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GeneE
25 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
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THRA
thyroid hormone receptor alpha
Chromosome 17 Β· 17q21.1
NCBI Gene: 7067Ensembl: ENSG00000126351.14HGNC: HGNC:11796UniProt: P10827
213PubMed Papers
21Diseases
7Drugs
19Pathogenic Variants
FUNCTIONAL ROLE
ReceptorTranscription Factor
RESEARCH IMPACT
Trending
CLINICAL
FDA Approved TargetOMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
TBP-class protein bindingprotein bindingtranscription cis-regulatory region bindingregulation of transcription by RNA polymerase IIperipheral resistance to thyroid hormoneshypothyroidismdifferentiated thyroid carcinomagenetic disorder
✦AI Summary

THRA (thyroid hormone receptor alpha) is a ligand-dependent transcription factor that mediates cellular effects of thyroid hormones through heterodimerization with retinoid X receptor and binding to thyroid hormone response elements 1. While THRA can bind thyroid hormone, it functions as a weak dominant negative inhibitor of thyroid hormone action [UniProt]. THRA and THRB have distinct, non-overlapping physiological functions 2. THRA is expressed during early nervous system development 3 and regulates spatiotemporal responses in skin wound healing through phase-coupled mechanisms: epidermal THRA activates glutathione metabolism to accelerate reepithelialization, while dermal THRA mediates extracellular matrix maturation 4. Mutations in THRA cause resistance to thyroid hormone alpha (RTHΞ±), characterized by abnormalities in growth and gastrointestinal function with minimal effects on the hypothalamic-pituitary-thyroid axis, contrasting with RTHΞ² 2. THRA is predominantly expressed in tissues including heart and bone, where selective THRB activation is preferred therapeutically to avoid THRA-mediated side effects 5. Genome-wide analysis identified THRA as a potential therapeutic target for migraine treatment 6.

Sources cited
1
THRA is a ligand-dependent transcription factor mediating thyroid hormone effects through heterodimerization with RXR and binding to thyroid hormone response elements
PMID: 39541421
2
THRA and THRB have distinct non-overlapping functions; THRA mutations cause RTHΞ± with growth and gastrointestinal abnormalities but minimal effects on the hypothalamic-pituitary-thyroid axis
PMID: 25135573
3
THRA is expressed during early nervous system development in developing human cerebral organoids
PMID: 38654093
4
THRA regulates spatiotemporal wound healing responses through epidermal glutathione metabolism and dermal extracellular matrix maturation
PMID: 40558382
5
THRA is predominantly expressed in heart and bone; selective THRB activation is preferred therapeutically to avoid THRA-mediated side effects
PMID: 39420154
6
THRA was identified as a potential druggable therapeutic target for migraine treatment through genome-wide Mendelian randomization analysis
PMID: 38867170
Disease Associationsβ“˜21
peripheral resistance to thyroid hormonesOpen Targets
0.70Strong
hypothyroidismOpen Targets
0.61Moderate
differentiated thyroid carcinomaOpen Targets
0.50Moderate
genetic disorderOpen Targets
0.48Moderate
congenital hypothyroidismOpen Targets
0.47Moderate
myxedemaOpen Targets
0.46Moderate
neurodegenerative diseaseOpen Targets
0.45Moderate
thyroid cancerOpen Targets
0.40Moderate
thyroid hormone resistance syndromeOpen Targets
0.37Weak
skeletal dysplasiaOpen Targets
0.37Weak
cardiovascular diseaseOpen Targets
0.37Weak
ConstipationOpen Targets
0.37Weak
constipation disorderOpen Targets
0.37Weak
Growth delayOpen Targets
0.37Weak
hypothyroidism, congenital, nongoitrousOpen Targets
0.37Weak
MacrocephalyOpen Targets
0.37Weak
macrocytic anemiaOpen Targets
0.37Weak
nontoxic goiterOpen Targets
0.37Weak
thyroid carcinomaOpen Targets
0.37Weak
ThyrotoxicosisOpen Targets
0.37Weak
Hypothyroidism, congenital, non-goitrous, 6UniProt
Pathogenic Variants19
NM_199334.5(THRA):c.1207G>A (p.Glu403Lys)Pathogenic
Congenital nongoitrous hypothyroidism 6|not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 403
