ATP6V0A1

Summary

ATP6V0A1 (ATPase H+ transporting V0 subunit a1, HGNC:865) is a protein-coding gene on chromosome 17q21.2, encoding V-type proton ATPase 116 kDa subunit a 1 (Q93050). Subunit of the V0 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 transports protons across cellular membranes.

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 A subunit proteins and the encoded protein is associated with clathrin-coated vesicles. Three transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 535 — RefSeq curated summary.

At a glance

• Gene–disease (curated): developmental and epileptic encephalopathy 104 (Definitive, GenCC) — +3 more curated relationships
• GWAS associations: 9
• Clinical variants (ClinVar): 171 total — 9 pathogenic, 5 likely-pathogenic
• Phenotypes (HPO): 42
• MANE Select transcript: NM_001130021

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:865
Approved symbol	ATP6V0A1
Name	ATPase H+ transporting V0 subunit a1
Location	17q21.2
Locus type	gene with protein product
Status	Approved
Aliases	a1, Vph1, Stv1
Ensembl gene	ENSG00000033627
Ensembl biotype	protein_coding
OMIM	192130
Entrez	535

Gene structure

Transcript identifiers

Ensembl transcripts: 55 — 34 protein_coding, 12 nonsense_mediated_decay, 7 retained_intron, 2 protein_coding_CDS_not_defined

ENST00000264649, ENST00000343619, ENST00000393829, ENST00000537728, ENST00000544137, ENST00000585525, ENST00000585828, ENST00000586001, ENST00000586201, ENST00000586315, ENST00000587299, ENST00000587375, ENST00000587510, ENST00000587797, ENST00000587824, ENST00000587882, ENST00000588138, ENST00000588629, ENST00000588806, ENST00000588901, ENST00000589213, ENST00000589727, ENST00000589759, ENST00000592324, ENST00000703888, ENST00000703889, ENST00000703890, ENST00000703891, ENST00000703892, ENST00000703893, ENST00000703894, ENST00000703895, ENST00000703896, ENST00000703897, ENST00000703898, ENST00000703899, ENST00000703900, ENST00000703901, ENST00000703902, ENST00000703903, ENST00000874939, ENST00000874940, ENST00000874941, ENST00000874942, ENST00000874943, ENST00000874944, ENST00000874945, ENST00000874946, ENST00000874947, ENST00000874948, ENST00000937356, ENST00000937357, ENST00000970983, ENST00000970984, ENST00000970985

RefSeq mRNA: 31 — MANE Select: NM_001130021 NM_001130020, NM_001130021, NM_001378522, NM_001378523, NM_001378530, NM_001378531, NM_001378532, NM_001378533, NM_001378534, NM_001378535, NM_001378536, NM_001378537, NM_001378538, NM_001378539, NM_001378540, NM_001378541, NM_001378542, NM_001378543, NM_001378544, NM_001378545, NM_001378546, NM_001378547, NM_001378548, NM_001378549, NM_001378550, NM_001378551, NM_001378552, NM_001378554, NM_001378556, NM_001378557, NM_005177

CCDS: CCDS11426, CCDS45683, CCDS45684, CCDS92317, CCDS92318, CCDS92319, CCDS92320, CCDS92321, CCDS92322, CCDS92323, CCDS92324

Canonical transcript exons

ENST00000343619 — 22 exons

Exon	Start	End
ENSE00000726015	42498924	42499042
ENSE00001179407	42500707	42500923
ENSE00001225900	42495626	42495716
ENSE00001225907	42495034	42495188
ENSE00001225912	42494334	42494473
ENSE00001225940	42480667	42480749
ENSE00001328685	42501197	42501304
ENSE00001339206	42507520	42507627
ENSE00002307427	42458878	42458963
ENSE00002859045	42521027	42522579
ENSE00003521387	42468010	42468107
ENSE00003524837	42483038	42483131
ENSE00003531318	42513861	42513978
ENSE00003543840	42477660	42477742
ENSE00003553296	42490487	42490637
ENSE00003600405	42487155	42487367
ENSE00003605402	42478463	42478589
ENSE00003621428	42460848	42461011
ENSE00003640260	42466429	42466507
ENSE00003667945	42470090	42470218
ENSE00003673823	42514289	42514460
ENSE00003990245	42508572	42508589

Expression profiles

Bgee: expression breadth ubiquitous, 287 present calls, max score 98.83.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 57.1811 / max 4636.2174, expressed in 1815 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
160944	55.9371	1814
160949	0.6761	388
160951	0.3111	154
160948	0.1372	45
160950	0.0774	23
160945	0.0422	12

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right frontal lobe	UBERON:0002810	98.83	gold quality
right hemisphere of cerebellum	UBERON:0014890	98.75	gold quality
cerebellar hemisphere	UBERON:0002245	98.67	gold quality
cerebellar cortex	UBERON:0002129	98.64	gold quality
prefrontal cortex	UBERON:0000451	98.19	gold quality
cingulate cortex	UBERON:0003027	98.14	gold quality
anterior cingulate cortex	UBERON:0009835	98.10	gold quality
Brodmann (1909) area 9	UBERON:0013540	98.07	gold quality
adenohypophysis	UBERON:0002196	98.03	gold quality
cerebellum	UBERON:0002037	97.96	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	97.83	gold quality
nucleus accumbens	UBERON:0001882	97.69	gold quality
frontal cortex	UBERON:0001870	97.66	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	97.65	gold quality
hypothalamus	UBERON:0001898	97.57	gold quality
neocortex	UBERON:0001950	97.50	gold quality
pituitary gland	UBERON:0000007	97.48	gold quality
amygdala	UBERON:0001876	97.47	gold quality
caudate nucleus	UBERON:0001873	97.31	gold quality
putamen	UBERON:0001874	96.96	gold quality
cerebral cortex	UBERON:0000956	96.93	gold quality
forebrain	UBERON:0001890	96.92	gold quality
telencephalon	UBERON:0001893	96.90	gold quality
spinal cord	UBERON:0002240	96.84	gold quality
brain	UBERON:0000955	96.80	gold quality
central nervous system	UBERON:0001017	96.80	gold quality
colonic epithelium	UBERON:0000397	96.72	gold quality
cortical plate	UBERON:0005343	96.68	gold quality
islet of Langerhans	UBERON:0000006	96.60	gold quality
mucosa of stomach	UBERON:0001199	96.46	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ENAD-20	yes	229.38
E-ANND-3	yes	11.65

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

52 targeting ATP6V0A1, 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-6758-5P	100.00	66.21	1470
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-6856-5P	100.00	65.47	1298
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-433-3P	99.98	69.37	1203
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-4648	99.91	67.00	710
HSA-MIR-4271	99.88	68.32	2244
HSA-MIR-4779	99.86	66.50	1583
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-92A-2-5P	99.75	67.01	2164
HSA-MIR-3913-3P	99.74	66.53	938
HSA-MIR-6752-3P	99.72	66.71	1587
HSA-MIR-6766-5P	99.68	67.70	2325
HSA-MIR-7150	99.62	66.80	1322
HSA-MIR-5003-5P	99.61	69.13	1624
HSA-MIR-6132	99.60	65.83	1554
HSA-MIR-6836-5P	99.60	65.62	1538
HSA-MIR-12123	99.52	71.79	2990
HSA-MIR-671-5P	99.52	67.11	1277
HSA-MIR-4708-3P	99.51	67.99	870
HSA-MIR-1207-5P	99.49	69.11	2983
HSA-MIR-6722-3P	99.45	67.62	1919
HSA-MIR-4284	99.36	65.25	1293
HSA-MIR-6731-5P	99.28	67.42	2375
HSA-MIR-8085	99.28	67.56	2362
HSA-MIR-4721	99.26	66.05	818
HSA-MIR-4763-3P	99.10	67.83	2649

Literature-anchored findings (GeneRIF, showing 6)

• The mRNA levels of POLR2F, ATP6V0A1 and PRNP were evaluated by quantitative RT-PCR in 70 colorectal carcinomas and 17 normal tissue specimens and were correlated with clinicopathological parameters. (PMID:18505059)
• a series of events whereby ATP6V0A1 3’-UTR variant T+3246C functioned: ATP6V0A1 expression probably was affected through differential micro-RNA effects, altering vacuolar pH and consequently CHGA processing and exocytotic secretion. (PMID:21558123)
• Inhibition of lysosome degradation on autophagosome formation and responses to GMI, an immunomodulatory protein from Ganoderma microsporum. ATP6V0A1 plays an important role in mediating autophagosome-lysosome fusion. (PMID:22708544)
• The function of vacuolar ATPase (V-ATPase) a subunit isoforms in invasiveness of MCF10a and MCF10CA1a human breast cancer cells. (PMID:24072707)
• ATP6V0A1 encoding the a1-subunit of the V0 domain of vacuolar H(+)-ATPases is essential for brain development in humans and mice. (PMID:33833240)
• V-ATPase V0a1 promotes Weibel-Palade body biogenesis through the regulation of membrane fission. (PMID:34904569)

Cross-species orthologs

12 orthologs

Organism	Symbol	Gene ID
danio_rerio	atp6v0a1b	ENSDARG00000015174
danio_rerio	atp6v0a1a	ENSDARG00000020847
mus_musculus	Atp6v0a1	ENSMUSG00000019302
rattus_norvegicus	Atp6v0a1	ENSRNOG00000036814
drosophila_melanogaster	Vha100-2	FBGN0028670
drosophila_melanogaster	Vha100-1	FBGN0028671
drosophila_melanogaster	Vha100-5	FBGN0032373
drosophila_melanogaster	Vha100-4	FBGN0038613
caenorhabditis_elegans		WBGENE00006768
caenorhabditis_elegans		WBGENE00006914
caenorhabditis_elegans		WBGENE00006915
caenorhabditis_elegans		WBGENE00006916

Paralogs (3): ATP6V0A4 (ENSG00000105929), TCIRG1 (ENSG00000110719), ATP6V0A2 (ENSG00000185344)

Protein

Protein identifiers

V-type proton ATPase 116 kDa subunit a 1 — Q93050 (reviewed: Q93050)

