FAH
Chr 15ARfumarylacetoacetate hydrolase
Fumarylacetoacetase catalyzes the final step in tyrosine catabolism, converting fumarylacetoacetate to fumarate and acetoacetate. Mutations cause tyrosinemia type I, an autosomal recessive disorder presenting in infancy with hepatomegaly, failure to thrive, and a characteristic cabbage-like odor, progressing to liver failure, renal tubular dysfunction, and neurologic crises if untreated. Early diagnosis and treatment with nitisinone (NTBC) and dietary restriction can prevent the severe complications of this metabolic disorder.
Definitive — sufficient evidence for diagnostic panels
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly tolerant — LoF variants common in population
Tolerant to missense variation
ClinVar Variant Classifications
400 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 12 | 0 | 7 | 0 | 19 |
Likely Pathogenic | 47 | 10 | 4 | 0 | 61 |
VUS | 2 | 110 | 13 | 7 | 132 |
Likely Benign | 0 | 0 | 117 | 51 | 168 |
Benign | 0 | 0 | 1 | 0 | 1 |
Conflicting | — | 5 | |||
| Total | 61 | 120 | 142 | 58 | 386 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
FAH · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
Global Patient Registry to Monitor Long-term Safety and Effectiveness of Increlex® in Children and Adolescents With Severe Primary Insulin-like Growth Factor-1 Deficiency (SPIGFD).
RECRUITINGLong-Term Follow-up of Subjects With Fanconi Anaemia Subtype A Treated With ex Vivo Gene Therapy
ACTIVE NOT RECRUITINGLentiviral-mediated Gene Therapy for Pediatric Patients With Fanconi Anemia Subtype A
ACTIVE NOT RECRUITINGGene Therapy for Fanconi Anemia, Complementation Group A
ACTIVE NOT RECRUITINGScrub Typhus Antibiotic Resistance Trial
ACTIVE NOT RECRUITINGLong-Term Follow-up: Phase I/II Clinical Study to Evaluate the Safety and Efficacy of the Infusion of RP-L102
ENROLLING BY INVITATIONExternal Resources
Links to major genomics databases and tools