TAT

Summary

TAT (tyrosine aminotransferase, HGNC:11573) is a protein-coding gene on chromosome 16q22.2, encoding Tyrosine aminotransferase (P17735). Transaminase involved in tyrosine breakdown.

This nuclear gene encodes a mitochondrial protein tyrosine aminotransferase which is present in the liver and catalyzes the conversion of L-tyrosine into p-hydroxyphenylpyruvate. Mutations in this gene cause tyrosinemia (type II, Richner-Hanhart syndrome), a disorder accompanied by major skin and corneal lesions, with possible cognitive disability. A regulator gene for tyrosine aminotransferase is X-linked.

Source: NCBI Gene 6898 — RefSeq curated summary.

At a glance

• Gene–disease (curated): tyrosinemia type II (Definitive, ClinGen)
• GWAS associations: 6
• Clinical variants (ClinVar): 376 total — 17 pathogenic, 26 likely-pathogenic
• Phenotypes (HPO): 24
• Druggable target: yes
• MANE Select transcript: NM_000353

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11573
Approved symbol	TAT
Name	tyrosine aminotransferase
Location	16q22.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000198650
Ensembl biotype	protein_coding
OMIM	613018
Entrez	6898

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 8 protein_coding, 3 retained_intron

ENST00000355962, ENST00000564007, ENST00000566010, ENST00000566094, ENST00000895691, ENST00000895692, ENST00000895693, ENST00000895694, ENST00000895695, ENST00000895696, ENST00000895697

RefSeq mRNA: 1 — MANE Select: NM_000353 NM_000353

CCDS: CCDS10903

Canonical transcript exons

ENST00000355962 — 12 exons

Exon	Start	End
ENSE00000945197	71575922	71576026
ENSE00000945198	71573539	71573606
ENSE00000945199	71572530	71572688
ENSE00000945200	71572186	71572324
ENSE00000945201	71571606	71571658
ENSE00000945202	71570679	71570831
ENSE00000945203	71570269	71570397
ENSE00000945204	71569854	71569937
ENSE00000945205	71568711	71568809
ENSE00001412070	71565660	71568284
ENSE00002587055	71577009	71577092
ENSE00003654066	71576181	71576427

Expression profiles

Bgee: expression breadth ubiquitous, 128 present calls, max score 99.00.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 4.7724 / max 2751.4768, expressed in 14 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
158029	4.7548	13
158027	0.0176	5

Top tissues by expression

265 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
right lobe of liver	UBERON:0001114	99.00	gold quality
liver	UBERON:0002107	96.40	gold quality
buccal mucosa cell	CL:0002336	90.81	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	78.41	gold quality
tendon of biceps brachii	UBERON:0008188	75.75	silver quality
diaphragm	UBERON:0001103	71.28	gold quality
mammary duct	UBERON:0001765	71.06	silver quality
secondary oocyte	CL:0000655	70.40	silver quality
epithelium of mammary gland	UBERON:0003244	69.65	silver quality
triceps brachii	UBERON:0001509	65.48	gold quality
gluteal muscle	UBERON:0002000	65.38	gold quality
thoracic mammary gland	UBERON:0005200	64.87	gold quality
mammary gland	UBERON:0001911	64.73	gold quality
parotid gland	UBERON:0001831	64.45	gold quality
oviduct epithelium	UBERON:0004804	63.27	silver quality
mucosa of transverse colon	UBERON:0004991	62.01	gold quality
endometrium epithelium	UBERON:0004811	61.40	gold quality
colonic epithelium	UBERON:0000397	60.82	gold quality
pancreatic ductal cell	CL:0002079	60.07	silver quality
nasal cavity epithelium	UBERON:0005384	59.60	gold quality
islet of Langerhans	UBERON:0000006	59.32	gold quality
Brodmann (1909) area 10	UBERON:0013541	58.91	gold quality
biceps brachii	UBERON:0001507	58.86	gold quality
upper leg skin	UBERON:0004262	58.71	gold quality
colonic mucosa	UBERON:0000317	58.28	gold quality
myocardium	UBERON:0002349	58.26	gold quality
periodontal ligament	UBERON:0008266	58.10	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	57.66	gold quality
trabecular bone tissue	UBERON:0002483	57.30	gold quality
epithelium of nasopharynx	UBERON:0001951	57.05	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-HCAD-9	yes	2069.46
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): BCL11B, CEBPB, CTNNBL1, DNMT1, ESR1, FOXA1, FOXA2, FOXA3, FOXM1, GMEB1, GRHL3, HAND1, HAND2, HMGA1, HNF4A, IRF1, IRF8, JUN, KAT5, KAT7, MYC, NCOA2, NCOA3, NFATC2, NFE2L2, NFIC, NFKBIA, NR1I3, NR3C1, PURA, SATB1, SP1, SP3, SP7, TAF1, TBP, TBXT, TP53, TP73, YBX1

miRNA regulators (miRDB)

73 targeting TAT, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-4455	100.00	65.48	1587
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-2110	99.96	66.68	1930
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-145-5P	99.92	71.13	1836
HSA-MIR-5195-3P	99.92	70.92	1877
HSA-MIR-10523-5P	99.91	69.22	2038
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-7162-3P	99.89	68.16	1682
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-MIR-182-5P	99.87	74.03	2589
HSA-MIR-12119	99.87	68.35	1653
HSA-MIR-548AJ-5P	99.78	71.12	3085
HSA-MIR-548F-5P	99.78	71.02	3093
HSA-MIR-548G-5P	99.78	71.12	3085
HSA-MIR-548X-5P	99.78	71.12	3085

Literature-anchored findings (GeneRIF, showing 11)

• two novel missense mutations were identified - (C151Y) and (L273P) within exon 5 and exon 8, respectively in tyrosinemia type II in three unrelated consanguinous Tunisian families (PMID:16574453)
• a silent exonic transversion in TAT causes complete missplicing by exon 11 skipping in oculocutaneous tyrosinaemia type II (PMID:16917729)
• Genetically modified adenoviral vector with the protein transduction domain of Tat improves gene transfer to CAR-deficient cells. (PMID:18721127)
• a heterozygous insertion mutation (c.446_447insA; p.D149DfsX28) was found in exon 4 leading to a frameshift and finally resulting in a premature stop codon and a heterozygous missense mutation (c.658C>T; p.P220S) was identified in exon 5. (PMID:18945316)
• tumor suppressive mechanism of TAT was associated with its proapoptotic role in a mitochondrial-dependent manner by promoting cytochrome-c release and activating caspase-9 and PARP. (PMID:20209601)
• A paternal inherited frameshift mutation c.1213delCinsAG at codon 405 causing a premature stop codon, and a maternally inherited deletion of 193kb encompassing the complete TAT gene yield the first complete TAT deletion in tyrosinaemia type II described. (PMID:21636300)
• Two known mutations and one novel mutation was found in the TAT gene of Tunesian Richner-Hanhart syndrome patients. The geographical distribution of RHS mutations shows regional specificities. (PMID:23954227)
• Sequencing of TAT indicated two new homozygous mutations p.L312P (c.935T>C) and p.T408M (c.1223C>T) for the proband and his asymptomatic sister. (PMID:27285949)
• Data analysis did not reveal a genotype-phenotype correlation, but stressed the need of early diagnosis: All patients improved the oculocutaneous lesions after dietary treatment but neurological symptoms prevailed. The discovery of founder mutations in isolated populations, and the benefits of early intervention, should increase diagnostic awareness in newborns. (PMID:28255985)
• Most synonymous allelic variants in HIV tat are not silent. (PMID:36893872)
• TRIM21-mediated ubiquitylation of TAT suppresses liver metastasis in gallbladder cancer. (PMID:38697462)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	tat	ENSDARG00000069630
mus_musculus	Tat	ENSMUSG00000001670
rattus_norvegicus	Tat	ENSRNOG00000016348
drosophila_melanogaster	Tat	FBGN0030558
caenorhabditis_elegans		WBGENE00009628

Paralogs (7): AADAT (ENSG00000109576), ACCS (ENSG00000110455), KYAT3 (ENSG00000137944), GPT2 (ENSG00000166123), GPT (ENSG00000167701), KYAT1 (ENSG00000171097), ACCSL (ENSG00000205126)

Protein

Protein identifiers

Tyrosine aminotransferase — P17735 (reviewed: P17735)

Alternative names: L-tyrosine:2-oxoglutarate aminotransferase

All UniProt accessions (2): P17735, A0A140VKB7

UniProt curated annotations — full annotation on UniProt →

Function. Transaminase involved in tyrosine breakdown. Converts tyrosine to p-hydroxyphenylpyruvate. Can catalyze the reverse reaction, using glutamic acid, with 2-oxoglutarate as cosubstrate (in vitro). Has much lower affinity and transaminase activity towards phenylalanine.

