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 (top 9% of genes corpus-wide)
• GTEx eGene: eQTL in 7 tissues, sQTL in 1 (q < 0.05)
• Phenotypes (HPO): 24
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 0.84 (unconstrained)
• 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: 14 — 10 protein_coding, 3 retained_intron, 1 nonsense_mediated_decay

MANE Select: ENST00000355962

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 2, TSL 2: 1, TSL 4: 1

ENST00000355962, ENST00000564007, ENST00000566010, ENST00000566094, ENST00000895691, ENST00000895692, ENST00000895693, ENST00000895694, ENST00000895695, ENST00000895696, ENST00000895697, ENST00000992004, ENST00001108552, ENST00001132748

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.

Highest expression (Bgee): lobe of liver, liver, buccal mucosa cell, male germ line stem cell (sensu Vertebrata) in testis, tendon of biceps brachii.

Genetic regulation across tissues (GTEx eQTL / sQTL)

TAT is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 7 tissues and its splicing (sQTL) in 1 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

8 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Testis	eqtl	5.5e-23	+0.42	16:71694409:C:T
Adrenal Gland	eqtl	2.7e-03	-0.59	16:71602022:G:A
Nerve Tibial	eqtl	8.9e-03	-0.29	16:71697582:T:C
Pituitary	eqtl	2.1e-02	+0.48	16:71566074:G:A
Liver	sqtl	2.1e-02	-0.41	16:71617515:T:C
Brain Spinal cord cervical c-1	eqtl	2.2e-02	-0.75	16:71391262:G:C
Prostate	eqtl	2.2e-02	+0.53	16:71987100:T:C
Brain Cerebellum	eqtl	2.5e-02	-0.36	16:71119869:G:A

FANTOM5 promoters

2 alternative TSS:

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

Top tissues by expression

showing 100 of 265 tissues 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
nasal cavity mucosa	UBERON:0001826	56.69	gold quality
mucosa of sigmoid colon	UBERON:0004993	56.64	gold quality
gall bladder	UBERON:0002110	56.24	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	55.81	gold quality
fallopian tube	UBERON:0003889	55.42	gold quality
quadriceps femoris	UBERON:0001377	55.04	gold quality
testis	UBERON:0000473	55.03	gold quality
medial globus pallidus	UBERON:0002477	54.94	gold quality
right testis	UBERON:0004534	54.48	gold quality
left testis	UBERON:0004533	54.47	gold quality
cerebellar vermis	UBERON:0004720	54.47	silver quality
middle temporal gyrus	UBERON:0002771	53.82	gold quality
vastus lateralis	UBERON:0001379	53.76	gold quality
tibialis anterior	UBERON:0001385	53.59	silver quality
right uterine tube	UBERON:0001302	53.29	gold quality
Brodmann (1909) area 23	UBERON:0013554	53.26	gold quality
skin of hip	UBERON:0001554	52.80	silver quality
lower lobe of lung	UBERON:0008949	52.76	gold quality
deltoid	UBERON:0001476	52.56	gold quality
skeletal muscle tissue	UBERON:0001134	51.89	gold quality
pancreas	UBERON:0001264	51.86	gold quality
globus pallidus	UBERON:0001875	51.74	gold quality
Brodmann (1909) area 46	UBERON:0006483	51.44	gold quality
cortical plate	UBERON:0005343	51.30	silver quality
muscle tissue	UBERON:0002385	51.15	gold quality
cervix squamous epithelium	UBERON:0006922	50.98	gold quality
right lung	UBERON:0002167	50.79	gold quality
mucosa of urinary bladder	UBERON:0001259	50.70	gold quality
small intestine Peyer’s patch	UBERON:0003454	50.54	gold quality
frontal pole	UBERON:0002795	50.41	gold quality
middle frontal gyrus	UBERON:0002702	50.30	gold quality
thymus	UBERON:0002370	50.26	gold quality
nephron tubule	UBERON:0001231	50.20	gold quality
paraflocculus	UBERON:0005351	50.18	gold quality
hair follicle	UBERON:0002073	50.08	gold quality
small intestine	UBERON:0002108	49.91	gold quality
bone marrow	UBERON:0002371	49.56	gold quality
cervix epithelium	UBERON:0004801	49.43	gold quality
blood vessel layer	UBERON:0004797	49.29	gold quality
layer of synovial tissue	UBERON:0007616	49.27	gold quality
transverse colon	UBERON:0001157	49.06	gold quality
olfactory bulb	UBERON:0002264	48.92	gold quality
choroid plexus epithelium	UBERON:0003911	48.89	gold quality
kidney epithelium	UBERON:0004819	48.85	gold quality
type B pancreatic cell	CL:0000169	48.83	gold quality
metanephric glomerulus	UBERON:0004736	48.73	gold quality
cardiac muscle of right atrium	UBERON:0003379	48.55	gold quality
CA1 field of hippocampus	UBERON:0003881	48.50	gold quality
renal glomerulus	UBERON:0000074	48.39	gold quality
kidney	UBERON:0002113	48.33	gold quality
left ventricle myocardium	UBERON:0006566	48.24	gold quality
orbitofrontal cortex	UBERON:0004167	48.20	gold quality
body of pancreas	UBERON:0001150	48.07	gold quality
upper arm skin	UBERON:0004263	48.06	gold quality
tongue squamous epithelium	UBERON:0006919	47.92	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	47.70	silver quality
adult organism	UBERON:0007023	47.47	gold quality
blood	UBERON:0000178	47.33	gold quality
tonsil	UBERON:0002372	46.95	gold quality
intestine	UBERON:0000160	46.85	gold quality
duodenum	UBERON:0002114	46.70	silver quality
lymph node	UBERON:0000029	46.66	gold quality
entorhinal cortex	UBERON:0002728	46.28	gold quality
rectum	UBERON:0001052	46.17	gold quality
large intestine	UBERON:0000059	45.79	gold quality
gingiva	UBERON:0001828	45.67	gold quality
uterine cervix	UBERON:0000002	45.43	silver quality
occipital lobe	UBERON:0002021	45.39	silver quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	45.35	gold quality
colon	UBERON:0001155	45.34	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

