ATP6V1G3

protein-coding

ATPase H+ transporting V1 subunit G3, the group of V-type ATPase subunits

Gene summary

This gene encodes a component of vacuolar ATPase (V-ATPase), a multisubunit enzyme that mediates acidification of eukaryotic intracellular organelles. V-ATPase dependent organelle acidification is necessary for such intracellular processes as protein sorting, zymogen activation, receptor-mediated endocytosis, and synaptic vesicle proton gradient generation. V-ATPase is composed of a cytosolic V1 domain and a transmembrane V0 domain. The V1 domain consists of three A and three B subunits, two G subunits plus the C, D, E, F, and H subunits. The V1 domain contains the ATP catalytic site. The V0 domain consists of five different subunits: a, c, c', c'' and d. Additional isoforms of many of the V1 and V0 subunit proteins are encoded by multiple genes or alternatively spliced transcript variants. This gene encodes one of three G subunit proteins. Transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

MANE transcript

NM_001376861.1

Inheritance

—

ClinVar variants

U:18B:3

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.4

Max pathogenic AF

—

Genomic locus

chr1:198,523,222-198,540,945

External References & Databases

Ensembl (ENSG00000151418)

Transcript & Mutation Effects

hg38 • Region Span ~17.7 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 ATP6V1G3 variants in ClinVar

1 Conditions Cataloged

not specifiedTotal: 20

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001376861.1. 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
missense			17 clinvar	2 clinvar		19
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	18	3	0	21

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 14 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001376861.1	RefSeq	NP_001363790.1	3	MANE Select
ENST00000367382.6	Ensembl	ENSP00000356352.2	3	MANE Select
NM_001320218.2	RefSeq	NP_001307147.1	4	Standard
NM_001376862.1	RefSeq	NP_001363791.1	4	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

mTOR signaling pathway - Homo sapiens (human)
Synaptic vesicle cycle - Homo sapiens (human)
Phagosome - Homo sapiens (human)
Epithelial cell signaling in Helicobacter pylori infection - Homo sapiens (human)
Oxidative phosphorylation - Homo sapiens (human)

Biological Process

insulin receptor signaling pathway
transferrin transport
ion transmembrane transport
proton transmembrane transport

Molecular Function

proton-exporting ATPase activity, phosphorylative mechanism
ATPase binding

Cellular Component

cytosol
plasma membrane
vacuolar proton-transporting V-type ATPase complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000281087
Coding exons: 3
Length: 17724
Individuals with no LoFs: 125393
Homozygous LoFs: 0
Heterozygous LoFs: 11
Defined: 125404
p: 0.0000439

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.254	51	56.4	0.905	0.00000248	783
Missense (PolyPhen)		11	17.973	0.61203		262
Synonymous	0.585	15	18.2	0.825	7.83e-7	185
Loss of Function	1.26	2	5.05	0.396	2.80e-7	60

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.00017	0.00015	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.000048	0.000044	rare
South Asian	0.000036	0.000033	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Catalytic subunit of the peripheral V1 complex of vacuolar ATPase (V-ATPase). V-ATPase is responsible for acidifying a variety of intracellular compartments in eukaryotic cells.;

Recessive Scores

pRec: 0.117

Intolerance Scores

LoFtool: 0.711
RVIS EVS: 1.1
RVIS percentile EVS: 91.93

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.114

Gene Damage Prediction

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