WNT4 rs144365558: Understanding This Rare Genetic Variant
The rs144365558 variant is a rare genetic change located within the WNT4 gene. It has been studied in the context of atypical Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome and certain disorders of sex development.
What each genotype means
Typical risk profile
You carry two copies of the common reference allele at this position in the WNT4 gene. This genotype is the standard baseline found across general populations and is not associated with Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome or related hyperandrogenism.
Carried by more than 99.9% of individuals across all major global populations.
Atypical MRKH risk variant
You carry one copy of the extremely rare missense variant in the WNT4 gene. Scientific case literature links heterozygous loss-of-function variants at this locus with atypical Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome accompanied by clinical hyperandrogenism, though overall population evidence remains limited and variable in presentation.
Extremely rare; observed only as an isolated singleton in gnomAD and reported in very few clinical cases worldwide.
Extremely rare homozygous variant
You carry two copies of this rare WNT4 missense variant. Homozygous occurrences are exceptionally rare or unobserved in general population datasets, and severe disruption of WNT4 signaling pathways could lead to significant reproductive and endocrine developmental differences.
Virtually absent in general population databases, with an estimated frequency well below 0.001%.
What is rs144365558?
The identifier rs144365558 refers to a specific single nucleotide polymorphism (SNP) located within the WNT4 gene. In genetics, a SNP represents a variation at a single position in the DNA sequence. This particular variant is classified as a missense mutation, meaning the change in the DNA code results in a different amino acid being incorporated into the protein produced by the gene. Because the WNT4 gene is critical for complex developmental processes, researchers monitor such variants to understand how they might alter protein function. This variant is cataloged in public databases as a rare genetic feature, and its presence is typically investigated when individuals present with specific clinical features related to reproductive or endocrine development.
The Role of the WNT4 Gene
The WNT4 gene provides instructions for making a protein that belongs to the Wnt family of signaling molecules. These proteins are essential for cell-to-cell communication during embryonic development. In humans, WNT4 plays a specialized role in the formation of the female reproductive system, specifically in the development of the Müllerian ducts, which eventually form the uterus and fallopian tubes. Furthermore, WNT4 is involved in ovarian development and the regulation of androgen biosynthesis. By promoting female-specific development and suppressing pathways that lead to testicular formation, WNT4 acts as a key regulator of sexual differentiation. Disruptions in this gene can interfere with these delicate biological processes, potentially leading to atypical development.
Research and Clinical Associations
Research into WNT4 has linked certain variants to Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome, a condition characterized by the underdevelopment or absence of the uterus and vagina in individuals with a 46,XX karyotype. Some cases of MRKH associated with WNT4 mutations also present with clinical signs of hyperandrogenism, or elevated levels of male-type hormones. While WNT4 is considered a candidate gene for these conditions, the evidence strength for any single variant, including rs144365558, is often described as limited. This means that while the gene's function is well-established, the specific impact of this individual variant requires further clinical validation. It is important to note that genetic associations are complex, and the presence of a variant does not automatically guarantee a specific clinical outcome.
Population Frequency and Interpretation
The rs144365558 variant is documented as being very rare across global populations. In human genetics, rare variants are often identified through large-scale sequencing projects that compare the genomes of thousands of individuals. Because this variant is not common, it is difficult to establish broad statistical trends or population-specific risks. When a variant is this rare, researchers often rely on case studies or small cohorts to understand its potential effects. For the general reader, it is essential to understand that having a rare variant does not constitute a medical diagnosis. Genetic information should always be interpreted by a qualified healthcare professional, such as a genetic counselor or a medical geneticist, who can place the finding in the context of an individual's personal and family health history.
Navigating Genetic Information
If you have received information about this variant, it is important to approach it with caution. Genetic testing results can be complex, and the clinical significance of rare variants is frequently updated as more research becomes available. You cannot use this information to self-diagnose or predict health outcomes on your own. If you are concerned about reproductive health or developmental conditions, the most appropriate step is to consult with a physician or a specialist. They can help determine if further testing is necessary and explain what the results mean for your specific situation. Avoid making any medical decisions based solely on online reports or database entries, as these are intended for educational and research purposes rather than clinical guidance.
How common is this variant?
The rs144365558 variant is classified as very rare in public genetic databases, with no significant frequency observed across major ancestral populations.
Frequently asked questions
What is MRKH syndrome?
Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome is a condition that affects the female reproductive system, typically causing the uterus and vagina to be underdeveloped or absent. It is often identified during adolescence when a young person does not begin menstruation.
Does having a WNT4 variant mean I have a disorder?
No, identifying a genetic variant does not equate to a medical diagnosis. Many genetic variations are benign, and the clinical impact of rare variants like rs144365558 is often not fully understood without clinical evaluation.
Can I use this information to change my medication?
No. You should never change or stop any medication based on genetic information without first consulting your doctor or pharmacist. They are the only ones qualified to manage your treatment plan.
Where can I get professional advice about this variant?
You should speak with a board-certified genetic counselor or a medical geneticist. They can review your specific test results and explain how they relate to your health.
Sources & further reading
Educational information only, last refreshed 10/8/2026. Not medical advice — these associations describe population statistics, not individual predictions.
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This regulatory variant in the WNT4 locus is a well-established genetic marker associated with susceptibility to endometriosis, though its effect size and significance vary across ethnic populations.
This variant in the WNT4 locus is significantly associated with the risk of endometriosis and influences reproductive tract development.
Variant associated with variation in bone mineral density, timing of menarche, and reproductive span traits.
Common regulatory variant near WNT4 consistently associated with endometriosis risk and female reproductive tract morphology.
Non-coding regulatory variant in the WNT4 region associated with pelvic endometriosis, uterine fibroid risk, and Müllerian duct development.
Regulatory variant near WNT4 associated with risk of endometriosis and ovarian cancer, influencing reproductive hormone regulation.