PNKD

PNKD metallo-beta-lactamase domain containing, the group of MicroRNA protein coding host genes|MBL domain containing glyoxalase 2 subfamily|Mitochondrial respiratory chain complex assembly factors

Basic information

Region (hg38): 2:218269651-218346793

Links

ENSG00000127838NCBI:25953OMIM:609023HGNC:9153Uniprot:Q8N490AlphaFoldGenCCjaxSfariGnomADPubmedClinVar

Phenotypes

GenCC

Source: genCC

  • paroxysmal nonkinesigenic dyskinesia 1 (Supportive), mode of inheritance: AD
  • Tourette syndrome (Limited), mode of inheritance: AD
  • paroxysmal nonkinesigenic dyskinesia 1 (Strong), mode of inheritance: AD

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PNKD gene.

  • Paroxysmal_nonkinesigenic_dyskinesia (483 variants)
  • not_provided (100 variants)
  • not_specified (62 variants)
  • Paroxysmal_nonkinesigenic_dyskinesia_1 (56 variants)
  • Inborn_genetic_diseases (50 variants)
  • PNKD-related_disorder (18 variants)
  • Episodic_hemiplegia (1 variants)
  • Paroxysmal_dystonia (1 variants)
  • Young-onset_Parkinson_disease (1 variants)
  • Paroxysmal_dyskinesia (1 variants)
  • Moyamoya_angiopathy (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PNKD gene is commonly pathogenic or not. These statistics are base on transcript: NM_000015488.5. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

EffectPLPVUSLBBSum
synonymous
7
clinvar
85
clinvar
5
clinvar
97
missense
3
clinvar
265
clinvar
27
clinvar
1
clinvar
296
nonsense
15
clinvar
15
start loss
1
1
frameshift
19
clinvar
1
clinvar
20
splice donor/acceptor (+/-2bp)
9
clinvar
9
Total 0 3 316 113 6

Highest pathogenic variant AF is 0.000022309063

Loading clinvar variants...

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
PNKDprotein_codingprotein_codingENST00000273077 1076402
pLI Probability
LOF Intolerant
pRec Probability
LOF Recessive
Individuals with
no LOFs
Individuals with
Homozygous LOFs
Individuals with
Heterozygous LOFs
Defined p
4.14e-80.5911256810671257480.000266
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense0.3232152290.9400.00001452413
Missense in Polyphen5664.7720.86457684
Synonymous1.088093.30.8570.00000527823
Loss of Function1.111419.20.7289.19e-7219

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.0004510.000451
Ashkenazi Jewish0.000.00
East Asian0.0001630.000163
Finnish0.000.00
European (Non-Finnish)0.0004370.000396
Middle Eastern0.0001630.000163
South Asian0.0001970.000196
Other0.000.00

dbNSFP

Source: dbNSFP

Function
FUNCTION: Probable hydrolase that plays an aggravative role in the development of cardiac hypertrophy via activation of the NF-kappa- B signaling pathway. {ECO:0000250}.;
Disease
DISEASE: Dystonia 8 (DYT8) [MIM:118800]: A paroxysmal non- kinesigenic dystonia/dyskinesia. Dystonia is defined by the presence of sustained involuntary muscle contractions, often leading to abnormal postures. Dystonia type 8 is characterized by attacks of involuntary movements brought on by stress, alcohol, fatigue or caffeine. The attacks generally last between a few seconds and four hours or longer. The attacks may begin in one limb and spread throughout the body, including the face. {ECO:0000269|PubMed:15262732, ECO:0000269|PubMed:15824259, ECO:0000269|PubMed:16632198, ECO:0000269|PubMed:16717228, ECO:0000269|PubMed:16972263}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec
0.258

Intolerance Scores

loftool
0.156
rvis_EVS
-0.36
rvis_percentile_EVS
29.31

Haploinsufficiency Scores

pHI
0.512
hipred
N
hipred_score
0.224
ghis
0.534

Essentials

essential_gene_CRISPR
N
essential_gene_CRISPR2
N
essential_gene_gene_trap
N
gene_indispensability_pred
E
gene_indispensability_score
0.998

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium

Mouse Genome Informatics

Gene name
Pnkd
Phenotype
homeostasis/metabolism phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan);

Gene ontology

Biological process
methylglyoxal catabolic process to D-lactate via S-lactoyl-glutathione;regulation of synaptic transmission, dopaminergic;regulation of dopamine metabolic process;negative regulation of neurotransmitter secretion;neuromuscular process controlling posture
Cellular component
nucleus;mitochondrion;membrane
Molecular function
hydroxyacylglutathione hydrolase activity;protein binding;metal ion binding