PNKP
Chr 19ARpolynucleotide kinase 3'-phosphatase
Also known as: AOA4, CMT2B2, EIEE10, MCSZ, PNK
The protein catalyzes 5' phosphorylation and 3' dephosphorylation of nucleic acids in response to ionizing radiation or oxidative damage as part of DNA repair. Autosomal recessive mutations cause microcephaly, seizures, and developmental delay, ataxia-oculomotor apraxia 4, and possibly Charcot-Marie-Tooth disease type 2B2. Pathogenicity results from impaired DNA repair mechanisms following cellular damage.
Definitive — sufficient evidence for diagnostic panels
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly tolerant — LoF variants common in population
Tolerant to missense variation
ClinVar Variant Classifications
590 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 34 | 3 | 7 | 0 | 44 |
Likely Pathogenic | 29 | 4 | 3 | 1 | 37 |
VUS | 4 | 146 | 20 | 5 | 175 |
Likely Benign | 0 | 6 | 128 | 125 | 259 |
Benign | 0 | 0 | 12 | 2 | 14 |
Conflicting | — | 45 | |||
| Total | 67 | 159 | 170 | 133 | 574 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
PNKP · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools