GeVIR Banner
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
PRMT5 ENST00000324366 4.72 2.20 1.46 3.62 3.66 4.33 0.31 0.29 0.22
SF3B4 ENST00000271628 0.41 6.61 1.52 4.37 2.64 4.33 0.17 0.37 0.22
PLK2 ENST00000274289 2.18 4.65 1.43 4.16 3.27 4.33 0.27 0.31 0.23
PAPOLA ENST00000216277 2.09 4.54 1.34 4.21 3.25 4.33 0.25 0.32 0.23
RUVBL1 ENST00000322623 1.66 5.26 1.46 4.29 3.14 4.33 0.22 0.32 0.22
EIF4A2 ENST00000323963 0.37 6.31 1.37 4.41 2.69 4.33 0.16 0.36 0.23
RANBP9 ENST00000011619 6.40 0.62 1.51 3.04 4.14 4.33 0.36 0.28 0.22
HSPA8 ENST00000534624 0.70 6.10 1.43 4.37 2.78 4.33 0.19 0.35 0.23
SF1 ENST00000377387 1.98 4.65 1.34 4.26 3.27 4.33 0.24 0.31 0.23
HNRNPU ENST00000283179 4.90 1.76 1.36 3.58 3.82 4.34 0.31 0.26 0.23
DDX39B ENST00000396172 0.25 6.78 1.51 4.48 2.67 4.34 0.17 0.37 0.22
NEDD4L ENST00000400345 2.36 4.41 1.42 4.10 3.27 4.34 0.27 0.32 0.23
NPEPPS ENST00000322157 6.32 0.30 1.33 3.04 4.13 4.34 0.35 0.29 0.23
GNAL ENST00000334049 0.83 6.19 1.50 4.35 2.73 4.34 0.18 0.35 0.22
ANKRD52 ENST00000267116 5.90 0.86 1.42 3.13 4.10 4.34 0.33 0.29 0.23
WDFY3 ENST00000295888 6.25 0.34 1.33 3.04 4.15 4.34 0.35 0.28 0.22
ACVR2A ENST00000241416 3.12 3.82 1.47 3.87 3.31 4.34 0.30 0.31 0.22
INTS6 ENST00000311234 4.50 2.51 1.50 3.70 3.56 4.34 0.29 0.29 0.22
ZMYM3 ENST00000353904 5.27 1.49 1.41 3.40 3.90 4.34 0.32 0.26 0.23
XPR1 ENST00000367590 3.16 3.40 1.32 3.86 3.42 4.34 0.30 0.29 0.22
HNF1B ENST00000225893 2.13 4.55 1.38 4.19 3.25 4.35 0.25 0.32 0.23
VCPIP1 ENST00000310421 5.30 1.69 1.49 3.39 3.84 4.35 0.32 0.25 0.22
UBE3A ENST00000397954 0.71 6.05 1.40 4.37 2.81 4.35 0.19 0.35 0.23
SMARCA2 ENST00000382203 1.42 5.19 1.32 4.32 3.19 4.35 0.20 0.32 0.22
CNOT2 ENST00000229195 1.64 5.03 1.37 4.29 3.23 4.35 0.22 0.32 0.23

Cookies disclaimer

I agree Our site saves small pieces of text information (cookies) on your device in order to deliver better content and for statistical purposes. You can disable the usage of cookies by changing the settings of your browser. By browsing our website without changing the browser settings you grant us permission to store that information on your device.