GNA11
protein-codingG protein subunit alpha 11, the group of G protein subunits alpha, group q
Gene summary
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]
- HHC2
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~29.6 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AD
Disease ID:MONDO:0018543
Submitter: Orphanet
Inheritance Pattern: AD
Disease ID:MONDO:0007792
Submitter: PanelApp Australia
Inheritance Pattern: AD
Disease ID:MONDO:0014146
Submitter: PanelApp Australia
Inheritance Pattern: AD
Disease ID:MONDO:0007792
Submitter: Labcorp Genetics (formerly Invitae)
Inheritance Pattern: AD
Disease ID:MONDO:0014146
Submitter: Genomics England PanelApp
Inheritance Pattern: AD
Disease ID:MONDO:0014146
Submitter: Labcorp Genetics (formerly Invitae)
Inheritance Pattern: AD
Disease ID:MONDO:0007792
Submitter: Genomics England PanelApp
Inheritance Pattern: AD
Disease ID:MONDO:0014146
Submitter: Ambry Genetics
Inheritance Pattern: AD
Disease ID:MONDO:0018715
Submitter: G2P
Inheritance Pattern: AD
Disease ID:MONDO:0007792
Submitter: Ambry Genetics
Inheritance Pattern: AD
Disease ID:MONDO:0007792
Submitter: Orphanet
Clinical Genomic Database (CGD)
Manifestation: Endocrine
Intervention: Endocrine
Rationale: 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
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to GNA11 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_002067.5. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 1 | 106 | 1 | 108 | ||
| missense | 9 | 10 | 138 | 2 | 159 | |
| nonsense | 1 | 5 | 6 | |||
| start loss | 0 | |||||
| frameshift | 5 | 5 | 10 | |||
| splice donor/acceptor (+/-2bp) | 1 | 2 | 9 | 12 | ||
| Total | 10 | 18 | 158 | 108 | 1 | 295 |
Highest pathogenic variant AF is 0.0000020536747
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_002058.2 | 7 | MANE Select | |
| Ensembl | ENSP00000078429.3 | 7 | MANE Select | |
| Ensembl | ENSP00000465935.1 | 6 | Standard | |
| Ensembl | ENSP00000479797.1 | 2 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- 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)
Biological Process
- skeletal system development
- action potential
- signal transduction
- G protein-coupled receptor signaling pathway
- adenylate cyclase-modulating G protein-coupled receptor signaling pathway
Molecular Function
- G protein-coupled receptor binding
- GTPase activity
- GTP binding
- G-protein beta/gamma-subunit complex binding
- type 2A serotonin receptor binding
Cellular Component
- photoreceptor outer segment
- cytoplasm
- lysosomal membrane
- heterotrimeric G-protein complex
- plasma membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000078429
- Coding exons
- 7
- Length
- 29595
- Individuals with no LoFs
- 125728
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 5
- Defined
- 125733
- p
- 0.0000199
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 3.77 | 84 | 252 | 0.333 | 0.0000177 | 2368 |
| Missense (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 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00025 | 0.00025 | rare |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.000054 | 0.000054 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0 | 0.0 | absent |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
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.;
Recessive Scores
- pRec
- 0.177
Intolerance Scores
- LoFtool
- 0.0208
- RVIS EVS
- -0.14
- RVIS percentile EVS
- 43.57
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- S
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.753
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |