Paroxysmal nonkinesigenic dyskinesia 1

Summary

Paroxysmal nonkinesigenic dyskinesia 1 (MONDO:0700089) is a disease caused by PNKD (GenCC Strong), with 3 cohort genes.

At a glance

• Causal gene: PNKD (GenCC Strong)
• Cohort genes: 3
• ClinVar variants: 92

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	paroxysmal nonkinesigenic dyskinesia 1
Mondo ID	MONDO:0700089
OMIM	118800
DOID	DOID:0090049
UMLS	C4551506
MedGen	1631383
GARD	0026355
MedDRA	10065657, 10065658
Is cancer (heuristic)	no

Also known as: paroxysmal dyskinesia caused by mutation in PNKD · paroxysmal nonkinesigenic dyskinesia 1 · paroxysmal nonkinesigenic dyskinesia type 1 · PNKD paroxysmal dyskinesia · PNKD1 · PxMD-PNKD

Data availability: 92 ClinVar variants · 1 GenCC gene-disease record.

Disease family

Classification path: 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 › paroxysmal nonkinesigenic dyskinesia 1

Related subtypes (1): paroxysmal nonkinesigenic dyskinesia 2

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

92 retrieved; paginated sample, class counts are floors:

40 uncertain significance, 26 benign, 12 conflicting classifications of pathogenicity, 8 benign/likely benign, 3 pathogenic/likely pathogenic, 3 likely benign

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
65758	NM_145239.3(PRRT2):c.649dup (p.Arg217fs)	MVP-DT	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
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
468634	NM_015488.5(PNKD):c.559C>T (p.Arg187Trp)	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
898560	NM_015488.5(PNKD):c.*155C>T	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
1042649	NM_015488.5(PNKD):c.408C>G (p.Ile136Met)	CATIP-AS2	Uncertain significance	criteria provided, single submitter
1062866	NM_015488.5(PNKD):c.465+3G>A	CATIP-AS2	Uncertain significance	criteria provided, multiple submitters, no conflicts
1328199	NM_015488.5(PNKD):c.293G>A (p.Arg98His)	CATIP-AS2	Uncertain significance	criteria provided, multiple submitters, no conflicts
1329493	NM_015488.5(PNKD):c.490A>G (p.Thr164Ala)	CATIP-AS2	Uncertain significance	criteria provided, single submitter
1698915	NM_015488.5(PNKD):c.318A>T (p.Lys106Asn)	CATIP-AS2	Uncertain significance	criteria provided, single submitter
1878571	NM_015488.5(PNKD):c.1108C>T (p.Gln370Ter)	CATIP-AS2	Uncertain significance	criteria provided, single submitter
1915237	NM_015488.5(PNKD):c.984+2T>G	CATIP-AS2	Uncertain significance	criteria provided, multiple submitters, no conflicts
193719	NM_015488.5(PNKD):c.1010G>A (p.Arg337His)	CATIP-AS2	Uncertain significance	criteria provided, multiple submitters, no conflicts
3241978	NM_015488.5(PNKD):c.670C>T (p.Leu224=)	CATIP-AS2	Uncertain significance	criteria provided, single submitter
334312	NM_015488.5(PNKD):c.302G>A (p.Arg101Gln)	CATIP-AS2	Uncertain significance	criteria provided, multiple submitters, no conflicts
334318	NM_015488.5(PNKD):c.476A>T (p.Glu159Val)	CATIP-AS2	Uncertain significance	criteria provided, multiple submitters, no conflicts
334322	NM_015488.5(PNKD):c.628C>A (p.His210Asn)	CATIP-AS2	Uncertain significance	criteria provided, multiple submitters, no conflicts
334334	NM_015488.5(PNKD):c.*206C>T	CATIP-AS2	Uncertain significance	criteria provided, single submitter
334340	NM_015488.5(PNKD):c.*826G>T	CATIP-AS2	Uncertain significance	criteria provided, single submitter
334341	NM_015488.5(PNKD):c.*838C>T	CATIP-AS2	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · Orphanet: 1 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
PNKD	Strong	Autosomal dominant	paroxysmal nonkinesigenic dyskinesia 1	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
PNKD	Orphanet:98810	Paroxysmal non-kinesigenic dyskinesia

Cohort genes → proteins

3 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	3

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
PNKD	HGNC:9153	ENSG00000127838	Q8N490	Probable thioesterase PNKD	gencc,clinvar
CATIP-AS2	HGNC:41079	ENSG00000237281		CATIP antisense RNA 2	clinvar
MVP-DT	HGNC:56029	ENSG00000238045		MVP divergent transcript	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
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)
PNKD	Other/Unknown	no		Metallo-B-lactamas, Hydroxyacylglutathione_Hdrlase, HAGH_C
CATIP-AS2	Other/Unknown	no
MVP-DT	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)	3
unknown	0

Top tissues across cohort

Tissue	Cohort genes
metanephros cortex	1
right lobe of liver	1
right uterine tube	1
bone marrow cell	1
male germ line stem cell (sensu Vertebrata) in testis	1
tonsil	1
mucosa of transverse colon	1
oviduct epithelium	1
tendon of biceps brachii	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
PNKD	257	ubiquitous	marker	metanephros cortex, right lobe of liver, right uterine tube
CATIP-AS2	108		yes	male germ line stem cell (sensu Vertebrata) in testis, bone marrow cell, tonsil
MVP-DT	191		marker	oviduct epithelium, mucosa of transverse colon, tendon of biceps brachii

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
PNKD	1,861
CATIP-AS2	0
MVP-DT	0

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
PNKD	Q8N490	83.69

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 1. Enrichment computed across 3 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
Complex IV assembly	1	228.4×	0.004	PNKD

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
obsolete methylglyoxal catabolic process to pyruvate via (R)-S-lactoyl-glutathione	1	4213.0×	6e-04	PNKD
regulation of synaptic transmission, dopaminergic	1	4213.0×	6e-04	PNKD
negative regulation of neurotransmitter secretion	1	2407.4×	7e-04	PNKD
regulation of dopamine metabolic process	1	1685.2×	7e-04	PNKD
neuromuscular process controlling posture	1	1053.2×	9e-04	PNKD

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
PNKD	0	0
CATIP-AS2	0	0
MVP-DT	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	3	PNKD, CATIP-AS2, MVP-DT

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)
PNKD	0	—
CATIP-AS2	0	—
MVP-DT	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.