ATP6V0D2

Summary

ATP6V0D2 (ATPase H+ transporting V0 subunit d2, HGNC:18266) is a protein-coding gene on chromosome 8q21.3, encoding V-type proton ATPase subunit d 2 (Q8N8Y2). 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.

Predicted to enable proton-transporting ATPase activity, rotational mechanism. Predicted to be involved in vacuolar acidification and vacuolar transport. Located in apical plasma membrane. Part of vacuolar proton-transporting V-type ATPase complex.

Source: NCBI Gene 245972 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Ehlers-Danlos syndrome (Limited, GenCC)
• GWAS associations: 2
• Clinical variants (ClinVar): 117 total — 4 pathogenic
• MANE Select transcript: NM_152565

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18266
Approved symbol	ATP6V0D2
Name	ATPase H+ transporting V0 subunit d2
Location	8q21.3
Locus type	gene with protein product
Status	Approved
Aliases	FLJ38708, VMA6
Ensembl gene	ENSG00000147614
Ensembl biotype	protein_coding
OMIM	618072
Entrez	245972

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 6 protein_coding

ENST00000285393, ENST00000521564, ENST00000523635, ENST00000885618, ENST00000885619, ENST00000885620

RefSeq mRNA: 1 — MANE Select: NM_152565 NM_152565

CCDS: CCDS6241

Canonical transcript exons

ENST00000285393 — 8 exons

Exon	Start	End
ENSE00000980876	86113709	86113880
ENSE00000980877	86139457	86139635
ENSE00000980878	86141450	86141529
ENSE00001195736	86142877	86142954
ENSE00001261853	86151466	86151540
ENSE00001261863	86150112	86150288
ENSE00001261913	86152816	86154225
ENSE00002122851	86098910	86099108

Expression profiles

Bgee: expression breadth ubiquitous, 144 present calls, max score 92.21.

FANTOM5 (CAGE): breadth broad, TPM avg 4.7508 / max 269.4716, expressed in 316 samples.

FANTOM5 promoters (10 alternative TSS)

Promoter ID	TPM avg	Samples expressed
89633	3.4882	258
89635	0.2636	85
89631	0.2581	92
89630	0.2286	94
89634	0.2110	87
89632	0.1930	83
89629	0.0694	39
89626	0.0213	5
89628	0.0135	1
89627	0.0040	1

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
adult mammalian kidney	UBERON:0000082	92.21	gold quality
buccal mucosa cell	CL:0002336	89.78	gold quality
metanephros cortex	UBERON:0010533	89.78	gold quality
kidney	UBERON:0002113	87.16	gold quality
cortex of kidney	UBERON:0001225	83.41	gold quality
amniotic fluid	UBERON:0000173	78.90	gold quality
metanephros	UBERON:0000081	75.27	gold quality
renal medulla	UBERON:0000362	75.20	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	73.95	gold quality
endothelial cell	CL:0000115	73.14	silver quality
rectum	UBERON:0001052	71.11	gold quality
tibia	UBERON:0000979	69.02	gold quality
hindlimb stylopod muscle	UBERON:0004252	64.49	gold quality
mucosa of transverse colon	UBERON:0004991	64.24	gold quality
skin of hip	UBERON:0001554	63.74	gold quality
colonic epithelium	UBERON:0000397	63.31	silver quality
lower lobe of lung	UBERON:0008949	62.76	gold quality
sperm	CL:0000019	62.62	gold quality
oocyte	CL:0000023	60.90	gold quality
upper leg skin	UBERON:0004262	60.35	gold quality
cardia of stomach	UBERON:0001162	60.32	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	59.38	gold quality
lymph node	UBERON:0000029	58.57	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	58.56	gold quality
mucosa of sigmoid colon	UBERON:0004993	57.75	gold quality
adult organism	UBERON:0007023	57.51	gold quality
vermiform appendix	UBERON:0001154	57.09	gold quality
apex of heart	UBERON:0002098	56.40	gold quality
caecum	UBERON:0001153	55.83	gold quality
cerebellar vermis	UBERON:0004720	55.45	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 5.

Experiment	Marker?	Max mean expression
E-MTAB-3929	yes	242.57
E-CURD-119	yes	47.21
E-CURD-112	yes	13.71
E-CURD-114	yes	11.17
E-ANND-3	yes	4.88

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): MITF, NFATC1

miRNA regulators (miRDB)

74 targeting ATP6V0D2, 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-3613-3P	100.00	76.36	7965
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-141-3P	99.94	72.79	2421
HSA-MIR-200A-3P	99.94	72.68	2420
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-6508-5P	99.92	70.67	2465
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-MIR-6124	99.87	69.78	3551
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-8067	99.86	69.59	2260
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-5003-3P	99.85	69.29	2517
HSA-MIR-5010-3P	99.83	70.60	2357
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-1273H-5P	99.77	66.32	2471
HSA-MIR-4524A-3P	99.72	66.85	2406
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-30B-3P	99.70	65.76	2325
HSA-MIR-3689A-3P	99.70	65.73	2306
HSA-MIR-3689B-3P	99.70	65.71	2311
HSA-MIR-3689C	99.70	65.71	2311
HSA-MIR-6779-5P	99.70	65.76	2363

Literature-anchored findings (GeneRIF, showing 6)

• these data suggest that Adrm1, a new Atp6v0d2-interacting protein, plays an important role in osteoclast differentiation, and in particular the fusion of preosteoclasts. (PMID:19818731)
• 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)
• gammadelta T cells suppressed iDCs osteoclastogenesis by downregulation of the RANK/cFos/ATP6V0D2 signaling pathway. (PMID:30066839)
• Lactate inhibits ATP6V0d2 expression in tumor-associated macrophages to promote HIF-2alpha-mediated tumor progression. (PMID:30431439)
• ATP6V0D2, a subunit associated with proton transport, serves an oncogenic role in esophagus cancer and is correlated with epithelial-mesenchymal transition. (PMID:32240421)
• Reticulophagy mediated by the V-ATPase-ATG16L1-LC3C axis. (PMID:38348842)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
mus_musculus	Atp6v0d2	ENSMUSG00000028238
rattus_norvegicus	Atp6v0d2	ENSRNOG00000006926
caenorhabditis_elegans	vha-16	WBGENE00016258

Paralogs (1): ATP6V0D1 (ENSG00000159720)

Protein

Protein identifiers

V-type proton ATPase subunit d 2 — Q8N8Y2 (reviewed: Q8N8Y2)

Alternative names: Vacuolar proton pump subunit d 2

All UniProt accessions (3): Q8N8Y2, E5RHJ7, E5RIR3

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. Regulator of osteoclast fusion and bone formation.

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 TM4SF19; this interaction inhibits V1-V0 complex assembly.

Tissue specificity. Kidney, osteoclast and lung.

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

RefSeq proteins (1): NP_689778* (*=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 (3 total): sequence variant 2, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8N8Y2-F1	85.88	0.44

Function

Pathways and Gene Ontology

Reactome pathways

5 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

MSigDB gene sets: 163 (showing top): TAKEDA_TARGETS_OF_NUP98_HOXA9_FUSION_6HR_DN, REACTOME_SIGNALING_BY_INSULIN_RECEPTOR, AP1_01, GOBP_REGULATION_OF_AUTOPHAGY, WANG_CLIM2_TARGETS_UP, REACTOME_INNATE_IMMUNE_SYSTEM, GOCC_VACUOLAR_MEMBRANE, GOBP_VACUOLAR_TRANSPORT, KEGG_LYSOSOME, GOBP_MONOATOMIC_CATION_TRANSPORT, GOBP_MACROAUTOPHAGY, GOBP_REGULATION_OF_CATABOLIC_PROCESS, GOBP_VACUOLAR_ACIDIFICATION, CREIGHTON_ENDOCRINE_THERAPY_RESISTANCE_5, TGANTCA_AP1_C

GO Biological Process (5): vacuolar transport (GO:0007034), vacuolar acidification (GO:0007035), regulation of macroautophagy (GO:0016241), monoatomic ion transport (GO:0006811), proton transmembrane transport (GO:1902600)

GO Molecular Function (2): proton-transporting ATPase activity, rotational mechanism (GO:0046961), protein binding (GO:0005515)

GO Cellular Component (11): 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), phagocytic vesicle membrane (GO:0030670), proton-transporting V-type ATPase, V0 domain (GO:0033179), plasma membrane proton-transporting V-type ATPase complex (GO:0033181), extracellular exosome (GO:0070062), endosome (GO:0005768)