HPA expression

RNA tissue specificity: Tissue enriched

28 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM
Liver	tissue	1188.4
Breast	tissue	55.3
Testis	tissue	1.7
Postcentral gyrus	tissue	1.2
Nucleus accumbens	tissue	0.9
Choroid plexus	tissue	0.8
Locus coeruleus	tissue	0.8
Hippocampus	tissue	0.8
Gallbladder	tissue	0.7
Retina	tissue	0.6
Small intestine	tissue	0.4
Colon	tissue	0.3
Kidney	tissue	0.3
Lymph node	tissue	0.2
Pancreas	tissue	0.2
Duodenum	tissue	0.2
Tonsil	tissue	0.2
Cervix	tissue	0.1
Pituitary gland	tissue	0.1
Stomach 1	tissue	0.1
Cerebral cortex	tissue	0.1
Adipose tissue	tissue	0.1
Salivary gland	tissue	0.1
Rectum	tissue	0.1
Retrosplenial and cingulate cortex	tissue	0.1
Fallopian tube	tissue	0.1
Appendix	tissue	0.1
Insular cortex	tissue	0.1

Brain sub-regions (HPA Brain Atlas): detected in 182; highest nTPM — Area striata (white matter) (1.5), Parieto-temporal junction (white matter) (1.3), Posterior insular cortex (1.3), Temporal white matter (1.3), Anterior cochlear nucleus, ventral (1.2).

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)

Targeting TAT by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 73 miRNAs:

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

Functional genomics

gnomAD constraint: pLI 9.33e-08, LOEUF 0.844, missense Z 1.05 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000355962 — one region, missense o/e 0.92.

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)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:98487) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 10 distinct phenotype terms.

Mouse phenotype (MP)	Records
persistence of hyaloid vascular system	1
abnormal retina morphology	1
hyperactivity	1
increased lean body mass	1
decreased heart rate	1
increased mean corpuscular hemoglobin	1
decreased total body fat amount	1
abnormal retina blood vessel morphology	1
prolonged RR interval	1
preweaning lethality, incomplete penetrance	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Bos taurus	Q58CZ9	92.2%	Diamond
Hordeum vulgare	Q9ST02	92.0%	Diamond
Oryza sativa Japonica Group	A0A0P0VI36	78.4%	Diamond
Arabidopsis thaliana	Q8VYP2	77.8%	Diamond
Dictyostelium discoideum	Q54K95	50.2%	Diamond
Saccharomyces cerevisiae S288C	P47039	48.5%	Diamond
Trypanosoma cruzi	P33447	40.3%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
MARVELD3	protein-coding	91862
TAT-AS1	ncRNA	100132529
PHLPP2	protein-coding	23035
CHST4	protein-coding	10164
SNORA70D	snoRNA	100379141

Protein

Protein identifiers

Tyrosine aminotransferase — P17735 (reviewed: P17735)

Alternative names: L-tyrosine:2-oxoglutarate aminotransferase

All UniProt accessions (2): A0A140VKB7, P17735

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_PLP_cs	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)

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

UniProt features (42 total): helix 19, strand 12, turn 4, modified residue 3, sequence variant 2, chain 1, mutagenesis site 1

Structure

Experimental structures (PDB)

1 structures by resolution:

PDB	Title	Method	Resolution (Å)
3DYD	Human Tyrosine Aminotransferase	X-RAY DIFFRACTION	2.3

Predicted structure (AlphaFold)

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

Human Protein Atlas

Protein class: Enzymes, ENZYME proteins, Transferases, Metabolic proteins, Predicted intracellular proteins, Plasma proteins, Disease related genes, Potential drug targets, Human disease related genes, Congenital disorders of metabolism, Congenital disorders of amino acid metabolism

Protein evidence: Evidence at protein level

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)

Type	Positions
N-acetylmethionine	1
N6-(pyridoxal phosphate)lysine	280
Phosphoserine	448

Mutagenesis-validated functional residues (1)

Position	Phenotype
294	reduced catalytic activity.

Function

Pathways and Gene Ontology

Reactome pathways

1 curated (TAS) of 4; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

4 pathways:

ID	Pathway	Evidence
R-HSA-8963684	Tyrosine catabolism	curated
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

3 top-level categories:

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

GO top-level categories

36 GO namespaces:

Category	Terms
dicarboxylic acid metabolic process	2
amino acid metabolic process	2
amino acid catabolic process	2
aromatic 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

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 5 of 28 annotations. The rest are phylogenetic / computational / electronic (IEA).

5 experimentally-supported GO terms:

GO term	NS	Evidence
2-oxoglutarate metabolic process	BP	direct assay
L-tyrosine catabolic process	BP	direct assay
glutamate metabolic process	BP	direct assay
L-tyrosine:2-oxoglutarate transaminase activity	MF	direct assay
identical protein binding	MF	physical interaction

Protein interactions and networks

STRING

showing 15 of 1,438 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TAT	HPD	P32754	940
TAT	FAH	P16930	922
TAT	GOT2	P00505	814
TAT	TDO2	P48775	753
TAT	APRT	P07741	741
TAT	HGD	Q93099	718
TAT	PRKAR1A	P10644	698
TAT	CTRB1	P17538	691
TAT	SDS	P20132	689
TAT	PAH	P00439	679
TAT	GCG	P01275	649
TAT	INS	P01308	618
TAT	AFP	P02771	589
TAT	G6PC3	Q9BUM1	588
TAT	G6PC1	P35575	575

IntAct

Human interaction partners of TAT in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

6 partners by confidence:

Partner	Interaction type	MIscore	Records
UBE3A	physical association	0.780	14
GRN	physical association	0.560	6
GLUL	physical association	0.560	3
AARSD1	physical association	0.400	2
DBNL	physical association	0.400	1
HSP90AB1	association	0.350	1

BioGRID (14 interactions; top human partners by supporting records): UBE3A (Two-hybrid; 5 records), AARSD1 (Affinity Capture-MS; 3 records), GRN (Reconstituted Complex; 2 records), DBNL (Affinity Capture-MS), GLUL (Two-hybrid)

Disease & clinical

Genetic variants

Variant evidence for TAT: 376 ClinVar records (43 pathogenic / likely pathogenic); 6 GWAS associations. Per-variant detail is on Sugi Variant.

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	220
Benign	10

Top pathogenic / likely-pathogenic (15)

