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10 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
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PNKD
PNKD metallo-beta-lactamase domain containing
Chromosome 2 Β· 2q35
NCBI Gene: 25953Ensembl: ENSG00000127838.16HGNC: HGNC:9153UniProt: Q8N490
80PubMed Papers
21Diseases
0Drugs
3Pathogenic Variants
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
negative regulation of neurotransmitter secretionprotein bindingmitochondrionmembraneparoxysmal nonkinesigenic dyskinesia 1paroxysmal nonkinesigenic dyskinesiaparoxysmal dyskinesiaparoxysmal dystonia
✦AI Summary

PNKD (PNKD metallo-beta-lactamase domain containing) is a probable thioesterase that likely plays a role in cellular detoxification processes, acting on unknown alpha-hydroxythioester substrates 1. While the protein can catalyze hydrolysis of S-D-lactoyl-glutathione to form glutathione and D-lactic acid in vitro, this reaction occurs at very low rates and is not physiologically relevant in vivo 1. The primary clinical significance of PNKD lies in its association with paroxysmal non-kinesigenic dyskinesia (PNKD), a movement disorder characterized by spontaneous attacks of abnormal involuntary movements without loss of consciousness 23. PNKD is caused by mutations in the MR-1 gene (now known as PNKD) and represents one of the three main forms of paroxysmal dyskinesias 34. The condition typically has a benign course and may not require treatment with advancing age 5. Additionally, genetic variations at the PNKD locus on chromosome 2 have been associated with colorectal cancer risk, with the susceptibility SNP showing strong linkage disequilibrium with inflammatory bowel disease risk variants, suggesting pleiotropic effects 6.

Sources cited
1
PNKD is a probable thioesterase involved in cellular detoxification and can hydrolyze S-D-lactoyl-glutathione at very low rates in vitro
PMID: 21487022
2
PNKD mutations cause paroxysmal non-kinesigenic dyskinesia, a movement disorder with spontaneous attacks
PMID: 29735119
3
PNKD is due to mutations of the MR-1 gene and is one of three recognized forms of paroxysmal dyskinesias
PMID: 21626559
4
PNKD (DYT8) is classified as a combined dystonia with paroxysmal characteristics
PMID: 24092288
5
MR-1-PNKD has a benign course and may not require treatment with advancing age
PMID: 32279719
6
Genetic variations at PNKD locus are associated with colorectal cancer risk and show pleiotropic effects with inflammatory bowel disease
PMID: 27005424
Disease Associationsβ“˜21
paroxysmal nonkinesigenic dyskinesia 1Open Targets
0.77Strong
paroxysmal nonkinesigenic dyskinesiaOpen Targets
0.63Moderate
paroxysmal dyskinesiaOpen Targets
0.33Weak
Episodic hemiplegiaOpen Targets
0.33Weak
paroxysmal dystoniaOpen Targets
0.33Weak
Moyamoya diseaseOpen Targets
0.26Weak
genetic disorderOpen Targets
0.19Weak
metabolic diseaseOpen Targets
0.12Weak
young-onset Parkinson diseaseOpen Targets
0.12Weak
colorectal cancerOpen Targets
0.12Weak
gallstonesOpen Targets
0.10Suggestive
response to statinOpen Targets
0.09Suggestive
inflammatory bowel diseaseOpen Targets
0.08Suggestive
ankylosing spondylitisOpen Targets
0.06Suggestive
hyperthyroxinemiaOpen Targets
0.05Suggestive
COVID-19Open Targets
0.05Suggestive
cholelithiasisOpen Targets
0.05Suggestive
ParagangliomaOpen Targets
0.05Suggestive
pheochromocytoma/paraganglioma syndrome 6Open Targets
0.05Suggestive
colorectal adenomaOpen Targets
0.04Suggestive
Paroxysmal non-kinesigenic dyskinesia 1UniProt
Pathogenic Variants3
NM_015488.5(PNKD):c.26C>T (p.Ala9Val)Pathogenic
Paroxysmal nonkinesigenic dyskinesia 1|Episodic hemiplegia;Paroxysmal dyskinesia;Paroxysmal dystonia|not provided|Paroxysmal nonkinesigenic dyskinesia
β˜…β˜…β˜†β˜†2023β†’ Residue 9
NM_015488.5(PNKD):c.20C>T (p.Ala7Val)Pathogenic
Paroxysmal nonkinesigenic dyskinesia 1|Paroxysmal nonkinesigenic dyskinesia
β˜…β˜…β˜†β˜†2023β†’ Residue 7
NM_015488.5(PNKD):c.293G>C (p.Arg98Pro)Likely pathogenic
not provided
β˜…β˜†β˜†β˜†2016β†’ Residue 98
View on ClinVar β†—
Related Genes
PRRT2Protein interaction96%PET117Protein interaction91%PET100Protein interaction90%ASIC4Protein interaction89%GGCXShared pathway20%KCNMA1Co-mentioned in literature20%
Tissue Expression6 tissues
Liver
100%
Lung
24%
Bone Marrow
21%
Heart
20%
Brain
19%
Ovary
10%
Gene Interaction Network
Click a node to explore
PNKDPRRT2PET117PET100ASIC4GGCXKCNMA1
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted Β· UniProt Q8N490
View on AlphaFold β†—
Constraintβ“˜
LOEUFβ“˜
1.13LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF0.85 [0.64–1.13]
RankingsWhere PNKD stands among ~20K protein-coding genes
  • #5,954of 20,598
    Most Researched80
  • #4,016of 5,498
    Most Pathogenic Variants3
  • #11,686of 17,882
    Most Constrained (LOEUF)1.13
Genes detectedPNKD
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
Impact of ambient air pollution on colorectal cancer risk and survival: insights from a prospective cohort and epigenetic Mendelian randomization study.
PMID: 38631091
EBioMedicine Β· 2024
1.00
2
Paroxysmal Dyskinesias.
PMID: 29735119
Semin Pediatr Neurol Β· 2018
0.90
3
PMID: 31427379
J Gen Physiol Β· 2019
0.80
4
Paroxysmal dyskinesias.
PMID: 21626559
Mov Disord Β· 2011
0.70
5
Dystonia.
PMID: 24092288
Continuum (Minneap Minn) Β· 2013
0.60