ATP6V1G3

Summary

ATP6V1G3 (ATPase H+ transporting V1 subunit G3, HGNC:18265) is a protein-coding gene on chromosome 1q31.3, encoding V-type proton ATPase subunit G 3 (Q96LB4). Subunit of the V1 complex of vacuolar(H+)-ATPase (V-ATPase), a multisubunit enzyme composed of a peripheral complex (V1) that hydrolyzes ATP and a membrane integral complex (V0) that translocates protons.

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.

Source: NCBI Gene 127124 — RefSeq curated summary.

At a glance

• GWAS associations: 10
• Clinical variants (ClinVar): 22 total
• MANE Select transcript: NM_001376861

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18265
Approved symbol	ATP6V1G3
Name	ATPase H+ transporting V1 subunit G3
Location	1q31.3
Locus type	gene with protein product
Status	Approved
Aliases	ATP6G3, Vma10
Ensembl gene	ENSG00000151418
Ensembl biotype	protein_coding
OMIM	618071
Entrez	127124

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 4 protein_coding

ENST00000281087, ENST00000309309, ENST00000367382, ENST00000489986

RefSeq mRNA: 6 — MANE Select: NM_001376861 NM_001320218, NM_001376861, NM_001376862, NM_001376863, NM_133262, NM_133326

CCDS: CCDS1395, CCDS1396, CCDS81414

Canonical transcript exons

ENST00000367382 — 3 exons

Exon	Start	End
ENSE00001444392	198540569	198540680
ENSE00003516824	198523222	198523564
ENSE00003541848	198529081	198529181

Expression profiles

Bgee: expression breadth broad, 42 present calls, max score 95.67.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0442 / max 33.8431, expressed in 13 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
16521	0.0442	13

Top tissues by expression

110 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	95.67	gold quality
adult mammalian kidney	UBERON:0000082	91.90	gold quality
metanephros cortex	UBERON:0010533	88.00	gold quality
kidney	UBERON:0002113	85.53	gold quality
cortex of kidney	UBERON:0001225	75.08	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	56.41	gold quality
hindlimb stylopod muscle	UBERON:0004252	51.49	gold quality
minor salivary gland	UBERON:0001830	47.42	gold quality
saliva-secreting gland	UBERON:0001044	46.76	gold quality
colonic epithelium	UBERON:0000397	44.10	silver quality
mucosa of transverse colon	UBERON:0004991	41.07	silver quality
lymph node	UBERON:0000029	41.03	gold quality
ganglionic eminence	UBERON:0004023	40.90	gold quality
bone marrow cell	CL:0002092	39.70	gold quality
tonsil	UBERON:0002372	38.72	gold quality
bone marrow	UBERON:0002371	37.19	silver quality
ventricular zone	UBERON:0003053	36.48	gold quality
cortical plate	UBERON:0005343	36.47	gold quality
prostate gland	UBERON:0002367	35.63	gold quality
skeletal muscle tissue	UBERON:0001134	33.38	gold quality
placenta	UBERON:0001987	31.76	gold quality
spleen	UBERON:0002106	31.13	silver quality
muscle tissue	UBERON:0002385	31.06	gold quality
sural nerve	UBERON:0015488	30.93	gold quality
liver	UBERON:0002107	30.89	gold quality
stromal cell of endometrium	CL:0002255	29.87	gold quality
prefrontal cortex	UBERON:0000451	29.77	gold quality
monocyte	CL:0000576	29.62	silver quality
leukocyte	CL:0000738	29.44	silver quality
right lung	UBERON:0002167	28.46	silver quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-HCAD-38	yes	378.13
E-CURD-119	yes	18.83
E-ANND-3	no	0.16

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

43 targeting ATP6V1G3, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-371A-3P	99.99	66.77	91
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-4487	99.96	64.58	1252
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-3912-5P	99.95	66.11	925
HSA-MIR-12119	99.87	68.35	1653
HSA-MIR-4495	99.82	72.08	3080
HSA-MIR-4659A-3P	99.80	72.62	4248
HSA-MIR-4659B-3P	99.80	72.62	4248
HSA-MIR-4677-5P	99.70	70.09	1940
HSA-MIR-29B-2-5P	99.67	68.98	1726
HSA-MIR-587	99.64	70.86	2611
HSA-MIR-142-3P	99.62	71.30	974
HSA-MIR-7152-5P	99.60	69.33	2094
HSA-MIR-6073	99.60	70.36	793
HSA-MIR-141-5P	99.57	67.86	897
HSA-MIR-12122	99.56	69.33	1672
HSA-MIR-4276	99.56	67.66	2514
HSA-MIR-486-5P	99.51	70.39	707
HSA-MIR-4251	99.40	69.19	3363
HSA-MIR-2116-5P	99.32	69.34	1273
HSA-MIR-20B-3P	99.29	67.05	784
HSA-MIR-4717-3P	99.06	66.34	1072
HSA-MIR-452-3P	99.01	66.25	1241
HSA-MIR-138-2-3P	98.91	68.33	1643
HSA-MIR-29B-1-5P	98.86	68.35	1364
HSA-MIR-3074-5P	98.82	66.56	1414
HSA-MIR-760	98.81	66.65	1392

Literature-anchored findings (GeneRIF, showing 2)

• V-ATPases affecting the pH of the cytosol and intracellular compartments, particularly those containing a3, are also involved in invasion in breast cancer (PMID:19366680)
• ATP6V1G3 Acts as a Key Gene in Recurrent Spontaneous Abortion: An Integrated Bioinformatics Analysis. (PMID:33028803)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Atp6v1g3	ENSMUSG00000026394
rattus_norvegicus	Atp6v1g3	ENSRNOG00000022480

Paralogs (2): ATP6V1G1 (ENSG00000136888), ATP6V1G2 (ENSG00000213760)

Protein

Protein identifiers

V-type proton ATPase subunit G 3 — Q96LB4 (reviewed: Q96LB4)

Alternative names: V-ATPase 13 kDa subunit 3, Vacuolar proton pump subunit G 3

All UniProt accessions (1): Q96LB4

UniProt curated annotations — full annotation on UniProt →

Function. Subunit of the V1 complex of vacuolar(H+)-ATPase (V-ATPase), a multisubunit enzyme composed of a peripheral complex (V1) that hydrolyzes ATP and a membrane integral complex (V0) that translocates protons. V-ATPase is responsible for acidifying and maintaining the pH of intracellular compartments and in some cell types, is targeted to the plasma membrane, where it is responsible for acidifying the extracellular environment.

Subunit / interactions. V-ATPase is a heteromultimeric enzyme made up of two complexes: the ATP-hydrolytic V1 complex and the proton translocation V0 complex. The V1 complex consists of three catalytic AB heterodimers that form a heterohexamer, three peripheral stalks each consisting of EG heterodimers, one central rotor including subunits D and F, and the regulatory subunits C and H. The proton translocation complex V0 consists of the proton transport subunit a, a ring of proteolipid subunits c9c’’, rotary subunit d, subunits e and f, and the accessory subunits ATP6AP1/Ac45 and ATP6AP2/PRR.

Tissue specificity. Kidney.

Similarity. Belongs to the V-ATPase G subunit family.

Isoforms (4)

UniProt ID	Names	Canonical?
Q96LB4-1	1	yes
Q96LB4-2	2
Q96LB4-3	3
Q96LB4-4	4

RefSeq proteins (6): NP_001307147, NP_001363790, NP_001363791, NP_001363792, NP_573569, NP_579872 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR005124	V-ATPase_G	Family

Pfam: PF03179

UniProt features (7 total): splice variant 2, chain 1, region of interest 1, coiled-coil region 1, compositionally biased region 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96LB4-F1	92.79	0.79

Function

Pathways and Gene Ontology

Reactome pathways

5 pathways

ID	Pathway
R-HSA-1222556	ROS and RNS production in phagocytes
R-HSA-77387	Insulin receptor recycling
R-HSA-917977	Transferrin endocytosis and recycling
R-HSA-9639288	Amino acids regulate mTORC1
R-HSA-983712	Ion channel transport

MSigDB gene sets: 93 (showing top): REACTOME_SIGNALING_BY_INSULIN_RECEPTOR, REACTOME_INNATE_IMMUNE_SYSTEM, GOCC_VACUOLAR_MEMBRANE, GOBP_VESICLE_ORGANIZATION, GOBP_VESICLE_MEDIATED_TRANSPORT, GOBP_MONOATOMIC_CATION_TRANSPORT, GOMF_PROTON_TRANSMEMBRANE_TRANSPORTER_ACTIVITY, TATA_C, HAND1E47_01, GOBP_TRANSMEMBRANE_TRANSPORT, KEGG_EPITHELIAL_CELL_SIGNALING_IN_HELICOBACTER_PYLORI_INFECTION, GOCC_EXOCYTIC_VESICLE, GOCC_SECRETORY_VESICLE, GOCC_PROTON_TRANSPORTING_TWO_SECTOR_ATPASE_COMPLEX_CATALYTIC_DOMAIN, GOBP_HOMEOSTATIC_PROCESS

GO Biological Process (3): synaptic vesicle lumen acidification (GO:0097401), monoatomic ion transport (GO:0006811), proton transmembrane transport (GO:1902600)

