ATP6V1C1

Summary

ATP6V1C1 (ATPase H+ transporting V1 subunit C1, HGNC:856) is a protein-coding gene on chromosome 8q22.3, encoding V-type proton ATPase subunit C 1 (P21283). 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 92.3% of cancer cell lines).

This gene encodes a component of vacuolar ATPase (V-ATPase), a multisubunit enzyme that mediates acidification of intracellular compartments of eukaryotic cells. V-ATPase dependent 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 is one of two genes that encode the V1 domain C subunit proteins and is found ubiquitously. This C subunit is analogous but not homologous to gamma subunit of F-ATPases. Previously, this gene was designated ATP6D.

Source: NCBI Gene 528 — RefSeq curated summary.

At a glance

• Gene–disease (curated): neurodevelopmental disorder (Limited, GenCC)
• GWAS associations: 3
• Clinical variants (ClinVar): 64 total — 3 pathogenic, 1 likely-pathogenic
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 92.3% of screened cell lines (common-essential)
• MANE Select transcript: NM_001695

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:856
Approved symbol	ATP6V1C1
Name	ATPase H+ transporting V1 subunit C1
Location	8q22.3
Locus type	gene with protein product
Status	Approved
Aliases	VATC, Vma5
Ensembl gene	ENSG00000155097
Ensembl biotype	protein_coding
OMIM	603097
Entrez	528

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 9 protein_coding, 2 retained_intron

ENST00000395862, ENST00000518738, ENST00000518857, ENST00000518959, ENST00000521514, ENST00000521671, ENST00000897219, ENST00000937666, ENST00000954069, ENST00000954070, ENST00000954071

RefSeq mRNA: 1 — MANE Select: NM_001695 NM_001695

CCDS: CCDS6296

Canonical transcript exons

ENST00000518738 — 13 exons

Exon	Start	End
ENSE00001019165	103064714	103064811
ENSE00001019167	103063135	103063228
ENSE00001019174	103051050	103051144
ENSE00001019175	103068652	103073051
ENSE00001019178	103040798	103040968
ENSE00002091678	103021083	103021225
ENSE00003489610	103052731	103052822
ENSE00003500376	103066321	103066447
ENSE00003507216	103062955	103063047
ENSE00003534657	103055868	103055936
ENSE00003540937	103048870	103048955
ENSE00003589513	103042340	103042407
ENSE00003624133	103053884	103053982

Expression profiles

Bgee: expression breadth ubiquitous, 291 present calls, max score 97.40.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 50.0751 / max 2885.0765, expressed in 1805 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
90087	46.7074	1805
90086	3.3677	1431

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sperm	CL:0000019	97.40	gold quality
lateral nuclear group of thalamus	UBERON:0002736	96.18	gold quality
prefrontal cortex	UBERON:0000451	96.00	gold quality
adrenal tissue	UBERON:0018303	95.68	gold quality
male germ cell	CL:0000015	95.38	gold quality
islet of Langerhans	UBERON:0000006	95.09	gold quality
superior frontal gyrus	UBERON:0002661	94.91	gold quality
middle temporal gyrus	UBERON:0002771	94.67	gold quality
substantia nigra pars compacta	UBERON:0001965	94.36	gold quality
Brodmann (1909) area 23	UBERON:0013554	94.19	gold quality
pons	UBERON:0000988	94.18	gold quality
frontal cortex	UBERON:0001870	94.16	gold quality
Brodmann (1909) area 9	UBERON:0013540	94.16	gold quality
parietal lobe	UBERON:0001872	94.08	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	94.04	gold quality
postcentral gyrus	UBERON:0002581	93.95	gold quality
neocortex	UBERON:0001950	93.58	gold quality
entorhinal cortex	UBERON:0002728	93.49	gold quality
heart right ventricle	UBERON:0002080	93.18	gold quality
cerebral cortex	UBERON:0000956	93.15	gold quality
Brodmann (1909) area 46	UBERON:0006483	93.07	gold quality
primary visual cortex	UBERON:0002436	92.91	gold quality
superior vestibular nucleus	UBERON:0007227	92.89	gold quality
right adrenal gland	UBERON:0001233	92.74	gold quality
right adrenal gland cortex	UBERON:0035827	92.71	gold quality
stromal cell of endometrium	CL:0002255	92.67	gold quality
occipital lobe	UBERON:0002021	92.62	gold quality
right frontal lobe	UBERON:0002810	92.50	gold quality
left adrenal gland	UBERON:0001234	92.40	gold quality
calcaneal tendon	UBERON:0003701	92.06	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-CURD-112	yes	659.46
E-ANND-3	yes	13.20
E-CURD-53	no	94.98

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CREB1

miRNA regulators (miRDB)

182 targeting ATP6V1C1, 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-5011-5P	100.00	83.46	5820
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-6748-5P	100.00	65.81	1057
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-3064-3P	100.00	70.09	1254
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-433-3P	99.98	69.37	1203
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-548N	99.98	71.94	4170
HSA-LET-7A-5P	99.98	72.29	1790
HSA-LET-7B-5P	99.98	72.31	1790

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 92.3% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 8)

• proximal promoter region contains cis-acting elements required for expression in cancer cells (PMID:12890556)
• Immunohistochemical localization of C1 subunit of V-ATPase (ATPase C1) in oral squamous cell cancer and normal oral mucosa. (PMID:21526910)
• results of our study suggest that high expression of Atp6v1c1 affects the actin structure of cancer cells such that it facilitates breast cancer metastasis (PMID:24454753)
• We assessed ATPaseC1 expression in a sample of oral squamous cell carcinoma using tissue microarrays to analyze the relation between ATPaseC1 expression and clinical, histopathological and prognostic parameters. (PMID:25901422)
• knockdown of C1 reduces breast cancer growth, metastasis, and osteolytic lesion formation. (PMID:28504970)
• MIR29a plays an important role during the trans-differentiation of Activated hepatic stellate cells in the resolution of liver fibrosis, in part, through regulation of ATP6V1C1. (PMID:30781750)
• Multi-cancer V-ATPase molecular signatures: A distinctive balance of subunit C isoforms in esophageal carcinoma. (PMID:31901859)
• The ATPase subunit of ATP6V1C1 inhibits autophagy and enhances radiotherapy resistance in esophageal squamous cell carcinoma. (PMID:33183740)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	atp6v1c1a	ENSDARG00000023967
danio_rerio	atp6v1c1b	ENSDARG00000035880
mus_musculus	Atp6v1c1	ENSMUSG00000022295
rattus_norvegicus	Atp6v1c1	ENSRNOG00000004846
drosophila_melanogaster	Vha44	FBGN0287825
caenorhabditis_elegans		WBGENE00006920

Paralogs (1): ATP6V1C2 (ENSG00000143882)

Protein

Protein identifiers

V-type proton ATPase subunit C 1 — P21283 (reviewed: P21283)

Alternative names: Vacuolar proton pump subunit C 1

All UniProt accessions (3): P21283, A0A024R9I0, E7EV59

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 C is necessary for the assembly of the catalytic sector of the enzyme and is likely to have a specific function in its catalytic activity.

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. Cytoplasmic vesicle. Secretory vesicle. Synaptic vesicle membrane. Clathrin-coated vesicle membrane.

Tissue specificity. Ubiquitous.

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

RefSeq proteins (1): NP_001686* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004907	ATPase_V1-cplx_csu	Family
IPR036132	Vac_ATP_synth_c_sf	Homologous_superfamily

Pfam: PF03223

UniProt features (34 total): strand 14, helix 10, turn 7, initiator methionine 1, chain 1, modified residue 1

Structure

Experimental structures (PDB)

5 structures.

PDB	Method	Resolution (Å)
6WM2	ELECTRON MICROSCOPY	3.1
6WM3	ELECTRON MICROSCOPY	3.4
6WM4	ELECTRON MICROSCOPY	3.6
7U4T	ELECTRON MICROSCOPY	3.6
7UNF	ELECTRON MICROSCOPY	4.08

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P21283-F1	91.91	0.84

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: 261 (showing top): AGGAAGC_MIR5163P, REACTOME_SIGNALING_BY_INSULIN_RECEPTOR, GOBP_REGULATION_OF_AUTOPHAGY, MODY_HIPPOCAMPUS_POSTNATAL, REACTOME_INNATE_IMMUNE_SYSTEM, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, GOCC_VACUOLAR_MEMBRANE, GOBP_VESICLE_ORGANIZATION, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, IVANOVA_HEMATOPOIESIS_LATE_PROGENITOR, GOBP_VESICLE_MEDIATED_TRANSPORT, CAGCTG_AP4_Q5, GOBP_MONOATOMIC_CATION_TRANSPORT, GOBP_MACROAUTOPHAGY, WEI_MYCN_TARGETS_WITH_E_BOX

GO Biological Process (4): regulation of macroautophagy (GO:0016241), 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), protein binding (GO:0005515), proton transmembrane transporter activity (GO:0015078)

GO Cellular Component (16): vacuolar proton-transporting V-type ATPase, V1 domain (GO:0000221), lysosomal membrane (GO:0005765), cytosol (GO:0005829), plasma membrane (GO:0005886), proton-transporting two-sector ATPase complex (GO:0016469), clathrin-coated vesicle membrane (GO:0030665), apical part of cell (GO:0045177), extracellular exosome (GO:0070062), extrinsic component of synaptic vesicle membrane (GO:0098850), membrane (GO:0016020), synaptic vesicle membrane (GO:0030672), cytoplasmic vesicle (GO:0031410), proton-transporting V-type ATPase complex (GO:0033176), proton-transporting V-type ATPase, V1 domain (GO:0033180), synapse (GO:0045202), 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	3
proton transmembrane transport	2
cytoplasm	2
regulation of autophagy	1
macroautophagy	1
intercellular transport	1
synaptic vesicle maturation	1
establishment of localization in cell	1
neuron cellular homeostasis	1
synaptic vesicle cycle	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
binding	1
monoatomic cation transmembrane transporter activity	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
membrane	1
cell periphery	1
membrane protein complex	1
clathrin-coated vesicle	1
coated vesicle membrane	1
extracellular vesicle	1
synaptic vesicle membrane	1
extrinsic component of organelle membrane	1
synaptic vesicle	1
exocytic vesicle membrane	1
intracellular vesicle	1
proton-transporting two-sector ATPase complex	1
cation-transporting ATPase complex	1
ATPase complex	1
proton-transporting V-type ATPase complex	1
proton-transporting two-sector ATPase complex, catalytic domain	1
cell junction	1
catalytic complex	1

Protein interactions and networks

STRING

1497 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ATP6V1C1	ATP6V1B2	P21281	941
ATP6V1C1	ATP6V1A	P38606	928
ATP6V1C1	ATP6V0C	P27449	909
ATP6V1C1	ATP6V1E1	P36543	886
ATP6V1C1	ATP6V1H	Q9UI12	867
ATP6V1C1	ATP6V1B1	P15313	863
ATP6V1C1	ATP6V1F	Q16864	857
ATP6V1C1	ATP6V1D	Q9Y5K8	853
ATP6V1C1	ATP6V1E2	Q96A05	832
ATP6V1C1	ATP6V0D1	P12953	812
ATP6V1C1	ATP6V0A1	Q93050	803
ATP6V1C1	ATP6V0A4	Q9HBG4	795
ATP6V1C1	TCIRG1	Q13488	782
ATP6V1C1	ATP6V0A2	Q9Y487	770
ATP6V1C1	ATP6V0D2	Q8N8Y2	739

IntAct

45 interactions, top by confidence:

