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PNKP gene
Reviewed by Medicinsk Expert•Last updated: 2026-10-22•Gene

PNKP gene

The PNKP gene provides instructions for making an enzyme essential for repairing damaged DNA strands within the body's cells.

Normal Function

The PNKP gene provides instructions for making the polynucleotide kinase-phosphatase (PNKP) enzyme. This enzyme is critical for repairing broken strands of DNA molecules. It can help fix damage that affects one DNA strand (single-strand breaks) or both strands (double-strand breaks). At the site of the damage, the PNKP enzyme modifies the broken ends of the DNA strands so that they can be joined back together.

Health Conditions Related to Genetic Changes

Ataxia with oculomotor apraxia

At least nine PNKP gene mutations have been found to cause ataxia with oculomotor apraxia type 4. This condition is characterized by poor coordination and balance (ataxia) and problems with side-to-side movement of the eyes (oculomotor apraxia). These problems are due to the breakdown (degeneration) of nerve cells in the part of the brain that coordinates movement (the cerebellum).

PNKP gene mutations that cause ataxia with oculomotor apraxia type 4 lead to production of an unstable enzyme that is quickly broken down in the cell. Shortage of the PNKP enzyme prevents efficient repair of damaged DNA. Researchers suggest that the repair of single-strand breaks is particularly impaired in ataxia with oculomotor apraxia type 4. It is thought that single-strand DNA damage increases after birth as the brain grows. Without repair, the accumulating damage leads to a loss of nerve cell in the brain, resulting in the movement problems characteristic of ataxia with oculomotor apraxia type 4.

Microcephaly, seizures, and developmental delay

At least six mutations in the PNKP gene have been found to cause microcephaly, seizures, and developmental delay (MCSZ). This condition is characterized by problems with brain development before birth that result in an unusually small head size (microcephaly), recurrent seizures (epilepsy), and delayed development of speech and motor skills. Rarely, affected individuals also have difficulty coordinating movements (ataxia) due to degeneration of nerve cells in the cerebellum.

PNKP gene mutations that cause MCSZ lead to production of an unstable enzyme that is quickly broken down in the cell. Shortage of the PNKP enzyme prevents efficient repair of damaged DNA. Researchers suggest that, in contrast to ataxia with oculomotor apraxia type 4, the repair of double-strand breaks is particularly impaired in MCSZ. The accumulating damage is especially harmful to nerve cells. It is thought that excessive DNA damage before birth leads to the death of nerve cell precursors, impairing normal brain development and causing microcephaly and the other neurological features of MCSZ.

It is unclear why mutations in the same gene, even the same mutation in some cases, can have different effects on single-strand or double-strand DNA damage repair and cause either ataxia with oculomotor apraxia type 4 or MCSZ.

Charcot-Marie-Tooth disease

MedlinePlus Genetics provides information about Charcot-Marie-Tooth disease.

Other Names for This Gene

  • AOA4
  • bifunctional polynucleotide phosphatase/kinase
  • DNA 5'-kinase/3'-phosphatase
  • EIEE10
  • Homo sapiens polynucleotide kinase 3'-phosphatase (PNKP)
  • MCSZ
  • PNK

Frequently Asked Questions

Parents may notice developmental delays, trouble walking or maintaining balance, and difficulty moving the eyes side‑to‑side (oculomotor apraxia). If a child shows a combination of ataxia, microcephaly, or seizures, a clinician may consider testing for PNKP mutations. How is a PNKP mutation confirmed, and what does the test involve?::A genetic test called a targeted gene panel or whole‑exome sequencing is performed on a blood sample. The lab looks for pathogenic variants in the PNKP gene. Results are usually available within 4–6 weeks. Is the condition inherited, and can it be passed to future children?::Yes, PNKP mutations are inherited in an autosomal recessive pattern. Both parents must carry one copy of the mutation for a child to be at risk. Prenatal or pre‑implantation genetic testing can identify affected embryos. What treatments or management strategies are available for people with PNKP‑related ataxia?::There is no cure, but supportive care can help. Physical and occupational therapy improve balance and coordination, while speech therapy addresses swallowing or speech issues. Antiepileptic drugs can control seizures, and regular monitoring of eye movements and neurological status is recommended.
Source: MedlinePlus, National Library of Medicine

MedlinePlus brings together authoritative health information from the National Library of Medicine (NLM), the National Institutes of Health (NIH), and other government agencies and health-related organizations.

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