Gene Details | GeDiPNet - Complete Gene Info, Disease Associations & Pathways

Gene Gene information from NCBI Gene database. Gene SNPs miRNA Transcription factors Gene ontology Other IDs Protein Pathways Associated diseases
Entrez ID	7054
Gene name	Tyrosine hydroxylase
Gene symbol	TH
Synonyms (NCBI Gene)	DYT14DYT5bTYH
Chromosome	11
Chromosome location	11p15.5
Summary	The protein encoded by this gene is involved in the conversion of tyrosine to dopamine. It is the rate-limiting enzyme in the synthesis of catecholamines, hence plays a key role in the physiology of adrenergic neurons. Mutations in this gene have been ass

Show/Hide all (49)

SNP ID	Visualize variation	Clinical significance	Consequence
rs11564716	C>T	Benign-likely-benign, conflicting-interpretations-of-pathogenicity, benign	Synonymous variant, coding sequence variant
rs28934581	T>G	Pathogenic	Coding sequence variant, missense variant
rs45471299	G>A	Pathogenic, uncertain-significance, likely-pathogenic	Coding sequence variant, missense variant
rs80338892	C>T	Pathogenic	Missense variant, coding sequence variant
rs121917762	G>A,T	Likely-pathogenic, pathogenic	Coding sequence variant, stop gained, missense variant
rs121917763	A>G	Likely-pathogenic, pathogenic	Coding sequence variant, missense variant
rs121917765	C>A	Pathogenic	Coding sequence variant, missense variant
rs151082354	C>G	Conflicting-interpretations-of-pathogenicity	Synonymous variant, coding sequence variant
rs184106392	C>G,T	Not-provided, conflicting-interpretations-of-pathogenicity	Missense variant, coding sequence variant
rs536382000	C>T	Conflicting-interpretations-of-pathogenicity, uncertain-significance	Missense variant, coding sequence variant
rs587776767	A>T	Pathogenic	Intron variant
rs771351747	T>C	Conflicting-interpretations-of-pathogenicity	Coding sequence variant, missense variant
rs771610752	G>A	Pathogenic-likely-pathogenic, pathogenic	Coding sequence variant, stop gained
rs775410637	A>C	Likely-pathogenic	Coding sequence variant, missense variant
rs777379609	G>A,C	Likely-pathogenic	Missense variant, coding sequence variant
rs786204540	G>A	Likely-pathogenic	Stop gained, coding sequence variant
rs797045111	C>-	Pathogenic	Frameshift variant, coding sequence variant
rs1057516491	C>-	Likely-pathogenic	Coding sequence variant, frameshift variant
rs1057516712	C>-	Likely-pathogenic	Coding sequence variant, frameshift variant
rs1057516736	C>T	Likely-pathogenic	Splice donor variant
rs1057516819	C>T	Likely-pathogenic	Splice donor variant
rs1057516874	CAATGAACCGCGGGGACTGTGGGGAC>-	Likely-pathogenic	Intron variant, splice acceptor variant, coding sequence variant
rs1057517003	A>G	Likely-pathogenic	Splice donor variant
rs1057517162	G>-	Likely-pathogenic	Coding sequence variant, frameshift variant
rs1057517423	G>A	Pathogenic	Stop gained, coding sequence variant
rs1057519220	G>A	Likely-pathogenic	Stop gained, coding sequence variant
rs1057520384	G>A,T	Likely-pathogenic	Missense variant, coding sequence variant
rs1064795631	A>G	Likely-pathogenic	Missense variant, coding sequence variant
rs1266265578	C>T	Likely-pathogenic	Splice donor variant
rs1288483479	C>T	Likely-pathogenic	Missense variant, coding sequence variant
rs1554922434	G>-	Likely-pathogenic	Coding sequence variant, frameshift variant
rs1554922441	G>T	Likely-pathogenic	Coding sequence variant, stop gained
rs1554922593	CAGCA>-	Likely-pathogenic	Coding sequence variant, frameshift variant
rs1554923004	->C	Likely-pathogenic	Coding sequence variant, frameshift variant
rs1554923121	T>C	Likely-pathogenic	Splice acceptor variant
rs1554923218	G>C	Pathogenic	Coding sequence variant, stop gained
rs1554923305	AGGGGCCCCTCACTGC>-	Likely-pathogenic	Coding sequence variant, splice donor variant, intron variant
rs1554923317	A>T	Likely-pathogenic	Splice donor variant
rs1554923513	C>G,T	Likely-pathogenic	Splice donor variant
rs1554923802	C>T	Likely-pathogenic	Splice donor variant
rs1554923810	->CGGGACAGCGCCGAGGGCT	Likely-pathogenic	Coding sequence variant, frameshift variant
rs1554923852	A>-	Likely-pathogenic	Coding sequence variant, frameshift variant
rs1564918287	CG>-	Likely-pathogenic	Coding sequence variant, frameshift variant
rs1590166832	GAACTGCGCGA>-	Likely-pathogenic, pathogenic	Coding sequence variant, frameshift variant
rs1590168246	G>C	Likely-pathogenic	Coding sequence variant, missense variant
rs1590168368	T>C	Likely-pathogenic	Splice acceptor variant
rs1590169710	G>A	Pathogenic	Coding sequence variant, stop gained
rs1590169802	A>T	Likely-pathogenic	Coding sequence variant, missense variant
rs1590170978	->CTC	Likely-pathogenic	Coding sequence variant, inframe insertion

