ABCC6

Summary

ABCC6 (ATP binding cassette subfamily C member 6, HGNC:57) is a protein-coding gene on chromosome 16p13.11, encoding ATP-binding cassette sub-family C member 6 (O95255). ATP-dependent transporter of the ATP-binding cassette (ABC) family that actively extrudes physiological compounds, and xenobiotics from cells.

The protein encoded by this gene is a member of the superfamily of ATP-binding cassette (ABC) transporters. ABC proteins transport various molecules across extra- and intra-cellular membranes. ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, White). The encoded protein, a member of the MRP subfamily, is involved in multi-drug resistance. Mutations in this gene cause pseudoxanthoma elasticum. Alternatively spliced transcript variants that encode different proteins have been described for this gene.

Source: NCBI Gene 368 — RefSeq curated summary.

At a glance

• Gene–disease (curated): inherited pseudoxanthoma elasticum (Definitive, ClinGen) — +3 more curated relationships
• GWAS associations: 5
• Clinical variants (ClinVar): 1,873 total — 160 pathogenic, 128 likely-pathogenic
• Phenotypes (HPO): 136
• Druggable target: yes
• MANE Select transcript: NM_001171

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:57
Approved symbol	ABCC6
Name	ATP binding cassette subfamily C member 6
Location	16p13.11
Locus type	gene with protein product
Status	Approved
Aliases	MRP6, EST349056, MLP1, URG7
Ensembl gene	ENSG00000091262
Ensembl biotype	protein_coding
OMIM	603234
Entrez	368

Gene structure

Transcript identifiers

Ensembl transcripts: 27 — 22 protein_coding, 3 nonsense_mediated_decay, 2 retained_intron

ENST00000205557, ENST00000456970, ENST00000574094, ENST00000575728, ENST00000576204, ENST00000576683, ENST00000577103, ENST00000622290, ENST00000909083, ENST00000909084, ENST00000909085, ENST00000909086, ENST00000909087, ENST00000909088, ENST00000909089, ENST00000909090, ENST00000909091, ENST00000909092, ENST00000909093, ENST00000909094, ENST00000909095, ENST00000909096, ENST00000909097, ENST00000946282, ENST00000946283, ENST00000946284, ENST00000946285

RefSeq mRNA: 3 — MANE Select: NM_001171 NM_001079528, NM_001171, NM_001351800

CCDS: CCDS10568, CCDS58430

Canonical transcript exons

ENST00000205557 — 31 exons

Exon	Start	End
ENSE00000670407	16182412	16182588
ENSE00000670409	16182804	16182930
ENSE00000670437	16221649	16221831
ENSE00001293454	16177452	16177626
ENSE00001318656	16178798	16178965
ENSE00001639528	16162993	16163192
ENSE00001851325	16223399	16223494
ENSE00002649611	16149565	16150241
ENSE00003477682	16150578	16150772
ENSE00003489767	16219554	16219682
ENSE00003498108	16219822	16219947
ENSE00003501018	16198021	16198182
ENSE00003506921	16208728	16208859
ENSE00003510061	16173284	16173404
ENSE00003531168	16187124	16187211
ENSE00003537315	16212185	16212246
ENSE00003555988	16190164	16190367
ENSE00003562953	16159482	16159583
ENSE00003585806	16165623	16165933
ENSE00003592923	16188831	16188974
ENSE00003602896	16175911	16175986
ENSE00003603055	16202001	16202178
ENSE00003618310	16192830	16192922
ENSE00003627359	16203410	16203613
ENSE00003629160	16154873	16155031
ENSE00003632719	16157663	16157809
ENSE00003639087	16154628	16154794
ENSE00003662846	16184959	16185034
ENSE00003669940	16214324	16214449
ENSE00003675149	16169646	16169853
ENSE00003675165	16161438	16161564

Expression profiles

Bgee: expression breadth ubiquitous, 136 present calls, max score 96.89.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right lobe of liver	UBERON:0001114	96.89	gold quality
liver	UBERON:0002107	96.47	gold quality
duodenum	UBERON:0002114	90.91	gold quality
adult mammalian kidney	UBERON:0000082	89.68	gold quality
body of pancreas	UBERON:0001150	87.37	gold quality
kidney	UBERON:0002113	86.55	gold quality
mucosa of transverse colon	UBERON:0004991	85.19	gold quality
cortex of kidney	UBERON:0001225	82.67	gold quality
pancreas	UBERON:0001264	80.68	gold quality
upper lobe of left lung	UBERON:0008952	79.25	gold quality
metanephros cortex	UBERON:0010533	79.22	gold quality
body of stomach	UBERON:0001161	79.11	gold quality
lung	UBERON:0002048	78.66	gold quality
right lung	UBERON:0002167	78.49	gold quality
right adrenal gland cortex	UBERON:0035827	78.08	gold quality
stomach	UBERON:0000945	77.83	gold quality
small intestine	UBERON:0002108	77.80	gold quality
transverse colon	UBERON:0001157	77.41	gold quality
small intestine Peyer’s patch	UBERON:0003454	77.31	gold quality
rectum	UBERON:0001052	77.11	gold quality
monocyte	CL:0000576	76.86	gold quality
leukocyte	CL:0000738	76.80	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	76.78	gold quality
right lobe of thyroid gland	UBERON:0001119	76.67	gold quality
right adrenal gland	UBERON:0001233	76.47	gold quality
thyroid gland	UBERON:0002046	76.11	gold quality
left lobe of thyroid gland	UBERON:0001120	75.84	gold quality
fundus of stomach	UBERON:0001160	75.80	gold quality
gall bladder	UBERON:0002110	75.74	gold quality
right uterine tube	UBERON:0001302	75.31	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	8.14

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): HNF4A, ID4, NFE2, NR1I3, PLAG1, PLAGL1, SOX2, SP1

miRNA regulators (miRDB)

