The NDUFAF2 gene helps cells make energy by helping assemble complex I, a key part of the mitochondria, which are your cells’ energy centers. This gene plays an important role in tissues that need steady energy, especially the brain and muscles. If the gene is not working properly, cells may not make enough energy. Pathogenic variants in the NDUFAF2 gene can cause mitochondrial complex I deficiency, a genetic condition that may lead to developmental delay, low muscle tone, weakness, movement problems, and changes seen on brain scans.
What is a gene?
Genes are stretches of DNA that give your cells instructions for making molecules or guiding processes in the body. Some genes carry the code for proteins, the parts of cells that do much of the work. Others are used mainly to regulate when certain processes happen, where they happen, and how strongly they run. Together, genes influence how the body develops and functions, and they can also shape how you respond to food, stress, or medications. For a more detailed look at this topic, you can find additional information in LearnHub.
Overview
NDUFAF2Gene function
What if the gene works
The NDUFAF2 gene helps your cells build complex I, a key part of the system that turns food into usable energy. This supports steady energy production, especially in organs with high energy needs.
Risk
What if the gene does not work
Variants in the NDUFAF2 gene can reduce energy production in mitochondria. More severe variants often cause Leigh syndrome, with developmental slowing or loss of skills and brain changes; milder variants may appear later or cause a less severe course.
Treatment
What does that mean for your treatment
No NDUFAF2-specific treatment or drug selection approach is currently established for people with a pathogenic variant in the NDUFAF2 gene. The NDUFAF2 gene is being studied in mitochondrial disease research as part of complex I biology, but this has not yet led to a targeted therapy.
Conditions associated with NDUFAF2
Gene function
What if the gene works
Your cells need the NDUFAF2 gene to help build one of the key parts of their energy system. Its job happens inside mitochondria, the parts of cells that turn food into usable energy. Rather than becoming a lasting part of the final structure, it acts as a helper during assembly so energy production can run smoothly.
The NDUFAF2 gene helps assemble complex I, a major part of the mitochondrial energy chain. Its protein supports this machine while it is being built so the final structure can form in the right order.
By helping complex I form correctly, NDUFAF2 supports one of the first steps in how cells make ATP, their main usable energy source. This is a central part of the NDUFAF2 gene’s role in mitochondrial energy production.
The protein made from this gene is a temporary helper, not a permanent piece of the finished energy machine. It guides partly built sections until the complex is ready for normal work inside mitochondria.
What is a variant?
A genetic variant is a minor change in the DNA sequence of a gene. These changes are common and help account for normal human diversity, such as differences in appearance, metabolism, or how the body responds to environmental influences. Many variants do not have any noticeable effect and simply represent natural genetic variation. In some situations, however, a variant can change how a gene functions more significantly and may contribute to or cause a genetic condition.
Genetic variants
What if the gene does not work
Variants in the NDUFAF2 gene often reduce or abolish the helper protein needed to build mitochondrial complex I. A way to understand how NDUFAF2 gene variants affect mitochondrial complex I is that assembly becomes incomplete, so the complex may be unstable or broken down before it can work well. Milder variants may leave some assembly activity, while more severe variants can block it more fully. In mitochondrial complex I deficiency, this can track with earlier onset and more marked features.
How variants are linked to conditions
Pathogenic variants in the NDUFAF2 gene cause mitochondrial complex I deficiency, often presenting as Leigh syndrome or Leigh-like disease in infancy or childhood. Children may develop developmental delay, low muscle tone, feeding problems, breathing changes, or movement difficulties, while brain imaging often shows changes typical of Leigh syndrome. This is a rare inherited condition, and a confirmed disease-causing variant in the NDUFAF2 gene can establish the diagnosis in the right clinical setting.
A variant is not necessarily a diagnosis
Genetic variants are a routine part of human biology and are common across the general population. Most do not have a direct effect on health and simply reflect natural human diversity. For many genes, carrying a variant associated with a condition indicates a possible link rather than a definite diagnosis, especially when several genes and environmental factors are involved. In some situations, though, a single well characterized variant in a specific gene can be enough to confirm a diagnosis.
Are there things that can increase or change my risk?
There is not yet broadly confirmed evidence on specific factors that increase or reduce health risk related to the NDUFAF2 gene. In families with a known NDUFAF2 change, risk mainly depends on the exact genetic findings rather than lifestyle, and a doctor or genetic counselor can explain what that means for you or your family.
Inheritance of NDUFAF2 variants
Variants in the NDUFAF2 gene are inherited in an autosomal recessive pattern. This means a person usually develops an NDUFAF2-related condition only when they inherit one altered copy from each parent. Parents who each carry one variant are typically unaffected carriers, and with each pregnancy they have a 25% chance of having an affected child, a 50% chance of having a child who is a carrier, and a 25% chance of having a child with two working copies. In families asking how variants of the NDUFAF2 gene are inherited, this pattern explains why the condition can appear unexpectedly in siblings.
What does my NDUFAF2 result mean for my family?
For families with a disease-causing change in the NDUFAF2 gene, the condition is usually passed down in a recessive pattern. This means parents are often healthy carriers, and brothers or sisters may also be affected or may be carriers even if they feel well. Close relatives may also carry the family’s gene change, so the result can matter beyond the person who was tested.
Genetic information
Genetic testing
How you find out about variants
NDUFAF2 genetic testing usually uses a blood sample or cheek swab. A lab reads the NDUFAF2 gene to look for changes in the DNA sequence, often through a mitochondrial disease panel or exome test. Results may show a disease causing variant, a benign variant, or a variant of uncertain significance.
When should I consider getting a genetic test?
Consider testing the NDUFAF2 gene if a child has signs of an inherited mitochondrial condition, especially Leigh syndrome, such as lost skills, weak muscle tone, seizures, or movement problems. Testing can also help when a close relative has a known NDUFAF2 variant.
A genetic result is only one part of your health story
Genetic results can provide meaningful insight, but how much they reveal varies by the condition and the type of variant involved. Many other influences, including lifestyle, environment, age, and medical history, shape how the body works over time. For some conditions, especially those influenced by many genes, genetic information offers context rather than certainty and is best understood alongside other parts of care. In other situations, a genetic result may give a clear answer. In areas such as medication response, genetic results can help put individual experiences into context.
Pharmacogenetics
How variants shape your response to medicine
Genetic variation can affect how your body handles certain medicines. Some people break down a drug faster or more slowly, or their cells respond to it differently, so the same treatment may work better for one person than another. These differences are common and can influence how much benefit you feel from a medicine or how sensitive you are to side effects. Medication response is also shaped by other factors, including age, liver and kidney function, and other medicines you take.
What is Pharmacogenetics?
Pharmacogenetics studies how differences in genes can shape a person’s response to medications. It examines relationships between genes and drugs to help explain why the same treatment can work differently from one person to another. For many medications, genes can affect both how strongly a drug works and how the body processes it. This information can support more informed, individualized treatment decisions. To learn more about this topic, you can explore the LearnHub.
Drugs influenced by the NDUFAF2 gene
When should I seek medical advice?
This gene is not currently used in a broadly confirmed way to predict how medicines will work or what side effects someone may have. Questions about medicines, side effects, or changes in treatment are best discussed with your doctor or pharmacist.