Subunit / interactions. Homodimer.

Disease relevance. Tyrosinemia 2 (TYRSN2) [MIM:276600] An inborn error of metabolism characterized by elevations of tyrosine in the blood and urine, and oculocutaneous manifestations. Typical features include palmoplantar keratosis, painful corneal ulcers, and intellectual disability. The disease is caused by variants affecting the gene represented in this entry.

Pathway. Amino-acid degradation; L-phenylalanine degradation; acetoacetate and fumarate from L-phenylalanine: step 2/6.

Similarity. Belongs to the class-I pyridoxal-phosphate-dependent aminotransferase family.

RefSeq proteins (1): NP_000344* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004838	NHTrfase_class1_PyrdxlP-BS	Binding_site
IPR004839	Aminotransferase_I/II_large	Domain
IPR005957	Tyrosine_aminoTrfase	Family
IPR005958	TyrNic_aminoTrfase	Family
IPR011715	Tyr_aminoTrfase_ubiquitination	Conserved_site
IPR015421	PyrdxlP-dep_Trfase_major	Homologous_superfamily
IPR015422	PyrdxlP-dep_Trfase_small	Homologous_superfamily
IPR015424	PyrdxlP-dep_Trfase	Homologous_superfamily

Pfam: PF00155, PF07706

Catalyzed reactions (Rhea), 1 shown:

• L-tyrosine + 2-oxoglutarate = 3-(4-hydroxyphenyl)pyruvate + L-glutamate (RHEA:15093)

UniProt features (40 total): helix 17, strand 12, turn 4, modified residue 3, sequence variant 2, chain 1, mutagenesis site 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
3DYD	X-RAY DIFFRACTION	2.3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P17735-F1	91.93	0.86

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (3): 1, 280, 448

Mutagenesis-validated functional residues (1):

Position	Phenotype
294	reduced catalytic activity.

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-8963684	Tyrosine catabolism
R-HSA-1430728	Metabolism
R-HSA-71291	Metabolism of amino acids and derivatives
R-HSA-8963691	Phenylalanine and tyrosine metabolism

MSigDB gene sets: 217 (showing top): GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_RESPONSE_TO_ETHANOL, GOBP_HEPATICOBILIARY_SYSTEM_DEVELOPMENT, chr16q22, PID_HNF3B_PATHWAY, GOBP_CELLULAR_RESPONSE_TO_LIPID, GNF2_GSTM1, GOBP_RESPONSE_TO_CORTICOSTEROID, GOBP_ALPHA_AMINO_ACID_METABOLIC_PROCESS, KEGG_CYSTEINE_AND_METHIONINE_METABOLISM, GNF2_HPN, GOBP_GLUTAMATE_METABOLIC_PROCESS, GOBP_REGENERATION, GOBP_GLUTAMINE_FAMILY_AMINO_ACID_METABOLIC_PROCESS, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND

GO Biological Process (18): 2-oxoglutarate metabolic process (GO:0006103), glutamate metabolic process (GO:0006536), L-phenylalanine catabolic process (GO:0006559), L-tyrosine catabolic process (GO:0006572), response to oxidative stress (GO:0006979), cellular response to insulin stimulus (GO:0032869), response to ethanol (GO:0045471), response to mercury ion (GO:0046689), response to cortisol (GO:0051414), response to cAMP (GO:0051591), cellular response to retinoic acid (GO:0071300), response to dexamethasone (GO:0071548), liver regeneration (GO:0097421), amino acid metabolic process (GO:0006520), biosynthetic process (GO:0009058), aromatic amino acid metabolic process (GO:0009072), aromatic amino acid catabolic process (GO:0009074), response to glucocorticoid (GO:0051384)