35 targeting ABCC6, 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-4803	99.98	71.99	3117
HSA-MIR-137-3P	99.87	74.74	2401
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-576-5P	99.84	70.46	2582
HSA-MIR-548AG	99.77	69.25	1492
HSA-MIR-548AI	99.69	69.24	1494
HSA-MIR-548BA	99.69	69.14	1514
HSA-MIR-570-5P	99.69	69.24	1494
HSA-MIR-5700	99.64	69.88	2280
HSA-MIR-567	99.63	68.57	1219
HSA-MIR-4472	99.56	66.08	1478
HSA-MIR-199A-5P	99.51	69.71	1107
HSA-MIR-199B-5P	99.51	69.74	1098
HSA-MIR-1275	99.47	67.90	2749
HSA-MIR-3614-5P	99.30	65.25	837
HSA-MIR-625-5P	99.02	68.64	2031
HSA-MIR-181A-2-3P	98.91	67.60	1168
HSA-MIR-887-5P	98.82	65.90	1347
HSA-MIR-5006-5P	98.79	66.92	1246
HSA-MIR-603	98.58	68.28	1603
HSA-MIR-6509-3P	98.32	67.33	1343
HSA-MIR-5088-3P	98.29	66.63	1310
HSA-MIR-5691	98.23	67.02	1335
HSA-MIR-6805-3P	98.23	67.02	1334
HSA-MIR-5007-5P	97.95	64.71	614
HSA-MIR-4665-5P	97.91	67.69	1536
HSA-MIR-676-3P	97.86	65.70	668
HSA-MIR-30C-1-3P	97.80	66.36	1499
HSA-MIR-30C-2-3P	97.80	66.45	1499
HSA-MIR-6788-5P	97.80	66.41	1532

Literature-anchored findings (GeneRIF, showing 40)

• point mutations in Pseudoxanthoma elasticum (PMID:11439001)
• mutations cause pseudoxanthoma elasticum (PMID:11536079)
• Loss of ATP-dependent transport activity in pseudoxanthoma elasticum-associated mutants of human ABCC6 (MRP6). (PMID:11880368)
• Presence of the R1141X mutation in the ABCC6 gene is associated with a sharply increased risk of premature coronary artery disease (PMID:12176944)
• We suggest that the severity of the Pseudoxanthoma elasticum phenotype is not directly correlated with the level of ABCC6/MRP6 activity. (PMID:12673275)
• A specific founder effect for the R1141X mutation exists in Dutch patients with PXE (pseudoxanthoma elasticum). (PMID:12714611)
• Using linkage analysis and mutation detection techniques, mutations in the ABCC6 gene were recently implicated in the etiology of pseudoxanthoma elasticum. (PMID:12850230)
• Asn15, which is located in the extracellular N-terminal region of human ABCC6, is the only N-glycosylation site in this protein. (PMID:12901863)
• Twenty-three different mutations were identified, among which 11 were new, in Italian patients with pseudoxanthoma elasticum (PMID:15459974)
• first report of missense mutation identification in the ABCC6 gene in Japanese pseudoxanthoma elasticum patients. (PMID:15645653)
• ABCC6 gene mutations is associated with German pseudoxanthoma elasticum patients (PMID:15723264)
• there is a DNA methylation-dependent activator sequence in the ABCC6 promoter (PMID:15760889)
• The widespread tissue distribution of ABCC6 suggests that ABCC6 fulfills multiple functions in different tissues. (PMID:15889270)
• ABCC6 mutations may have roles in Pseudoxanthoma elasticum (PMID:15894595)
• mutations in ABCC6 may have a role in pseudoxanthoma elasticum (PMID:16086317)
• alterations in ABCC6 are not a genetic risk factor for abdominal aortic aneurysm (PMID:16127278)
• Human ABCC6 displays tissue-specific gene expression, which can be modulated by proinflammatory cytokines. (PMID:16374464)
• Finds 16 PXE causing mutations and 11 neutral polymorphisms or sequence variations in particular ABCC6 exons of German patients and their relatives. (PMID:16392638)
• ABCC6 deficiency in Pseudoxanthoma elasticum (PXE) patients induces a persistent imbalance in circulating metabolite(s), which may impair the synthetic abilities of normal elastoblasts or specifically alter elastic fiber assembly. (PMID:16543900)
• 10 novel mutations within the ABCC6 gene are associated with pseudoxanthoma elasticum. (PMID:16835894)
• This suggests ABCC6 gene expression and the first identification of a transcription factor which is relevant to regulation of ABCC6 level in tissues and in some PXE patients. (PMID:17045963)
• heterozygote carriers had changes in dermal elastic fibre organization, morphology & labelling midway between those seen in pseudoxanthoma elasticum & normal skin; having a single mutation in the ABCC6 gene seems enough to modify dermal elastic fibres (PMID:17309461)
• ABCC6 mutations have a role in the pathogenesis of pseudoxanthoma elasticum (PMID:17617515)
• The mechanism underlying retinal dysfunction is unknown but may result from metabolic disturbance leading to retinal toxicity with a possible role of modifying genetic or environmental factors rather than specific ABCC6 mutations. (PMID:17724214)
• ABCC6 genomic rearrangements may have a role in pseudoxanthoma elasticum in French patients (PMID:17823974)
• This study shows elastic fibers like in the lesional skin of patients with a variety of inflammatory skin diseases in the absence of clinical evidence of pseudoxanthoma elasticum; and some of these patients harbor changes in ABCC6. (PMID:17880583)
• Compound heterozygosity for a novel and a recurrent ABCC6 gene mutation in an Italian family with Pseudoxanthoma elasticum. (PMID:18029147)
• ABCC6 is the most important, and probably only, causative gene of pseudoxanthoma elasticum(PXE). In total, 188 different ABCC6 mutations have now been reported in PXE in the literature. (PMID:18253096)
• ABCC6 is unlikely to be a modifier gene for familial Mediterranean fever severity. (PMID:18305351)
• study to illustrate phenotypic overlap consisting of usual, but limited, or atypical manifestations of PXE between heterozygous carriers of single ABCC6 mutation & patients diagnosed with PXE, carriers of homozygous or compound heterozygous mutations (PMID:18347285)
• Expression and localization MRP6 were significantly higher in hepatoid than in control adenocarcinoma (PMID:18439156)
• Study demonstrates that partial duplication of PKD1 and ABCC6 has many consequences: pseudogenes give rise to new transcripts and mediate gene conversion, which results in disease-causing mutations and also serves as a reservoir for sequence variation. (PMID:18791038)
• analysis of GGCX and ABCC6 mutations in a family with pseudoxanthoma elasticum-like phenotypes [case report] (PMID:18800149)
• identified ABCC6 as a target gene for transcriptional induction by PLAG1 and PLAGL1, transcription factors from the PLAG family of cell cycle progression-related DNA-binding proteins (PMID:18850323)
• These data provide a genetic proof of the importance of these domain-domain interactions in the ABCC6 transporter. (PMID:19133228)
• Very recently, the ABCC6 gene on chromosome 16p13.1 was found to be associated with the disease. (PMID:19298904)
• Delineation of the ABCC6 mutation profile in South African PXE patients will be used as a guide for molecular genetic testing in a clinical setting and for genetic counselling. (PMID:19339160)
• novel sequence determinants of liver-specific transcription of the ABCC6 gene with direct relevance for at least some pseudoxanthoma elasticum patients were identified. (PMID:19341707)
• Studies show that individuals homozygous for the c.3775delT mutation in the ABCC6 gene can have a highly variable phenotype. (PMID:19904211)
• The R1141X loss-of-function mutation of the ABCC6 gene is a strong genetic risk factor for coronary artery disease. (PMID:19929409)

Cross-species orthologs

14 orthologs

Organism	Symbol	Gene ID
danio_rerio	abcc13	ENSDARG00000062519
mus_musculus	Abcc6	ENSMUSG00000030834
rattus_norvegicus	Abcc6	ENSRNOG00000028781
drosophila_melanogaster	l(2)03659	FBGN0010549
drosophila_melanogaster	CG7627	FBGN0032026
drosophila_melanogaster	MRP	FBGN0032456
drosophila_melanogaster	CG9270	FBGN0032908
drosophila_melanogaster	CG10505	FBGN0034612
drosophila_melanogaster	Mrp5	FBGN0038740
drosophila_melanogaster	rdog	FBGN0039644
drosophila_melanogaster	CG11898	FBGN0039645
drosophila_melanogaster	CG31792	FBGN0051792
drosophila_melanogaster	Mrp4	FBGN0263316
caenorhabditis_elegans		WBGENE00000477

Paralogs (11): CFTR (ENSG00000001626), ABCC8 (ENSG00000006071), ABCC2 (ENSG00000023839), ABCC9 (ENSG00000069431), ABCC1 (ENSG00000103222), ABCC3 (ENSG00000108846), ABCC5 (ENSG00000114770), ABCC11 (ENSG00000121270), ABCC10 (ENSG00000124574), ABCC4 (ENSG00000125257), ABCC12 (ENSG00000140798)

Protein

Protein identifiers

ATP-binding cassette sub-family C member 6 — O95255 (reviewed: O95255)

Alternative names: Anthracycline resistance-associated protein, Multi-specific organic anion transporter E, Multidrug resistance-associated protein 6

All UniProt accessions (4): O95255, A0A804HJ04, A0A8C8Q0G8, I3L1Z6

UniProt curated annotations — full annotation on UniProt →

Function. ATP-dependent transporter of the ATP-binding cassette (ABC) family that actively extrudes physiological compounds, and xenobiotics from cells. Mediates ATP-dependent transport of glutathione conjugates such as leukotriene-c4 (LTC4) and N-ethylmaleimide S-glutathione (NEM-GS) (in vitro), and an anionic cyclopentapeptide endothelin antagonist, BQ-123. May contribute to regulate the transport of organic compounds in testes across the blood-testis-barrier. Does not appear to actively transport drugs outside the cell. Confers low levels of cellular resistance to etoposide, teniposide, anthracyclines and cisplatin. Mediates the release of nucleoside triphosphates, predominantly ATP, into the circulation, where it is rapidly converted into AMP and the mineralization inhibitor inorganic pyrophosphate (PPi) by the ecto-enzyme ectonucleotide pyrophosphatase phosphodiesterase 1 (ENPP1), therefore playing a role in PPi homeostasis. Inhibits TNF-mediated apoptosis through blocking one or more caspases.

Subcellular location. Basal cell membrane Basolateral cell membrane Endoplasmic reticulum membrane.

Tissue specificity. Expressed in kidney and liver. Very low expression in other tissues. In testis, localized to peritubular myoid cells, Leydig cells, along the basal membrane of Sertoli cells and moderately in the adluminal compartment of the seminiferous tubules.

Post-translational modifications. Glycosylated.

Disease relevance. Pseudoxanthoma elasticum (PXE) [MIM:264800] A multisystem disorder characterized by accumulation of mineralized and fragmented elastic fibers in the skin, vascular walls, and Burch membrane in the eye. Clinically, patients exhibit characteristic lesions of the posterior segment of the eye including peau d’orange, angioid streaks, and choroidal neovascularizations, of the skin including soft, ivory colored papules in a reticular pattern that predominantly affect the neck and large flexor surfaces, and of the cardiovascular system with peripheral and coronary arterial occlusive disease as well as gastrointestinal bleedings. The disease is caused by variants affecting the gene represented in this entry. Homozygous or compound heterozygous ABCC6 mutations have been found in the overwhelming majority of cases. Individuals carrying heterozygous mutations express limited manifestations of the pseudoxanthoma elasticum phenotype. Arterial calcification of infancy, generalized, 2 (GACI2) [MIM:614473] A severe autosomal recessive disorder characterized by calcification of the internal elastic lamina of muscular arteries and stenosis due to myointimal proliferation. The disorder is often fatal within the first 6 months of life because of myocardial ischemia resulting in refractory heart failure. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. LTC4 transport is completely inhibited by 1 mM orthovanadate.

Induction. Induced by HBV x antigen upon hepatitis B viral infection.

Miscellaneous. May function as a half transporter.

Similarity. Belongs to the ABC transporter superfamily. ABCC family. Conjugate transporter (TC 3.A.1.208) subfamily.

