FAH (gen)

FAH
Dostupne strukture
PDB	Pretraga ortologa: PDBe RCSB
Spisak PDB ID kodova
	1HYO, 1QCN, 1QCO, 1QQJ, 2HZY
Identifikatori
Aliasi	FAH
Vanjski ID-jevi	OMIM: 613871 MGI: 95482 HomoloGene: 110 GeneCards: FAH
Lokacija gena (čovjek)
Hrom.	Hromosom 15 (čovjek)
Kraj	80,186,946 bp
Lokacija gena (miš)
Hrom.	Hromosom 7 (miš)
Kraj	84,255,930 bp
Obrazac RNK ekspresije
	Više referentnih podataka o ekspresiji
Ontologija gena
Molekularna funkcija	• fumarylacetoacetase activity; • GO:0001948, GO:0016582 vezivanje za proteine; • catalytic activity; • hydrolase activity; • vezivanje iona metala;
Ćelijska komponenta	• citosol; • Egzosom;
Biološki proces	• aromatic amino acid family metabolic process; • metabolizam; • L-phenylalanine catabolic process; • arginine catabolic process; • tyrosine catabolic process; • homogentisate catabolic process;
	Izvori:Amigo / QuickGO
Ortolozi
	2184
	14085
	ENSG00000103876
	ENSMUSG00000030630
	P16930
	P35505
	NM_000137; NM_001374377; NM_001374380
	NM_010176
	NP_000128; NP_001361306; NP_001361309
	NP_034306
	Wikipodaci
Pogledaj/uredi – čovjek	Pogledaj/uredi – miš

Fumarilacetoacetaza je enzim koji je kod ljudi kodiran genom FAH lociranom na hromosomu 15. Smatra se da je kod ljudi FAH uključen u katabolizam aminokiseline fenilalanina.^[5]^[6]^[7]

Aminokiselinska sekvenca

Dužina polipeptidnog lanca je 419 aminokiselina, a molekulska težina 46.374 Da.^[8].

10	20	30	40	50
MSFIPVAEDS	DFPIHNLPYG	VFSTRGDPRP	RIGVAIGDQI	LDLSIIKHLF
TGPVLSKHQD	VFNQPTLNSF	MGLGQAAWKE	ARVFLQNLLS	VSQARLRDDT
ELRKCAFISQ	ASATMHLPAT	IGDYTDFYSS	RQHATNVGIM	FRDKENALMP
NWLHLPVGYH	GRASSVVVSG	TPIRRPMGQM	KPDDSKPPVY	GACKLLDMEL
EMAFFVGPGN	RLGEPIPISK	AHEHIFGMVL	MNDWSARDIQ	KWEYVPLGPF
LGKSFGTTVS	PWVVPMDALM	PFAVPNPKQD	PRPLPYLCHD	EPYTFDINLS
VNLKGEGMSQ	AATICKSNFK	YMYWTMLQQL	THHSVNGCNL	RPGDLLASGT
ISGPEPENFG	SMLELSWKGT	KPIDLGNGQT	RKFLLDGDEV	IITGYCQGDG
YRIGFGQCAG	KVLPALLPS

Simboli

C: Cistein
D: Asparaginska kiselina
E: Glutaminska kiselina
F: Fenilalanin
G: Glicin
H: Histidin
I: Izoleucin
K: Lizin
L: Leucin
M: Metionin
N: Asparagin
P: Prolin
Q: Glutamin
R: Arginin
S: Serin
T: Treonin
V: Valin
W: Triptofan
Y: Tirozin

Struktura

Kompletni genotip FAH je prethodno uspostavljen. Svi mogući opsezi pokazuju dvije štetne mutacije. Analiziran je njihov učinak na većinu abnormalnosti na mHNK FAH. Identifikacija genskih defekata na oba alela omogućava početnu analizu genotipa i fenotipa za hronične, subakutne i akutne HT1 pacijente. FAH gen nalazi se na području hromozoma 15q25.1 i sadrži 14 egzona. Kodira protein dužine 46 kDa. Otkriveno je više izoformi proteina nastalih alternativnom preradom. Gen se uglavnom eksprimira u jetri i bubrezima.

Funkcija

Fumarilacetoacetat-hidrolaza (FAH) je proteinski homodimer koji cijepa fumarilacetoacetat na njegovoj vezi ugljik-ugljik, tokom reakcije hidrolize.^[9] Kao kritični enzim u metabolizmu fenilalanina i tirozina, 4-fumarilacetoacetat-hidrolaza katalizira završni korak u katabolizmu 4-fumarilacetoacetata i vode u acetoacetat, fumarat i H⁺.^[10] These hydrolytic reactions are essential during aromatic amino acid human metabolism. Furthermore, FAH does not share known protein sequence homologs with other nucleotides or amino acids.^[9]

Mehanizam reakcije

Model aktivnog mjesta 4-fumarilacetoacetazne veze sa veznim mjestom metalnog liganda i fumarilacetoacetatnog analoga.
Fumarilacetoacetatni analog (zeleno), Mg²⁺ (plavo), Ca²⁺ (crveno), substrat-koordiniranih ostataka (Beige)^[10]^[11]

Aktivno mjesto FAH-a sadrži Ca +²⁺ koji djeluje na vezanje supstrata i katalitska trijada ]Glu-His-voda funkcionira gdje imidaksolni prsten His133 aktivira nukleofilnu molekulu vode za napad na vezu ugljik-ugljik fumarilaktoacetata, stvarajući tako fumarat i acetoacetat.^[12] Slično putevima povezanim sa fenilalaninom, reakciona molekulska osnova je presudna u metabolizmu sisara, što dokazuje i opažena aktivnost enzima jetre u nedostatku FAH-a, tokom nasljednog tipa tirozinemije 1.^[13]^[14] U ljudi se ovaj enzim uglavnom eksprimira u jetri. FAH je među aminokiselinskim hidroksilazama.^[11] Tirozin-aminotransferaza (TAT), 4-hidroksifenilpiruvat-dioksigenaza (HPD, homogentizat 1,2-dioksigenaza (HGD , tirozin-aminotransferaza (TAT), 4-hidroksifenilpiruvat-dioksigenaza (HPD, homogentizat 1,2-dioksigenaza (HGD , fenilalanin-4-hidroksilaza (PAH), maleleketoacetat-izomeraza (GSTZ1) i druge aminokiselinske kataboličke hidroksilaze takođe su povezane u biološkom procesu hidroksilaza.^[7]^[15] FAH potput je dio glavne razgradnje aminokiselina L-fenilalanina. Za promet unesenog fenilalanina za sintezu proteina, FAH je izravno povezan sa metodima zasnovanim na liječenju.

Konverzija 4-fumarilacetoacetata u fumarat i acetoacetat međuodnosi pstalih puteva razlaganja fenilalanina, koji kataliziraju odgovarajuće korake i kofaktore.

Mutacije

Aktivnost fumarilacetoacetatne fumarilhidrolazeljudske jetre određena je fumarilacetoacetatom kao supstratom.^[16] Kao urođena greška metabolizma, tirozinemija tip I proizlazi iz nedostatka enzimskog kataboličkog puta fumarilacetoacetat-hidrolaze (FAH). Do sada prijavljene mutacije uključuju tihe mutacije, zamjene aminokiselina unutar jednobaznih supstitucija, besmislene kodone i nedostatke prerade.^[16]^[17]^[18] Mutacije širom gena FAH stvaraju nakupine aminokiselinskih ostataka kao što su ostaci alanina i asparaginske kiseline. Nasljedna tirozinemija tip 1 je metabolički poremećaj s autosomno recesivnim načinom nasljeđivanja. Bolest je uzrokovana nedostatkom fumarilacetoacetat-hidrolaze (FAH), posljednjeg enzima na putu razgradnje tirozina. Očituje se u akutnom ili hroničnom obliku.^[19] Međutim, simptomi se mogu pojaviti kod mutiranih heterozigota u genu FAH, kao što je dokumentirano u slučaju 12-godišnjeg američkog dječaka s hroničnom tirozinemijom tipa 1.^[20] Konkretno, majčinski aleli za kodon 234 pokazuju ovu mutaciju koja mijenja triptofan u glicin. To vjerovatno sugerira misens mutacije HT1, koje također inhibiraju enzimsku aktivnost. To se također pripisuje primijećenom klasterizmu između aktivnih mjesta ostataka aminokiselina 230 i 250, među stotinama drugih mutacija u genu FAH. Korelacija gena FAH sa HT1 ne povezuje klinički fenotip s genotipom.

