ATP6V0D1

Summary

ATP6V0D1 (ATPase H+ transporting V0 subunit d1, HGNC:13724) is a protein-coding gene on chromosome 16q22.1, encoding V-type proton ATPase subunit d 1 (P61421). 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 translocates protons. It is a common-essential gene (DepMap: required in 95.9% of cancer cell lines).

This gene encodes a component of vacuolar ATPase (V-ATPase), a multisubunit enzyme that mediates acidification of eukaryotic intracellular organelles. V-ATPase dependent organelle acidification is necessary for such intracellular processes as protein sorting, zymogen activation, receptor-mediated endocytosis, and synaptic vesicle proton gradient generation. V-ATPase is composed of a cytosolic V1 domain and a transmembrane V0 domain. The V1 domain consists of three A 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 encoded protein is known as the D subunit and is found ubiquitously.

Source: NCBI Gene 9114 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 43 total — 1 pathogenic
• Cancer dependency (DepMap): dependent in 95.9% of screened cell lines (common-essential)
• MANE Select transcript: NM_004691

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:13724
Approved symbol	ATP6V0D1
Name	ATPase H+ transporting V0 subunit d1
Location	16q22.1
Locus type	gene with protein product
Status	Approved
Aliases	ATP6DV, VATX, VPATPD, P39, Vma6
Ensembl gene	ENSG00000159720
Ensembl biotype	protein_coding
OMIM	607028
Entrez	9114

Gene structure

Transcript identifiers

Ensembl transcripts: 27 — 14 protein_coding, 7 nonsense_mediated_decay, 4 retained_intron, 2 protein_coding_CDS_not_defined

ENST00000290949, ENST00000426604, ENST00000540149, ENST00000561658, ENST00000561852, ENST00000563064, ENST00000563305, ENST00000564191, ENST00000564615, ENST00000564788, ENST00000565835, ENST00000566322, ENST00000567170, ENST00000567694, ENST00000568101, ENST00000568298, ENST00000568620, ENST00000898460, ENST00000898461, ENST00000898462, ENST00000898463, ENST00000936171, ENST00000956177, ENST00000956178, ENST00000956179, ENST00000956180, ENST00000956181

RefSeq mRNA: 1 — MANE Select: NM_004691 NM_004691

CCDS: CCDS10838

Canonical transcript exons

ENST00000290949 — 8 exons

Exon	Start	End
ENSE00001289997	67480957	67481157
ENSE00001305944	67438019	67438689
ENSE00003512948	67453544	67453715
ENSE00003518885	67439274	67439351
ENSE00003522890	67438971	67439147
ENSE00003595636	67438793	67438870
ENSE00003656427	67444528	67444706
ENSE00003676623	67443099	67443178

Expression profiles

Bgee: expression breadth ubiquitous, 297 present calls, max score 98.78.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 84.1038 / max 689.8100, expressed in 1826 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
157789	83.6405	1826
157788	0.1614	71
157784	0.1335	57
157787	0.0600	16
157783	0.0586	7
157786	0.0498	12

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
mucosa of transverse colon	UBERON:0004991	98.78	gold quality
type B pancreatic cell	CL:0000169	98.62	gold quality
lateral nuclear group of thalamus	UBERON:0002736	98.47	gold quality
adult organism	UBERON:0007023	98.42	gold quality
granulocyte	CL:0000094	98.32	gold quality
leukocyte	CL:0000738	98.31	gold quality
monocyte	CL:0000576	98.30	gold quality
mononuclear cell	CL:0000842	98.30	gold quality
substantia nigra pars compacta	UBERON:0001965	98.27	gold quality
prefrontal cortex	UBERON:0000451	98.17	gold quality
right frontal lobe	UBERON:0002810	98.14	gold quality
lower lobe of lung	UBERON:0008949	98.11	gold quality
adenohypophysis	UBERON:0002196	98.10	gold quality
Brodmann (1909) area 46	UBERON:0006483	98.02	gold quality
blood	UBERON:0000178	98.00	gold quality
pituitary gland	UBERON:0000007	97.97	gold quality
pons	UBERON:0000988	97.96	gold quality
substantia nigra pars reticulata	UBERON:0001966	97.84	gold quality
right hemisphere of cerebellum	UBERON:0014890	97.82	gold quality
colonic mucosa	UBERON:0000317	97.81	gold quality
mucosa of sigmoid colon	UBERON:0004993	97.80	gold quality
transverse colon	UBERON:0001157	97.77	gold quality
left adrenal gland	UBERON:0001234	97.76	gold quality
right adrenal gland cortex	UBERON:0035827	97.76	gold quality
right adrenal gland	UBERON:0001233	97.71	gold quality
hypothalamus	UBERON:0001898	97.69	gold quality
left adrenal gland cortex	UBERON:0035825	97.68	gold quality
Brodmann (1909) area 9	UBERON:0013540	97.59	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	97.58	gold quality
postcentral gyrus	UBERON:0002581	97.56	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)

28 targeting ATP6V0D1, 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-8485	100.00	77.57	4731
HSA-MIR-6758-5P	100.00	66.21	1470
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-4650-5P	99.98	64.69	999
HSA-MIR-1321	99.84	65.30	1811
HSA-MIR-4739	99.84	65.25	1832
HSA-MIR-4756-5P	99.84	64.98	1809
HSA-MIR-6764-5P	99.75	67.89	2304
HSA-MIR-1915-3P	99.58	66.79	1988
HSA-MIR-4328	99.57	71.06	4094
HSA-MIR-7106-5P	99.53	67.47	3574
HSA-MIR-4441	99.49	66.56	3216
HSA-MIR-1207-5P	99.49	69.11	2983
HSA-MIR-103A-1-5P	99.39	67.78	1545
HSA-MIR-103A-2-5P	99.39	67.72	1577
HSA-MIR-6734-3P	99.15	66.27	1627
HSA-MIR-4270	99.02	66.26	1987
HSA-MIR-5701	98.97	69.54	1502
HSA-MIR-423-5P	98.69	67.48	1522
HSA-MIR-6754-5P	98.60	65.54	1627
HSA-MIR-3184-5P	98.56	67.13	1491
HSA-MIR-4768-3P	98.16	66.02	2330
HSA-MIR-4446-3P	97.91	64.29	991
HSA-MIR-3162-5P	95.67	67.53	794

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 95.9% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 4)

• Using shotgun mass spectrometry, we found this protein differentially expressed in the dorsolateral prefrontal cortex from patients with schizophrenia (PMID:19165527)
• two adjacent enhancers inside the first intron of the neighboring (1.4 kb downstream) ATPase gene (ATP6V0D1) modulate the human AgRP promoter with profound spatiotemporal variation (PMID:19285986)
• The secondary structures of d1 and d2 subunits were highly similar, but the relative stability against thermal stress was higher for d1 than d2. (PMID:24631925)
• ATP6V0D1 promotes alkaliptosis by blocking STAT3-mediated lysosomal pH homeostasis. (PMID:36640329)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	atp6v0d1	ENSDARG00000069090
mus_musculus	Atp6v0d1	ENSMUSG00000013160
rattus_norvegicus	Atp6v0d1	ENSRNOG00000017235
drosophila_melanogaster	VhaAC39-2	FBGN0039058
caenorhabditis_elegans	vha-16	WBGENE00016258

Paralogs (1): ATP6V0D2 (ENSG00000147614)

Protein

Protein identifiers

V-type proton ATPase subunit d 1 — P61421 (reviewed: P61421)

Alternative names: 32 kDa accessory protein, V-ATPase 40 kDa accessory protein, V-ATPase AC39 subunit, Vacuolar proton pump subunit d 1

All UniProt accessions (11): P61421, F5GYQ1, F8WEN9, H3BPS0, H3BQB4, H3BQJ1, H3BSG7, H3BTB4, H3BTB5, H3BUQ0, J3QL14

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 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. May play a role in coupling of proton transport and ATP hydrolysis. In aerobic conditions, involved in intracellular iron homeostasis, thus triggering the activity of Fe(2+) prolyl hydroxylase (PHD) enzymes, and leading to HIF1A hydroxylation and subsequent proteasomal degradation. May play a role in cilium biogenesis through regulation of the transport and the localization of proteins to the cilium.

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 ATP6AP2; ATP6AP2 is a V-ATPase accessory protein and the interaction promotes v-ATPase complex assembly. Interacts with TMEM9; TMEM9 is a v-ATPase assembly regulator and the interaction induces the interaction with ATP6AP2. Interacts with PIP4P1.

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

Tissue specificity. Ubiquitous.

Similarity. Belongs to the V-ATPase V0D/AC39 subunit family.

RefSeq proteins (1): NP_004682* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002843	ATPase_V0-cplx_csu/dsu	Family
IPR016727	ATPase_V0-cplx_dsu	Family
IPR035067	V-type_ATPase_csu/dsu	Homologous_superfamily
IPR036079	ATPase_csu/dsu_sf	Homologous_superfamily
IPR044911	V-type_ATPase_csu/dsu_dom_3	Homologous_superfamily

Pfam: PF01992

UniProt features (46 total): helix 24, turn 13, strand 4, modified residue 2, sequence conflict 2, chain 1

Structure

Experimental structures (PDB)

9 structures.

PDB	Method	Resolution (Å)
6WLW	ELECTRON MICROSCOPY	3
9DET	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
7UNF	ELECTRON MICROSCOPY	4.08

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P61421-F1	86.17	0.49

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 (2): 270, 283

Function

Pathways and Gene Ontology

Reactome pathways

7 pathways

ID	Pathway
R-HSA-1222556	ROS and RNS production in phagocytes
R-HSA-381038	XBP1(S) activates chaperone genes
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: 305 (showing top): REACTOME_SIGNALING_BY_INSULIN_RECEPTOR, GOBP_REGULATION_OF_AUTOPHAGY, REACTOME_UNFOLDED_PROTEIN_RESPONSE_UPR, WANG_CLIM2_TARGETS_UP, REACTOME_INNATE_IMMUNE_SYSTEM, chr16q22, MORF_RAB5A, GOCC_VACUOLAR_MEMBRANE, GOBP_VESICLE_ORGANIZATION, CHIANG_LIVER_CANCER_SUBCLASS_UNANNOTATED_DN, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_UP, GOBP_INTRACELLULAR_IRON_ION_HOMEOSTASIS, GOBP_VACUOLAR_TRANSPORT, KEGG_LYSOSOME

GO Biological Process (11): intracellular iron ion homeostasis (GO:0006879), vacuolar transport (GO:0007034), vacuolar acidification (GO:0007035), regulation of macroautophagy (GO:0016241), cellular response to increased oxygen levels (GO:0036295), cilium assembly (GO:0060271), synaptic vesicle lumen acidification (GO:0097401), proton transmembrane transport (GO:1902600), monoatomic ion transport (GO:0006811), cell projection organization (GO:0030030), homeostatic process (GO:0042592)

GO Molecular Function (3): protein-containing complex binding (GO:0044877), proton-transporting ATPase activity, rotational mechanism (GO:0046961), protein binding (GO:0005515)

GO Cellular Component (20): vacuolar proton-transporting V-type ATPase, V0 domain (GO:0000220), lysosomal membrane (GO:0005765), early endosome (GO:0005769), endosome membrane (GO:0010008), membrane (GO:0016020), apical plasma membrane (GO:0016324), vacuolar proton-transporting V-type ATPase complex (GO:0016471), clathrin-coated vesicle membrane (GO:0030665), phagocytic vesicle membrane (GO:0030670), synaptic vesicle membrane (GO:0030672), plasma membrane proton-transporting V-type ATPase complex (GO:0033181), axon terminus (GO:0043679), extracellular exosome (GO:0070062), lysosome (GO:0005764), centrosome (GO:0005813), synaptic vesicle (GO:0008021), cytoplasmic vesicle (GO:0031410), protein-containing complex (GO:0032991), proton-transporting V-type ATPase complex (GO:0033176), proton-transporting V-type ATPase, V0 domain (GO:0033179)

