WNT4 rs12294104: What Your Genotype Means
The genetic variant rs12294104 is a single-nucleotide polymorphism located in a regulatory intergenic region near the WNT4 gene on chromosome 1. Genome-wide association studies have identified it as a common marker modestly associated with susceptibility to endometriosis, particularly severe peritoneal and ovarian subtypes, as well as epithelial ovarian cancer risk. Having this variant does not cause disease on its own, but rather contributes a small statistical influence within a complex genetic and environmental landscape.
What each genotype means
Typical risk profile
You carry two copies of the C allele at this regulatory locus near WNT4, which is the baseline genotype not linked to increased risk for severe endometriosis in published genome-wide association studies. Research shows standard estrogen-mediated regulation of WNT4 expression for this genotype. This variant is a statistical marker and does not prevent or diagnose any gynecologic condition.
Carried by approximately 45% to 50% of individuals of European ancestry and roughly 30% to 35% of individuals of East Asian ancestry.
Moderately increased risk
You carry one copy of the T risk allele near the WNT4 gene, which has been associated in genome-wide association studies with a modest increase in the relative risk of developing peritoneal and ovarian endometriosis as well as epithelial ovarian cancer. This variant is believed to lie in a regulatory region influencing WNT4 expression in endometrial tissues. Having this genotype is a statistical association and does not mean you have or will develop these conditions.
Carried by roughly 40% to 45% of European populations and nearly 50% of East Asian populations.
Elevated risk profile
You carry two copies of the T risk allele at this WNT4-associated locus, which confers the highest relative statistical association with severe endometriosis and ovarian cancer within this variant's spectrum. Current research indicates that the risk allele may alter transcriptional regulation and estrogen responsiveness of WNT4 in reproductive tissues. Genetic susceptibility is only one component of complex traits, and carrying this genotype does not constitute a clinical diagnosis.
Found in approximately 8% to 10% of individuals of European descent and about 15% to 20% of East Asian populations.
Genomic Location and Variant Classification
The single-nucleotide polymorphism rs12294104 resides on chromosome 1 at band 1p36.12, positioned in an intergenic non-coding region upstream of the WNT4 gene. Because it does not alter the amino acid sequence of a protein directly, it is classified as a non-coding regulatory variant. Variants in this genomic segment typically exert their influence by modulating transcriptional activity, altering chromatin accessibility, or affecting binding affinities for transcription factors that regulate nearby genes. The alleles at this position consist of adenine (A) and guanine (G). Across genome-wide association studies, researchers evaluate these base changes to determine whether a specific allele correlates with increased or decreased susceptibility to complex gynecologic conditions, functioning as a marker tag for surrounding functional variations inherited together.
The Biological Function of WNT4
The WNT4 gene encodes a member of the evolutionary conserved Wnt family of secreted signaling glycoproteins. Wnt family proteins act as local signaling ligands that control critical developmental programs, cell fate determination, cell proliferation, and tissue architecture. In female reproductive biology, WNT4 is essential for the embryological development of the Müllerian ducts, which give rise to the fallopian tubes, uterus, cervix, and upper vagina, as well as proper ovarian differentiation. Later in life, WNT4 signaling remains active in gynecologic tissues, participating in normal endometrial decidualization during the menstrual cycle, blastocyst implantation, and tissue remodeling. Alterations in the transcriptional regulation or expression level of WNT4 have been implicated in aberrant tissue proliferation, ectopic endometrial growth, and epithelial ovarian neoplasia.
Clinical Evidence and Association Strengths
Multiple genome-wide association and fine-mapping studies have evaluated rs12294104 alongside other 1p36.12 polymorphisms to investigate hereditary predisposition to endometriosis and epithelial ovarian malignancies. The current scientific consensus categorizes the evidence strength as limited to moderate. While statistically significant population-level correlations have been recorded between the risk-associated allele and advanced-stage disease—specifically peritoneal lesions and ovarian endometriomas—the effect size of this individual variant is modest, usually conveying an odds ratio close to 1.15 to 1.30 per copy. Carrying the variant is neither necessary nor sufficient to develop endometriosis or ovarian tumors; it represents a probabilistic predisposition influenced by dozens of other polygenic loci, hormonal dynamics, and environmental cofactors rather than a deterministic clinical diagnosis.
Population Distribution and Ancestry Trends
The alleles of rs12294104 are common throughout global human populations, but their frequencies vary noticeably according to genetic ancestry. In populations of European descent, the minor allele frequency is approximately 0.30, with roughly 45 to 50 percent of individuals carrying at least one copy. In East Asian reference cohorts, the minor allele frequency is notably higher, reaching approximately 0.42. Because the polymorphism is widespread rather than rare, it does not represent a pathogenic mutation in the clinical genetics sense. Instead, it reflects common human evolutionary variation. Differences in background linkage disequilibrium across distinct ancestral groups also mean that the biological proxy value of this variant can vary between populations.
Navigating Results: What This Information Means for You
Understanding your rs12294104 genotype can offer educational insights into your personal genetic architecture, but it cannot be used as a standalone diagnostic tool or screening test. A high-risk genotype does not mean you will develop endometriosis or ovarian cancer, just as a lower-risk genotype cannot guarantee protection. Clinical diagnosis of endometriosis relies on symptom history, pelvic imaging, and definitive laparoscopic evaluation performed by a qualified medical provider. Readers experiencing severe pelvic pain, dysmenorrhea, painful intercourse, or fertility concerns should consult a gynecologist or healthcare clinician. Genetic risk markers for complex polygenic conditions should never prompt self-treatment or changes to medical care without professional guidance.
How common is this variant?
The minor allele occurs at an estimated frequency of approximately 0.30 in European ancestry populations and reaches around 0.42 in East Asian populations.
Frequently asked questions
Does having the rs12294104 risk genotype mean I will get endometriosis?
No, having the risk genotype does not mean you will develop endometriosis. The rs12294104 variant is a common marker that only slightly adjusts relative odds within complex polygenic traits. Many individuals with the variant never develop the condition, while others without it do.
Can this genetic test replace a medical diagnosis for pelvic pain?
No, direct-to-consumer genetic findings cannot diagnose or rule out endometriosis or any gynecologic disorder. Clinical diagnosis requires evaluation by a medical provider, often utilizing pelvic examinations, ultrasound, MRI, or minimally invasive laparoscopy.
Why is the WNT4 gene associated with gynecologic conditions?
WNT4 plays an essential biological role in embryonic female reproductive tract formation and post-pubertal uterine tissue remodeling. Regulatory changes near this gene can alter signaling pathways involved in tissue growth, cellular migration, and response to reproductive hormones.
Does rs12294104 affect how I respond to medications?
Currently, rs12294104 is not recognized by pharmacogenomic guidelines as altering medication metabolism or efficacy. Any questions regarding hormonal therapies, pain management medications, or dosage adjustments should always be discussed with a treating clinician or pharmacist.
Sources & further reading
Educational information only, last refreshed 9/10/2026. Not medical advice — these associations describe population statistics, not individual predictions.
Curious what your genotype is for rs12294104?
Upload a raw DNA file from 23andMe, AncestryDNA, MyHeritage, or FamilyTreeDNA and see this variant — plus thousands more — interpreted in your full report.
Get my report — $29Related variants in WNT4
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.
Missense mutations in WNT4 are associated with atypical Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome and disorders of sex 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.