Isoforms (3)

UniProt ID	Names	Canonical?
O95255-1	1	yes
O95255-2	2, URG7
O95255-3	3, Delta19Delta24

RefSeq proteins (3): NP_001072996, NP_001162, NP_001338729 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003439	ABC_transporter-like_ATP-bd	Domain
IPR003593	AAA+_ATPase	Domain
IPR005292	MRP	Family
IPR011527	ABC1_TM_dom	Domain
IPR017871	ABC_transporter-like_CS	Conserved_site
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR036640	ABC1_TM_sf	Homologous_superfamily
IPR050173	ABC_transporter_C-like	Family
IPR056227	TMD0_ABC	Domain

Pfam: PF00005, PF00664, PF24357

Enzyme classification (BRENDA):

• EC 7.6.2.3 — ABC-type glutathione-S-conjugate transporter (BRENDA: 8 organisms, 145 substrates, 63 inhibitors, 16 Km, 0 kcat entries)

Substrate kinetics (BRENDA)

7 substrates with measured Km, best-characterized 7. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
ATP	0.0865–0.91	5
MONOMETHYLARSONOUS ACID DIGLUTATHIONE[SIDE 1]	0.023–0.033	4
S-(2,4-DINITROPHENYL)GLUTATHIONE[SIDE 1]	0.0141–0.032	2
S-(LEUKOTRIENE C4)GLUTATHIONE[SIDE 1]	0.0001	2
4-(GLUTATHIONE-S-YL)-QUINOLINE-1-OXIDE[SIDE 1]	0.0095	1
ARSENIC TRIGLUTATHIONE[SIDE 1]	0.0003	1
S-GLUTATHIONE[SIDE 1]	12	1

Catalyzed reactions (Rhea), 2 shown:

• an S-substituted glutathione(in) + ATP + H2O = an S-substituted glutathione(out) + ADP + phosphate + H(+) (RHEA:19121)
• leukotriene C4(in) + ATP + H2O = leukotriene C4(out) + ADP + phosphate + H(+) (RHEA:38963)

UniProt features (228 total): sequence variant 122, strand 26, helix 22, topological domain 18, transmembrane region 17, sequence conflict 6, domain 4, splice variant 4, turn 2, binding site 2, chain 1, region of interest 1, compositionally biased region 1, modified residue 1, glycosylation site 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
6BZS	X-RAY DIFFRACTION	2.3
6BZR	X-RAY DIFFRACTION	2.8
6P7F	X-RAY DIFFRACTION	2.85
6NLO	X-RAY DIFFRACTION	2.85

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O95255-F1	81.32	0.29

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (2): 663–670; 1299–1306

Post-translational modifications (1): 1286

Glycosylation sites (1): 15

Function

Pathways and Gene Ontology

Reactome pathways

6 pathways

ID	Pathway
R-HSA-382556	ABC-family protein mediated transport
R-HSA-5690338	Defective ABCC6 causes PXE
R-HSA-1643685	Disease
R-HSA-382551	Transport of small molecules
R-HSA-5619084	ABC transporter disorders
R-HSA-5619115	Disorders of transmembrane transporters

MSigDB gene sets: 412 (showing top): GSE45365_HEALTHY_VS_MCMV_INFECTION_CD8_TCELL_IFNAR_KO_UP, GSE18804_SPLEEN_MACROPHAGE_VS_BRAIN_TUMORAL_MACROPHAGE_DN, GNF2_GSTM1, MODULE_418, GNF2_HPN, GOBP_INORGANIC_ANION_TRANSPORT, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_NUCLEOTIDE_TRANSPORT, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, GOBP_ORGANIC_ACID_TRANSPORT, KEGG_ABC_TRANSPORTERS, GOBP_RESPONSE_TO_METAL_ION, PATIL_LIVER_CANCER, GOBP_NUCLEOBASE_CONTAINING_SMALL_MOLECULE_METABOLIC_PROCESS, GOBP_ORGANOPHOSPHATE_ESTER_TRANSPORT

GO Biological Process (16): visual perception (GO:0007601), response to xenobiotic stimulus (GO:0009410), gene expression (GO:0010467), ATP transport (GO:0015867), inorganic diphosphate transport (GO:0030505), intracellular phosphate ion homeostasis (GO:0030643), response to magnesium ion (GO:0032026), ATP metabolic process (GO:0046034), phosphate ion homeostasis (GO:0055062), calcium ion homeostasis (GO:0055074), transmembrane transport (GO:0055085), leukotriene transport (GO:0071716), inhibition of non-skeletal tissue mineralization (GO:0140928), response to sodium phosphate (GO:1904383), carboxylic acid transport (GO:0046942), monoatomic anion transmembrane transport (GO:0098656)

GO Molecular Function (8): ATP binding (GO:0005524), ABC-type glutathione S-conjugate transporter activity (GO:0015431), ATP hydrolysis activity (GO:0016887), ATPase-coupled transmembrane transporter activity (GO:0042626), obsolete ATPase-coupled inorganic anion transmembrane transporter activity (GO:0043225), ABC-type transporter activity (GO:0140359), nucleotide binding (GO:0000166), transmembrane transporter activity (GO:0022857)

GO Cellular Component (8): extracellular region (GO:0005576), nucleoplasm (GO:0005654), endoplasmic reticulum membrane (GO:0005789), plasma membrane (GO:0005886), basal plasma membrane (GO:0009925), basolateral plasma membrane (GO:0016323), endoplasmic reticulum (GO:0005783), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
Transport of small molecules	1
ABC transporter disorders	1
Disorders of transmembrane transporters	1
Disease	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
inorganic ion homeostasis	2
ATP-dependent activity	2
plasma membrane region	2
sensory perception of light stimulus	1
response to chemical	1
macromolecule biosynthetic process	1
purine ribonucleotide transport	1
adenine nucleotide transport	1
inorganic anion transport	1
phosphate ion homeostasis	1
intracellular chemical homeostasis	1
response to metal ion	1
purine ribonucleotide metabolic process	1
purine ribonucleoside triphosphate metabolic process	1
monoatomic cation homeostasis	1
transport	1
cellular process	1
icosanoid transport	1
tissue homeostasis	1
response to salt	1
organic acid transport	1
monoatomic anion transport	1
monoatomic ion transmembrane transport	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
ABC-type transporter activity	1
sulfur compound transmembrane transporter activity	1
ribonucleoside triphosphate phosphatase activity	1
primary active transmembrane transporter activity	1
ATP hydrolysis activity	1
ATPase-coupled transmembrane transporter activity	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
transporter activity	1
transmembrane transport	1
nuclear lumen	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

