GNG4

protein-coding

G protein subunit gamma 4, the group of G protein subunits gamma

Gene summary

Predicted to enable G-protein beta-subunit binding activity. Involved in negative regulation of cell growth. Located in extracellular exosome. [provided by Alliance of Genome Resources, Jul 2025]

MANE transcript

NM_001098722.2

Inheritance

—

ClinVar variants

U:7

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.47

Max pathogenic AF

—

Genomic locus

chr1:235,547,685-235,650,754

External References & Databases

Ensembl (ENSG00000168243)

Transcript & Mutation Effects

hg38 • Region Span ~103.1 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 GNG4 variants in ClinVar

1 Conditions Cataloged

not specifiedTotal: 7

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001098722.2. 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						0
missense			7 clinvar			7
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	7	0	0	7

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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_001098722.2	RefSeq	NP_001092192.1	2	MANE Select
ENST00000391854.7	Ensembl	ENSP00000375727.2	2	MANE Select
NM_001098721.2	RefSeq	NP_001092191.1	2	Standard
NM_004485.4	RefSeq	NP_004476.1	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

G protein-coupled receptor signaling pathway
regulation of G protein-coupled receptor signaling pathway
negative regulation of cell growth

Molecular Function

GTPase activity
protein binding
G-protein beta-subunit binding

Cellular Component

heterotrimeric G-protein complex
plasma membrane
extracellular exosome

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000391854
Coding exons: 2
Length: 103068
Individuals with no LoFs: 125742
Homozygous LoFs: 0
Heterozygous LoFs: 4
Defined: 125746
p: 0.0000159

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.677	32	44.7	0.715	0.00000246	495
Missense (PolyPhen)		12	19.205	0.62484		224
Synonymous	1.26	9	15.3	0.589	8.28e-7	139
Loss of Function	0.723	1	2.14	0.467	9.00e-8	27

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	0.000054	0.000054	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000026	0.000026	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. {ECO:0000305}.;

Recessive Scores

pRec: 0.110

Intolerance Scores

LoFtool: 0.474
RVIS EVS: 0.06
RVIS percentile EVS: 58

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.892

Gene Damage Prediction

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