FAR1 across dismech

FAR1 (fatty acyl-CoA reductase 1) is named by 2 disorder entries, one for each direction of change in its activity.

Normal function

ai-gene-review gives FAR1's core molecular function as alcohol-forming long-chain fatty acyl-CoA reductase activity, acting in ether lipid biosynthetic process; and long-chain fatty-acyl-CoA metabolic process at the peroxisomal membrane. The upstream review is being updated to drop the long-chain fatty-acyl-CoA process from the core set and to use the current GO label of the reductase term.

Disease records

Both entries type FAR1 as causative: Rhizomelic Chondrodysplasia Punctata, Plasmalogen-Synthesis Defect; and Spastic Paraparesis-Cataracts-Speech Delay Syndrome. In the recessive plasmalogen-deficiency entry the variant origin is germline and FAR1 sits on the node Plasmalogen-Synthesis Enzyme Deficiency, as the RCDP4 subtype.

Spastic Paraparesis-Cataracts-Speech Delay Syndrome is the opposite lesion. Its variant origin is de novo, the functional impact is recorded as hypermorphic, and FAR1 sits on the node De Novo Heterozygous FAR1 Arg480 Variant. ClinGen rates this relationship moderate.

Where the layers agree and disagree

The KB and ai-gene-review share the GO process ether lipid biosynthetic process: decreased in the recessive entry and unregulated in the dominant one. ClinGen classifies FAR1 for 2 diseases; both entries are matched to one of them.