ESR2 rs61748238: What Your Genotype Means
The rs61748238 single nucleotide polymorphism is a coding variant located within the ESR2 gene, which encodes the estrogen receptor beta (ERβ) protein. Research suggests an association between this variant and altered local endometrial estrogen responsiveness, potentially contributing to a predisposition toward deep infiltrating endometriosis. However, the current scientific evidence remains limited, and possessing the variant does not guarantee the development of the condition.
What each genotype means
Typical estrogen receptor profile
This is the most common genotype observed in the general population. Research into the ESR2 gene suggests that individuals with this profile do not carry the specific variant associated with altered estrogen signaling linked to endometriosis risk in some studies.
This is the major allele genotype and is found in the vast majority of individuals across all global populations.
Potential altered signaling risk
Carrying one copy of the T allele may be associated with variations in local endometrial estrogen signaling. While some research links this variant to a predisposition for deep infiltrating endometriosis, the evidence remains limited and may vary significantly based on individual genetic background.
This heterozygous genotype is observed at low frequencies, with higher prevalence noted in certain East Asian and South Asian populations compared to others.
Increased signaling variant profile
Individuals with this genotype carry two copies of the variant allele, which has been investigated for its potential role in dysregulated estrogen signaling within the endometrium. Because the evidence linking this specific variant to endometriosis is limited, this result should be interpreted with caution and discussed in the context of your overall health history.
This homozygous genotype is rare, occurring at a very low frequency in most populations, including those where the variant is more commonly identified.
Variant Architecture and Molecular Context
The single nucleotide polymorphism rs61748238 is located on chromosome 14 within the coding sequence of the ESR2 gene. Because it falls within a coding region, the variation can alter the amino acid sequence of the estrogen receptor beta (ERβ) protein. ERβ is a key nuclear hormone receptor that functions as a transcription factor, regulating gene expression in response to circulating and local estrogen levels. In healthy reproductive tissue, estrogen receptor alpha (ERα) and ERβ maintain a tight functional balance, with ERβ often acting as a check against excessive cellular proliferation. Molecular variations such as rs61748238 are hypothesized to influence the conformation, stability, or ligand-binding properties of ERβ, subtly shifting how target cells interpret hormonal cues in estrogen-sensitive tissues.
Biological Role of the ESR2 Gene in Endometrial Tissue
The ESR2 gene encodes estrogen receptor beta, an essential component of human reproductive physiology expressed across tissues including the ovaries, endometrium, and breast. In the endometrium, local estrogen production and signaling orchestrate the cyclical growth, differentiation, and shedding of the mucosal lining during the menstrual cycle. Estrogen receptor beta plays an immunomodulatory and anti-proliferative role, counterbalancing the potent mitogenic actions of estrogen receptor alpha. Dysregulation or altered functional characteristics of ERβ can lead to aberrant local hormonal responses, abnormal inflammatory cytokine secretion, and altered apoptotic signaling within endometrial cells. When these regulatory mechanisms are perturbed, endometrial tissue may exhibit enhanced cell survival and an increased potential to implant, persist, and invade ectopic sites outside the uterine cavity.
Evidence for Association with Endometriosis
Scientific investigations have explored whether variations in the ESR2 gene, including rs61748238, predispose individuals to gynecological conditions such as endometriosis. Preliminary association studies indicate that this coding variant may be linked to dysregulated local estrogen signaling, creating an environment favorable for the development of severe phenotypes, specifically deep infiltrating endometriosis. However, the scientific evidence supporting this association is currently categorized as limited. Endometriosis is a complex, multifactorial disorder influenced by a combination of multiple polygenic variants, hormonal pathways, and environmental factors. Studies to date have often been constrained by moderate sample sizes, and large-scale genome-wide association studies (GWAS) have demonstrated substantial genetic heterogeneity across diverse populations, meaning rs61748238 cannot be considered a deterministic or standalone diagnostic marker.
Population Frequency and Ancestral Patterns
The distribution of rs61748238 varies noticeably across global populations. Population genetics data indicate that the minor allele reaches an estimated frequency of approximately 4% to 8% (MAF ~0.04-0.08) in individuals of East Asian and South Asian ancestries. In contrast, the variant is observed at significantly lower frequencies or remains rare in European, African, and other ancestral groups. Because baseline allele frequencies fluctuate considerably between different biogeographic groups, genetic association signals discovered in one ancestral background cannot automatically be generalized to others without thorough replication. Ongoing large-scale genomic initiatives and diverse reference datasets continue to refine frequency benchmarks and clarify whether the statistical associations observed for this variant remain consistent across multi-ethnic populations.
Practical Implications and Clinical Perspective
Learning your genotype for rs61748238 provides educational insight into personal genomic variation, but it does not serve as a clinical diagnosis of endometriosis or any other medical condition. The presence of a risk-associated allele reflects a modest statistical shift in odds within surveyed populations, not an inevitability of disease. Similarly, carrying the reference genotype does not eliminate the risk of developing reproductive disorders. Individuals experiencing pelvic pain, severe dysmenorrhea, painful intercourse, or fertility concerns should not rely on direct-to-consumer genetic information to make diagnostic assumptions. Any evaluation, symptom assessment, or potential medical intervention—such as hormone therapy or surgical evaluation—should be directed by a qualified gynecologist or healthcare provider.
How common is this variant?
The minor allele of rs61748238 exhibits an estimated frequency of approximately 4% to 8% (MAF ~0.04-0.08) in East Asian and South Asian populations, while it is observed at much lower rates in other global ancestries.
Frequently asked questions
Does having the rs61748238 variant mean I will get endometriosis?
No, possessing this variant does not mean you will develop endometriosis. The variant is associated only with a small statistical variation in population risk rather than deterministic causation. Endometriosis is a complex disease driven by numerous interacting genetic and environmental factors.
Can a genetic test for rs61748238 replace a laparoscopy?
No, genetic testing cannot replace medical diagnostic procedures. Endometriosis, particularly deep infiltrating endometriosis, requires clinical evaluation, specialized pelvic imaging, or surgical visualization via laparoscopy for a definitive diagnosis. Genetic markers provide exploratory biological information, not diagnostic verification.
How does ESR2 influence reproductive health?
The ESR2 gene produces estrogen receptor beta, an essential nuclear receptor that helps manage how tissues respond to estrogen. In the uterus and ovaries, it regulates cell growth, differentiation, and inflammation. Subtle genetic variations in the gene can influence these regulatory pathways.
Why is the evidence for rs61748238 described as limited?
The scientific evidence is classified as limited because the association has primarily been evaluated in smaller candidate-gene studies rather than consistently replicated in massive, genome-wide studies across diverse populations. Further peer-reviewed research is required to validate the exact functional impact of this specific variant.
Sources & further reading
Educational information only, last refreshed 9/6/2026. Not medical advice — these associations describe population statistics, not individual predictions.
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Synonymous polymorphism in estrogen receptor beta that modulates transcriptional responsiveness to estrogens and correlates with ovulatory function.
ESR2 variant associated with age at natural menopause and estrogen signaling.
Coding variant in estrogen receptor beta (ESR2) associated with ovulatory dysfunction and endometriosis risk.