MIM – P8, Px, K1 Variants

In our previous article, we covered a general introduction and P2, P3, and P4 variants. Now, we will take a closer look at the three remaining – P8, Px, and K1.

The P8 variant is associated with the PYROXD1 gene, which encodes nuclear-cytoplasmic pyridine nucleotide-disulphide oxidoreductase domain 1, or in other words, a protein important for oxidative defense of cells. In humans, mutations in this gene have been confirmed as one of the known causes of Myofibrillar Myopathy (MFM). In horses, however, the association between a genetic mutation and the clinical onset of the disease has not been described to date.

Researchers at EquiSeq, which is a company that has developed the genetic tests for MIM, describe two more variants – Px and K1. The Px variant is mentioned in relation to the CACNA2D3 gene, which encodes a protein that is part of the voltage-dependent calcium channel complex. Calcium channels regulate the influx of calcium ions into cells and thus play an important role in signaling processes in the body. The K1 variant is linked to the COL6A3 gene, a gene encoding the collagen type VI alpha 3 chain. Collagen is an important structural protein commonly found in connective tissues. Several types of collagen have been described, and type VI is mainly found in skeletal muscles, tendons, bone, and cartilage.

EquiSeq connects the K1 variant with exercise intolerance and a diagnosis of MIM and says the Px variant doesn’t seem to be a direct cause of MIM-like symptoms. To date, there seem to be no published scientific studies that would have confirmed the correlation between these genetic variants and clinical symptoms. The information on the EquiSeq website is based on the company’s internal data, which cannot be confirmed or refuted using publicly available sources. EquineTest is therefore unable to provide further details or recommendations regarding these variants, because our test is strictly based on scientifically solid data and its content is derived from curated databases of traits well described in scientific literature.

The MIM diagnosis, while its cause might indeed be hidden within the horse’s genetic code,  should be based on clinical symptoms, ruling out other possible causes (such as PSSM1) and a muscle biopsy. However, WGS (whole genome sequencing) might be the right tool to help uncover the true cause of the disease, and it is already highly effective in ruling out other genetic disorders – read more about why to choose EquineTest.