ATP6V1H

Summary

ATP6V1H (ATPase H+ transporting V1 subunit H, HGNC:18303) is a protein-coding gene on chromosome 8q11.23, encoding V-type proton ATPase subunit H (Q9UI12). 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 selective cancer dependency (DepMap: 64.6% of cell lines).

This gene encodes a component of vacuolar ATPase (V-ATPase), a multisubunit enzyme that mediates acidification of intracellular organelles. V-ATPase-dependent organelle acidification is necessary for multiple processes including protein sorting, zymogen activation, receptor-mediated endocytosis, and synaptic vesicle proton gradient generation. The encoded protein is the regulatory H subunit of the V1 domain of V-ATPase, which is required for catalysis of ATP but not the assembly of V-ATPase. Decreased expression of this gene may play a role in the development of type 2 diabetes. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene.

Source: NCBI Gene 51606 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 87 total
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 64.6% of screened cell lines
• MANE Select transcript: NM_015941

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18303
Approved symbol	ATP6V1H
Name	ATPase H+ transporting V1 subunit H
Location	8q11.23
Locus type	gene with protein product
Status	Approved
Aliases	CGI-11, SFD, VMA13, SFDalpha, SFDbeta
Ensembl gene	ENSG00000047249
Ensembl biotype	protein_coding
OMIM	608861
Entrez	51606

Gene structure

Transcript identifiers

Ensembl transcripts: 47 — 34 protein_coding, 5 retained_intron, 5 protein_coding_CDS_not_defined, 3 nonsense_mediated_decay

ENST00000355221, ENST00000359530, ENST00000396774, ENST00000518072, ENST00000519588, ENST00000519922, ENST00000520188, ENST00000521275, ENST00000521335, ENST00000521377, ENST00000521707, ENST00000521900, ENST00000522159, ENST00000522849, ENST00000523343, ENST00000523426, ENST00000523899, ENST00000524164, ENST00000524234, ENST00000884425, ENST00000884426, ENST00000884427, ENST00000884428, ENST00000884429, ENST00000884430, ENST00000884431, ENST00000884432, ENST00000884433, ENST00000915523, ENST00000915524, ENST00000915525, ENST00000915526, ENST00000915527, ENST00000915528, ENST00000915529, ENST00000915530, ENST00000915531, ENST00000915532, ENST00000915533, ENST00000915534, ENST00000957343, ENST00000957344, ENST00000957345, ENST00000957346, ENST00000957347, ENST00000957348, ENST00000957349

RefSeq mRNA: 3 — MANE Select: NM_015941 NM_015941, NM_213619, NM_213620

CCDS: CCDS6153, CCDS6154

Canonical transcript exons

ENST00000359530 — 14 exons

Exon	Start	End
ENSE00002100015	53843034	53843245
ENSE00003459095	53769618	53769743
ENSE00003475672	53771989	53772167
ENSE00003491721	53795647	53795839
ENSE00003539216	53801799	53801896
ENSE00003566866	53811164	53811217
ENSE00003597989	53743577	53743690
ENSE00003599916	53817417	53817530
ENSE00003642724	53814662	53814766
ENSE00003663362	53756555	53756656
ENSE00003677414	53832984	53833086
ENSE00003684303	53841578	53841725
ENSE00003788740	53829444	53829533
ENSE00003850833	53715543	53716024

Expression profiles

Bgee: expression breadth ubiquitous, 293 present calls, max score 98.70.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 42.7446 / max 431.1545, expressed in 1823 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
93079	40.7893	1823
93078	1.7000	905
93077	0.1888	88
93076	0.0533	18
93075	0.0131	6

