The RSPO1 gene helps control signals that guide early body development and support healthy skin, hair follicles, and the lining of the gut. If it does not work properly, a person may be born with differences in sex development and may develop thick skin on the palms and soles, sometimes with a higher chance of certain skin cancers. This gene plays an important role in how tissues grow and repair themselves.
What is a gene?
Genes are stretches of DNA that carry instructions your cells use to make molecules or regulate activities in the body. Some provide the directions for producing proteins, which do much of the cell’s work. Others mainly guide when certain processes happen, where they happen, and how active they are. Taken together, genes affect how your body develops and functions, and they can also influence how you respond to food, stress, or medications. For a deeper look at this topic, you can find more in the LearnHub.
Overview
RSPO1Gene function
What if the gene works
The RSPO1 gene helps control cell growth signals, especially Wnt signaling, a system that guides tissue development and repair. It supports normal development of the skin, hair follicles, gut lining, and ovaries.
Risk
What if the gene does not work
Variants in the RSPO1 gene can cause thick skin on the palms and soles, raise squamous cell skin cancer risk, and in some people with XX chromosomes affect sex development; milder or more severe variants can change which features appear.
Treatment
What does that mean for your treatment
No RSPO1-specific treatment or drug choice is currently established for people with a pathogenic variant in the RSPO1 gene. Care is guided by a person’s clinical needs rather than by RSPO1-directed medicines.
Conditions associated with RSPO1
Gene function
What if the gene works
Your cells use the RSPO1 gene to strengthen messages that tell tissues when to grow, renew, and organize themselves. It makes a signaling protein that works outside cells and fine tunes the Wnt pathway, a communication system that helps guide normal development and tissue upkeep. This helps explain how the RSPO1 gene supports tissue growth and renewal in everyday cell life.
The RSPO1 gene boosts Wnt signaling, a key system cells use to share growth and development instructions. Its protein helps these messages stay available at the cell surface so cells can respond in a controlled way.
RSPO1 helps stem cells keep renewing tissues that wear down and replace themselves over time. This is especially important in lining tissues, where steady repair and regrowth help maintain normal structure.
During normal development, RSPO1 helps cells coordinate where they should grow and what roles they should take on. This supports organized tissue formation rather than scattered or poorly timed growth.
What is a variant?
A genetic variant is a small difference in the DNA sequence of a gene. These changes are common and help shape normal human diversity, such as differences in appearance, metabolism, or how the body responds to environmental influences. Many variants have no noticeable effect and are simply part of natural genetic variation. In some cases, though, a variant can more substantially change how a gene functions and may contribute to or cause a genetic condition.
Genetic variants
What if the gene does not work
Variants in the RSPO1 gene often reduce how much working RSPO1 protein a cell can make or release, which weakens WNT signaling, a key cell communication pathway. Some changes only partly lower activity, while more severe loss-of-function variants can leave little or no active protein. This range helps show how RSPO1 gene variants affect protein function and why skin findings or differences in sex development may vary in timing and extent.
How variants are linked to conditions
When both copies of the RSPO1 gene carry a pathogenic variant, this can cause a rare inherited condition with thickened skin on the palms and soles and a higher chance of squamous cell skin cancer. In some people with 46,XX chromosomes, variants in the RSPO1 gene are also linked to differences in sex development, including testicular or ovotesticular development.
A variant is not necessarily a diagnosis
Genetic variants are a routine part of human biology and are widely seen across the general population. Most do not directly affect health and simply reflect normal human variation. For many genes, having a variant associated with a condition points to a possible link rather than a confirmed diagnosis, particularly when several genes and environmental influences play a role. In some situations, though, one well-characterized variant in a specific gene is enough to confirm a diagnosis.
Are there things that can increase or change my risk?
For RSPO1, risk is mainly shaped by inheritance: it is higher when both biological parents carry a changed RSPO1 gene, which can be more likely in some families and when close relatives have children together. There is not enough evidence that diet, exercise, or other everyday habits change the chance of having an RSPO1-related condition.
Inheritance of RSPO1 variants
RSPO1-related conditions are inherited in an autosomal recessive pattern. This means a person usually inherits one altered copy of the RSPO1 gene from each parent, and both parents are typically healthy carriers. For families wanting to understand how RSPO1 variants are inherited, two carrier parents have a 25% chance with each pregnancy of having a child with an RSPO1-related condition, a 50% chance of having a carrier child, and a 25% chance of having a child who did not inherit either altered copy. These chances are the same for boys and girls.
What does my RSPO1 result mean for my family?
Changes in the RSPO1 gene are most often linked to recessive conditions, so family members may be healthy carriers without knowing it. Brothers and sisters could have the same condition or could also be carriers, and relatives planning children may also want to know whether the variant runs in the family. The exact meaning for relatives depends on the specific RSPO1 result and the condition linked to it.
Genetic information
Genetic testing
How you find out about variants
To find out whether you carry a variant, genetic testing of the RSPO1 gene uses DNA from blood, saliva, or a cheek swab. This kind of test for variants in the RSPO1 gene reads the gene's sequence and compares it with a reference sequence to identify changes a lab can classify.
When should I consider getting a genetic test?
Genetic testing for the RSPO1 gene may be worth discussing if a child is born with differences in sex development, especially when chromosome results and physical sex do not match in the usual way. It can also help explain inherited thick, rough skin on the palms and soles, particularly when squamous cell skin cancer runs in the family.
A genetic result is only one part of your health story
A genetic result can be very informative, but what it tells you varies based on the condition and the kind of variant involved. How your body works over time is also influenced by many other factors, including lifestyle, environment, age, and medical history. For some conditions, especially those shaped by many genes, genetic information provides context rather than certainty and is most useful when viewed alongside other parts of care. In other situations, a genetic result may offer a clear answer. In areas like medication response, these results can also help put individual experiences into context.
Pharmacogenetics
How variants shape your response to medicine
Genetic variation can affect how your body handles certain medicines, so the same treatment may work differently from one person to another. Some people break down a drug more slowly or more quickly, while others are more or less sensitive to its effects. These common differences can influence how well a medicine works or the chance of side effects. Medication response is also shaped by other factors, including age, liver and kidney function, and other medicines you take.
What is Pharmacogenetics?
Pharmacogenetics focuses on how genetic differences affect the way people respond to medications. It examines links between genes and drugs to help explain why the same treatment can work differently from one person to another. For many medicines, genes can influence both how strongly a drug works and how the body processes it. This information can support treatment decisions that are more informed and more individualized. More on this topic is available in the LearnHub.
Drugs influenced by the RSPO1 gene
When should I seek medical advice?
There is not yet a broadly confirmed role for this gene in guiding medication choice or dose, so general questions about side effects, treatment response, or other health concerns are best discussed with your doctor.
History
The RSPO1 gene entered the medical literature in the early 2000s, when researchers identified it as part of the newly described R-spondin family. Interest grew further when studies connected changes in the RSPO1 gene with inherited differences in sex development and certain skin findings, helping clarify a rare but important clinical pattern. Building on this early work, scientists recognized that the gene could also be relevant to some skin cancers in affected families. These reports made the RSPO1 gene notable in both genetics and dermatology. Over time, descriptions became more precise as genetic testing allowed doctors to link specific RSPO1 variants with a wider range of features in different people.