Simptomi

Mogući simptom bolesti je razvoj nasljedne tirozinemije tipa 1 (HT1). Uzrokovan je nedostatkom fumarilacetoacetat hidrolaze (FAH), posljednjeg enzima u kataboličkom putu tirozina, HT 1 se nasljeđuje kao rijetka autosomno recesivna bolest s prevalencijom u Evropi od 1/50.000. Međutim, u izoliranim dijelovima provincija Quebeca učestalost može biti tako visoka kao ½.000 sa frekvencijom nositelja od 1:20, moguće zbog mutacije jednog osnivača. Nedostatak FAH dovodi do nakupljanja alkilafing-metabolita koji uzrokuju oštećenje jetre. Poremećaj se predstavlja kao akutni, hronični ili srednje blagi fenotip. Akutni oblik manifestira se u prvoj polovini godine, a karakterizira ga zatajenje jetre, oštećenje bubrega i moguće smrt u prvoj godini života.^[21] Hronični oblik javlja se u dobi početka više od godinu dana nakon rođenja;^[22] rahitis i progresivna bolest jetre često dovode do razvoja hepatoćelijskog karcinoma. Ostali simptomi mogu uključivati ozljedu bubrežnih tubula, nekrozu jetre, epizodnu slabost, napadae. Bibrežni Fanconijev sindrom i porfirinska kriza se također navode, uz oštećenje jetre i bubrega.^[19]

Liječenje

Još ne postoji lijek za tirozinemiju tipa 1. Dijagnosticiranim osobama trebaju posebna prehrambena ograničenja tokom cijelog života za aminokiseline, fenilalanin i tirozin.^[23]^[24] Pogođene osobe mogu se liječiti i lijekom odobrenim od strane FDA, nazvanim nitisinon. Preporučeni tretman treba započeti što je ranije moguće kada se dijagnosticira stanje. Analiza inhibicije bakterija, poput Guthrie testa, može pored novonastale bolesti kod djece utvrditi i nedostatak FAH uz povećani nivo fenilalanina.^[24]^[25] Ostale dijagnostičke metode uključuju mjerenja s tandemskom fragmentacijom masene spektrometrije. Nekim osobama je potrebna transplantacija jetre ako bolest jetre napreduje u napredni razvoj prije nego što počne dijetalno liječenje.

