LHCGR rs2292076: Receptor Function & Fertility Genetics
The rs2292076 polymorphism is a missense variant (N291S) located in the LHCGR gene, which encodes the receptor that responds to luteinizing hormone and human chorionic gonadotropin. Research suggests this change subtly alters downstream signaling efficiency and sensitivity to hormonal stimulation during assisted reproductive technologies such as IVF. Because the overall scientific evidence remains limited and heterogeneous, rs2292076 serves as a research trait rather than a standalone clinical diagnostic tool.
What each genotype means
Typical receptor signaling
This genotype represents the most common version of the LHCGR gene at this position. Research suggests this version is associated with standard receptor sensitivity to luteinizing hormone and human chorionic gonadotropin during reproductive processes. Please consult with a fertility specialist or endocrinologist if you have questions regarding how your genetic profile may influence responses to hormonal stimulation protocols.
This is the most common genotype in many populations, though frequencies vary significantly by ancestry.
Varied receptor sensitivity
This genotype includes one copy of the N291S variant, which has been studied for its potential to influence the signaling efficiency of the luteinizing hormone receptor. Some studies suggest this variant may alter the receptor's sensitivity to exogenous gonadotropins used in fertility treatments, though the clinical impact remains a subject of ongoing research. Discuss your specific reproductive health goals and any planned stimulation protocols with your clinician.
The G allele is found in approximately 30-40% of European populations, making this heterozygous genotype relatively common.
Altered receptor signaling
This genotype consists of two copies of the N291S variant, which may influence how your cells respond to luteinizing hormone and human chorionic gonadotropin. Research into this variant suggests it may affect the efficiency of receptor signaling, which can be relevant in the context of ovarian stimulation protocols. Because the clinical significance of this variant is still being established, please discuss the implications of this result with a fertility specialist or reproductive endocrinologist.
This genotype is less common than the heterozygous state, occurring in a smaller subset of individuals of European ancestry.
Genetic Identity and Molecular Nature of rs2292076
The single nucleotide polymorphism rs2292076 represents an A-to-G transition located within exon 10 of the luteinizing hormone/choriogonadotropin receptor (LHCGR) gene on chromosome 2p16.3. At the protein level, this nucleotide substitution alters codon 291, replacing an asparagine residue with a serine (commonly designated as N291S or p.Asn291Ser; historically labeled N312S when counting the full signal peptide). The alteration sits in the extracellular domain of the receptor, a region crucial for high-affinity ligand binding and initiating the intracellular signaling cascade. Because the substitution preserves overall receptor assembly and cell-surface delivery, it does not ablate receptor function entirely. Instead, it creates subtle differences in how the receptor couples to intracellular G proteins, modestly modulating adenylyl cyclase activation and secondary messenger signaling following endocrine stimulation.
Biological Role of the LHCGR Gene
The LHCGR gene provides instructions for constructing a transmembrane G-protein coupled receptor essential for mammalian reproduction. In females, LHCGR is expressed predominantly in ovarian theca, granulosa, and luteal cells, where it mediates the physiological effects of luteinizing hormone (LH) and human chorionic gonadotropin (hCG). These signals drive steroidogenesis, promote follicular maturation, trigger ovulation, and sustain the corpus luteum during early pregnancy. In males, the receptor operates within testicular Leydig cells to stimulate testosterone biosynthesis necessary for fetal sexual differentiation and adult spermatogenesis. Rare loss-of-function variants in LHCGR can lead to severe endocrine conditions like Leydig cell hypoplasia and amenorrhea, whereas common polymorphisms like rs2292076 modulate receptor sensitivity within normal physiological ranges.
Association with Ovarian Stimulation and Reproductive Outcomes
In reproductive medicine, rs2292076 has been evaluated as a pharmacogenetic biomarker for ovarian response during in vitro fertilization (IVF) cycles. Studies have observed that individuals carrying the G (Ser) allele often demonstrate altered sensitivity to exogenous gonadotropins, occasionally requiring modified dosages of recombinant LH or FSH to achieve optimal follicular development. Some research groups have reported statistical differences in oocyte maturation and pregnancy rates across genotype groups when standardized stimulation protocols were applied. However, the available evidence is categorized as limited because findings vary across study designs, sample sizes are modest, and outcomes are influenced by confounding factors such as age, body mass index, and baseline ovarian reserve.
