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

ENSG00000088256 ∙ NCBI:2767 ∙ OMIM:139313 ∙ HGNC:4379 ∙ Uniprot:P29992 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• autosomal dominant hypocalcemia 2 (Moderate), mode of inheritance: AD
• familial hypocalciuric hypercalcemia 2 (Limited), mode of inheritance: AD
• autosomal dominant hypocalcemia 2 (Strong), mode of inheritance: AD
• familial hypocalciuric hypercalcemia 2 (Strong), mode of inheritance: AD
• familial hypocalciuric hypercalcemia 2 (Strong), mode of inheritance: AD
• autosomal dominant hypocalcemia 2 (Strong), mode of inheritance: AD
• autosomal dominant hypocalcemia (Supportive), mode of inheritance: AD
• familial hypocalciuric hypercalcemia 2 (Supportive), mode of inheritance: AD
• congenital hemangioma (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

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 ClinVar and linked to the GNA11 gene.

• not_provided (319 variants)
• Autosomal_dominant_hypocalcemia_2 (56 variants)
• Familial_hypocalciuric_hypercalcemia_2 (54 variants)
• not_specified (40 variants)
• Inborn_genetic_diseases (17 variants)
• GNA11-related_disorder (12 variants)
• Familial_hyperparathyroidism_or_Hypocalciuric_hypercalcaemia (2 variants)
• Familial_multiple_nevi_flammei (1 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)
• Familial_hypoparathyroidism (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	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			1	104	1	106
missense	8	9	122	2		141
nonsense		1	4			5
start loss						0
frameshift		1	5			6
splice donor/acceptor (+/-2bp)		1	9			10
Total	8	12	141	106	1

Highest pathogenic variant AF is 0.0000020536747

GnomAD

Source: gnomAD

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
		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: dbNSFP

• 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

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

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