CFTR rs121908075 (R117H): What Your Genotype Means
The rs121908075 variant, commonly referred to as R117H, is a genetic change in the CFTR gene. It is associated with a spectrum of conditions, ranging from mild forms of cystic fibrosis to congenital bilateral absence of the vas deferens (CBAVD).
What each genotype means
Typical CFTR function
This genotype represents the common, non-variant form of the CFTR gene at this position. It is not associated with the R117H mutation, which is linked to milder forms of cystic fibrosis or congenital absence of the vas deferens.
This is the most common genotype found in the vast majority of the global population.
R117H carrier status
This genotype indicates you carry one copy of the R117H variant. The clinical impact of this variant is highly variable and is often modulated by other genetic factors, such as the poly-T tract length in the CFTR gene, which can influence the severity of potential symptoms like congenital absence of the vas deferens or mild cystic fibrosis.
The R117H variant is found in approximately 0.3% of individuals of European ancestry.
R117H variant present
This genotype indicates the presence of the R117H variant on both copies of the CFTR gene. This variant is classified as a mild mutation, and clinical outcomes can range from no symptoms to mild cystic fibrosis or congenital absence of the vas deferens, depending heavily on other genetic modifiers and environmental factors.
This homozygous genotype is rare, occurring in a very small fraction of the population even within groups where the variant is more common.
Understanding the Variant
The rs121908075 variant is a single nucleotide polymorphism (SNP) located within the CFTR gene. In clinical literature, it is frequently identified by the protein-level change it causes, known as R117H, where the amino acid arginine is replaced by histidine at position 117. This specific change affects the function of the protein produced by the gene. Because the CFTR gene is large and complex, the specific location of this variant is critical to how it impacts cellular processes. Researchers track this variant to understand how it alters the protein's ability to transport ions across cell membranes, which is the primary role of the CFTR protein. By studying this SNP, scientists have gained insights into why some individuals experience milder symptoms compared to those with more severe mutations in the same gene.
The Role of the CFTR Gene
The CFTR gene provides the instructions for creating the cystic fibrosis transmembrane conductance regulator protein. This protein functions as a channel that transports negatively charged particles called chloride ions into and out of cells. This movement of ions is essential for maintaining the proper balance of salt and water on cell surfaces, which helps keep mucus thin and free-flowing in organs like the lungs, pancreas, and reproductive tract. When the CFTR protein is dysfunctional, this balance is disrupted, leading to the production of thick, sticky mucus. While severe mutations can lead to classic cystic fibrosis, variants like R117H result in a protein that still retains some function, albeit at a reduced level. This partial function is why the clinical presentation associated with this variant is often described as non-classic or mild.
Research and Clinical Associations
Research indicates that the R117H variant is a Class IV mutation, meaning it primarily affects the conductance or the flow of ions through the channel. Studies have shown that R117H-CFTR has a reduced single-channel conductance and a lower probability of the channel being open. Importantly, the clinical impact of this variant is often modulated by other genetic factors, specifically the length of a polythymidine (poly-T) tract in intron 8 of the CFTR gene. The combination of R117H with different poly-T lengths (such as 5T, 7T, or 9T) can significantly change the severity of the resulting phenotype. For instance, R117H paired with a 5T allele is more likely to be associated with classic cystic fibrosis symptoms, whereas other combinations may lead only to CBAVD. Because of this complexity, the evidence for its association with mild disease is strong, but the clinical outcome is highly dependent on the individual's broader genetic context.
Population Frequency
The rs121908075 variant is found in approximately 0.3% of the European population. While it is considered a relatively rare variant in the general population, it is one of the more frequently studied mutations in the context of non-classic cystic fibrosis. Because it is a founder mutation in certain ethnic groups, its frequency can vary depending on ancestral background. It is important to note that population frequency alone does not determine an individual's health status. Genetic testing results should always be interpreted by a qualified healthcare professional who can consider the full genetic profile, including the status of the poly-T tract and other potential modifiers, to provide accurate clinical context.
Navigating Genetic Information
Understanding your genetic status regarding the CFTR gene can be complex. If you have received information about the rs121908075 variant, it is essential to recognize that this information is not a medical diagnosis. The presence of this variant does not guarantee the development of any specific condition, as the clinical expression is influenced by other genetic and environmental factors. You cannot use this information to self-diagnose or make decisions about medical treatments. If you are concerned about your health or the health of your family, you should consult with a genetic counselor or a physician who specializes in cystic fibrosis or reproductive health. They can help you understand the implications of your results, discuss the necessity of further testing, and provide guidance based on your specific clinical history and family background.
How common is this variant?
The rs121908075 variant is found in approximately 0.3% of the European population.
Frequently asked questions
Is R117H the same as cystic fibrosis?
R117H is a specific variant in the CFTR gene that can be associated with mild forms of cystic fibrosis or CBAVD. It is not a diagnosis of the disease itself, as clinical outcomes vary significantly based on other genetic factors.
What is the difference between R117H and classic cystic fibrosis?
Classic cystic fibrosis is often caused by severe mutations that result in little to no functional CFTR protein. R117H is considered a mild mutation because the protein it produces retains some function, leading to a less severe clinical presentation.
How does the poly-T tract affect R117H?
The poly-T tract in intron 8 acts as a modifier for the R117H variant. The number of thymidines (5T, 7T, or 9T) influences how much functional protein is produced, which in turn dictates the severity of the associated symptoms.
Should I be tested for the R117H variant?
Genetic testing is a personal decision that should be made in consultation with a healthcare provider. A doctor or genetic counselor can help determine if testing is appropriate based on your family history and clinical needs.
Sources & further reading
Educational information only, last refreshed 9/30/2026. Not medical advice — these associations describe population statistics, not individual predictions.
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Severe pathogenic mutation (p.Gly542Ter) associated with cystic fibrosis.
Classic cystic fibrosis in-frame 3-bp deletion variant (p.Phe508del / deltaF508) causing misfolding and impaired chloride channel trafficking.
Pathogenic frameshift mutation (c.3659delC) in CFTR linked to cystic fibrosis.
Pathogenic nonsense variant (p.Gly542Ter / G542X) causing autosomal recessive cystic fibrosis when inherited in trans with another CFTR pathogenic allele.
Also known as p.Arg117His (R117H), this CFTR variant is associated with mild or atypical cystic fibrosis and congenital bilateral absence of the vas deferens, with clinical severity influenced by the poly-T tract background.
A CFTR mutation associated with cystic fibrosis and CFTR-related disorders.