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I was trying to map a mouse gene: Arfgap1 to it's human ortholog. Uniprot shows there are two human orthologs of this gene:

https://www.uniprot.org/uniprot/?query=yourlist:M2021081292C7BAECDB1C5C413EE0E0348724B68210A46CH&sort=yourlist:M2021081292C7BAECDB1C5C413EE0E0348724B68210A46CH&columns=yourlist(M2021081292C7BAECDB1C5C413EE0E0348724B68210A46CH),id,entry%20name,protein%20names,genes,organism,length,reviewed

The two human genes are: ARFGAP1 and ARFGAP3 (it says ARFGAP3 is a synonym of ARFGAP1)

When I tried to find the human homolog in the Mouse Genome Informatics (MGI) database: http://www.informatics.jax.org/downloads/reports/index.html#homology

I found that mouse gene, Arfgap1 only maps to human gene ARFGAP1. What could be a possible explanation for this? Is it possible for a mouse gene to have multiple human orthologs?

Edit: This is just one example. I have encountered mouse genes that have four human orthologs.

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    $\begingroup$ ARFGAP1 and ARFGAP3 are distinct proteins. I think the "synonym" deal is that the two proteins were both referred to as ARFGAP1 in early literature, and one had to be renamed. So, if you're searching for ARFGAP3 literature and want early literature, you may also need to search for the term 'ARFGAP1'. $\endgroup$
    – mgkrebbs
    Aug 13, 2021 at 3:05

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Yes.

If duplication of the human gene happened after the speciation event, we have multiple orthologues. This is shown in the following diagram from Ensembl as one-to-many orthologue (ortholog_one2many). In the example from the figure, one human gene has two mouse orthologues, but it could be vice-versa as in your case.

Ensembl homology types

This is an answer to your general question about orthologues. I haven't looked into details about your particular gene (ARFGAP1).

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