How can I find mutations associated with disease in human histone residues?

Question

I would like to look if there are mutations in residues of human histones associated with any disease. For instance, if a mutation in residue K6 (lysine 6) of histone H2A1A is associated with any human disease, (with PUBMED evidence, preferably), but in a systematic way (for all types of histones and all residues).

The purpose of this is to get some candidate residues to study. I have checked the OMIM database but I didn't find anything relevant. It seems that there is no systematic way to connect specific residues to diseases and search for them.

Is there any web database or API available for this purpose?

Answer 1

Ensembl contains this information: When you go to the “phenotype” menu item of a given gene, you will see a list of variants (potentially after clicking on “ALL associated variants”) with their associated genomic position.

You can subtract the transcript’s start position from that position to find out the residue (of the translated sequence, and be careful to subtract the lengths of all preceding introns!). Unfortunately this seems to require some manual work.

Alternatively you can query the individual SNPs, which will tell you their position in all transcripts (in this case: Leu 298/68/244):

Answer 2

I found DisGeNET useful for my purpose, a database that associates genes with diseases and, if known, gene variants with diseases. It integrates several sources of information for computing a score of association of gene/variation with the disease ( Piñero et al., 2016, Piñero et al., 2015):

• Gene Disease Associations from UniProt, PsyGeNET, ClinVar, Orphanet, the GWAS Catalog, CTD (human data), and Human Phenotype Ontology, RGD, MGD, and CTD (mouse and rat data) GAD, LHGDN and BeFree

• Variants Disease Associations from ClinVar, the GWAS Catalog, Uniprot, GAD, and from BEFREE

If available, it provides the Pubmed ID of articles supporting the proposed association and the rs id from the dbSNP for variants associated to disease.

In addition it provides an experimental R package, disgenet2r, that allows to query the database in a programmatic manner and that provides some plot functions to generate representations of the associations founded.

Using this approach, I have been able to found several human histone-disease associations (not my original purpose), together with some concrete histone residues that are mutated in specific diseases.