Paroxysmal nonkinesigenic dyskinesia

Summary

Paroxysmal nonkinesigenic dyskinesia (MONDO:0700088) is a disease with 3 cohort genes.

At a glance

• Prevalence: 1-9 / 1 000 000 (Worldwide) [Orphanet-validated]
• Cohort genes: 3
• ClinVar variants: 521
• Phenotypes (HPO): 15

Clinical features

Epidemiology

Prevalence records

1 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Point prevalence	1-9 / 1 000 000	0.1	Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

15 HPO clinical features (Orphanet curated; top 15 by frequency):

HPO ID	Term	Frequency
HP:0001332	Dystonia	Very frequent (80-99%)
HP:0007166	Paroxysmal dyskinesia	Very frequent (80-99%)
HP:0001266	Choreoathetosis	Frequent (30-79%)
HP:0002072	Chorea	Frequent (30-79%)
HP:0002487	Hyperkinetic movements	Frequent (30-79%)
HP:0004305	Involuntary movements	Frequent (30-79%)
HP:0000211	Trismus	Occasional (5-29%)
HP:0000473	Torticollis	Occasional (5-29%)
HP:0001387	Joint stiffness	Occasional (5-29%)
HP:0002063	Rigidity	Occasional (5-29%)
HP:0002094	Dyspnea	Occasional (5-29%)
HP:0002167	Abnormality of speech or vocalization	Occasional (5-29%)
HP:0003324	Generalized muscle weakness	Occasional (5-29%)
HP:0025401	Staring gaze	Occasional (5-29%)
HP:0100660	Dyskinesia	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	paroxysmal nonkinesigenic dyskinesia
Mondo ID	MONDO:0700088
Orphanet	98810
UMLS	C1869117
MedGen	401504
GARD	0008722
Is cancer (heuristic)	no

Also known as: DYT-MR-1 · Paroxysomal nonkinesigenic dyskinesia · Paroxystic non-kinesigenic choreoathetosis

Data availability: 521 ClinVar variants.

Disease family

An umbrella term covering 2 Mondo subtypes.

Classification path: human disease › disease by body system or component › nervous system disorder › movement disorder › extrapyramidal and movement disease › dystonic disorder › inherited dystonia › combined dystonia › paroxysmal dystonia › paroxysmal dyskinesia › paroxysmal nonkinesigenic dyskinesia

Related subtypes (4): infantile convulsions and choreoathetosis, childhood onset GLUT1 deficiency syndrome 2, episodic kinesigenic dyskinesia, ECHS1-related paroxysmal dyskinesia

Subtypes (2): paroxysmal nonkinesigenic dyskinesia 2, paroxysmal nonkinesigenic dyskinesia 1

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

521 retrieved; paginated sample, class counts are floors:

304 uncertain significance, 173 likely benign, 20 conflicting classifications of pathogenicity, 14 benign, 8 benign/likely benign, 2 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1892	NM_015488.5(PNKD):c.26C>T (p.Ala9Val)	LOC129935594	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1893	NM_015488.5(PNKD):c.20C>T (p.Ala7Val)	LOC129935594	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1149077	NM_015488.5(PNKD):c.1102C>T (p.Arg368Trp)	CATIP-AS2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
334311	NM_015488.5(PNKD):c.299C>T (p.Ala100Val)	CATIP-AS2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
334313	NM_015488.5(PNKD):c.331A>G (p.Thr111Ala)	CATIP-AS2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
334317	NM_015488.5(PNKD):c.466-3C>A	CATIP-AS2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
334321	NM_015488.5(PNKD):c.597C>T (p.Asp199=)	CATIP-AS2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
334326	NM_015488.5(PNKD):c.785G>A (p.Arg262Gln)	CATIP-AS2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
334328	NM_015488.5(PNKD):c.959G>A (p.Arg320Gln)	CATIP-AS2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
377052	NM_015488.5(PNKD):c.323A>G (p.His108Arg)	CATIP-AS2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
468628	NM_015488.5(PNKD):c.301C>T (p.Arg101Trp)	CATIP-AS2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
468629	NM_015488.5(PNKD):c.350A>G (p.Asn117Ser)	CATIP-AS2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
468634	NM_015488.5(PNKD):c.559C>T (p.Arg187Trp)	CATIP-AS2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
468636	NM_015488.5(PNKD):c.887A>G (p.Glu296Gly)	CATIP-AS2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
536498	NM_015488.5(PNKD):c.1126C>T (p.Arg376Cys)	CATIP-AS2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
654532	NM_015488.5(PNKD):c.293G>T (p.Arg98Leu)	CATIP-AS2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
800259	NM_015488.5(PNKD):c.340C>T (p.Arg114Cys)	CATIP-AS2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
834117	NM_015488.5(PNKD):c.984G>A (p.Thr328=)	CATIP-AS2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1894	NM_015488.5(PNKD):c.97G>C (p.Ala33Pro)	PNKD	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2040226	NM_015488.5(PNKD):c.1046C>T (p.Ala349Val)	PNKD	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2804690	NM_015488.5(PNKD):c.113C>T (p.Thr38Ile)	PNKD	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
468635	NM_015488.5(PNKD):c.76_103del (p.Ala26fs)	PNKD	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1000439	NM_015488.5(PNKD):c.1135A>T (p.Lys379Ter)	CATIP-AS2	Uncertain significance	criteria provided, single submitter
1004107	NM_015488.5(PNKD):c.371T>C (p.Ile124Thr)	CATIP-AS2	Uncertain significance	criteria provided, single submitter
1006163	NM_015488.5(PNKD):c.465+2T>G	CATIP-AS2	Uncertain significance	criteria provided, single submitter
1008167	NM_015488.5(PNKD):c.566G>T (p.Arg189Leu)	CATIP-AS2	Uncertain significance	criteria provided, single submitter
1009575	NM_015488.5(PNKD):c.302G>C (p.Arg101Pro)	CATIP-AS2	Uncertain significance	criteria provided, multiple submitters, no conflicts
1011051	NM_015488.5(PNKD):c.641_649del (p.Val214_Val216del)	CATIP-AS2	Uncertain significance	criteria provided, single submitter
1016709	NM_015488.5(PNKD):c.308G>A (p.Arg103His)	CATIP-AS2	Uncertain significance	criteria provided, single submitter
1026902	NM_015488.5(PNKD):c.538G>A (p.Gly180Arg)	CATIP-AS2	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 5 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
WNT10A	Orphanet:248	Autosomal recessive hypohidrotic ectodermal dysplasia
WNT10A	Orphanet:2721	Odonto-onycho-dermal dysplasia
WNT10A	Orphanet:50944	Schöpf-Schulz-Passarge syndrome
WNT10A	Orphanet:99798	Oligodontia
PNKD	Orphanet:98810	Paroxysmal non-kinesigenic dyskinesia