Alternative names: Clathrin-coated vesicle/synaptic vesicle proton pump 116 kDa subunit, Vacuolar adenosine triphosphatase subunit Ac116, Vacuolar proton pump subunit 1, Vacuolar proton translocating ATPase 116 kDa subunit a isoform 1

All UniProt accessions (25): A0A994J3Z0, A0A994J3Z4, A0A994J3Z9, A0A994J403, A0A994J473, A0A994J4L1, A0A994J4L6, Q93050, A0A994J4L9, A0A994J6N0, A0A994J6N3, A0A994J728, A0A994J731, A0A994J735, B7Z2A9, B7Z641, F5H1T6, K7ELZ6, K7EM24, K7EN36, K7ENA1, K7EPG4, K7EQW2, K7ERA0, K7ERA6

UniProt curated annotations — full annotation on UniProt →

Function. Subunit of the V0 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 transports protons across cellular membranes. V-ATPase is responsible for the acidification of various organelles, such as lysosomes, endosomes, the trans-Golgi network, and secretory granules, including synaptic vesicles. In certain cell types, can be exported to the plasma membrane, where it is involved in the acidification of the extracellular environment. Required for assembly and activity of the vacuolar ATPase. Through its action on compartment acidification, plays an essential role in neuronal development in terms of integrity and connectivity of neurons.

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. Interacts with SPAAR.

Subcellular location. Cytoplasmic vesicle. Clathrin-coated vesicle membrane. Secretory vesicle. Synaptic vesicle membrane. Melanosome.

Disease relevance. Developmental and epileptic encephalopathy 104 (DEE104) [MIM:619970] A form of epileptic encephalopathy, a heterogeneous group of early-onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. Development is normal prior to seizure onset, after which cognitive and motor delays become apparent. DEE104 is an autosomal dominant form characterized by onset of developmental delay and drug-resistant focal and generalized tonic-clonic seizures in the first few months of life. The disease is caused by variants affecting the gene represented in this entry. Neurodevelopmental disorder with epilepsy and brain atrophy (NEDEBA) [MIM:619971] An autosomal recessive disorder characterized by global developmental delay, early-onset progressive myoclonus epilepsy and ataxia. Brain imaging shows progressive atrophy. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the V-ATPase 116 kDa subunit family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q93050-2	1, I	yes
Q93050-1	2, II
Q93050-3	3

RefSeq proteins (31): NP_001123492, NP_001123493, NP_001365451, NP_001365452, NP_001365459, NP_001365460, NP_001365461, NP_001365462, NP_001365463, NP_001365464, NP_001365465, NP_001365466, NP_001365467, NP_001365468, NP_001365469, NP_001365470, NP_001365471, NP_001365472, NP_001365473, NP_001365474, NP_001365475, NP_001365476, NP_001365477, NP_001365478, NP_001365479, NP_001365480, NP_001365481, NP_001365483, NP_001365485, NP_001365486, NP_005168 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002490	V-ATPase_116kDa_su	Family
IPR026028	V-type_ATPase_116kDa_su_euka	Family

Pfam: PF01496

UniProt features (83 total): helix 34, strand 12, topological domain 9, transmembrane region 8, sequence variant 7, turn 5, modified residue 3, splice variant 2, chain 1, glycosylation site 1, sequence conflict 1

Structure

Experimental structures (PDB)

7 structures.

PDB	Method	Resolution (Å)
6WLW	ELECTRON MICROSCOPY	3
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

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q93050-F1	84.84	0.51

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 (3): 250, 360, 364

Glycosylation sites (1): 488

Function

Pathways and Gene Ontology

Reactome pathways

6 pathways

ID	Pathway
R-HSA-1222556	ROS and RNS production in phagocytes
R-HSA-6798695	Neutrophil degranulation
R-HSA-77387	Insulin receptor recycling
R-HSA-917977	Transferrin endocytosis and recycling
R-HSA-983712	Ion channel transport
R-HSA-9857377	Regulation of MITF-M-dependent genes involved in lysosome biogenesis and autophagy

MSigDB gene sets: 391 (showing top): GSE45365_NK_CELL_VS_CD8_TCELL_UP, REACTOME_SIGNALING_BY_INSULIN_RECEPTOR, GOBP_REGULATION_OF_AUTOPHAGY, REACTOME_INNATE_IMMUNE_SYSTEM, GOBP_ENDOSOME_ORGANIZATION, GOBP_VACUOLE_ORGANIZATION, GOCC_VACUOLAR_MEMBRANE, GOCC_SECRETORY_GRANULE, GOBP_VESICLE_ORGANIZATION, ENK_UV_RESPONSE_KERATINOCYTE_UP, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, IVANOVA_HEMATOPOIESIS_MATURE_CELL, KEGG_LYSOSOME, GOBP_VESICLE_MEDIATED_TRANSPORT, GOBP_MONOATOMIC_CATION_TRANSPORT

GO Biological Process (7): vacuolar acidification (GO:0007035), lysosomal lumen acidification (GO:0007042), regulation of macroautophagy (GO:0016241), endosomal lumen acidification (GO:0048388), synaptic vesicle lumen acidification (GO:0097401), proton transmembrane transport (GO:1902600), monoatomic ion transport (GO:0006811)