132 interactions, top by confidence:

A	B	Type	Score
ABCC6	ZMYND11	psi-mi:“MI:0407”(direct interaction)	0.440
MAP1LC3B	ABCC6	psi-mi:“MI:0407”(direct interaction)	0.440
ABCC6	MAP1LC3A	psi-mi:“MI:0407”(direct interaction)	0.440
ABCC6	RADIL	psi-mi:“MI:0407”(direct interaction)	0.440
ABCC6	PICK1	psi-mi:“MI:0407”(direct interaction)	0.440
ABCC6	PARD3B	psi-mi:“MI:0407”(direct interaction)	0.440
ABCC6	ARHGAP21	psi-mi:“MI:0407”(direct interaction)	0.440
ABCC6	MAST2	psi-mi:“MI:0407”(direct interaction)	0.440
ABCC6	PDZD7	psi-mi:“MI:0407”(direct interaction)	0.440
ABCC6	LIN7C	psi-mi:“MI:0407”(direct interaction)	0.440
ABCC6	HTRA1	psi-mi:“MI:0407”(direct interaction)	0.440
ABCC6	WHRN	psi-mi:“MI:0407”(direct interaction)	0.440
ABCC6	APBA3	psi-mi:“MI:0407”(direct interaction)	0.440
ABCC6	LNX1	psi-mi:“MI:0407”(direct interaction)	0.440
ABCC6	DLG3	psi-mi:“MI:0407”(direct interaction)	0.440
ABCC6	MPP2	psi-mi:“MI:0407”(direct interaction)	0.440
TIAM2	ABCC6	psi-mi:“MI:0407”(direct interaction)	0.440
ABCC6	MAGI2	psi-mi:“MI:0407”(direct interaction)	0.440
ABCC6	LIMK2	psi-mi:“MI:0407”(direct interaction)	0.440
ABCC6	ARHGEF11	psi-mi:“MI:0407”(direct interaction)	0.440
ABCC6	PATJ	psi-mi:“MI:0407”(direct interaction)	0.440
ABCC6	MAGI1	psi-mi:“MI:0407”(direct interaction)	0.440
ABCC6	PTPN13	psi-mi:“MI:0407”(direct interaction)	0.440
ABCC6	GRIP1	psi-mi:“MI:0407”(direct interaction)	0.440
ABCC6	CASK	psi-mi:“MI:0407”(direct interaction)	0.440
ABCC6	CARD11	psi-mi:“MI:0407”(direct interaction)	0.440
ABCC6	TJP2	psi-mi:“MI:0407”(direct interaction)	0.440
ABCC6	APBA2	psi-mi:“MI:0407”(direct interaction)	0.440

BioGRID (54): GCN1L1 (Affinity Capture-MS), CLTC (Affinity Capture-MS), A2M (Affinity Capture-MS), ROCK2 (Affinity Capture-MS), UGGT1 (Affinity Capture-MS), EPRS (Affinity Capture-MS), COPA (Affinity Capture-MS), SEC31A (Affinity Capture-MS), PSMD1 (Affinity Capture-MS), IPO5 (Affinity Capture-MS), COPB1 (Affinity Capture-MS), HSPA5 (Affinity Capture-MS), EZR (Affinity Capture-MS), HSD17B4 (Affinity Capture-MS), HADHA (Affinity Capture-MS)

ESM2 similar proteins: A0A8C2M425, A1L1J9, B0BNG2, O60725, O75908, O77759, O88269, O88908, O95255, Q0P4J9, Q290J8, Q3T1L5, Q3TAE8, Q3UV71, Q499P8, Q49LS7, Q4R4E1, Q4VV71, Q5F380, Q5KR61, Q5R8F6, Q5RAH7, Q5RKL5, Q6AZ83, Q6NVG1, Q7SXZ1, Q7T310, Q7TPN3, Q7TQM4, Q86VD9, Q8AVI9, Q8BTP0, Q8C0T0, Q8C3X8, Q8CI59, Q8IUR5, Q8K2A8, Q8L638, Q8R1J1, Q8R4P9

Diamond homologs: A0A0D1CZ63, A0A0U1LQE1, A0A1U8QTJ9, A2XCD4, A7KVC2, B2RX12, E9Q236, F1M3J4, F9X9V4, G4N2B5, J9VQH1, O15438, O15439, O15440, O31708, O35379, O60706, O70127, O88269, O88563, O95255, P0CE69, P14772, P16875, P16877, P21439, P21440, P32386, P33527, P38735, P39109, P53049, P70170, P82451, P91660, P9WEL8, Q07QX6, Q08201, Q09427, Q0VQP5

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
PLAG1	“up-regulates quantity by expression”	ABCC6	“transcriptional regulation”
PLAGL1	“up-regulates quantity by expression”	ABCC6	“transcriptional regulation”
SOX2	“up-regulates quantity by expression”	ABCC6	“transcriptional regulation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 88 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
Ras activation upon Ca2+ influx through NMDA receptor	5	48.4×	3e-06
Unblocking of NMDA receptors, glutamate binding and activation	5	46.1×	3e-06
Negative regulation of NMDA receptor-mediated neuronal transmission	5	46.1×	3e-06
Assembly and cell surface presentation of NMDA receptors	10	43.0×	2e-12
Dopamine Neurotransmitter Release Cycle	5	42.1×	4e-06
Long-term potentiation	5	40.3×	4e-06
Neurexins and neuroligins	11	36.7×	1e-12
Protein-protein interactions at synapses	7	31.5×	2e-07

GO biological processes:

GO term	Partners	Fold	FDR
establishment or maintenance of epithelial cell apical/basal polarity	11	77.0×	4e-16
protein localization to synapse	6	55.4×	1e-07
receptor clustering	7	52.6×	1e-08
regulation of postsynaptic membrane neurotransmitter receptor levels	7	41.8×	5e-08
cell-cell adhesion	10	12.2×	8e-07
protein-containing complex assembly	8	11.0×	4e-05
regulation of small GTPase mediated signal transduction	5	8.7×	6e-03
chemical synaptic transmission	7	6.5×	3e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

