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GeneE
25 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
β“˜GeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
TH
tyrosine hydroxylase
Chromosome 11 Β· 11p15.5
NCBI Gene: 7054Ensembl: ENSG00000180176.16HGNC: HGNC:11782UniProt: P07101
257PubMed Papers
21Diseases
1Drugs
189Pathogenic Variants
FUNCTIONAL ROLE
Hub Gene
RESEARCH IMPACT
TrendingVariant-Rich
CLINICAL
FDA Approved TargetOMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
cytoplasmic vesicleneuron projectioncytoplasmic side of plasma membranesmooth endoplasmic reticulumAutosomal recessive dopa-responsive dystoniaTH-deficient dopa-responsive dystoniadopa-responsive dystoniatyrosine hydroxylase deficiency
✦AI Summary

Tyrosine hydroxylase (TH) is a crucial enzyme catalyzing the first committed step in catecholamine biosynthesis, converting tyrosine to L-DOPA, a precursor for dopamine, norepinephrine, and epinephrine production. TH is predominantly expressed in dopaminergic and noradrenergic neurons throughout the central and peripheral nervous systems, with localization to cytoplasmic compartments, synaptic vesicles, and the plasma membrane. The enzyme's activity is essential for midbrain dopamine neuron (mDAN) function and survival 1. Loss or dysfunction of TH-positive dopaminergic neurons is pathologically relevant to Parkinson's disease, where dopamine depletion causes progressive motor dysfunction 1. Segawa syndrome, an autosomal recessive neurological disorder, results from TH mutations causing severe reduction in dopamine and catecholamine synthesis, leading to early-onset dystonia, hypokinesia, and diurnal motor fluctuations. Beyond dopaminergic functions, TH participates in regulating cardiovascular function, stress responses, and neuroendocrine signaling. Recent evidence from cell transplantation studies demonstrates that TH expression marks functional dopaminergic grafts, with poor survival of TH+ neurons in initial transplantation contexts but improved outcomes when combined with immunomodulatory strategies 1. These findings establish TH as a critical molecular marker and functional determinant of dopaminergic neuron identity with direct implications for neurodegenerative disease pathogenesis and regenerative therapeutic approaches.

Sources cited
1
TH marks midbrain dopamine neurons; less than 10% of TH+ mDANs survived two weeks after transplantation; TH expression indicates functional dopaminergic neurons; poor survival of TH+ grafted cells in Parkinson's disease models
PMID: 37438521
⚠Limited data available β€” This gene has 1 indexed publication. Summary and analysis may be incomplete.
Disease Associationsβ“˜21
Autosomal recessive dopa-responsive dystoniaOpen Targets
0.85Strong
TH-deficient dopa-responsive dystoniaOpen Targets
0.78Strong
dopa-responsive dystoniaOpen Targets
0.64Moderate
tyrosine hydroxylase deficiencyOpen Targets
0.56Moderate
dystonia 5Open Targets
0.53Moderate
pheochromocytomaOpen Targets
0.47Moderate
adrenal gland pheochromocytomaOpen Targets
0.46Moderate
Intellectual disabilityOpen Targets
0.45Moderate
DystoniaOpen Targets
0.42Moderate
dystonic disorderOpen Targets
0.42Moderate
genetic disorderOpen Targets
0.42Moderate
type 2 diabetes mellitusOpen Targets
0.41Moderate
diabetes mellitusOpen Targets
0.38Weak
hypertensionOpen Targets
0.38Weak
type 1 diabetes mellitusOpen Targets
0.34Weak
diabetic eye diseaseOpen Targets
0.34Weak
Abnormality of the skeletal systemOpen Targets
0.31Weak
diabetic neuropathyOpen Targets
0.30Weak
diabetic retinopathyOpen Targets
0.29Weak
neuroinflammatory disorderOpen Targets
0.28Weak
Segawa syndrome autosomal recessiveUniProt
Pathogenic Variants189
NM_000360.4(TH):c.364C>T (p.Arg122Ter)Pathogenic
not provided|Autosomal recessive DOPA responsive dystonia
β˜…β˜…β˜†β˜†2026β†’ Residue 122
NM_000360.4(TH):c.605G>A (p.Arg202His)Pathogenic
Autosomal recessive DOPA responsive dystonia|not provided
β˜…β˜…β˜†β˜†2026β†’ Residue 202