Reactome top-level categories

Rollup of top-5 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

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
proton-transporting V-type ATPase complex	3
endosome	2
intracellular transport	1
intracellular pH reduction	1
regulation of autophagy	1
macroautophagy	1
transport	1
monoatomic cation transmembrane 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
lysosome	1
lytic vacuole membrane	1
cytoplasmic vesicle membrane	1
bounding membrane of organelle	1
cellular anatomical structure	1
apical part of cell	1
plasma membrane region	1
vacuolar membrane	1
endocytic vesicle membrane	1
phagocytic vesicle	1
proton-transporting two-sector ATPase complex, proton-transporting domain	1
plasma membrane	1
plasma membrane protein complex	1
extracellular vesicle	1
endomembrane system	1
cytoplasmic vesicle	1

Protein interactions and networks

STRING

1124 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ATP6V0D2	DCSTAMP	Q9H295	830
ATP6V0D2	ATP6V1G3	Q96LB4	793
ATP6V0D2	ATP6V0A4	Q9HBG4	793
ATP6V0D2	TCIRG1	Q13488	792
ATP6V0D2	ATP6V1E2	Q96A05	790
ATP6V0D2	ATP6V1H	Q9UI12	790
ATP6V0D2	CTSK	P43235	786
ATP6V0D2	ATP6V1F	Q16864	782
ATP6V0D2	ATP6V0A1	Q93050	780
ATP6V0D2	ATP6V1D	Q9Y5K8	777
ATP6V0D2	OCSTAMP	Q9BR26	774
ATP6V0D2	ATP6V0C	P27449	757
ATP6V0D2	ATP6V1C2	Q8NEY4	756
ATP6V0D2	ATP6V0A2	Q9Y487	749
ATP6V0D2	ATP6V1G1	O75348	747

IntAct

59 interactions, top by confidence:

A	B	Type	Score
ATP6V0D2	NICN1	psi-mi:“MI:0915”(physical association)	0.560
ATP6V0D2	SEPTIN2	psi-mi:“MI:0915”(physical association)	0.560
PAX6	ATP6V0D2	psi-mi:“MI:0915”(physical association)	0.560
REL	ATP6V0D2	psi-mi:“MI:0915”(physical association)	0.560
CRX	ATP6V0D2	psi-mi:“MI:0915”(physical association)	0.560
INCA1	ATP6V0D2	psi-mi:“MI:0915”(physical association)	0.560
POMC	ATP6V0D2	psi-mi:“MI:0915”(physical association)	0.560
ARID5A	ATP6V0D2	psi-mi:“MI:0915”(physical association)	0.560
CENPP	ATP6V0D2	psi-mi:“MI:0915”(physical association)	0.560
ATP6V0D2	RUSC1	psi-mi:“MI:0915”(physical association)	0.560
ZNF474	ATP6V0D2	psi-mi:“MI:0915”(physical association)	0.560
RIBC1	ATP6V0D2	psi-mi:“MI:0915”(physical association)	0.560
SEPTIN2	ATP6V0D2	psi-mi:“MI:0915”(physical association)	0.560
ATP6V0D2	IKZF3	psi-mi:“MI:0915”(physical association)	0.560
MEOX2	ATP6V0D2	psi-mi:“MI:0915”(physical association)	0.560
ATP6V0D2	PHF12	psi-mi:“MI:0915”(physical association)	0.560
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
ATP6V0A4	ATP6AP2	psi-mi:“MI:0914”(association)	0.530
ATP6V1G2	ATP6V1B1	psi-mi:“MI:0914”(association)	0.530
ATP6V0D2	NDUFB8	psi-mi:“MI:0915”(physical association)	0.370
ATP6V0D2	RPS3	psi-mi:“MI:0915”(physical association)	0.370
ATP6V0D2	RBM15B	psi-mi:“MI:0915”(physical association)	0.370
AGO3	ATP6V0D2	psi-mi:“MI:0915”(physical association)	0.370
MAPT	NCAN	psi-mi:“MI:0914”(association)	0.350
ATP6V0D1		psi-mi:“MI:0914”(association)	0.350

BioGRID (82): ATP6V0D2 (Affinity Capture-MS), ATP6V0D2 (Affinity Capture-MS), ATP6V0D2 (Affinity Capture-MS), ATP6V0D2 (Affinity Capture-MS), ATP6V0D2 (Affinity Capture-MS), VMA21 (Affinity Capture-MS), TMEM199 (Affinity Capture-MS), TCIRG1 (Affinity Capture-MS), CCDC115 (Affinity Capture-MS), ATP6V0A1 (Affinity Capture-MS), ATP6V0C (Affinity Capture-MS), FKBP15 (Affinity Capture-MS), KIAA2013 (Affinity Capture-MS), ATP6V0D2 (Affinity Capture-MS), ATP6V0D2 (Synthetic Lethality)

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

2 interactions.

