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Atlas / Disease / Resistance to thyroid hormone due to a mutation in thyroid hormone receptor beta

Resistance to thyroid hormone due to a mutation in thyroid hormone receptor beta

disease
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Summary

Resistance to thyroid hormone due to a mutation in thyroid hormone receptor beta (MONDO:0700478) is a disease with 1 cohort gene.

At a glance

  • Prevalence: Unknown (United States) [Orphanet-validated]
  • Cohort genes: 1
  • ClinVar variants: 1
  • Phenotypes (HPO): 20

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

TypeClassValueGeographyValidation
Prevalence at birth1-9 / 100 0002.47United StatesValidated
Prevalence at birth1-9 / 100 0002.4JapanValidated

Signs & symptoms

Clinical features (HPO)

20 HPO clinical features (Orphanet curated; top 20 by frequency):

HPO IDTermFrequency
HP:0000853GoiterVery frequent (80-99%)
HP:0001649TachycardiaVery frequent (80-99%)
HP:0033075Inappropriately normal thyroid-stimulating hormone levelVery frequent (80-99%)
HP:0033077Increased circulating free T4 concentrationVery frequent (80-99%)
HP:0000403Recurrent otitis mediaFrequent (30-79%)
HP:0000739AnxietyFrequent (30-79%)
HP:0000752HyperactivityFrequent (30-79%)
HP:0001328Specific learning disabilityFrequent (30-79%)
HP:0002750Delayed skeletal maturationFrequent (30-79%)
HP:0007018Attention deficit hyperactivity disorderFrequent (30-79%)
HP:0011788Increased circulating free T3Frequent (30-79%)
HP:0025379Anti-thyroid peroxidase antibody positivityFrequent (30-79%)
HP:0032069Anti-thyroglobulin antibody positivityFrequent (30-79%)
HP:0034288Elevated circulating reverse T3 concentrationFrequent (30-79%)
HP:0000407Sensorineural hearing impairmentOccasional (5-29%)
HP:0001530Mild postnatal growth retardationOccasional (5-29%)
HP:0001962PalpitationsOccasional (5-29%)
HP:0012758Neurodevelopmental delayOccasional (5-29%)
HP:0025484Increased circulating thyroglobulin concentrationOccasional (5-29%)
HP:0031098Decreased thyroid-stimulating hormone levelExcluded (0%)

Identifiers

Disease identifiers

FieldValue
Canonical nameresistance to thyroid hormone due to a mutation in thyroid hormone receptor beta
Mondo IDMONDO:0700478
Orphanet566243
GARD0028049
Is cancer (heuristic)no

Data availability: 1 ClinVar variant.

Disease family

An umbrella term covering 3 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › endocrine system disorder › thyroid gland disorder › inherited thyroid metabolism disease › thyroid hormone resistance syndrome › resistance to thyroid hormone due to a mutation in thyroid hormone receptor beta

Related subtypes (3): generalized resistance to thyroid hormone, selective peripheral resistance to thyroid hormone, resistance to thyroid hormone due to a mutation in thyroid hormone receptor alpha

Subtypes (3): selective pituitary resistance to thyroid hormone, thyroid hormone resistance, generalized, autosomal dominant, thyroid hormone resistance, generalized, autosomal recessive

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

1 retrieved; paginated sample, class counts are floors:

1 pathogenic/likely pathogenic

ClinVarVariant (HGVS)GeneClassificationReview
492926NM_001354712.2(THRB):c.1378G>A (p.Glu460Lys)THRBPathogenic/Likely pathogeniccriteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 1 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

GeneOrphanet IDRare disease
THRBOrphanet:566243Resistance to thyroid hormone due to a mutation in thyroid hormone receptor beta

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

SubsetGenes
multi_evidence1

Cohort genes (full)

SymbolHGNCEnsemblUniProtNameEvidence
THRBHGNC:11799ENSG00000151090P10828Thyroid hormone receptor betaclinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

SymbolProtein nameFunction (lead sentence)
THRBThyroid hormone receptor betaNuclear hormone receptor that can act as a repressor or activator of transcription.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

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 receptor1385.9×0.003

Per-gene assignment

SymbolFamilyDruggable?ECInterPro (top 3)
THRBNuclear receptoryesNucl_hrmn_rcpt_lig-bd, Znf_hrmn_rcpt, Nuclear_hrmn_rcpt

Expression context

Cohort genes with no expression data: 0.