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
middle temporal gyrus	UBERON:0002771	98.70	gold quality
Brodmann (1909) area 9	UBERON:0013540	98.29	gold quality
prefrontal cortex	UBERON:0000451	98.16	gold quality
right frontal lobe	UBERON:0002810	98.03	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	97.95	gold quality
amygdala	UBERON:0001876	97.93	gold quality
nucleus accumbens	UBERON:0001882	97.86	gold quality
caudate nucleus	UBERON:0001873	97.71	gold quality
cingulate cortex	UBERON:0003027	97.64	gold quality
Ammon’s horn	UBERON:0001954	97.62	gold quality
anterior cingulate cortex	UBERON:0009835	97.59	gold quality
frontal cortex	UBERON:0001870	97.51	gold quality
putamen	UBERON:0001874	97.49	gold quality
cerebral cortex	UBERON:0000956	97.38	gold quality
neocortex	UBERON:0001950	97.38	gold quality
superior frontal gyrus	UBERON:0002661	97.34	gold quality
telencephalon	UBERON:0001893	97.32	gold quality
temporal lobe	UBERON:0001871	97.31	gold quality
pons	UBERON:0000988	97.25	gold quality
forebrain	UBERON:0001890	97.12	gold quality
lateral nuclear group of thalamus	UBERON:0002736	97.01	gold quality
Brodmann (1909) area 23	UBERON:0013554	96.93	gold quality
postcentral gyrus	UBERON:0002581	96.84	gold quality
brain	UBERON:0000955	96.71	gold quality
parietal lobe	UBERON:0001872	96.68	gold quality
adenohypophysis	UBERON:0002196	96.67	gold quality
central nervous system	UBERON:0001017	96.63	gold quality
orbitofrontal cortex	UBERON:0004167	96.62	gold quality
entorhinal cortex	UBERON:0002728	96.42	gold quality
hypothalamus	UBERON:0001898	96.39	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

43 targeting ATP6V1H, 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-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-381-3P	99.93	71.87	2854
HSA-MIR-300	99.92	71.76	2856
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-380-3P	99.89	70.18	1978
HSA-MIR-629-3P	99.85	67.99	1875
HSA-MIR-3180-5P	99.82	69.12	2422
HSA-MIR-4495	99.82	72.08	3080
HSA-MIR-4713-5P	99.78	67.80	1794
HSA-MIR-5002-5P	99.76	70.84	1763
HSA-MIR-132-3P	99.73	70.56	1424
HSA-MIR-212-3P	99.73	70.65	1424
HSA-MIR-379-3P	99.69	69.60	1524
HSA-MIR-411-3P	99.69	69.63	1524
HSA-MIR-12124	99.68	69.17	2700
HSA-MIR-4470	99.66	69.35	1767
HSA-MIR-12131	99.48	68.72	1673
HSA-MIR-520A-5P	99.35	66.72	1632
HSA-MIR-525-5P	99.35	66.85	1615
HSA-MIR-532-3P	99.34	65.76	1195
HSA-MIR-4311	99.31	70.47	3041
HSA-MIR-410-3P	99.27	69.98	2457
HSA-MIR-3973	99.20	69.19	1990
HSA-MIR-3125	99.14	68.49	2269

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 64.6% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 8)

• Our study shows that multiple mechanisms of pump dysfunction result from B1 subunit mutations with a common outcome being defective assembly (PMID:18368028)
• Data show that the BCG phagosome is relatively depleted in LAMP-2, NPC1, flotillin-1, vATPase, and syntaxin 3. (PMID:19815536)
• ATP6V1H may represent a critical molecular mechanism involved in the development of type 2 diabetes and its compilations through its important regulatory effect on vacuolar-ATPase activity. (PMID:21871445)
• A protein encoded by this locus was found to be differentially expressed in postmortem brains from patients with atypical frontotemporal lobar degeneration. (PMID:22360420)
• These data provide evidence that partial loss of ATP6V1H function results in osteoporosis/osteopenia. (PMID:27924156)
• These studies have uncovered a new, ATP6V1H-mediated pathway that regulates bone formation, and defines a new mechanism of disease that leads to bone loss. We propose that MMP9/MMP13 could be therapeutic targets for patients with this rare genetic disease. (PMID:28158191)
• Study identified rs1481950 within ATP6V1H influencing human CSF BACE activity, which indicated that ATP6V1H gene may play some roles in the pathogenesis of neurodegenerative diseases such as Alzheimer disease. (PMID:29751835)
• Long Noncoding RNA lnc-TCEA1-3 Affects Osteoclastic Function by Regulating ATP6V1H. (PMID:37824389)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	atp6v1h	ENSDARG00000006370
mus_musculus	Atp6v1h	ENSMUSG00000033793
rattus_norvegicus	Atp6v1h	ENSRNOG00000030862
drosophila_melanogaster	VhaSFD	FBGN0027779
caenorhabditis_elegans		WBGENE00018698
caenorhabditis_elegans		WBGENE00020507

Protein

Protein identifiers

V-type proton ATPase subunit H — Q9UI12 (reviewed: Q9UI12)

Alternative names: Nef-binding protein 1, Protein VMA13 homolog, V-ATPase 50/57 kDa subunits, Vacuolar proton pump subunit H, Vacuolar proton pump subunit SFD

All UniProt accessions (7): E5RG49, Q9UI12, E5RHH0, E5RJG1, E5RK31, G3V126, H0YB41

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 H is essential for V-ATPase activity, but not for the assembly of the complex. Involved in the endocytosis mediated by clathrin-coated pits, required for the formation of endosomes.

