GNG3

protein-coding

G protein subunit gamma 3, the group of G protein subunits gamma

Gene summary

Guanine nucleotide binding proteins are heterotrimeric signal-transducing molecules consisting of alpha, beta, and gamma subunits. The gamma subunit determines the specificity of which signaling pathways will be affected by this particular complex. The protein encoded by this gene represents the gamma subunit of both inhibitory and stimulatory complexes. [provided by RefSeq, Jan 2012]

MANE transcript

NM_012202.5

Inheritance

—

ClinVar variants

P:1U:4B:2

Top phenotype

Inborn genetic diseases

gnomAD constraint

pLI —, LoF o/e 0

Max pathogenic AF

—

Genomic locus

chr11:62,707,676-62,709,201

External References & Databases

Ensembl (ENSG00000162188)

Transcript & Mutation Effects

hg38 • Region Span ~1.5 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 GNG3 variants in ClinVar

3 Conditions Cataloged

not providedTotal: 5

not specifiedTotal: 2

Inborn genetic diseasesTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_012202.5. 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 clinvar	2 clinvar		3
missense			3 clinvar			3
nonsense						0
start loss						0
frameshift		1 clinvar				1
splice donor/acceptor (+/-2bp)						0
Total	0	1	4	2	0	7

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 25 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_012202.5	RefSeq	NP_036334.1	2	MANE Select
ENST00000294117.6	Ensembl	ENSP00000294117.5	2	MANE Select
ENST00000850846.1	Ensembl	ENSP00000520935.1	2	Standard
ENST00000850846.2	Ensembl	ENSP00000520935.1	2	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

PI3K-Akt signaling pathway - Homo sapiens (human)
Relaxin signaling pathway - Homo sapiens (human)
Kaposi,s sarcoma-associated herpesvirus infection - Homo sapiens (human)
Retrograde endocannabinoid signaling - Homo sapiens (human)
GABAergic synapse - Homo sapiens (human)

Biological Process

activation of MAPK activity
G protein-coupled receptor signaling pathway
positive regulation of cytosolic calcium ion concentration

Molecular Function

GTPase activity
protein binding

Cellular Component

heterotrimeric G-protein complex
plasma membrane
postsynaptic density
dendrite
cell body

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000294117
Coding exons: 2
Length: 1544
Individuals with no LoFs: 125723
Homozygous LoFs: 0
Heterozygous LoFs: 1
Defined: 125724
p: 0.00000398

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.16	24	46.2	0.519	0.00000265	495
Missense (PolyPhen)		5	19.936	0.25081		232
Synonymous	-0.308	18	16.4	1.10	9.77e-7	141
Loss of Function	1.41	0	2.32	0.00	9.69e-8	31

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 a modulator or transducer in various transmembrane signaling systems. The beta and gamma chains are required for the GTPase activity, for replacement of GDP by GTP, and for G protein- effector interaction.;

Intolerance Scores

RVIS EVS: 0.17
RVIS percentile EVS: 65.04

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.731

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Low	Low	Low
Primary Immunodeficiency	Low	Low	Low
Cancer	Low	Low	Low