Reference

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000103876 - Ensembl, maj 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000030630 - Ensembl, maj 2017
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ Phaneuf D, Labelle Y, Bérubé D, Arden K, Cavenee W, Gagné R, Tanguay RM (mart 1991). "Cloning and expression of the cDNA encoding human fumarylacetoacetate hydrolase, the enzyme deficient in hereditary tyrosinemia: assignment of the gene to chromosome 15". American Journal of Human Genetics. 48 (3): 525–35. PMC 1682993. PMID 1998338.
^ Agsteribbe E, van Faassen H, Hartog MV, Reversma T, Taanman JW, Pannekoek H, Evers RF, Welling GM, Berger R (april 1990). "Nucleotide sequence of cDNA encoding human fumarylacetoacetase". Nucleic Acids Research. 18 (7): 1887. doi:10.1093/nar/18.7.1887. PMC 330610. PMID 2336361.
^ ^a ^b "Entrez Gene: FAH fumarylacetoacetate hydrolase (fumarylacetoacetase)".
^ "UniProt, P16930". Pristupljeno 13. 7. 2021.
^ ^a ^b Timm DE, Mueller HA, Bhanumoorthy P, Harp JM, Bunick GJ (septembar 1999). "Crystal structure and mechanism of a carbon-carbon bond hydrolase". Structure. 7 (9): 1023–33. doi:10.1016/s0969-2126(99)80170-1. PMID 10508789.
^ ^a ^b Universal protein resource accession number P16930 for "FAH - Fumarylacetoacetase - Homo sapiens (Human) - FAH gene & protein" na UniProt.
^ ^a ^b Tanguay RM, Valet JP, Lescault A, Duband JL, Laberge C, Lettre F, Plante M (august 1990). "Different molecular basis for fumarylacetoacetate hydrolase deficiency in the two clinical forms of hereditary tyrosinemia (type I)". American Journal of Human Genetics. 47 (2): 308–16. PMC 1683717. PMID 2378356.
^ Bateman RL, Bhanumoorthy P, Witte JF, McClard RW, Grompe M, Timm DE (maj 2001). "Mechanistic inferences from the crystal structure of fumarylacetoacetate hydrolase with a bound phosphorus-based inhibitor". The Journal of Biological Chemistry. 276 (18): 15284–91. doi:10.1074/jbc.M007621200. PMID 11154690.
^ Kvittingen, E.A.; Jellum, E.; Stokke, O. (24. 9. 1981). "Assay of fumarylacetoacetate fumarylhydrolase in human liver — deficient activity in a case of hereditary tyrosinemia". Clinica Chimica Acta (jezik: engleski). 115 (3): 311–319. doi:10.1016/0009-8981(81)90244-8. PMID 7296877.
^ Kvittingen, E.A.; Jellum, E.; Stokke, O. (24. 9. 1981). "Assay of fumarylacetoacetate fumarylhydrolase in human liver — deficient activity in a case of hereditary tyrosinemia". Clinica Chimica Acta (jezik: engleski). 115 (3): 311–319. doi:10.1016/0009-8981(81)90244-8. ISSN 0009-8981. PMID 7296877.
^ Sniderman King L, Trahms C, Scott CR (juli 2006). "Tyrosinemia Type I". u Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJ, Stephens K, Amemiya A (ured.). GeneReviews. Seattle: University of Washington. PMID 20301688.
^ ^a ^b Labelle Y, Phaneuf D, Leclerc B, Tanguay RM (juli 1993). "Characterization of the human fumarylacetoacetate hydrolase gene and identification of a missense mutation abolishing enzymatic activity". Human Molecular Genetics. 2 (7): 941–6. doi:10.1093/hmg/2.7.941. PMID 8364576.
^ Rootwelt H, Berger R, Gray G, Kelly DA, Coşkun T, Kvittingen EA (oktobar 1994). "Novel splice, missense, and nonsense mutations in the fumarylacetoacetase gene causing tyrosinemia type 1". American Journal of Human Genetics. 55 (4): 653–8. PMC 1918286. PMID 7942842.
^ St-Louis, Maryse; Tanguay, Robert M. (1997). "Mutations in the fumarylacetoacetate hydrolase gene causing hereditary tyrosinemia type I: Overview". Human Mutation. 9 (4): 291–299. doi:10.1002/(sici)1098-1004(1997)9:4<291::aid-humu1>3.0.co;2-9. ISSN 1059-7794. PMID 9101289.
^ ^a ^b Ploos van Amstel JK, Bergman AJ, van Beurden EA, Roijers JF, Peelen T, van den Berg IE, Poll-The BT, Kvittingen EA, Berger R (januar 1996). "Hereditary tyrosinemia type 1: novel missense, nonsense and splice consensus mutations in the human fumarylacetoacetate hydrolase gene; variability of the genotype-phenotype relationship". Human Genetics. 97 (1): 51–9. doi:10.1007/BF00218833. PMID 8557261.
^ Hahn SH, Krasnewich D, Brantly M, Kvittingen EA, Gahl WA (1995). "Heterozygosity for an exon 12 splicing mutation and a W234G missense mutation in an American child with chronic tyrosinemia type 1". Human Mutation. 6 (1): 66–73. doi:10.1002/humu.1380060113. PMID 7550234.
^ Phaneuf D, Lambert M, Laframboise R, Mitchell G, Lettre F, Tanguay RM (oktobar 1992). "Type 1 hereditary tyrosinemia. Evidence for molecular heterogeneity and identification of a causal mutation in a French Canadian patient". The Journal of Clinical Investigation. 90 (4): 1185–92. doi:10.1172/JCI115979. PMC 443158. PMID 1401056.
^ Mohamed S, Kambal MA, Al Jurayyan NA, Al-Nemri A, Babiker A, Hasanato R, Al-Jarallah AS (septembar 2013). "Tyrosinemia type 1: a rare and forgotten cause of reversible hypertrophic cardiomyopathy in infancy". BMC Research Notes. 6: 362. doi:10.1186/1756-0500-6-362. PMC 3846631. PMID 24016420.
^ OMIM: Tyrosinemia, Type I; TYRSN1 -276700
^ ^a ^b Chinsky JM, Singh R, Ficicioglu C, van Karnebeek CD, Grompe M, Mitchell G, Waisbren SE, Gucsavas-Calikoglu M, Wasserstein MP, Coakley K, Scott CR (decembar 2017). "Diagnosis and treatment of tyrosinemia type I: a US and Canadian consensus group review and recommendations". Genetics in Medicine. 19 (12): 1380. doi:10.1038/gim.2017.101. PMC 5729346. PMID 28771246.
^ "Tyrosinemia type 1 | Genetic and Rare Diseases Information Center (GARD) – an NCATS Program". rarediseases.info.nih.gov. Pristupljeno 13. 12. 2018.