A	B	Type	Score
PAK2	NCK2	psi-mi:“MI:0914”(association)	0.840
CDCA3	CTDSPL	psi-mi:“MI:0914”(association)	0.670
ATP6V1C2	ATP6V1G1	psi-mi:“MI:0914”(association)	0.640
ATP6V0A2	B4GALT3	psi-mi:“MI:0914”(association)	0.530
ATP6AP2	ATP6V1C1	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
ATP6V0A4	ATP6AP2	psi-mi:“MI:0914”(association)	0.530
ATP6V1G2	ATP6V1B1	psi-mi:“MI:0914”(association)	0.530
TCIRG1	AP3D1	psi-mi:“MI:0914”(association)	0.530
ATP6V1C1	ARF6	psi-mi:“MI:0915”(physical association)	0.520
ARF6	ATP6V1C1	psi-mi:“MI:0915”(physical association)	0.520
GPC1	SNAP23	psi-mi:“MI:0915”(physical association)	0.400
GPC1	GANAB	psi-mi:“MI:0915”(physical association)	0.400
ATP6V1C1	Arf6	psi-mi:“MI:0915”(physical association)	0.400
ATP6V1C1	ATP6V1C1	psi-mi:“MI:0915”(physical association)	0.370
SMS	BAP1	psi-mi:“MI:0914”(association)	0.350
PPP2R1A	INTS2	psi-mi:“MI:0914”(association)	0.350
PLEKHA7	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
ESR1	ESYT2	psi-mi:“MI:0914”(association)	0.350
ATP6V1C2	POTEF	psi-mi:“MI:0914”(association)	0.350
NUFIP1	MAP1LC3B2	psi-mi:“MI:0914”(association)	0.350
DGUOK	DNM1L	psi-mi:“MI:0914”(association)	0.350
DNAAF2	DNM1L	psi-mi:“MI:0914”(association)	0.350
ATP6V1B1	ATP6V1G1	psi-mi:“MI:0914”(association)	0.350

BioGRID (140): ATP6V1C1 (Two-hybrid), ATP6V1C1 (Affinity Capture-MS), ATP6V1C1 (Affinity Capture-MS), ATP6V1C1 (Affinity Capture-MS), ATP6V1C1 (Affinity Capture-MS), ATL3 (Co-fractionation), ATP6V1C1 (Co-fractionation), ATP6V1C1 (Co-fractionation), ATP6V1C1 (Co-fractionation), ATP6V1C1 (Co-fractionation), ATP6V1C1 (Co-fractionation), ATP6V1C1 (Co-fractionation), ATP6V1C1 (Co-fractionation), ATP6V1C1 (Affinity Capture-MS), ATP6V1C1 (Affinity Capture-MS)

ESM2 similar proteins: A4FUD6, A4FVD8, A6QQL9, A7YWS7, B2GUZ5, B5KFI0, O22969, O54956, O95803, P11497, P13984, P16254, P16255, P21282, P21283, P37108, P52865, P52907, P56282, Q01750, Q13085, Q1RMS5, Q28H91, Q29S16, Q2T9L9, Q2TAD4, Q4R5C7, Q4R5H9, Q4R959, Q5FVI6, Q5NVM0, Q5RBS7, Q5RBX7, Q5RCC1, Q5RDQ7, Q5SQF8, Q5SWU9, Q5ZKQ6, Q6NYV5, Q7T385

Diamond homologs: P21282, P21283, P31412, P54648, Q4R5H9, Q5FVI6, Q5RDQ7, Q5XH14, Q5XIY6, Q612A4, Q6AYE4, Q6P4Y9, Q7T385, Q8NEY4, Q99L60, Q9NDR5, Q9SCB9, Q9SDS7, Q9U5N1, Q9V7N5, Q9XXU9, Q9Z1G3, Q9HDW6

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
ATP6V1C1	“form complex”	V-ATPase	binding
TFE3	“up-regulates quantity by expression”	ATP6V1C1	“transcriptional regulation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 50 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	10	181.6×	5e-20
Insulin receptor recycling	15	154.3×	7e-29
Transferrin endocytosis and recycling	15	149.3×	7e-29
ROS and RNS production in phagocytes	15	136.2×	3e-28
Amino acids regulate mTORC1	12	65.0×	6e-18
Ion channel transport	15	38.9×	3e-19

GO biological processes:

GO term	Partners	Fold	FDR
synaptic vesicle lumen acidification	12	234.1×	5e-25
vacuolar acidification	12	183.2×	2e-23
lysosomal lumen acidification	7	98.3×	3e-11
proton transmembrane transport	13	84.5×	2e-20
regulation of macroautophagy	12	73.9×	4e-18

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	3
Likely pathogenic	1
Uncertain significance	39
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (4)

