FAH

Chr 15

fumarylacetoacetate hydrolase

NCBI Gene: 2184 ENSG00000103876 UniProt: P16930

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.

GeneReviews ResearchSummary from RefSeq, OMIM

Predicted to enable fumarylacetoacetase activity. Predicted to be involved in L-phenylalanine catabolic process; homogentisate catabolic process; and tyrosine catabolic process. Predicted to act upstream of or within arginine catabolic process. Located in extracellular exosome. Implicated in tyrosinemia type I. [provided by Alliance of Genome Resources, Apr 2025]

GeneReviews ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtTyrosinemia 1

Clinical highlights

Gene-disease validity (ClinGen)

tyrosinemia type I · ARDefinitivesufficient evidence for diagnostic panels

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.41

LOEUF

LOF

Mechanism· G2P

📖

GeneReview available — FAH

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.41LOEUF

pLI 0.000

Z-score -0.06

OE 1.01 (0.74–1.41)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.03Z-score

OE missense 1.01 (0.91–1.12)

244 obs / 242.6 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?1.01 (0.74–1.41)

0≤0.351.4

Missense OE?1.01 (0.91–1.12)

0≤0.61.4

Synonymous OE?1.08

0≤1.21.6

LoF obs/exp: 25 / 24.7Missense obs/exp: 244 / 242.6Syn Z: -0.61

ClinVar Variant Classifications

0 submitted variants in ClinVar

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.

External Resources

Links to major genomics databases and tools

Franklin by Genoox

AI-powered variant curation and clinical analysis

DECIPHER

Genomic variants and phenotypes in rare disease patients

📖

GeneReview available — FAH

Authoritative clinical overview · NCBI Bookshelf · Recommended first read

Open GeneReview ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

Fanconi Anemia Complementation Group A

Gene Therapy for Fanconi Anemia, Complementation Group A

ACTIVE NOT RECRUITING

NCT04248439Phase PHASE2Rocket Pharmaceuticals Inc.Started 2020-07-15

RP-L102

IGF1 Deficiency

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).

RECRUITING

NCT00903110Esteve Pharmaceuticals, S.A.Started 2008-12-09

Increlex®

Fanconi Anemia Complementation Group AFanconi Anemia

Long-Term Follow-up of Subjects With Fanconi Anaemia Subtype A Treated With ex Vivo Gene Therapy

ACTIVE NOT RECRUITING

NCT04437771Rocket Pharmaceuticals Inc.Started 2020-06-01

Safety and efficacy assessments

Scrub Typhus

Scrub Typhus Antibiotic Resistance Trial

ACTIVE NOT RECRUITING

NCT03083197Phase PHASE4University of OxfordStarted 2017-10-15