GNA12

protein-coding

G protein subunit alpha 12

Gene summary

Enables G protein activity; protein phosphatase 2A binding activity; and protein phosphatase activator activity. Involved in Rho-activating G protein-coupled receptor signaling pathway; regulation of TOR signaling; and regulation of proteasomal ubiquitin-dependent protein catabolic process. Located in several cellular components, including cytosol; lateral plasma membrane; and neuronal cell body. [provided by Alliance of Genome Resources, Jun 2026]

MANE transcript

NM_007353.3

Inheritance

—

ClinVar variants

U:48B:4

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0

Max pathogenic AF

—

Genomic locus

chr7:2,721,822-2,870,786

External References & Databases

Ensembl (ENSG00000146535)

Transcript & Mutation Effects

hg38 • Region Span ~149.0 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to GNA12 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 47

not providedTotal: 3

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_007353.3. 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 clinvar	1 clinvar	2
missense			46 clinvar	2 clinvar		48
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	48	3	1	52

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 29 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_007353.3	RefSeq	NP_031379.2	4	MANE Select
ENST00000275364.8	Ensembl	ENSP00000275364.3	4	MANE Select
NM_001282440.1	RefSeq	NP_001269369.1	3	Standard
NM_001282441.2	RefSeq	NP_001269370.1	5	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

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)

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

Molecular Function

G protein-coupled receptor binding
GTPase activity
protein binding
GTP binding
G-protein beta/gamma-subunit complex binding

Cellular Component

cytoplasm
heterotrimeric G-protein complex
plasma membrane
focal adhesion
lateral plasma membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000275364
Coding exons: 4
Length: 116213
Individuals with no LoFs: 125299
Homozygous LoFs: 0
Heterozygous LoFs: 1
Defined: 125300
p: 0.00000399

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.09	131	218	0.601	0.0000135	2515
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.0000088	0.0000088	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

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}.;

Recessive Scores

pRec: 0.212

Intolerance Scores

RVIS EVS: -0.47
RVIS percentile EVS: 23.04

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.996

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium