The NAE1 gene helps your cells run a protein tagging system that controls when other proteins are used, repaired, or cleared away. When this gene does not work well, cells may lose control over growth and upkeep, which can affect early development. What this gene does can influence how your body grows and how the brain develops early in life. People with pathogenic variants in the NAE1 gene may have developmental delay, low muscle tone, seizures, or vision differences.
What is a gene?
Genes are sections of DNA that hold instructions your cells use to make molecules or regulate processes in the body. Some genes carry the directions for making proteins, the parts of cells that do much of the work. Other genes are mainly involved in controlling when certain processes happen, where they happen, and how strongly they take place. Together, genes affect how the body develops and functions, and they can also influence how you respond to food, stress, or medications. To go further into this topic, you can find more in the LearnHub.
Overview
NAE1Gene function
What if the gene works
The NAE1 gene helps start a process for tagging proteins. This lets cells control growth, division, and protein cleanup.
Risk
What if the gene does not work
Changes in the NAE1 gene can cause a neurodevelopmental condition with developmental delay, low muscle tone, movement or balance problems, and vision issues. Milder to more severe variants may affect when symptoms begin and how strongly they appear.
Treatment
What does that mean for your treatment
For conditions linked to pathogenic variants in the NAE1 gene, no gene-specific treatment or management approach is currently established. In cancer research, the NAE1 gene is being studied as a drug target because it helps control how cells handle certain proteins. Drugs that block this pathway are under investigation in some cancers.
Gene function
What if the gene works
Many routine cell jobs stay organized because the NAE1 gene helps launch a protein-tagging system inside cells. This system uses a small tag called NEDD8 to fine-tune how other proteins work. In practical terms, it supports steady cell growth, timely protein cleanup, and normal cell division.
The NAE1 gene helps start neddylation (adding the small NEDD8 tag to selected proteins). It activates NEDD8 first so the tag can be handed to other cell helpers.
NEDD8 tagging helps turn on protein cleanup teams that label used or extra proteins for removal. This keeps protein levels controlled and helps short-lived signals end on time.
By supporting these tagging and cleanup steps, the NAE1 gene helps cells move through growth and division in an orderly way. This steady timing is part of what the NAE1 gene does in the body during everyday cell renewal.
What is a variant?
A genetic variant is a minor difference in a gene’s DNA sequence. These differences are common and help shape 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 simply represent natural genetic variation. In some situations, though, a variant can change how a gene works more significantly and may contribute to or cause a genetic condition.
Genetic variants
What if the gene does not work
Variants in the NAE1 gene can change the shape or stability of the NAE1 protein, making it less able to pair with its partner protein and start the process that attaches the NEDD8 tag, a small control label, to other proteins. NAE1 gene variants may weaken this cell-control pathway, so fewer target proteins are modified on time. Some variants have a milder effect and leave partial activity, while more severe variants can sharply reduce or nearly stop this process.
How variants are linked to conditions
Pathogenic variants in the NAE1 gene are linked to a rare inherited neurodevelopmental condition. Reported health conditions linked to NAE1 gene variants include developmental delay or intellectual disability, low muscle tone, seizures in some children, hearing loss, and vision or growth differences. When a disease-causing variant is identified in the right clinical setting, it can help confirm the diagnosis.
A variant is not necessarily a diagnosis
Genetic variants are a usual part of human biology and are widely found across the general population. Most do not directly affect health and instead reflect natural human diversity. For many genes, having a variant associated with a condition suggests a possible link rather than a certain diagnosis, especially when several genes and environmental factors also play a role. Still, in some situations, a single well-characterized variant in a particular gene is 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 NAE1 gene. People with concerns about their own or their family’s risk can talk with a doctor or genetic counselor for personalized guidance.
Inheritance of NAE1 variants
NAE1-related conditions that have been described so far follow an autosomal recessive inheritance pattern. This means a child inherits one NAE1 gene variant from each parent, and parents are usually healthy carriers. When both parents carry a variant in the NAE1 gene, each pregnancy has a 25% chance of the child inheriting both altered copies, a 50% chance of being a carrier, and a 25% chance of inheriting neither variant. In practical terms, how NAE1 variants are inherited usually involves both sides of the family, even when no one else seems affected.
What does my NAE1 result mean for my family?
For the condition linked to the NAE1 gene, the family pattern is usually recessive, which means parents are often healthy carriers. Brothers and sisters could also be affected or be carriers, and other relatives on both sides of the family may carry the same change without knowing it. This can matter for future pregnancies and for relatives who are planning children.
Genetic information
Genetic testing
How you find out about variants
Genetic testing for NAE1 variants usually uses a blood or saliva sample to read the DNA sequence and look for changes in the NAE1 gene. It may be done as part of a broader epilepsy or developmental panel, whole exome sequencing, or a targeted test to confirm a known family variant.
When should I consider getting a genetic test?
Testing for changes in the NAE1 gene may be considered when a child has unexplained developmental delay, low muscle tone, seizures, or other signs of a rare inherited brain and nerve condition, especially if more than one family member is affected. If a NAE1 change has already been found in a relative, testing can help clarify the diagnosis and family risk.
A genetic result is only one part of your health story
A genetic result can provide valuable information, but how much it explains depends on the condition and the specific type of variant. Many factors, including lifestyle, environment, age, and medical history, influence how the body functions over time. In some conditions, especially those shaped by many genes, genetic information provides context rather than certainty and is best interpreted along with other parts of care. In other situations, a genetic result can offer a clear answer. In areas such as medication response, genetic results can also help put individual experiences into context.
Pharmacogenetics
How variants shape your response to medicine
Genetic variation can affect how your body responds to medicines, so the same treatment may work differently from one person to another. Some inherited differences change how quickly a drug is processed, how much of it reaches its target, or how sensitive your body is to its effects. These common differences can influence how well a medicine works and whether side effects are more or less likely.
What is Pharmacogenetics?
Pharmacogenetics examines how differences in genes can affect a person’s response to medications. It looks at the relationship 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 treatment decisions that are more informed and more individualized. To explore this subject further, more information is available in the LearnHub.
Drugs influenced by the NAE1 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 questions about side effects, treatment changes, or new symptoms are best discussed with your doctor or pharmacist.
History
NAE1 entered the genetics literature in the late 1990s, when researchers were mapping the newly recognized NEDD8 pathway and identifying the proteins involved in it. From these first observations, research expanded steadily as scientists showed that the NAE1 gene worked alongside UBA3 in the same enzyme complex. In the 2000s, this pathway drew wider interest because of its role in cell growth and cancer biology. That led to the development of drugs designed to block NEDD8 activation, including pevonedistat, which brought the NAE1 gene into cancer research and early clinical studies. Over time, descriptions became more precise as laboratory work clarified how changes in this pathway affect human cells. While NAE1 is not a gene widely known in public culture, it has become an established part of modern research on targeted cancer treatment.