PNKP

Chr 19

polynucleotide kinase 3'-phosphatase

Also known as: AOA4, CMT2B2, EIEE10, MCSZ, PNK

NCBI Gene: 11284ENSG00000039650UniProt: Q96T60

This locus represents a gene involved in DNA repair. In response to ionizing radiation or oxidative damage, the protein encoded by this locus catalyzes 5' phosphorylation and 3' dephosphorylation of nucleic acids. Mutations at this locus have been associated with microcephaly, seizures, and developmental delay.[provided by RefSeq, Sep 2010]

GeneReviewsResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtMicrocephaly, seizures, and developmental delay
UniProtAtaxia-oculomotor apraxia 4

Clinical highlights

Gene-disease validity (ClinGen)
microcephaly, seizures, and developmental delay · ARDefinitivesufficient evidence for diagnostic panels
Interpreting a novel variant
Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.
0
Active trials
25
Pubs (1 yr)
—
P/LP submissions
—
P/LP missense
1.21
LOEUF
LOF
Mechanism· G2P
📖
GeneReview available — PNKP
Authoritative clinical overview · Recommended first read
Open GeneReview ↗
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?
1.21LOEUF
pLI 0.000
Z-score 0.70
OE 0.85 (0.61–1.21)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?
-1.31Z-score
OE missense 1.21 (1.11–1.31)
383 obs / 317.4 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?
LoF OE?0.85 (0.61–1.21)
0≤0.351.4
Missense OE?1.21 (1.11–1.31)
0≤0.61.4
Synonymous OE?1.49
0≤1.21.6
LoF obs/exp: 23 / 26.9Missense obs/exp: 383 / 317.4Syn Z: -4.53

ClinVar Variant Classifications

0 submitted variants in ClinVar

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.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients