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Bruxism

disease
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Also known as bruxism (disease)sleep related bruxism

Summary

Bruxism (MONDO:0002443) is a disease with 2 cohort genes (1 GWAS associations across 1 studies) and 112 clinical trials. Top therapeutic interventions include salicylic acid, orphenadrine, and botulinum toxin type a.

At a glance

  • Cohort genes: 2
  • GWAS associations: 1
  • ClinVar variants: 2
  • Clinical trials: 112

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

FieldValue
Canonical namebruxism
Mondo IDMONDO:0002443
MeSHD002012
DOIDDOID:2846
ICD-10-CMG47.63
ICD-111046319083
UMLSC0006325
MedGen676
Is cancer (heuristic)no

Also known as: bruxism · bruxism (disease) · sleep related bruxism

Data availability: 2 ClinVar variants · 1 GWAS association (1 study) · 1 HPO phenotype · 3 cell lines.

Disease family

Classification path: disease › human disease › disease by developmental or physiological process › sleep disorder › sleep-wake disorder › bruxism

Related subtypes (11): recurrent hypersomnia, sleep apnea syndrome, hypersomnia, periodic limb movement disorder, REM sleep behavior disorder, autosomal dominant cerebellar ataxia, deafness and narcolepsy, hereditary sensory neuropathy-deafness-dementia syndrome, autoimmune encephalopathy with parasomnia and obstructive sleep apnea, narcolepsy, circadian rhythm sleep disorder, sleep disorder, initiating and maintaining sleep

Genetics & variants

GWAS landscape

1 GWAS associations across 1 studies. Top hits map to 1 distinct genes (as reported by GWAS).

Top associations by p-value

rsIDp-valueGeneRisk alleleOdds ratio
rs101931792e-08MYO3B?1.08

Top studies (by case count)

StudyLead authorYearCasesControlsTitle
GCST90296383Strausz T202312,297364,980Genetic analysis of probable sleep bruxism and its associations with clinical and behavioral traits.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

TierVariants
Tier 1: coding0
Tier 2: splice/UTR0
Tier 3: regulatory0
Tier 4: intronic/intergenic1

MAF distribution

BucketVariants
common (>=0.05)1
low_freq (0.01-0.05)0
rare (<0.01)0
unknown0

Functional consequences

ConsequenceCount
intron_variant1

Top variants

rsIDChrPosAllelesMAFConsequenceGenep-valueTier
rs101931792170577791C>A,T0.05intron_variantMYO3B2e-08Tier 4: intronic/intergenic

ClinVar germline variants

2 retrieved; paginated sample, class counts are floors:

2 pathogenic

ClinVarVariant (HGVS)GeneClassificationReview
158186NM_001323289.2(CDKL5):c.622C>T (p.Gln208Ter)CDKL5Pathogeniccriteria provided, multiple submitters, no conflicts
156053NM_001110792.2(MECP2):c.413+1G>TMECP2Pathogeniccriteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 11 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

GeneOrphanet IDRare disease
CDKL5Orphanet:1934Early infantile developmental and epileptic encephalopathy
CDKL5Orphanet:3095Atypical Rett syndrome
CDKL5Orphanet:505652CDKL5-deficiency disorder
CDKL5Orphanet:697160Infantile epileptic spasms syndrome
MECP2Orphanet:1762Proximal Xq28 duplication syndrome
MECP2Orphanet:209370MECP2-related severe neonatal encephalopathy
MECP2Orphanet:3077X-linked intellectual disability-psychosis-macroorchidism syndrome
MECP2Orphanet:3095Atypical Rett syndrome
MECP2Orphanet:536Systemic lupus erythematosus
MECP2Orphanet:777X-linked non-syndromic intellectual disability
MECP2Orphanet:778Rett syndrome

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

SubsetGenes
multi_evidence2

Cohort genes (full)

SymbolHGNCEnsemblUniProtNameEvidence
CDKL5HGNC:11411ENSG00000008086O76039Cyclin-dependent kinase-like 5clinvar
MECP2HGNC:6990ENSG00000169057P51608Methyl-CpG-binding protein 2clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

SymbolProtein nameFunction (lead sentence)
CDKL5Cyclin-dependent kinase-like 5Mediates phosphorylation of MECP2.
MECP2Methyl-CpG-binding protein 2Chromosomal protein that binds to methylated DNA.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.5

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
Kinase113.9×0.142
Other/Unknown10.9×0.805

Per-gene assignment

SymbolFamilyDruggable?ECInterPro (top 3)
CDKL5Kinaseyes2.7.11.22Prot_kinase_dom, Ser/Thr_kinase_AS, Kinase-like_dom_sf
MECP2Other/UnknownnoMethyl_CpG_DNA-bd, DNA-bd_dom_sf, Me_CpG-bd_MeCP2

Expression context

Cohort genes with no expression data: 0.

