Oppositional defiant disorder

Summary

Oppositional defiant disorder (MONDO:0000495) is a disease with 1 cohort gene and 73 clinical trials. Top therapeutic interventions include atomoxetine, guanfacine, and methylphenidate.

At a glance

• Cohort genes: 1
• ClinVar variants: 4
• Clinical trials: 73

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	oppositional defiant disorder
Mondo ID	MONDO:0000495
MeSH	D019958
DOID	DOID:0050856
ICD-10-CM	F91.3
ICD-11	1487528823
NCIT	C92565
SNOMED CT	18941000
UMLS	C0029121
MedGen	18178
Is cancer (heuristic)	no

Also known as: oppositional defiant disorder · oppositional defiant disorder (disease)

Data availability: 4 ClinVar variants · 1 HPO phenotype.

Disease family

Classification path: disease › human disease › disease by developmental or physiological process › psychiatric disorder › mental disorder › developmental disorder of mental health › specific developmental disorder › oppositional defiant disorder

Related subtypes (9): fetal alcohol spectrum disorder, fetal nicotine spectrum disorder, communication disorder, stereotypic movement disorder, tic disorder, learning disability, developmental coordination disorder, conduct disorder, attention deficit-hyperactivity disorder

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

4 retrieved; paginated sample, class counts are floors:

4 uncertain significance

ClinVar	Variant (HGVS)	Gene	Classification	Review
267865	46;XY;t(2;11)(q31;q13.5)pat		Uncertain significance	criteria provided, single submitter
267911	46;XY;t(4;7)(q31;q22)dn		Uncertain significance	criteria provided, single submitter
267966	46;XX;t(2;5)(q33;p15.3)		Uncertain significance	criteria provided, single submitter
692091	GRCh37/hg19 22q11.21(chr22:20728956-21465662)x3	AIFM3	Uncertain significance	no assertion criteria provided

Genes & proteins

Mendelian disease overlap and somatic drivers

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

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
AIFM3	HGNC:26398	ENSG00000183773	Q96NN9	Apoptosis-inducing factor 3	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
AIFM3	Apoptosis-inducing factor 3	Induces apoptosis through a caspase dependent pathway.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.0

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.

Family	Genes	Fold	FDR
Other/Unknown	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
AIFM3	Other/Unknown	no		FAD/NAD-linked_Rdtase_dimer_sf, Rieske_2Fe-2S, FAD/NAD-binding_dom

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)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
mucosa of transverse colon	1
right frontal lobe	1
right hemisphere of cerebellum	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
AIFM3	180	tissue_specific	marker	mucosa of transverse colon, right frontal lobe, right hemisphere of cerebellum

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
AIFM3	2,051

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
AIFM3	Q96NN9	7

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 1 evidence-associated genes (0 with Reactome annotation).

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 term	Cohort genes	Fold	FDR	Sample cohort genes
execution phase of apoptosis	1	766.0×	0.001	AIFM3

Therapeutics

Drugs indicated for this disease

0 approved, 1 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Risperidone	Phase 3 (in late-stage trials)

Drug target analysis

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

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
AIFM3	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

0 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.

