Methamphetamine-induced psychosis

Summary

Methamphetamine-induced psychosis (MONDO:0005465) is a disease with 3 cohort genes (1 GWAS associations across 1 studies) and 7 clinical trials. Top therapeutic interventions include cinnarizine and diazepam.

At a glance

• Cohort genes: 3
• GWAS associations: 1
• Clinical trials: 7

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	methamphetamine-induced psychosis
Mondo ID	MONDO:0005465
EFO	EFO:0005242
Is cancer (heuristic)	no

Data availability: 1 GWAS association (1 study).

Disease family

Classification path: disease › human disease › disease by developmental or physiological process › psychiatric disorder › cognitive disorder › psychotic disorder › methamphetamine-induced psychosis

Related subtypes (7): schizophreniform disorder, alcoholic psychosis, delusional disorder, substance-induced psychosis, schizophrenia, schizoaffective disorder, postpartum psychosis

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

rsID	p-value	Gene	Risk allele	Odds ratio
rs12591257	4e-06	AGBL1	A	5.26

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST001975	Ikeda M	2013	193	0	Evidence for shared genetic risk between methamphetamine-induced psychosis and schizophrenia.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

Tier	Variants
Tier 1: coding	0
Tier 2: splice/UTR	0
Tier 3: regulatory	0
Tier 4: intronic/intergenic	1

MAF distribution

Bucket	Variants
common (>=0.05)	1
low_freq (0.01-0.05)	0
rare (<0.01)	0
unknown	0

Functional consequences

Consequence	Count
intron_variant	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs12591257	15	86520858	A>C	0.183	intron_variant	AGBL1	4e-06	Tier 4: intronic/intergenic

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)

Gene	Orphanet ID	Rare disease
AGBL1	Orphanet:98974	Fuchs endothelial corneal dystrophy

Cohort genes → proteins

3 cohort genes, 3 distinct canonical proteins.

Evidence partition

Subset	Genes
gwas_only	3

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
KLHL25	HGNC:25732	ENSG00000183655	Q9H0H3	Kelch-like protein 25	gwas
LINC00052	HGNC:26455	ENSG00000259527	Q96N35	Putative uncharacterized protein encoded by LINC00052	gwas
AGBL1	HGNC:26504	ENSG00000273540	Q96MI9	Cytosolic carboxypeptidase 4	gwas

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
KLHL25	Kelch-like protein 25	Substrate-specific adapter of a BCR (BTB-CUL3-RBX1) E3 ubiquitin ligase complex involved in various processes, such as translation homeostasis and lipid synthesis.
AGBL1	Cytosolic carboxypeptidase 4	Metallocarboxypeptidase that mediates deglutamylation of tubulin and non-tubulin target proteins.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 2 · Druggable fraction: 0.33

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
Protease	1	12.2×	0.159
Other/Unknown	2	1.2×	0.587

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
KLHL25	Other/Unknown	no		BTB/POZ_dom, Kelch_1, SKP1/BTB/POZ_sf
LINC00052	Other/Unknown	no
AGBL1	Protease	yes		Peptidase_M14, ARM-like, ARM-type_fold

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)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	3
unknown	0

Top tissues across cohort

Tissue	Cohort genes
ventricular zone	2
cortical plate	1
ganglionic eminence	1
mucosa of paranasal sinus	1
primordial germ cell in gonad	1
biceps brachii	1
deltoid	1
hindlimb stylopod muscle	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
KLHL25	182	ubiquitous	yes	ventricular zone, ganglionic eminence, cortical plate
LINC00052	21	broad	marker	primordial germ cell in gonad, ventricular zone, mucosa of paranasal sinus
AGBL1	82	broad	marker	biceps brachii, hindlimb stylopod muscle, deltoid

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
KLHL25	755
AGBL1	442
LINC00052	0

Structural data

PDB: 0 · AlphaFold-only: 3 · No structure: 0

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
KLHL25	Q9H0H3	88.89
AGBL1	Q96MI9	78.53
LINC00052	Q96N35	51.30

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 8. Enrichment computed across 3 evidence-associated genes (2 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 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Post-translational protein modification	2	19.2×	0.022	KLHL25, AGBL1
Carboxyterminal post-translational modifications of tubulin	1	119.0×	0.022	AGBL1
Metabolism of proteins	2	12.4×	0.022	KLHL25, AGBL1
Class I MHC mediated antigen processing & presentation	1	35.0×	0.057	KLHL25
Neddylation	1	23.7×	0.067	KLHL25
Antigen processing: Ubiquitination & Proteasome degradation	1	18.6×	0.071	KLHL25
Adaptive Immune System	1	14.9×	0.075	KLHL25
Immune System	1	6.5×	0.148	KLHL25

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 term	Cohort genes	Fold	FDR	Sample cohort genes
C-terminal protein deglutamylation	1	2106.5×	0.002	AGBL1
positive regulation of CD4-positive, CD25-positive, alpha-beta regulatory T cell differentiation	1	1685.2×	0.002	KLHL25
protein side chain deglutamylation	1	1404.3×	0.002	AGBL1
positive regulation of fatty acid oxidation	1	1203.7×	0.002	KLHL25
negative regulation of fatty acid biosynthetic process	1	443.5×	0.004	KLHL25
regulation of translational initiation	1	234.1×	0.006	KLHL25
ubiquitin-dependent protein catabolic process	1	37.1×	0.034	KLHL25
protein ubiquitination	1	20.7×	0.054	KLHL25
proteolysis	1	17.1×	0.058	AGBL1

Therapeutics

Drug target analysis

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

Druggability breadth: 0 of 3 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
KLHL25	0	0
LINC00052	0	0
AGBL1	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 3; 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	1	AGBL1
E	Difficult family or no structure, no drug	2	KLHL25, LINC00052

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
KLHL25	0	—
LINC00052	0	—
AGBL1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 7.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	6
PHASE4	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT01939093	PHASE4	COMPLETED	Therapeutic Effect of Quetiapine on Methamphetamine-Induced Psychosis
NCT07184710	Not specified	NOT_YET_RECRUITING	This Hospital-based Observational Study Employed a Study Will be Conducted in Sohag University Hospital Clinics Aiming to Ensure Cases Presented With Psychosis in Two Phases to Differentiate Into Two Groups a Case of Schizophrenia or a Case of Methamphetamine Induced Psychosis.
NCT07450027	Not specified	RECRUITING	LRFN5 and OLFM4 in Methamphetamine-Induced Psychosis
NCT07459244	Not specified	RECRUITING	ECG Findings in Methamphetamine Use
NCT07459257	Not specified	RECRUITING	Psychiatric Symptom Predictors in Methamphetamine-Induced Psychosis
NCT07459270	Not specified	NOT_YET_RECRUITING	Psychiatric Symptom Characteristics in Methamphetamine-Induced Psychosis With and Without Lifetime Cannabis Use
NCT07434401	Not specified	COMPLETED	α-N-acetylgalactosaminidase in Methamphetamine Psychosis

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
CINNARIZINE	4	1
DIAZEPAM	4	1