GNA11

Chr 19AD

G protein subunit alpha 11

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

NCBI Gene: 2767ENSG00000088256UniProt: P29992

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]

Primary Disease Associations & Inheritance

Hypocalcemia, autosomal dominant 2MIM #615361
AD
Hypocalciuric hypercalcemia, type IIMIM #145981
AD
0
ClinVar variants
0
Pathogenic / LP
0.89
pLI score
3
Active trials
Clinical Summary— GNA11
⚡
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.89) — some intolerance to loss-of-function variants.
💊
Clinical Trials
3 active or recruiting trials — potential therapeutic options may be available
Some data sources returned errors (1)

clinvarCount: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esearch.fcgi

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Missense constrained — critical functional residues
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
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?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
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?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.13 (0.05–0.40)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.33 (0.28–0.40)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.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.

Gene2Phenotype Curations

GNA11-related congenital hemangioma

strong
ADGain Of FunctionAltered Gene Product Structure
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Hypocalcemia, autosomal dominant 2

MIM #615361

Molecular basis of disorder known

Autosomal dominant

Hypocalciuric hypercalcemia, type II

MIM #145981

Molecular basis of disorder known

Autosomal dominant
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Uveal melanoma: From diagnosis to treatment and the science in between.
Chattopadhyay C et al.·Cancer
2016Review
Molecular Frontiers in Melanoma: Pathogenesis, Diagnosis, and Therapeutic Advances.
Kim HJ et al.·Int J Mol Sci
2024Review
Melanoma.
Schadendorf D et al.·Nat Rev Dis Primers
2015Review
Integrative Analysis Identifies Four Molecular and Clinical Subsets in Uveal Melanoma.
Robertson AG et al.·Cancer Cell
2017
GNAQ and GNA11 mutations in uveal melanoma.
Shoushtari AN et al.·Melanoma Res
2014Review
The biology of uveal melanoma.
Amaro A et al.·Cancer Metastasis Rev
2017Review
Oncogenic signaling in uveal melanoma.
Park JJ et al.·Pigment Cell Melanoma Res
2018Review
Diseases associated with calcium-sensing receptor.
Vahe C et al.·Orphanet J Rare Dis
2017Review
INPP5A phosphatase is a synthetic lethal target in GNAQ and GNA11-mutant melanomas.
Elbatsh AMO et al.·Nat Cancer
2024
Clinicopathological correlates of hyperparathyroidism.
Duan K et al.·J Clin Pathol
2015Review
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Autosomal Dominant Hypocalcemia

ADH1 and ADH2 Disease Monitoring Study (DMS)

ACTIVE NOT RECRUITING
NCT05227287Calcilytix Therapeutics, Inc., a BridgeBio companyStarted 2022-01-20
Advanced LymphomaAdvanced Malignant Solid NeoplasmBladder Carcinoma

Targeted Therapy Directed by Genetic Testing in Treating Patients With Advanced Refractory Solid Tumors, Lymphomas, or Multiple Myeloma (The MATCH Screening Trial)

ACTIVE NOT RECRUITING
NCT02465060Phase PHASE2National Cancer Institute (NCI)Started 2015-08-17
AdavosertibAfatinibAfatinib Dimaleate
Metastatic Uveal MelanomaCutaneous MelanomaColorectal Cancer

Study of IDE196 in Patients With Solid Tumors Harboring GNAQ/11 Mutations or PRKC Fusions

RECRUITING
NCT03947385Phase PHASE1, PHASE2IDEAYA BiosciencesStarted 2019-06-28
IDE196BinimetinibCrizotinib

External Resources

Links to major genomics databases and tools