GO Molecular Function (8): L-tyrosine:2-oxoglutarate transaminase activity (GO:0004838), amino acid binding (GO:0016597), pyridoxal phosphate binding (GO:0030170), identical protein binding (GO:0042802), catalytic activity (GO:0003824), protein binding (GO:0005515), transaminase activity (GO:0008483), transferase activity (GO:0016740)

GO Cellular Component (2): cytosol (GO:0005829), cellular_component (GO:0005575)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Phenylalanine and tyrosine metabolism	1
Metabolism	1
Metabolism of amino acids and derivatives	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
dicarboxylic acid metabolic process	2
amino acid metabolic process	2
aromatic amino acid catabolic process	2
L-amino acid catabolic process	2
proteinogenic amino acid catabolic process	2
response to alcohol	2
response to glucocorticoid	2
response to ketone	2
binding	2
response to stress	1
response to insulin	1
cellular response to peptide hormone stimulus	1
response to metal ion	1
response to purine-containing compound	1
response to organophosphorus	1
response to oxygen-containing compound	1
response to retinoic acid	1
cellular response to lipid	1
cellular response to oxygen-containing compound	1
liver development	1
animal organ regeneration	1
primary metabolic process	1
metabolic process	1
carboxylic acid metabolic process	1
aromatic amino acid metabolic process	1
carboxylic acid catabolic process	1
response to corticosteroid	1
aromatic-amino-acid:2-oxoglutarate transaminase activity	1
anion binding	1
vitamin B6 binding	1
protein binding	1
molecular_function	1
transferase activity, transferring nitrogenous groups	1
catalytic activity	1
cytoplasm	1
cellular anatomical structure	1

Protein interactions and networks

STRING

2220 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TAT	HPD	P32754	940
TAT	FAH	P16930	929
TAT	GOT2	P00505	814
TAT	TDO2	P48775	791
TAT	APRT	P07741	742
TAT	PRKAR1A	P10644	737
TAT	SDS	P20132	725
TAT	HGD	Q93099	710
TAT	G6PC3	Q9BUM1	707
TAT	CTRB1	P17538	705
TAT	AFP	P02771	632
TAT	G6PC1	P35575	626
TAT	G6PC2	Q9NQR9	619
TAT	PAH	P00439	615
TAT	ALB	P02768	589

IntAct

33 interactions, top by confidence:

A	B	Type	Score
UBE3A	TAT	psi-mi:“MI:0915”(physical association)	0.780
TAT	UBE3A	psi-mi:“MI:0915”(physical association)	0.780
TAT	TAT	psi-mi:“MI:0915”(physical association)	0.740
UBE3A	TAT	psi-mi:“MI:0915”(physical association)	0.620
TAT	GLUL	psi-mi:“MI:0915”(physical association)	0.560
GRN	TAT	psi-mi:“MI:0915”(physical association)	0.560
TAT	AARSD1	psi-mi:“MI:0915”(physical association)	0.400
TAT	DBNL	psi-mi:“MI:0915”(physical association)	0.400
TAT	HSP90AB1	psi-mi:“MI:0914”(association)	0.350
UBE3A	TAT	psi-mi:“MI:0915”(physical association)	0.000
TAT	TAT	psi-mi:“MI:0915”(physical association)	0.000
TAT	UBE3A	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (14): TAT (Two-hybrid), UBE3A (Two-hybrid), AARSD1 (Affinity Capture-MS), GLUL (Two-hybrid), UBE3A (Two-hybrid), TAT (Two-hybrid), AARSD1 (Affinity Capture-MS), GRN (Reconstituted Complex), TAT (Affinity Capture-Western), TAT (Two-hybrid), TAT (Two-hybrid), AARSD1 (Affinity Capture-MS), DBNL (Affinity Capture-MS), TAT (Two-hybrid)

ESM2 similar proteins: A0A0P0UZP7, A0A0P0VI36, F4I7I0, P04694, P0DO72, P17735, P18485, P23279, P23599, P27486, P29535, P31531, P37821, Q00379, Q06402, Q06429, Q07262, Q37001, Q3E6S9, Q43309, Q58CZ9, Q67Y55, Q7G4P2, Q7XQ85, Q8GYY0, Q8L5Z4, Q8QZR1, Q8VYP2, Q93Z38, Q94A02, Q94IB8, Q9FE98, Q9FN30, Q9LDV4, Q9LQ10, Q9LR29, Q9LVY1, Q9M1R1, Q9MB73, Q9MB95

