Angioosteohypertrophic syndrome: genes and variants
Angioosteohypertrophic syndrome is linked to 3 analyzed proteins (PIK3CA, GNAQ and RASA1). 3 DNA variants are known to cause it; 0 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 Angioosteohypertrophic syndrome
PIK3CA: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform
Its p110-alpha catalytic activity generates PIP3 and activates AKT-dependent growth, survival, and metabolic signaling downstream of many receptors. Activating variants are frequent cancer drivers and, when present mosaically during development, can cause PIK3CA-related overgrowth spectrum.
2 disease-causing and 0 uncertain variants in PIK3CA are linked to Angioosteohypertrophic syndrome.
GNAQ: Guanine nucleotide-binding protein G(q) subunit alpha
It links Gq-coupled receptors to phospholipase C signaling and intracellular calcium release. Somatic activating variants are major drivers of uveal melanoma and Sturge-Weber-associated vascular malformations, depending on the developmental timing and cell type affected.
1 disease-causing and 0 uncertain variants in GNAQ are linked to Angioosteohypertrophic syndrome.
RASA1: Ras GTPase-activating protein 1
It accelerates hydrolysis of RAS-GTP and therefore limits RAS-MAPK signaling downstream of growth-factor receptors. Haploinsufficiency causes capillary malformation-arteriovenous malformation syndrome and related fast-flow vascular anomalies.
0 disease-causing and 0 uncertain variants in RASA1 are linked to Angioosteohypertrophic syndrome.
Known disease-causing variants in Angioosteohypertrophic syndrome
| Variant | Position | Protein part | Clinical label |
|---|---|---|---|
| GNAQ R183Q | 183 | G-alpha | Disease-causing (★★) |
| PIK3CA G118D | 118 | Disease-causing (★★) | |
| PIK3CA E365K | 365 | C2 PI3K-type | Disease-causing (★★) |
Same protein, different disease
- PIK3CA related overgrowth syndrome is also caused by PIK3CA variants; they fall mostly in different places as the Angioosteohypertrophic syndrome variants (30 disease-causing).
- Cowden syndrome is also caused by PIK3CA variants; they fall mostly in different places as the Angioosteohypertrophic syndrome variants (23 disease-causing).
- Megalencephaly-capillary malformation-polymicrogyria syndrome is also caused by PIK3CA variants; they fall mostly in different places as the Angioosteohypertrophic syndrome variants (22 disease-causing).
- Ovarian neoplasm is also caused by PIK3CA variants; they fall mostly in different places as the Angioosteohypertrophic syndrome variants (5 disease-causing).
- PIK3CA constitutional syndrome is also caused by PIK3CA variants; they fall mostly in different places as the Angioosteohypertrophic syndrome variants (4 disease-causing).
Diseases related to Angioosteohypertrophic syndrome
- Noonan syndrome, also linked to PIK3CA
- Cowden syndrome, also linked to PIK3CA
- Ovarian cancer, also linked to PIK3CA
- PIK3CA related overgrowth syndrome, also linked to PIK3CA
- Familial cancer of breast, also linked to PIK3CA
- Megalencephaly-capillary malformation-polymicrogyria syndrome, also linked to PIK3CA
- Colorectal cancer, also linked to PIK3CA
- Gastric cancer, also linked to PIK3CA
- Malignant tumor of urinary bladder, also linked to PIK3CA
- Overgrowth syndrome and/or cerebral malformations due to abnormalities in MTOR pathway genes, also linked to PIK3CA
- Non-small cell lung carcinoma, also linked to PIK3CA
- Ovarian neoplasm, also linked to PIK3CA
Frequently asked questions
Which genes are linked to Angioosteohypertrophic syndrome?
In CATVariant, Angioosteohypertrophic syndrome is linked to 3 analyzed proteins: PIK3CA (Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform), GNAQ (Guanine nucleotide-binding protein G(q) subunit alpha) and RASA1 (Ras GTPase-activating protein 1).
How many genetic variants are linked to Angioosteohypertrophic syndrome?
5 variants: 3 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 0 are of uncertain significance or have conflicting reports.
Which uncertain variants in Angioosteohypertrophic syndrome 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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