GNA11

Chr 19AD

G protein subunit alpha 11

Also known as: FBH, FBH2, FHH2, GNA-11, HG1K, HHC2, HYPOC2

NCBI Gene: 2767ENSG00000088256UniProt: P29992OMIM: 139313

The protein encoded by this gene belongs to the family of guanine nucleotide-binding proteins (G proteins), which function as modulators or transducers in various transmembrane signaling systems. G proteins are composed of 3 units: alpha, beta and gamma. This gene encodes one of the alpha subunits (subunit alpha-11). Mutations in this gene have been associated with hypocalciuric hypercalcemia type II (HHC2) and hypocalcemia dominant 2 (HYPOC2). Patients with HHC2 and HYPOC2 exhibit decreased or increased sensitivity, respectively, to changes in extracellular calcium concentrations. [provided by RefSeq, Dec 2013]

OMIMResearchGenerating clinical summary…
GOFmechanismADLOEUF 0.402 OMIM phenotypes
Clinical Summary— GNA11
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Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.89) — some intolerance to loss-of-function variants.
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Clinical Trials
3 active or recruiting trials — potential therapeutic options may be available
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Missense constrained — critical functional residues
LoF Constraint?
0.40LOEUF
pLI 0.889
Z-score 3.24
OE 0.13 (0.05–0.40)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?
3.77Z-score
OE missense 0.33 (0.28–0.40)
84 obs / 252.5 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios?
LoF OE?0.13 (0.05–0.40)
0≤0.351.4
Missense OE?0.33 (0.28–0.40)
0≤0.61.4
Synonymous OE?1.00
0≤1.21.6
LoF obs/exp: 2 / 15.9Missense obs/exp: 84 / 252.5Syn Z: -0.01
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
strongGNA11-related congenital hemangiomaGOFAD

This gene — mechanism propensity

DN
0.4289th %ile
GOF
0.6444th %ile
LOF
0.52top 25%

The highest-scoring mechanism for this gene is gain-of-function.

GOFprediction above median · 1 literature citation

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

GOFAutosomal dominant hypocalcemia (ADH) types 1 and 2 are due to calcium-sensing receptor (CASR) and G-protein subunit-a11 (GNA11) gain-of-function mutations, respectively, whereas CASR and GNA11 loss-of-function mutations result in familial hypocalciuric hypercalcemia (FHH) types 1 and 2, respectivel1

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

References

  1. 1.PMID 24708097 ↗

ClinVar Variant Classifications

0 submitted variants in ClinVar

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.

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients