FA2H

Chr 16AR

fatty acid 2-hydroxylase

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

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.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt, Mechanism
LOFmechanismARLOEUF 0.561 OMIM phenotype
Clinical SummaryFA2H
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Gene-Disease Validity (ClinGen)
hereditary spastic paraplegia 35 · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.26) despite low pLI — interpret in context.
📖
GeneReview available — FA2H
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.56LOEUF
pLI 0.147
Z-score 2.96
OE 0.26 (0.140.56)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
0.46Z-score
OE missense 0.91 (0.801.03)
179 obs / 197.0 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.26 (0.140.56)
00.351.4
Missense OE0.91 (0.801.03)
00.61.4
Synonymous OE1.07
01.21.6
LoF obs/exp: 5 / 18.9Missense obs/exp: 179 / 197.0Syn Z: -0.52
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveFA2H-related spastic paraplegiaLOFAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.6841th %ile
GOF
0.5464th %ile
LOF
0.3162th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

FA2H · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
Open Research Assistant →
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