PROKR2 rs121918410: Understanding Reproductive Genetic Variants
The rs121918410 variant is a specific change in the PROKR2 gene associated with reproductive health conditions. It is linked to normosmic hypogonadotropic hypogonadism, a condition characterized by delayed puberty and impaired hormone production.
What each genotype means
Typical PROKR2 genotype
This genotype represents the most common sequence found in the general population for this location in the PROKR2 gene. It is not associated with the specific reproductive or olfactory conditions linked to the variant. No clinical action is indicated based on this result.
This is the major allele genotype, carried by the vast majority of individuals across all global populations.
Variant carrier status
This genotype indicates you carry one copy of the variant associated with normosmic hypogonadotropic hypogonadism and Kallmann syndrome. While PROKR2 variants can be inherited in a complex manner, including digenic inheritance where other genes may also be involved, carrying one copy does not guarantee the development of these conditions. You should discuss these findings with a genetic counselor or endocrinologist to understand your personal health context.
This genotype is rare, with the variant allele occurring at a global frequency of approximately 0.3% in the gnomAD database.
Increased risk profile
This genotype indicates you carry two copies of the variant, which has been linked to impaired prokineticin receptor 2 function and associated reproductive or olfactory disorders. Research indicates that insufficient signaling through this receptor can affect the development of the reproductive axis and the olfactory system. Please consult with a medical professional to discuss whether this finding is relevant to your personal health history.
This genotype is extremely rare in the general population.
What is the rs121918410 Variant?
The rs121918410 variant is a missense mutation located within the PROKR2 gene, which is situated on chromosome 20. In genetics, a missense variant occurs when a single nucleotide change results in the substitution of one amino acid for another in the protein sequence. This specific alteration can affect the structure and function of the resulting protein. Because this variant is located in a gene critical for developmental signaling, researchers study it to understand how minor changes in DNA sequence can influence complex biological processes like sexual development. It is categorized as a reproductive variant, and its presence is often investigated in clinical settings when individuals present with symptoms related to delayed puberty or hormonal imbalances.
The Role of the PROKR2 Gene
The PROKR2 gene provides instructions for making the prokineticin receptor 2 protein. This receptor is a G-protein-coupled receptor that plays a vital role in the development of the olfactory system and the migration of gonadotropin-releasing hormone (GnRH) neurons. GnRH neurons are essential for the production of hormones that trigger puberty and regulate reproductive function. When the PROKR2 protein is functioning normally, it transmits signals that ensure these neurons reach their proper destination in the brain. If the receptor is impaired due to a genetic variant, the signaling pathway may be disrupted, potentially leading to conditions such as Kallmann syndrome or normosmic isolated hypogonadotropic hypogonadism (nIHH). Understanding this gene is key to grasping how the body coordinates the complex timing of sexual maturation.
Research and Clinical Associations
Research has identified that variants in PROKR2, including rs121918410, are associated with normosmic hypogonadotropic hypogonadism. This condition involves a deficiency in the hormones that direct sexual development, leading to delayed or absent puberty. Evidence for the pathogenicity of such variants is considered moderate, as the inheritance patterns can be complex. In some cases, the condition follows an autosomal recessive pattern, while in others, it may be autosomal dominant or involve oligogenic mechanisms, where variants in multiple genes contribute to the phenotype. Because some PROKR2 variants are found in the general population, clinical interpretation can be challenging, often requiring careful analysis of a patient's family history and clinical presentation to determine the significance of the finding.
Interpreting Your Genetic Information
Genetic information regarding variants like rs121918410 should be interpreted within the context of a professional medical evaluation. It is important to understand that the presence of a variant does not automatically result in a clinical diagnosis. Many factors, including other genetic modifiers and environmental influences, play a role in how a trait or condition manifests. If you have received information about this variant, you cannot use it to self-diagnose or predict specific health outcomes. Instead, this information should be discussed with a qualified healthcare provider or a genetic counselor. They can help place the finding in the context of your overall health, family history, and current symptoms, ensuring that any medical decisions are based on a comprehensive clinical assessment rather than a single genetic result.
How common is this variant?
The rs121918410 variant is relatively rare, with a global minor allele frequency (MAF) of approximately 0.003 according to gnomAD data.
Frequently asked questions
What is normosmic hypogonadotropic hypogonadism?
It is a condition where the body does not produce enough sex hormones, leading to delayed or absent puberty, but the individual retains a normal sense of smell.
Does having this variant mean I will have fertility issues?
Not necessarily. Genetic variants are only one factor in reproductive health, and the presence of a variant does not guarantee a specific clinical outcome. You should consult a reproductive endocrinologist for a personalized assessment.
Is this variant the same as Kallmann syndrome?
While PROKR2 variants are associated with both Kallmann syndrome and normosmic hypogonadotropic hypogonadism, they are distinct conditions. Kallmann syndrome specifically includes an impaired sense of smell, whereas normosmic hypogonadotropic hypogonadism does not.
Can I change my genotype for this variant?
No, your genotype is determined at conception and cannot be altered. Genetic testing provides information about your inherited DNA sequence.
Sources & further reading
Educational information only, last refreshed 10/16/2026. Not medical advice — these associations describe population statistics, not individual predictions.
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