FA2H

Chr 16AR

fatty acid 2-hydroxylase

Also known as: FAAH, FAH1, FAXDC1, SCS7, SPG35

NCBI Gene: 79152 ENSG00000103089 UniProt: Q7L5A8 OMIM: 611026

This protein catalyzes the synthesis of 2-hydroxysphingolipids in the endoplasmic reticulum, which are essential components of myelin. Mutations cause autosomal recessive spastic paraplegia 35, a leukodystrophy characterized by dysmyelination with spastic paraparesis and variable dystonia. The pathogenic mechanism involves loss of function leading to defective myelin formation and maintenance.

OMIM ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

This gene encodes a protein that catalyzes the synthesis of 2-hydroxysphingolipids, a subset of sphingolipids that contain 2-hydroxy fatty acids. Sphingolipids play roles in many cellular processes and their structural diversity arises from modification of the hydrophobic ceramide moiety, such as by 2-hydroxylation of the N-acyl chain, and the existence of many different head groups. Mutations in this gene have been associated with leukodystrophy dysmyelinating with spastic paraparesis with or without dystonia.[provided by RefSeq, Mar 2010]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Spastic paraplegia 35, autosomal recessiveMIM #612319

Clinical highlights

Gene-disease validity (ClinGen)

hereditary spastic paraplegia 35 · ARDefinitivesufficient evidence for diagnostic panels

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

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P/LP missense

0.56

LOEUF

LOF

Mechanism· G2P