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

ENSG00000127838 ∙ NCBI:25953 ∙ OMIM:609023 ∙ HGNC:9153 ∙ Uniprot:Q8N490 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

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.

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.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			6	77	8	91
missense		3	243	13	1	260
nonsense			14			14
start loss			2			2
frameshift			15			15
inframe indel			4	1		5
splice donor/acceptor (+/-2bp)			8			8
splice region			9	15		24
non coding			45	73	55	173
Total	0	3	337	164	64

Variants in PNKD

This is a list of pathogenic ClinVar variants found in the PNKD region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
2-218269974-G-A		not specified	Uncertain significance (Mar 10, 2025)
2-218270029-T-C		not specified	Uncertain significance (Mar 07, 2024)
2-218270043-G-T		not specified	Uncertain significance (Mar 08, 2025)
2-218270044-G-C		not specified	Uncertain significance (Mar 07, 2025)
2-218270044-G-T		not specified	Uncertain significance (Aug 30, 2021)
2-218270141-T-A			Likely benign (Sep 02, 2019)
2-218270142-C-A			Likely benign (Sep 02, 2019)
2-218270205-A-G			Benign (Jul 05, 2018)
2-218270227-C-T			Benign (Jul 05, 2018)
2-218270290-G-A			Benign (Jul 17, 2018)
2-218270431-A-T		Paroxysmal nonkinesigenic dyskinesia 1	Likely benign (Dec 24, 2018)
2-218270457-C-A		Paroxysmal nonkinesigenic dyskinesia 1	Uncertain significance (Jun 14, 2016)
2-218270471-G-A		Paroxysmal nonkinesigenic dyskinesia 1	Uncertain significance (Jun 14, 2016)
2-218270527-G-GATCTGAACATGGCGGCGGTGGT			Uncertain significance (Aug 14, 2024)
2-218270536-A-T			Uncertain significance (Jul 28, 2023)
2-218270537-T-G		Paroxysmal nonkinesigenic dyskinesia 1	Uncertain significance (Apr 27, 2017)
2-218270540-C-T		Inborn genetic diseases	Uncertain significance (Aug 21, 2023)
2-218270541-G-T		Paroxysmal nonkinesigenic dyskinesia	Likely benign (Jul 02, 2021)
2-218270543-C-T		Paroxysmal nonkinesigenic dyskinesia	Uncertain significance (Dec 05, 2019)
2-218270546-T-C		Paroxysmal nonkinesigenic dyskinesia	Uncertain significance (Jan 14, 2024)
2-218270549-T-G		Paroxysmal nonkinesigenic dyskinesia	Uncertain significance (Aug 27, 2021)
2-218270550-A-G		Paroxysmal nonkinesigenic dyskinesia	Likely benign (Aug 27, 2023)
2-218270551-G-A		Paroxysmal nonkinesigenic dyskinesia	Uncertain significance (Sep 04, 2024)
2-218270551-G-T			Uncertain significance (Feb 08, 2023)
2-218270552-C-T		Paroxysmal nonkinesigenic dyskinesia	Uncertain significance (Jan 19, 2025)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PNKD	protein_coding	protein_coding	ENST00000273077	10	76402

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
4.14e-8	0.591	125681	0	67	125748	0.000266

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.323	215	229	0.940	0.0000145	2413
Missense in Polyphen		56	64.772	0.86457		684
Synonymous	1.08	80	93.3	0.857	0.00000527	823
Loss of Function	1.11	14	19.2	0.728	9.19e-7	219

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000451	0.000451
Ashkenazi Jewish	0.00	0.00
East Asian	0.000163	0.000163
Finnish	0.00	0.00
European (Non-Finnish)	0.000437	0.000396
Middle Eastern	0.000163	0.000163
South Asian	0.000197	0.000196
Other	0.00	0.00

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

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

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