NM_199334.5(THRA):c.788C>T (p.Ala263Val)Pathogenic
Inborn genetic diseases|Congenital nongoitrous hypothyroidism 6|not provided
β˜…β˜…β˜†β˜†2022β†’ Residue 263
NM_199334.5(THRA):c.1196dup (p.Leu400fs)Pathogenic
Inborn genetic diseases
β˜…β˜†β˜†β˜†2025β†’ Residue 400
NM_199334.5(THRA):c.1141C>T (p.His381Tyr)Likely pathogenic
Congenital nongoitrous hypothyroidism 6
β˜…β˜†β˜†β˜†2024β†’ Residue 381
NM_199334.5(THRA):c.1151G>A (p.Arg384His)Pathogenic
not provided
β˜…β˜†β˜†β˜†2023β†’ Residue 384
NM_199334.5(THRA):c.872G>A (p.Gly291Asp)Likely pathogenic
not provided
β˜…β˜†β˜†β˜†2022β†’ Residue 291
NM_199334.5(THRA):c.818C>A (p.Thr273Asn)Likely pathogenic
Congenital nongoitrous hypothyroidism 6
β˜…β˜†β˜†β˜†2022β†’ Residue 273
NM_199334.5(THRA):c.871G>A (p.Gly291Ser)Pathogenic
not provided
β˜…β˜†β˜†β˜†2022β†’ Residue 291
NM_003250.6(THRA):c.1416dup (p.Ser473fs)Pathogenic
Congenital nongoitrous hypothyroidism 6
β˜…β˜†β˜†β˜†2021β†’ Residue 473
NM_199334.5(THRA):c.518A>G (p.Glu173Gly)Likely pathogenic
Congenital nongoitrous hypothyroidism 6
β˜…β˜†β˜†β˜†2020β†’ Residue 173
NM_199334.5(THRA):c.1132_1141del (p.Gly378fs)Likely pathogenic
Neurodevelopmental disorder
β˜…β˜†β˜†β˜†2020β†’ Residue 378
NM_199334.5(THRA):c.1150C>T (p.Arg384Cys)Pathogenic
not provided
β˜…β˜†β˜†β˜†2020β†’ Residue 384
NM_199334.5(THRA):c.641C>G (p.Ala214Gly)Likely pathogenic
not provided
β˜…β˜†β˜†β˜†2019β†’ Residue 214
NM_199334.5(THRA):c.1137del (p.Cys380fs)Pathogenic
Inborn genetic diseases
β˜…β˜†β˜†β˜†2014β†’ Residue 380
NM_199334.5(THRA):c.896T>C (p.Ile299Thr)Likely pathogenic
Congenital nongoitrous hypothyroidism 6
β˜…β˜†β˜†β˜†β†’ Residue 299
NM_199334.5(THRA):c.1193C>G (p.Pro398Arg)Pathogenic
Congenital nongoitrous hypothyroidism 6
β˜†β˜†β˜†β˜†2015β†’ Residue 398
NM_199334.5(THRA):c.1176C>A (p.Cys392Ter)Pathogenic
Congenital nongoitrous hypothyroidism 6
β˜†β˜†β˜†β˜†2015β†’ Residue 392
NM_199334.5(THRA):c.134G>T (p.Ser45Ile)Pathogenic
Congenital nongoitrous hypothyroidism 6
β˜†β˜†β˜†β˜†2015β†’ Residue 45
NM_199334.5(THRA):c.1110G>C (p.Lys370Asn)Pathogenic
Congenital nongoitrous hypothyroidism 6
β˜†β˜†β˜†β˜†2012β†’ Residue 370
View on ClinVar β†—
Drug Targets7
DEXTROTHYROXINEApproved
Thyroid hormone receptor agonist
cardiovascular disease
DEXTROTHYROXINE SODIUMApproved
Thyroid hormone receptor agonist
LEVOTHYROXINEApproved
Thyroid hormone receptor agonist
hypothyroidism
LEVOTHYROXINE SODIUMApproved
Thyroid hormone receptor agonist
hypothyroidism
LIOTHYRONINEApproved
Thyroid hormone receptor agonist
hypothyroidism
LIOTHYRONINE SODIUMApproved
Thyroid hormone receptor agonist
differentiated thyroid carcinoma
TIRATRICOLApproved
Thyroid hormone receptor agonist
Related Genes
PIK3R3Protein interaction100%PIK3R1Protein interaction100%PIK3CBProtein interaction100%PIK3CDProtein interaction100%PIK3CAProtein interaction100%MED12Protein interaction100%
Tissue Expression6 tissues
Heart
100%
Brain
96%
Ovary
84%
Bone Marrow
72%
Lung
37%
Liver
13%
Gene Interaction Network
Click a node to explore
THRAPIK3R3PIK3R1PIK3CBPIK3CDPIK3CAMED12
PROTEIN STRUCTURE
Preparing viewer…
PDB3ILZ Β· 1.85 Γ… Β· X-ray
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
0.44Moderately Constrained
pLIβ“˜
1.00Intolerant
Observed/Expected LoF0.28 [0.18–0.44]
RankingsWhere THRA stands among ~20K protein-coding genes
  • #1,956of 20,598
    Most Researched213 Β· top 10%
  • #220of 1,025
    FDA-Approved Drug Targets7 Β· top quartile
  • #2,220of 5,498
    Most Pathogenic Variants19
  • #2,392of 17,882
    Most Constrained (LOEUF)0.44 Β· top quartile
Genes detectedTHRA
Sources retrieved25 papers
Response timeβ€”
πŸ“„ Sources
25β–Ό
1
Thyroid hormone receptors and resistance to thyroid hormone disorders.
PMID: 25135573
Nat Rev Endocrinol Β· 2014
1.00
2
PMID: 25905404
0.90
3
Actions of thyroid hormones and thyromimetics on the liver.
PMID: 39420154
Nat Rev Gastroenterol Hepatol Β· 2025
0.80
4
T3 Promotes Glioma Cell Senescence and Apoptosis via THRA and THRB.
PMID: 34936295
J Environ Pathol Toxicol Oncol Β· 2021
0.72
5
Identifying therapeutic target genes for migraine by systematic druggable genome-wide Mendelian randomization.
PMID: 38867170
J Headache Pain Β· 2024
0.70