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. 2025 Jan 18:2025:baaf049.
doi: 10.1093/database/baaf049.

CobVar-a comprehensive resource of vitamin B12-associated genomic variants

Neha H Suresh  1 , Chaitra A Kilpady  1 , Akshata A Kamath  1 , Ashikh Ahmed  2 , Tinku Thomas  2 , Anura V Kurpad  3 , Ambily Sivadas  4
Affiliations

CobVar-a comprehensive resource of vitamin B12-associated genomic variants

Neha H Suresh et al. Database (Oxford). .

Abstract

The importance of vitamin B12 (cobalamin) in numerous biological processes, including DNA synthesis and cellular energy production, underscores the need for therapeutic and public health strategies to address B12 insufficiency/deficiency in the population. Genetic variations in pathways influencing cobalamin absorption, transport, and metabolism can affect various direct and indirect measures of vitamin B12 status. To facilitate a structured approach to studying these genetic factors, we aimed to systematically curate and create a user-friendly web database that offers comprehensive data on genetic variants influencing B12 biomarkers. A PubMed search was performed for 5 B12 traits [total serum/plasma B12, holotranscobalamin (active B12), total transcobalamin, holohaptocorrin, and methylmalonic acid] resulting in 493 research publications, of which 47 relevant publications were reviewed further. The database backend was built using MongoDB and the web interface was coded in PHP, JavaScript, HTML, and CSS on an Apache HTTP server. We have manually curated and compiled the Cobalamin Associated Genetic Variant (CobVar) database, comprising a total of 324 genetic variant associations for 5 different vitamin B12 traits involving 222 unique genetic variants and 84 genes identified across several genome-wide association studies and candidate gene studies. About one-third of the total genetic variant associations have been reported in >1 independent studies and 15 variants in >1 ethnic group. FUT2 gene showed the maximum number of associations for total serum/plasma B12 (N = 39), followed by MTHFR (N = 24) and TCN2 (N = 23). The database is accessible online at https://datatools.sjri.res.in/VBG/. CobVar is a vital resource for researchers and nutritionists, offering quick access to the latest developments in B12-related genetic variant research and serves as a valuable tool for advancing personalized treatment. Database URL: https://datatools.sjri.res.in/VBG/.

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Conflict of interest statement

None declared.

Figures

Figure 1.
Figure 1.
A summary schematic of the key genes involved in the absorption, transport, and metabolic utilization of B12 across different body compartments. TCN1: transcobalamin I (haptocorrin); TCN2: transcobalamin II; GIF: gastric intrinsic factor (IF); FUT2: fucosyltransferase 2; FUT6: fucosyltransferase 6; CUBN: cubilin; PON1: paraoxonase 1; CD320 (TCblR): transcobalamin receptor; MMACHC: methylmalonic aciduria and homocystinuria type C; LMBRD1: LMBR1 domain containing 1; ABCD4: ATP binding cassette subfamily D member 4; MTHFR: methylenetetrahydrofolate reductase; MTR: 5-methyltetrahydrofolate-homocysteine methyltransferase; MTRR: methionine synthase reductase; DNMT2: DNA methyltransferase 2; MS4A3: membrane spanning 4-domains A3; MUT: methylmalonyl-CoA mutase; MMAB: methylmalonic aciduria type B (adenosyltransferase); MMMAA: methylmalonic aciduria type A (GTPase); CLYBL: citrate lyase beta-like; PRELID2: PRELI domain containing protein 2.
Figure 2.
Figure 2.
A schematic workflow of data collection and database integration for CobVar database.
Figure 3.
Figure 3.
An overlap analysis of genetic variant associations across B12 traits.
Figure 4.
Figure 4.
Distribution of genes reported to be associated with different B12 traits: (a) total plasma/serum B12, (b) holoTC (active B12), (c) holohaptocorrin (holoHC), (d) MMA, and (e) total transcobalamin (totalTC) levels. The number in parentheses next to each gene name represents the count of reported variants within that gene.
Figure 5.
Figure 5.
Screenshots of the CobVar database application featuring the Home page, and the different search query formats that can be used by the user.
Figure 6.
Figure 6.
Screenshots of (a) the expanded database query results, (b) the detailed view of the Variant section, and (c) the Association section.
See this image and copyright information in PMC

References

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