Variant ID	HGVS	Classification
147649	GRCh38/hg38 8q22.3-23.1(chr8:101199826-105802098)x1	Pathogenic
3069170	NM_001695.5(ATP6V1C1):c.865G>A (p.Glu289Lys)	Pathogenic
57125	GRCh38/hg38 8q22.3(chr8:101962098-103357772)x3	Pathogenic
441918	GRCh37/hg19 8q22.3(chr8:102590127-104034598)x1	Likely pathogenic

SpliceAI

2359 predictions. Top by Δscore:

Variant	Effect	Δscore
8:103048868:A:AG	acceptor_gain	1.0000
8:103048868:AGAGT:A	acceptor_gain	1.0000
8:103048869:G:GG	acceptor_gain	1.0000
8:103048869:GA:G	acceptor_gain	1.0000
8:103048869:GAGT:G	acceptor_gain	1.0000
8:103048869:GAGTG:G	acceptor_gain	1.0000
8:103048954:AGG:A	donor_loss	1.0000
8:103048957:T:G	donor_loss	1.0000
8:103051048:A:AG	acceptor_gain	1.0000
8:103051048:AGT:A	acceptor_gain	1.0000
8:103051048:AGTG:A	acceptor_gain	1.0000
8:103051049:G:GT	acceptor_gain	1.0000
8:103051049:GT:G	acceptor_gain	1.0000
8:103051049:GTG:G	acceptor_gain	1.0000
8:103051049:GTGG:G	acceptor_gain	1.0000
8:103051140:CCAAG:C	donor_loss	1.0000
8:103051141:CAAG:C	donor_loss	1.0000
8:103051142:AAG:A	donor_loss	1.0000
8:103051145:GT:G	donor_loss	1.0000
8:103051146:T:G	donor_loss	1.0000
8:103052173:C:G	donor_gain	1.0000
8:103052727:A:AG	acceptor_gain	1.0000
8:103052727:AAAG:A	acceptor_gain	1.0000
8:103052727:AAAGG:A	acceptor_gain	1.0000
8:103052728:A:G	acceptor_gain	1.0000
8:103052728:AAG:A	acceptor_gain	1.0000
8:103052728:AAGG:A	acceptor_gain	1.0000
8:103052729:A:G	acceptor_gain	1.0000
8:103052729:AG:A	acceptor_gain	1.0000
8:103052730:G:GG	acceptor_gain	1.0000

AlphaMissense

2536 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:103040856:T:A	I7K	1.000
8:103040859:C:T	S8F	1.000
8:103040862:C:A	A9D	1.000
8:103042343:G:C	G46R	1.000
8:103042344:G:A	G46D	1.000
8:103042350:T:C	L48S	1.000
8:103042350:T:G	L48W	1.000
8:103042359:T:C	L51S	1.000
8:103042359:T:G	L51W	1.000
8:103042380:T:C	L58P	1.000
8:103051076:T:C	F105L	1.000
8:103051078:C:A	F105L	1.000
8:103051078:C:G	F105L	1.000
8:103051082:T:A	W107R	1.000
8:103051082:T:C	W107R	1.000
8:103051083:G:C	W107S	1.000
8:103051084:G:C	W107C	1.000
8:103051084:G:T	W107C	1.000
8:103051092:C:A	A110D	1.000
8:103051096:A:C	K111N	1.000
8:103051096:A:T	K111N	1.000
8:103051097:T:G	Y112D	1.000
8:103052756:T:C	L136P	1.000
8:103052776:T:G	Y143D	1.000
8:103052798:T:C	L150P	1.000
8:103053955:T:C	L182P	1.000
8:103053976:T:A	V189D	1.000
8:103055884:T:A	W197R	1.000
8:103055884:T:C	W197R	1.000
8:103055921:T:A	V209D	1.000

dbSNP variants (sampled 300 via entrez): RS1000010313 (8:103044858 C>G,T), RS1000097426 (8:103043730 TC>T), RS1000119698 (8:103019776 T>C), RS1000120186 (8:103051909 A>G), RS1000204091 (8:103023896 AT>A,ATT), RS1000240889 (8:103069125 T>C), RS1000292812 (8:103027421 T>C), RS1000360859 (8:103057745 A>G), RS1000392289 (8:103057966 C>T), RS1000451426 (8:103043966 G>A,T), RS1000451785 (8:103021084 T>G), RS1000486534 (8:103031634 G>A), RS1000516484 (8:103039104 A>T), RS1000618692 (8:103027516 T>C,G), RS1000683727 (8:103026093 C>T)

Disease associations

OMIM: gene MIM:603097 | disease phenotypes: MIM:220500

GenCC curated gene-disease

Disease	Classification	Inheritance
neurodevelopmental disorder	Limited	Autosomal dominant

Mondo (2): DOORS syndrome (MONDO:0009079), neurodevelopmental disorder (MONDO:0700092)

Orphanet (2): Deafness-onychodystrophy syndrome (Orphanet:3231), DOORS syndrome (Orphanet:79500)

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST005057_6	Small vessel stroke	7.000000e-06
GCST009306_14	Spatial processing	8.000000e-06
GCST009312_19	Antisaccade task score	5.000000e-06

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:1001504	small vessel stroke
EFO:0008354	cognitive function measurement
EFO:0007969	cognitive inhibition measurement

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D065886	Neurodevelopmental Disorders	F03.625
C563052	Digitorenocerebral Syndrome (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5465286 (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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, affects cotreatment, increases expression	6
sodium arsenite	decreases expression, increases expression	3
mercuric bromide	affects cotreatment, increases expression	2
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression, increases expression	2
Quercetin	decreases expression	2
Tobacco Smoke Pollution	increases expression	2
aristolochic acid I	increases expression	1
bisphenol F	increases expression	1
2,4,6-tribromophenol	increases expression	1
methylmercuric chloride	decreases expression, increases expression	1
bisphenol A	increases expression	1
decabromobiphenyl ether	increases expression	1
trichostatin A	affects expression	1
beta-lapachone	increases expression	1
cupric oxide	increases expression	1
K 7174	increases expression	1
14-deoxy-11,12-didehydroandrographolide	decreases expression	1
dorsomorphin	affects cotreatment, increases expression	1
(4-amino-1,4-dihydro-3-(2-pyridyl)-5-thioxo-1,2,4-triazole)copper(II)	increases expression	1
pentabrominated diphenyl ether 100	increases expression	1
hexabrominated diphenyl ether 153	increases expression	1
2-(1H-indazol-4-yl)-6-(4-methanesulfonylpiperazin-1-ylmethyl)-4-morpholin-4-ylthieno(3,2-d)pyrimidine	increases expression, increases response to substance	1
bisphenol S	increases expression	1
LDN 193189	affects cotreatment, decreases expression	1
NSC 689534	affects binding, increases expression	1
PCI 5002	affects cotreatment, increases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Sunitinib	increases expression	1
Air Pollutants, Occupational	decreases expression	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
CHEMBL5338475	Binding	Binding affinity to Atp6v1c1 (unknown origin) assessed as fold change in protein upregulation at 200 uM preincubated for 2 hrs followed by pronase addition and measured after 30 mins by coomassie blue staining based SDS-PAGE gel analysis	Structurally Diverse Alkaloids with Anti-Renal-Fibrosis Activity from the Centipede Scolopendra subspinipes mutilans. — J Nat Prod

Clinical trials (associated diseases)

202 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,
NCT02559102	PHASE3	COMPLETED	Dexmedetomidine Sedation Versus General Anaesthesia for Inguinal Hernia Surgery in Infants
NCT02757079	PHASE3	COMPLETED	Study of the Efficacy and Safety of NPC-15 for Sleep Disorders of Children With Neurodevelopmental Disorders
NCT06915480	PHASE3	RECRUITING	Reducing Missed Appointments
NCT07377032	PHASE3	RECRUITING	TAP-GRIN: Interventional Study on Patients With GRIN-related Neurodevelopmental Disorders
NCT02909959	PHASE2	COMPLETED	Sulforaphane for the Treatment of Young Men With Autism Spectrum Disorder
NCT06081348	PHASE2	RECRUITING	Sertraline vs. Placebo in the Treatment of Anxiety in Children and AdoLescents With NeurodevelopMental Disorders
NCT06352372	PHASE2	COMPLETED	Safety and Efficacy of tPBM for Epileptiform Activity in Autism
NCT00503191	PHASE1	COMPLETED	NeuroModulation Technique Treatment of Autism
NCT04475848	PHASE1	COMPLETED	A Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Food Effect of RO6953958 in Healthy Participants
NCT06300398	PHASE1	COMPLETED	IAMA-6 Oral Dose Study in Healthy Adults
NCT01783041	PHASE2/PHASE3	COMPLETED	Effect of Early L-Carnitine Supplementation on Neurodevelopmental Outcomes in Very Preterm Infants
NCT05767385	PHASE2/PHASE3	RECRUITING	Fetal Cerebrovascular Autoregulation in Congenital Heart Disease and Association With Neonatal Neurobehavior
NCT05675098	EARLY_PHASE1	NOT_YET_RECRUITING	Central Nervous System Stimulants and Physical Function in Children With Cerebral Palsy
NCT00783783	Not specified	COMPLETED	CYP2D6 Pharmacogenetics in Risperidone-Treated Children
NCT01778504	Not specified	RECRUITING	Studying Childhood-onset Behavioral, Psychiatric, and Developmental Disorders
NCT01850784	Not specified	UNKNOWN	High Energy Formula Feeding in Infants With Congenital Heart Disease
NCT01922791	Not specified	COMPLETED	Nutrition and Pregnancy Intervention Study
NCT01942525	Not specified	UNKNOWN	Influence of Intrauterine Growth Restriction on Amplitude-integrated EEG in Preterm Infants
NCT02003170	Not specified	COMPLETED	Etiology and Early Diagnosis of Neurodevelopmental Disorders
NCT02118649	Not specified	ACTIVE_NOT_RECRUITING	Enhancing Behavior and Brain Response to Visual Targets Using a Computer Game
NCT02557191	Not specified	TERMINATED	Biomarkers, Neurodevelopment and Preterm Infants
NCT02690675	Not specified	COMPLETED	Iron Supplement Effect on Child Development
NCT02694003	Not specified	COMPLETED	Better Nights, Better Days for Children With Neurodevelopment Disorders
NCT02792894	Not specified	COMPLETED	Family Networks (FaNs) for Children With Developmental Disorders and Delays
NCT02871674	Not specified	UNKNOWN	Good Night Project: Behavioural Sleep Interventions for Children With ADHD: A Randomised Controlled Trial
NCT02887157	Not specified	COMPLETED	Analyzing Retinal Microanatomy in ROP
NCT02898298	Not specified	COMPLETED	Positive Emotion Regulation Training in Children, Adolescents and Young Adults With and Without Developmental Disorder
NCT02912780	Not specified	UNKNOWN	Introduction of Microsystems in a Level 3 Neonatal Intensive Care Unit
NCT03023293	Not specified	COMPLETED	n-3 PUFAs, Irisin and Maternal Glucose Metabolism From Pregnancy to Postpartum
NCT03023644	Not specified	COMPLETED	Improving Neurodevelopmental Outcomes in Children With Congenital Heart Disease: An Intervention Study
NCT03032991	Not specified	UNKNOWN	Early Biomarkers of Neurodevelopment in Offspring of Diabetic Mothers
NCT03088189	Not specified	TERMINATED	Effect of Parental Peri-conceptional Vitamin B12 Supplementation on Infant Neurocognitive Development in Offspring
NCT03096028	Not specified	COMPLETED	Developmental Origins of Mental Health Disorders
NCT03148782	Not specified	COMPLETED	Brain Plasticity Underlying Acquisition of New Organizational Skills in Children-R61 Phase
NCT03172104	Not specified	COMPLETED	Neurobehavioural Development of Infants Born <30 Weeks Gestational Age Between Birth and Five Years of Age
NCT03222375	Not specified	RECRUITING	SQUED™ Series 28.1 Home-use and Treatment of Autowave Reverberator of Autism
NCT03229928	Not specified	COMPLETED	Clinical Testing of a Real-Time Behavior Measurement Tool: Measuring Outcomes for CHAnge
NCT03232489	Not specified	UNKNOWN	Study for the Evaluation of the Feasibility of Applying Advanced MRI Scanning in Pediatric Clinical Practice