2 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)2
unknown0

Top tissues across cohort

TissueCohort genes
Brodmann (1909) area 231
cortical plate1
frontal pole1
Brodmann (1909) area 101
paraflocculus1
sural nerve1

Per-gene tissue summary (top 30)

SymbolBgee breadthFANTOM5 breadthSCXATop tissues
CDKL5257ubiquitousmarkerfrontal pole, Brodmann (1909) area 23, cortical plate
MECP2277ubiquitousmarkerparaflocculus, Brodmann (1909) area 10, sural nerve

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

SymbolInteractor count
MECP25,688
CDKL51,357

Intra-cohort edges

ABSources
CDKL5MECP2string_interaction

Structural data

PDB: 2 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

SymbolUniProtPDB entries
MECP2P516089
CDKL5O760393

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 11. Enrichment computed across 2 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
Loss of MECP2 binding ability to 5hmC-DNA111420.0×1e-03MECP2
MECP2 regulates transcription of genes involved in GABA signaling13806.7×1e-03MECP2
Loss of phosphorylation of MECP2 at T30812855.0×1e-03MECP2
Loss of MECP2 binding ability to 5mC-DNA12855.0×1e-03MECP2
MECP2 regulates transcription factors12284.0×1e-03MECP2
Loss of MECP2 binding ability to the NCoR/SMRT complex11631.4×0.001MECP2
MECP2 regulates transcription of neuronal ligands11427.5×0.001MECP2
MECP2 regulates neuronal receptors and channels1601.0×0.002MECP2
Regulation of MECP2 expression and activity1368.4×0.003MECP2
Nuclear events stimulated by ALK signaling in cancer1326.3×0.003MECP2
Transcriptional Regulation by MECP21317.2×0.003MECP2

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO termCohort genesFoldFDRSample cohort genes
catecholamine secretion18426.0×0.003MECP2
trans-synaptic signaling by BDNF18426.0×0.003MECP2
cardiolipin metabolic process14213.0×0.003MECP2
nervous system process involved in regulation of systemic arterial blood pressure12808.7×0.003MECP2
biogenic amine metabolic process12808.7×0.003MECP2
response to other organism12808.7×0.003MECP2
proprioception12106.5×0.004MECP2
glucocorticoid metabolic process11404.3×0.005MECP2
inositol metabolic process11203.7×0.005MECP2
positive regulation of microtubule nucleation11053.2×0.005MECP2
negative regulation of smooth muscle cell differentiation1936.2×0.005MECP2
regulation of respiratory gaseous exchange by nervous system process1648.1×0.006MECP2
L-glutamine metabolic process1648.1×0.006MECP2
startle response1561.7×0.006MECP2
negative regulation of gene expression via chromosomal CpG island methylation1526.6×0.006MECP2
regulation of dendrite development1495.6×0.006CDKL5
genomic imprinting1495.6×0.006MECP2
glial cell proliferation1443.5×0.006MECP2
positive regulation of dendrite morphogenesis1443.5×0.006CDKL5
ventricular system development1421.3×0.006MECP2
neuron maturation1401.2×0.006MECP2
phosphatidylcholine metabolic process1401.2×0.006MECP2
negative regulation of blood vessel endothelial cell migration1366.4×0.006MECP2
positive regulation of glial cell proliferation1351.1×0.006MECP2
positive regulation of Rac protein signal transduction1324.1×0.007CDKL5
respiratory gaseous exchange by respiratory system1312.1×0.007MECP2
regulation of cilium assembly1300.9×0.007CDKL5
regulation of postsynapse organization1263.3×0.007CDKL5
positive regulation of axon extension1255.3×0.007CDKL5
excitatory postsynaptic potential1221.7×0.008MECP2

Therapeutics

Drugs indicated for this disease

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

DrugDevelopment status
IncobotulinumtoxinaPhase 3 (in late-stage trials)
OnabotulinumtoxinaPhase 3 (in late-stage trials)