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 AP2M1. Interacts with TM9SF4 in colon cancer cells. (Microbial infection) Interacts with HIV-1 Nef protein. (Microbial infection) Interacts with M.tuberculosis PtpA, which blocks V-ATPase trafficking and phagosome acidification.

Subcellular location. Cytoplasmic vesicle. Clathrin-coated vesicle membrane.

Tissue specificity. Widely expressed.

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

Isoforms (2)

UniProt ID	Names	Canonical?
Q9UI12-1	1	yes
Q9UI12-2	2

RefSeq proteins (3): NP_057025, NP_998784, NP_998785 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004908	ATPase_V1-cplx_hsu	Family
IPR011987	ATPase_V1-cplx_hsu_C	Domain
IPR011989	ARM-like	Homologous_superfamily
IPR016024	ARM-type_fold	Homologous_superfamily
IPR038497	ATPase_V1-cplx_hsu_C_sf	Homologous_superfamily

Pfam: PF03224, PF11698

UniProt features (49 total): helix 34, turn 9, strand 2, chain 1, modified residue 1, splice variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

8 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
7FDA	ELECTRON MICROSCOPY	4.2
7FDB	ELECTRON MICROSCOPY	4.8
7FDC	ELECTRON MICROSCOPY	6.6

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UI12-F1	88.03	0.75

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): 483

Function

Pathways and Gene Ontology

Reactome pathways

9 pathways

ID	Pathway
R-HSA-1222556	ROS and RNS production in phagocytes
R-HSA-167590	Nef Mediated CD4 Down-regulation
R-HSA-182218	Nef Mediated CD8 Down-regulation
R-HSA-77387	Insulin receptor recycling
R-HSA-917977	Transferrin endocytosis and recycling
R-HSA-9636467	Blockage of phagosome acidification
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: 279 (showing top): GSE18804_BRAIN_VS_COLON_TUMORAL_MACROPHAGE_DN, GSE45365_NK_CELL_VS_BCELL_UP, REACTOME_SIGNALING_BY_INSULIN_RECEPTOR, GOBP_REGULATION_OF_AUTOPHAGY, REACTOME_INNATE_IMMUNE_SYSTEM, GOBP_ENDOSOME_ORGANIZATION, GOBP_VACUOLE_ORGANIZATION, MORF_RAB5A, GOCC_VACUOLAR_MEMBRANE, GOBP_VESICLE_ORGANIZATION, KEGG_LYSOSOME, REACTOME_THE_ROLE_OF_NEF_IN_HIV_1_REPLICATION_AND_DISEASE_PATHOGENESIS, GOBP_VESICLE_MEDIATED_TRANSPORT, MORF_PSMC2, GOBP_MONOATOMIC_CATION_TRANSPORT

GO Biological Process (9): endocytosis (GO:0006897), vacuolar acidification (GO:0007035), lysosomal lumen acidification (GO:0007042), regulation of macroautophagy (GO:0016241), endosomal lumen acidification (GO:0048388), intracellular pH reduction (GO:0051452), Golgi lumen acidification (GO:0061795), proton transmembrane transport (GO:1902600), monoatomic ion transport (GO:0006811)

GO Molecular Function (4): enzyme regulator activity (GO:0030234), proton-transporting ATPase activity, rotational mechanism (GO:0046961), protein binding (GO:0005515), ATP hydrolysis activity (GO:0016887)

GO Cellular Component (12): Golgi membrane (GO:0000139), vacuolar proton-transporting V-type ATPase, V1 domain (GO:0000221), lysosomal membrane (GO:0005765), cytosol (GO:0005829), plasma membrane (GO:0005886), endosome membrane (GO:0010008), membrane (GO:0016020), clathrin-coated vesicle membrane (GO:0030665), proton-transporting V-type ATPase complex (GO:0033176), extracellular exosome (GO:0070062), extrinsic component of synaptic vesicle membrane (GO:0098850), cytoplasmic vesicle (GO:0031410)

Reactome top-level categories

Rollup of top-8 pathways:

Category	Pathways
Nef-mediates down modulation of cell surface receptors by recruiting them to clathrin adapters	2
Innate Immune System	1
Signaling by Insulin receptor	1
Iron uptake and transport	1
Suppression of phagosomal maturation	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
intracellular pH reduction	3
bounding membrane of organelle	2
cytoplasm	2
cellular anatomical structure	2
vesicle budding from membrane	1
membrane invagination	1
vesicle-mediated transport	1
import into cell	1
vacuolar acidification	1
regulation of autophagy	1
macroautophagy	1
endosome organization	1
regulation of intracellular pH	1
monoatomic cation transmembrane transport	1
transport	1
catalytic activity	1
molecular function regulator 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
binding	1
ribonucleoside triphosphate phosphatase activity	1
ATP-dependent activity	1
Golgi apparatus	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
endosome	1
cytoplasmic vesicle membrane	1
clathrin-coated vesicle	1
coated vesicle membrane	1
proton-transporting two-sector ATPase complex	1
cation-transporting ATPase complex	1
ATPase complex	1
extracellular vesicle	1
synaptic vesicle membrane	1

Protein interactions and networks

STRING

1744 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ATP6V1H	ATP6V1B2	P21281	877
ATP6V1H	ATP6V1C1	P21283	867
ATP6V1H	ATP6V1E1	P36543	866
ATP6V1H	ATP6V0B	Q99437	857
ATP6V1H	ATP6V0D1	P12953	847
ATP6V1H	ATP6V1B1	P15313	833
ATP6V1H	ATP6V1E2	Q96A05	832
ATP6V1H	ATP6V1C2	Q8NEY4	799
ATP6V1H	ATP6V1D	Q9Y5K8	794
ATP6V1H	ATP6V0D2	Q8N8Y2	790
ATP6V1H	ATP6V1A	P38606	774
ATP6V1H	ATP6V0A1	Q93050	771
ATP6V1H	AP1B1	P78436	767
ATP6V1H	ATP6V1G1	O75348	760
ATP6V1H	ATP6V1F	Q16864	760

IntAct

143 interactions, top by confidence:

A	B	Type	Score
MED20	MED19	psi-mi:“MI:0914”(association)	0.840
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
IGF2BP1	IGF2BP3	psi-mi:“MI:0914”(association)	0.640
PPP1R12C	ATP6V1H	psi-mi:“MI:0915”(physical association)	0.560
FLACC1	ATP6V1H	psi-mi:“MI:0915”(physical association)	0.560
SNPH	ATP6V1H	psi-mi:“MI:0915”(physical association)	0.560
ATP6V1H	SPATA2	psi-mi:“MI:0915”(physical association)	0.560
CDKN2B	ATP6V1H	psi-mi:“MI:0915”(physical association)	0.560
BOD1	ATP6V1H	psi-mi:“MI:0915”(physical association)	0.560
HTT	ATP6V1H	psi-mi:“MI:0915”(physical association)	0.560
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
MAS1	POTEF	psi-mi:“MI:0914”(association)	0.530
LPAR4	POTEF	psi-mi:“MI:0914”(association)	0.530
TMEM184A	SLC33A1	psi-mi:“MI:0914”(association)	0.530
NPTN	TNPO2	psi-mi:“MI:0914”(association)	0.530
DDX21	MED19	psi-mi:“MI:2364”(proximity)	0.480
GPC1	SNAP23	psi-mi:“MI:0915”(physical association)	0.400
GPC1	GANAB	psi-mi:“MI:0915”(physical association)	0.400
SOX9	ATP6V1H	psi-mi:“MI:0915”(physical association)	0.370
TANK	ATP6V1H	psi-mi:“MI:0915”(physical association)	0.370
MAPK6		psi-mi:“MI:0914”(association)	0.350
M	NPEPPSL1	psi-mi:“MI:0914”(association)	0.350
NS1	ESYT2	psi-mi:“MI:0914”(association)	0.350

BioGRID (211): ATP6V1H (Affinity Capture-MS), ATP6V1H (Affinity Capture-RNA), C6orf211 (Co-fractionation), ATP6V0D1 (Co-fractionation), ATP6V1A (Co-fractionation), ATP6V1F (Co-fractionation), ATP6V1H (Co-fractionation), ATP6V1H (Co-fractionation), ATP6V1H (Co-fractionation), ATP6V1H (Co-fractionation), CDC42 (Co-fractionation), HSD17B10 (Co-fractionation), STMN1 (Co-fractionation), ATP6V1H (Affinity Capture-MS), ATP6V1H (Affinity Capture-MS)

ESM2 similar proteins: A5D785, A5WW24, O00410, O04375, O04376, O15397, O35638, O46563, O60518, O95373, Q08AM6, Q16401, Q499Y0, Q569Z2, Q5IFJ8, Q5R9G4, Q5R9J2, Q5ZLT0, Q5ZMR9, Q68F38, Q6GMY9, Q704U0, Q7PC79, Q7TMY7, Q802D3, Q8AY73, Q8BIV3, Q8BKC5, Q8GUL2, Q8K2V6, Q8N3U4, Q8VI75, Q8WVM7, Q91YE6, Q924C1, Q96P70, Q99NF8, Q9C0E2, Q9D3E6, Q9DGN0

Diamond homologs: A8XDF8, O14265, O46563, Q20666, Q22494, Q619W9, Q8BVE3, Q9TVC1, Q9U5N0, Q9UI12, Q9V3J1, P41807, Q84ZC0, Q8MML6

SIGNOR signaling

5 interactions.

A	Effect	B	Mechanism
TM9SF4	“up-regulates activity”	ATP6V1H	binding
ATP6V1H	“form complex”	V-ATPase	binding
ATP6V1H	“up-regulates activity”	TGFBR1	binding
ATP6V1H	“up-regulates activity”	“AP-2 complex”	binding
TFEB	“up-regulates quantity by expression”	ATP6V1H	“transcriptional regulation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 158 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	59.9×	3e-12
Insulin receptor recycling	9	33.9×	8e-10
Transferrin endocytosis and recycling	9	32.8×	8e-10
ROS and RNS production in phagocytes	9	29.9×	2e-09
Amino acids regulate mTORC1	8	15.9×	4e-06
Ion channel transport	9	8.6×	1e-04

GO biological processes:

GO term	Partners	Fold	FDR
synaptic vesicle lumen acidification	10	69.3×	3e-14
vacuolar acidification	8	43.4×	3e-09
lysosomal lumen acidification	5	25.0×	2e-04
proton transmembrane transport	9	20.8×	1e-07
regulation of macroautophagy	8	17.5×	4e-06
negative regulation of translation	7	10.2×	7e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	61
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

3313 predictions. Top by Δscore:

Variant	Effect	Δscore
8:53716023:CC:C	acceptor_gain	1.0000
8:53716024:CC:C	acceptor_gain	1.0000
8:53716024:CCTGA:C	acceptor_loss	1.0000
8:53716025:C:CA	acceptor_loss	1.0000
8:53716025:C:CC	acceptor_gain	1.0000
8:53716026:T:A	acceptor_loss	1.0000
8:53743571:GCATA:G	donor_loss	1.0000
8:53743572:CATA:C	donor_loss	1.0000
8:53743573:ATACC:A	donor_loss	1.0000
8:53743574:TACC:T	donor_loss	1.0000
8:53743575:A:AC	donor_gain	1.0000
8:53743575:ACCAG:A	donor_loss	1.0000
8:53743576:C:A	donor_loss	1.0000
8:53743576:C:CC	donor_gain	1.0000
8:53743686:TGACC:T	acceptor_gain	1.0000
8:53743688:ACCC:A	acceptor_loss	1.0000
8:53743689:CC:C	acceptor_gain	1.0000
8:53743690:CC:C	acceptor_gain	1.0000
8:53743691:C:CC	acceptor_gain	1.0000
8:53756553:A:AC	donor_gain	1.0000
8:53756554:C:CC	donor_gain	1.0000
8:53769616:A:AC	donor_gain	1.0000
8:53769617:C:CC	donor_gain	1.0000
8:53769617:CTT:C	donor_gain	1.0000
8:53769744:C:CC	acceptor_gain	1.0000
8:53771991:AAGGT:A	donor_gain	1.0000
8:53772163:AAGTT:A	acceptor_gain	1.0000
8:53795640:CACT:C	donor_loss	1.0000
8:53795642:CTTA:C	donor_loss	1.0000
8:53795643:TTAC:T	donor_loss	1.0000

AlphaMissense

3222 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:53716016:A:T	L467H	1.000
8:53716024:C:A	W464C	1.000
8:53716024:C:G	W464C	1.000
8:53743578:A:G	W464R	1.000
8:53743578:A:T	W464R	1.000
8:53743589:A:C	M460R	1.000
8:53743589:A:G	M460T	1.000
8:53743589:A:T	M460K	1.000
8:53743592:A:G	L459P	1.000
8:53743594:C:A	K458N	1.000
8:53743594:C:G	K458N	1.000
8:53743596:T:C	K458E	1.000
8:53743597:C:A	Q457H	1.000
8:53743597:C:G	Q457H	1.000
8:53743598:T:G	Q457P	1.000
8:53743601:A:T	V456E	1.000
8:53743604:G:T	A455D	1.000
8:53743605:C:G	A455P	1.000
8:53743607:A:G	L454P	1.000
8:53743610:A:G	L453P	1.000
8:53743610:A:T	L453Q	1.000
8:53743613:G:T	A452D	1.000
8:53743614:C:G	A452P	1.000
8:53743622:C:G	R449P	1.000
8:53743625:A:T	V448D	1.000
8:53743655:A:G	M438T	1.000
8:53743655:A:T	M438K	1.000
8:53743658:A:T	V437D	1.000
8:53743666:C:A	K434N	1.000
8:53743666:C:G	K434N	1.000

dbSNP variants (sampled 300 via entrez): RS1000015185 (8:53725366 T>C), RS1000041457 (8:53772564 T>G), RS1000048773 (8:53788455 A>G), RS1000078147 (8:53757865 T>C), RS1000119672 (8:53748694 A>G), RS1000128766 (8:53731443 G>A), RS1000135676 (8:53801682 G>A,T), RS1000141942 (8:53753409 G>C,T), RS1000150019 (8:53829694 G>A,T), RS1000176652 (8:53763762 G>A), RS1000200832 (8:53803322 G>C), RS1000204839 (8:53763453 T>C), RS1000223256 (8:53805898 A>G), RS1000237092 (8:53718666 G>A), RS1000263786 (8:53726752 T>A)

Disease associations

OMIM: gene MIM:608861 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST001715_6	Bipolar disorder with mood-incongruent psychosis	2.000000e-06
GCST003830_33	Response to bronchodilator in chronic obstructive pulmonary disease (change in FEV1)	1.000000e-06
GCST005714_8	Cerebrospinal fluid beta-site APP cleaving enzyme levels	5.000000e-09
GCST009368_78	HDL cholesterol levels x long total sleep time interaction (2df test)	9.000000e-12

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0005921	FEV change measurement
EFO:0009179	beta-secretase 1 measurement
EFO:0004612	high density lipoprotein cholesterol measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6067086 (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

4 potent at pChembl≥5 of 4 total, top 4 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.76	Kd	1.752	nM	CHEMBL3752910
8.76	ED50	1.752	nM	CHEMBL3752910
5.62	Kd	2376	nM	CHEMBL5653589
5.62	ED50	2376	nM	CHEMBL5653589

PubChem BioAssay actives

2 with measured affinity, of 4 total; 2 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-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2147926: Binding affinity to human ATP6V1H incubated for 45 mins by Kinobead based pull down assay	kd	0.0018	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2147926: Binding affinity to human ATP6V1H incubated for 45 mins by Kinobead based pull down assay	kd	2.3763	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases methylation, increases expression	3
sodium arsenite	increases expression, affects cotreatment, increases abundance	2
Copper Sulfate	increases expression	2
bisphenol F	affects cotreatment, increases methylation	1
triphenyl phosphate	affects expression	1
pirinixic acid	affects binding, decreases expression, increases activity	1
deoxynivalenol	decreases expression	1
trichostatin A	increases expression	1
cobaltous chloride	increases expression	1
manganese chloride	affects cotreatment, increases abundance, increases expression	1
aflatoxin B2	decreases methylation	1
cupric oxide	increases expression	1
oligomycin A	affects response to substance, affects cotreatment, affects expression	1
yessotoxin	increases expression	1
K 7174	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
apatinib	affects cotreatment, increases expression	1
LDN 193189	affects cotreatment, increases expression	1
PP242	increases expression	1
bisphenol AF	increases expression	1
Imatinib Mesylate	increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Arsenic Trioxide	affects cotreatment, increases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Leflunomide	increases expression	1
Antimycin A	affects cotreatment, affects expression, affects response to substance	1
Arsenic	affects cotreatment, increases abundance, increases expression	1
Atrazine	increases expression	1
Benzo(a)pyrene	affects methylation	1
Cisplatin	affects response to substance	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
CHEMBL5650968	Binding	Binding affinity to human ATP6V1H 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

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_SE19	HAP1 ATP6V1H (-) 1	Cancer cell line	Male
CVCL_SE20	HAP1 ATP6V1H (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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