GO Molecular Function (3): proton-transporting ATPase activity, rotational mechanism (GO:0046961), ATPase binding (GO:0051117), protein binding (GO:0005515)

GO Cellular Component (22): vacuolar proton-transporting V-type ATPase, V0 domain (GO:0000220), lysosomal membrane (GO:0005765), Golgi apparatus (GO:0005794), cytosol (GO:0005829), plasma membrane (GO:0005886), endosome membrane (GO:0010008), membrane (GO:0016020), vacuolar proton-transporting V-type ATPase complex (GO:0016471), nuclear speck (GO:0016607), clathrin-coated vesicle membrane (GO:0030665), secretory granule membrane (GO:0030667), phagocytic vesicle membrane (GO:0030670), synaptic vesicle membrane (GO:0030672), proton-transporting V-type ATPase complex (GO:0033176), melanosome (GO:0042470), perinuclear region of cytoplasm (GO:0048471), extracellular exosome (GO:0070062), ficolin-1-rich granule membrane (GO:0101003), cytoplasm (GO:0005737), cytoplasmic vesicle (GO:0031410), proton-transporting V-type ATPase, V0 domain (GO:0033179), synapse (GO:0045202)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
Innate Immune System	2
Signaling by Insulin receptor	1
Iron uptake and transport	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
cytoplasm	4
cellular anatomical structure	4
intracellular pH reduction	2
vacuolar membrane	2
cytoplasmic vesicle membrane	2
bounding membrane of organelle	2
vacuolar acidification	1
regulation of autophagy	1
macroautophagy	1
endosome organization	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
monoatomic cation transmembrane transport	1
transport	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
vacuolar proton-transporting V-type ATPase complex	1
proton-transporting V-type ATPase, V0 domain	1
lysosome	1
lytic vacuole membrane	1
endomembrane system	1
intracellular membrane-bounded organelle	1
membrane	1
cell periphery	1
endosome	1
proton-transporting V-type ATPase complex	1
nuclear ribonucleoprotein granule	1
clathrin-coated vesicle	1
coated vesicle membrane	1
secretory granule	1
endocytic vesicle membrane	1
phagocytic vesicle	1
synaptic vesicle	1

Protein interactions and networks

STRING

1651 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ATP6V0A1	ATP6V1B1	P15313	900
ATP6V0A1	ATP4A	P20648	886
ATP6V0A1	ATP12A	P54707	885
ATP6V0A1	ATP6V1E1	P36543	847
ATP6V0A1	ATP6V1A	P38606	841
ATP6V0A1	ATP6V1B2	P21281	835
ATP6V0A1	ATP6V0D1	P12953	827
ATP6V0A1	ATP6V0C	P27449	823
ATP6V0A1	ATP6V1F	Q16864	806
ATP6V0A1	ATP6V1C1	P21283	803
ATP6V0A1	ATP6V0B	Q99437	801
ATP6V0A1	ATP6V1E2	Q96A05	796
ATP6V0A1	ATP6V1C2	Q8NEY4	786
ATP6V0A1	ATP6V0D2	Q8N8Y2	780
ATP6V0A1	ATP6V1D	Q9Y5K8	774

IntAct

153 interactions, top by confidence:

A	B	Type	Score
LAMTOR1	LAMTOR5	psi-mi:“MI:0914”(association)	0.870
ATP6AP2	ATP6V0C	psi-mi:“MI:0914”(association)	0.730
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
TCIRG1	ATP6AP2	psi-mi:“MI:0914”(association)	0.640
SLC12A2	CLGN	psi-mi:“MI:0914”(association)	0.640
	ATP6V0A1	psi-mi:“MI:0915”(physical association)	0.560
SYNGAP1	SEC16A	psi-mi:“MI:0914”(association)	0.530
ATP6V0A1	ATP6V1G1	psi-mi:“MI:0914”(association)	0.530
ATP6V1A	ATP6V1G1	psi-mi:“MI:0914”(association)	0.530
ATP6V1B2	ATP6V1G1	psi-mi:“MI:0914”(association)	0.530
atp6v0d_human	ATP6AP2	psi-mi:“MI:0914”(association)	0.530
CD4	CCDC85C	psi-mi:“MI:0914”(association)	0.530
LGALS1	PODXL	psi-mi:“MI:0914”(association)	0.530
TCIRG1	AP3D1	psi-mi:“MI:0914”(association)	0.530
TMEM185A	TSPAN6	psi-mi:“MI:0914”(association)	0.530
MEAK7	NMT2	psi-mi:“MI:0914”(association)	0.530
ATP6V0A1	ATP6AP2	psi-mi:“MI:0914”(association)	0.530
SERINC2	STOM	psi-mi:“MI:0914”(association)	0.530
SLC2A1	ATP11C	psi-mi:“MI:0914”(association)	0.530
LGALS3	PODXL	psi-mi:“MI:0914”(association)	0.530
TMEM63A	AP3D1	psi-mi:“MI:0914”(association)	0.530
MARCKSL1	NMT2	psi-mi:“MI:0914”(association)	0.530
CUEDC1	TOM1	psi-mi:“MI:0914”(association)	0.530
ATP6V0A1	ATP6V1B1	psi-mi:“MI:0403”(colocalization)	0.490
LDHB	ATP6V0A1	psi-mi:“MI:2364”(proximity)	0.470
LDHB	ATP6V0A1	psi-mi:“MI:0915”(physical association)	0.470