Showing the 15 best-reviewed of 43 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
402	NM_000353.3(TAT):c.169C>T (p.Arg57Ter)	Pathogenic	criteria provided, multiple submitters, no conflicts	5
404	NM_000353.3(TAT):c.1249C>T (p.Arg417Ter)	Pathogenic	criteria provided, multiple submitters, no conflicts	5
557491	NM_000353.3(TAT):c.177dup (p.Val60fs)	Pathogenic	criteria provided, multiple submitters, no conflicts	3
1683242	NM_000353.3(TAT):c.912+1G>A	Likely pathogenic	criteria provided, multiple submitters, no conflicts	2
3240560	NM_000353.3(TAT):c.341G>C (p.Gly114Ala)	Likely pathogenic	criteria provided, multiple submitters, no conflicts	2
553660	NM_000353.3(TAT):c.1047del (p.Asn349fs)	Pathogenic	criteria provided, single submitter	2
1074025	NM_000353.3(TAT):c.9dup (p.Tyr4fs)	Pathogenic	criteria provided, single submitter	1
1440254	NM_000353.3(TAT):c.966del (p.Ile322fs)	Pathogenic	criteria provided, single submitter	1
1452969	NM_000353.3(TAT):c.89del (p.Val30fs)	Pathogenic	criteria provided, single submitter	1
1454381	NM_000353.3(TAT):c.825del (p.Cys275fs)	Pathogenic	criteria provided, single submitter	1
2019658	NM_000353.3(TAT):c.358del (p.Glu120fs)	Pathogenic	criteria provided, single submitter	1
2129086	NM_000353.3(TAT):c.1125+1del	Pathogenic	criteria provided, single submitter	1
2703184	NM_000353.3(TAT):c.742G>T (p.Glu248Ter)	Pathogenic	criteria provided, single submitter	1
2711453	NM_000353.3(TAT):c.1188_1191del (p.Val397fs)	Pathogenic	criteria provided, single submitter	1
2743466	NM_000353.3(TAT):c.825T>A (p.Cys275Ter)	Pathogenic	criteria provided, single submitter	1

Per-variant reference — Sugi Variant

Explore TAT’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 41 predictions of 554):

Position(s)	Effect	Δscore	Sites
16:71570267–71570268	donor_loss	1.0000	5
16:71570399	acceptor_loss	1.0000
16:71571659–71571660	acceptor_loss	1.0000	6
16:71572184–71572185	donor_loss	1.0000	5
16:71572325–71572326	acceptor_loss	1.0000	6
16:71572570	donor_gain	1.0000
16:71575920–71575921	donor_loss	1.0000	5
16:71576031	acceptor_gain	1.0000
16:71568285–71568286	acceptor_loss	0.9900	6
16:71569852–71569853	donor_loss	0.9900	5

AlphaMissense

955 missense substitutions predicted likely pathogenic (of 2,981 scored), across 267 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
D247	8	0.991	0.997
D80	8	0.977	0.997
N219	8	0.963	0.998
F410	8	0.962	0.991
F169	8	0.958	1.000
S145	8	0.906	0.997
D296	8	0.886	0.964
F392	8	0.852	0.993
D389	8	0.837	0.962
D61	8	0.730	0.931
R288	7	0.986	0.999
W291	7	0.978	0.999
K280	7	0.977	0.999
W194	7	0.972	0.997
F437	7	0.970	0.994
W287	7	0.964	0.999
N54	7	0.952	0.998
W41	7	0.951	0.992
E248	7	0.911	0.988
F255	7	0.910	0.954

HPA cancer prognostics

RNA cancer specificity: Cancer enriched (Liver Hepatocellular Carcinoma)

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

2 prognostic cancer types:

Cancer	Prognostic	p-value
Liver Hepatocellular Carcinoma (validation)	favorable	2.46e-05
Liver Hepatocellular Carcinoma (TCGA)	favorable	0.000911

Disease associations

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

GenCC curated gene-disease

1 curated gene-disease records:

Disease	Classification	Inheritance	Records
tyrosinemia type II	Definitive	Autosomal recessive	6

ClinGen Gene-Disease Validity

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

1 validity classifications:

Disease	Classification	Inheritance
tyrosinemia type II	Definitive	AR

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (10 panels, 10 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

10 panels:

Panel	Rating
DDG2P	green
Hypotonic infant	green
Ichthyosis and erythrokeratoderma	green
Intellectual disability	green
Leukodystrophy, childhood onset	green
Likely inborn error of metabolism	green
Paediatric disorders	green
Palmoplantar keratoderma and erythrokeratodermas	green
Undiagnosed metabolic disorders	green
Unexplained death in infancy and sudden unexplained death in childhood	green

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

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

HPO phenotypes

24 phenotypes (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:

Study	Trait	p-value
GCST001391_5	Metabolite levels	2e-17
GCST007565_14	Morning person	1e-15
GCST007576_150	Chronotype	1e-15
GCST008972_171	Urate levels	3e-13
GCST001639_28	Metabolite levels	4e-13
GCST008971_130	Urate levels	7e-11

EFO canonical traits (from GWAS)

4 canonical traits:

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 (CPIC guideline: no)

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	affects expression, increases 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)

Via MONDO — disease-level, not drug-specific.

2 trials:

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