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	AIFM3

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
AIFM3	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 73.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	56
PHASE3	7
PHASE4	5
PHASE2	2
PHASE1	2
PHASE1/PHASE2	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT00205699	PHASE4	COMPLETED	Metabolic Effects of Antipsychotics in Children
NCT00228046	PHASE4	COMPLETED	Medication Strategies for Treating Aggressive Behavior in Youth With Attention Deficit Hyperactivity Disorder
NCT00406354	PHASE4	COMPLETED	Comparison of Atomoxetine Versus Placebo in Children and Adolescents With ADHD and Comorbid ODD in Germany
NCT02048241	PHASE4	COMPLETED	Intuniv vs Placebo in the Treatment of Childhood Intermittent Explosive Disorder
NCT02063945	PHASE4	TERMINATED	Methylphenidate vs. Risperidone for the Treatment of Children and Adolescents With ADHD and Disruptive Disorders
NCT00191698	PHASE3	COMPLETED	Comparison of Atomoxetine and Placebo in Children and Adolescents With ADHD and ODD
NCT00192023	PHASE3	COMPLETED	An Italian Study of the Efficacy of Atomoxetine in the Treatment of Children and Adolescents With Attention-Deficit/Hyperactivity Disorder (ADHD) and Comorbid Oppositional Defiant Disorder (ODD).
NCT00250354	PHASE3	COMPLETED	A Study of the Safety and Effectiveness of Risperidone for the Treatment of Conduct Disorder and Other Disruptive Behavior Disorders in Children Ages 5 to 12 With Mild, Moderate, or Borderline Mental Retardation
NCT00266552	PHASE3	COMPLETED	A Study of the Safety and Effectiveness of Risperidone Versus Placebo for the Treatment of Conduct Disorder in Children With Mild, Moderate, or Borderline Mental Retardation
NCT00399698	PHASE3	COMPLETED	Study to Determine Whether There Are Any Cognitive or Motor Effects From Taking the Medicine Risperidone.
NCT01406067	PHASE3	COMPLETED	Treatment of Children With Peer Related Aggressive Behavior
NCT01473511	PHASE3	COMPLETED	Strongest Families Ontario (Formerly the Family Help Program)
NCT06831123	PHASE1/PHASE2	RECRUITING	Pathways 2 Success
NCT00280228	PHASE2	COMPLETED	Home Based Treatment for Drug Use in Early Adolescents
NCT00676429	PHASE2	COMPLETED	Ziprasidone for Severe Conduct and Other Disruptive Behavior Disorders
NCT01267773	PHASE1	UNKNOWN	Treatment of Conduct Problems and Depression
NCT03292848	PHASE1	COMPLETED	Trial to Assess the Pharmacokinetics, Safety, Tolerability of Oral Brexpiprazole in Children (6 to <13 Years Old) With Central Nervous System Disorders
NCT05637320	Not specified	RECRUITING	Big Feelings: A Study on Children’s Emotions in Therapy
NCT06194994	Not specified	RECRUITING	Emotion Regulation as a Moderator of Two Different Treatments for Children With ODD
NCT06350292	Not specified	RECRUITING	SLEEP-COPE: Sleep Intervention for Oppositional Children
NCT06373484	Not specified	RECRUITING	Matching Assessment and Treatment for Children With Disruptive Behaviour and Their Parents
NCT06410495	Not specified	RECRUITING	Digital Dyadic Family Based Intervention to Improve Sleep in Children with ODD and Their Parents: NiteCAPP SINCC (Pilot)
NCT06559800	Not specified	NOT_YET_RECRUITING	Pilot Study of Cognitive Behavior Therapy With Role-plays in Virtual Reality for Children With Behavior Problems
NCT06559813	Not specified	NOT_YET_RECRUITING	Pilot Study of Parent Training With Role-plays in Virtual Reality for Parents of Children With Behavior Problems
NCT06902649	Not specified	RECRUITING	Step-by-Step: Evaluation of a Stepped Care Model
NCT07042347	Not specified	RECRUITING	Testing a Measurement Feedback App to Improve Data Quality, Supervision & Outcomes in Behavioral Health
NCT07181928	Not specified	NOT_YET_RECRUITING	Is Mentalization-based Therapy More Effective Than Treatment-as-usual for Adolescents With Dissocial Disorders?
NCT07201090	Not specified	NOT_YET_RECRUITING	Effects and Implementation of a Brief Version of Parent-Child Interaction Therapy
NCT07322055	Not specified	ACTIVE_NOT_RECRUITING	Genetic and Clinical Correlates of Disruptive Behavior Disorder With and Without Callous-Unemotional Traits
NCT07456631	Not specified	RECRUITING	ACTsocially: The (Dis)Similarities of ACT for Changing Internalizing and Externalizing Symptomatology in Adolescence
NCT00189189	Not specified	UNKNOWN	Prevention of Oppositional Defiant and Conduct Disorders in Preschool Children
NCT00404911	Not specified	COMPLETED	Multi-Family Group Therapy for Reducing Behavioral Difficulties in Youth
NCT00486551	Not specified	COMPLETED	Anger Control Training for Youth With Tourette Syndrome
NCT00510120	Not specified	COMPLETED	Comparison of Two Psychosocial Therapies for Treating Children With Oppositional-Defiant Disorder
NCT00579267	Not specified	COMPLETED	Reliability and Validity of the MINI International Neuropsychiatric Interview for Children and Adolescents (MINI-KID)
NCT00612690	Not specified	COMPLETED	School-Based Mental Health Services for Urban Children
NCT00819429	Not specified	COMPLETED	Supplements and Social Skills Intervention Study
NCT00820001	Not specified	COMPLETED	Resources to Enhance the Adjustment of Children (REACH)
NCT01085305	Not specified	COMPLETED	The Effectiveness of Parent-Child Interaction Therapy (PCIT)
NCT01350986	Not specified	UNKNOWN	Guided Self-Help for Parents of Children With Externalizing Problem Behavior

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
ATOMOXETINE	4	7
GUANFACINE	4	3
METHYLPHENIDATE	4	2
ARIPIPRAZOLE	4	1
BREXPIPRAZOLE	4	1
DEXTROAMPHETAMINE	4	1
DIVALPROEX SODIUM	4	1
LEVAMFETAMINE	4	1
OLANZAPINE	4	1
RISPERIDONE	4	1
ZIPRASIDONE HYDROCHLORIDE	4	1