Show/Hide all (14)

miRTarBase ID	miRNA	Experiments	Reference
MIRT437777	hsa-miR-1-3p	Luciferase reporter assay	25512392
MIRT1422303	hsa-miR-1226	CLIP-seq
MIRT1422304	hsa-miR-148a	CLIP-seq
MIRT1422305	hsa-miR-148b	CLIP-seq
MIRT1422306	hsa-miR-152	CLIP-seq
MIRT1422307	hsa-miR-2861	CLIP-seq
MIRT1422308	hsa-miR-3670	CLIP-seq
MIRT1422309	hsa-miR-3918	CLIP-seq
MIRT1422310	hsa-miR-4497	CLIP-seq
MIRT1422311	hsa-miR-4512	CLIP-seq
MIRT1422312	hsa-miR-4685-5p	CLIP-seq
MIRT1422313	hsa-miR-4733-3p	CLIP-seq
MIRT2395779	hsa-miR-140-3p	CLIP-seq
MIRT2395780	hsa-miR-197	CLIP-seq

Show/Hide all (14)

Transcription factor	Regulation	Reference
AR	Activation	16356647
ATF1	Unknown	11108136
CREB1	Unknown	11108136
CREM	Unknown	11108136
EGR1	Unknown	20124442
HOXA4	Unknown	12670698
HOXA5	Unknown	12670698
PITX3	Activation	22223473
REST	Activation	16764822
REST	Repression	16764822
SFPQ	Unknown	16731528
SP1	Unknown	20124442
SRY	Unknown	20124442;22568433
TFAP2A	Unknown	11146001

Show/Hide all (79)