Dopunska literatura

St-Louis M, Tanguay RM (1997). "Mutations in the fumarylacetoacetate hydrolase gene causing hereditary tyrosinemia type I: overview". Human Mutation. 9 (4): 291–9. doi:10.1002/(SICI)1098-1004(1997)9:4<291::AID-HUMU1>3.0.CO;2-9. PMID 9101289.
Phaneuf D, Lambert M, Laframboise R, Mitchell G, Lettre F, Tanguay RM (oktobar 1992). "Type 1 hereditary tyrosinemia. Evidence for molecular heterogeneity and identification of a causal mutation in a French Canadian patient". The Journal of Clinical Investigation. 90 (4): 1185–92. doi:10.1172/JCI115979. PMC 443158. PMID 1401056.
Tanguay RM, Valet JP, Lescault A, Duband JL, Laberge C, Lettre F, Plante M (august 1990). "Different molecular basis for fumarylacetoacetate hydrolase deficiency in the two clinical forms of hereditary tyrosinemia (type I)". American Journal of Human Genetics. 47 (2): 308–16. PMC 1683717. PMID 2378356.
Laberge C, Grenier A, Valet JP, Morissette J (august 1990). "Fumarylacetoacetase measurement as a mass-screening procedure for hereditary tyrosinemia type I". American Journal of Human Genetics. 47 (2): 325–8. PMC 1683713. PMID 2378358.
Kvittingen EA, Halvorsen S, Jellum E (juli 1983). "Deficient fumarylacetoacetate fumarylhydrolase activity in lymphocytes and fibroblasts from patients with hereditary tyrosinemia". Pediatric Research. 17 (7): 541–4. doi:10.1203/00006450-198307000-00005. PMID 6622096.
Kvittingen EA, Jellum E, Stokke O (septembar 1981). "Assay of fumarylacetoacetate fumarylhydrolase in human liver-deficient activity in a case of hereditary tyrosinemia". Clinica Chimica Acta; International Journal of Clinical Chemistry. 115 (3): 311–9. doi:10.1016/0009-8981(81)90244-8. PMID 7296877.
Hahn SH, Krasnewich D, Brantly M, Kvittingen EA, Gahl WA (1995). "Heterozygosity for an exon 12 splicing mutation and a W234G missense mutation in an American child with chronic tyrosinemia type 1". Human Mutation. 6 (1): 66–73. doi:10.1002/humu.1380060113. PMID 7550234.
St-Louis M, Poudrier J, Phaneuf D, Leclerc B, Laframboise R, Tanguay RM (februar 1995). "Two novel mutations involved in hereditary tyrosinemia type I". Human Molecular Genetics. 4 (2): 319–20. doi:10.1093/hmg/4.2.319. PMID 7757089.
Kato S, Sekine S, Oh SW, Kim NS, Umezawa Y, Abe N, Yokoyama-Kobayashi M, Aoki T (decembar 1994). "Construction of a human full-length cDNA bank". Gene. 150 (2): 243–50. doi:10.1016/0378-1119(94)90433-2. PMID 7821789.
Rootwelt H, Berger R, Gray G, Kelly DA, Coşkun T, Kvittingen EA (oktobar 1994). "Novel splice, missense, and nonsense mutations in the fumarylacetoacetase gene causing tyrosinemia type 1". American Journal of Human Genetics. 55 (4): 653–8. PMC 1918286. PMID 7942842.
Rootwelt H, Brodtkorb E, Kvittingen EA (decembar 1994). "Identification of a frequent pseudodeficiency mutation in the fumarylacetoacetase gene, with implications for diagnosis of tyrosinemia type I". American Journal of Human Genetics. 55 (6): 1122–7. PMC 1918441. PMID 7977370.
Rootwelt H, Chou J, Gahl WA, Berger R, Coşkun T, Brodtkorb E, Kvittingen EA (juni 1994). "Two missense mutations causing tyrosinemia type 1 with presence and absence of immunoreactive fumarylacetoacetase". Human Genetics. 93 (6): 615–9. doi:10.1007/BF00201558. PMID 8005583.
Grompe M, St-Louis M, Demers SI, al-Dhalimy M, Leclerc B, Tanguay RM (august 1994). "A single mutation of the fumarylacetoacetate hydrolase gene in French Canadians with hereditary tyrosinemia type I". The New England Journal of Medicine. 331 (6): 353–7. doi:10.1056/NEJM199408113310603. PMID 8028615.
St-Louis M, Leclerc B, Laine J, Salo MK, Holmberg C, Tanguay RM (januar 1994). "Identification of a stop mutation in five Finnish patients suffering from hereditary tyrosinemia type I". Human Molecular Genetics. 3 (1): 69–72. doi:10.1093/hmg/3.1.69. PMID 8162054.
Grompe M, al-Dhalimy M (1993). "Mutations of the fumarylacetoacetate hydrolase gene in four patients with tyrosinemia, type I". Human Mutation. 2 (2): 85–93. doi:10.1002/humu.1380020205. PMID 8318997.
Labelle Y, Phaneuf D, Leclerc B, Tanguay RM (juli 1993). "Characterization of the human fumarylacetoacetate hydrolase gene and identification of a missense mutation abolishing enzymatic activity". Human Molecular Genetics. 2 (7): 941–6. doi:10.1093/hmg/2.7.941. PMID 8364576.
Labelle Y, Puymirat J, Tanguay RM (januar 1993). "Localization of cells in the rat brain expressing fumarylacetoacetate hydrolase, the deficient enzyme in hereditary tyrosinemia type 1". Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease. 1180 (3): 250–6. doi:10.1016/0925-4439(93)90046-4. PMID 8422430.
Ploos van Amstel JK, Bergman AJ, van Beurden EA, Roijers JF, Peelen T, van den Berg IE, Poll-The BT, Kvittingen EA, Berger R (januar 1996). "Hereditary tyrosinemia type 1: novel missense, nonsense and splice consensus mutations in the human fumarylacetoacetate hydrolase gene; variability of the genotype-phenotype relationship". Human Genetics. 97 (1): 51–9. doi:10.1007/bf00218833. PMID 8557261.

