GNAI2

protein-coding

G protein subunit alpha i2, the group of G protein subunits alpha, group i|MicroRNA protein coding host genes

Gene summary

The protein encoded by this gene is an alpha subunit of guanine nucleotide binding proteins (G proteins). The encoded protein contains the guanine nucleotide binding site and is involved in the hormonal regulation of adenylate cyclase. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2013]

Previous symbols:

GNAI2B

MANE transcript

NM_002070.4

Inheritance

ClinVar variants

P:8U:33B:6

Top phenotype

MAGIS SYNDROME

gnomAD constraint

pLI —, LoF o/e 0.12

Max pathogenic AF

—

Genomic locus

chr3:50,226,292-50,259,362

External References & Databases

Ensembl (ENSG00000114353)

Transcript & Mutation Effects

hg38 • Region Span ~33.1 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

ventricular tachycardia, familialNO_KNOWN

Inheritance Pattern: Unknown

Disease ID:MONDO:0008648

Submitter: Labcorp Genetics (formerly Invitae)

ventricular tachycardia, familialMODERATE

Inheritance Pattern: AD

Disease ID:MONDO:0008648

Submitter: PanelApp Australia

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to GNAI2 variants in ClinVar

19 Conditions Cataloged

not providedTotal: 16

not specifiedTotal: 13

MAGIS SYNDROMETotal: 5

GNAI2-related disorderTotal: 2

Ovarian granulosa cell tumorTotal: 2

THECOMA, SOMATICTotal: 2

Adrenocortical tumor, somaticTotal: 2

Retractile testisTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_002070.4. 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			2 clinvar	5 clinvar		7
missense	6 clinvar	2 clinvar	24 clinvar	1 clinvar		33
nonsense						0
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)			6 clinvar			6
Total	6	2	33	6	0	47

Highest pathogenic variant AF is 0.000001281207

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 31 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_002070.4	RefSeq	NP_002061.1	8	MANE Select
ENST00000313601.11	Ensembl	ENSP00000312999.6	8	MANE Select
NM_001166425.2	RefSeq	NP_001159897.1	8	Standard
NM_001282617.2	RefSeq	NP_001269546.1	7	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Platelet activation - Homo sapiens (human)
Relaxin signaling pathway - Homo sapiens (human)
Regulation of lipolysis in adipocytes - Homo sapiens (human)
Oxytocin signaling pathway - Homo sapiens (human)
Pertussis - Homo sapiens (human)

Biological Process

adenosine receptor signaling pathway
protein folding
cell cycle
signal transduction
G protein-coupled receptor signaling pathway

Molecular Function

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

Cellular Component

nucleoplasm
cytoplasm
centrosome
cytosol
heterotrimeric G-protein complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000313601
Coding exons: 8
Length: 33064
Individuals with no LoFs: 124933
Homozygous LoFs: 0
Heterozygous LoFs: 6
Defined: 124939
p: 0.0000240

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	3.15	91	224	0.407	0.0000140	2359
Missense (PolyPhen)		24	95.332	0.25175		1091
Synonymous	1.58	78	97.8	0.797	0.00000689	645
Loss of Function	3.25	2	16.0	0.125	6.77e-7	201

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	0.000081	0.000054	rare
Finnish	0.00019	0.00019	rare
European (Non-Finnish)	0.0000092	0.0000089	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. The G(i) proteins are involved in hormonal regulation of adenylate cyclase: they inhibit the cyclase in response to beta-adrenergic stimuli. May play a role in cell division. {ECO:0000269|PubMed:17635935}.;

Recessive Scores

pRec: 0.260

Intolerance Scores

LoFtool: 0.0199
RVIS EVS: -0.34
RVIS percentile EVS: 30.37

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.935

Gene Damage Prediction

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