Drug target analysis

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

Druggability breadth: 2 of 2 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
CDKL5FEDRATINIB

Top cohort targets by molecule count

SymbolMoleculesMax phase
CDKL5144
MECP200

Drugs targeting cohort genes (top 30)

MoleculeMax phaseTargets in cohort
FEDRATINIB4CDKL5
CAPMATINIB4CDKL5
DEFACTINIB3CDKL5
ALVOCIDIB3CDKL5
LESTAURTINIB3CDKL5
RUBOXISTAURIN3CDKL5
FORETINIB2CDKL5
RG-5472CDKL5
AT-75192CDKL5
TOZASERTIB2CDKL5
BMS-3870321CDKL5
PF-037583091CDKL5
5-(6-BENZOTHIAZOLYLMETHYLENE)-3,5-DIHYDRO-2-(((1S)-1-(METHOXYMETHYL)-3-METHYLBUTYL)AMINO)-4H-IMIDAZOL-4-ONE, (5Z)-1CDKL5
AST-4871CDKL5

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

SymbolAssaysType breakdown
CDKL574Binding:74
MECP21Binding:1

Cohort enzymes (BRENDA EC)

SymbolEC numbersNames
CDKL52.7.11.22cyclin-dependent kinase

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

14 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)
FEDRATINIB4CDKL5
CAPMATINIB4CDKL5
DEFACTINIB3CDKL5
ALVOCIDIB3CDKL5
LESTAURTINIB3CDKL5
RUBOXISTAURIN3CDKL5
FORETINIB2CDKL5
RG-5472CDKL5
AT-75192CDKL5
TOZASERTIB2CDKL5
BMS-3870321CDKL5
PF-037583091CDKL5
5-(6-BENZOTHIAZOLYLMETHYLENE)-3,5-DIHYDRO-2-(((1S)-1-(METHOXYMETHYL)-3-METHYLBUTYL)AMINO)-4H-IMIDAZOL-4-ONE, (5Z)-1CDKL5
AST-4871CDKL5

Druggability pyramid

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

TierDefinitionGenesSymbols
AApproved (phase 4 drug)1CDKL5
BPhased (≥1) drug, not yet approved0
CDruggable family + PDB, no drug0
DDruggable family + AlphaFold only, no drug0
EDifficult family or no structure, no drug1MECP2

Undrugged target profiles

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

SymbolChEMBL assaysDrugged partners (top 3)
MECP21—

Clinical trials & evidence

Clinical trials

Clinical trials: 112.

Phase distribution (across all retrieved trials)

PhaseTrials
Not specified103
PHASE43
PHASE2/PHASE32
PHASE32
PHASE12

Top trials by phase / activity

NCTPhaseStatusTitle
NCT07109882PHASE4RECRUITINGEffectiveness of Chlorzoxazone Versus Orphenadrine Citrate in Alleviating Bruxism Pain
NCT00908050PHASE4COMPLETEDStudy of the Safety and Efficacy of Botox in Bruxism
NCT07586072PHASE4COMPLETEDNon-Randomized Trial of Bruxism-Related TMD Treatments
NCT03371888PHASE2/PHASE3COMPLETEDThe Platelet-Rich Plasma in the Therapy of Temporomandibular Disorders
NCT04722809PHASE3TERMINATEDEfficacy of Botulinum Toxin A in the Treatment of Bruxism-related Symptomatology
NCT05562635PHASE2/PHASE3UNKNOWNCBD (Cannabidiol) Intraoral Application and TMD (Temporomandibular Disorders)
NCT05980559PHASE3UNKNOWNEvaluation of BTX Injections in Treatment of Bruxism
NCT02202070PHASE1WITHDRAWNBotox for Treatment of TMJ Disorder With Bruxism
NCT07361900PHASE1COMPLETEDManagement of Bruxism in Patients With Implant Overdenture
NCT05751694Not specifiedRECRUITINGEffectiveness of Visceral Manual Therapy in Bruxist Patients
NCT05995431Not specifiedRECRUITINGImpact of Bruxism in the Outcome of Subgingival Instrumentation for the Management of Stage 2 and Stage 3 Periodontitis.
NCT06435208Not specifiedRECRUITINGImpact of Subgingival Instrumentation on Psychological Distress and Mental Health Status in Bruxers With Periodontitis
NCT06457646Not specifiedNOT_YET_RECRUITINGmRNA Expression and Genetic Polymorphisms Affecting DRD3 (rs6280) and HTR2A (rs6313) in Bruxism
NCT06623643Not specifiedNOT_YET_RECRUITING“Salivary Melatonin and Cortisol Levels in Individuals with Bruxism”
NCT06652217Not specifiedNOT_YET_RECRUITINGAnalysis of Occlusal Force Distribution in Digital and Conventional Occlusal Splint
NCT06894472Not specifiedNOT_YET_RECRUITINGA Comparative Study of EMG Biofeedback and Pharmacotherapy for the Treatment of Masticatory Muscle Hyperactivity in Bruxism Patients
NCT07022795Not specifiedRECRUITINGBehavioral Interventions for Controlling Oral Behaviors
NCT07028151Not specifiedENROLLING_BY_INVITATIONComparison of the Effects of Classical Massage and Conventional Treatment Methods in Phone Addicted Bruxist Patients
NCT07090551Not specifiedRECRUITINGEffect of Occlusal Splint on Head and Neck Muscles in Patients With Bruxism and Myofascial Pain
NCT07133035Not specifiedACTIVE_NOT_RECRUITINGInvestigation of Respiratory Function in Bruxism
NCT07241728Not specifiedRECRUITINGBruxism and Diadinamic Current
NCT07266701Not specifiedENROLLING_BY_INVITATIONThe General Aim is to Implement Clinical Assessment of Overload by Voluntary Bite Force Registration to Enable Future Simple But Precise Risk Assessment to Provide Individualized Treatment Plans.
NCT07308145Not specifiedRECRUITINGThe Effect of Bruxism on Balance
NCT07336082Not specifiedRECRUITINGSomatosensory Training Versus Exercise Therapy in Awake Bruxism
NCT07433595Not specifiedNOT_YET_RECRUITINGAssociation Between Child and Parental Stress and Bruxism in Children Aged 8-11 Years
NCT07437924Not specifiedENROLLING_BY_INVITATIONBruxism and Pelvic Floor Dysfunction in Young Women
NCT07469345Not specifiedENROLLING_BY_INVITATIONBruxism, Pelvic Pain, Erectile Dysfunction, and Anxiety in Young Adult Men
NCT07506733Not specifiedRECRUITINGEffects of Different Graston Technique Application Speeds on Trapezius Muscle Stiffness, Pressure Pain Threshold, Pain, and Muscle Oxygenation in Patients With Bruxism
NCT07548502Not specifiedRECRUITINGEffect of Night Guard Use on Masseter Muscle Thickness in Children With Bruxism
NCT07556211Not specifiedENROLLING_BY_INVITATIONNeuromuscular Function and Performance in Athletes With or Without Bruxism
NCT07567183Not specifiedNOT_YET_RECRUITINGComparison of the Effects of Different Massage Techniques in Individuals With Bruxism
NCT07579416Not specifiedRECRUITINGBruxism, Anxiety, and Periodontal Status Among Dental Students
NCT07584642Not specifiedNOT_YET_RECRUITINGEfficacy and Safety of HA35 Gel Nighttime Occlusive Application for TMD Pain
NCT07611643Not specifiedRECRUITINGBruxism Therapy of Facial Pain
NCT07615140Not specifiedNOT_YET_RECRUITINGPsychological Resilience, Perceived Stress and Periodontal Status Among Bruxers
NCT07615153Not specifiedNOT_YET_RECRUITINGImpact of Distress Level, Sleep Quality and Occlusal Trauma on Periodontal Status Among Bruxers
NCT00807430Not specifiedTERMINATEDTreatment Period and Long-term Effect of Functional Electric Stimulation (FES) for Bruxism
NCT00868244Not specifiedUNKNOWNRelationship of Facial Pattern With Bruxism
NCT01005511Not specifiedTERMINATEDTreatment Period and Long-term Efficacy of Functional Electrical Stimulation (FES) on Sleep Bruxism
NCT01463826Not specifiedCOMPLETEDRespiratory Problems and Caries in Children With Bruxism

Drugs tested across these trials (top 30)

MoleculeMax phaseTrials referencing
SALICYLIC ACID45
ORPHENADRINE43
BOTULINUM TOXIN TYPE A42
ABOBOTULINUMTOXINA41
CHLORZOXAZONE41
PRABOTULINUMTOXIN A41
THIOCOLCHICOSIDE31
TENOXICAM21
CHEMBL135439801

About this page

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

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This page pulls from 71 datasets indexed by BioBTree:

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