GNA12
G protein subunit alpha 12
Basic information
Region (hg38): 7:2721822-2870786
Links
Phenotypes
GenCC
Source:
No genCC data.
ClinVar
This is a list of variants' phenotypes submitted to
- not_specified (42 variants)
- not_provided (3 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the GNA12 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000007353.3. 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 | 2 | |||||
| missense | 40 | 42 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 40 | 3 | 1 |
Loading clinvar variants...
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| GNA12 | protein_coding | protein_coding | ENST00000275364 | 4 | 116213 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.970 | 0.0300 | 125299 | 0 | 1 | 125300 | 0.00000399 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 2.09 | 131 | 218 | 0.601 | 0.0000135 | 2515 |
| Missense in Polyphen | 52 | 104.63 | 0.49699 | 1236 | ||
| Synonymous | -1.74 | 116 | 94.5 | 1.23 | 0.00000646 | 747 |
| Loss of Function | 3.05 | 0 | 10.8 | 0.00 | 5.61e-7 | 125 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.00 | 0.00 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.00000883 | 0.00000883 |
| Middle Eastern | 0.00 | 0.00 |
| 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 (PubMed:22609986, PubMed:15525651, PubMed:15240885, PubMed:17565996, PubMed:12515866, PubMed:16787920, PubMed:16705036, PubMed:23762476, PubMed:27084452). Activates effector molecule RhoA by binding and activating RhoGEFs (ARHGEF12/LARG) (PubMed:15240885, PubMed:12515866, PubMed:16202387). GNA12-dependent Rho signaling subsequently regulates transcription factor AP-1 (activating protein-1) (By similarity). GNA12-dependent Rho signaling also regulates protein phosphatese 2A activation causing dephosphorylation of its target proteins (PubMed:15525651, PubMed:17565996). Promotes tumor cell invasion and metastasis by activating RhoA/ROCK signaling pathway and up-regulating proinflammatory cytokine production (PubMed:23762476, PubMed:16787920, PubMed:16705036, PubMed:27084452). Inhibits CDH1- mediated cell adhesion in process independent from Rho activation (PubMed:11976333, PubMed:16787920). Together with NAPA promotes CDH5 localization to plasma membrane (PubMed:15980433). May play a role in the control of cell migration through the TOR signaling cascade (PubMed:22609986). {ECO:0000250|UniProtKB:P27600, ECO:0000269|PubMed:11976333, ECO:0000269|PubMed:12515866, ECO:0000269|PubMed:15240885, ECO:0000269|PubMed:15525651, ECO:0000269|PubMed:15980433, ECO:0000269|PubMed:16705036, ECO:0000269|PubMed:16787920, ECO:0000269|PubMed:17565996, ECO:0000269|PubMed:22609986, ECO:0000269|PubMed:23762476, ECO:0000269|PubMed:27084452}.;
- Pathway
- Long-term depression - Homo sapiens (human);Regulation of actin cytoskeleton - Homo sapiens (human);Vascular smooth muscle contraction - Homo sapiens (human);MAPK signaling pathway - Homo sapiens (human);Sphingolipid signaling pathway - Homo sapiens (human);Phospholipase D signaling pathway - Homo sapiens (human);Pathways in cancer - Homo sapiens (human);cGMP-PKG signaling pathway - Homo sapiens (human);Platelet Aggregation Inhibitor Pathway, Pharmacodynamics;Human Thyroid Stimulating Hormone (TSH) signaling pathway;G Protein Signaling Pathways;MAPK Signaling Pathway;Regulation of Actin Cytoskeleton;Signaling by GPCR;Signal Transduction;pkc-catalyzed phosphorylation of inhibitory phosphoprotein of myosin phosphatase;rho-selective guanine exchange factor akap13 mediates stress fiber formation;thrombin signaling and protease-activated receptors;Thrombin signalling through proteinase activated receptors (PARs);Platelet activation, signaling and aggregation;S1P5 pathway;Hemostasis;Thromboxane A2 receptor signaling;Posttranslational regulation of adherens junction stability and dissassembly;G alpha (12/13) signalling events;TSH;GPCR downstream signalling;PAR1-mediated thrombin signaling events;LPA receptor mediated events;S1P3 pathway;S1P4 pathway;Sphingosine 1-phosphate (S1P) pathway;Endothelins;S1P2 pathway
(Consensus)
Recessive Scores
- pRec
- 0.212
Intolerance Scores
- loftool
- rvis_EVS
- -0.47
- rvis_percentile_EVS
- 23.04
Haploinsufficiency Scores
- pHI
- 0.133
- hipred
- Y
- hipred_score
- 0.825
- ghis
- 0.593
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.996
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Gna12
- Phenotype
- endocrine/exocrine gland phenotype; cellular phenotype; homeostasis/metabolism phenotype; muscle 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); 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; embryo phenotype; immune system phenotype;
Gene ontology
- Biological process
- in utero embryonic development;G protein-coupled receptor signaling pathway;adenylate cyclase-modulating G protein-coupled receptor signaling pathway;Rho protein signal transduction;blood coagulation;regulation of cell shape;regulation of fibroblast migration;cell differentiation;platelet activation;regulation of TOR signaling;regulation of proteasomal ubiquitin-dependent protein catabolic process;response to drug;embryonic digit morphogenesis
- Cellular component
- cytoplasm;heterotrimeric G-protein complex;plasma membrane;focal adhesion;lateral plasma membrane;brush border membrane
- Molecular function
- G protein-coupled receptor binding;GTPase activity;protein binding;GTP binding;G-protein beta/gamma-subunit complex binding;D5 dopamine receptor binding;metal ion binding