The NDUFAF8 gene helps build complex I, an important part of the mitochondria, the parts of cells that turn food into usable energy. This gene plays an important role in keeping energy production steady, especially in organs with high energy needs like the brain, muscles, and heart. If you carry disruptive variants in both copies, energy supply can drop and cause a rare inherited mitochondrial condition with developmental delay, low muscle tone, seizures, feeding problems, or heart and breathing difficulties.
What is a gene?
Genes are pieces of DNA that carry instructions your cells use to make molecules or manage processes throughout the body. Some genes hold the directions for producing proteins, the parts of cells that do much of the work. Others mostly regulate when certain processes take place, where they happen, and how strongly they operate. Taken together, genes affect how the body develops and functions, and they can influence how you respond to food, stress, and medications. For a deeper look at this subject, you can find more in the LearnHub.
Overview
NDUFAF8Gene function
What if the gene works
The NDUFAF8 gene helps cells build complex I, a key part of the mitochondria that make energy. This supports steady energy production, especially in organs with high energy needs like the brain, muscles, and heart.
Risk
What if the gene does not work
More disruptive variants in the NDUFAF8 gene can lead to a mitochondrial energy disorder, often with early feeding problems, low muscle tone, movement difficulties, and developmental delay. Milder variants may cause a later onset or less severe features.
Treatment
What does that mean for your treatment
At present, no treatment or management approach specific to a pathogenic or loss-of-function variant in the NDUFAF8 gene is established. Care is guided by the person’s symptoms and the broader mitochondrial condition, not by a drug choice tied specifically to the NDUFAF8 gene.
Conditions associated with NDUFAF8
Gene function
What if the gene works
Your cells need the NDUFAF8 gene to help mitochondria, the parts of cells that make most energy, assemble complex I. When this process runs smoothly, cells can turn fuel from food into ATP, their usable energy source. This steady energy supply supports everyday work across the body.
NDUFAF8 helps mitochondria build complex I, a large energy making machine in the respiratory chain. It supports mitochondrial complex I assembly so the parts come together in an organized way.
By helping complex I form properly, this gene supports the early steps of ATP production, the main fuel your cells use. This helps cells keep up with routine tasks like movement, signaling, and repair.
NDUFAF8 works with other helper proteins inside mitochondria to guide complex I into a stable working form. This teamwork helps the cell’s energy machinery be put together correctly before regular use.
What is a variant?
A genetic variant is a minor change in the DNA sequence within a gene. These changes are common and help account for normal human diversity, including differences in appearance, metabolism, and the way the body responds to environmental influences. Many variants do not have any noticeable effect and are simply part of natural genetic variation. In some situations, though, a variant can change how a gene works to a greater extent and may contribute to or cause a genetic condition.
Genetic variants
What if the gene does not work
A key part of how variants in the NDUFAF8 gene affect mitochondrial complex I is that they can leave the NDUFAF8 protein unstable, shortened, or missing. This can impair complex I assembly inside mitochondria, so cells make less energy. Some variants appear milder and may leave partial function, while more severe variants can cause little or no function and are often linked to earlier or more marked features of mitochondrial disease.
How variants are linked to conditions
Pathogenic variants in both copies of the NDUFAF8 gene cause a rare mitochondrial condition called isolated complex I deficiency. In affected families, variants in the NDUFAF8 gene have been linked to developmental delay, low muscle tone, feeding problems, seizures, lactic acidosis, and Leigh syndrome, which affects the brain. Symptoms often begin in infancy or early childhood, though severity can vary.
A variant is not necessarily a diagnosis
Genetic variants are a routine part of human biology and are widely present in the general population. Most do not have a direct effect on health and simply reflect normal 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 is enough to confirm a diagnosis.
Are there things that can increase or change my risk?
There isn't yet broadly confirmed evidence on specific factors that increase or reduce risk related to the NDUFAF8 gene. If a disease-causing change is present, the main risk usually comes from the inherited gene change itself, and a doctor or genetic counselor can help explain what that means for you or your family.
Inheritance of NDUFAF8 variants
NDUFAF8-related conditions are inherited in an autosomal recessive pattern. This means a child usually inherits one NDUFAF8 gene variant from each parent, while the parents often carry one variant each and may not have symptoms. When both parents are carriers, each pregnancy has a 25% chance that the child will inherit both variants and be affected, a 50% chance that the child will be a carrier, and a 25% chance that the child will inherit neither variant. Because the NDUFAF8 gene is on an autosome, this pattern is the same in boys and girls.
What does my NDUFAF8 result mean for my family?
For families with a disease-causing change in the NDUFAF8 gene, the pattern is usually recessive, which often means both parents are healthy carriers. Brothers and sisters may also have the condition or be carriers, so close relatives may want to learn whether the same gene change is present in the family. Children of someone with two changed copies will usually be carriers unless the other parent also carries a NDUFAF8 change.
Genetic information
Genetic testing
How you find out about variants
To find variants in the NDUFAF8 gene, doctors use NDUFAF8 genetic testing, usually with a blood or saliva sample. A lab reads the DNA code and looks for changes that may help explain a person’s symptoms or show whether they carry a known family variant.
When should I consider getting a genetic test?
Consider testing the NDUFAF8 gene when a baby or child has signs of a serious mitochondrial condition, such as developmental loss, low muscle tone, feeding or breathing problems, or brain scan findings linked with Leigh syndrome. Testing can also help when a sibling or close family member has a confirmed NDUFAF8 gene change.
A genetic result is only one part of your health story
A genetic finding can give useful insight, but how much it explains depends on the condition and on the kind of variant identified. How the body functions over time is shaped by many factors, including lifestyle, environment, age, and medical history. For some conditions, particularly those affected by many genes, genetic information provides context rather than certainty and is most helpful when considered with other parts of care. In other situations, a genetic result can offer a clear answer. In areas like medication response, it can also help put personal experiences in context.
Pharmacogenetics
How variants shape your response to medicine
Genetic variation can affect how people respond to medicines. This helps explain why the same treatment works well for one person, seems less effective for another, or causes more side effects in someone else. Small differences in genes can change how the body breaks down a drug, moves it through the body, or responds to it at its target. These differences are common and can influence both how well a medicine works and how sensitive a person may be to it.
What is Pharmacogenetics?
Pharmacogenetics examines the ways genetic differences shape how people respond to medicines. It focuses on gene-drug patterns to clarify why the same treatment can affect one person differently than another. With many medications, genes influence either how powerfully a drug works or how the body handles it. This information can support more informed, more personalized treatment choices. To explore this topic further, you can find more in the LearnHub.
Drugs influenced by the NDUFAF8 gene
When should I seek medical advice?
There is not yet a broadly confirmed role for this gene in guiding medication choices, so general concerns about symptoms, side effects, or how a medicine is working are best discussed with your doctor.
History
The NDUFAF8 gene first appeared in genome catalogs under an earlier label, C17orf89, before researchers understood its medical importance. As medical science evolved, so did understanding of this gene. It was later renamed NDUFAF8 as studies connected it to mitochondrial energy production and to inherited complex I deficiency. In more recent years, reports of affected families helped establish the NDUFAF8 gene as part of the growing group of genes linked to Leigh syndrome and related mitochondrial conditions.