FAR1 was first reported in relation to autosomal recessive fatty acyl-CoA reductase 1 deficiency in 2014 (Buchert et al., PMID: 25439727). 2 nonsense, 1 missense, and 1 in-frame delins variants have been reported in humans. Evidence supporting this gene-disease relationship includes case-level data and experimental data. Summary of case level and experimental data: 6.5 points. Variants in this gene have been reported in at least 3 probands in 2 publications (PMID: 25439727, 33586168). The mechanism for disease is loss of function. This gene-disease association is supported by in vitro functional assays and a knock-out mouse model (PMID: 15220348, 24108123, 36781603). In summary, there is moderate evidence to support this gene-disease relationship. While more evidence is needed to establish this relationship definitively, no convincing contradictory evidence has emerged. This gene-disease pair was originally evaluated by thePeroxisomal GCEP on Jan 12, 2023. It was reevaluated on June 6, 2025 (SOP v 10). Although a new animal model was published (PMID: 36781603), the classification did not change.
Lumping and Splitting Considerations: OMIM entities: Cataracts, spastic paraparesis, and speech delay (MIM# 619338), Peroxisomal fatty acyl-CoA reductase 1 disorder (MIM# 616154). Per criteria outlined by the ClinGen Lumping and Splitting Working Group, we found differences in the molecular mechanisms, inheritance patterns AND phenotypic presentation. Therefore, we have split curations for the disease entities, FAR1 deficiency and FAR1 dysregulation (terms introduced by the peroxisomal GCEP).
The GenCC data are available free of restriction under a CC0 1.0 Universal (CC0 1.0) Public Domain Dedication. The GenCC requests that you give attribution to GenCC and the contributing sources whenever possible and appropriate. The accepted Flagship manuscript is now available from Genetics in Medicine (https://www.gimjournal.org/article/S1098-3600(22)00746-8/fulltext).
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