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Atlas / Disease / Hyperthyroidism

Hyperthyroidism

disease
On this page

Also known as overactive thyroid

Summary

Hyperthyroidism (MONDO:0004425) is a disease (an umbrella term covering 10 Mondo subtypes) with 14 cohort genes (92 GWAS associations across 17 studies) and 76 clinical trials. The dominant Reactome pathway is G alpha (s) signalling events (3 cohort genes). Top therapeutic interventions include propranolol, methimazole, and doxycycline anhydrous.

At a glance

  • Umbrella term: 10 Mondo subtypes
  • Cohort genes: 14
  • GWAS associations: 92
  • ClinVar variants: 14
  • Clinical trials: 76

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

FieldValue
Canonical namehyperthyroidism
Mondo IDMONDO:0004425
EFOEFO:0009189
MeSHD006980
DOIDDOID:7998
NCITC3123
SNOMED CT34486009
UMLSC0020550
MedGen6972
Is cancer (heuristic)no

Also known as: overactive thyroid

Data availability: 14 ClinVar variants · 92 GWAS associations (17 studies).

Disease family

An umbrella term covering 10 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › endocrine system disorder › thyroid gland disorder › hyperthyroidism

Related subtypes (11): thyrocalcitonin secretion disease, thyroiditis, thyroid malformation, hyperthyroxinemia, goiter, hypothyroidism, C-cell hyperplasia, atrophy of thyroid, euthyroid sick syndrome, thyroid tumor, inherited thyroid metabolism disease

Subtypes (10): toxic diffuse goiter, thyroid crisis, selective pituitary resistance to thyroid hormone, generalized resistance to thyroid hormone, thyrotoxicosis, familial gestational hyperthyroidism, familial hyperthyroidism due to mutations in TSH receptor, hyperthyroxinemia, familial dysalbuminemic, primary hyperthyroidism, secondary hyperthyroidism

Genetics & variants

GWAS landscape

92 GWAS associations across 17 studies. Top hits map to 21 distinct genes (as reported by GWAS).

Top associations by p-value

rsIDp-valueGeneRisk alleleOdds ratio
chr6:326339605e-147AG0.51
rs77472368e-117HLA-DRB5 - RNU1-61PT0.67
rs121483312e-66LINC01586T1.68
chr14:809909135e-54C0.25
rs17942802e-44HLA-DQB1 - MTCO3P1T0.55
rs21602152e-37TSHRC1.29
chr2:2038741963e-35A0.2
rs23005198e-34TSHRA0.3
rs286874185e-32LINC01586A1.78
rs412692658e-32ZNF184C0.39
rs587221867e-30MAFTRR, LINC01229T1.43
rs283662726e-29HLA-DRB1 - HLA-DQA1A0.4
rs67545063e-28TESHLA0.63
chr1:1137611861e-23A0.25
rs30872431e-22CTLA4 - ICOSA0.24
rs115712972e-22CTLA4 - ICOST1.2
rs20460454e-22PDE8BT0.33
rs10337012e-21PDE10AA1.5
rs24766016e-21AP4B1-AS1, PTPN22A1.28
rs7148624e-20DIRC3G1.41
rs3347061e-18NFIAG1.59
rs1478286536e-18HCG27 - HLA-CC0.37
rs78734634e-17GLIS3A0.76
rs125154986e-17PDE8BT1.37
rs66796776e-17PHTF1 - RSBN1A0.32
chr10:60568612e-16C0.13
rs340389213e-16ZNF70P1 - HTATSF1P1C1.41
rs22159813e-16TSHRA0.8
chr11:955782588e-16C0.17
rs31183581e-15NOP56P1 - LINC01623G1.82

Top studies (by case count)

StudyLead authorYearCasesControlsTitle
GCST90473161UK Biobank Whole-Genome Sequencing Consortium20257,956450,484Whole-genome sequencing of 490,640 UK Biobank participants.
GCST90667836UK Biobank Whole-Genome Sequencing Consortium20257,956450,484Whole-genome sequencing of 490,640 UK Biobank participants.
GCST90319319Figueredo J20246,442736,566Uncovering the Shared Genetic Components of Thyroid Disorders and Reproductive Health.
GCST90435199Wei Y20244,49168,140Genome-wide association studies of thyroid-related hormones, dysfunction, and autoimmunity among 85,421 Chinese pregnancies.
GCST90038636Donertas HM20213,731480,867Common genetic associations between age-related diseases.
GCST90018860Sakaue S20213,557456,942A cross-population atlas of genetic associations for 220 human phenotypes.
GCST90077728Backman JD20213,510328,244Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90081714Backman JD20213,510328,244Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90103389Fitzgerald T20222,581168,176CNest: A novel copy number association discovery method uncovers 862 new associations from 200,629 whole-exome sequence datasets in the UK Biobank.
GCST006897Teumer A20181,84049,983Genome-wide analyses identify a role for SLC17A4 and AADAT in thyroid hormone regulation.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

