Pseudopseudohypoparathyroidism: genes and variants
Pseudopseudohypoparathyroidism is linked to 1 analyzed protein (GNAS). 7 DNA variants are known to cause it; 12 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 Pseudopseudohypoparathyroidism
GNAS: Guanine nucleotide-binding protein G(s) subunit alpha isoforms short
It produces the stimulatory G-alpha subunit that activates adenylyl cyclase downstream of many hormone receptors, with complex tissue-specific imprinting at the locus. Inactivating variants cause pseudohypoparathyroidism-spectrum disorders, while activating somatic variants cause McCune-Albright syndrome and some endocrine tumors.
7 disease-causing and 12 uncertain variants in GNAS are linked to Pseudopseudohypoparathyroidism.
Known disease-causing variants in Pseudopseudohypoparathyroidism
| Variant | Position | Protein part | Clinical label |
|---|---|---|---|
| GNAS R201H | 201 | G-alpha | Disease-causing (★★) |
| GNAS I103T | 103 | G-alpha | Disease-causing (★★) |
| GNAS G353R | 353 | G-alpha | Disease-causing (★★) |
| GNAS K100N | 100 | G-alpha | Disease-causing (★) |
| GNAS V107G | 107 | G-alpha | Disease-causing (★) |
| GNAS P122A | 122 | G-alpha | Disease-causing (★) |
| GNAS R258A | 258 | G-alpha | Disease-causing |
Same protein, different disease
- Pseudohypoparathyroidism type I A is also caused by GNAS variants; they fall mostly in different places as the Pseudopseudohypoparathyroidism variants (29 disease-causing).
- Pseudohypoparathyroidism is also caused by GNAS variants; they fall mostly in different places as the Pseudopseudohypoparathyroidism variants (13 disease-causing).
- McCune-Albright syndrome is also caused by GNAS variants; they fall mostly in different places as the Pseudopseudohypoparathyroidism variants (5 disease-causing).
Diseases related to Pseudopseudohypoparathyroidism
- Hereditary spastic paraplegia, also linked to GNAS
- Pseudohypoparathyroidism type I A, also linked to GNAS
- Pseudohypoparathyroidism, also linked to GNAS
- McCune-Albright syndrome, also linked to GNAS
- Pituitary adenoma 3, multiple types, also linked to GNAS
- Progressive osseous heteroplasia, also linked to GNAS
Frequently asked questions
Which genes are linked to Pseudopseudohypoparathyroidism?
In CATVariant, Pseudopseudohypoparathyroidism is linked to 1 analyzed protein: GNAS (Guanine nucleotide-binding protein G(s) subunit alpha isoforms short).
How many genetic variants are linked to Pseudopseudohypoparathyroidism?
27 variants: 7 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 12 are of uncertain significance or have conflicting reports.
Which uncertain variants in Pseudopseudohypoparathyroidism 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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