Reactome top-level categories

Rollup of top-7 pathways:

Category	Pathways
Innate Immune System	1
IRE1alpha activates chaperones	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
proton-transporting V-type ATPase complex	3
binding	2
vacuolar membrane	2
endosome	2
presynapse	2
intracellular monoatomic cation homeostasis	1
inorganic ion homeostasis	1
intracellular transport	1
intracellular pH reduction	1
regulation of autophagy	1
macroautophagy	1
response to increased oxygen levels	1
cellular response to oxygen levels	1
axoneme assembly	1
intraciliary transport involved in cilium assembly	1
cilium organization	1
protein localization to cilium	1
organelle assembly	1
trans-Golgi to periciliary membrane compartment transport	1
plasma membrane bounded cell projection assembly	1
ciliary transition zone assembly	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
cellular component organization	1
biological_process	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
vacuolar proton-transporting V-type ATPase complex	1
proton-transporting V-type ATPase, V0 domain	1
lysosome	1
lytic vacuole membrane	1
cytoplasmic vesicle membrane	1
bounding membrane of organelle	1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

120 interactions, top by confidence:

A	B	Type	Score
SMARCB1	ARID1A	psi-mi:“MI:0914”(association)	0.860
ATP6V0C	ATP6AP2	psi-mi:“MI:0914”(association)	0.730
LAMTOR3	LAMTOR5	psi-mi:“MI:0914”(association)	0.730
ATXN1	ATP6V0D1	psi-mi:“MI:0915”(physical association)	0.670
VMA12	ATP6AP2	psi-mi:“MI:0914”(association)	0.640
ATP6V1C2	ATP6V1G1	psi-mi:“MI:0914”(association)	0.640
TLX3	ATP6V0D1	psi-mi:“MI:0915”(physical association)	0.560
ATP6V0D1	DMRT3	psi-mi:“MI:0915”(physical association)	0.560
HTT	ATP6V0D1	psi-mi:“MI:0915”(physical association)	0.560
SLC10A7	APOB	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
ATP6V0D1	IKZF3	psi-mi:“MI:0915”(physical association)	0.490
ATP6V0D1	IHO1	psi-mi:“MI:0915”(physical association)	0.490
ATP6V0D1	RBPMS	psi-mi:“MI:0915”(physical association)	0.490
ATP6V0D1	TLE5	psi-mi:“MI:0915”(physical association)	0.490

BioGRID (343): ATP6V0D1 (Affinity Capture-MS), ATP6V0D1 (Affinity Capture-MS), ATP6V0D1 (Affinity Capture-MS), ATP6V0D1 (Affinity Capture-MS), ATP1A1 (Co-fractionation), ATP5A1 (Co-fractionation), ATP5C1 (Co-fractionation), ATP5O (Co-fractionation), ATP6V0A1 (Co-fractionation), ATP6V0D1 (Co-fractionation), ATP6V0D1 (Co-fractionation), ATP6V0D1 (Co-fractionation), ATP6V0D1 (Co-fractionation), ATP6V0D1 (Co-fractionation), ATP6V0D1 (Co-fractionation)

ESM2 similar proteins: A0A0A7HFE6, A3PFD7, A6ZRW6, A8X485, A9A1D3, B3PLX9, O13753, O84311, P0ACY3, P0ACY4, P0ACY5, P0DW40, P21826, P30952, P32366, P39812, P51863, P53659, P54641, P61420, P61421, Q12019, Q12680, Q12WL3, Q25531, Q2KJB6, Q2NF85, Q4MKK8, Q5FVL0, Q5R6I1, Q5R7B7, Q5ZHL0, Q6C5F1, Q6P335, Q6PGV1, Q74P24, Q7UZL3, Q80SY3, Q8N8Y2, Q8RU33