GO ID	Ontology	Definition	Evidence	Reference
GO:0001666	Process	Response to hypoxia	IDA	17520326
GO:0001963	Process	Synaptic transmission, dopaminergic	IBA
GO:0001963	Process	Synaptic transmission, dopaminergic	IEA
GO:0001963	Process	Synaptic transmission, dopaminergic	ISS
GO:0003007	Process	Heart morphogenesis	NAS	12113410
GO:0004497	Function	Monooxygenase activity	IEA
GO:0004511	Function	Tyrosine 3-monooxygenase activity	IBA
GO:0004511	Function	Tyrosine 3-monooxygenase activity	IDA	1680128, 2896667, 11943812, 12631248, 16338639, 19703902
GO:0004511	Function	Tyrosine 3-monooxygenase activity	IEA
GO:0005506	Function	Iron ion binding	IEA
GO:0005515	Function	Protein binding	IPI	11943812, 19703902, 32296183
GO:0005634	Component	Nucleus	IDA	21392500
GO:0005634	Component	Nucleus	IEA
GO:0005634	Component	Nucleus	ISS
GO:0005737	Component	Cytoplasm	IBA
GO:0005737	Component	Cytoplasm	IDA	10907721, 21392500
GO:0005737	Component	Cytoplasm	IEA
GO:0005790	Component	Smooth endoplasmic reticulum	IDA	12457228
GO:0005829	Component	Cytosol	TAS
GO:0006585	Process	Dopamine biosynthetic process from tyrosine	IBA
GO:0006585	Process	Dopamine biosynthetic process from tyrosine	IEA
GO:0006585	Process	Dopamine biosynthetic process from tyrosine	NAS	10907721
GO:0007507	Process	Heart development	IEA
GO:0007507	Process	Heart development	ISS
GO:0007601	Process	Visual perception	IEA
GO:0007601	Process	Visual perception	ISS
GO:0007612	Process	Learning	IEA
GO:0007612	Process	Learning	ISS
GO:0007613	Process	Memory	IEA
GO:0007613	Process	Memory	ISS
GO:0007617	Process	Mating behavior	IBA
GO:0007617	Process	Mating behavior	IEA
GO:0007626	Process	Locomotory behavior	IEA
GO:0007626	Process	Locomotory behavior	ISS
GO:0008016	Process	Regulation of heart contraction	IEA
GO:0008016	Process	Regulation of heart contraction	ISS
GO:0008021	Component	Synaptic vesicle	IEA
GO:0009072	Process	Aromatic amino acid metabolic process	IEA
GO:0009653	Process	Anatomical structure morphogenesis	TAS	7715703
GO:0009887	Process	Animal organ morphogenesis	IEA
GO:0009887	Process	Animal organ morphogenesis	ISS
GO:0009898	Component	Cytoplasmic side of plasma membrane	IDA	12457228
GO:0016491	Function	Oxidoreductase activity	IEA
GO:0016714	Function	Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced pteridine as one donor, and incorporation of one atom of oxygen	IEA
GO:0019899	Function	Enzyme binding	IPI	19703902
GO:0030424	Component	Axon	IBA
GO:0030424	Component	Axon	IEA
GO:0031410	Component	Cytoplasmic vesicle	IDA	12457228
GO:0031410	Component	Cytoplasmic vesicle	IEA
GO:0033162	Component	Melanosome membrane	IDA	12631248
GO:0042416	Process	Dopamine biosynthetic process	IDA	12457228, 19703902
GO:0042416	Process	Dopamine biosynthetic process	IEA
GO:0042418	Process	Epinephrine biosynthetic process	IBA
GO:0042418	Process	Epinephrine biosynthetic process	IDA	12457228
GO:0042421	Process	Norepinephrine biosynthetic process	IBA
GO:0042421	Process	Norepinephrine biosynthetic process	IDA	12457228
GO:0042423	Process	Catecholamine biosynthetic process	IEA
GO:0042427	Process	Serotonin biosynthetic process	IBA
GO:0042462	Process	Eye photoreceptor cell development	IEA
GO:0042462	Process	Eye photoreceptor cell development	ISS
GO:0042755	Process	Eating behavior	IEA
GO:0042802	Function	Identical protein binding	IPI	32296183
GO:0042995	Component	Cell projection	IEA
GO:0043005	Component	Neuron projection	IDA	17135716
GO:0043005	Component	Neuron projection	IEA
GO:0043204	Component	Perikaryon	IBA
GO:0043204	Component	Perikaryon	IEA
GO:0043204	Component	Perikaryon	ISS
GO:0043473	Process	Pigmentation	TAS	12631248
GO:0045202	Component	Synapse	IEA
GO:0045471	Process	Response to ethanol	IDA	18343820
GO:0046872	Function	Metal ion binding	IEA
GO:0048471	Component	Perinuclear region of cytoplasm	IEA
GO:0048471	Component	Perinuclear region of cytoplasm	ISS
GO:0048596	Process	Embryonic camera-type eye morphogenesis	IEA
GO:0048596	Process	Embryonic camera-type eye morphogenesis	ISS
GO:0050890	Process	Cognition	IBA
GO:1990384	Process	Hyaloid vascular plexus regression	IEA
GO:1990384	Process	Hyaloid vascular plexus regression	ISS

