Cyclic vomiting syndrome

Summary

Cyclic vomiting syndrome (MONDO:0010778) is a disease with 2 cohort genes and 12 clinical trials. Top therapeutic interventions include droperidol, haloperidol, and ondansetron.

At a glance

• Cohort genes: 2
• ClinVar variants: 2
• Clinical trials: 12

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	cyclic vomiting syndrome
Mondo ID	MONDO:0010778
OMIM	500007
ICD-11	1434288855
UMLS	C0152164
MedGen	57509
Is cancer (heuristic)	no

Also known as: CVS · cyclic vomiting syndrome

Data availability: 2 ClinVar variants.

Disease family

Classification path: disease › human disease › disease by body system or component › nervous system disorder › neuroendocrine disorder › cyclic vomiting syndrome

Related subtypes (3): posterior pituitary gland neoplasm, central diabetes insipidus, pineal body neoplasm

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

2 retrieved; paginated sample, class counts are floors:

2 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1703687	GRCh37/hg19 7p15.3-14.3(chr7:25451740-33864069)	ADCYAP1R1	Pathogenic	no assertion criteria provided
9589	NC_012920.1(MT-TL1):m.3243A>G	MT-TL1	Pathogenic	reviewed by expert panel

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 6 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
MT-TL1	Orphanet:255210	Mitochondrial DNA-associated Leigh syndrome
MT-TL1	Orphanet:324525	Hypertrophic cardiomyopathy with kidney anomalies due to mitochondrial DNA mutation
MT-TL1	Orphanet:480	Kearns-Sayre syndrome
MT-TL1	Orphanet:550	MELAS
MT-TL1	Orphanet:551	MERRF
MT-TL1	Orphanet:663	Mitochondrial DNA-related progressive external ophthalmoplegia

Cohort genes → proteins

2 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
ADCYAP1R1	HGNC:242	ENSG00000078549	P41586	Pituitary adenylate cyclase-activating polypeptide type I receptor	clinvar
MT-TL1	HGNC:7490	ENSG00000209082		mitochondrially encoded tRNA-Leu (UUA/G) 1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ADCYAP1R1	Pituitary adenylate cyclase-activating polypeptide type I receptor	G protein-coupled receptor activated by the neuropeptide pituitary adenylate cyclase-activating polypeptide (ADCYAP1/PACAP).

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.

Family	Genes	Fold	FDR
GPCR	1	12.0×	0.164
Other/Unknown	1	0.9×	0.805

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
ADCYAP1R1	GPCR	yes		GPCR_2_secretin-like, GPCR_2_extracellular_dom, GPCR_2_PACAP_1_rcpt
MT-TL1	Other/Unknown	no

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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
cortical plate	1
ganglionic eminence	1
nucleus accumbens	1
caudate nucleus	1
frontal cortex	1
right frontal lobe	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ADCYAP1R1	191	broad	marker	cortical plate, ganglionic eminence, nucleus accumbens
MT-TL1	118	ubiquitous	marker	frontal cortex, right frontal lobe, caudate nucleus

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ADCYAP1R1	1,518
MT-TL1	0

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
ADCYAP1R1	P41586	11

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 3. 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.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
NGF-independant TRKA activation	1	2284.0×	0.001	ADCYAP1R1
Glucagon-type ligand receptors	1	346.1×	0.004	ADCYAP1R1
G alpha (s) signalling events	1	73.2×	0.014	ADCYAP1R1

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
negative regulation of response to reactive oxygen species	1	16852.0×	9e-04	ADCYAP1R1
development of primary female sexual characteristics	1	4213.0×	0.002	ADCYAP1R1
positive regulation of inositol phosphate biosynthetic process	1	2407.4×	0.002	ADCYAP1R1
positive regulation of small GTPase mediated signal transduction	1	2106.5×	0.002	ADCYAP1R1
cAMP/PKA signal transduction	1	1404.3×	0.002	ADCYAP1R1
multicellular organismal response to stress	1	1296.3×	0.002	ADCYAP1R1
positive regulation of calcium ion transport into cytosol	1	1203.7×	0.002	ADCYAP1R1
positive regulation of cAMP/PKA signal transduction	1	1053.2×	0.002	ADCYAP1R1
adenylate cyclase-modulating G protein-coupled receptor signaling pathway	1	337.0×	0.005	ADCYAP1R1
response to estradiol	1	198.3×	0.008	ADCYAP1R1
response to ethanol	1	146.5×	0.010	ADCYAP1R1
adenylate cyclase-activating G protein-coupled receptor signaling pathway	1	113.1×	0.012	ADCYAP1R1
response to xenobiotic stimulus	1	69.1×	0.018	ADCYAP1R1
cell surface receptor signaling pathway	1	64.1×	0.018	ADCYAP1R1
spermatogenesis	1	35.2×	0.030	ADCYAP1R1
cell differentiation	1	29.1×	0.034	ADCYAP1R1

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 2

Druggability breadth: 1 of 2 evidence-associated genes (50%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
ADCYAP1R1	0	0
MT-TL1	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
ADCYAP1R1	42	Binding:34, Functional:8

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

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	1	ADCYAP1R1
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	MT-TL1

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
ADCYAP1R1	42	—
MT-TL1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 12.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	10
PHASE3	1
PHASE2	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT05065567	PHASE3	TERMINATED	Haloperidol, Droperidol, Ondansetron in Cannabis Hyperemesis
NCT04645953	PHASE2	COMPLETED	Staccato Granisetron® (AZ 010) for the Treatment of Cyclic Vomiting Syndrome
NCT05256160	Not specified	RECRUITING	Cortical Excitability in Cyclic Vomiting Syndrome
NCT06863207	Not specified	RECRUITING	Autonomic Reactivity and Personalized Neurostimulation
NCT07465614	Not specified	RECRUITING	A Study of Auricular Neurostimulation for Children With Cyclic Vomiting Syndrome
NCT00728104	Not specified	WITHDRAWN	The Use of L-Carnitine And CoQ10 Supplements In the Treatment of Cyclic Vomiting Syndrome (CVS)
NCT03295760	Not specified	COMPLETED	Analysis of Q10 Coenzyme Efficacy for Long-term Treatment of Cyclic Vomiting Syndrome in Children
NCT03434652	Not specified	COMPLETED	Auricular Neurostimulation for Cyclic Vomiting Syndrome
NCT03470181	Not specified	COMPLETED	Applying Nutrient Drink Test in Understanding Pathophysiology of CVS
NCT04329637	Not specified	COMPLETED	Effects of an Integrative Health Care Model With Meditation and Care Cordination in CVS
NCT04721171	Not specified	TERMINATED	Effectiveness of Electrical Neurostimulation in Cyclic Vomiting Syndrome.
NCT05961995	Not specified	COMPLETED	Heartfulness Meditation (HFM) in Cyclic Vomiting Syndrome (CVS)

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
DROPERIDOL	4	1
HALOPERIDOL	4	1
ONDANSETRON	4	1