CASR rs193922419: Understanding Familial Hypocalciuric Hypercalcemia
The rs193922419 variant is a rare genetic alteration located within the CASR gene. It is associated with familial hypocalciuric hypercalcemia type 1 (FHH1), a condition characterized by elevated blood calcium levels and reduced urinary calcium excretion.
What each genotype means
Typical calcium regulation
You carry two reference copies of the CASR gene at this position. This genotype is associated with normal calcium-sensing receptor function and standard regulation of blood and urine calcium levels. It does not confer an inherited predisposition to familial hypocalciuric hypercalcemia type 1.
Found in greater than 99.9% of individuals across all major global ancestries.
Predisposition to FHH type 1
Carrying one copy of this missense variant is associated with familial hypocalciuric hypercalcemia type 1 (FHH1), an autosomal dominant condition. Published research shows that inactivating alterations in the CASR gene reduce calcium sensitivity in the kidneys and parathyroid glands, typically resulting in lifelong, benign, and asymptomatic elevations in serum calcium with low calcium excretion in the urine. Because this benign condition closely mimics primary hyperparathyroidism on standard blood panels, genetic identification helps clinicians avoid unnecessary surgical parathyroid interventions.
Extremely rare in the general population, identified in fewer than 1 in 10,000 individuals globally and typically detected through familial investigations.
What is the rs193922419 Variant?
The rs193922419 variant is a specific change in the DNA sequence of the CASR gene. In genetics, a variant like this is often identified through targeted sequencing when individuals or families present with clinical signs of calcium imbalance. This variant is classified as a missense mutation, meaning it results in a single amino acid change within the protein produced by the gene. Because the CASR gene provides instructions for making a protein that acts as a sensor for calcium levels in the body, changes to its structure can alter how the body perceives and regulates calcium. This variant is categorized as a health predisposition, specifically linked to the development of familial hypocalciuric hypercalcemia type 1 (FHH1). It is important to note that genetic variants are simply differences in DNA; they do not inherently cause symptoms in every individual, though this specific variant is recognized in clinical literature for its role in FHH1.
The Role of the CASR Gene
The CASR gene encodes the calcium-sensing receptor, a G-protein-coupled receptor found primarily on the surface of cells in the parathyroid glands and the kidneys. This receptor acts like a thermostat for calcium; it constantly monitors the concentration of calcium ions in the blood. When calcium levels are high, the receptor signals the parathyroid glands to decrease the production of parathyroid hormone (PTH). Simultaneously, it signals the kidneys to excrete more calcium into the urine. When the CASR gene contains a loss-of-function mutation, the receptor becomes less sensitive to calcium. The body mistakenly perceives that calcium levels are lower than they actually are, leading to an inappropriate increase in PTH and a decrease in the amount of calcium released into the urine. This results in the hallmark signs of FHH1: mild-to-moderate hypercalcemia (high blood calcium) and hypocalciuria (low urinary calcium).
Research and Clinical Associations
Research into CASR variants has established a clear link between loss-of-function mutations and FHH1. The evidence for this association is considered moderate to strong in clinical genetics, as these variants are frequently identified in families exhibiting the classic biochemical profile of the condition. FHH1 is typically inherited in an autosomal dominant pattern, meaning an individual only needs to inherit the variant from one parent to be at risk for the condition. While many individuals with FHH1 are asymptomatic and may not require treatment, the condition is a lifelong trait. Clinical studies emphasize that because FHH1 is a genetic condition, it is distinct from other causes of hypercalcemia, such as primary hyperparathyroidism. Distinguishing between these is crucial, as unnecessary surgeries or treatments for hypercalcemia can be avoided if the underlying genetic cause is correctly identified through clinical evaluation and, if necessary, genetic testing.
Population Frequency and Interpretation
The rs193922419 variant is extremely rare in the general population. It is not a common polymorphism found in the average person; rather, it is typically identified during targeted screenings of families who have already been diagnosed with or suspected of having FHH1. Because of its rarity, it does not appear in large-scale population frequency databases with high prevalence. If you have received information about this variant, it is likely the result of a specific clinical investigation. It is important to understand that having a genetic variant does not constitute a medical diagnosis. Genetic information should always be interpreted by a qualified healthcare professional, such as a genetic counselor or an endocrinologist, who can place the finding in the context of your personal and family medical history, as well as your current blood chemistry results.
How common is this variant?
The rs193922419 variant is extremely rare in global populations and is typically identified only through targeted familial screenings.
Frequently asked questions
What is FHH1?
Familial hypocalciuric hypercalcemia type 1 (FHH1) is a lifelong, usually benign genetic condition characterized by mild-to-moderate high blood calcium levels and low urinary calcium excretion. It is caused by mutations in the CASR gene that make the body's calcium-sensing mechanism less sensitive.
Do I need treatment if I have this variant?
Most individuals with FHH1 are asymptomatic and do not require medical treatment. However, you should discuss your specific clinical profile and blood test results with an endocrinologist to determine if any management is necessary.
Is this variant the same as primary hyperparathyroidism?
No, they are different. While both can cause high blood calcium, FHH1 is a genetic condition that generally does not require surgery, whereas primary hyperparathyroidism is often caused by a growth on a parathyroid gland that may require medical intervention.
How is this variant inherited?
This variant follows an autosomal dominant inheritance pattern. This means that an affected individual has a 50% chance of passing the variant to each of their children.
Sources & further reading
Educational information only, last refreshed 10/17/2026. Not medical advice — these associations describe population statistics, not individual predictions.
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Variant in the CASR gene, which encodes the calcium-sensing receptor critical for systemic calcium homeostasis.
Variants in CASR are associated with calcium homeostasis disorders, including familial hypocalciuric hypercalcemia and autosomal dominant hypocalcemia.
Variant in the CASR gene involved in the regulation of the calcium-sensing receptor.
Variant in the CASR gene associated with altered calcium-sensing receptor sensitivity and regulation of parathyroid hormone secretion.
Variant in the CASR gene associated with the calcium-sensing receptor protein.