TierVariants
Tier 1: coding2
Tier 2: splice/UTR0
Tier 3: regulatory0
Tier 4: intronic/intergenic48

MAF distribution

BucketVariants
common (>=0.05)33
low_freq (0.01-0.05)2
rare (<0.01)0
unknown15

Functional consequences

ConsequenceCount
intron_variant22
unknown15
intergenic_variant9
non_coding_transcript_exon_variant2
missense_variant2

Top variants

rsIDChrPosAllelesMAFConsequenceGenep-valueTier
chr6:326339605e-147Tier 4: intronic/intergenic
rs7747236632534622C>T0.138intergenic_variantHLA-DRB5 - RNU1-61P8e-117Tier 4: intronic/intergenic
rs121483311588566850C>G,T0.249intron_variantLINC015862e-66Tier 4: intronic/intergenic
chr14:809909135e-54Tier 4: intronic/intergenic
rs1794280632699394A>T0.05intergenic_variantHLA-DQB1 - MTCO3P12e-44Tier 4: intronic/intergenic
rs21602151480995128T>A,C0.05intron_variantTSHR2e-37Tier 4: intronic/intergenic
chr2:2038741963e-35Tier 4: intronic/intergenic
rs23005191480992418T>A,G0.383intron_variantTSHR8e-34Tier 4: intronic/intergenic
rs286874181588572631G>A0.26intron_variantLINC015865e-32Tier 4: intronic/intergenic
rs41269265627457570T>C,G0.114non_coding_transcript_exon_variantZNF1848e-32Tier 4: intronic/intergenic
rs587221861679717694C>A,T0.229intron_variantMAFTRR, LINC012297e-30Tier 4: intronic/intergenic
rs28366272632592198C>A0.162intergenic_variantHLA-DRB1 - HLA-DQA16e-29Tier 4: intronic/intergenic
rs67545062216749927G>A0.497intron_variantTESHL3e-28Tier 4: intronic/intergenic
chr1:1137611861e-23Tier 4: intronic/intergenic
rs30872432203874196G>A,T0.451intergenic_variantCTLA4 - ICOS1e-22Tier 4: intronic/intergenic
rs115712972203880280T>C0.05intergenic_variantCTLA4 - ICOS2e-22Tier 4: intronic/intergenic
rs2046045577239986T>A,C,G0.4intron_variantPDE8B4e-22Tier 4: intronic/intergenic
rs10337016165627371G>A0.149intron_variantPDE10A2e-21Tier 4: intronic/intergenic
rs24766011113834946A>G,T0.05missense_variantAP4B1-AS1, PTPN226e-21Tier 1: coding
rs7148622217374703A>C,G,T0.472intron_variantDIRC34e-20Tier 4: intronic/intergenic
rs334706161150575G>A,C0.039intron_variantNFIA1e-18Tier 4: intronic/intergenic
rs147828653631257783G>C0.097intergenic_variantHCG27 - HLA-C6e-18Tier 4: intronic/intergenic
rs787346394221298A>C,T0.321intron_variantGLIS34e-17Tier 4: intronic/intergenic
rs12515498577244147T>A,C,G0.166intron_variantPDE8B6e-17Tier 4: intronic/intergenic
rs66796771113761186C>A,T0.102intergenic_variantPHTF1 - RSBN16e-17Tier 4: intronic/intergenic
chr10:60568612e-16Tier 4: intronic/intergenic
rs34038921633227606G>A,C0.05intergenic_variantZNF70P1 - HTATSF1P13e-16Tier 4: intronic/intergenic
rs22159811480978623G>A,T0.323intron_variantTSHR3e-16Tier 4: intronic/intergenic
chr11:955782588e-16Tier 4: intronic/intergenic
rs3118358628831611T>C,G0.05intergenic_variantNOP56P1 - LINC016231e-15Tier 4: intronic/intergenic

ClinVar germline variants

14 retrieved; paginated sample, class counts are floors:

6 pathogenic, 4 conflicting classifications of pathogenicity, 3 likely pathogenic, 1 pathogenic/likely pathogenic

