Familial hyperparathyroidism or Hypocalciuric hypercalcaemia: genes and variants
Familial hyperparathyroidism or Hypocalciuric hypercalcaemia is linked to 2 analyzed proteins (CASR and RET). 5 DNA variants are known to cause it; 20 more are uncertain, and 0 of those already look disease-causing on computable evidence.
Last updated 2026-09-30. Research information, not medical advice.
Genes linked to Familial hyperparathyroidism or Hypocalciuric hypercalcaemia
CASR: Extracellular calcium-sensing receptor
It senses extracellular calcium in the parathyroid gland and kidney and adjusts parathyroid-hormone secretion and renal calcium handling accordingly. Loss-of-function variants cause familial hypocalciuric hypercalcemia or neonatal severe hyperparathyroidism, whereas activating variants cause autosomal dominant hypocalcemia.
5 disease-causing and 12 uncertain variants in CASR are linked to Familial hyperparathyroidism or Hypocalciuric hypercalcaemia.
RET: Proto-oncogene tyrosine-protein kinase receptor Ret
Its activation by GDNF-family ligands guides development of the enteric nervous system, kidney, and other tissues. Activating variants cause multiple endocrine neoplasia type 2 and can drive cancer, whereas loss-of-function variants are an important cause of Hirschsprung disease.
0 disease-causing and 6 uncertain variants in RET are linked to Familial hyperparathyroidism or Hypocalciuric hypercalcaemia.
Weakly linked (only a few uncertain records): CDC73 and CDKN1B.
Where Familial hyperparathyroidism or Hypocalciuric hypercalcaemia variants cluster
- CASR Ligand-binding 1 (LB1) (positions 22–188): 4 of 5 disease-causing changes, 5.2× more than its size predicts.
Known disease-causing variants in Familial hyperparathyroidism or Hypocalciuric hypercalcaemia
| Variant | Position | Protein part | Clinical label |
|---|---|---|---|
| CASR T138M | 138 | Ligand-binding 1 (LB1) | Disease-causing (★★) |
| CASR S147L | 147 | Ligand-binding 1 (LB1) | Disease-causing (★★) |
| CASR G553R | 553 | Cysteine-rich (CR) | Disease-causing (★★) |
| CASR F183L | 183 | Ligand-binding 1 (LB1) | Disease-causing (★) |
| CASR S171R | 171 | Ligand-binding 1 (LB1) | Disease-causing (★) |
Same protein, different disease
- Familial hypocalciuric hypercalcemia is also caused by CASR variants; they fall mostly in different places as the Familial hyperparathyroidism or Hypocalciuric hypercalcaemia variants (81 disease-causing).
- Autosomal dominant hypocalcemia is also caused by CASR variants; they fall mostly in different places as the Familial hyperparathyroidism or Hypocalciuric hypercalcaemia variants (69 disease-causing).
- Nephrolithiasis/nephrocalcinosis is also caused by CASR variants; they fall mostly in different places as the Familial hyperparathyroidism or Hypocalciuric hypercalcaemia variants (14 disease-causing).
- Neonatal severe primary hyperparathyroidism is also caused by CASR variants; they fall mostly in different places as the Familial hyperparathyroidism or Hypocalciuric hypercalcaemia variants (11 disease-causing).
- Epilepsy, idiopathic generalized, susceptibility to, 13 is also caused by CASR variants; they fall mostly in different places as the Familial hyperparathyroidism or Hypocalciuric hypercalcaemia variants (8 disease-causing).
Diseases related to Familial hyperparathyroidism or Hypocalciuric hypercalcaemia
- Hypertrophic cardiomyopathy, also linked to CASR
- Multiple endocrine neoplasia, also linked to RET
- Gastrointestinal stromal tumor, also linked to RET
- Familial hypocalciuric hypercalcemia, also linked to CASR
- Autosomal dominant hypocalcemia, also linked to CASR
- Pheochromocytoma, also linked to RET
- Ovarian cancer, also linked to RET
- Epilepsy, idiopathic generalized, susceptibility to, 13, also linked to CASR
- Idiopathic generalized epilepsy, also linked to CASR
- Colorectal cancer, also linked to RET
- Non-small cell lung carcinoma, also linked to RET
- Hirschsprung disease, also linked to RET
Frequently asked questions
Which genes are linked to Familial hyperparathyroidism or Hypocalciuric hypercalcaemia?
In CATVariant, Familial hyperparathyroidism or Hypocalciuric hypercalcaemia is linked to 2 analyzed proteins: CASR (Extracellular calcium-sensing receptor) and RET (Proto-oncogene tyrosine-protein kinase receptor Ret).
How many genetic variants are linked to Familial hyperparathyroidism or Hypocalciuric hypercalcaemia?
25 variants: 5 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 20 are of uncertain significance or have conflicting reports.
Which uncertain variants in Familial hyperparathyroidism or Hypocalciuric hypercalcaemia look disease-causing?
None of the uncertain variants currently reaches the likely-pathogenic range on computable evidence alone.
About this data
Variant–disease links come from ClinVar, Open Targets and UniProt, pooled from the latest public CATVariant analysis of each human protein. Evidence scores use the ACMG/AMP Bayesian points scale with computable criteria only (position among known disease variants, rarity in gnomAD, calibrated predictors, deep mutational scanning); there is no family or patient data, so they prioritise variants for expert review and never classify them.
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