The HAL gene helps your body break down histidine, a building block of protein, mainly in the liver and skin. If this gene does not work well, histidine can build up and lead to histidinemia, a rare inherited condition found on some newborn screening tests. Many people with variants in the HAL gene stay healthy, while some may have speech, learning, or developmental differences. Understanding this gene can help clarify why a newborn screen may be abnormal even when a child seems well.
What is a gene?
A gene is a stretch of DNA that carries instructions your cells can use to make molecules or regulate processes in the body. Some genes provide the information needed to produce proteins, the parts of cells that do the work. Other genes mainly guide when, where, and how strongly certain processes take place. Together, genes affect how the body develops and functions, and they can influence how you respond to food, stress, or medicines. If you want to explore this topic more deeply, you can learn more in the LearnHub.
Overview
HALGene function
What if the gene works
The HAL gene helps your body break down histidine, a building block of proteins. It is most active in the liver and skin, where it supports normal amino acid processing and makes urocanic acid, a natural skin chemical.
Risk
What if the gene does not work
When the HAL gene works less well, histidine may build up in the body, causing histidinemia. Many people have no symptoms, while others may have mild speech, learning, or developmental differences. Effects can vary with milder and more severe variants.
Treatment
What does that mean for your treatment
No HAL-specific treatment or drug-selection approach is currently established for people with pathogenic variants in the HAL gene.
Conditions associated with HAL
Gene function
What if the gene works
Your body uses the HAL gene to process histidine, one of the building blocks of protein. It makes an enzyme that starts breaking histidine down after food is digested or proteins are recycled. Understanding how the HAL gene works helps explain a routine part of metabolism in the liver and skin.
Inside liver cells, the HAL gene starts the breakdown of histidine, an amino acid from food and normal protein turnover. Its enzyme turns histidine into urocanic acid, a normal substance your body makes during this process.
By moving histidine into a normal breakdown pathway, this gene supports the body's day to day handling of amino acids from food and from worn out proteins. This helps metabolism stay balanced during routine cell activity.
In the outer skin layer, HAL activity helps make urocanic acid, which is part of normal skin surface chemistry. This supports the skin's usual mildly acidic environment.
What is a variant?
A genetic variant is a minor change in a gene’s DNA sequence. These changes are common and are part of normal human diversity, including differences in appearance, metabolism, and the way the body reacts to environmental influences. Many do not produce any noticeable effect and simply represent natural genetic variation. Sometimes, though, a variant changes how a gene works more significantly and can contribute to or cause a genetic condition.
Genetic variants
What if the gene does not work
Variants in the HAL gene can lower or switch off histidase activity, so cells break down histidine less effectively. Some variants slightly reduce enzyme stability or folding, while more severe variants can leave little or no working enzyme. These differences explain how HAL gene variants affect histidine breakdown in cells and why histidinemia may range from very mild to more noticeable.
How variants are linked to conditions
Pathogenic variants in the HAL gene cause histidinemia, a rare inherited condition usually detected on newborn screening. In many people it is mild and may cause no noticeable symptoms, though follow-up may look at development and learning over time. When lab results fit, finding a HAL gene variant linked to histidinemia can confirm the diagnosis.
A variant is not necessarily a diagnosis
Gene variants are a usual part of human biology, and they are common across the general population. Most variants do not have a direct effect on health and instead reflect natural human diversity. For many genes, carrying a variant tied to a condition suggests a possible association rather than a definite diagnosis, especially when several genes and environmental factors also play a role. In some situations, though, one well-characterized variant in a particular 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 health risks related to the HAL gene itself. For people with disease-causing changes in both copies of HAL, the main factor is the inherited gene change, while symptoms can vary from person to person.
Inheritance of HAL variants
HAL gene variants linked to histidinemia are inherited in an autosomal recessive pattern. This means a child usually inherits one altered copy of the HAL gene from each parent. If both parents are carriers, each pregnancy has a 25% chance of the child inheriting both variants, a 50% chance of being a carrier, and a 25% chance of inheriting neither variant. In practical terms, HAL gene inheritance often becomes clear only after family testing or when a child is diagnosed.
What does my HAL result mean for my family?
Changes in the HAL gene are linked to histidinemia, which usually runs in families in a recessive pattern. For family members, this often means parents can be healthy carriers, and brothers or sisters may also be affected or be carriers even if they feel well. Other relatives may also carry the gene change, especially on the same side of the family.
Genetic information
Genetic testing
How you find out about variants
To find out about variants in the HAL gene, HAL genetic testing usually uses a blood sample or cheek swab. A lab reads the HAL gene’s DNA code and looks for changes that may help explain symptoms or confirm a suspected inherited condition. Results may be reported as benign, uncertain, or linked to disease.
When should I consider getting a genetic test?
Genetic testing for the HAL gene may be considered if newborn screening or blood tests show unusually high histidine, or if this runs in your family. It can help confirm histidinemia, a condition where histidine builds up in the blood, and may clarify whether relatives also carry the same gene change.
A genetic result is only one part of your health story
A genetic finding can provide useful information, but how much it explains varies by the condition and the kind of variant involved. Over time, factors such as age, environment, lifestyle, and medical history also affect how the body works. For some conditions, especially those shaped by many genes, genetic information offers context rather than certainty and is best understood together with other aspects of care. In other situations, a genetic result can give a clear answer. In areas like medication response, genetic results 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. A treatment that works well for one person may work less well for another, or cause more side effects, because the body can absorb, break down, transport, or respond to drugs in different ways. These differences are common and can influence how strongly a medicine works or how sensitive someone is to it.
What is Pharmacogenetics?
The study of how genetic differences shape responses to medicines is known as pharmacogenetics. It examines relationships between genes and drugs to help explain why a treatment works differently from one person to another. For many medicines, genes can affect both how strongly a drug works and how the body processes it. This information can support more informed, individualized treatment decisions. You can read more about this topic in the LearnHub.
Drugs influenced by the HAL gene
When should I seek medical advice?
If you have questions about a medicine, side effects, or new symptoms after starting treatment, talk with your doctor or pharmacist; there is not yet a broadly confirmed role for this gene in guiding medication response.
History
The history of the HAL gene began with the study of histidinemia, a rare inherited condition first described in the 1960s through newborn screening and amino acid testing. At that time, doctors recognized a pattern of unusually high histidine levels in some infants, but the genetic cause was not yet clear. Inheritance patterns were noticed long before the gene was identified. Building on this early work, researchers linked histidinemia to changes in the HAL gene, which provided a clearer explanation for earlier biochemical findings. Over time, follow-up studies showed that many people with HAL-related histidinemia had milder outcomes than first expected. This shift helped refine how clinicians interpret positive screening results and genetic findings today.