A	Effect	B	Mechanism
ATP6V0D2	“form complex”	V-ATPase	binding
TFE3	“up-regulates quantity by expression”	ATP6V0D2	“transcriptional regulation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 32 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	6	175.2×	2e-11
Insulin receptor recycling	9	149.0×	2e-16
Transferrin endocytosis and recycling	9	144.2×	2e-16
ROS and RNS production in phagocytes	9	131.4×	3e-16
Amino acids regulate mTORC1	6	52.3×	4e-08
Ion channel transport	9	37.5×	3e-11

GO biological processes:

GO term	Partners	Fold	FDR
synaptic vesicle lumen acidification	9	271.8×	8e-19
vacuolar acidification	7	165.4×	1e-12
proton transmembrane transport	8	80.5×	4e-12
regulation of macroautophagy	8	76.3×	5e-12

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	4
Likely pathogenic	0
Uncertain significance	77
Likely benign	5
Benign	28

Top pathogenic / likely-pathogenic (4)

Variant ID	HGVS	Classification
1527444	GRCh37/hg19 8q21.11-21.3(chr8:77906471-88917707)	Pathogenic
2685315	GRCh37/hg19 8q21.13-22.1(chr8:84127576-98263585)x1	Pathogenic
60379	GRCh38/hg38 8q21.13-21.3(chr8:77765431-91839285)x1	Pathogenic
60380	GRCh38/hg38 8q21.13-22.1(chr8:78672463-95366868)x1	Pathogenic

SpliceAI

1850 predictions. Top by Δscore:

Variant	Effect	Δscore
8:86099104:AGAAG:A	donor_gain	1.0000
8:86099105:GAAG:G	donor_gain	1.0000
8:86099105:GAAGG:G	donor_gain	1.0000
8:86099106:AAG:A	donor_gain	1.0000
8:86099107:AG:A	donor_gain	1.0000
8:86099108:GG:G	donor_gain	1.0000
8:86099109:G:GG	donor_gain	1.0000
8:86113878:GAC:G	donor_gain	1.0000
8:86113881:G:GG	donor_gain	1.0000
8:86139633:TAG:T	donor_loss	1.0000
8:86139634:AG:A	donor_loss	1.0000
8:86139636:GTA:G	donor_loss	1.0000
8:86139637:T:C	donor_loss	1.0000
8:86141448:A:AG	acceptor_gain	1.0000
8:86141449:G:GG	acceptor_gain	1.0000
8:86141449:GCTCC:G	acceptor_gain	1.0000
8:86141525:ACAAG:A	donor_loss	1.0000
8:86141526:CAAG:C	donor_loss	1.0000
8:86141527:AAGGT:A	donor_loss	1.0000
8:86141528:AGGT:A	donor_loss	1.0000
8:86141529:GGTAA:G	donor_loss	1.0000
8:86141530:G:GC	donor_loss	1.0000
8:86141531:T:A	donor_loss	1.0000
8:86142874:A:AG	acceptor_gain	1.0000
8:86142875:A:G	acceptor_gain	1.0000
8:86142876:G:GG	acceptor_gain	1.0000
8:86150104:A:AG	acceptor_gain	1.0000
8:86150105:A:G	acceptor_gain	1.0000
8:86150156:T:A	acceptor_gain	1.0000
8:86150285:CGGA:C	donor_gain	1.0000

AlphaMissense

2323 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:86152912:T:A	W330R	0.997
8:86152912:T:C	W330R	0.997
8:86152918:G:C	A332P	0.997
8:86150118:G:C	A216P	0.996
8:86150128:G:C	R219P	0.996
8:86152905:T:A	N327K	0.996
8:86152905:T:G	N327K	0.996
8:86152883:T:C	L320P	0.995
8:86152924:T:C	C334R	0.995
8:86152926:T:G	C334W	0.995
8:86099040:G:C	R21P	0.994
8:86099085:T:C	L36P	0.994
8:86113724:T:C	L49P	0.994
8:86150121:G:C	D217H	0.994
8:86152914:G:C	W330C	0.994
8:86152914:G:T	W330C	0.994
8:86150119:C:A	A216D	0.993
8:86150206:G:A	G245D	0.992
8:86099030:G:C	G18R	0.991
8:86139478:T:A	N108K	0.991
8:86139478:T:G	N108K	0.991
8:86150151:T:C	S227P	0.991
8:86141513:G:C	R182P	0.990
8:86150182:G:C	R237P	0.990
8:86152901:G:T	R326I	0.990
8:86113712:T:C	L45P	0.989
8:86139551:G:C	G133R	0.989
8:86139552:G:A	G133D	0.989
8:86150122:A:T	D217V	0.989
8:86150206:G:T	G245V	0.989

dbSNP variants (sampled 300 via entrez): RS1000037737 (8:86148347 C>A,T), RS1000039794 (8:86141944 C>T), RS1000061633 (8:86106834 T>G), RS1000069317 (8:86128243 G>A), RS1000126912 (8:86099986 C>T), RS1000149009 (8:86151418 T>C), RS1000192082 (8:86142670 T>C), RS1000193830 (8:86111610 G>A,C), RS1000194518 (8:86098792 TGA>T), RS1000259857 (8:86112662 G>C), RS1000305178 (8:86136705 C>T), RS1000322316 (8:86105740 G>A), RS1000354235 (8:86146404 A>G), RS1000424355 (8:86140254 G>A), RS1000454420 (8:86134558 A>G)

Disease associations

OMIM: gene MIM:618072 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
Ehlers-Danlos syndrome	Limited	Autosomal recessive

Mondo (1): Ehlers-Danlos syndrome (MONDO:0020066)

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST001431_4	Adverse response to lamotrigine and phenytoin	5.000000e-06
GCST90002398_232	Neutrophil count	6.000000e-10

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004833	neutrophil count

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D004535	Ehlers-Danlos Syndrome	C14.907.454.240; C15.378.463.515.240; C16.131.831.428; C16.320.850.260; C17.300.200.310; C17.800.804.428; C17.800.827.260

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

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression, decreases methylation	8
trichostatin A	affects cotreatment, increases expression	3
sodium arsenite	increases expression	2
Panobinostat	affects cotreatment, increases expression	2
Silicon Dioxide	decreases expression, increases expression	2
Cyclosporine	increases expression	2
sotorasib	affects cotreatment, decreases expression	1
methylmercuric chloride	increases expression	1
bisphenol A	affects expression	1
3,4-dichloroaniline	increases expression	1
tetrabromobisphenol A	increases expression	1
benzo(e)pyrene	increases methylation	1
aflatoxin B2	increases methylation	1
S-(1,2-dichlorovinyl)cysteine	decreases expression, affects cotreatment	1
caffeic acid	decreases expression, increases reaction	1
avobenzone	increases expression	1
4-methoxycinnamate methyl ester	decreases expression, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
clothianidin	increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
jinfukang	affects cotreatment, increases expression	1
NSC 689534	affects binding, increases expression	1
trametinib	decreases expression, affects cotreatment	1
(+)-JQ1 compound	decreases expression	1
NVP-BKM120	decreases expression, affects cotreatment	1
Benzo(a)pyrene	affects methylation, decreases methylation	1
Cadmium	affects expression, increases response to substance	1
Cisplatin	affects cotreatment, increases expression	1
Copper	affects binding, increases expression	1
Diuron	increases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04890431	PHASE4	UNKNOWN	Impact of Oxygen Therapy on Fatigue in Patients With Hypermobile-type Ehlers-Danlos Syndrome
NCT05603741	PHASE4	ACTIVE_NOT_RECRUITING	Local Anesthetic Response in Ehlers-Danlos Syndrome (EDS) and Healthy Volunteers
NCT05279937	PHASE3	NOT_YET_RECRUITING	The Ultrasound-Guided Dextrose Prolotherapy in Ehlers-Danlos Syndrome Patients
NCT00001966	PHASE2	COMPLETED	Mind-Body Therapy for Pain in Ehlers-Danlos Syndrome
NCT03686748	EARLY_PHASE1	ACTIVE_NOT_RECRUITING	Two Point Discrimination
NCT00001641	Not specified	COMPLETED	Study of Heritable Connective Tissue Disorders
NCT00270686	Not specified	COMPLETED	Studies of Heritable Disorders of Connective Tissue
NCT01322165	Not specified	COMPLETED	National Registry of Genetically Triggered Thoracic Aortic Aneurysms and Cardiovascular Conditions
NCT01356134	Not specified	COMPLETED	Vascular Fundus Changes in Patients With High Probability of Chronic Cerebrospinal Venous Insufficiency (CCSVI)
NCT01367977	Not specified	COMPLETED	Head Circumference Growth in Children With Ehlers-Danlos Syndrome Who Develop Dysautonomia Later in Life
NCT02050113	Not specified	RECRUITING	Complex Aortic Aneurysm Repair Using Physician Modified Endografts and Custom Made Devices
NCT02435745	Not specified	COMPLETED	Obstructive Sleep Apnoea in Ehlers-Danlos Syndrome
NCT02721797	Not specified	UNKNOWN	Origins and Impact of EDS in Connective Tissues and Skin
NCT02985710	Not specified	COMPLETED	Assessment of Small Fiber Neuropathy in Rare Diseases Using Sudoscan
NCT03093493	Not specified	COMPLETED	Genetics of Ehlers-Danlos Syndrome
NCT03330977	Not specified	UNKNOWN	Efficiency Clinical Study of NOVATEX MEDICAL Compression Garments in Patients With Ehlers-Danlos Syndrome
NCT03575182	Not specified	UNKNOWN	Gait Retraining in Patients With Joint Hypermobility Syndrome/Hypermobile Ehlers Danlos Syndrome
NCT03596437	Not specified	UNKNOWN	Study of Arterial Properties by Ultra-high Frequency Ultrasound in Fibromuscular Dysplasia and Vascular Ehlers-Danlos Syndrome
NCT03602482	Not specified	COMPLETED	Standing Cognition and Co-morbidities of POTS Evaluation
NCT03681080	Not specified	COMPLETED	Concentration and Attentional Deficits in POTS and Other Autonomic Neuropathies
NCT03986229	Not specified	COMPLETED	Evaluation of the Effect of Custom Compression Garments on Standing Static Balance in Ehlers Danlos Syndrome
NCT04036305	Not specified	ACTIVE_NOT_RECRUITING	Local Anesthetic Response in Ehlers-Danlos Syndrome (EDS) and Healthy Volunteers
NCT04133272	Not specified	RECRUITING	Registry of Ehlers-Danlos Syndrome
NCT04437589	Not specified	COMPLETED	Opioid-Free Anesthesia for Patients With Joint Hypermobility Syndrome Undergoing Craneo-Cervical Fixation: A Case-series
NCT04680793	Not specified	COMPLETED	Effects of a Multidisciplinary Outpatient Rehabilitation Program in Patients With Ehlers-Danlos Syndrome.
NCT04734041	Not specified	COMPLETED	Integrative Medicine for Hypermobility Spectrum Disorder and Ehlers-Danlos Syndromes (IMforHSDandEDS)
NCT04742803	Not specified	COMPLETED	Straberi Epistamp Needling Treatment For Skin Rejuvenation
NCT04806620	Not specified	RECRUITING	Unhide® Project: A Digital Health Platform to Collect Lifestyle Data for Brain Inflammation Research
NCT05137379	Not specified	COMPLETED	Evaluation of a Cohort of Patients With Ehlers-Danlos Syndrome Treated With Orthopedic Surgery (SED-eval)
NCT05366114	Not specified	UNKNOWN	Vision-based Assessment of Joint Extensibility in Ehlers Danlos Syndrome
NCT05389865	Not specified	ACTIVE_NOT_RECRUITING	Proximal Aortopathy in Scotland - Epidemiology and Surgical Outcomes
NCT05429996	Not specified	UNKNOWN	Ultrastructural Collagen Markers in Ehlers Danlos Syndromes
NCT05434728	Not specified	UNKNOWN	Characterization of Bleeding Disorders in EDS
NCT05516043	Not specified	COMPLETED	Safety and Performance of POLYTHESE® Vascular Prosthesis
NCT05561270	Not specified	RECRUITING	Light Exposure on Pain in Hypermobile Ehlers-Danlos Syndrome
NCT05720923	Not specified	ACTIVE_NOT_RECRUITING	Analysis of Muscular Properties in Patients With MFS and EDS
NCT05871216	Not specified	RECRUITING	Functional Instability in Patients Suffering From Collagen Disease and Joint Hypermobility
NCT05945784	Not specified	COMPLETED	Exploring Accessible Beauty for Individuals With Upper Extremity Deficits
NCT06074276	Not specified	RECRUITING	The Effects of Almond on Facial Skin Collagen and Wrinkles
NCT06105541	Not specified	COMPLETED	Hypermobile Ehlers-Danlos Syndrome - Transcutaneous Auricular Neuromodulation