GO Molecular Function (4): ATP hydrolysis activity (GO:0016887), proton-transporting ATPase activity, rotational mechanism (GO:0046961), ATPase binding (GO:0051117), protein binding (GO:0005515)

GO Cellular Component (5): vacuolar proton-transporting V-type ATPase, V1 domain (GO:0000221), cytosol (GO:0005829), plasma membrane (GO:0005886), synaptic vesicle membrane (GO:0030672), vacuolar proton-transporting V-type ATPase complex (GO:0016471)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
Innate Immune System	1
Signaling by Insulin receptor	1
Iron uptake and transport	1
Cellular response to starvation	1
Transport of small molecules	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
intercellular transport	1
synaptic vesicle maturation	1
establishment of localization in cell	1
neuron cellular homeostasis	1
synaptic vesicle cycle	1
proton transmembrane transport	1
transport	1
monoatomic cation transmembrane transport	1
ribonucleoside triphosphate phosphatase activity	1
ATP-dependent activity	1
proton transmembrane transporter activity	1
ATPase-coupled monoatomic cation transmembrane transporter activity	1
ATPase activity, coupled to transmembrane movement of ions, rotational mechanism	1
enzyme binding	1
binding	1
vacuole	1
vacuolar proton-transporting V-type ATPase complex	1
proton-transporting V-type ATPase, V1 domain	1
cytoplasm	1
cellular anatomical structure	1
membrane	1
cell periphery	1
synaptic vesicle	1
exocytic vesicle membrane	1
vacuolar membrane	1
proton-transporting V-type ATPase complex	1

Protein interactions and networks

STRING

724 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ATP6V1G3	ATP6V1E2	Q96A05	886
ATP6V1G3	ATP6V1E1	P36543	847
ATP6V1G3	ATP6V1F	Q16864	818
ATP6V1G3	ATP6V1D	Q9Y5K8	806
ATP6V1G3	ATP6V0D2	Q8N8Y2	793
ATP6V1G3	ATP6V0A4	Q9HBG4	788
ATP6V1G3	ATP6V0D1	P12953	761
ATP6V1G3	ATP6V0A1	Q93050	743
ATP6V1G3	ATP6V0A2	Q9Y487	743
ATP6V1G3	ATP6V1B1	P15313	733
ATP6V1G3	ATP6V1C2	Q8NEY4	733
ATP6V1G3	TCIRG1	Q13488	703
ATP6V1G3	ATP6V1H	Q9UI12	696
ATP6V1G3	ATP6V0B	Q99437	693
ATP6V1G3	ATP6V1C1	P21283	661

IntAct

1 interactions, top by confidence:

BioGRID (5): MTMR4 (Affinity Capture-MS), OTX2 (Two-hybrid), ATP6V1G3 (Negative Genetic), ATP6V1G3 (Cross-Linking-MS (XL-MS)), CHCHD3 (Cross-Linking-MS (XL-MS))

ESM2 similar proteins: A4QNE9, A5DG59, A6MVW6, A6ZL57, A7M8Z0, A8PKH2, A8WM57, A9V549, B1A921, B3LN41, B4UN38, B5RSM1, O00780, O13687, O74174, O75348, O78477, O95670, P06453, P22203, P34339, P42171, P48836, P79251, P87150, P91303, Q00822, Q07508, Q0VCV6, Q19VA4, Q1XHY9, Q25532, Q40609, Q54Z13, Q5TM18, Q5WR09, Q5XGW0, Q617N0, Q6MGM3, Q6WNK7

Diamond homologs: A4QNE9, O75348, O95670, P79251, P91303, Q0VCV6, Q1XHY9, Q25532, Q5TM18, Q5WR09, Q5XGW0, Q617N0, Q862Z6, Q8BMC1, Q96LB4, Q9CR51, Q9TSV6, Q9WTT4, Q9XZH6, O74174, P48836, O82628, O82629, O82702, O82703, Q9SP55, Q9SZH0

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

22 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	18
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

252 predictions. Top by Δscore:

Variant	Effect	Δscore
1:198523561:TTAT:T	acceptor_gain	1.0000
1:198523564:TCTA:T	acceptor_loss	1.0000
1:198523565:C:A	acceptor_loss	1.0000
1:198523565:C:CC	acceptor_gain	1.0000
1:198523569:C:CT	acceptor_gain	1.0000
1:198529076:CTCA:C	donor_gain	1.0000
1:198529077:TCAC:T	donor_loss	1.0000
1:198529078:CA:C	donor_loss	1.0000
1:198529079:A:AC	donor_gain	1.0000
1:198529079:A:AT	donor_loss	1.0000
1:198529080:C:CA	donor_loss	1.0000
1:198529080:C:CC	donor_gain	1.0000
1:198529080:CCTT:C	donor_gain	1.0000
1:198529179:TTC:T	acceptor_gain	1.0000
1:198540563:ACTT:A	donor_loss	1.0000
1:198540564:CTT:C	donor_loss	1.0000
1:198540565:TTA:T	donor_loss	1.0000
1:198540566:TAC:T	donor_loss	1.0000
1:198540567:A:AC	donor_gain	1.0000
1:198540567:A:AT	donor_loss	1.0000
1:198540567:ACT:A	donor_gain	1.0000
1:198540568:C:CG	donor_gain	1.0000
1:198540568:CT:C	donor_gain	1.0000
1:198540568:CTC:C	donor_gain	1.0000
1:198540568:CTCT:C	donor_gain	1.0000
1:198540568:CTCTT:C	donor_gain	1.0000
1:198540580:T:TA	donor_gain	1.0000
1:198523560:ATTAT:A	acceptor_gain	0.9900
1:198523562:TAT:T	acceptor_gain	0.9900
1:198523570:A:T	acceptor_gain	0.9900

AlphaMissense

796 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:198529146:C:G	A40P	0.987
1:198529158:C:G	A36P	0.986
1:198540578:C:G	A25P	0.985
1:198540611:C:G	A14P	0.985
1:198540619:A:G	L11P	0.984
1:198529169:C:G	R32P	0.978
1:198540599:C:G	A18P	0.977
1:198540619:A:T	L11H	0.976
1:198529177:T:A	K29N	0.968
1:198529177:T:G	K29N	0.968
1:198540616:A:G	L12P	0.968
1:198540598:G:T	A18D	0.965
1:198540601:C:G	R17P	0.950
1:198529157:G:T	A36D	0.946
1:198540573:C:A	K26N	0.942
1:198540573:C:G	K26N	0.942
1:198523452:A:G	L99P	0.936
1:198523497:A:G	L84P	0.930
1:198540577:G:T	A25D	0.920
1:198529178:T:A	K29I	0.917
1:198540619:A:C	L11R	0.916
1:198540632:C:G	G7R	0.913
1:198540632:C:T	G7R	0.913
1:198529099:A:C	F55L	0.908
1:198529099:A:T	F55L	0.908
1:198529101:A:G	F55L	0.908
1:198540607:T:A	E15V	0.907
1:198540620:G:A	L11F	0.906
1:198540628:A:G	I8T	0.905
1:198540586:A:G	L22P	0.904

dbSNP variants (sampled 300 via entrez): RS1000084319 (1:198538633 A>G), RS1000435028 (1:198538844 C>G), RS1001202095 (1:198532992 A>G), RS1001230033 (1:198531702 A>T), RS1001255623 (1:198538218 G>A), RS1001256162 (1:198532719 G>A), RS1001292461 (1:198526469 A>G), RS1001701268 (1:198539598 T>A), RS1001713544 (1:198540035 A>G), RS1001750364 (1:198525181 T>C), RS1001762947 (1:198532025 T>A), RS1001790430 (1:198537914 G>A), RS1001946502 (1:198527089 T>C), RS1002099795 (1:198533184 G>A), RS1002607511 (1:198524181 A>G)

Disease associations

OMIM: gene MIM:618071 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

10 associations (top):

Study	Trait	p-value
GCST000587_11	Mean corpuscular hemoglobin	7.000000e-10
GCST002002_1	Adverse response to chemotherapy (neutropenia/leucopenia) (cyclophosphamide)	6.000000e-06
GCST005992_26	Mean corpuscular hemoglobin concentration	1.000000e-08
GCST005993_64	Mean corpuscular hemoglobin	2.000000e-47
GCST005996_52	Red blood cell count	3.000000e-18
GCST006011_91	Mean corpuscular volume	3.000000e-44
GCST007325_66	General risk tolerance (MTAG)	4.000000e-10
GCST008158_148	Body mass index	7.000000e-06
GCST009597_299	Multiple sclerosis	2.000000e-07
GCST009798_23	Asthma	7.000000e-10

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0004509	hemoglobin measurement
EFO:0004527	mean corpuscular hemoglobin
EFO:0004528	mean corpuscular hemoglobin concentration
EFO:0004305	erythrocyte count
EFO:0008579	risk-taking behaviour
EFO:0004340	body mass index

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: transporter — V-type ATPase

CTD chemical–gene interactions

4 total (human), top 4 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	increases methylation	1
CGP 52608	affects binding, increases reaction	1
Benzo(a)pyrene	decreases expression	1
Aflatoxin B1	decreases methylation	1

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.