ClinVarVariant (HGVS)GeneClassificationReview
26800946;X;t(X;3)(p21.3;p25.1)dnPathogeniccriteria provided, single submitter
4682120NM_000477.7(ALB):c.724C>A (p.Arg242Ser)ALBPathogeniccriteria provided, single submitter
12542NM_001354712.2(THRB):c.949G>A (p.Ala317Thr)THRBPathogeniccriteria provided, multiple submitters, no conflicts
12567NM_001354712.2(THRB):c.727C>T (p.Arg243Trp)THRBPathogeniccriteria provided, multiple submitters, no conflicts
439310NM_001354712.2(THRB):c.1357C>T (p.Pro453Ser)THRBPathogeniccriteria provided, multiple submitters, no conflicts
492920NM_001354712.2(THRB):c.1293A>G (p.Ile431Met)THRBPathogeniccriteria provided, single submitter
548123NM_001354712.2(THRB):c.1286G>A (p.Arg429Gln)THRBPathogenic/Likely pathogeniccriteria provided, multiple submitters, no conflicts
4682108NM_001354712.2(THRB):c.959G>C (p.Arg320Pro)THRBLikely pathogeniccriteria provided, single submitter
4820259NM_001354712.2(THRB):c.964G>A (p.Asp322Asn)THRBLikely pathogeniccriteria provided, single submitter
4820253NM_000369.5(TSHR):c.1454C>T (p.Ala485Val)TSHRLikely pathogeniccriteria provided, single submitter
619915NM_001354712.2(THRB):c.1147C>T (p.Arg383Cys)THRBConflicting classifications of pathogenicitycriteria provided, conflicting classifications
2237467NM_000369.5(TSHR):c.2170G>T (p.Val724Phe)TSHRConflicting classifications of pathogenicitycriteria provided, conflicting classifications
13434NM_000371.4(TTR):c.416C>T (p.Thr139Met)TTRConflicting classifications of pathogenicitycriteria provided, conflicting classifications
43454NM_000371.4(TTR):c.385G>A (p.Ala129Thr)TTRConflicting classifications of pathogenicitycriteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 25 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

GeneOrphanet IDRare disease
SOX9Orphanet:140Campomelic dysplasia
SOX9Orphanet:213846,XX ovotesticular difference of sex development
SOX9Orphanet:24246,XY complete gonadal dysgenesis
SOX9Orphanet:25151046,XY partial gonadal dysgenesis
SOX9Orphanet:39346,XX testicular difference of sex development
SOX9Orphanet:718Isolated Pierre Robin sequence
TGOrphanet:95716Familial thyroid dyshormonogenesis
THRBOrphanet:566243Resistance to thyroid hormone due to a mutation in thyroid hormone receptor beta
TSHROrphanet:424Familial hyperthyroidism due to mutations in TSH receptor
TSHROrphanet:90673Hypothyroidism due to TSH receptor mutations
TSHROrphanet:95713Athyreosis
TSHROrphanet:95720Thyroid hypoplasia
TSHROrphanet:99819Familial gestational hyperthyroidism
TTROrphanet:597939Euthyroid dysprealbuminemic hyperthyroxinemia
TTROrphanet:85447ATTRV30M amyloidosis
TTROrphanet:85451ATTRV122I amyloidosis
FOXE1Orphanet:1226Bamforth-Lazarus syndrome
FOXE1Orphanet:146Differentiated thyroid carcinoma
FOXE1Orphanet:319487Familial papillary or follicular thyroid carcinoma
FOXE1Orphanet:95713Athyreosis
ALBOrphanet:86816Congenital analbuminemia
PDE10AOrphanet:494526Infantile-onset generalized dyskinesia with orofacial involvement
PDE10AOrphanet:494541Childhood-onset benign chorea with striatal involvement
PDE8BOrphanet:228169Autosomal dominant striatal neurodegeneration
PDE8BOrphanet:647782Isolated micronodular adrenocortical disease

Cohort genes → proteins

14 cohort genes, 13 distinct canonical proteins.

Evidence partition

SubsetGenes
gwas_only9
multi_evidence5

Cohort genes (full)

SymbolHGNCEnsemblUniProtNameEvidence
SOX9HGNC:11204ENSG00000125398P48436Transcription factor SOX-9gwas
TGHGNC:11764ENSG00000042832P01266Thyroglobulingwas
THRBHGNC:11799ENSG00000151090P10828Thyroid hormone receptor betaclinvar
TSHRHGNC:12373ENSG00000165409P16473Thyrotropin receptorclinvar
TTRHGNC:12405ENSG00000118271P02766Transthyretinclinvar
VEGFAHGNC:12680ENSG00000112715P15692Vascular endothelial growth factor A, long formgwas
PRDM11HGNC:13996ENSG00000019485Q9NQV5PR domain-containing protein 11gwas
CAPZBHGNC:1491ENSG00000077549P47756F-actin-capping protein subunit betagwas
FBF1HGNC:24674ENSG00000188878Q8TES7Fas-binding factor 1clinvar
FOXE1HGNC:3806ENSG00000178919O00358Forkhead box protein E1gwas
ALBHGNC:399ENSG00000163631P02768Albuminclinvar
LINC01512HGNC:51201ENSG00000289313long intergenic non-protein coding RNA 1512gwas
PDE10AHGNC:8772ENSG00000112541Q9Y233cAMP and cAMP-inhibited cGMP 3’,5’-cyclic phosphodiesterase 10Agwas
PDE8BHGNC:8794ENSG00000113231O95263High affinity cAMP-specific and IBMX-insensitive 3’,5’-cyclic phosphodiesterase 8Bgwas

Cohort function summary

Lead sentence per gene, UniProt-curated.

