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POLR3A gene
Reviewed by Medicinsk Expert•Last updated: 2026-10-22•Gene

POLR3A gene

The POLR3A gene encodes a critical subunit of the RNA polymerase III enzyme, which is essential for synthesizing RNA molecules required for cell survival and protein production.

Normal Function

The POLR3A gene provides instructions for making the largest subunit of the enzyme RNA polymerase III. This enzyme is responsible for transcription, the process of synthesizing RNA molecules from DNA instructions. Specifically, it helps synthesize ribosomal RNA (rRNA) and transfer RNA (tRNA), which are essential for assembling amino acids into functional proteins.

Health Conditions Related to Genetic Changes

Pol III-related leukodystrophy

Variants in the POLR3A gene can prevent the RNA polymerase III enzyme from assembling or binding to DNA correctly. This leads to hypomyelination—a reduced ability to form the myelin that insulates nerve fibers—resulting in:

  • Intellectual disabilities
  • Ataxia (difficulty with coordination and balance)
  • Abnormal tooth development

Various clinical presentations, such as 4H syndrome, TACH, and ADDH, are now grouped under the spectrum of Pol III-related leukodystrophy.

Wiedemann-Rautenstrauch syndrome

This condition is caused by POLR3A variants that are thought to impair RNA polymerase III function more severely than those associated with leukodystrophy. Features include:

  • Slow growth before and after birth
  • Characteristic facial appearance
  • Lipodystrophy (lack of fatty tissue under the skin)
  • Sparse hair
  • Abnormal tooth development

Other disorders

Some POLR3A variants cause ataxia and dental abnormalities without the reduced myelination seen in Pol III-related leukodystrophy. Symptoms typically begin in adolescence and may include rhythmic shaking (tremor) and a reduced ability to sense vibrations in the feet.

Other Names for This Gene

  • DNA-directed RNA polymerase III largest subunit
  • DNA-directed RNA polymerase III subunit A
  • polymerase (RNA) III subunit A
  • RNA polymerase III 155 kDa subunit
  • RPC1
  • RPC155
  • RPC1_HUMAN

Frequently Asked Questions

Early symptoms often appear in infancy or early childhood and can include delayed motor milestones, difficulty with coordination (ataxia), speech delays, and subtle changes in tone or reflexes. Parents may notice that their child has trouble walking steadily, has a wide-based gait, or shows unusual tremors. Eye exams may reveal nystagmus or abnormal eye movements, and dental exams can uncover missing or malformed teeth. If these signs appear, a pediatric neurologist should evaluate the child for further testing.
There is no cure that reverses the genetic defect, but multidisciplinary care can improve quality of life. Physical and occupational therapy help maintain motor function and balance. Speech therapy addresses communication delays. Early intervention for hearing and vision problems is essential. Some patients benefit from medications that reduce spasticity or manage seizures if they occur. Regular monitoring of growth, dental health, and endocrine function is also recommended, as many patients experience growth delays and dental abnormalities.
POLR3A mutations are inherited in an autosomal recessive pattern. If both parents carry a pathogenic variant, each pregnancy has a 25 % chance of producing a child with the disease, a 50 % chance of producing a carrier, and a 25 % chance of being unaffected. Carrier testing for family members and pre‑conception counseling can help families understand and manage this risk.===
Diagnosis typically starts with a brain MRI that shows characteristic hypomyelination patterns, especially in the periventricular white matter. If imaging suggests a Pol III disorder, a geneticist will order a targeted gene panel or whole‑exome sequencing that includes POLR3A. A positive result is confirmed by finding pathogenic variants in both copies of the gene (biallelic) or a single pathogenic variant with a second variant of uncertain significance that is likely pathogenic. Blood or saliva samples are used for DNA extraction, and the results are interpreted by a clinical geneticist.
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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