GNA11
G protein subunit alpha 11, the group of G protein subunits alpha, group q
Basic information
Region (hg38): 19:3094362-3123999
Previous symbols: [ "HHC2" ]
Links
Phenotypes
GenCC
Source:
- familial hypocalciuric hypercalcemia 2 (Strong), mode of inheritance: AD
- autosomal dominant hypocalcemia 2 (Strong), mode of inheritance: AD
- familial hypocalciuric hypercalcemia 2 (Strong), mode of inheritance: AD
- autosomal dominant hypocalcemia 2 (Moderate), mode of inheritance: AD
- familial hypocalciuric hypercalcemia 2 (Limited), mode of inheritance: AD
- autosomal dominant hypocalcemia (Supportive), mode of inheritance: AD
- familial hypocalciuric hypercalcemia 2 (Supportive), mode of inheritance: AD
- autosomal dominant hypocalcemia 2 (Strong), mode of inheritance: AD
- congenital hemangioma (Strong), mode of inheritance: AD
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Hypocalcemia, autosomal dominant 2; Hypocalciuric hypercalcemia, familial, type II | AD | Endocrine | In Hypocalcemia, early recognition of electrolyte abnormalitities (eg, hypocalcemia) can allow prompt appropriate management in order to avoid and/or promptly treat severe sequelae, which can include hypocalcemic seizures; In Hypocalciuric hypercalcemia, accurate diagnosis may be important in order to decrease the use of unhelpful therapies | Endocrine | 6278146; 23782177; 23802516; 23802536; 24823460 |
ClinVar
This is a list of variants' phenotypes submitted to
- not_provided (289 variants)
- Autosomal_dominant_hypocalcemia_2 (55 variants)
- Familial_hypocalciuric_hypercalcemia_2 (54 variants)
- not_specified (31 variants)
- Inborn_genetic_diseases (15 variants)
- GNA11-related_disorder (12 variants)
- Vascular_malformation (1 variants)
- Schwartz-Jampel_syndrome_type_1 (1 variants)
- CLOVES_syndrome (1 variants)
- See_cases (1 variants)
- Capillary_malformation (1 variants)
- Segmental_undergrowth_associated_with_capillary_malformation (1 variants)
- Venous_malformation (1 variants)
- Lobular_capillary_hemangiomas (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the GNA11 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000002067.5. Only rare variants are included in the table.
In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.
Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUSVUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 94 | 97 | ||||
| missense | 104 | 120 | ||||
| nonsense | 5 | |||||
| start loss | 0 | |||||
| frameshift | 6 | |||||
| splice donor/acceptor (+/-2bp) | 5 | |||||
| Total | 8 | 9 | 118 | 96 | 2 |
Highest pathogenic variant AF is 0.00000186332
Loading clinvar variants...
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| GNA11 | protein_coding | protein_coding | ENST00000078429 | 7 | 29595 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.889 | 0.111 | 125728 | 0 | 5 | 125733 | 0.0000199 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 3.77 | 84 | 252 | 0.333 | 0.0000177 | 2368 |
| Missense in Polyphen | 22 | 102.26 | 0.21513 | 961 | ||
| Synonymous | -0.0134 | 120 | 120 | 1.00 | 0.00000966 | 685 |
| Loss of Function | 3.24 | 2 | 15.9 | 0.125 | 6.81e-7 | 185 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.000249 | 0.000246 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.0000544 | 0.0000544 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.00 | 0.00 |
| Middle Eastern | 0.0000544 | 0.0000544 |
| South Asian | 0.00 | 0.00 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Guanine nucleotide-binding proteins (G proteins) are involved as modulators or transducers in various transmembrane signaling systems. Acts as an activator of phospholipase C.;
- Disease
- DISEASE: Hypocalciuric hypercalcemia, familial 2 (HHC2) [MIM:145981]: A form of hypocalciuric hypercalcemia, a disorder of mineral homeostasis that is transmitted as an autosomal dominant trait with a high degree of penetrance. It is characterized biochemically by lifelong elevation of serum calcium concentrations and is associated with inappropriately low urinary calcium excretion and a normal or mildly elevated circulating parathyroid hormone level. Hypermagnesemia is typically present. Affected individuals are usually asymptomatic and the disorder is considered benign. However, chondrocalcinosis and pancreatitis occur in some adults. {ECO:0000269|PubMed:23802516}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Hypocalcemia, autosomal dominant 2 (HYPOC2) [MIM:615361]: A form of hypocalcemia, a disorder of mineral homeostasis characterized by blood calcium levels below normal, and low or normal serum parathyroid hormone concentrations. Disease manifestations include hypocalcemia, paresthesias, carpopedal spasm, seizures, hypercalciuria with nephrocalcinosis or kidney stones, and ectopic and basal ganglia calcifications. {ECO:0000269|PubMed:23782177, ECO:0000269|PubMed:23802516}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
