The NDUFA5 gene helps mitochondria, the cell’s energy makers, power a step your body uses to produce energy from food. This gene plays an important role in tissues that need steady energy, especially the brain, muscles, and heart. When the gene does not work properly, cells may not make enough energy, and pathogenic variants in the NDUFA5 gene can cause a mitochondrial condition with developmental delay, low muscle tone, movement problems, seizures, or heart issues. Effects can vary from person to person.
What is a gene?
Genes are stretches of DNA that carry instructions your cells use to make molecules or regulate activities in the body. Some provide the directions for producing proteins, which do much of the work inside cells. Others mainly guide when specific processes happen, where they happen, and how active they are. In combination, genes affect how your body develops and functions, and they may also influence how you react to food, stress, and medications. More detailed information on this topic is available in the LearnHub.
Overview
NDUFA5Gene function
What if the gene works
The NDUFA5 gene helps mitochondria, your cells’ energy centers, make energy through complex I, an early step in breathing at the cell level. This supports routine cell work, especially in energy-hungry tissues like the brain and muscles.
Risk
What if the gene does not work
Variants in the NDUFA5 gene can impair mitochondrial energy production and cause complex I deficiency. Milder and more severe variants can differ in timing and impact, with developmental delay, muscle weakness, high lactic acid levels, or heart problems.
Treatment
What does that mean for your treatment
No NDUFA5-specific treatment or management approach is currently established for people with a pathogenic or loss-of-function variant in the NDUFA5 gene.
Gene function
What if the gene works
Every organ needs a steady supply of energy to work, from brain signaling to muscle movement. The NDUFA5 gene helps mitochondria, the parts of cells that make most cellular energy, keep that supply moving. Its main job is supporting complex I, an early step in the process cells use to turn food into ATP, the cell’s usable energy.
The NDUFA5 gene provides instructions for one small part of complex I, the first large protein team in mitochondrial energy production. This helps your cells start turning energy from food into ATP, the fuel cells use every day.
Within complex I, the protein made from the NDUFA5 gene supports the controlled transfer of electrons to the next carrier in the chain. This helps mitochondria create the charge difference needed to make ATP.
The NDUFA5 gene also supports the stable function of complex I within the larger energy making system of mitochondria. This steady teamwork matters most in organs with high energy needs, including the brain, heart, and muscles.
What is a variant?
Genetic variants are small differences in a gene’s DNA sequence. They are common and help explain normal differences among people, such as appearance, metabolism, or the way the body responds to environmental influences. Many do not have any noticeable effect and are simply part of natural genetic variation. Sometimes, though, a variant changes how a gene works to a greater extent and can contribute to or cause a genetic condition.
Genetic variants
What if the gene does not work
Variants in the NDUFA5 gene that affect mitochondrial complex I can make the protein unstable or stop it from fitting properly into this energy system in mitochondria, the parts of cells that make energy. This lowers complex I activity and reduces cellular energy. Milder variants may leave some activity, while more severe variants, including truncating or major splice changes, can cause a greater loss of function and are more often linked to earlier or more marked mitochondrial disease.
How variants are linked to conditions
Pathogenic variants in the NDUFA5 gene can cause a rare inherited mitochondrial disease called complex I deficiency, and some affected people develop a brain condition called Leigh syndrome or a similar condition. In practice, the main NDUFA5 gene variants and mitochondrial disease link involves symptoms that often begin in infancy or childhood, with features that can vary from person to person.
A variant is not necessarily a diagnosis
Genetic variants are common across the general population and are a routine part of human biology. Most do not directly affect health and instead reflect normal human diversity. For many genes, a variant associated with a condition points to a possible link rather than a certain diagnosis, particularly when several genes and environmental influences contribute. In some situations, though, one well-understood variant in a particular gene is enough to confirm a diagnosis.
Are there things that can increase or change my risk?
Risk is mainly shaped by whether someone inherits harmful changes in both copies of the NDUFA5 gene, so family history and parents who are blood relatives can raise the chance in a child. Once those gene changes are present, there is not enough evidence that lifestyle changes lower the underlying genetic risk.
Inheritance of NDUFA5 variants
NDUFA5-related conditions are inherited in an autosomal recessive pattern. This means a child usually inherits one NDUFA5 gene variant from each parent, and both parents are typically healthy carriers. When both parents carry a variant, each pregnancy has a 25% chance of being affected, a 50% chance of producing a carrier child, and a 25% chance of producing a child without the familial variants. In practical terms, how NDUFA5 variants are inherited does not usually depend on whether the child is male or female.
What does my NDUFA5 result mean for my family?
For families, an NDUFA5 result usually means close relatives could also carry the same gene change. Parents of a child with an NDUFA5-related condition are often healthy carriers, and brothers or sisters may also be affected or be carriers. Because this condition is usually passed down in a recessive pattern, relatives may want to discuss family testing if the result is confirmed.
Genetic information
Genetic testing
How you find out about variants
To look for changes linked to an inherited condition, genetic testing for variants in the NDUFA5 gene usually uses a blood or saliva sample. A lab reads the DNA and compares it with a reference sequence to look for variants. Results may confirm a diagnosis, support one, or show a variant of uncertain significance (meaning the effect is unclear).
When should I consider getting a genetic test?
Consider genetic testing for the NDUFA5 gene if you or your child has signs of a rare condition that affects how cells make energy, such as developmental delay, low muscle tone, seizures, or muscle weakness, especially if similar problems run in the family. Testing can help confirm whether a change in NDUFA5 is the cause.
A genetic result is only one part of your health story
A genetic result can provide useful insight, but the amount it explains varies with the condition and the kind of variant involved. Factors like lifestyle, environment, age, and medical history also influence how the body functions over time. For some conditions, especially those shaped by many genes, genetic information offers context rather than certainty and is best understood together with other parts of care. In other situations, a genetic result can give a clear answer. In areas like medication response, it can also help put individual experiences into perspective.
Pharmacogenetics
How variants shape your response to medicine
Genetic variation can affect how people respond to medicines. Small differences in DNA can change how the body breaks down a drug, moves it into tissues, or responds to it at its target, so the same treatment may work better for one person than another. This is a common reason why some people get more benefit, fewer benefits, or more side effects from the same medication.
What is Pharmacogenetics?
Pharmacogenetics is the area of study that focuses on how genetic differences affect a person’s response to medications. It examines links between genes and drugs to help explain why the same treatment may work differently from one person to another. For many medicines, genes influence how strongly a drug works or how the body handles it. This information can support more informed, personalized treatment decisions. To learn more about this topic, you can explore the LearnHub.
Drugs influenced by the NDUFA5 gene
When should I seek medical advice?
There is not yet a broadly confirmed role for this gene in how people respond to medicines, so concerns about side effects, new prescriptions, or changes in treatment are best discussed with your doctor.