-The MPRAVarDB track shows 242,818 variants from 18 MPRA studies compiled -in the MPRAVarDB database +The MPRAVarDB track shows 239,028 variants successfully mapped to hg38 +(from 242,818 total) across 18 MPRA studies compiled in the MPRAVarDB database (Wang et al., 2024). Each variant was experimentally tested in an MPRA experiment to evaluate whether it affects transcriptional regulatory activity. The database covers over 30 cell lines and 30 human diseases and traits, including neurodegenerative diseases, immune disorders, melanoma, multiple myeloma, and autoimmune diseases.
++Note on cell lines: The cell line shown for each variant is the reporter +cell line in which the human regulatory element was assayed. Several studies +used mouse cell lines (e.g. Neuro-2a, N2A, NIH/3T3, MIN6) as reporter systems +for human sequences; these variants retain human (hg38) coordinates. +
Items are colored by statistical significance:
Each item shows the variant name (rsID when available, otherwise chr:pos:ref>alt), the reference and alternate alleles, the associated disease or trait, cell line, log2 fold change, p-value, and FDR.
The following table lists the 18 MPRA studies included in MPRAVarDB, with the number of tested variants, diseases/traits, cell lines, and a brief description of the variant selection.
| Study | Variants | Disease/Trait | Cell Line(s) | Description |
|---|---|---|---|---|
| Griesemer et al., 2021 | 72,588 | NHGRI-EBI GWAS catalog | GM12878, HEK293FT, HMEC, HepG2, K562, SKNSH | 3'UTR SNPs and indels in LD with GWAS catalog variants, variants under positive selection, and rare outlier expression variants from GTEx |
| Kircher et al., 2019 | 44,647 | Various (18 diseases including diabetes, cancer, blood disorders, limb malformations) | HEK293T, HEL92.1.7, HaCaT, HeLa, HepG2, K562, LNCaP, MIN6, NIH/3T3, Neuro-2a, SK-MEL-28, SF7996 | Saturation mutagenesis of 20 disease-associated regulatory elements at single base-pair resolution |
| Abell et al., 2022 | 29,582 | eQTL (no specific disease) | GM12878 | 30,893 variants in LD with independent, common, top-ranked eQTL across 744 eGenes in the CEU cohort |
| Tewhey et al., 2016 | 27,138 | eQTL (no specific disease) | GM12878 | 32,373 variants associated with eQTLs in lymphoblastoid cell lines |
| Schuster et al., 2023 | 26,546 | Prostate cancer | PC3 | 14,497 single-nucleotide mutations enriched in oncogenic pathways and 3'UTR regulatory elements |
| Mouri et al., 2022 | 14,551 | Autoimmune diseases (Crohn's, IBD, psoriasis, MS, RA, T1D, ulcerative colitis) | Jurkat | GWAS variants from autoimmune disease loci tested for regulatory element activity in T cells |
| McAfee et al., 2023 | 10,310 | Schizophrenia | HEK293s, HNPS | 5,173 fine-mapped schizophrenia GWAS variants |
| Cooper et al., 2022 | 5,340 | Alzheimer's disease, Progressive supranuclear palsy | HEK293T | 5,706 noncoding SNVs from 25 AD and 9 PSP genome-wide significant loci |
| Long et al., 2022 | 3,980 | Melanoma | C283T, UACC903 | 1,992 risk-associated variants in tight LD (r2>0.8) from 54 melanoma risk loci |
| Myint et al., 2020 | 2,158 | Schizophrenia, Alzheimer's disease | K562, SH-SY5Y | 1,049 SZ and 30 AD variants in 64 SZ loci and 9 AD loci |
| Choi et al., 2020 | 1,664 | Melanoma | HEK293FT, UACC903 | GWAS melanoma risk variants |
| Ajore et al., 2022 | 1,582 | Multiple myeloma | L363, MOLP8 | 1,039 variants in high LD (r2>0.8) at 23 MM risk loci |
| Klein et al., 2019 | 1,119 | Osteoarthritis | Saos-2 | 1,605 SNPs in high LD (r2>0.8) at 35 lead SNPs associated with OA via GWAS |
| Lu et al., 2021 | 1,038 | Systemic lupus erythematosus | GM12878, Jurkat | 18,312 variants in tight LD (r2>0.8) with 578 GWAS index variants at 531 loci |
| Mulvey & Dougherty, 2021 | 275 | Major depressive disorder | N2A | Over 1,000 SNPs from 39 neuropsychiatric GWAS loci, selected by overlap with eQTL and histone marks |
| Ferraro et al., 2020 | 150 | Rare variant expression (no specific disease) | GM12878 | Rare variants contributing to extreme expression, allelic expression, and splicing across 49 GTEx tissues |
| Rao et al., 2021 | 88 | Alcohol use disorder | BLA, CE, NAC, SFC | SNPs in 3'UTR of 88 genes from allele-specific expression analysis (30 AUD subjects vs 30 controls) |
| Ulirsch et al., 2016 | 62 | Red blood cell traits | K562, K562+GATA1 | 2,756 variants in strong LD with 75 sentinel variants associated with RBC traits |
+Variant counts above are from the source publications (pre-liftOver totals). +Of 242,818 total source variants, 239,028 lifted successfully to hg38; see Methods. +
Data was downloaded from the
MPRAVarDB web server.
Variants originally mapped to hg19 (213,689 of 242,818) were lifted to hg38
using liftOver. 114 variants could not be mapped and were excluded.
The remaining variants were merged with the 29,129 natively hg38-mapped variants
to produce a total of 239,028 hg38 records.
The data can be explored interactively in table format with the Table Browser or the Data Integrator and exported from there to spreadsheet or tab-sep tables. From scripts, the data can be accessed through our API, track=mpraVarDb.
For automated download and analysis, the genome annotation is stored in a bigBed file that can be downloaded from -our download server. +our download server. The file for this track is called mpravardb.bb. Individual regions or the whole genome annotation can be obtained using our tool bigBedToBed, which can be compiled from the source code or downloaded as a precompiled binary for your system. Instructions for downloading source code and binaries can be found here. The tool can also be used to obtain features within a given range, e.g. -bigBedToBed http://hgdownload.soe.ucsc.edu/gbdb/hg38/mpra/mpravardb.bb -chrom=chr21 -start=0 -end=100000000 stdout +bigBedToBed http://hgdownload.soe.ucsc.edu/gbdb/hg38/mpra/mpravardb/mpravardb.bb -chrom=chr21 -start=0 -end=100000000 stdout
The original annotation source data can be downloaded from the MPRAVarDB web server.
Thanks to Tao Wang and colleagues at the University of Florida for creating and maintaining the MPRAVarDB database.
Wang T, Matreyek KA, Yang X. MPRAVarDB: an online database and web server for exploring regulatory effects of genetic variants using MPRA data. Bioinformatics. 2024 Apr 15;40(4):btae201. PMID: 38617248; PMC: PMC11014600