What is MendelVar?

MendelVar webserver's goal is testing for enrichment of human phenotype and disease ontology terms amongst genes linked to Mendelian disorders situated within a list of custom genomic intervals.

MendelVar provides a quick overview of possible impact of Mendelian disease-related genes on user's complex phenotype of interest. It returns the details of all known broadly defined Mendelian diseases and their causal genes found in the custom genomic intervals as well as overlapping pathogenic rare mutations responsible for Mendelian disease. Enrichment of Disease Ontology, Human Phenotype Ontology terms among the Mendelian genes gives the researcher an overview of any shared features with their trait of interest, e.g. in terms of anatomy.

When should I use MendelVar?

We envisage MendelVar will be especially useful for post-GWAS annotation. MendelVar adds a useful step in triangulating genetic evidence when prioritising candidate causal genes in a complex phenotype, so called in silico fine mapping.

The number of genes with a known disruption resulting in Mendelian disorder currently totals ~4,500 genes and ~300 new Mendelian phenotypes are discovered every year. It has been hypothesised that subtle dysregulation of these gene's function, mainly through regulatory changes affecting expression, can contribute to risk for phenotypically similar complex disease. Recently, Freund et al. (2018) have shown that genes with confirmed phenotypically-matching Mendelian lesions are enriched for among all GWAS genes across 62 human traits.

Knowledge that:

‐a given gene, out of all the genes in linkage disequilibrium (LD) with the top variant is associated with a term that is found at other GWAS loci;

‐that the term is enriched among the GWAS genes relative to background;

‐that the term refers to confirmed aspect of the disease biology: anatomical entity or symptom

can strengthen the case for importance of these GWAS genes

in contributing to the complex trait.

MendelVar Features

MendelVar accepts a user defined list of genomic intervals or a list of top SNPs. Top SNPs can be used to create genomic intervals in two ways in MendelVar: using pre-set basepair flanks or via generation of individual LD-based boundaries around each top SNP, identified either through dbSNP rsIDs or positional coordinates. The LD-based intervals can be also optionally extended to the nearest recombination hotspot.
Full support for hg19/GRCh37 and hg38/GRCh38 human genome builds for input. Six 1000 Genomes populations - EUR, CEU, AFR, AMR, EAS, SAS supported via LDlink for LD-based genomic interval generation.
MendelVar contains ~11,500 gene-Mendelian disease relationships linked to ~4,600 unique genes sourced from OMIM, ORPHANET, Genomics England PanelApp and DECIPHER.
MendelVar annotates user genomic intervals with ~105,000 overlapping pathogenic or likely pathogenic Mendelian disease-causing rare mutations from ClinVar.
Out of ~11,500 gene-disease entries in the MendelVar database, ~9,700 contain a disease description, ~9,400 are annotated with at least one Human Phenotype Ontology term and ~6,500 have a Disease Ontology term assigned.
Using INRICH, an enrichment tool especially suited for GWAS data, MendelVar can test for enrichment of terms in discovered Mendelian disease-associated genes from Disease Ontology, Human Phenotype Ontology, Gene Ontology and their slims as well as Freund et al. (2018) gene sets, Pathway Commons, ConsensusPathDb and Reactome.
MendelVar uses up-to-date ontology definitions and annotations, with weekly updates, unlike a lot of popular tools. Using tools with obsolete databases can result in capture of only up to 25% of relevant processes and pathways.


Easy step-through-step guide to MendelVar and its settings is available on Notion. Includes MendelVar's Terms of Use.

Sample MendelVar input and results for the Yap et al. (2018) baldness GWAS can be downloaded here (input file) and here (results)

Citation & Contact

If you found MendelVar useful, please cite our paper:
Sobczyk MK, Gaunt TR, Paternoster L. (2020). MendelVar: gene prioritization at GWAS loci using phenotypic enrichment of Mendelian disease genes. bioRvix doi: https://doi.org/10.1101/2020.04.20.050237

In addition, please cite the core MendelVar resources listed below.
(Please note that MendelVar is not affiliated with or endorsed by any of them.)
Bibtex | RIS citation file

For any queries, bugs and suggestions, please e-mail the lead developer

OMIM database
ClinVar database
INRICH enrichment
Giggle search engine
ORPHANET database
Genomics England PanelApp
DECIPHER project
Disease Ontology
Human Phenotype Ontology
LDlink webserver


MendelVar development was supported by Springboard award (SBF003\1094).

Ⓒ MRC Integrative Epidemiology Unit, University of Bristol. Last update: 01/Oct/2020