Neonatal severe primary hyperparathyroidism: genes and variants
Explore variant evidence for Neonatal severe primary hyperparathyroidism across 1 analyzed protein (CASR). Linked ClinVar records include 11 pathogenic or likely pathogenic variants, 31 variants of uncertain significance and 14 with conflicting classifications.
Coverage includes proteins already analyzed in CATVariant, not every gene involved in this condition. Database links are associations, not an assessment of clinical gene–disease validity. Computable evidence prioritizes variants for expert review and does not reclassify them. Counts refer to the selected disease label.
Data updated 2026-10-10. Automated aggregation, not a clinical review date.
Download variant evidence (CSV)
Genes linked to Neonatal severe primary hyperparathyroidism
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.
11 ClinVar pathogenic / likely pathogenic and 45 uncertain variants in CASR have source records linked to Neonatal severe primary hyperparathyroidism. Association strength is not clinical gene validity.
Where Neonatal severe primary hyperparathyroidism variants cluster
- CASR Ligand-binding 1 (LB1) (positions 22–188): 3 of 11 ClinVar pathogenic / likely pathogenic variants, 1.8× more than its size predicts.
ClinVar pathogenic and likely pathogenic variants linked to Neonatal severe primary hyperparathyroidism
| Variant | Position | Protein part | Clinical label |
|---|---|---|---|
| CASR R220W | 220 | Ligand-binding 2 (LB2) | Pathogenic / likely pathogenic (★★) |
| CASR N64D | 64 | Ligand-binding 1 (LB1) | Pathogenic / likely pathogenic (★★) |
| CASR E127K | 127 | Ligand-binding 1 (LB1) | Pathogenic / likely pathogenic (★★) |
| CASR G509R | 509 | Extracellular | Pathogenic / likely pathogenic (★★) |
| CASR G613E | 613 | Transmembrane | Pathogenic / likely pathogenic (★★) |
| CASR R680H | 680 | Transmembrane | Pathogenic / likely pathogenic (★★) |
| CASR V689M | 689 | Transmembrane | Pathogenic / likely pathogenic (★★) |
| CASR F832S | 832 | Extracellular | Pathogenic / likely pathogenic (★★) |
| CASR R227L | 227 | Ligand-binding 2 (LB2) | Pathogenic / likely pathogenic (★★) |
| CASR R69S | 69 | Ligand-binding 1 (LB1) | Pathogenic / likely pathogenic (★) |
| CASR G670E | 670 | Extracellular | Pathogenic / likely pathogenic |
Which prediction tools work for Neonatal severe primary hyperparathyroidism
Observed separation of ClinVar pathogenic / likely pathogenic from benign / likely benign variants (AUROC × 100). This benchmark is not a clinical recommendation.
- PolyPhen-2: 93 out of 100 (learned from overlapping clinical labels, so this is optimistic)
- CATVariant: 90 out of 100 (learned from overlapping clinical labels, so this is optimistic)
- SIFT: 83 out of 100
Same protein, different disease
- Familial hypocalciuric hypercalcemia also has ClinVar records linked to CASR variants; they fall mostly in different places as the Neonatal severe primary hyperparathyroidism variants (81 pathogenic / likely pathogenic).
- Autosomal dominant hypocalcemia also has ClinVar records linked to CASR variants; they fall mostly in different places as the Neonatal severe primary hyperparathyroidism variants (69 pathogenic / likely pathogenic).
- Nephrolithiasis/nephrocalcinosis also has ClinVar records linked to CASR variants; they fall partly in the same places as the Neonatal severe primary hyperparathyroidism variants (14 pathogenic / likely pathogenic).
- Epilepsy, idiopathic generalized, susceptibility to, 13 also has ClinVar records linked to CASR variants; they fall in the same places as the Neonatal severe primary hyperparathyroidism variants (8 pathogenic / likely pathogenic).
- Familial hyperparathyroidism or Hypocalciuric hypercalcaemia also has ClinVar records linked to CASR variants; they fall mostly in different places as the Neonatal severe primary hyperparathyroidism variants (5 pathogenic / likely pathogenic).
Diseases related to Neonatal severe primary hyperparathyroidism
- Hypertrophic cardiomyopathy, also linked to CASR
- Familial hypocalciuric hypercalcemia, also linked to CASR
- Autosomal dominant hypocalcemia, also linked to CASR
- Epilepsy, idiopathic generalized, susceptibility to, 13, also linked to CASR
- Idiopathic generalized epilepsy, also linked to CASR
- Nephrolithiasis/nephrocalcinosis, also linked to CASR
- Familial hyperparathyroidism or Hypocalciuric hypercalcaemia, also linked to CASR
- Parathyroid carcinoma, also linked to CASR
- Familial hypoparathyroidism, also linked to CASR
Frequently asked questions
Which genes have records linked to Neonatal severe primary hyperparathyroidism?
This view contains 1 analyzed proteins: CASR. Links come from clinical records and association databases. They do not imply that every listed gene is a validated cause, and missing genes may not yet be analyzed.
What do the clinical classifications mean?
Linked records include 11 pathogenic or likely pathogenic variants, 31 variants of uncertain significance and 14 with conflicting classifications. Labels summarize source records; multi-condition records may not make a separate assertion for this disease. Check the original record and review status.
Does the evidence score change a VUS classification?
No. 0 VUS or conflicting variants reach the likely-pathogenic points range on the computable criteria available here. This is a research prioritization signal, not a clinical classification. Patient, family and other required evidence may be missing.
Can I download the variant evidence?
Download the CSV for all 66 variants in the selected disease scope, including clinical labels, review status, evidence criteria, predictor scores, functional measurements and population frequency where available.
About this data
Variant–disease links come from ClinVar, Open Targets and UniProt, pooled from eligible public CATVariant analyses 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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