1873 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	160
Likely pathogenic	128
Uncertain significance	759
Likely benign	577
Benign	71

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1068874	NC_000016.9:g.(?16248465)(16259810_?)del	Pathogenic
1179156	GRCh37/hg19 16p13.11(chr16:16248464-16259810)	Pathogenic
1363672	NC_000016.9:g.(?16243990)(16292059_?)del	Pathogenic
1367116	NC_000016.9:g.(?16291858)(16292059_?)del	Pathogenic
1390356	NM_001171.6(ABCC6):c.3497del (p.Val1166fs)	Pathogenic
1391272	NM_001171.6(ABCC6):c.2889C>A (p.Cys963Ter)	Pathogenic
1391421	NM_001171.6(ABCC6):c.2407del (p.Gln803fs)	Pathogenic
1413432	NM_001171.6(ABCC6):c.2536dup (p.Ala846fs)	Pathogenic
1430179	NM_001171.6(ABCC6):c.4063_4080del (p.Ser1355_Leu1360del)	Pathogenic
1453742	NM_001171.6(ABCC6):c.2781C>A (p.Tyr927Ter)	Pathogenic
1456657	NM_001171.6(ABCC6):c.2698dup (p.Thr900fs)	Pathogenic
1458858	NM_001171.6(ABCC6):c.3315T>G (p.Tyr1105Ter)	Pathogenic
1701283	NM_001171.6(ABCC6):c.3634-1G>T	Pathogenic
1802149	NM_001171.6(ABCC6):c.2738_2739del (p.Pro913fs)	Pathogenic
1981514	NM_001171.6(ABCC6):c.1791del (p.Phe598fs)	Pathogenic
2022821	NM_001171.6(ABCC6):c.3913_3931dup (p.Gly1311fs)	Pathogenic
208558	NM_001171.6(ABCC6):c.3306+1del	Pathogenic
2099772	NM_001171.6(ABCC6):c.4093del (p.Glu1365fs)	Pathogenic
2116451	NM_001171.6(ABCC6):c.1786del (p.Val596fs)	Pathogenic
2120735	NM_001171.6(ABCC6):c.3077G>A (p.Trp1026Ter)	Pathogenic
2135683	NM_001171.6(ABCC6):c.3335dup (p.Arg1113fs)	Pathogenic
2186680	NM_001171.6(ABCC6):c.3256_3257dup (p.Ala1087fs)	Pathogenic
2423918	NC_000016.9:g.(?16263483)(16292059_?)del	Pathogenic
2423919	NC_000016.9:g.(?16259460)(16292059_?)del	Pathogenic
2572576	NM_001171.6(ABCC6):c.2035G>T (p.Glu679Ter)	Pathogenic
2578774	GRCh37/hg19 16p13.11(chr16:16248485-16259790)x1	Pathogenic
2580302	GRCh37/hg19 16p13.11(chr16:15475455-16308356)x1	Pathogenic
2628399	NM_001171.6(ABCC6):c.982_988delinsTTCCCC (p.Val328fs)	Pathogenic
2698001	NM_001171.6(ABCC6):c.2044_2045del (p.Lys682fs)	Pathogenic
2764901	NM_001171.6(ABCC6):c.1755del (p.Phe586fs)	Pathogenic

SpliceAI

5151 predictions. Top by Δscore:

Variant	Effect	Δscore
16:16150771:CG:C	acceptor_gain	1.0000
16:16154622:CCATA:C	donor_loss	1.0000
16:16154623:CATA:C	donor_loss	1.0000
16:16154626:A:AC	donor_gain	1.0000
16:16154627:C:CC	donor_gain	1.0000
16:16154790:GGGTC:G	acceptor_gain	1.0000
16:16154791:GGTC:G	acceptor_gain	1.0000
16:16154792:GTC:G	acceptor_gain	1.0000
16:16154793:TC:T	acceptor_gain	1.0000
16:16154794:CC:C	acceptor_gain	1.0000
16:16154794:CCTG:C	acceptor_loss	1.0000
16:16154795:C:CA	acceptor_loss	1.0000
16:16154795:C:CC	acceptor_gain	1.0000
16:16154796:T:C	acceptor_loss	1.0000
16:16154799:C:CT	acceptor_gain	1.0000
16:16157659:TCA:T	donor_loss	1.0000
16:16157660:CACCT:C	donor_loss	1.0000
16:16157810:C:CC	acceptor_gain	1.0000
16:16159483:T:TA	donor_gain	1.0000
16:16173280:TTACC:T	donor_loss	1.0000
16:16173281:TACC:T	donor_loss	1.0000
16:16173282:AC:A	donor_gain	1.0000
16:16173283:C:CG	donor_loss	1.0000
16:16173283:CC:C	donor_gain	1.0000
16:16173283:CCCTG:C	donor_gain	1.0000
16:16173303:T:TA	donor_gain	1.0000
16:16173308:T:A	donor_gain	1.0000
16:16173403:ACCT:A	acceptor_loss	1.0000
16:16173405:C:CC	acceptor_gain	1.0000
16:16173406:T:A	acceptor_loss	1.0000

AlphaMissense

9670 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:16188906:A:C	F568L	0.984
16:16188906:A:T	F568L	0.984
16:16188908:A:G	F568L	0.984
16:16221735:A:G	W45R	0.983
16:16221735:A:T	W45R	0.983
16:16198041:A:G	C440R	0.976
16:16182892:A:T	V661D	0.973
16:16198068:A:G	W431R	0.972
16:16198068:A:T	W431R	0.972
16:16219680:G:C	S116R	0.972
16:16219680:G:T	S116R	0.972
16:16219682:T:G	S116R	0.972
16:16161563:A:G	W1170R	0.968
16:16161563:A:T	W1170R	0.968
16:16212195:A:G	W218R	0.967
16:16212195:A:T	W218R	0.967
16:16187211:C:G	A594P	0.966
16:16212199:G:C	F216L	0.965
16:16212199:G:T	F216L	0.965
16:16212201:A:G	F216L	0.965
16:16165879:G:A	S1017F	0.964
16:16177622:C:G	R807P	0.964
16:16178922:G:T	A764D	0.964
16:16177616:A:G	L809P	0.963
16:16178925:A:G	L763P	0.962
16:16198039:G:C	C440W	0.962
16:16198090:G:C	S423R	0.962
16:16198090:G:T	S423R	0.962
16:16198092:T:G	S423R	0.962
16:16188907:A:C	F568C	0.960

