ATP6V1G1

Summary

ATP6V1G1 (ATPase H+ transporting V1 subunit G1, HGNC:864) is a protein-coding gene on chromosome 9q32, encoding V-type proton ATPase subunit G 1 (O75348). 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. It is a common-essential gene (DepMap: required in 91.7% of cancer cell lines).

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, three B, and two G subunits, as well as a C, D, E, F, and H subunit. The V1 domain contains the ATP catalytic site. The protein encoded by this gene is one of three V1 domain G subunit proteins. Pseudogenes of this gene have been characterized.

Source: NCBI Gene 9550 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 24 total
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 91.7% of screened cell lines (common-essential)
• MANE Select transcript: NM_004888

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:864
Approved symbol	ATP6V1G1
Name	ATPase H+ transporting V1 subunit G1
Location	9q32
Locus type	gene with protein product
Status	Approved
Aliases	ATP6GL, Vma10, ATP6G, DKFZp547P234
Ensembl gene	ENSG00000136888
Ensembl biotype	protein_coding
OMIM	607296
Entrez	9550

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 6 protein_coding, 2 nonsense_mediated_decay, 1 retained_intron

ENST00000374050, ENST00000473413, ENST00000677115, ENST00000677452, ENST00000677498, ENST00000677543, ENST00000678234, ENST00000679150, ENST00000928169

RefSeq mRNA: 1 — MANE Select: NM_004888 NM_004888

CCDS: CCDS6807

Canonical transcript exons

ENST00000374050 — 3 exons

Exon	Start	End
ENSE00000926910	114592552	114592652
ENSE00001462283	114597570	114598879
ENSE00001462286	114587769	114587920

Expression profiles

Bgee: expression breadth ubiquitous, 295 present calls, max score 98.76.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 222.1950 / max 1552.9261, expressed in 1828 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
98172	222.1950	1828

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
adrenal tissue	UBERON:0018303	98.76	gold quality
renal medulla	UBERON:0000362	98.65	gold quality
cardia of stomach	UBERON:0001162	98.59	gold quality
pylorus	UBERON:0001166	98.59	gold quality
adult organism	UBERON:0007023	98.54	gold quality
ganglionic eminence	UBERON:0004023	98.47	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	98.43	gold quality
pigmented layer of retina	UBERON:0001782	98.41	gold quality
corpus epididymis	UBERON:0004359	98.37	gold quality
adenohypophysis	UBERON:0002196	98.34	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	98.32	gold quality
oral cavity	UBERON:0000167	98.28	gold quality
pharyngeal mucosa	UBERON:0000355	98.22	gold quality
pituitary gland	UBERON:0000007	98.21	gold quality
substantia nigra pars compacta	UBERON:0001965	98.20	gold quality
superior surface of tongue	UBERON:0007371	98.16	gold quality
mucosa of paranasal sinus	UBERON:0005030	98.10	gold quality
monocyte	CL:0000576	98.09	gold quality
dorsal root ganglion	UBERON:0000044	98.08	gold quality
mononuclear cell	CL:0000842	98.06	gold quality
leukocyte	CL:0000738	98.03	gold quality
islet of Langerhans	UBERON:0000006	97.99	gold quality
penis	UBERON:0000989	97.93	gold quality
bronchial epithelial cell	CL:0002328	97.91	gold quality
substantia nigra pars reticulata	UBERON:0001966	97.91	gold quality
lymph node	UBERON:0000029	97.86	gold quality
tongue	UBERON:0001723	97.83	gold quality
ventricular zone	UBERON:0003053	97.83	gold quality
right adrenal gland cortex	UBERON:0035827	97.82	gold quality
endometrium epithelium	UBERON:0004811	97.81	gold quality

Single-cell (SCXA)

Detected in 14 experiment(s), a significant marker in 7.

Experiment	Marker?	Max mean expression
E-HCAD-4	yes	27.09
E-MTAB-10042	yes	11.78
E-HCAD-13	yes	11.61
E-HCAD-25	yes	7.61
E-GEOD-125970	yes	7.35
E-CURD-122	yes	5.66
E-MTAB-8559	no	864.23
E-MTAB-7381	no	724.99
E-MTAB-8911	no	572.03
E-HCAD-5	no	23.76
E-GEOD-135922	no	9.26
E-GEOD-93593	no	6.80
E-GEOD-83139	no	2.70
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

79 targeting ATP6V1G1, 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-3924	100.00	72.09	2394
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-3667-3P	99.99	67.17	1636
HSA-LET-7A-5P	99.98	72.29	1790
HSA-LET-7B-5P	99.98	72.31	1790
HSA-LET-7C-5P	99.98	72.29	1790
HSA-LET-7E-5P	99.98	72.29	1790
HSA-LET-7F-5P	99.98	72.56	1784
HSA-LET-7G-5P	99.98	72.37	1784
HSA-LET-7I-5P	99.98	72.37	1788
HSA-MIR-98-5P	99.98	72.33	1787
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-LET-7D-5P	99.96	71.76	1632
HSA-MIR-4458	99.96	71.64	1650
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-589-3P	99.91	69.62	2088
HSA-MIR-5003-3P	99.85	69.29	2517
HSA-MIR-576-5P	99.84	70.46	2582
HSA-MIR-202-3P	99.84	71.41	1290
HSA-MIR-6875-3P	99.82	70.26	2983
HSA-MIR-4659A-3P	99.80	72.62	4248

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 91.7% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 6)

• RILP regulates the activity of the V-ATPase through its interaction with V1G1. (PMID:24762812)
• RILP regulates vacuolar ATPase through interaction with the V1G1 subunit (PMID:26180254)
• genome-wide association study in population in China: Data suggest 4 SNPs upstream of ATP6V1G1 (rs10817638, rs7851259, rs10982287, rs4979427) are associated (in bivariate manner) with age at menarche and bone density. [includes META-ANALYSIS] (PMID:26312577)
• Three genes-ATP6V1G1 in 9q32, GMPS in 3q25.31, and TBX5 in 12q24.21-exhibited concomitant hypermethylation and decreased expression. The i(12p)-positive cells displayed global hypomethylation of gene-poor regions on 12p, a footprint previously associated with constitutional and acquired gains of whole chromosomes as well as with X-chromosome inactivation in females (PMID:26890086)
• Role of the V1G1 subunit of V-ATPase in breast cancer cell migration. (PMID:33633298)
• Plasma exosomes impair microglial degradation of alpha-synuclein through V-ATPase subunit V1G1. (PMID:38702933)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	atp6v1g1	ENSDARG00000022315
mus_musculus	Atp6v1g1	ENSMUSG00000039105
rattus_norvegicus	Atp6v1g1	ENSRNOG00000063197

Paralogs (2): ATP6V1G3 (ENSG00000151418), ATP6V1G2 (ENSG00000213760)

Protein

Protein identifiers

V-type proton ATPase subunit G 1 — O75348 (reviewed: O75348)

Alternative names: V-ATPase 13 kDa subunit 1, Vacuolar proton pump subunit G 1, Vacuolar proton pump subunit M16

All UniProt accessions (6): A0A7I2V2N1, A0A7I2V375, A0A7I2V3Q6, A0A7I2V4K4, A0A7I2YQH3, O75348

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. In aerobic conditions, involved in intracellular iron homeostasis, thus triggering the activity of Fe(2+) prolyl hydroxylase (PHD) enzymes, and leading to HIF1A hydroxylation and subsequent proteasomal degradation.

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.

Subcellular location. Apical cell membrane.

Tissue specificity. Kidney; localizes to early distal nephron, encompassing thick ascending limbs and distal convoluted tubules (at protein level). Ubiquitous.

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

RefSeq proteins (1): NP_004879* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR005124	V-ATPase_G	Family

Pfam: PF03179

UniProt features (5 total): helix 2, initiator methionine 1, chain 1, modified residue 1

Structure

Experimental structures (PDB)

8 structures.

PDB	Method	Resolution (Å)
6WLZ	ELECTRON MICROSCOPY	2.9
6WM2	ELECTRON MICROSCOPY	3.1
6WM3	ELECTRON MICROSCOPY	3.4
9CF8	ELECTRON MICROSCOPY	3.46
9CFC	ELECTRON MICROSCOPY	3.47
6WM4	ELECTRON MICROSCOPY	3.6
7U4T	ELECTRON MICROSCOPY	3.6
7UNF	ELECTRON MICROSCOPY	4.08

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O75348-F1	93.19	0.77

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (1): 2

Function

Pathways and Gene Ontology

Reactome pathways

6 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
R-HSA-9857377	Regulation of MITF-M-dependent genes involved in lysosome biogenesis and autophagy

MSigDB gene sets: 241 (showing top): REACTOME_SIGNALING_BY_INSULIN_RECEPTOR, GOBP_REGULATION_OF_AUTOPHAGY, REACTOME_INNATE_IMMUNE_SYSTEM, FAELT_B_CLL_WITH_VH_REARRANGEMENTS_DN, GOCC_VACUOLAR_MEMBRANE, GOBP_VESICLE_ORGANIZATION, GOBP_INTRACELLULAR_IRON_ION_HOMEOSTASIS, GOBP_VESICLE_MEDIATED_TRANSPORT, GOBP_MONOATOMIC_CATION_TRANSPORT, GOBP_MACROAUTOPHAGY, MISSIAGLIA_REGULATED_BY_METHYLATION_UP, GOBP_RESPONSE_TO_INCREASED_OXYGEN_LEVELS, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_LEVELS, GOBP_REGULATION_OF_CATABOLIC_PROCESS, GOBP_RESPONSE_TO_OXYGEN_LEVELS

GO Biological Process (6): intracellular iron ion homeostasis (GO:0006879), regulation of macroautophagy (GO:0016241), cellular response to increased oxygen levels (GO:0036295), 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 (13): vacuolar proton-transporting V-type ATPase, V1 domain (GO:0000221), lysosomal membrane (GO:0005765), cytosol (GO:0005829), plasma membrane (GO:0005886), apical plasma membrane (GO:0016324), synaptic vesicle membrane (GO:0030672), extracellular exosome (GO:0070062), extrinsic component of synaptic vesicle membrane (GO:0098850), membrane (GO:0016020), vacuolar proton-transporting V-type ATPase complex (GO:0016471), proton-transporting V-type ATPase complex (GO:0033176), proton-transporting V-type ATPase, V1 domain (GO:0033180), ATPase complex (GO:1904949)

Reactome top-level categories

Rollup of top-6 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
MITF-M-dependent gene expression	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
proton-transporting V-type ATPase complex	2
intracellular monoatomic cation homeostasis	1
inorganic ion homeostasis	1
regulation of autophagy	1
macroautophagy	1
response to increased oxygen levels	1
cellular response to oxygen levels	1
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
lysosome	1
lytic vacuole membrane	1
cytoplasm	1
membrane	1
cell periphery	1
apical part of cell	1
plasma membrane region	1
synaptic vesicle	1
exocytic vesicle membrane	1
extracellular vesicle	1
synaptic vesicle membrane	1
extrinsic component of organelle membrane	1
vacuolar membrane	1
proton-transporting two-sector ATPase complex	1

Protein interactions and networks

STRING

1356 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ATP6V1G1	ATP6V1E1	P36543	876
ATP6V1G1	ATP6V1E2	Q96A05	875
ATP6V1G1	ATP6V1F	Q16864	843
ATP6V1G1	ATP6V0B	Q99437	839
ATP6V1G1	ATP6V1D	Q9Y5K8	837
ATP6V1G1	ATP6V1B2	P21281	832
ATP6V1G1	ATP6V0D1	P12953	790
ATP6V1G1	ATP6V0A1	Q93050	772
ATP6V1G1	ATP6V1H	Q9UI12	760
ATP6V1G1	ATP6V0D2	Q8N8Y2	747
ATP6V1G1	ATP6V1B1	P15313	744
ATP6V1G1	ATP6V0A4	Q9HBG4	743
ATP6V1G1	ATP6V0A2	Q9Y487	743
ATP6V1G1	ATP6V1C1	P21283	732
ATP6V1G1	ATP6AP1	Q15904	723

IntAct

109 interactions, top by confidence:

A	B	Type	Score
ATP6V1G1	ATP6V1E2	psi-mi:“MI:0915”(physical association)	0.830
ATP6V1E2	ATP6V1G1	psi-mi:“MI:0915”(physical association)	0.830
LDOC1	ATP6V1G1	psi-mi:“MI:0915”(physical association)	0.670
ATP6V1G1	LDOC1	psi-mi:“MI:0915”(physical association)	0.670
ATP6V1G1	rep	psi-mi:“MI:0194”(cleavage reaction)	0.660
rep	ATP6V1G1	psi-mi:“MI:0407”(direct interaction)	0.660
ATP6V1G1	rep	psi-mi:“MI:0915”(physical association)	0.660
rep	ATP6V1G1	psi-mi:“MI:0915”(physical association)	0.660
ATP6V1C2	ATP6V1G1	psi-mi:“MI:0914”(association)	0.640
ATP6V1G1	MAGEA6	psi-mi:“MI:0915”(physical association)	0.560
GOLGA2	ATP6V1G1	psi-mi:“MI:0915”(physical association)	0.560
MAGEA6	ATP6V1G1	psi-mi:“MI:0915”(physical association)	0.560
ATP6V1G1	GOLGA2	psi-mi:“MI:0915”(physical association)	0.560
ATP6V1G1	LHX3	psi-mi:“MI:0915”(physical association)	0.560
ATP6V1G1	PNMA1	psi-mi:“MI:0915”(physical association)	0.560
GOLGA6L9	ATP6V1G1	psi-mi:“MI:0915”(physical association)	0.560
ATP6V1G1	GORASP2	psi-mi:“MI:0915”(physical association)	0.560
ATP6V1G1	NTAQ1	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (160): ATP6V1G1 (Two-hybrid), ATP6V1G1 (Two-hybrid), LDOC1 (Two-hybrid), ATP6V1E2 (Two-hybrid), ATP6V1G1 (Affinity Capture-MS), ATP6V1G1 (Affinity Capture-MS), ATP6V1G1 (Two-hybrid), ATP6V1D (Co-fractionation), ATP6V1G1 (Two-hybrid), ATP6V1G1 (Affinity Capture-MS), ATP6V1G1 (Affinity Capture-MS), ATP6V1G1 (Affinity Capture-MS), ATP6V1G1 (Affinity Capture-MS), ATP6V1G1 (Affinity Capture-MS), ATP6V1G1 (Affinity Capture-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, O82702, O82703, P48836, Q9SP55, Q9SZH0, O82628, O82629

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
“3C-like proteinase”	“down-regulates activity”	ATP6V1G1	cleavage

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 69 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Regulation of MITF-M-dependent genes involved in lysosome biogenesis and autophagy	9	147.5×	6e-17
Insulin receptor recycling	13	120.7×	5e-23
Transferrin endocytosis and recycling	13	116.8×	5e-23
ROS and RNS production in phagocytes	12	98.3×	3e-20
Amino acids regulate mTORC1	10	48.9×	2e-13
Ion channel transport	13	30.4×	6e-15
RHOQ GTPase cycle	5	22.1×	1e-04
RHOA GTPase cycle	5	9.1×	4e-03

GO biological processes:

GO term	Partners	Fold	FDR
synaptic vesicle lumen acidification	10	164.2×	8e-19
vacuolar acidification	11	141.4×	1e-19
lysosomal lumen acidification	7	82.8×	1e-10
proton transmembrane transport	12	65.7×	3e-17
regulation of macroautophagy	11	57.1×	4e-15
exocytosis	5	13.3×	1e-03
protein transport	7	5.4×	7e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

473 predictions. Top by Δscore:

Variant	Effect	Δscore
9:114587920:AGTGA:A	donor_loss	1.0000
9:114587921:G:GG	donor_gain	1.0000
9:114587922:T:A	donor_loss	1.0000
9:114592622:G:GT	donor_gain	1.0000
9:114592644:GAAGC:G	donor_gain	1.0000
9:114592645:A:T	donor_gain	1.0000
9:114592648:C:G	donor_gain	1.0000
9:114592746:TCG:T	donor_gain	1.0000
9:114587918:AAA:A	donor_gain	0.9900
9:114587919:AA:A	donor_gain	0.9900
9:114587924:AGTTT:A	donor_loss	0.9900
9:114592644:G:T	donor_gain	0.9900
9:114592551:GGAAA:G	acceptor_gain	0.9800
9:114592650:GCG:G	donor_gain	0.9800
9:114592653:G:GG	donor_gain	0.9800
9:114592763:G:GA	donor_gain	0.9800
9:114597563:T:G	acceptor_gain	0.9800
9:114597566:CCA:C	acceptor_loss	0.9800
9:114597567:CA:C	acceptor_loss	0.9800
9:114597568:A:AG	acceptor_gain	0.9800
9:114597568:A:G	acceptor_loss	0.9800
9:114597569:G:GG	acceptor_gain	0.9800
9:114587903:TGTCC:T	donor_gain	0.9700
9:114587904:GTCCG:G	donor_gain	0.9700
9:114592638:GC:G	donor_gain	0.9700
9:114592639:CC:C	donor_gain	0.9700
9:114597562:A:AG	acceptor_gain	0.9700
9:114587916:CAAAA:C	donor_gain	0.9600
9:114592548:ACAG:A	acceptor_loss	0.9600
9:114592551:G:GC	acceptor_loss	0.9600

