GNA11
Chr 19ADG protein subunit alpha 11
Also known as: FBH, FBH2, FHH2, GNA-11, HG1K, HHC2, HYPOC2
This protein functions as a G protein alpha subunit that transduces signals from G protein-coupled receptors by activating phospholipase C-beta, leading to intracellular calcium signaling cascades. Mutations cause autosomal dominant hypocalcemia or hypocalciuric hypercalcemia, disorders affecting calcium homeostasis and parathyroid hormone sensitivity. The gene is highly constrained against loss-of-function variants (pLI 0.89, LOEUF 0.40), indicating that complete protein loss is likely incompatible with normal development.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
More LoF-intolerant than ~75% of genes
Highly missense-constrained (top ~0.1%)
The highest-scoring mechanism for this gene is gain-of-function.
Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.
Literature Evidence
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
GNA11 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
Study of IDE196 in Patients With Solid Tumors Harboring GNAQ/11 Mutations or PRKC Fusions
RECRUITINGTargeted Therapy Directed by Genetic Testing in Treating Patients With Advanced Refractory Solid Tumors, Lymphomas, or Multiple Myeloma (The MATCH Screening Trial)
ACTIVE NOT RECRUITINGADH1 and ADH2 Disease Monitoring Study (DMS)
ACTIVE NOT RECRUITINGExternal Resources
Links to major genomics databases and tools