Your cells use the PSENEN gene to help run a protein-cutting system that supports cell signaling, especially pathways that guide skin and hair follicle growth. If the gene does not work properly, these signals can become disrupted. People with harmful variants may develop hidradenitis suppurativa, with repeated painful lumps and drainage in areas such as the armpits or groin, and some also have changes in skin pigmentation.
What is a gene?
A gene is a stretch of DNA that carries instructions your cells use to make molecules or regulate activities in the body. Some genes provide the directions for producing proteins, which are the functional parts of cells. Others are mainly involved in controlling when certain activities happen, where they happen, and how active they are. Taken together, genes affect how the body grows and works, and they can influence how you respond to food, stress, or medications. For a deeper look at this topic, more information is available in the LearnHub.
Overview
PSENENGene function
What if the gene works
The PSENEN gene helps form gamma-secretase, a protein team that trims certain proteins so cells can communicate. This supports normal development and upkeep of skin, hair follicles, and other tissues.
Risk
What if the gene does not work
PSENEN gene changes are linked to hidradenitis suppurativa, with recurring painful skin lumps and scarring, and sometimes to Dowling-Degos disease, which causes darker skin spots. Milder or more severe variants can affect when signs begin and how extensive they are.
Treatment
What does that mean for your treatment
No treatment or management approach specific to the PSENEN gene is currently established in clinical guidelines. Pathogenic variants in the PSENEN gene are being studied through the cell signaling pathways involved in skin inflammation and some cancers, but this has not yet led to established drug choices based on this gene.
Conditions associated with PSENEN
Gene function
What if the gene works
Cells use the PSENEN gene to process selected proteins that sit in the cell membrane. Its protein, called PEN-2, is part of gamma-secretase (a protein group that cuts certain membrane proteins). A key part of PSENEN gene function is helping cells pass signals and keep routine growth and renewal on track.
PSENEN helps assemble and steady the gamma-secretase complex. This lets the protein group stay active and ready to process selected membrane proteins.
As part of gamma-secretase, it helps cut certain proteins within the cell membrane after an earlier trimming step. This controlled cutting releases small pieces that cells can use for signaling.
This processing is especially important for Notch, a major cell communication system. When that signal is released at the right time, cells can coordinate growth, timing, and normal maturation.
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, 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, 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
How variants in the PSENEN gene affect protein function depends on the change: some leave partial activity, while others prevent PEN-2 from being made or from joining the protein cutting complex in the cell membrane. This can destabilize the whole complex and reduce trimming of proteins on the cell surface that cells use to send signals.
How variants are linked to conditions
Among the conditions linked to PSENEN gene variants, hidradenitis suppurativa is the best established. Pathogenic variants in the PSENEN gene can cause a familial form of this long-term skin condition, which often brings painful boils, tunnels under the skin, and scarring in areas such as the armpits or groin. Some variants are also linked to Dowling-Degos disease, a skin condition with a net-like pattern of darker spots, sometimes occurring alongside hidradenitis suppurativa.
A variant is not necessarily a diagnosis
Genetic variants are common across the general population and are a normal feature of human biology. Most do not directly affect health and simply reflect natural variation among people. For many genes, having a variant associated with a condition points to a possible link rather than a certain diagnosis, particularly when several genes and environmental influences 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?
For people with a harmful PSENEN variant, the gene change itself is a major reason for risk, especially for hidradenitis suppurativa, a long-term skin condition with painful lumps and draining areas. Smoking and carrying extra body weight are linked with a higher chance of symptoms and with more severe flares. Family history also matters, since these variants can run in families.
Inheritance of PSENEN variants
PSENEN gene variants linked to inherited skin conditions are usually passed down in an autosomal dominant pattern. This means a person with a disease causing variant in one of their two PSENEN gene copies can pass it to a child, and each pregnancy carries a 50% chance of inheriting that variant. In practice, how PSENEN gene variants are inherited is often seen across multiple generations, with affected mothers or fathers able to pass the variant to sons or daughters equally.
What does my PSENEN result mean for my family?
For PSENEN, the best-known family pattern is dominant, which means a result linked to a PSENEN-related condition can also matter for close relatives such as parents, brothers, sisters, and children. Each child of someone who carries a disease-causing PSENEN variant has a 1 in 2, or 50%, chance of inheriting it. In some families, relatives who carry the same variant may have similar skin problems, while others may be affected more mildly.
Genetic information
Genetic testing
How you find out about variants
To find out whether you carry a change in the PSENEN gene, clinicians use genetic testing for PSENEN variants on blood, saliva, or a cheek swab. This test reads the gene’s DNA code and looks for variants that may help confirm a suspected inherited skin condition or clarify whether a known family variant is present.
When should I consider getting a genetic test?
Testing may be worth discussing if you or close relatives have repeated painful lumps, draining sores, or scarring in skin folds such as the armpits or groin, especially when this starts young or runs in the family. A PSENEN test can sometimes help confirm an inherited form of hidradenitis suppurativa.
A genetic result is only one part of your health story
A genetic result can provide valuable insight, but how much it reveals depends on the condition and the kind of variant involved. Over time, many factors, including lifestyle, environment, age, and medical history, also influence how the body functions. For some conditions, especially those shaped by many genes, genetic information provides context rather than certainty and is best considered alongside 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 people respond to medicines. Small differences in genes can change how the body breaks down a drug, moves it through the body, or reacts to it at its target. This helps explain why the same medication works well for one person, seems weaker for another, or causes more side effects in someone else.
What is Pharmacogenetics?
Pharmacogenetics examines how genetic differences can affect a person’s response to medication. It studies 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 can influence how strongly a drug works or how the body handles it. This information can support more informed and more individualized treatment decisions. To explore this subject in greater detail, you can learn more in the LearnHub.
Drugs influenced by the PSENEN gene
When should I seek medical advice?
There is not yet a broadly confirmed role for this gene in guiding how medicines are chosen or how well they work, so questions about symptoms, treatment options, or side effects are best discussed with your doctor or pharmacist.
History
PSENEN entered the research literature in the early 2000s during work on the γ secretase complex, a protein group already drawing intense interest in Alzheimer’s disease research. Building on this early work, scientists identified PSENEN as the gene for PEN-2, a small but essential part of that complex. This helped clarify how several γ secretase components fit together and matured as a working unit. A few years later, inherited variants in the PSENEN gene were linked to rare family cases of hidradenitis suppurativa, also called acne inversa. Researchers then connected some PSENEN variants with Dowling-Degos disease, expanding the gene’s place in dermatology. Over time, PSENEN became recognized not only in basic cell biology but also in the study of inherited skin conditions.