SymbolProtein nameFunction (lead sentence)
SOX9Transcription factor SOX-9Transcription factor that plays a key role in chondrocytes differentiation and skeletal development.
TGThyroglobulinActs as a substrate for the production of iodinated thyroid hormones thyroxine (T4) and triiodothyronine (T3).
THRBThyroid hormone receptor betaNuclear hormone receptor that can act as a repressor or activator of transcription.
TSHRThyrotropin receptorReceptor for the thyroid-stimulating hormone (TSH) or thyrotropin.
TTRTransthyretinThyroid hormone-binding protein.
VEGFAVascular endothelial growth factor A, long formParticipates in the induction of key genes involved in the response to hypoxia and in the induction of angiogenesis such as HIF1A.
PRDM11PR domain-containing protein 11May be involved in transcription regulation.
CAPZBF-actin-capping protein subunit betaF-actin-capping proteins bind in a Ca(2+)-independent manner to the fast growing ends of actin filaments (barbed end) thereby blocking the exchange of subunits at these ends.
FBF1Fas-binding factor 1Keratin-binding protein required for epithelial cell polarization.
FOXE1Forkhead box protein E1Transcription factor that binds consensus sites on a variety of gene promoters and activate their transcription.
ALBAlbuminBinds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs.
PDE10AcAMP and cAMP-inhibited cGMP 3’,5’-cyclic phosphodiesterase 10APlays a role in signal transduction by regulating the intracellular concentration of cyclic nucleotides.
PDE8BHigh affinity cAMP-specific and IBMX-insensitive 3’,5’-cyclic phosphodiesterase 8BHydrolyzes the second messenger cAMP, which is a key regulator of many important physiological processes.

Protein-family classification

Druggable: 2 · Difficult: 5 · Unknown: 7 · Druggable fraction: 0.14

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

FamilyGenesFoldFDR
Nuclear receptor127.6×0.071
Transcription factor53.0×0.071
GPCR11.7×0.600
Other/Unknown70.9×0.761

Per-gene assignment

SymbolFamilyDruggable?ECInterPro (top 3)
SOX9Transcription factornoHMG_box_dom, Sox_N, HMG_box_dom_sf
TGOther/UnknownnoThyroglobulin_1, CarbesteraseB, Tyr-kin_ephrin_A/B_rcpt-like
THRBNuclear receptoryesNucl_hrmn_rcpt_lig-bd, Znf_hrmn_rcpt, Nuclear_hrmn_rcpt
TSHRGPCRyesGPCR_Rhodpsn, Gphrmn_rcpt_fam, TSH_rcpt
TTROther/UnknownnoTransthyretin/HIU_hydrolase, Transthyretin/HIU_hydrolase_d, Thyroxine_BS
VEGFAOther/UnknownnoPDGF/VEGF_dom, PD_growth_factor_CS, VEGF_C
PRDM11Transcription factornoSET_dom, PRDM11_PR/SET, SET_dom_sf
CAPZBOther/UnknownnoCAPZB, F-actin_capping_bsu_CS, CapZ_alpha/beta
FBF1Other/UnknownnoFBF1, FBF1_C
FOXE1Transcription factornoFork_head_dom, TF_fork_head_CS_1, TF_fork_head_CS_2
ALBOther/UnknownnoALB/AFP/VDB, Serum_albumin_N, Serum_albumin_CS
LINC01512Other/Unknownno
PDE10ATranscription factorno3.1.4.17PDEase_catalytic_dom, GAF, HD/PDEase_dom
PDE8BTranscription factorno3.1.4.53PAS, PDEase_catalytic_dom, HD/PDEase_dom

Expression context

Cohort genes with no expression data: 0.

11 cohort genes are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

BucketGenes
narrow (1-5 tissues)0
moderate (6-20)0
broad (>20)13
unknown1

Top tissues across cohort

TissueCohort genes
right lobe of thyroid gland6
left lobe of thyroid gland5
thyroid gland5
right lobe of liver2
cranial nerve II1
hair follicle1
ventricular zone1
Brodmann (1909) area 231
middle temporal gyrus1
tibia1
choroid plexus epithelium1
type B pancreatic cell1
descending thoracic aorta1
epithelial cell of pancreas1
thoracic aorta1
monocyte1
muscle layer of sigmoid colon1
smooth muscle tissue1
left testis1
right testis1

Per-gene tissue summary (top 30)

SymbolBgee breadthFANTOM5 breadthSCXATop tissues
SOX9274ubiquitousmarkerventricular zone, cranial nerve II, hair follicle
TG169tissue_specificmarkerright lobe of thyroid gland, left lobe of thyroid gland, thyroid gland
THRB267ubiquitousmarkerBrodmann (1909) area 23, middle temporal gyrus, tibia
TSHR169broadmarkerright lobe of thyroid gland, left lobe of thyroid gland, thyroid gland
TTR185broadmarkerchoroid plexus epithelium, type B pancreatic cell, right lobe of liver
VEGFA297ubiquitousmarkerright lobe of thyroid gland, left lobe of thyroid gland, thyroid gland
PRDM11214ubiquitousyesepithelial cell of pancreas, descending thoracic aorta, thoracic aorta
CAPZB303ubiquitousmarkermuscle layer of sigmoid colon, monocyte, smooth muscle tissue
FBF1163ubiquitousyesright testis, left testis, right lobe of thyroid gland
FOXE194tissue_specificmarkerright lobe of thyroid gland, left lobe of thyroid gland, thyroid gland
ALB178tissue_specificmarkerright lobe of liver, liver, body of pancreas
LINC01512tissue_specific
PDE10A219broadmarkeradrenal tissue, left uterine tube, cartilage tissue
PDE8B170markerleft lobe of thyroid gland, right lobe of thyroid gland, thyroid gland

Protein interactions among cohort

Intra-cohort edges: 9.