Diamond homologs: A0A0P0VI36, A0AK37, P04694, P17735, P33447, Q2SBJ7, Q46DU3, Q54K95, Q58CZ9, Q67Y55, Q8QZR1, Q8VYP2, Q8Y5X8, Q92A83, Q93703, Q9FN30, Q9LVY1, Q9SIV0, Q9SK47, Q9ST02, Q9ST03, Q9SUR6, P24298, Q03VY3, Q3UX83, Q5E9H2, P47039, Q31GD4, O14209, O28277, O86459, P36692, P9WPZ4, P9WPZ5, Q08415, Q0P5G4, Q16773, Q17CS8, Q54KM6, Q58FK9

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

376 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	17
Likely pathogenic	26
Uncertain significance	83
Likely benign	219
Benign	11

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1071272	NC_000016.9:g.(?71609815)(71610328_?)del	Pathogenic
1074025	NM_000353.3(TAT):c.9dup (p.Tyr4fs)	Pathogenic
1440254	NM_000353.3(TAT):c.966del (p.Ile322fs)	Pathogenic
1452969	NM_000353.3(TAT):c.89del (p.Val30fs)	Pathogenic
2019658	NM_000353.3(TAT):c.358del (p.Glu120fs)	Pathogenic
2129086	NM_000353.3(TAT):c.1125+1del	Pathogenic
2703184	NM_000353.3(TAT):c.742G>T (p.Glu248Ter)	Pathogenic
2711453	NM_000353.3(TAT):c.1188_1191del (p.Val397fs)	Pathogenic
2743466	NM_000353.3(TAT):c.825T>A (p.Cys275Ter)	Pathogenic
3643231	NM_000353.3(TAT):c.861G>A (p.Trp287Ter)	Pathogenic
402	NM_000353.3(TAT):c.169C>T (p.Arg57Ter)	Pathogenic
404	NM_000353.3(TAT):c.1249C>T (p.Arg417Ter)	Pathogenic
406	NM_000353.3(TAT):c.236-5A>G	Pathogenic
553180	NM_000353.3(TAT):c.1297C>T (p.Arg433Trp)	Pathogenic
553660	NM_000353.3(TAT):c.1047del (p.Asn349fs)	Pathogenic
557491	NM_000353.3(TAT):c.177dup (p.Val60fs)	Pathogenic
832602	NC_000016.10:g.(?71569834)(71576435_?)del	Pathogenic
1495481	NM_000353.3(TAT):c.759+1G>A	Likely pathogenic
1683242	NM_000353.3(TAT):c.912+1G>A	Likely pathogenic
1724128	NM_000353.3(TAT):c.1015del (p.Tyr339fs)	Likely pathogenic
1724378	NM_000353.3(TAT):c.632_634delinsA (p.Cys211fs)	Likely pathogenic
1724403	NM_000353.3(TAT):c.18_19del (p.Gln7fs)	Likely pathogenic
1724862	NM_000353.3(TAT):c.1037_1038del (p.Leu346fs)	Likely pathogenic
1725598	NM_000353.3(TAT):c.274_275del (p.Glu92fs)	Likely pathogenic
1725713	NM_000353.3(TAT):c.283C>T (p.Gln95Ter)	Likely pathogenic
1726727	NM_000353.3(TAT):c.313A>T (p.Lys105Ter)	Likely pathogenic
1726828	NM_000353.3(TAT):c.8dup (p.Tyr4fs)	Likely pathogenic
2026898	NM_000353.3(TAT):c.396_408+201del	Likely pathogenic
2679098	NM_000353.3(TAT):c.1028_1029del (p.Leu343fs)	Likely pathogenic
2679099	NM_000353.3(TAT):c.706+2T>C	Likely pathogenic

SpliceAI

1069 predictions. Top by Δscore:

Variant	Effect	Δscore
16:71568160:T:TA	donor_gain	1.0000
16:71568281:AGCA:A	acceptor_gain	1.0000
16:71568282:GCA:G	acceptor_gain	1.0000
16:71568283:CA:C	acceptor_gain	1.0000
16:71568283:CAC:C	acceptor_gain	1.0000
16:71568284:ACT:A	acceptor_loss	1.0000
16:71568285:C:CC	acceptor_gain	1.0000
16:71569933:TTGGA:T	acceptor_gain	1.0000
16:71569934:TGGA:T	acceptor_gain	1.0000
16:71569938:C:CC	acceptor_gain	1.0000
16:71570263:CCTTA:C	donor_loss	1.0000
16:71570264:CTTA:C	donor_loss	1.0000
16:71570265:TTA:T	donor_loss	1.0000
16:71570266:TACCT:T	donor_loss	1.0000
16:71570267:A:AC	donor_gain	1.0000
16:71570267:ACCT:A	donor_loss	1.0000
16:71570268:C:CC	donor_gain	1.0000
16:71570268:C:G	donor_loss	1.0000
16:71570393:CGGAT:C	acceptor_gain	1.0000
16:71570394:GGAT:G	acceptor_gain	1.0000
16:71570395:GATC:G	acceptor_loss	1.0000
16:71570396:AT:A	acceptor_gain	1.0000
16:71570397:TC:T	acceptor_loss	1.0000
16:71570398:C:CC	acceptor_gain	1.0000
16:71570399:T:C	acceptor_loss	1.0000
16:71571654:AGCCA:A	acceptor_gain	1.0000
16:71571655:GCCA:G	acceptor_gain	1.0000
16:71571656:CCA:C	acceptor_gain	1.0000
16:71571656:CCAC:C	acceptor_gain	1.0000
16:71571657:CA:C	acceptor_gain	1.0000

AlphaMissense

2981 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:71572590:G:C	F169L	1.000
16:71572590:G:T	F169L	1.000
16:71572592:A:G	F169L	1.000
16:71568730:A:T	V402D	0.999
16:71570720:A:G	W291R	0.999
16:71570720:A:T	W291R	0.999
16:71570728:C:G	R288T	0.999
16:71570732:A:G	W287R	0.999
16:71570732:A:T	W287R	0.999
16:71570751:C:A	K280N	0.999
16:71570751:C:G	K280N	0.999
16:71568211:C:G	R433P	0.998
16:71570728:C:A	R288M	0.998
16:71570734:C:T	G286D	0.998
16:71572228:C:A	G222W	0.998
16:71572235:G:C	N219K	0.998
16:71572235:G:T	N219K	0.998
16:71576246:C:G	R57P	0.998
16:71576254:G:C	N54K	0.998
16:71576254:G:T	N54K	0.998
16:71570727:C:A	R288S	0.997
16:71570727:C:G	R288S	0.997
16:71570752:T:G	K280T	0.997
16:71571626:C:G	D247H	0.997
16:71572227:C:T	G222E	0.997
16:71572312:A:G	W194R	0.997
16:71572312:A:T	W194R	0.997
16:71572591:A:G	F169S	0.997
16:71572658:C:G	A147P	0.997
16:71572662:G:C	S145R	0.997

dbSNP variants (sampled 300 via entrez): RS1000113935 (16:71570489 A>C,G,T), RS1000537933 (16:71566033 C>G), RS1000896099 (16:71574503 C>T), RS1000937556 (16:71578897 A>G), RS1001291627 (16:71570933 C>T), RS1001474537 (16:71567665 A>G,T), RS1001627149 (16:71571011 A>G), RS1001760490 (16:71578024 G>A,C,T), RS1002177087 (16:71572303 C>A), RS1002348687 (16:71565838 C>A,G), RS1002450141 (16:71566097 CT>C), RS1002526442 (16:71577955 A>T), RS1002702881 (16:71579027 T>G), RS1002734917 (16:71575031 C>T), RS1003092406 (16:71575550 T>C)

Disease associations

OMIM: gene MIM:613018 | disease phenotypes: MIM:276600

GenCC curated gene-disease

Disease	Classification	Inheritance
tyrosinemia type II	Definitive	Autosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
tyrosinemia type II	Definitive	AR

