FAH

fumarylacetoacetate hydrolase

Basic information

Region (hg38): 15:80152489-80186946

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 (Supportive), mode of inheritance: AR
• tyrosinemia type I (Definitive), 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 (531 variants)
• not provided (126 variants)
• not specified (51 variants)
• Inborn genetic diseases (11 variants)
• FAH-related condition (6 variants)
• Hypertyrosinemia (2 variants)
• Fumarylacetoacetase pseudodeficiency (1 variants)
• T-substance anomaly (1 variants)
• See cases (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.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			5	133	7	145
missense	5	20	98	3	1	127
nonsense	14	19				33
start loss	2	2				4
frameshift	18	18	1			37
inframe indel			2			2
splice donor/acceptor (+/-2bp)	8	31				39
splice region	2	1	10	26	1	40
non coding			3	80	48	131
Total	47	90	109	216	56

Highest pathogenic variant AF is 0.000269

Variants in FAH

This is a list of pathogenic ClinVar variants found in the FAH region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
15-80152695-GCGGGGTCGGGGCAAGGGGAGGGGCGGGGCTCAGGGAGGGAGGAGAGACTGGAGGACCTGAGGCCCA-G			Likely benign (Apr 25, 2019)
15-80152846-G-C			Benign (Jun 29, 2018)
15-80152847-G-T			Likely benign (Mar 06, 2020)
15-80152877-G-A		Hypertyrosinemia • Tyrosinemia type I	Benign/Likely benign (Jun 29, 2018)
15-80152896-C-G		Tyrosinemia type I	Uncertain significance (Jan 13, 2018)
15-80152950-G-C		Tyrosinemia type I	Benign (Jul 01, 2021)
15-80152988-C-A		Tyrosinemia type I	Uncertain significance (Jan 12, 2018)
15-80152992-C-A		Tyrosinemia type I	Uncertain significance (Jan 13, 2018)
15-80153012-G-T		Tyrosinemia type I • not specified • FAH-related disorder	Conflicting classifications of pathogenicity (Jul 09, 2021)
15-80153015-C-G		Tyrosinemia type I	Uncertain significance (Jan 13, 2018)
15-80153021-C-T		Tyrosinemia type I • not specified	Benign (Jan 13, 2018)
15-80153032-A-C		Tyrosinemia type I	Uncertain significance (Jan 12, 2018)
15-80153048-C-T		not specified	Likely benign (Nov 21, 2017)
15-80153055-A-C		Tyrosinemia type I	Likely pathogenic (Jul 09, 2020)
15-80153055-A-G		Tyrosinemia type I • See cases	Pathogenic (Jan 05, 2024)
15-80153056-T-A		Tyrosinemia type I	Likely pathogenic (Mar 03, 2022)
15-80153057-G-A		Tyrosinemia type I	Pathogenic (Dec 30, 2023)
15-80153063-C-T		Tyrosinemia type I	Likely benign (Sep 08, 2021)
15-80153064-A-C		Tyrosinemia type I	Likely benign (Dec 19, 2023)
15-80153065-TC-T		Tyrosinemia type I	Pathogenic/Likely pathogenic (Dec 01, 2023)
15-80153069-G-A		Tyrosinemia type I	Likely benign (May 30, 2023)
15-80153075-C-T		Tyrosinemia type I	Likely benign (Apr 15, 2023)
15-80153077-A-C		Tyrosinemia type I	Uncertain significance (Sep 12, 2020)
15-80153084-C-T		Tyrosinemia type I	Likely benign (Nov 01, 2022)
15-80153087-C-T		Tyrosinemia type I	Likely benign (Dec 04, 2023)

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
4.03e-17	0.00566	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

Haploinsufficiency Scores

• pHI: 0.141
• hipred: Y
• hipred_score: 0.564
• ghis: 0.508

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

Mouse Genome Informatics

• Gene name: Fah
• Phenotype: liver/biliary system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); neoplasm; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); renal/urinary system phenotype; cellular phenotype; immune system phenotype; homeostasis/metabolism phenotype; endocrine/exocrine gland phenotype; growth/size/body region phenotype

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