Population Prevalence and Allelic Distribution
The rs2292076 polymorphism is common across several global populations, though its frequency exhibits distinct ancestral variation. In European cohorts, the minor G (Ser) allele is relatively frequent, typically occurring at frequencies between 0.30 and 0.40, resulting in a substantial proportion of heterozygous (AG) and homozygous minor (GG) individuals. In contrast, population databases indicate that the allele distribution differs markedly among East Asian, African, and Indigenous populations, where the ancestral A (Asn) allele is often much more prevalent. Because background genetic architecture and linkage disequilibrium patterns vary globally, genotype associations observed in European cohorts cannot be directly extrapolated to other ancestries without dedicated replication.
Clinical Interpretation and Limitations
It is critical to distinguish exploratory pharmacogenetic associations from actionable clinical guidelines. Currently, neither the Clinical Pharmacogenetics Implementation Consortium (CPIC) nor major reproductive endocrinology guidelines recommend routine testing for rs2292076 to determine medication protocols. An individual's genotype at rs2292076 cannot diagnose infertility, predict whether an IVF cycle will succeed, or dictate hormone prescriptions. Medication dosing, protocol selection, and fertility evaluations are complex clinical decisions guided by comprehensive physical assessments, basal hormone panels, and ultrasound findings. Anyone reviewing direct-to-consumer genetic data should consult their reproductive endocrinologist or pharmacist before drawing conclusions or contemplating changes to any medical regimen.
How common is this variant?
The minor G allele has an estimated frequency of approximately 0.30 to 0.40 in European populations, making both heterozygous (AG) and homozygous variant (GG) genotypes relatively common, while frequency distributions vary substantially in other ancestral groups.
Frequently asked questions
Can rs2292076 tell me if I am infertile?
No, rs2292076 is not a diagnostic marker for infertility. It is a common genetic trait associated with minor differences in hormone receptor sensitivity, not a disease-causing mutation. Most individuals carrying any combination of these alleles conceive naturally without difficulty.
Does my rs2292076 genotype affect my IVF medications?
While preliminary research links the G allele to subtle differences in how the ovaries respond to LH and FSH during ovarian stimulation, these findings are considered exploratory. Clinical guidelines do not recommend altering medication doses based on this SNP alone, and any protocol decisions must be directed by your fertility specialist.
What is the difference between N291S and N312S in LHCGR?
N291S and N312S describe the exact same genetic variant in the LHCGR protein. The difference stems from legacy protein numbering systems: older literature included the initial 21-amino-acid signal peptide (calling it N312S), whereas modern standard nomenclature numbers from the mature protein (N291S).
Is the G allele considered a dangerous or harmful mutation?
No, the G allele is a benign, common natural polymorphism carried by millions of healthy individuals worldwide. It simply represents a normal biological variation in the structure of the receptor rather than a pathological defect.
Sources & further reading
Educational information only, last refreshed 9/6/2026. Not medical advice — these associations describe population statistics, not individual predictions.
Curious what your genotype is for rs2292076?
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 LHCGR
Intronic regulatory variant in LHCGR modulating luteinizing hormone and human chorionic gonadotropin signaling sensitivity during human folliculogenesis.
Polymorphism in the luteinizing hormone/choriogonadotropin receptor gene linked to variation in ovarian sensitivity to gonadotropins during assisted reproduction.
Regulatory SNP in LHCGR associated with ovarian responsiveness.
Luteinizing hormone/choriogonadotropin receptor gene locus polymorphism linked to polycystic ovary syndrome susceptibility.
Intronic regulatory variant in LHCGR modulating luteinizing hormone and human chorionic gonadotropin signaling, linked to susceptibility to polycystic ovary syndrome (PCOS).
Activating missense mutation in LHCGR causing familial male-limited precocious puberty (testotoxicosis).