Diamond homologs: O13753, P32366, P51863, P53659, P54641, P61420, P61421, Q25531, Q2KJB6, Q5FVL0, Q5R6I1, Q5R7B7, Q5ZHL0, Q6P335, Q6PGV1, Q80SY3, Q8N8Y2, Q8RU33, Q9LHA4, Q9LJI5, Q9VCQ3, Q9W4P5

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
TFE3	“up-regulates quantity by expression”	ATP6V0D1	“transcriptional regulation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 129 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	8	67.2×	8e-12
Insulin receptor recycling	14	66.6×	1e-20
Transferrin endocytosis and recycling	13	59.9×	2e-18
ROS and RNS production in phagocytes	12	50.4×	5e-16
Amino acids regulate mTORC1	13	32.6×	9e-15
Ion channel transport	14	16.8×	7e-12
RHOF GTPase cycle	5	16.2×	7e-04
RHOQ GTPase cycle	6	13.6×	4e-04

GO biological processes:

GO term	Partners	Fold	FDR
synaptic vesicle lumen acidification	11	100.0×	8e-18
vacuolar acidification	11	78.2×	2e-16
lysosomal lumen acidification	9	58.9×	5e-12
proton transmembrane transport	11	33.3×	5e-12
regulation of macroautophagy	10	28.7×	2e-10
intracellular iron ion homeostasis	5	11.9×	4e-03
exocytosis	8	11.8×	4e-05
endocytosis	7	6.5×	6e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	33
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
145310	GRCh38/hg38 16q21-22.1(chr16:66245888-67473023)x1	Pathogenic

SpliceAI

1985 predictions. Top by Δscore:

Variant	Effect	Δscore
16:67438688:ACC:A	acceptor_loss	1.0000
16:67438689:CCTGT:C	acceptor_loss	1.0000
16:67438690:CT:C	acceptor_loss	1.0000
16:67438691:T:A	acceptor_loss	1.0000
16:67438789:TCA:T	donor_loss	1.0000
16:67438790:CA:C	donor_loss	1.0000
16:67438791:A:AC	donor_gain	1.0000
16:67438791:AC:A	donor_gain	1.0000
16:67438791:ACCT:A	donor_gain	1.0000
16:67438792:C:CC	donor_gain	1.0000
16:67438792:C:CG	donor_loss	1.0000
16:67438792:CC:C	donor_gain	1.0000
16:67438792:CCT:C	donor_gain	1.0000
16:67438792:CCTC:C	donor_gain	1.0000
16:67438868:CTC:C	acceptor_gain	1.0000
16:67438869:TCC:T	acceptor_loss	1.0000
16:67438871:C:CC	acceptor_gain	1.0000
16:67438876:C:CT	acceptor_gain	1.0000
16:67438876:C:T	acceptor_gain	1.0000
16:67438877:A:T	acceptor_gain	1.0000
16:67438883:G:C	acceptor_gain	1.0000
16:67438883:G:GC	acceptor_gain	1.0000
16:67438965:ACTC:A	donor_loss	1.0000
16:67438966:CTCA:C	donor_loss	1.0000
16:67438967:TCACC:T	donor_loss	1.0000
16:67438968:CACC:C	donor_loss	1.0000
16:67438969:A:AC	donor_gain	1.0000
16:67438969:A:T	donor_loss	1.0000
16:67438969:AC:A	donor_gain	1.0000
16:67438970:C:CA	donor_gain	1.0000