Cohort genes → proteins

3 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	3

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
WNT10A	HGNC:13829	ENSG00000135925	Q9GZT5	Protein Wnt-10a	clinvar
CATIP-AS2	HGNC:41079	ENSG00000237281		CATIP antisense RNA 2	clinvar
PNKD	HGNC:9153	ENSG00000127838	Q8N490	Probable thioesterase PNKD	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
WNT10A	Protein Wnt-10a	Ligand for members of the frizzled family of seven transmembrane receptors.
PNKD	Probable thioesterase PNKD	Probable thioesterase that may play a role in cellular detoxification processes; it likely acts on a yet-unknown alpha-hydroxythioester substrate.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 3 · 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	3	1.8×	0.174

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
WNT10A	Other/Unknown	no		Wnt, Wnt10, Wnt_CS
CATIP-AS2	Other/Unknown	no
PNKD	Other/Unknown	no		Metallo-B-lactamas, Hydroxyacylglutathione_Hdrlase, HAGH_C

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
bone marrow cell	2
lower esophagus mucosa	1
primordial germ cell in gonad	1
male germ line stem cell (sensu Vertebrata) in testis	1
tonsil	1
metanephros cortex	1
right lobe of liver	1
right uterine tube	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
WNT10A	151	broad	marker	primordial germ cell in gonad, lower esophagus mucosa, bone marrow cell
CATIP-AS2	108		yes	male germ line stem cell (sensu Vertebrata) in testis, bone marrow cell, tonsil
PNKD	257	ubiquitous	marker	metanephros cortex, right lobe of liver, right uterine tube

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
PNKD	1,861
WNT10A	1,092
CATIP-AS2	0

Structural data

PDB: 0 · AlphaFold-only: 2 · No structure: 1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
PNKD	Q8N490	83.69
WNT10A	Q9GZT5	82.36

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 3. 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
WNT ligand biogenesis and trafficking	1	211.5×	0.010	WNT10A
Complex IV assembly	1	114.2×	0.010	PNKD
Class B/2 (Secretin family receptors)	1	95.2×	0.010	WNT10A

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
obsolete methylglyoxal catabolic process to pyruvate via (R)-S-lactoyl-glutathione	1	2106.5×	0.003	PNKD
regulation of synaptic transmission, dopaminergic	1	2106.5×	0.003	PNKD
epidermis morphogenesis	1	1404.3×	0.003	WNT10A
regulation of odontogenesis of dentin-containing tooth	1	1203.7×	0.003	WNT10A
negative regulation of neurotransmitter secretion	1	1203.7×	0.003	PNKD
tongue development	1	1053.2×	0.003	WNT10A
sebaceous gland development	1	1053.2×	0.003	WNT10A
regulation of dopamine metabolic process	1	842.6×	0.003	PNKD
neural crest cell differentiation	1	766.0×	0.003	WNT10A
neuromuscular process controlling posture	1	526.6×	0.004	PNKD
odontogenesis	1	263.3×	0.006	WNT10A
hair follicle morphogenesis	1	247.8×	0.006	WNT10A
skin development	1	221.7×	0.007	WNT10A
hair follicle development	1	191.5×	0.007	WNT10A
cell fate commitment	1	147.8×	0.009	WNT10A
cellular response to transforming growth factor beta stimulus	1	138.1×	0.009	WNT10A
canonical Wnt signaling pathway	1	76.6×	0.015	WNT10A
neuron differentiation	1	50.1×	0.021	WNT10A
positive regulation of gene expression	1	19.4×	0.051	WNT10A

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
WNT10A	0	0
CATIP-AS2	0	0
PNKD	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	3	WNT10A, CATIP-AS2, PNKD

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)
WNT10A	0	—
CATIP-AS2	0	—
PNKD	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.