dbSNP variants (sampled 300 via entrez): RS1000026562 (16:16157013 G>A), RS1000029685 (16:16223932 C>T), RS1000056295 (16:16156693 G>A), RS1000085426 (16:16216307 G>A), RS1000116891 (16:16216647 G>C), RS1000118799 (16:16193708 C>T), RS1000130250 (16:16179549 A>G), RS1000184278 (16:16190384 A>G), RS1000211396 (16:16184647 C>T), RS1000211989 (16:16173846 T>A), RS1000236988 (16:16162279 C>T), RS1000295692 (16:16210462 G>A), RS1000378543 (16:16195063 G>A), RS1000388461 (16:16167879 T>C), RS1000442345 (16:16151791 G>T)

Disease associations

OMIM: gene MIM:603234 | disease phenotypes: MIM:177850, MIM:264800, MIM:614473, MIM:256300, MIM:109730, MIM:192200

GenCC curated gene-disease

Disease	Classification	Inheritance
inherited pseudoxanthoma elasticum	Definitive	Semidominant
autosomal recessive inherited pseudoxanthoma elasticum	Definitive	Autosomal recessive
arterial calcification, generalized, of infancy, 2	Definitive	Autosomal recessive
arterial calcification of infancy	Supportive	Autosomal dominant

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
inherited pseudoxanthoma elasticum	Definitive	SD

Mondo (13): pseudoxanthoma elasticum, forme fruste (MONDO:0008333), autosomal recessive inherited pseudoxanthoma elasticum (MONDO:0009925), arterial calcification, generalized, of infancy, 2 (MONDO:0013768), pseudoxanthoma elasticum (inherited or acquired) (MONDO:0024308), inherited retinal dystrophy (MONDO:0019118), optic atrophy (MONDO:0003608), congenital nephrotic syndrome, Finnish type (MONDO:0009732), retinal disorder (MONDO:0005283), aortic valve disease 1 (MONDO:0024523), varicose disease (MONDO:0008638), cutis laxa (MONDO:0016175), inherited pseudoxanthoma elasticum (MONDO:0100091), arterial calcification of infancy (MONDO:0018870)

Orphanet (5): Generalized arterial calcification of infancy (Orphanet:51608), Pseudoxanthoma elasticum (Orphanet:758), OBSOLETE: Inherited retinal disorder (Orphanet:71862), Congenital nephrotic syndrome, Finnish type (Orphanet:839), Cutis laxa (Orphanet:209)

HPO phenotypes

136 total (30 of 136 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000121	Nephrocalcinosis
HP:0000218	High palate
HP:0000365	Hearing impairment
HP:0000381	Stapes ankylosis
HP:0000405	Conductive hearing impairment
HP:0000407	Sensorineural hearing impairment
HP:0000410	Mixed hearing impairment
HP:0000474	Thickened nuchal skin fold
HP:0000488	Retinopathy
HP:0000505	Visual impairment
HP:0000545	Myopia
HP:0000573	Retinal hemorrhage
HP:0000592	Blue sclerae
HP:0000608	Macular degeneration
HP:0000630	Abnormal retinal arterial/arteriolar morphology
HP:0000737	Irritability
HP:0000765	Abnormal thorax morphology
HP:0000766	Abnormal sternum morphology
HP:0000822	Hypertension
HP:0000951	Abnormality of the skin
HP:0000961	Cyanosis
HP:0000969	Edema
HP:0000973	Cutis laxa
HP:0000974	Hyperextensible skin
HP:0000978	Bruising susceptibility
HP:0001012	Multiple lipomas
HP:0001065	Striae distensae
HP:0001102	Angioid streaks

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST003051_1	Multiple myeloma (survival)	7.000000e-09
GCST010083_316	Hemoglobin levels	9.000000e-14
GCST90002383_238	Hematocrit	6.000000e-14
GCST90002384_357	Hemoglobin	3.000000e-15
GCST90002403_669	Red blood cell count	7.000000e-17

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0000638	overall survival
EFO:0004509	hemoglobin measurement
EFO:0004348	hematocrit
EFO:0004305	erythrocyte count

MeSH disease descriptors (7)

Descriptor	Name	Tree numbers
D003483	Cutis Laxa	C16.320.850.180; C17.300.230; C17.800.827.180
D009896	Optic Atrophy	C10.292.700.225; C11.640.451
D011561	Pseudoxanthoma Elasticum	C14.907.454.530; C15.378.463.515.530; C16.131.831.766; C16.320.850.750; C17.300.766; C17.800.804.766; C17.800.827.750
D012164	Retinal Diseases	C11.768
D058499	Retinal Dystrophies	C11.768.585.658
D014648	Varicose Veins	C14.907.927
C537440	Arterial calcification of infancy (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2073661 (SINGLE PROTEIN)

PharmGKB: 1 entry (VIP=true, CPIC=false)

PharmGKB clinical annotations

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs2238472	Toxicity	3	docetaxel;thalidomide	Prostatic Neoplasms

PharmGKB variants

5 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs2238472	ABCC6	3	2.00	1	docetaxel;thalidomide
rs8058694	ABCC6		0.00	0
rs12929610	ABCC6		0.00	0
rs12935089	ABCC6		0.00	0
rs4781732	ABCC6		0.00	0

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: transporter — ABCC subfamily