AlphaMissense

2330 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:67438579:A:C	C335W	1.000
16:67438581:A:G	C335R	1.000
16:67438586:G:T	A333D	1.000
16:67438587:C:G	A333P	1.000
16:67438591:C:A	W331C	1.000
16:67438591:C:G	W331C	1.000
16:67438593:A:G	W331R	1.000
16:67438593:A:T	W331R	1.000
16:67438600:G:C	N328K	1.000
16:67438600:G:T	N328K	1.000
16:67438604:C:G	R327P	1.000
16:67438622:A:G	L321P	1.000
16:67438984:G:T	A268D	1.000
16:67439023:A:G	L255P	1.000
16:67439053:C:T	G245E	1.000
16:67439054:C:A	G245W	1.000
16:67439068:A:G	L240P	1.000
16:67439077:C:G	R237P	1.000
16:67439078:G:T	R237S	1.000
16:67439092:A:G	L232P	1.000
16:67439107:G:A	S227F	1.000
16:67439108:A:G	S227P	1.000
16:67439109:A:C	N226K	1.000
16:67439109:A:T	N226K	1.000
16:67439131:C:G	R219P	1.000
16:67439132:G:T	R219S	1.000
16:67439134:C:G	R218P	1.000
16:67439138:C:G	D217H	1.000
16:67439141:C:G	A216P	1.000
16:67443106:A:G	L185P	1.000

dbSNP variants (sampled 300 via entrez): RS1000006514 (16:67473727 A>G), RS1000026455 (16:67475657 T>C), RS1000399199 (16:67442448 G>A,C), RS1000441512 (16:67473476 G>T), RS1000447396 (16:67444935 G>A), RS1000546346 (16:67476005 G>A), RS1000547525 (16:67480898 C>A,G,T), RS1000571576 (16:67443518 C>G,T), RS1000587305 (16:67478954 C>A), RS1000713030 (16:67449992 C>T), RS1000727041 (16:67441302 G>A), RS1000785793 (16:67451534 G>C,T), RS1000934545 (16:67457067 T>C), RS1001095727 (16:67454035 C>A,T), RS1001158759 (16:67473123 TG>T)

Disease associations

OMIM: gene MIM:607028 | 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
GCST005359_24	Disease progression in age-related macular degeneration	1.000000e-06
GCST005751_5	Empathy quotient	8.000000e-07
GCST007932_13	Medication use (thyroid preparations)	3.000000e-11
GCST010002_113	Refractive error	2.000000e-14

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0008336	disease progression measurement
EFO:0009183	empathy measurement
EFO:0009933	Thyroid preparation use measurement

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

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression, affects expression, affects cotreatment	6
sodium arsenite	increases expression	4
bisphenol A	increases expression	3
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	2
Arsenic Trioxide	decreases reaction, increases expression, affects reaction, affects cotreatment	2
Acetylcysteine	decreases reaction, increases expression, increases abundance	2
Acrolein	affects cotreatment, increases oxidation, increases abundance	2
Ozone	increases abundance, affects cotreatment, increases oxidation	2
Rotenone	increases lipidation, increases expression, affects reaction, decreases reaction	2
Tetrachlorodibenzodioxin	increases expression	2
Tretinoin	affects cotreatment, increases expression	2
Aflatoxin B1	increases methylation, affects cotreatment, increases expression	2
Cadmium Chloride	decreases reaction, increases abundance, increases expression, affects reaction	2
aristolochic acid I	increases expression	1
bisphenol F	affects cotreatment, increases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	increases oxidation, increases abundance, affects cotreatment	1
trichostatin A	affects expression	1
beta-lapachone	increases expression	1
benzo(e)pyrene	decreases methylation	1
yessotoxin	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	increases expression, affects cotreatment	1
bisphenol B	increases expression	1
14-deoxy-11,12-didehydroandrographolide	decreases expression	1
dorsomorphin	affects cotreatment, increases expression	1
bisphenol S	affects expression	1
PP242	increases expression	1
bisphenol AF	increases expression	1
Temozolomide	decreases expression	1
Sunitinib	increases expression	1

Clinical trials (associated diseases)

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