 32.36 31.07 29.90 0.99 1.04 0.86 1.71 1.36 1.44
ZNF584 ENST00000306910 75.39 61.93 71.10 0.37 0.56 0.43 0.75 1.35 0.86
ZNF585A ENST00000292841 68.07 36.30 51.29 0.57 0.82 0.63 1.02 1.60 1.92
ZNF585B ENST00000532828 71.98 43.60 57.78 0.34 0.62 0.51 0.81 1.95 1.67
ZNF586 ENST00000396154 89.53 90.00 92.46 0.16 0.25 0.14 0.30 0.37 0.15
ZNF587 ENST00000339656 96.55 84.85 93.47 0.10 0.27 0.11 0.11 0.42 0.15
ZNF587B ENST00000442832 97.46 89.26 96.11 0.10 0.27 0.07 0.11 0.36 0.10
ZNF589 ENST00000354698 99.78 80.97 93.13 0.12 0.35 0.14 0.13 0.57 0.15
ZNF592 ENST00000299927 31.43 2.25 14.55 0.95 3.65 1.99 1.68 0.30 0.59
ZNF593 ENST00000374266 49.48 85.71 69.79 0.56 0.27 0.44 1.82 0.44 0.93
ZNF594 ENST00000399604 87.50 88.24 90.91 0.23 0.23 0.15 0.38 0.37 0.20
ZNF595 ENST00000526473 100.00 67.01 86.68 0.10 0.53 0.30 0.14 1.24 0.33
ZNF596 ENST00000398612 86.80 79.26 86.26 0.24 0.38 0.33 0.40 0.67 0.33

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