Progressive osseous heteroplasia: genes and variants
Progressive osseous heteroplasia is linked to 1 analyzed protein (GNAS). 1 DNA variants are known to cause it; 2 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 Progressive osseous heteroplasia
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.
1 disease-causing and 2 uncertain variants in GNAS are linked to Progressive osseous heteroplasia.
Known disease-causing variants in Progressive osseous heteroplasia
| Variant | Position | Protein part | Clinical label |
|---|---|---|---|
| GNAS M1V | 1 | Disease-causing (★★) |
Same protein, different disease
- Pseudohypoparathyroidism type I A is also caused by GNAS variants; they fall mostly in different places as the Progressive osseous heteroplasia variants (29 disease-causing).
- Pseudohypoparathyroidism is also caused by GNAS variants; they fall mostly in different places as the Progressive osseous heteroplasia variants (13 disease-causing).
- Pseudopseudohypoparathyroidism is also caused by GNAS variants; they fall mostly in different places as the Progressive osseous heteroplasia variants (7 disease-causing).
- McCune-Albright syndrome is also caused by GNAS variants; they fall mostly in different places as the Progressive osseous heteroplasia variants (5 disease-causing).
Diseases related to Progressive osseous heteroplasia
- Hereditary spastic paraplegia, also linked to GNAS
- Pseudohypoparathyroidism type I A, also linked to GNAS
- Pseudohypoparathyroidism, also linked to GNAS
- Pseudopseudohypoparathyroidism, also linked to GNAS
- McCune-Albright syndrome, also linked to GNAS
- Pituitary adenoma 3, multiple types, also linked to GNAS
Frequently asked questions
Which genes are linked to Progressive osseous heteroplasia?
In CATVariant, Progressive osseous heteroplasia is linked to 1 analyzed protein: GNAS (Guanine nucleotide-binding protein G(s) subunit alpha isoforms short).
How many genetic variants are linked to Progressive osseous heteroplasia?
10 variants: 1 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 2 are of uncertain significance or have conflicting reports.
Which uncertain variants in Progressive osseous heteroplasia 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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