The TMPRSS15 gene helps start protein digestion in the small intestine by turning on other digestive enzymes after food leaves the stomach. This gene helps your body break down protein from foods such as milk, eggs, beans, and meat so nutrients can be absorbed. If the TMPRSS15 gene is not working well, some babies and children can develop ongoing diarrhea, poor weight gain, swelling from low blood protein, and slower growth because protein is not digested properly.
What is a gene?
Genes are stretches of DNA that carry instructions your cells use to make molecules or guide activities in the body. Some genes provide the information needed to produce proteins, which do much of the cell’s work. Others mainly regulate when certain processes take place, where they occur, and how strongly they operate. Together, genes affect how the body develops and works, and they can influence how you respond to food, stress, and medications. To explore this topic in greater detail, you can find more in the LearnHub.
Overview
TMPRSS15Gene function
What if the gene works
The TMPRSS15 gene helps your small intestine start protein digestion. Its protein turns on a key enzyme for protein digestion, which then activates other digestive enzymes from the pancreas.
Risk
What if the gene does not work
Variants in the TMPRSS15 gene can reduce or block activation of digestive enzymes, causing congenital enteropeptidase deficiency. Many babies develop diarrhea, poor growth, and low blood protein, while milder variants may lead to later or less severe symptoms.
Treatment
What does that mean for your treatment
Pathogenic variants in the TMPRSS15 gene can make treatment center on pancreatic enzyme replacement, which supplies active digestive enzymes and can bypass the missing step. Protein hydrolysate or amino acid based feeding may also help support growth, especially in infancy.
Conditions associated with TMPRSS15
Gene function
What if the gene works
TMPRSS15 helps your small intestine start digesting protein from food. It provides the instructions for enteropeptidase, an enzyme attached to the surface of the upper small intestine. After a meal, this enzyme switches on key digestive enzymes so protein digestion in the small intestine can begin in an orderly way.
The TMPRSS15 gene makes a gut surface enzyme that turns trypsinogen, an inactive digestive helper, into trypsin. This switch is one of the first steps that starts protein digestion after food enters the small intestine.
Active trypsin then helps switch on other pancreatic enzymes. This creates a coordinated chain of digestion that breaks food proteins into smaller pieces your body can absorb.
TMPRSS15 works at the brush border (the tiny projections on the gut lining) of the upper small intestine. Keeping this activation step at the intestinal surface helps digestion begin where food and pancreatic juices meet.
What is a variant?
A genetic variant is a small difference in the DNA sequence within a gene. These changes are common and help shape normal human diversity, including differences in appearance, metabolism, and how the body responds to environmental influences. Many variants do not have any noticeable effect and are simply part of natural genetic variation. In some cases, though, a variant can change how a gene functions more substantially and may contribute to or cause a genetic condition.
Genetic variants
What if the gene does not work
Variants in the TMPRSS15 gene can leave the protein shortened, misshapen, poorly placed on the surface of small intestine cells, or less able to switch on digestive enzymes. This pattern shows how TMPRSS15 gene variants affect protein function: milder changes may partly reduce activity, while more severe variants can stop the protein from being made or working at all. That range often shapes enteropeptidase deficiency, with more disruptive variants tending to cause earlier and more noticeable feeding and growth problems.
How variants are linked to conditions
Pathogenic variants in the TMPRSS15 gene cause enteropeptidase deficiency, a rare inherited condition that often starts in infancy with ongoing diarrhea, poor weight gain, and low blood protein levels. TMPRSS15 gene variants are linked to enteropeptidase deficiency rather than to a broad range of well confirmed conditions. When pathogenic variants are found in both copies of the gene, the result can confirm the diagnosis.
A variant is not necessarily a diagnosis
Variants in genes are a usual feature of human biology and are widely found across the population. Most do not directly affect health and instead reflect normal human variation. For many genes, having a variant associated with a condition points to a possible link, not a certain diagnosis, particularly when several genes and environmental influences also play a role. In other situations, though, one well-characterized variant in a particular gene may be enough to confirm a diagnosis.
Are there things that can increase or change my risk?
For TMPRSS15, risk is mainly tied to the gene change itself, especially when a child inherits a nonworking copy from both parents. There is not broadly confirmed evidence that diet, exercise, or other everyday factors meaningfully change the chance of having this condition, though early care can help manage symptoms if it is present.
Inheritance of TMPRSS15 variants
TMPRSS15-related conditions are inherited in an autosomal recessive pattern. This means a child needs to inherit one TMPRSS15 variant from each parent to be affected, while parents who carry one variant usually do not have the condition themselves. When both parents carry a variant in the TMPRSS15 gene, each pregnancy has a 25% chance of an affected child, a 50% chance of a child who is a carrier, and a 25% chance of a child with neither variant. This is the main pattern described for how TMPRSS15 gene variants are inherited.
What does my TMPRSS15 result mean for my family?
Changes in the TMPRSS15 gene are linked to a rare inherited condition that usually runs in families in a recessive pattern. For family members, this mainly means siblings could also have the condition or be carriers, and parents are often carriers even if they have never had symptoms. 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 look for inherited changes linked to trouble digesting protein from birth, TMPRSS15 genetic testing uses a blood or saliva sample to read the TMPRSS15 gene. Results may find two pathogenic (disease-causing) variants that support a diagnosis of enteropeptidase deficiency, or they may show no relevant variant; some labs also check for missing or extra pieces of DNA.
When should I consider getting a genetic test?
Testing for changes in the TMPRSS15 gene may be worth considering when a baby or young child has ongoing diarrhea, poor growth, and low blood protein levels, especially if doctors suspect a rare problem with digesting protein. It can also be helpful when this condition runs in the family.
A genetic result is only one part of your health story
A genetic finding can provide useful insight, although how much it explains depends on the condition and the kind of variant involved. Lifestyle, environment, age, and medical history also shape how the body functions over time. For some conditions, especially those influenced 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 may 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. Small differences in DNA can change how the body breaks down a drug, moves it through the body, or responds to it at its target. Because of this, the same medication may work better for one person than another, or one person may be more sensitive to side effects. These differences are common and are one part of why treatment response can vary from person to person.
What is Pharmacogenetics?
Pharmacogenetics examines how genetic differences affect the way people respond to medications. By looking at connections between genes and drugs, it helps explain why treatments can work differently from one person to another. For many medicines, genes influence both how strongly a drug works and how the body processes it. This information can help support treatment decisions that are more informed and more individualized. More detailed information on this topic is available in the LearnHub.
Drugs influenced by the TMPRSS15 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, new symptoms after starting a treatment, or whether a medicine is a good fit are best discussed with your doctor.
History
The history of the TMPRSS15 gene begins with the enzyme it encodes, historically called enterokinase and now more often called enteropeptidase. In the late 1800s, digestive researchers recognized this enzyme as an important clue in how the intestine activates pancreatic enzymes. Initially understood only through visible traits, later recognized as tied to a specific gene, it became part of a broader shift from physiology to molecular genetics. By the late 20th century, scientists had linked inherited enteropeptidase deficiency to changes in the TMPRSS15 gene. This helped explain why some infants with the condition had poor growth, low protein absorption, and ongoing diarrhea. From these first observations, research expanded steadily, placing the TMPRSS15 gene within a larger family of digestive enzyme genes.