MIM	HGNC	e!Ensembl
191290	11782	ENSG00000180176

P07101

Protein name

Tyrosine 3-monooxygenase (EC 1.14.16.2) (Tyrosine 3-hydroxylase) (TH)

Protein function

Catalyzes the conversion of L-tyrosine to L-dihydroxyphenylalanine (L-Dopa), the rate-limiting step in the biosynthesis of catecholamines, dopamine, noradrenaline, and adrenaline. Uses tetrahydrobiopterin and molecular oxygen to convert tyrosine

PDB

2XSN , 4J6S , 6ZN2 , 6ZVP , 6ZZU , 7A2G , 7PIM

Family and domains

Pfam

Accession	ID	Position in sequence	Description	Type
PF12549	TOH_N	2 → 26	Tyrosine hydroxylase N terminal	Family
PF12549	TOH_N	37 → 61	Tyrosine hydroxylase N terminal	Family
PF12549	TOH_N	57 → 80	Tyrosine hydroxylase N terminal	Family
PF00351	Biopterin_H	195 → 525	Biopterin-dependent aromatic amino acid hydroxylase	Domain

Tissue specificity

TISSUE SPECIFICITY: Mainly expressed in the brain and adrenal glands.

Sequence

MPTPDATTPQAKGFRRAVSELDAKQAEAIMVRGQGAPGPSLTGSPWPGTAAPAASYTPTP
RSPRFIGRRQSLIEDARKEREAAVAAAAAAVPSEPGDPLEAVAFEEKEGKAVLNLLFSPR
ATKPSALSRAVKVFETFEAKIHHLETRPAQRPRAGGPHLEYFVRLEVRRGDLAALLSGVR
QVSEDVRSPAGPKVPWFPRKVSELDKCHHLVTKFDPDLDLDHPGFSDQVYRQRRKLIAEI
AFQYRHGDPIPRVEYTAEEIATWKEVYTTLKGLYATHACGEHLEAFALLERFSGYREDNI
PQLEDVSRFLKERTGFQLRPVAGLLSARDFLASLAFRVFQCTQYIRHASSPMHSPEPDCC
HELLGHVPMLADRTFAQFSQDIGLASLGASDEEIEKLSTLYWFTVEFGLCKQNGEVKAYG
AGLLSSYGELLHCLSEEPEIRAFDPEAAAVQPYQDQTYQSVYFVSESFSDAKDKLRSYAS
RIQRPFSVKFDPYTLAIDVLDSPQAVRRSLEGVQDELDTLAHALSAIG

Sequence length

528

Interactions

View interactions

	KEGG		Reactome
	Tyrosine metabolism Folate biosynthesis Metabolic pathways Dopaminergic synapse Prolactin signaling pathway Parkinson disease Cocaine addiction Amphetamine addiction Alcoholism		Catecholamine biosynthesis

1101

Show/Hide Causal Diseases (3)

Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession
Causal Diseases associated with Pathogenic or Likely Pathogenic variants in ClinVar
Autosomal recessive DOPA responsive dystonia	Likely pathogenic; Pathogenic	rs2133690169, rs2133691221, rs1285458218, rs2133693561, rs2133692304, rs1367289835, rs2133689319, rs2133689285, rs2133690361, rs755922032, rs2133697599, rs1264884607, rs2133696288, rs2133690407, rs200751977 View all (135 more)	RCV001378224 RCV001379177 RCV001377711 RCV001379802 RCV001385616 RCV001582439 RCV001775267 RCV001959523 RCV001957338 RCV001904337 RCV002032110 RCV001999835 RCV001999899 RCV001999172 RCV001950773 RCV002044068 RCV001889566 RCV001878783 RCV002011534 RCV001946812 RCV002043113 RCV002026426 RCV001953643 RCV001984058 RCV002306620 RCV002306643 RCV002306717 RCV002309930 RCV002309950 RCV002308249 RCV002308261 RCV002309019 RCV002309020 RCV002309434 RCV002307050 RCV002307086 RCV000169247 RCV003058271 RCV002624255 RCV002685854 RCV002654430 RCV002796916 RCV000190632 RCV002843670 RCV002846820 RCV002881694 RCV002853217 RCV002881195 RCV002848382 RCV002885995 RCV002932749 RCV003014555 RCV003018608 RCV003032358 RCV003041879 RCV003132891 RCV003132893 RCV000013117 RCV000013118 RCV000013120 RCV000013121 RCV000013124 RCV000013125 RCV000013127 RCV003314471 RCV003340814 RCV003474109 RCV003474110 RCV003474111 RCV003474112 RCV003474113 RCV003474114 RCV003474115 RCV003474116 RCV003474117 RCV003474118 RCV003474119 RCV003474120 RCV003474121 RCV003474122 RCV003474123 RCV003474124 RCV003474125 RCV003474127 RCV003474128 RCV003512294 RCV003512413 RCV003512827 RCV003513459 RCV003511573 RCV003513603 RCV003625595 RCV003625871 RCV003626012 RCV003625962 RCV003625972 RCV003623967 RCV003624328 RCV003624339 RCV003625084 RCV000364341 RCV003864990 RCV004573736 RCV004573737 RCV004573738 RCV004573739 RCV004573740 RCV000410415 RCV000411713 RCV000410635 RCV000412367 RCV000409078 RCV000411945 RCV000409354 RCV000409032 RCV000410048 RCV000672619 RCV001782901 RCV000671827 RCV001860448 RCV001390236 RCV000667974 RCV000673660 RCV000673119 RCV000668727 RCV000671625 RCV000666718 RCV000673779 RCV000670358 RCV000668836 RCV000666731 RCV000673081 RCV000668510 RCV000667848 RCV000665867 RCV000671087 RCV000669954 RCV000674959 RCV000666054 RCV000674870 RCV000666984 RCV000669515 RCV000671082 RCV000670214 RCV000671003 RCV000721988 RCV001004555 RCV001825549 RCV001376813 RCV005606716 RCV005606715 RCV000988470 RCV000988471 RCV000995669 RCV001041901 RCV001220234 RCV001217693 RCV001245005 RCV001300835
Dystonia 5	Likely pathogenic; Pathogenic	rs762304556	RCV001353113
Dystonic disorder	Likely pathogenic; Pathogenic	rs1590168246, rs1590169710	RCV000853251 RCV000853250

Show/Hide Unknown Diseases (6)

Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession
Unknown Diseases with uncertain, conflicting, or no pathogenic evidence in ClinVar
Gastric cancer	Benign	rs4072824, rs11826260	RCV005924451 RCV005892960
Intellectual disability	Uncertain significance	rs373964946	RCV005626163
Lung cancer	Benign	rs4072824	RCV005924453
Schizophrenia	Benign; Likely benign	rs10770141, rs6356	RCV003633586 RCV003633482
TH-related disorder	Conflicting classifications of pathogenicity; Likely benign; Benign	rs777421313, rs749856378, rs372002058, rs11042950, rs74555599, rs202149985, rs758016812, rs776510373, rs1468608879, rs147852210, rs184106392, rs778613708, rs118175546, rs544661832, rs139742336 View all (4 more)	RCV003930916 RCV003946101 RCV003980417 RCV003919991 RCV003919990 RCV003930285 RCV003940150 RCV003924045 RCV003937139 RCV003960115 RCV003935376 RCV003953238 RCV003975370 RCV003918346 RCV003928326 RCV003938214 RCV003965719 RCV003948114 RCV003938452
Uterine carcinosarcoma	Benign	rs4072824	RCV005924452

