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
G6PC3 ENST00000269097 24.39 56.97 39.02 1.33 0.56 0.78 1.12 1.53 2.07
ZNF259 ENST00000227322 30.85 50.71 39.14 0.99 0.63 0.77 1.65 1.94 2.07
WNT7B ENST00000339464 36.76 44.81 39.15 0.96 0.68 0.77 1.75 1.97 2.07
DBX1 ENST00000227256 38.72 42.82 39.13 0.92 0.63 0.77 1.75 1.92 2.07
PTPN13 ENST00000436978 49.69 31.88 39.14 0.54 0.94 0.77 1.84 1.48 2.07
HDX ENST00000297977 50.78 30.77 39.13 0.59 1.06 0.77 1.83 1.37 2.07
FAM222A ENST00000538780 59.83 21.50 38.98 0.59 1.42 0.80 1.39 0.79 2.07
PKN1 ENST00000342216 62.12 19.20 39.00 0.70 1.48 0.80 1.27 0.76 2.07
CFL2 ENST00000341223 1.85 79.52 39.03 4.28 0.38 0.78 0.22 0.66 2.06
NPC2 ENST00000555619 6.86 74.78 39.19 2.92 0.54 0.78 0.36 0.96 2.06
POLR2J ENST00000292614 10.48 81.80 44.73 2.01 0.34 0.63 0.54 0.51 2.06
AP3S1 ENST00000316788 12.16 80.13 44.74 1.67 0.37 0.63 0.60 0.60 2.06
OLIG2 ENST00000333337 14.20 71.14 40.86 1.62 0.51 0.80 0.72 1.06 2.06
KCTD4 ENST00000405872 16.58 64.93 39.09 1.43 0.48 0.77 0.81 1.24 2.06
SLC9A8 ENST00000417961 27.78 57.66 40.93 1.20 0.56 0.78 1.44 1.48 2.06
TMEM185A ENST00000316916 27.97 57.47 40.93 1.16 0.56 0.78 1.47 1.48 2.06
GGCX ENST00000233838 27.99 53.26 38.95 1.16 0.66 0.80 1.48 1.73 2.06
DFNB59 ENST00000409117 28.72 63.44 44.63 1.15 0.49 0.62 1.53 1.27 2.06
ATP6V1C2 ENST00000272238 29.97 51.50 39.07 1.09 0.63 0.77 1.59 1.87 2.06
GPR6 ENST00000275169 30.27 51.34 39.16 1.02 0.63 0.77 1.62 1.90 2.06
TPH1 ENST00000250018 30.49 51.04 39.11 1.00 0.65 0.77 1.62 1.92 2.06
ME3 ENST00000543262 31.50 60.69 44.66 0.95 0.54 0.62 1.69 1.40 2.06
LRRC58 ENST00000295628 32.50 49.02 39.11 0.97 0.66 0.77 1.70 2.03 2.06
NPY ENST00000407573 34.30 57.88 44.65 0.96 0.57 0.62 1.78 1.48 2.06
DSCR3 ENST00000309117 34.85 57.30 44.64 0.94 0.54 0.62 1.83 1.49 2.06

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.