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]

GeneReviewsOMIMResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Hypocalcemia, autosomal dominant 2MIM #615361
AD
Hypocalciuric hypercalcemia, type IIMIM #145981
AD

Clinical highlights

Interpreting a novel variant
Gain of function is the curated mechanism (Gene2Phenotype), so a variant that simply removes the protein may not be the pathogenic class here — missense variants in functional domains often carry more weight.Curated gene-level mechanism — a prior for triage, not a per-variant call.
3
Active trials
101
Pubs (1 yr)
—
P/LP submissions
—
P/LP missense
0.40
LOEUF
GOF
Mechanism· G2P
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GeneReview available — GNA11
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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

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