GNA12

G protein subunit alpha 12

Basic information

Region (hg38): 7:2728104-2844308

Links

ENSG00000146535 ∙ NCBI:2768 ∙ OMIM:604394 ∙ HGNC:4380 ∙ Uniprot:Q03113 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the GNA12 gene.

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.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				1	1	2
missense			16	2		18
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding				1		1
Total	0	0	16	4	1

Variants in GNA12

This is a list of pathogenic ClinVar variants found in the GNA12 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
7-2731252-C-T		not specified	Likely benign (May 15, 2023)
7-2731264-C-A		not specified	Uncertain significance (Dec 28, 2022)
7-2731302-C-A		not specified	Uncertain significance (Jun 09, 2022)
7-2731321-C-T		not specified	Uncertain significance (Dec 11, 2023)
7-2731341-C-T		not specified	Uncertain significance (Feb 22, 2023)
7-2731349-G-A			Benign (Dec 20, 2018)
7-2731353-T-G		not specified	Uncertain significance (Sep 22, 2022)
7-2731542-A-G		not specified	Uncertain significance (Jun 27, 2022)
7-2731590-G-A		not specified	Uncertain significance (Mar 18, 2024)
7-2731624-G-A		not specified	Uncertain significance (Jun 17, 2024)
7-2731678-C-T		not specified	Uncertain significance (Jan 24, 2023)
7-2794947-C-T		not specified	Uncertain significance (Apr 25, 2022)
7-2794987-C-T		not specified	Uncertain significance (Mar 01, 2023)
7-2794999-G-C		not specified	Uncertain significance (Aug 15, 2023)
7-2795026-C-G		not specified	Uncertain significance (Mar 19, 2024)
7-2795092-A-G		not specified	Likely benign (Dec 07, 2023)
7-2795139-G-A		not specified	Uncertain significance (Feb 05, 2024)
7-2814361-C-T			Likely benign (Dec 01, 2022)
7-2843895-C-G			Likely benign (Dec 01, 2022)
7-2843904-G-C		not specified	Uncertain significance (Dec 19, 2022)
7-2843920-T-C		not specified	Uncertain significance (May 28, 2024)
7-2843990-C-T		not specified	Uncertain significance (Dec 06, 2022)
7-2843998-C-T		not specified	Uncertain significance (Jun 09, 2022)
7-2844002-C-A		not specified	Uncertain significance (Jan 08, 2024)
7-2844071-C-T		not specified	Uncertain significance (Oct 13, 2023)

GnomAD

Source: gnomAD

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: dbNSFP

• 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

• 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