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
SF3B1 ENST00000335508 0.06 0.36 0.01 4.58 4.14 4.91 0.15 0.28 0.15
SMC3 ENST00000361804 0.51 0.03 0.01 4.39 4.10 4.90 0.19 0.26 0.15
SMC1A ENST00000322213 0.43 0.28 0.02 4.38 4.12 4.90 0.17 0.29 0.15
GRIN2B ENST00000609686 0.49 0.23 0.02 4.40 4.11 4.89 0.18 0.28 0.15
OGT ENST00000373719 0.23 0.58 0.03 4.48 4.15 4.89 0.16 0.28 0.15
TOP1 ENST00000361337 0.69 0.22 0.03 4.34 4.12 4.88 0.19 0.28 0.15
SMARCA4 ENST00000429416 0.95 0.17 0.04 4.38 4.12 4.88 0.18 0.28 0.15
ATP1A3 ENST00000545399 0.88 0.27 0.04 4.35 4.11 4.87 0.18 0.29 0.15
XPO1 ENST00000401558 1.14 0.12 0.05 4.39 4.10 4.87 0.17 0.28 0.15
BRD4 ENST00000263377 1.23 0.09 0.05 4.39 4.13 4.86 0.17 0.27 0.15
DHX15 ENST00000336812 0.05 1.30 0.06 4.59 3.96 4.86 0.15 0.27 0.15
CNOT3 ENST00000406403 0.87 0.48 0.06 4.35 4.09 4.85 0.18 0.28 0.15
CLTC ENST00000269122 0.56 0.80 0.07 4.40 4.11 4.85 0.19 0.27 0.15
KDM2A ENST00000529006 1.31 0.07 0.07 4.38 4.12 4.87 0.17 0.27 0.15
KPNB1 ENST00000290158 0.54 0.90 0.08 4.39 4.08 4.86 0.19 0.29 0.15
SMARCA5 ENST00000283131 0.99 0.46 0.08 4.38 4.10 4.88 0.18 0.28 0.15
SATB2 ENST00000417098 0.61 0.88 0.09 4.36 4.09 4.88 0.19 0.29 0.15
CASK ENST00000378166 1.19 0.42 0.09 4.39 4.13 4.87 0.17 0.28 0.16
FBXO11 ENST00000403359 0.62 1.03 0.10 4.34 4.05 4.89 0.19 0.28 0.16
RPS6KA3 ENST00000379565 0.89 0.78 0.10 4.36 4.12 4.89 0.18 0.27 0.17
CNOT1 ENST00000317147 1.74 0.01 0.11 4.30 4.12 4.88 0.22 0.26 0.17
ZEB2 ENST00000558170 0.42 1.34 0.11 4.36 3.97 4.88 0.17 0.27 0.17
SCN8A ENST00000354534 0.20 1.58 0.12 4.50 3.87 4.87 0.16 0.26 0.18
HDAC2 ENST00000519065 0.64 1.21 0.12 4.35 4.02 4.87 0.19 0.27 0.18
HNRNPK ENST00000376263 0.91 0.96 0.13 4.35 4.08 4.86 0.18 0.29 0.18

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.