Show/Hide Text Mining Associations (62)

Disease Name	Relationship Type	References
Associations from Text MiningDisease associations identified through Pubtator
6 pyruvoyl tetrahydropterin synthase deficiency	Associate	27798097
Abdominal Injuries	Associate	18840642
Adenomyosis	Associate	23755957
Adjustment Disorders	Associate	17329957
Albinism Oculocutaneous	Associate	8651291
Alzheimer Disease	Associate	16407544
Atrial Fibrillation	Associate	24301786, 35461705
Bipolar Disorder	Associate	2880337
Breast Neoplasms	Associate	37192740
Carcinoma Hepatocellular	Associate	31188160
Death	Associate	15735319
Diabetes Mellitus Type 1	Associate	15303408, 33753784
Disease	Associate	14993794
Drug Related Side Effects and Adverse Reactions	Inhibit	33652595
Dystonia	Associate	15468323, 2565377
Dystonia Dopa responsive	Associate	23762320, 23939262, 24753243, 25181484, 29405179, 32018151
Dystonic Disorders	Associate	15468323, 2565377
Essential Hypertension	Associate	15735319
Gait Ataxia	Associate	26732803
Genetic Diseases Inborn	Associate	25758715
Glut1 Deficiency Syndrome	Inhibit	39847894
Hypertension	Associate	20571875, 23489065
Hypertrophy	Associate	15735319
Hypotension	Associate	21844155, 7760324
Infantile Epileptic Dyskinetic Encephalopathy	Associate	23939262
Leukemia Myeloid Acute	Associate	27016413
Lewy Body Disease	Associate	16407544
Lewy Body Disease	Inhibit	28949048, 34983390
Long QT Syndrome	Associate	8818942
Major Affective Disorder 2	Associate	2898127
Mental Disorders	Associate	17329957
Metabolic Diseases	Associate	27934587
Metabolism Inborn Errors	Associate	32018151
Migraine Disorders	Associate	25929431
Mood Disorders	Associate	2880337
Multiple Endocrine Neoplasia Type 2b	Associate	8913331
Myocardial Infarction	Associate	15735319
Neoplasms	Associate	14716776, 18980998, 26700559
Neoplasms	Stimulate	27034145
Neoplasms	Inhibit	34678150
Nerve Degeneration	Associate	17288595, 31234228
Neuroblastoma	Associate	10393831, 11483656, 12358785, 14716776, 14993794, 18520032, 19285077, 20650311, 21951066, 27034145, 8577710, 9591338
Neurodegenerative Diseases	Associate	26558463, 29039448
Neuroendocrine Tumors	Associate	32668278
Obesity	Associate	26808524
Obesity Abdominal	Associate	26808524
Pain	Associate	30904518
Paraganglioma	Associate	25946206
Parkinson Disease	Associate	20809526, 21951066, 26732803, 31048719, 38245794, 39847894
Parkinson Disease	Inhibit	34983390
Phenylketonurias	Associate	11179966
Pheochromocytoma	Associate	25946206, 30468801, 8913331
Prostatic Neoplasms	Associate	25183411
Restless Legs Syndrome	Associate	18226951
Rhabdomyosarcoma	Associate	30468801
Segawa syndrome autosomal recessive	Inhibit	23939262, 37041529
Segawa syndrome autosomal recessive	Associate	23939262, 24753243, 27934587, 30411798, 37041529
Stomach Diseases	Associate	21075859
Supranuclear Palsy Progressive	Associate	9920892
Tarlov Cysts	Associate	36418844
Timothy syndrome	Associate	22120178
Uniparental Disomy	Associate	30952972

TH (tyrosine hydroxylase)