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Is there an accepted boundary of the extended major histocompatibility complex (xMHC) in human? Specifically, I am interested in the boundary coordinates for Genome Reference Consortium Human Build 38 (GRCh38 / hg38).

I'd like to use these coordinates to query MyGene.info to retrieve a list of genes in the xMHC. For example, King et al 2019 used the following definition:

we excluded drugs with nonhuman or xMHC gene targets. We considered xMHC to include HIST1H2AA and KIFC1 and all genes between them (Chromosome 6 25.7 Mb-33.4 Mb).

But I was curious whether there was an authoritative definition of the xMHC region in humans that would specify down the the base pair rather than just megabase pair.

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  • $\begingroup$ This is an extremely good question, these genomic coordinates of course exist, the only thing is MHC ... would include mice as well as humans. The HLA.is very well defined but I think you need to ask an immunologist because it is common knowledge, but I don't think any one here knows. $\endgroup$
    – M__
    Oct 29 '20 at 1:53
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Here is one definition of the classical MHC region: https://www.ncbi.nlm.nih.gov/grc/human/regions/MHC?asm=GRCh38.p13

which defines it as the 5mb region chr6:28510120-33480577 in GRCh38 coordinates.

The "extended MHC" defined here [1] is 7.2 mb and encompasses an additional "extended Class I" region upstream of the region given above. The xMHC is defined in [1] as the regions between HIST1H2AA and RPL12P1 genes, which would give you chr6:25726063-33400644 in Grch38. This is very similar to your HIST1H2AA - KIFC1 definition (chr6:25726063-33410226). Of course if you're trying to reproduce a result, probably better to use the original paper's definition.

[1] https://www.nature.com/articles/nrg1489

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  • $\begingroup$ Thanks! Sounds like the 2004 Nat Rev Genetics article titled Gene map of the extended human MHC that you link to is the most authoritative source for the xMHC boundaries. I see in Figure 1, the xMHC goes from HIST1H2AA (extended class I subregion) to RPL12P1 (extended class II subregion). The flanking regions in grey are not part of the xMHC. Note that RPL12P1 is contained within KIFC1, such that KIFC1 starts before and ends after RPL12P1 in coordinate space. $\endgroup$ Nov 2 '20 at 21:56
  • $\begingroup$ Here is a MyGene.info query that returns all NCBI gene IDs and symbols in between chr6:25,726,063-33,410,226 for GRCh38. I like these boundaries since KIFC1 extends past RPL12P1. For some reason RPL12P1 is not included in the MyGene results. Not sure why. It is a pseudogene, but other pseudogenes are included. The MyGene query currently returns 318 genes. $\endgroup$ Nov 2 '20 at 22:56
  • $\begingroup$ The approved symbol for ncbigene:221613 is now H2AC1 rather than HIST1H2AA. KIFC1 is ncbigene:3833. RPL12P1 is ncbigene:729727. $\endgroup$ Nov 2 '20 at 23:18

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