Mondo (1): tyrosinemia type II (MONDO:0010160)

Orphanet (1): Tyrosinemia type 2 (Orphanet:28378)

HPO phenotypes

24 total (24 of 24 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000252	Microcephaly
HP:0000272	Malar flattening
HP:0000572	Visual loss
HP:0000613	Photophobia
HP:0000639	Nystagmus
HP:0000708	Atypical behavior
HP:0000951	Abnormality of the skin
HP:0000962	Hyperkeratosis
HP:0000975	Hyperhidrosis
HP:0000982	Palmoplantar keratoderma
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001251	Ataxia
HP:0001337	Tremor
HP:0001510	Growth delay
HP:0001597	Abnormal nail morphology
HP:0002167	Abnormal speech pattern
HP:0003161	4-Hydroxyphenylpyruvic aciduria
HP:0003231	Hypertyrosinemia
HP:0004337	Abnormality of amino acid metabolism
HP:0007812	Herpetiform corneal ulceration
HP:0007957	Corneal opacity
HP:6000479	Elevated urine N-acetyltyrosine level

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST001391_5	Metabolite levels	2.000000e-17
GCST001639_28	Metabolite levels	4.000000e-13
GCST007565_35	Morning person	1.000000e-15
GCST007576_405	Chronotype	1.000000e-15
GCST008971_63	Urate levels	7.000000e-11
GCST008972_38	Urate levels	3.000000e-13

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004725	metabolite measurement
EFO:0004723	coronary artery calcification
EFO:0008328	chronotype measurement
EFO:0004531	urate measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3043 (SINGLE PROTEIN)

PharmGKB: 1 entry (VIP=true, CPIC=false)

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — Catecholamine turnover

CTD chemical–gene interactions

43 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Dexamethasone	decreases reaction, increases expression, decreases expression, affects reaction	5
Benzo(a)pyrene	affects expression, affects methylation, decreases expression	3
Cyclosporine	decreases expression, increases expression	3
perfluorooctanoic acid	decreases expression, increases expression	2
Acetaminophen	decreases expression	2
Ketoconazole	decreases expression	2
Tetrachlorodibenzodioxin	increases expression, affects expression	2
Valproic Acid	increases expression	2
Mifepristone	decreases reaction, increases expression	2
Aflatoxin B1	affects expression, decreases expression, decreases methylation	2
OTX015	decreases expression	1
mivebresib	decreases expression	1
bismuth tripotassium dicitrate	increases expression	1
methyleugenol	decreases expression	1
bisphenol A	decreases expression	1
withaferin A	decreases expression	1
sodium arsenite	decreases expression	1
perfluorooctane sulfonic acid	decreases expression	1
methylprednisolone aceponate	increases activity	1
CGP 52608	affects binding, increases reaction	1
2-palmitoylglycerol	increases expression	1
pyrazolanthrone	decreases expression, decreases reaction	1
abrine	decreases expression	1
R-1,1,1-trifluoro-4-(5-fluoro-2,3-dihydrobenzofuran-7-yl)-4-methyl-2-(((2-methyl-5-quinolyl)amino)methyl)pentan-2-ol	affects activity	1
(+)-JQ1 compound	decreases expression	1
ortho-topolin riboside	affects cotreatment, decreases expression	1
Mometasone Furoate	increases activity	1
Arsenic Trioxide	increases expression	1
Bosentan	affects expression	1
Leflunomide	increases expression	1

ChEMBL screening assays

2 unique, capped per target: 1 functional, 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL829812	Functional	Inhibition of glucocorticoid receptor mediated tyrosine aminotransferase activity	Liver-selective glucocorticoid antagonists: a novel treatment for type 2 diabetes. — J Med Chem
CHEMBL934185	Binding	Induction of tyrosine aminotransferase	Exploring the molecular basis of action of the passive antiglucocorticoid 21-hydroxy-6,19-epoxyprogesterone. — J Med Chem

Clinical trials (associated diseases)

2 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT04196959	Not specified	COMPLETED	Evaluation of TYR Sphere
NCT06298292	Not specified	NOT_YET_RECRUITING	Acceptability/Tolerance of Protein Substitutes in Tablet Form for the Dietary Management of Rare Aminoacidopathies