BioGRID (354): ATP6V0A1 (Affinity Capture-MS), ATP6V0A1 (Affinity Capture-MS), ATP6V0A1 (Affinity Capture-MS), ATP6V0A1 (Affinity Capture-MS), ATP6V0A1 (Affinity Capture-MS), ATP6V0A1 (Affinity Capture-MS), ATP6V0A1 (Affinity Capture-MS), ATP6V0A1 (Affinity Capture-MS), ATP6V0A1 (Affinity Capture-MS), ATP6V0A1 (Affinity Capture-MS), ATP6V0A1 (Affinity Capture-MS), ATP6V0A1 (Affinity Capture-MS), ATP6V0A1 (Affinity Capture-MS), ATP6V0A1 (Co-fractionation), ATP6V0A1 (Co-fractionation)

ESM2 similar proteins: A0A078H868, A0A8I3MKU8, A1C7T5, A1DIF7, A2R616, A6S950, B0XUW3, B2B2N5, B6HJA3, B8N6H2, B9RK42, C0NLX2, C0RZV6, C1G565, C1GZK1, C4JDF8, C5FZ62, C5GN10, C5JCV0, C5PEI5, C6H4B5, C7Z7C3, D1ZIW5, D4AT37, D4DGR3, I6VSD2, O94673, O96005, Q0CVD7, Q0IJ20, Q28FY5, Q29BL9, Q2H0U8, Q2TA63, Q2UDE5, Q3SZR6, Q4WZS1, Q5BBC6, Q5BIY5, Q6DFI2

Diamond homologs: A1A5G6, B2MZD0, G5EEK9, G5EGP4, O13742, O29106, O57721, O97681, P15920, P25286, P30628, P32563, P37296, Q01290, Q13488, Q29466, Q54E04, Q57675, Q5JDS2, Q5R422, Q8AVM5, Q8RWZ7, Q8W4S4, Q920R6, Q93050, Q9HBG4, Q9I8D0, Q9SJT7, Q9UWW3, Q9UXU2, Q9Y487, Q9Z1G4, Q9YEA0, O27041, Q9HND8, O83544

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 190 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	48.4×	6e-12
Insulin receptor recycling	12	36.5×	4e-14
Transferrin endocytosis and recycling	11	32.4×	3e-12
ROS and RNS production in phagocytes	10	26.9×	2e-10
Amino acids regulate mTORC1	15	24.0×	2e-14
SLC-mediated transport of neurotransmitters	5	16.3×	8e-04
Amino acid transport across the plasma membrane	5	12.0×	3e-03
Ion channel transport	15	11.5×	3e-10

GO biological processes:

GO term	Partners	Fold	FDR
synaptic vesicle lumen acidification	9	50.5×	1e-11
vacuolar acidification	11	48.3×	9e-14
post-Golgi vesicle-mediated transport	5	31.5×	4e-05
lysosomal lumen acidification	7	28.2×	6e-07
proton transmembrane transport	13	24.3×	2e-12
regulation of macroautophagy	8	14.2×	1e-05
ATP metabolic process	5	14.0×	2e-03
amino acid transport	7	13.1×	1e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	9
Likely pathogenic	5
Uncertain significance	121
Likely benign	6
Benign	0

Top pathogenic / likely-pathogenic (14)

Variant ID	HGVS	Classification
1698397	NM_001130021.3(ATP6V0A1):c.1513G>C (p.Ala505Pro)	Pathogenic
1698398	NC_000017.10:g.40599557_40649783del	Pathogenic
1698399	NM_001130021.3(ATP6V0A1):c.1579A>G (p.Asn527Asp)	Pathogenic
1698400	NM_001130021.3(ATP6V0A1):c.196+1G>A	Pathogenic
1698401	NM_001130021.3(ATP6V0A1):c.1429T>C (p.Ser477Pro)	Pathogenic
1698402	NM_001130021.3(ATP6V0A1):c.1631G>A (p.Gly544Asp)	Pathogenic
1698403	NM_001130021.3(ATP6V0A1):c.2411G>A (p.Arg804His)	Pathogenic
1698405	NM_001130021.3(ATP6V0A1):c.445del (p.Glu149fs)	Pathogenic
3377270	NM_001130021.3(ATP6V0A1):c.118-1del	Pathogenic
2921041	NM_001130021.3(ATP6V0A1):c.2381A>T (p.Glu794Val)	Likely pathogenic
3068292	NM_001130021.3(ATP6V0A1):c.118-2A>G	Likely pathogenic
3769842	NM_001130021.3(ATP6V0A1):c.2456G>A (p.Gly819Asp)	Likely pathogenic
4535425	NM_001130021.3(ATP6V0A1):c.2219G>C (p.Arg740Pro)	Likely pathogenic
4845866	NM_001130021.3(ATP6V0A1):c.948_949del (p.Lys317fs)	Likely pathogenic

SpliceAI

4104 predictions. Top by Δscore:

