FAH

fumarylacetoacetate hydrolase

Basic information

Region (hg38): 15:80152490-80186946

Links

ENSG00000103876 ∙ NCBI:2184 ∙ OMIM:613871 ∙ HGNC:3579 ∙ Uniprot:P16930 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• tyrosinemia type I (Definitive), mode of inheritance: AR
• tyrosinemia type I (Definitive), mode of inheritance: AR
• tyrosinemia type I (Strong), mode of inheritance: AR
• tyrosinemia type I (Definitive), mode of inheritance: AR
• tyrosinemia type I (Definitive), mode of inheritance: AR
• tyrosinemia type I (Supportive), mode of inheritance: AR
• tyrosinemia type I (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Tyrosinemia, type I	AR	Biochemical; Oncologic	Dietary (controlled intake of phenylalanine and tyrosine) and medical (eg, nitsinone) treatment can be beneficial, and may reduce risks related to manifestations (eg, hepatocellular carcinoma) that are part of the natural history in untreated individuals; Some individuals require liver transplantation	Biochemical; Gastrointestinal; Musculoskeletal; Oncologic; Renal	14085846; 14271358; 6016174; 2536631; 2153931; 2378357; 1383656; 1440864; 8028615; 7977370; 7603784; 8829657; 9101289; 9728331; 10603099; 11575602; 12203990; 15759101; 20301688; 22554029

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the FAH gene.

• Tyrosinemia_type_I (737 variants)
• not_provided (113 variants)
• not_specified (51 variants)
• FAH-related_disorder (49 variants)
• Inborn_genetic_diseases (45 variants)
• Tyrosinemia (3 variants)
• Renal_tubulopathies (1 variants)
• Beta-D-mannosidosis (1 variants)
• T-substance_anomaly (1 variants)
• See_cases (1 variants)
• Hypertyrosinemia (1 variants)
• Tyrosinemia_type_II (1 variants)
• Fumarylacetoacetase_pseudodeficiency (1 variants)
• Hepatoblastoma (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the FAH gene is commonly pathogenic or not. These statistics are base on transcript: NM_000000137.4. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous		1	10	189	5	205
missense	7	38	180	12	1	238
nonsense	18	17	1			36
start loss	2	3				5
frameshift	21	26	2			49
splice donor/acceptor (+/-2bp)	9	43	1			53
Total	57	128	194	201	6

Highest pathogenic variant AF is 0.00037998284

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
FAH	protein_coding	protein_coding	ENST00000407106	14	34457

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
		125619	0	129	125748	0.000513

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.0329	244	243	1.01	0.0000143	2765
Missense in Polyphen		88	97.401	0.90348		1110
Synonymous	-0.613	104	96.3	1.08	0.00000645	806
Loss of Function	-0.0581	25	24.7	1.01	0.00000128	268

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00110	0.00110
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.000754	0.000739
European (Non-Finnish)	0.000660	0.000659
Middle Eastern	0.00	0.00
South Asian	0.000229	0.000229
Other	0.000327	0.000326

dbNSFP

Source: dbNSFP

• Pathway: Tyrosine metabolism - Homo sapiens (human);Tyrosinemia, transient, of the newborn;Dopamine beta-hydroxylase deficiency;Disulfiram Action Pathway;Phenylalanine and Tyrosine Metabolism;Tyrosine Metabolism;Alkaptonuria;Monoamine oxidase-a deficiency (MAO-A);Hawkinsinuria;Tyrosinemia Type I;Phenylketonuria;Tyrosinemia Type 3 (TYRO3);Tyrosinemia Type 2 (or Richner-Hanhart syndrome);Amino Acid metabolism;Citrate cycle;Histidine, lysine, phenylalanine, tyrosine, proline and tryptophan catabolism;Metabolism of amino acids and derivatives;Phenylalanine and tyrosine catabolism;Metabolism;tyrosine degradation;Tyrosine metabolism (Consensus)

Recessive Scores

• pRec: 0.243

Intolerance Scores

• loftool: 0.239
• rvis_EVS: -0.91
• rvis_percentile_EVS: 10.03

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.981

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Gene ontology

• Biological process: arginine catabolic process;L-phenylalanine catabolic process;tyrosine catabolic process;homogentisate catabolic process
• Cellular component: cytosol;extracellular exosome
• Molecular function: fumarylacetoacetase activity;protein binding;metal ion binding