NM_000360.4(TH):c.1147G>A (p.Gly383Arg)Pathogenic
Autosomal recessive DOPA responsive dystonia
β˜…β˜…β˜†β˜†2026β†’ Residue 383
NM_000360.4(TH):c.90+13G>ALikely pathogenic
Autosomal recessive DOPA responsive dystonia
β˜…β˜…β˜†β˜†2026
NM_000360.4(TH):c.646G>A (p.Gly216Ser)Pathogenic
Dystonia 5|Autosomal recessive DOPA responsive dystonia|not provided|Tyrosine hydroxylase deficiency
β˜…β˜…β˜†β˜†2026β†’ Residue 216
NM_000360.4(TH):c.1400A>G (p.Asp467Gly)Pathogenic
Autosomal recessive DOPA responsive dystonia|not provided
β˜…β˜…β˜†β˜†2026β†’ Residue 467
NM_000360.4(TH):c.412C>T (p.Arg138Ter)Pathogenic
Autosomal recessive DOPA responsive dystonia|not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 138
NM_000360.4(TH):c.1382C>T (p.Pro461Leu)Pathogenic
Autosomal recessive DOPA responsive dystonia
β˜…β˜…β˜†β˜†2025β†’ Residue 461
NM_000360.4(TH):c.1088T>C (p.Ile363Thr)Likely pathogenic
Autosomal recessive DOPA responsive dystonia
β˜…β˜…β˜†β˜†2025β†’ Residue 363
NM_000360.4(TH):c.90+7dupPathogenic
Autosomal recessive DOPA responsive dystonia
β˜…β˜…β˜†β˜†2025
NM_000360.4(TH):c.601C>T (p.Gln201Ter)Pathogenic
Autosomal recessive DOPA responsive dystonia
β˜…β˜…β˜†β˜†2025β†’ Residue 201
NC_000011.10:g.2171856C>TPathogenic
Autosomal recessive DOPA responsive dystonia|not provided
β˜…β˜…β˜†β˜†2025
NM_000360.4(TH):c.889C>T (p.Arg297Trp)Pathogenic
Autosomal recessive DOPA responsive dystonia|not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 297
NM_000360.4(TH):c.917G>A (p.Arg306His)Pathogenic
Autosomal recessive DOPA responsive dystonia
β˜…β˜…β˜†β˜†2025β†’ Residue 306
NM_000360.4(TH):c.644+1G>ALikely pathogenic
Autosomal recessive DOPA responsive dystonia
β˜…β˜…β˜†β˜†2025
NM_000360.4(TH):c.1032C>G (p.Phe344Leu)Likely pathogenic
Autosomal recessive DOPA responsive dystonia|not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 344
NM_000360.4(TH):c.628G>A (p.Ala210Thr)Pathogenic
Autosomal recessive DOPA responsive dystonia
β˜…β˜…β˜†β˜†2025β†’ Residue 210
NM_000360.4(TH):c.983G>T (p.Cys328Phe)Likely pathogenic
Autosomal recessive DOPA responsive dystonia
β˜…β˜…β˜†β˜†2025β†’ Residue 328
NM_000360.4(TH):c.1334+1G>ALikely pathogenic
Autosomal recessive DOPA responsive dystonia
β˜…β˜…β˜†β˜†2025
NM_000360.4(TH):c.614T>C (p.Leu205Pro)Pathogenic
Autosomal recessive DOPA responsive dystonia|not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 205
View on ClinVar β†—
Drug Targets1
METYROSINEApproved
Tyrosine 3-hydroxylase inhibitor
adrenal gland pheochromocytoma
Related Genes
DHFR2Protein interaction99%YWHAZProtein interaction99%AKR1B1Protein interaction97%DHFRProtein interaction97%GCH1Protein interaction97%PCBD1Protein interaction97%
Tissue Expression6 tissues
Liver
100%
Brain
50%
Ovary
46%
Bone Marrow
6%
Lung
1%
Heart
1%
Gene Interaction Network
Click a node to explore
THDHFR2YWHAZAKR1B1DHFRGCH1PCBD1
PROTEIN STRUCTURE
Preparing viewer…
PDB2XSN Β· 2.68 Γ… Β· X-ray
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
1.27LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF1.00 [0.80–1.27]
RankingsWhere TH stands among ~20K protein-coding genes
  • #1,495of 20,598
    Most Researched257 Β· top 10%
  • #823of 1,025
    FDA-Approved Drug Targets1
  • #369of 5,498
    Most Pathogenic Variants189 Β· top 10%
  • #13,393of 17,882
    Most Constrained (LOEUF)1.27
Genes detectedTH
Sources retrieved25 papers
Response timeβ€”
πŸ“„ Sources
25β–Ό
1
Genetic Disease and Therapy.
PMID: 33497260
Annu Rev Pathol Β· 2021
1.00
2
The Laboratory Rat: Relating Its Age With Human's.
PMID: 23930179
Int J Prev Med Β· 2013
0.90
3
Selenium and selenoproteins: it's role in regulation of inflammation.
PMID: 32144521
Inflammopharmacology Β· 2020
0.80
4
T Helper (Th) Cell Profiles in Pregnancy and Recurrent Pregnancy Losses: Th1/Th2/Th9/Th17/Th22/Tfh Cells.
PMID: 32973809
Front Immunol Β· 2020
0.70
5
Dopa-responsive dystonia and phenotypes associated with TH gene variants: a systematic review and Mexican case series.
PMID: 40437309
Neurol Sci Β· 2025
0.64