Vanjski linkovi

GeneReviews/NIH/NCBI/UW entry on Tyrosinemia Type 1, FAH Deficiency, Hepatorenal Tyrosinemia, Hereditary Tyrosinemia Type I, Fumarylacetoacetase Deficiency, Fumarylacetoacetate Hydrolase Deficiency
fumarylacetoacetase na US National Library of Medicine Medical Subject Headings (MeSH)

Šablon:Hidrolaze ugljik-ugljik Šablon:Enzimei

Portal Biologija

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000103876 - Ensembl, maj 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000030630 - Ensembl, maj 2017

[3] "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[4] "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[pmid1998338-5] Phaneuf D, Labelle Y, Bérubé D, Arden K, Cavenee W, Gagné R, Tanguay RM (mart 1991). "Cloning and expression of the cDNA encoding human fumarylacetoacetate hydrolase, the enzyme deficient in hereditary tyrosinemia: assignment of the gene to chromosome 15". American Journal of Human Genetics. 48 (3): 525–35. PMC 1682993. PMID 1998338.

[pmid2336361-6] Agsteribbe E, van Faassen H, Hartog MV, Reversma T, Taanman JW, Pannekoek H, Evers RF, Welling GM, Berger R (april 1990). "Nucleotide sequence of cDNA encoding human fumarylacetoacetase". Nucleic Acids Research. 18 (7): 1887. doi:10.1093/nar/18.7.1887. PMC 330610. PMID 2336361.

[entrez-7] "Entrez Gene: FAH fumarylacetoacetate hydrolase (fumarylacetoacetase)".

[UniProt-8] "UniProt, P16930". Pristupljeno 13. 7. 2021.

[:0-9] Timm DE, Mueller HA, Bhanumoorthy P, Harp JM, Bunick GJ (septembar 1999). "Crystal structure and mechanism of a carbon-carbon bond hydrolase". Structure. 7 (9): 1023–33. doi:10.1016/s0969-2126(99)80170-1. PMID 10508789.

[:10-10] Universal protein resource accession number P16930 for "FAH - Fumarylacetoacetase - Homo sapiens (Human) - FAH gene & protein" na UniProt.

[:1-11] Tanguay RM, Valet JP, Lescault A, Duband JL, Laberge C, Lettre F, Plante M (august 1990). "Different molecular basis for fumarylacetoacetate hydrolase deficiency in the two clinical forms of hereditary tyrosinemia (type I)". American Journal of Human Genetics. 47 (2): 308–16. PMC 1683717. PMID 2378356.

[12] Bateman RL, Bhanumoorthy P, Witte JF, McClard RW, Grompe M, Timm DE (maj 2001). "Mechanistic inferences from the crystal structure of fumarylacetoacetate hydrolase with a bound phosphorus-based inhibitor". The Journal of Biological Chemistry. 276 (18): 15284–91. doi:10.1074/jbc.M007621200. PMID 11154690.

[13] Kvittingen, E.A.; Jellum, E.; Stokke, O. (24. 9. 1981). "Assay of fumarylacetoacetate fumarylhydrolase in human liver — deficient activity in a case of hereditary tyrosinemia". Clinica Chimica Acta (jezik: engleski). 115 (3): 311–319. doi:10.1016/0009-8981(81)90244-8. PMID 7296877.

[14] Kvittingen, E.A.; Jellum, E.; Stokke, O. (24. 9. 1981). "Assay of fumarylacetoacetate fumarylhydrolase in human liver — deficient activity in a case of hereditary tyrosinemia". Clinica Chimica Acta (jezik: engleski). 115 (3): 311–319. doi:10.1016/0009-8981(81)90244-8. ISSN 0009-8981. PMID 7296877.

