GNRHR rs11554205: Understanding the p.Gln106Arg Variant
The rs11554205 variant is a specific genetic change in the GNRHR gene, known as p.Gln106Arg. It is associated with normosmic congenital hypogonadotropic hypogonadism, a condition characterized by delayed or absent puberty and potential infertility.
What each genotype means
Typical receptor function
This is the most common, ancestral form of the gene and is associated with normal receptor activity as typically observed in the general population. Carrying this genotype means you do not have the specific p.Gln106Arg change linked to these reproductive disorders.
This is the reference genotype and is the most common state across all major human populations.
Potential carrier status
You carry one copy of the p.Gln106Arg (G) variant and one copy of the common (A) allele. In the context of GNRHR-related conditions, which often follow a recessive pattern, carriers of a single copy typically do not exhibit the clinical symptoms of hypogonadotropic hypogonadism. If you have concerns about reproductive health or family history, you may wish to discuss this result with a genetic counselor or your clinician.
Carried by a small fraction of the population; allele frequencies are generally low (e.g., ~0.002 in European populations, though slightly higher in some others like the Ashkenazi Jewish population).
Reduced receptor activity
You carry two copies of the p.Gln106Arg (G) variant. Research indicates this genotype is associated with a partial loss of function of the GnRH receptor, which can contribute to reproductive challenges such as delayed or stalled puberty, infertility, or partial hypogonadotropic hypogonadism. Clinical presentation can be variable; please consult with a reproductive endocrinologist or medical specialist to interpret these findings in the context of your personal health history.
This genotype is very rare in the general population.
What is the rs11554205 Variant?
The rs11554205 variant is a single nucleotide polymorphism (SNP) located within the GNRHR gene. In genetic terms, this is a missense mutation, meaning the change in the DNA sequence results in a different amino acid being incorporated into the protein structure. Specifically, this variant causes a substitution of glutamine for arginine at position 106 of the gonadotropin-releasing hormone receptor protein (p.Gln106Arg). Because this receptor is critical for the body's hormonal signaling, changes to its structure can potentially alter how cells respond to chemical signals. This variant is well-documented in clinical databases, where it has been studied for its impact on the function of the receptor and its subsequent effects on human development and reproductive health.
The Role of the GNRHR Gene
The GNRHR gene provides instructions for making the gonadotropin-releasing hormone receptor. This receptor is found on the surface of cells in the pituitary gland, a small organ at the base of the brain. When gonadotropin-releasing hormone (GnRH) binds to this receptor, it triggers the pituitary gland to release other hormones, such as luteinizing hormone and follicle-stimulating hormone. These hormones are essential for the development of secondary sexual characteristics and the regulation of reproductive functions in both males and females. When the GNRHR gene contains a variant that impairs the receptor's ability to function, the signaling pathway can be disrupted. This disruption often leads to a condition known as congenital hypogonadotropic hypogonadism (CHH), where the body fails to produce enough of the hormones necessary for normal pubertal development.
Research and Clinical Associations
Research has linked the rs11554205 variant to normosmic congenital hypogonadotropic hypogonadism, a condition where individuals experience delayed or absent puberty but maintain a normal sense of smell. Clinical diagnostic laboratories have submitted numerous assessments to ClinVar, with many classifying this specific variant as pathogenic. Studies indicate that GNRHR mutations, including this one, are responsible for a notable percentage of sporadic cases of normosmic CHH. The evidence suggests that this variant acts through a loss-of-function mechanism, reducing the receptor's efficiency in responding to hormonal signals. While the association with CHH is well-characterized in clinical literature, it is important to note that the severity of the clinical presentation can vary between individuals. Because this is a complex genetic condition, researchers continue to study how this variant interacts with other genetic and environmental factors to influence reproductive outcomes.
Understanding Your Results
If you have received information about your status regarding the rs11554205 variant, it is important to understand that this information is for educational purposes only. Genetic variants do not act in isolation, and the presence of a specific genotype does not guarantee a particular health outcome. If you are concerned about reproductive health, delayed puberty, or fertility, the most appropriate step is to consult with a qualified healthcare provider or a reproductive endocrinologist. They can provide a comprehensive evaluation, which may include hormone level testing and a detailed clinical history, to determine if any symptoms are related to your genetic profile. Never use genetic data to make medical decisions or change treatments without professional guidance. A clinician can help interpret these findings within the context of your overall health and family history.
How common is this variant?
The rs11554205 variant is relatively rare in the general population, with a reported allele frequency of approximately 0.002 in European non-Finnish populations according to gnomAD data.
Frequently asked questions
What is normosmic congenital hypogonadotropic hypogonadism?
It is a condition where the body does not produce enough reproductive hormones, leading to delayed or absent puberty. The term 'normosmic' means that the individual's sense of smell is unaffected, which distinguishes it from other forms of hypogonadism.
Is the rs11554205 variant always associated with disease?
While this variant is classified as pathogenic in clinical databases, genetic expression can be complex. Clinical presentation depends on many factors, and you should discuss any concerns with a medical professional.
Can I be tested for this variant?
Genetic testing is available through clinical laboratories, usually ordered by a physician. If you are interested in testing, speak with a genetic counselor or your primary care doctor.
Does having this variant mean I am infertile?
Not necessarily. While this variant is linked to reproductive challenges, the impact on fertility varies significantly between individuals. A reproductive specialist can provide an accurate assessment based on your specific health profile.
Sources & further reading
Educational information only, last refreshed 9/17/2026. Not medical advice — these associations describe population statistics, not individual predictions.
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This synonymous variant in the gonadotropin-releasing hormone receptor gene is studied for its potential role in modulating reproductive hormone responsiveness.
Pathogenic missense substitution (p.Arg262Gln) in GNRHR linked to autosomal recessive normosmic congenital hypogonadotropic hypogonadism.
Gonadotropin-releasing hormone receptor variant associated with altered gonadotropin pulsatility and susceptibility to delayed puberty.
Recessive pathogenic missense variant in gonadotropin-releasing hormone receptor causing normosmic idiopathic hypogonadotropic hypogonadism and delayed puberty.
Common missense variant (p.Gln106Arg) in the gonadotropin-releasing hormone receptor associated with hypogonadotropic hypogonadism and delayed puberty when compound heterozygous.
Pathogenic missense variant disrupting GnRH binding in the pituitary gonadotropes, causing severe hypogonadotropic hypogonadism.