A mutation (c.947A>T) in CYP2U1 has been associated in a very small number of patients with hereditary spastic paraplegia in that it segregates with the disease at the homozygous state in two afflicted families.

This mutation affects an amino acid (p.Asp316Val) that is highly conserved among CYP2U1 orthologs as well as other cytochrome P450 proteins; this p.Asp314Val mutation is located in the enzyme's functional domain, is predicted to be damaging to the enzyme's activity, and is associated with mitochondria dysfunction.

[8][9] A second homozygous enzyme-disabling mutation has been identified in CYP2U1, c.1A>C/p.Met1?, that is associated with <1% of hereditary spastic paraplegia sufferers.

[10] The reduction in 20-HETE production by these mutations, and thereby in 20-HETE's activation of the TRPV1 neural receptor, it is hypothesized, may contribute to the development of this disease (see 20-Hydroxyeicosatetraenoic acid for details).

[12][13][14] This article incorporates text from the United States National Library of Medicine, which is in the public domain.