[:4-15] Sniderman King L, Trahms C, Scott CR (juli 2006). "Tyrosinemia Type I". u Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJ, Stephens K, Amemiya A (ured.). GeneReviews. Seattle: University of Washington. PMID 20301688.

[:6-16] Labelle Y, Phaneuf D, Leclerc B, Tanguay RM (juli 1993). "Characterization of the human fumarylacetoacetate hydrolase gene and identification of a missense mutation abolishing enzymatic activity". Human Molecular Genetics. 2 (7): 941–6. doi:10.1093/hmg/2.7.941. PMID 8364576.

[:7-17] Rootwelt H, Berger R, Gray G, Kelly DA, Coşkun T, Kvittingen EA (oktobar 1994). "Novel splice, missense, and nonsense mutations in the fumarylacetoacetase gene causing tyrosinemia type 1". American Journal of Human Genetics. 55 (4): 653–8. PMC 1918286. PMID 7942842.

[:8-18] St-Louis, Maryse; Tanguay, Robert M. (1997). "Mutations in the fumarylacetoacetate hydrolase gene causing hereditary tyrosinemia type I: Overview". Human Mutation. 9 (4): 291–299. doi:10.1002/(sici)1098-1004(1997)9:4<291::aid-humu1>3.0.co;2-9. ISSN 1059-7794. PMID 9101289.

[:5-19] Ploos van Amstel JK, Bergman AJ, van Beurden EA, Roijers JF, Peelen T, van den Berg IE, Poll-The BT, Kvittingen EA, Berger R (januar 1996). "Hereditary tyrosinemia type 1: novel missense, nonsense and splice consensus mutations in the human fumarylacetoacetate hydrolase gene; variability of the genotype-phenotype relationship". Human Genetics. 97 (1): 51–9. doi:10.1007/BF00218833. PMID 8557261.

[20] Hahn SH, Krasnewich D, Brantly M, Kvittingen EA, Gahl WA (1995). "Heterozygosity for an exon 12 splicing mutation and a W234G missense mutation in an American child with chronic tyrosinemia type 1". Human Mutation. 6 (1): 66–73. doi:10.1002/humu.1380060113. PMID 7550234.

[21] Phaneuf D, Lambert M, Laframboise R, Mitchell G, Lettre F, Tanguay RM (oktobar 1992). "Type 1 hereditary tyrosinemia. Evidence for molecular heterogeneity and identification of a causal mutation in a French Canadian patient". The Journal of Clinical Investigation. 90 (4): 1185–92. doi:10.1172/JCI115979. PMC 443158. PMID 1401056.

[:3-22] Mohamed S, Kambal MA, Al Jurayyan NA, Al-Nemri A, Babiker A, Hasanato R, Al-Jarallah AS (septembar 2013). "Tyrosinemia type 1: a rare and forgotten cause of reversible hypertrophic cardiomyopathy in infancy". BMC Research Notes. 6: 362. doi:10.1186/1756-0500-6-362. PMC 3846631. PMID 24016420.

[23] OMIM: Tyrosinemia, Type I; TYRSN1 -276700

[:9-24] Chinsky JM, Singh R, Ficicioglu C, van Karnebeek CD, Grompe M, Mitchell G, Waisbren SE, Gucsavas-Calikoglu M, Wasserstein MP, Coakley K, Scott CR (decembar 2017). "Diagnosis and treatment of tyrosinemia type I: a US and Canadian consensus group review and recommendations". Genetics in Medicine. 19 (12): 1380. doi:10.1038/gim.2017.101. PMC 5729346. PMID 28771246.

[25] "Tyrosinemia type 1 | Genetic and Rare Diseases Information Center (GARD) – an NCATS Program". rarediseases.info.nih.gov. Pristupljeno 13. 12. 2018.

[5]

[6]

[7]

[1]

[2]

[3]

[4]

[8]

[9]

[10]

[11]

[12]

[13]

[14]

[15]

[16]

[17]

[18]

[19]

[20]

[21]

[22]

[23]

[24]

[25]