Variant	Effect	Δscore
17:42460842:CTTCA:C	acceptor_loss	1.0000
17:42460845:CAG:C	acceptor_loss	1.0000
17:42460846:A:AT	acceptor_loss	1.0000
17:42460847:G:A	acceptor_loss	1.0000
17:42461007:GTGAC:G	donor_gain	1.0000
17:42461008:TGAC:T	donor_gain	1.0000
17:42461009:GAC:G	donor_gain	1.0000
17:42461009:GACG:G	donor_gain	1.0000
17:42461012:G:C	donor_loss	1.0000
17:42461012:G:GG	donor_gain	1.0000
17:42461013:T:TG	donor_loss	1.0000
17:42461014:AAG:A	donor_loss	1.0000
17:42466424:TTCA:T	acceptor_loss	1.0000
17:42466425:TCA:T	acceptor_loss	1.0000
17:42466426:CA:C	acceptor_loss	1.0000
17:42466427:A:AG	acceptor_gain	1.0000
17:42466427:A:G	acceptor_loss	1.0000
17:42466428:G:GA	acceptor_gain	1.0000
17:42466428:GT:G	acceptor_gain	1.0000
17:42466428:GTT:G	acceptor_gain	1.0000
17:42466428:GTTA:G	acceptor_gain	1.0000
17:42466428:GTTAA:G	acceptor_gain	1.0000
17:42466503:GCTTC:G	donor_gain	1.0000
17:42466504:C:G	donor_gain	1.0000
17:42466504:CTTC:C	donor_gain	1.0000
17:42466505:TTC:T	donor_gain	1.0000
17:42466506:TC:T	donor_gain	1.0000
17:42466507:CGTA:C	donor_loss	1.0000
17:42466508:G:GG	donor_gain	1.0000
17:42466508:GT:G	donor_loss	1.0000

AlphaMissense

5574 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:42460938:T:C	L15P	1.000
17:42460940:T:C	F16L	1.000
17:42460941:T:C	F16S	1.000
17:42460941:T:G	F16C	1.000
17:42460942:T:A	F16L	1.000
17:42460942:T:G	F16L	1.000
17:42460944:T:C	L17P	1.000
17:42460955:G:C	A21P	1.000
17:42460959:C:A	A22D	1.000
17:42460971:T:A	V26D	1.000
17:42460982:G:A	G30R	1.000
17:42460982:G:C	G30R	1.000
17:42460983:G:A	G30E	1.000
17:42461004:T:C	F37S	1.000
17:42461009:G:C	D39H	1.000
17:42466434:T:A	N41K	1.000
17:42466434:T:G	N41K	1.000
17:42466450:T:C	F47L	1.000
17:42466451:T:C	F47S	1.000
17:42466451:T:G	F47C	1.000
17:42466452:C:A	F47L	1.000
17:42466452:C:G	F47L	1.000
17:42466456:C:T	R49W	1.000
17:42466457:G:C	R49P	1.000
17:42466462:T:A	F51I	1.000
17:42466462:T:C	F51L	1.000
17:42466462:T:G	F51V	1.000
17:42466463:T:C	F51S	1.000
17:42466463:T:G	F51C	1.000
17:42466464:T:A	F51L	1.000

dbSNP variants (sampled 300 via entrez): RS1000031262 (17:42500305 C>G,T), RS1000045658 (17:42477007 A>G), RS1000142155 (17:42463470 C>T), RS1000208531 (17:42473367 A>G), RS1000279800 (17:42480103 C>T), RS1000281706 (17:42520071 A>G), RS1000307260 (17:42460319 T>C), RS1000310782 (17:42479865 A>G,T), RS1000425416 (17:42517983 T>G), RS1000452771 (17:42497770 G>A,T), RS1000462863 (17:42482157 T>G), RS1000463802 (17:42513677 G>A), RS1000491003 (17:42500516 T>G), RS1000509839 (17:42472128 A>G), RS1000609085 (17:42523063 G>C)

Disease associations

OMIM: gene MIM:192130 | disease phenotypes: MIM:619970, MIM:619971, MIM:209850

GenCC curated gene-disease

Disease	Classification	Inheritance
developmental and epileptic encephalopathy 104	Definitive	Autosomal dominant
neurodevelopmental disorder with epilepsy and brain atrophy	Strong	Autosomal recessive
neurodevelopmental disorder	Strong	Semidominant
complex neurodevelopmental disorder	Limited	Autosomal dominant

Mondo (11): developmental and epileptic encephalopathy 104 (MONDO:0031021), prostate cancer (MONDO:0008315), neurodevelopmental disorder with epilepsy and brain atrophy (MONDO:0859265), cerebellar ataxia (MONDO:0000437), intellectual disability (MONDO:0001071), microcephaly (MONDO:0001149), autism (MONDO:0005260), esophageal atresia (MONDO:0001044), pyloric stenosis (MONDO:0001561), complex neurodevelopmental disorder (MONDO:0100038), neurodevelopmental disorder (MONDO:0700092)

Orphanet (3): Familial prostate cancer (Orphanet:1331), Rare ataxia (Orphanet:102002), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

42 total (30 of 42 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000303	Mandibular prognathia
HP:0000505	Visual impairment
HP:0000713	Agitation
HP:0000729	Autistic behavior
HP:0000750	Delayed speech and language development
HP:0000752	Hyperactivity
HP:0000939	Osteoporosis
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001251	Ataxia
HP:0001263	Global developmental delay
HP:0001272	Cerebellar atrophy
HP:0001321	Cerebellar hypoplasia
HP:0001336	Myoclonus
HP:0001561	Polyhydramnios
HP:0002020	Gastroesophageal reflux
HP:0002033	Poor suck
HP:0002069	Bilateral tonic-clonic seizure
HP:0002100	Recurrent aspiration pneumonia
HP:0002254	Intermittent diarrhea
HP:0002384	Focal impaired awareness seizure
HP:0002510	Spastic tetraplegia
HP:0002521	Hypsarrhythmia
HP:0002539	Cortical dysplasia
HP:0003593	Infantile onset
HP:0003621	Juvenile onset
HP:0003623	Neonatal onset
HP:0004395	Malnutrition

GWAS associations

9 associations (top):

Study	Trait	p-value
GCST002219_1	Triglycerides	3.000000e-128
GCST004131_42	Inflammatory bowel disease	2.000000e-17
GCST004132_58	Crohn’s disease	2.000000e-11
GCST004133_53	Ulcerative colitis	1.000000e-10
GCST010043_34	Asthma	4.000000e-12
GCST90020025_1439	Waist-to-hip ratio adjusted for BMI	2.000000e-08
GCST90020025_1442	Waist-to-hip ratio adjusted for BMI	8.000000e-10
GCST90020027_414	Waist-hip index	4.000000e-10
GCST90020027_461	Waist-hip index	1.000000e-08

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004530	triglyceride measurement
EFO:0007788	BMI-adjusted waist-hip ratio

MeSH disease descriptors (9)

Descriptor	Name	Tree numbers
D001321	Autistic Disorder	F03.625.164.113.500
D002524	Cerebellar Ataxia	C10.228.140.252.190; C10.597.350.090.500; C23.888.592.350.090.200
D004933	Esophageal Atresia	C06.198.330; C06.405.117.260; C16.131.314.330
D017219	Gastric Outlet Obstruction	C06.405.748.340
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D008831	Microcephaly	C05.660.207.620; C10.500.507.400.500; C16.131.621.207.620; C16.131.666.507.400.500
D065886	Neurodevelopmental Disorders	F03.625
D011471	Prostatic Neoplasms	C04.588.945.440.770; C12.100.500.260.750; C12.100.500.565.625; C12.200.294.260.750; C12.200.294.565.625; C12.200.758.409.750; C12.900.619.750
D011707	Pyloric Stenosis	C06.405.748.340.690

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

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases expression	3
Acetaminophen	decreases expression	2
Tobacco Smoke Pollution	decreases expression, increases expression	2
Tunicamycin	increases expression	2
Cadmium Chloride	decreases expression, increases abundance, increases expression	2
aristolochic acid I	increases expression	1
FR900359	increases phosphorylation	1
bisphenol F	affects cotreatment, decreases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
bisphenol A	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
sulindac sulfide	increases expression	1
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	1
beta-methylcholine	affects expression	1
tamibarotene	increases expression	1
yessotoxin	increases expression	1
CGP 52608	affects binding, increases reaction	1
abrine	increases expression	1
bisphenol S	decreases expression, affects cotreatment	1
PP242	decreases expression	1
bisphenol AF	increases expression	1
Leflunomide	decreases expression	1
Acrolein	affects cotreatment, increases oxidation, increases abundance	1
Air Pollutants	affects cotreatment, increases abundance, increases oxidation	1
Benzo(a)pyrene	decreases methylation, increases methylation	1
Cadmium	decreases expression, increases abundance	1
Dichlorodiphenyl Dichloroethylene	decreases expression	1
Dexamethasone	decreases expression, affects cotreatment	1
Dimethyl Sulfoxide	increases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04586348	PHASE4	UNKNOWN	Prenatal Iodine Supplementation and Early Childhood Neurodevelopment
NCT04873115	PHASE4	UNKNOWN	Double-blind, Placebo-controlled, Randomized Clinical Trial Comparing the Efficacy and Safety of Sialanar Plus orAl rehabiLitation Against Placebo Plus Oral Rehabilitation for chIldren and Adolescents With seVere Sialorrhoea and Neurodisabilties,
NCT00029224	PHASE4	COMPLETED	Treatment With Zoledronic Acid in Patients With Breast Cancer, Multiple Myeloma, and Prostate Cancer With Cancer Related Bone Lesions
NCT00035997	PHASE4	COMPLETED	Open-label Trial on the Effect of I.V. Zoledronic Acid 4 mg on Bone Density in Hormone Sensitive Prostate Cancer Patients With Bone Metastasis
NCT00063609	PHASE4	COMPLETED	The Effect of Zoledronic Acid on Bone Loss in Prostate Cancer Patients Undergoing Androgen Deprivation Therapy
NCT00103623	PHASE4	SUSPENDED	The Plenaxis® Experience Study
NCT00106392	PHASE4	COMPLETED	A Safety and Efficacy Study of Prograf in the Prevention of Erectile Dysfunction After Radical Prostatectomy
NCT00185029	PHASE4	UNKNOWN	MR-Lymphography and Lymph Node Staging in Prostate Cancer
NCT00199485	PHASE4	COMPLETED	Angelica Sinensis for the Treatment of Hot Flashes in Men Undergoing LHRH Therapy for Prostate Cancer
NCT00219219	PHASE4	COMPLETED	Zoledronic Acid in the Prevention of Skeletal-related Events in Hormone Refractory and Hormone-sensitive Prostate Cancer Patients With Bone Metastases
NCT00219271	PHASE4	COMPLETED	Effect Of Zoledronic Acid On Circulating And Bone Marrow-Residing Prostate Cancer Cells In Patients With Clinically Localized Prostate Cancer
NCT00237146	PHASE4	COMPLETED	Study to Evaluate Zoledronic Acid on Quality of Life and Skeletal-related Events as Adjuvant Treatment in Patients With Hormone-naïve Prostate Cancer and Bone Metastasis Who Have Undergone Orchiectomy
NCT00242554	PHASE4	COMPLETED	Open-label Phase IV Clinical Trial to Evaluate the Safety and Tolerability of Zoledronic Acid in Patients With Prostate Cancer and Bone Metastases
NCT00280098	PHASE4	COMPLETED	Docetaxel in the Treatment of Hormone Refractory Prostate Cancer
NCT00293696	PHASE4	COMPLETED	Casodex/Zoladex Biomarkers in Localised Prostate Cancer
NCT00334139	PHASE4	COMPLETED	Effect of Zoledronic Acid on Bone Metabolism in Patients With Bone Metastasis and Prostate or Breast Cancer
NCT00375765	PHASE4	COMPLETED	Effects On Dihydrotestosterone Regulated Gene Expression In Benign Prostatic Hyperplasia Or Prostate Cancer
NCT00391690	PHASE4	COMPLETED	Evaluation of Bone Markers as Diagnostic Tools for Early Detection of Bone Metastases in Patients With High Risk Prostate Cancer
NCT00422708	PHASE4	COMPLETED	Local Anesthesia for Prostate Biopsy
NCT00526331	PHASE4	COMPLETED	Evaluation of Arterial Pressure Based Cardiac Output for Goal-Directed Perioperative Therapy
NCT00590213	PHASE4	COMPLETED	Compare the Value of Prophylactic Versus Therapeutic Breast Radiotherapy in CASODEX
NCT00629330	PHASE4	TERMINATED	Dissemination of Prostate Cancer Screening to PCP’s in African American Communities
NCT00771966	PHASE4	COMPLETED	Radical Prostatectomy and Perioperative Fluid Therapy
NCT00805701	PHASE4	COMPLETED	Study Assessing The Efficacy And Safety Of Avodart (Dutasteride) At Improving Urinary Symptoms In Men With Prostate Cancer Who Are Undergoing Seed Implantation
NCT00859027	PHASE4	COMPLETED	Effect Of Risedronate On Bone Mass In Older Men Receiving Neoadjuvant Therapy For Prostate Cancer
NCT00906269	PHASE4	UNKNOWN	Can Hyperbaric Oxygen Improve Erectile Function Following Surgery for Prostate Cancer
NCT00953277	PHASE4	COMPLETED	Study of Nerve Reconstruction Using AVANCE in Subjects Who Undergo Robotic Assisted Prostatectomy for Treatment of Prostate Cancer
NCT00982800	PHASE4	COMPLETED	Does Postoperative Gabapentin Reduce Pain, Opioid Consumption and Anxiety and Have a Positive Effect on Health Related Quality of Life After Radical Prostatectomy?
NCT01083199	PHASE4	COMPLETED	Global Performance Evaluation of the AMS CONTINUUM™ Device
NCT01136226	PHASE4	COMPLETED	Evaluate Recovery of Testosterone for Patients Using Eligard
NCT01161563	PHASE4	COMPLETED	Randomized Crossover Trial to Assess the Tolerability of Gonadotropin Releasing Hormone (GnRH) Analogue Administration
NCT01230905	PHASE4	COMPLETED	Study to Monitor the Effects of Androgen Suppression Treatment on the Heart
NCT01296672	PHASE4	COMPLETED	3 Month Finasteride Challenge Test Can Significantly Improve the Performance of Screening for Prostate Cancer
NCT01365143	PHASE4	TERMINATED	Prospective Randomized Trial Comparing Robotic Versus Open Radical Prostatectomy
NCT01379742	PHASE4	UNKNOWN	Comparison of Between ThinSeed™ and OncoSeed™ for Permanent Prostate Brachytherapy
NCT01486563	PHASE4	COMPLETED	Hydroxyethyl Starch and Renal Function After Radical Prostatectomy
NCT01511874	PHASE4	COMPLETED	Efficacy and Safety Study of ELIGARD 22.5mg With Prostate Cancer
NCT01512472	PHASE4	TERMINATED	Firmagon (Degarelix) Intermittent Therapy
NCT01547416	PHASE4	COMPLETED	The Effect of Combined General/Epidural Anesthesia Versus General Anesthesia on Diaphragmatic Function
NCT01571544	PHASE4	COMPLETED	The Use of Thermal Suits as Preventing Hypothermia During Surgery