AlphaMissense

776 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:114587870:T:C	L11P	0.998
9:114587870:T:A	L11Q	0.997
9:114587873:T:C	L12P	0.997
9:114592556:G:C	K29N	0.997
9:114592556:G:T	K29N	0.997
9:114592575:G:C	A36P	0.997
9:114587893:G:C	A19P	0.996
9:114587911:G:C	A25P	0.996
9:114587914:C:A	R26S	0.996
9:114592567:T:C	L33P	0.996
9:114592587:G:C	A40P	0.996
9:114587857:G:A	G7R	0.995
9:114587857:G:C	G7R	0.995
9:114587861:T:A	I8N	0.995
9:114587861:T:C	I8T	0.995
9:114587878:G:C	A14P	0.995
9:114592565:G:C	R32S	0.995
9:114592565:G:T	R32S	0.995
9:114587890:G:C	A18P	0.994
9:114587882:A:T	E15V	0.993
9:114587915:G:C	R26P	0.993
9:114592571:G:C	K34N	0.993
9:114592571:G:T	K34N	0.993
9:114587881:G:A	E15K	0.992
9:114592554:A:G	K29E	0.992
9:114592576:C:A	A36D	0.992
9:114587883:G:C	E15D	0.991
9:114587883:G:T	E15D	0.991
9:114587891:C:A	A18E	0.991
9:114592588:C:A	A40D	0.991

dbSNP variants (sampled 300 via entrez): RS1000149562 (9:114591761 A>G,T), RS1001097590 (9:114590486 G>T), RS1001118018 (9:114586133 GC>G), RS1001149799 (9:114590626 A>G,T), RS1001235167 (9:114592898 A>T), RS1001353757 (9:114590923 G>C), RS1001499550 (9:114589971 G>C), RS1001708973 (9:114596336 G>A), RS1002106200 (9:114596603 A>G), RS1002705691 (9:114595305 G>A,T), RS1003128587 (9:114594777 T>C), RS1003353235 (9:114588437 G>T), RS1003688985 (9:114588605 A>C), RS1004159646 (9:114598367 T>C), RS1004173832 (9:114587452 A>C,G)

Disease associations

OMIM: gene MIM:607296 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST003101_9	Bone mineral density (spine) and age at menarche	9.000000e-06
GCST003102_2	Bone mineral density (hip) and age at menarche	5.000000e-07
GCST003102_8	Bone mineral density (hip) and age at menarche	3.000000e-09

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004703	age at menarche
EFO:0007701	spine bone mineral density
EFO:0007702	hip bone mineral density

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6067014 (SINGLE PROTEIN)

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: transporter — V-type ATPase

ChEMBL bioactivities

2 potent at pChembl≥5 of 3 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
5.03	Kd	9375	nM	CHEMBL5653589
5.03	ED50	9375	nM	CHEMBL5653589

PubChem BioAssay actives

1 with measured affinity, of 4 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2147925: Binding affinity to human ATP6V1G1 incubated for 45 mins by Kinobead based pull down assay	kd	9.3753	uM

CTD chemical–gene interactions

40 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, affects cotreatment, increases abundance, increases expression	4
bisphenol A	decreases expression, increases expression	2
Tobacco Smoke Pollution	affects expression, increases expression	2
Tretinoin	increases expression	2
aristolochic acid I	increases expression	1
triphenyl phosphate	affects expression	1
deoxynivalenol	decreases expression	1
mono-(2-ethylhexyl)phthalate	decreases methylation, increases abundance	1
zinc chromate	increases abundance, increases expression	1
manganese chloride	increases abundance, increases expression, affects cotreatment	1
cupric oxide	increases expression	1
chromium hexavalent ion	increases abundance, increases expression	1
CGP 52608	affects binding, increases reaction	1
chloropicrin	affects expression	1
K 7174	increases expression	1
(4-amino-1,4-dihydro-3-(2-pyridyl)-5-thioxo-1,2,4-triazole)copper(II)	increases expression	1
bisphenol S	increases expression	1
Sunitinib	increases expression	1
Arsenic Trioxide	increases expression	1
Air Pollutants	decreases expression, increases abundance	1
Arsenic	increases expression, affects cotreatment, increases abundance	1
Atrazine	decreases expression	1
Copper	affects binding, decreases expression	1
Diethylhexyl Phthalate	decreases methylation, increases abundance	1
Disulfiram	affects binding, decreases expression	1
Doxorubicin	increases expression	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Isoniazid	increases expression	1
Ivermectin	decreases expression	1
Manganese	increases abundance, increases expression, affects cotreatment	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5650967	Binding	Binding affinity to human ATP6V1G1 incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Clinical trials (associated diseases)

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