1 cohort gene 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)1
unknown0

Top tissues across cohort

TissueCohort genes
Brodmann (1909) area 231
middle temporal gyrus1
tibia1

Per-gene tissue summary (top 30)

SymbolBgee breadthFANTOM5 breadthSCXATop tissues
THRB267ubiquitousmarkerBrodmann (1909) area 23, middle temporal gyrus, tibia

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

SymbolInteractor count
THRB2,044

Structural data

PDB: 1 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

SymbolUniProtPDB entries
THRBP1082834

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 9. Enrichment computed across 1 evidence-associated genes (1 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 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

PathwayCohort genesFoldFDRSample cohort genes
SUMOylation of intracellular receptors1335.9×0.014THRB
Nuclear Receptor transcription pathway1200.3×0.014THRB
SUMO E3 ligases SUMOylate target proteins1178.4×0.014THRB
SUMOylation1163.1×0.014THRB
RNA Polymerase II Transcription122.5×0.072THRB
Post-translational protein modification119.2×0.072THRB
Gene expression (Transcription)117.8×0.072THRB
Generic Transcription Pathway115.1×0.074THRB
Metabolism of proteins112.4×0.081THRB

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO termCohort genesFoldFDRSample cohort genes
female courtship behavior15617.3×9e-04THRB
retinal cone cell apoptotic process15617.3×9e-04THRB
thyroid hormone receptor signaling pathway14213.0×9e-04THRB
positive regulation of thyroid hormone receptor signaling pathway14213.0×9e-04THRB
negative regulation of female receptivity13370.4×9e-04THRB
type I pneumocyte differentiation11532.0×0.001THRB
cellular response to thyroid hormone stimulus11532.0×0.001THRB
retinal cone cell development11404.3×0.001THRB
retinoic acid receptor signaling pathway1648.1×0.003THRB
regulation of heart contraction1495.6×0.003THRB
mRNA transcription by RNA polymerase II1330.4×0.004THRB
DNA-templated transcription1224.7×0.006THRB
sensory perception of sound1100.9×0.012THRB
cell differentiation129.1×0.039THRB
negative regulation of transcription by RNA polymerase II117.7×0.060THRB
positive regulation of transcription by RNA polymerase II114.9×0.067THRB

Therapeutics

Drug target analysis

Approved (phase 4): 1 · Phase ≥3: 1 · Phased (≥1): 1 · Undrugged: 0

Druggability breadth: 1 of 1 evidence-associated genes (100%) 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

Top cohort targets by molecule count

SymbolMoleculesMax phase
THRB1174

Drugs targeting cohort genes (top 30)

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

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

SymbolAssaysType breakdown
THRB169Binding:129, Functional:40

Cohort genes with high screening signal

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

SymbolChEMBL assays
THRB169

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; 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
IDARUBICIN4THRB
DYCLONINE HYDROCHLORIDE4THRB
ISOSORBIDE4THRB
CLOMIPRAMINE HYDROCHLORIDE4THRB
CHLORMEZANONE4THRB
PHENOXYBENZAMINE HYDROCHLORIDE4THRB
METHYSERGIDE MALEATE4THRB
LIOTHYRONINE SODIUM4THRB
DYCLONINE4THRB
ROSE BENGAL FREE ACID4THRB
INAMRINONE4THRB
MOLSIDOMINE4THRB
METRONIDAZOLE4THRB
AMILORIDE HYDROCHLORIDE4THRB
ALTRETAMINE4THRB
BISOPROLOL FUMARATE4THRB
ATORVASTATIN4THRB
OXYTETRACYCLINE4THRB
LIOTHYRONINE4THRB
MECLOFENAMATE SODIUM4THRB
DAUNORUBICIN HYDROCHLORIDE4THRB
AMANTADINE HYDROCHLORIDE4THRB
ACETOHEXAMIDE4THRB
DEBRISOQUIN SULFATE4THRB
PHENYTOIN SODIUM4THRB
LEVOTHYROXINE4THRB

Druggability pyramid

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

TierDefinitionGenesSymbols
AApproved (phase 4 drug)1THRB
BPhased (≥1) drug, not yet approved0
CDruggable family + PDB, no drug0
DDruggable family + AlphaFold only, no drug0
EDifficult family or no structure, no drug0

Undrugged target profiles

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

Clinical trials & evidence

Clinical trials

Clinical trials: 0.

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 66

This page pulls from 66 datasets indexed by BioBTree:

alphafoldantibodybgeebgee_evidencebindingdbbiogrid_interactionbrendabrenda_kineticscellosauruschembl_activitychembl_assaychembl_documentchembl_moleculechembl_targetcivic_evidenceclingen_dosageclinical_trialsclinvarctd_gene_interactiondepmapdiamond_similarityefoensemblentrezesm2_similarityfantom5_genefantom5_promotergardgenccgenerifgogtopdbgtopdb_interactiongwasgwas_studyhgncintactinterpromeshmimmondomondochildmondoparentorphanetpatentpatent_compoundpdbpfampharmgkb_clinicalpharmgkb_genepharmgkb_guidelinepharmgkb_variantpubchempubchem_activitypubchem_assayreactomerefseqrhearnacentralscxa_expressionscxa_gene_experimentsignorstring_interactiontranscriptufeatureuniprot