- Pathway
- Cortisol synthesis and secretion - Homo sapiens (human);Aldosterone synthesis and secretion - Homo sapiens (human);Cushing,s syndrome - Homo sapiens (human);Long-term depression - Homo sapiens (human);GnRH signaling pathway - Homo sapiens (human);Gap junction - Homo sapiens (human);Amoebiasis - Homo sapiens (human);Chagas disease (American trypanosomiasis) - Homo sapiens (human);Calcium signaling pathway - Homo sapiens (human);Vascular smooth muscle contraction - Homo sapiens (human);Pathways in cancer - Homo sapiens (human);cGMP-PKG signaling pathway - Homo sapiens (human);Cholinergic synapse - Homo sapiens (human);Insulin secretion - Homo sapiens (human);Platelet Aggregation Inhibitor Pathway, Pharmacodynamics;Corticotropin-releasing hormone signaling pathway;G Protein Signaling Pathways;GPR40 Pathway;Calcium Regulation in the Cardiac Cell;Signaling by GPCR;Signal Transduction;bioactive peptide induced signaling pathway;role of egf receptor transactivation by gpcrs in cardiac hypertrophy;Thromboxane signalling through TP receptor;Metabolism;Fatty Acids bound to GPR40 (FFAR1) regulate insulin secretion;Acetylcholine regulates insulin secretion;Free fatty acids regulate insulin secretion;Regulation of insulin secretion;Signal amplification;CRH;Thrombin signalling through proteinase activated receptors (PARs);Platelet activation, signaling and aggregation;ADP signalling through P2Y purinoceptor 1;Hemostasis;Thromboxane A2 receptor signaling;TSH;Integration of energy metabolism;G alpha (q) signalling events;GPCR downstream signalling;PAR4-mediated thrombin signaling events;PAR1-mediated thrombin signaling events;LPA receptor mediated events;S1P3 pathway;Arf6 signaling events;Plasma membrane estrogen receptor signaling;Sphingosine 1-phosphate (S1P) pathway;Endothelins;S1P2 pathway
(Consensus)
Recessive Scores
- pRec
- 0.177
Intolerance Scores
- loftool
- 0.0208
- rvis_EVS
- -0.14
- rvis_percentile_EVS
- 43.57
Haploinsufficiency Scores
- pHI
- 0.475
- hipred
- Y
- hipred_score
- 0.762
- ghis
- 0.533
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- S
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.753
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Gna11
- Phenotype
- immune system phenotype; skeleton phenotype; renal/urinary system phenotype; limbs/digits/tail phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); hearing/vestibular/ear phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); hematopoietic system phenotype; normal phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); pigmentation phenotype; liver/biliary system phenotype; respiratory system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); homeostasis/metabolism phenotype; muscle phenotype; craniofacial phenotype; growth/size/body region phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); endocrine/exocrine gland phenotype;
Gene ontology
- Biological process
- skeletal system development;action potential;signal transduction;G protein-coupled receptor signaling pathway;adenylate cyclase-modulating G protein-coupled receptor signaling pathway;G protein-coupled acetylcholine receptor signaling pathway;heart development;phototransduction, visible light;entrainment of circadian clock;platelet activation;regulation of melanocyte differentiation;developmental pigmentation;phospholipase C-activating dopamine receptor signaling pathway;cellular response to pH
- Cellular component
- photoreceptor outer segment;cytoplasm;lysosomal membrane;heterotrimeric G-protein complex;plasma membrane;extracellular exosome
- Molecular function
- G protein-coupled receptor binding;GTPase activity;GTP binding;G-protein beta/gamma-subunit complex binding;type 2A serotonin receptor binding;metal ion binding