Hub genes (top 10 by interactor count)

SymbolInteractor count
ALB11,544
CAPZB5,209
SOX94,935
TTR4,528
THRB2,044
TSHR1,672
FOXE11,606
TG1,493
FBF11,413
PDE10A1,318

Intra-cohort edges

ABSources
ALBTGstring_interaction
ALBTTRstring_interaction
CAPZBPDE8Bstring_interaction
FOXE1PDE8Bstring_interaction
FOXE1TGstring_interaction
FOXE1TSHRstring_interaction
PDE10APRDM11string_interaction
PDE8BPRDM11string_interaction
TGTSHRstring_interaction

Structural data

PDB: 10 · AlphaFold-only: 3 · No structure: 1

Cohort genes with PDB structures (top 30)

SymbolUniProtPDB entries
TTRP02766462
PDE10AQ9Y233359
ALBP02768189
VEGFAP1569256
THRBP1082834
TSHRP164739
CAPZBP477568
TGP012663
SOX9P484361
PRDM11Q9NQV51

AlphaFold-only cohort genes (top 30 by pLDDT)

SymbolUniProtpLDDT
PDE8BO9526374.88
FBF1Q8TES764.11
FOXE1O0035862.02

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 91. Enrichment computed across 14 evidence-associated genes (10 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 10 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

PathwayCohort genesFoldFDRSample cohort genes
G alpha (s) signalling events322.0×0.025TSHR, PDE10A, PDE8B
Defective visual phototransduction due to STRA6 loss of function1380.7×0.070TTR
Ciprofloxacin ADME1228.4×0.070ALB
VEGF ligand-receptor interactions1190.3×0.070VEGFA
Metabolism of porphyrins1142.8×0.070ALB
VEGF binds to VEGFR leading to receptor dimerization1126.9×0.070VEGFA
Prednisone ADME1126.9×0.070ALB
HDL remodeling1114.2×0.070ALB
Regulation of gene expression by Hypoxia-inducible Factor195.2×0.070VEGFA
Hormone ligand-binding receptors195.2×0.070TSHR
Scavenging of heme from plasma187.8×0.070ALB
Heme degradation181.6×0.070ALB
Heme biosynthesis176.1×0.070ALB
TFAP2 (AP-2) family regulates transcription of growth factors and their receptors176.1×0.070VEGFA
cGMP effects171.4×0.070PDE10A
Transcriptional regulation of testis differentiation171.4×0.070SOX9
Platelet degranulation217.6×0.070VEGFA, ALB
Post-translational protein modification35.8×0.070THRB, CAPZB, ALB
Recycling of bile acids and salts160.1×0.075ALB
Developmental Lineage of Multipotent Pancreatic Progenitor Cells160.1×0.075SOX9
VEGFR2 mediated cell proliferation157.1×0.075VEGFA
Binding and Uptake of Ligands by Scavenger Receptors154.4×0.075ALB
The canonical retinoid cycle in rods (twilight vision)151.9×0.076TTR
Bile acid and bile salt metabolism149.6×0.076ALB
Plasma lipoprotein remodeling147.6×0.076ALB
SUMOylation of intracellular receptors133.6×0.093THRB
Aspirin ADME131.7×0.093ALB
Sensory processing of sound130.9×0.093CAPZB
Developmental Lineage of Pancreatic Acinar Cells130.1×0.093SOX9
Cellular responses to stress27.4×0.093CAPZB, ALB

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 13 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO termCohort genesFoldFDRSample cohort genes
cAMP catabolic process2288.1×0.005PDE10A, PDE8B
type I pneumocyte differentiation2235.7×0.005SOX9, THRB
thyroid hormone generation2152.5×0.008TG, FOXE1
positive regulation of branching involved in ureteric bud morphogenesis2123.5×0.009SOX9, VEGFA
negative regulation of miRNA transcription296.0×0.010SOX9, VEGFA
negative regulation of cAMP/PKA signal transduction292.6×0.010PDE10A, PDE8B
thyroid gland development283.6×0.011TG, FOXE1
basophil chemotaxis11296.3×0.016VEGFA
positive regulation of endothelial cell chemotaxis by VEGF-activated vascular endothelial growth factor receptor signaling pathway11296.3×0.016VEGFA
thyroid-stimulating hormone signaling pathway11296.3×0.016TSHR
negative regulation of steroid hormone biosynthetic process11296.3×0.016PDE8B
cellular response to thyrotropin-releasing hormone11296.3×0.016TSHR
negative regulation of immune system process1648.1×0.016SOX9
coronary vein morphogenesis1648.1×0.016VEGFA
obsolete regulation of nitric oxide mediated signal transduction1648.1×0.016VEGFA
bilirubin transport1648.1×0.016ALB
VEGF-activated neuropilin signaling pathway1648.1×0.016VEGFA
epithelial cell proliferation involved in prostatic bud elongation1648.1×0.016SOX9
regulation of cell proliferation involved in tissue homeostasis1648.1×0.016SOX9
regulation of branching involved in lung morphogenesis1648.1×0.016SOX9
cell proliferation involved in heart morphogenesis1648.1×0.016SOX9
cellular stress response to acid chemical1648.1×0.016VEGFA
negative regulation of establishment of endothelial barrier1648.1×0.016VEGFA
negative regulation of adherens junction organization1648.1×0.016VEGFA
regulation of epithelial cell proliferation involved in lung morphogenesis1648.1×0.016SOX9
heart valve formation1432.1×0.016SOX9
female courtship behavior1432.1×0.016THRB
neural crest cell fate specification1432.1×0.016SOX9
male germ-line sex determination1432.1×0.016SOX9
intrahepatic bile duct development1432.1×0.016SOX9

Therapeutics

Drugs indicated for this disease

2 approved, 4 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

DrugDevelopment status
MethimazoleApproved (phase 4)
PropylthiouracilApproved (phase 4)
CholestyraminePhase 3 (in late-stage trials)
LevocarnitinePhase 3 (in late-stage trials)
Potassium IodidePhase 3 (in late-stage trials)
PrednisolonePhase 3 (in late-stage trials)

Drug target analysis

Approved (phase 4): 6 · Phase ≥3: 6 · Phased (≥1): 6 · Undrugged: 8

Druggability breadth: 10 of 14 evidence-associated genes (71%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

SymbolExample approved molecule
THRBAMINOCAPROIC ACID
TSHRLEVOSALBUTAMOL
TTRTRICLABENDAZOLE
VEGFAVADADUSTAT
ALBDIAZEPAM
PDE10AVARDENAFIL

Top cohort targets by molecule count

SymbolMoleculesMax phase
TSHR3544
THRB1174
ALB364
TTR294
PDE10A164
VEGFA54
SOX900
TG00
PRDM1100
CAPZB00

Drugs targeting cohort genes (top 30)

MoleculeMax phaseTargets in cohort
AMINOCAPROIC ACID4THRB
INDIGOTINDISULFONATE4THRB
CHLORMADINONE ACETATE4THRB
AMOXAPINE4THRB, TSHR
IDARUBICIN4THRB
DYCLONINE HYDROCHLORIDE4THRB
ISOSORBIDE4THRB
CLOMIPRAMINE HYDROCHLORIDE4THRB
CHLORMEZANONE4THRB
PHENOXYBENZAMINE HYDROCHLORIDE4THRB, TSHR
METHYSERGIDE MALEATE4THRB
LIOTHYRONINE SODIUM4THRB
DYCLONINE4THRB
ROSE BENGAL FREE ACID4THRB
INAMRINONE4THRB
MOLSIDOMINE4THRB
METRONIDAZOLE4THRB, TSHR
AMILORIDE HYDROCHLORIDE4THRB
ALTRETAMINE4THRB
BISOPROLOL FUMARATE4THRB
ATORVASTATIN4THRB
OXYTETRACYCLINE4THRB
LIOTHYRONINE4THRB
MECLOFENAMATE SODIUM4THRB, TSHR
DAUNORUBICIN HYDROCHLORIDE4THRB, TSHR
AMANTADINE HYDROCHLORIDE4THRB
ACETOHEXAMIDE4THRB, TSHR
DEBRISOQUIN SULFATE4THRB, TSHR
PHENYTOIN SODIUM4THRB
LEVOTHYROXINE4THRB, TTR

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 2.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

SymbolAssaysType breakdown
ALB953ADMET:767, Binding:168, Functional:18
TTR423Binding:391, Functional:32
PDE10A357Binding:345, ADMET:9, Functional:3
THRB169Binding:129, Functional:40
VEGFA64Binding:64
PDE8B35Binding:33, ADMET:1, Functional:1
TSHR33Functional:24, Binding:9
CAPZB9Binding:9
SOX93Binding:3
PRDM111Binding:1

Cohort enzymes (BRENDA EC)

SymbolEC numbersNames
PDE10A3.1.4.173’,5’-cyclic-nucleotide phosphodiesterase
PDE8B3.1.4.533’,5’-cyclic-AMP phosphodiesterase

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

SymbolChEMBL assays
THRB169
TTR423
ALB953
PDE10A357

Pharmacogenomics

Cohort genes with a PharmGKB record: 13; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

30 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

CompoundMax phaseCohort target (bioactivity)
AMINOCAPROIC ACID4THRB
INDIGOTINDISULFONATE4THRB
CHLORMADINONE ACETATE4THRB
AMOXAPINE4THRB, TSHR
IDARUBICIN4THRB
DYCLONINE HYDROCHLORIDE4THRB
ISOSORBIDE4THRB
CLOMIPRAMINE HYDROCHLORIDE4THRB
CHLORMEZANONE4THRB
PHENOXYBENZAMINE HYDROCHLORIDE4THRB, TSHR
METHYSERGIDE MALEATE4THRB
LIOTHYRONINE SODIUM4THRB
DYCLONINE4THRB
ROSE BENGAL FREE ACID4THRB
INAMRINONE4THRB
MOLSIDOMINE4THRB
METRONIDAZOLE4THRB, TSHR
AMILORIDE HYDROCHLORIDE4THRB
ALTRETAMINE4THRB
BISOPROLOL FUMARATE4THRB
ATORVASTATIN4THRB
OXYTETRACYCLINE4THRB
LIOTHYRONINE4THRB
MECLOFENAMATE SODIUM4THRB, TSHR
DAUNORUBICIN HYDROCHLORIDE4THRB, TSHR
AMANTADINE HYDROCHLORIDE4THRB
ACETOHEXAMIDE4THRB, TSHR
DEBRISOQUIN SULFATE4THRB, TSHR
PHENYTOIN SODIUM4THRB
LEVOTHYROXINE4THRB, TTR

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

TierDefinitionGenesSymbols
AApproved (phase 4 drug)6THRB, TSHR, TTR, VEGFA, ALB, PDE10A
BPhased (≥1) drug, not yet approved0
CDruggable family + PDB, no drug0
DDruggable family + AlphaFold only, no drug0
EDifficult family or no structure, no drug8SOX9, TG, PRDM11, CAPZB, FBF1, FOXE1, LINC01512, PDE8B

Undrugged target profiles

8 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

SymbolChEMBL assaysDrugged partners (top 3)
TG0TSHR
FOXE10TSHR
SOX93—
PRDM111—
CAPZB9—
FBF10—
LINC015120—
PDE8B35—

Clinical trials & evidence

Clinical trials

Clinical trials: 76.

Phase distribution (across all retrieved trials)

PhaseTrials
Not specified65
PHASE44
PHASE33
PHASE22
PHASE1/PHASE21
PHASE11

Top trials by phase / activity

NCTPhaseStatusTitle
NCT00946296PHASE4COMPLETEDImpact of SSKI Pre-Treatment on Blood Loss in Thyroidectomy for Graves Disease
NCT03379181PHASE4COMPLETEDThermogenesis in Hyperthyroidism and Effect of Anti-Adrenergic Therapy
NCT03393728PHASE4COMPLETEDHeart Rate Variability and Hyperthyroidism: Evaluation of the Short-term Effects of Propanolol
NCT05512715PHASE4COMPLETEDLIthium as Bridging thErapy Prior to Radioactiveiodine in hyperThYroidism
NCT04856488PHASE3RECRUITINGPreoperative Lugol’s Solution in Graves’ Disease and Toxic Nodular Goiter
NCT03303053PHASE3UNKNOWNEfficacy and Safety of Cholestyramine and Prednisolone as Adjunctive Therapy in Treatment of Overt Hyperthyroidism
NCT05118542PHASE3COMPLETEDEffect of Hyperthyroidism and Its Treatment in Graves’ Disease to Early Marker of Atherosclerosis
NCT07369063PHASE2RECRUITINGImpact of Vitamin D Therapy on Thyroid Function and Antibody Levels in Pediatric Graves’ Disease
NCT01727973PHASE1/PHASE2COMPLETEDEfficacy of Subantimicrobial Dose Doxycycline for Moderate to Severe and Active Graves’ Orbitopathy
NCT02203682PHASE2UNKNOWNDoxycycline Treatment in Mild Thyroid-Associated Ophthalmopathy
NCT04346901PHASE1COMPLETEDComparative Study of mMASI Before and After Hyperthyroid Therapy in Hyperthyroid Subjects With Melasma
NCT00001159Not specifiedRECRUITINGNatural History of Thyroid Function Disorders
NCT06452823Not specifiedENROLLING_BY_INVITATIONEfficacy and Safety of Catheter Ablation of Atrial Fibrillation in Patients With Thyroid Hormone Stabilization
NCT06540469Not specifiedNOT_YET_RECRUITINGIodine Supplementation in Graves’ Hyperthyroidism
NCT06570967Not specifiedRECRUITINGA Clinical Study of Hyperthyroidism in Children
NCT06583395Not specifiedENROLLING_BY_INVITATIONQuest to Analyze One Thousand Humans Meditating
NCT06591858Not specifiedNOT_YET_RECRUITINGEvaluation of Renal Function in Patients With Hyperthyroidism
NCT06779747Not specifiedRECRUITINGEvaluation of Different Diagnostic Therapeutic Strategies in Patients with Thyroid Pathology
NCT06794203Not specifiedRECRUITINGHyperthyroidism as a Potential Predictive of Worse Outcome of Renal Graft
NCT06868459Not specifiedENROLLING_BY_INVITATIONPressure-enabled Retrograde Occlusive Therapy With Embolization for Control of Thyroid Disease (PROTECT Registry): A Multicenter Registry
NCT07017907Not specifiedNOT_YET_RECRUITINGEvaluating an AI Tool for Detecting Thyrotoxic States
NCT07048548Not specifiedACTIVE_NOT_RECRUITINGAssessment of THL and Potential Risk of Hypothyroidism in Healthcare Workers Exposed to Low-dose Ionizing Radiation
NCT07405320Not specifiedNOT_YET_RECRUITINGA Brief Video Intervention to Improve Patient Outcomes Following Radioiodine Treatment
NCT07472062Not specifiedACTIVE_NOT_RECRUITINGDevelopment of a Non-Invasive Prognostic Test for Graves Orbitopathy
NCT07557810Not specifiedRECRUITINGEfficacy of Thermal Ablation Combined With Antithyroid Drugs in the Treatment of Primary Hyperthyroidism
NCT00151723Not specifiedUNKNOWNDoes Radioiodine Treatment Prevent Atrial Fibrillation and Bone Loss in Endogenous Subclinical Hyperthyroidism?
NCT00437931Not specifiedCOMPLETEDColor Flow Doppler Ultrasound in Subclinical Thyroid Dysfunction
NCT00471458Not specifiedCOMPLETEDFollow-up Study of the RAI-Treated Hyperthyroid Patients
NCT00525122Not specifiedUNKNOWNTreatment of M.Graves With Radioactive Iodine: Follow-up Study
NCT00796913Not specifiedCOMPLETEDRemission Induction and Sustenance in Graves’ Disease 2
NCT00822289Not specifiedUNKNOWNThe Effect of Radioactive Iodine Administration for Thyroid Diseases on H.Pylori Eradication
NCT01095341Not specifiedCOMPLETEDPostoperative Hyperthyroidism
NCT01105923Not specifiedUNKNOWNStudy of an Intervention to Improve Problem List Accuracy and Use
NCT01145040Not specifiedUNKNOWNNOMOTHETICOS: Nonlinear Modelling of Thyroid Hormones’ Effect on Thyrotropin Incretion in Confirmed Open-loop Situation
NCT01306916Not specifiedCOMPLETEDCoexisting Thyroid Disease and Hyperparathyroidism
NCT01376648Not specifiedUNKNOWNThyroid Hormones Effect on Brown Adipose Tissue
NCT01945229Not specifiedTERMINATEDThumb-ECG Ambulant Screening for Atrial Fibrillation in Patients Treated for Hyperthyroidism (TAMBOURINE)
NCT02005250Not specifiedCOMPLETEDBone Structure and Strength Evaluated by Extreme-CT Scan Before and After Treatment of Hyper- and Hypothyroidism
NCT02107794Not specifiedCOMPLETEDShared Decision Making in Graves Disease - Graves Disease (GD) Choice
NCT02133040Not specifiedUNKNOWNEffects of Hyperthyroidism on Amount and Activity of Brown Adipose Tissue

Drugs tested across these trials (top 30)

MoleculeMax phaseTrials referencing
PROPRANOLOL45
METHIMAZOLE43
DOXYCYCLINE ANHYDROUS42
POTASSIUM IODIDE41
PROPYLTHIOURACIL41
IODINE31
SELENIUM31
DEXPROPRANOLOL21
LEVOPROPRANOLOL21
CHEMBL5024101
CHEMBL477852001
POTASSIUM ION01
THYROXINE01

About this page

Generated deterministically by Sugi Atlas from primary biomedical databases via BioBTree. Every record on this page traces to a primary source.

Generated
Atlas version
v1.1.2
BioBTree
v2.0.2

Sources 71

This page pulls from 71 datasets indexed by BioBTree:

alphafoldantibodybgeebgee_evidencebindingdbbiogrid_interactionbrendabrenda_kineticscellosauruschembl_activitychembl_assaychembl_documentchembl_moleculechembl_targetcivic_evidenceclingen_dosageclinical_trialsclinvarctd_gene_interactiondbsnpdepmapdiamond_similaritydoidefoensemblentrezesm2_similarityfantom5_genefantom5_promotergenccgenerifgogtopdbgtopdb_interactiongwasgwas_studyhgncintactinterpromedgenmeshmimmondomondochildmondoparentncitorphanetpatentpatent_compoundpdbpfampharmgkb_clinicalpharmgkb_genepharmgkb_guidelinepharmgkb_variantpubchempubchem_activitypubchem_assayreactomerefseqrhearnacentralsctidscxa_expressionscxa_gene_experimentsignorstring_interactiontranscriptufeatureumlsuniprot