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases expression	6
Cyclosporine	decreases expression	3
Aflatoxin B1	affects expression, decreases expression, increases methylation	3
Docetaxel	affects response to substance, affects expression, decreases response to substance	2
Acetaminophen	decreases expression	2
Benzbromarone	decreases reaction, decreases activity, affects transport	2
Indomethacin	decreases activity, affects transport, decreases reaction	2
Phenobarbital	decreases expression, increases expression	2
Tobacco Smoke Pollution	decreases expression	2
Valproic Acid	decreases expression, increases expression	2
methylmercuric chloride	decreases expression	1
methyleugenol	decreases expression	1
triphenyl phosphate	affects expression	1
propionaldehyde	decreases expression	1
bisphenol A	affects expression	1
fluorexon	affects transport	1
senecionine	decreases expression	1
senkirkine	decreases expression	1
heliotrine	decreases expression	1
trichostatin A	decreases expression	1
sodium arsenite	decreases expression	1
butyraldehyde	decreases expression	1
diallyl disulfide	decreases expression, increases expression	1
diallyl trisulfide	increases expression	1
N-ethylmaleimide-S-glutathione	affects transport, decreases reaction	1
di-n-butylphosphoric acid	affects expression	1
calcein AM	affects transport, increases reaction	1
belinostat	decreases expression	1
bisphenol S	decreases methylation	1
Rosiglitazone	decreases expression	1

ChEMBL screening assays

10 unique, capped per target: 9 functional, 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL2075388	Functional	TP_TRANSPORTER: uptake in membrane vesicles from MRP6-expressing Sf9 cells	Loss of ATP-dependent transport activity in pseudoxanthoma elasticum-associated mutants of human ABCC6 (MRP6). — J Biol Chem
CHEMBL4423073	Binding	Inhibition of ABCC6 (unknown origin) expressed in HEK293 cells assessed as increase in doxorubicin efflux at 100 uM after 30 mins by fluorescence assay	The P-glycoprotein inhibitor diltiazem-like 8-(4-chlorophenyl)-5-methyl-8-[(2Z)-pent-2-en-1-yloxy]-8H-[1,2,4]oxadiazolo[3,4-c][1,4]thiazin-3-one inhibits esterase activity and H3 histone acetylation. — Eur J Med Chem

Cellosaurus cell lines

4 cell lines: 2 cancer cell line, 1 transformed cell line, 1 finite cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B6A3	C2BBe1 MRP6 KO	Cancer cell line	Male
CVCL_B6AK	HepaRG MRP6 KO	Cancer cell line	Female
CVCL_LN32	HEK293/hABCC6	Transformed cell line	Female
CVCL_Y109	GM04994	Finite cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT01955135	PHASE4	COMPLETED	Anesthesia for Retinopathy of Prematurity
NCT01287702	PHASE4	UNKNOWN	Early Feeding Following Ligation of Acute Bleeding Varices
NCT01611324	PHASE4	COMPLETED	Painless Local Infiltration Anesthesia
NCT02010723	PHASE4	COMPLETED	Surgery Versus Sclerotherapy for Isolated Accessory Great Saphenous Vein Varicosis
NCT02054325	PHASE4	COMPLETED	Study Protocol Comparing Polidocanol Versus Hypertonic Glucose for Treatment of Reticular Veins
NCT02462720	PHASE4	COMPLETED	COMFORT: A Multicenter, Open-label, Randomized, Crossover Study
NCT02627846	PHASE4	COMPLETED	Laser Ablation Versus Mechanochemical Ablation Trial
NCT02657252	PHASE4	COMPLETED	Polidocanol Versus Glucose Treatment of Telangiectasia Trial
NCT02988063	PHASE4	WITHDRAWN	Effect of PEM Treatment of Superficial Axial and Tributary Vein Reflux on Improvement of Wound Healing in VLUs
NCT03416413	PHASE4	RECRUITING	Study of Foam Sclerotherapy Versus Ambulatory Phlebectomy
NCT05312970	PHASE4	TERMINATED	Varithena Versus Endothermal Ablation of the Great Saphenous Vein (VERITAS)
NCT05735639	PHASE4	RECRUITING	THRomboprophylaxis in Individuals Undergoing Superficial endoVEnous Treatment (THRIVE)
NCT05832580	PHASE3	RECRUITING	The Prevention of Systemic Ectopic Mineralization in Pseudoxanthoma Elasticum
NCT06046820	PHASE3	ACTIVE_NOT_RECRUITING	The ENERGY 3 Study: Evaluation of Efficacy and Safety of INZ-701 in Children With ENPP1 Deficiency
NCT04224207	PHASE3	COMPLETED	Management of Retinitis Pigmentosa by Mesenchymal Stem Cells by Wharton’s Jelly Derived Mesenchymal Stem Cells
NCT07082855	PHASE3	NOT_YET_RECRUITING	A Multicenter, Randomized, Double-Blind, Controlled Clinical Study of Minocycline for the Treatment of Retinitis Pigmentosa
NCT00500669	PHASE3	TERMINATED	A Randomised Study to Assess Betadine in the Groin Wound of Patients Undergoing Primary Varicose Vein Surgery
NCT01072877	PHASE3	COMPLETED	Efficacy and Safety Study of Polidocanol Injectable Foam for the Treatment of Saphenofemoral Junction (SFJ) Incompetence
NCT01203397	PHASE3	WITHDRAWN	Safety And Efficacy Study Of Topic Mucopolysaccharide Polysulfate In The Superficial Varicose Veins Treatment
NCT01231373	PHASE3	COMPLETED	Polidocanol Endovenous Microfoam (PEM) Versus Vehicle for the Treatment of Saphenofemoral Junction (SFJ) Incompetence
NCT01426035	PHASE3	WITHDRAWN	Safety And Efficacy Study Of Topic Mucopolysaccharide Polysulfate Cream In The Superficial Varicose Veins Treatment
NCT01525875	PHASE2	COMPLETED	Magnesium Supplements In The Treatment Of Pseudoxanthoma Elasticum (PXE)
NCT02537054	PHASE2	COMPLETED	Intravitreal Aflibercept for Therapy of Patients With Pseudoxanthoma Elasticum (PXE)
NCT04441671	PHASE2	WITHDRAWN	Oral Pyrophosphate Absorption in PXE Disease
NCT05569252	PHASE2	COMPLETED	A Study of DS-1211b in Individuals With PseudoXanthoma Elasticum
NCT06462547	PHASE2	RECRUITING	ADAPT Study: Long-term Safety Study of INZ-701 in Patients With ENPP1 Deficiency and ABCC6 Deficiency
NCT03763227	PHASE2	COMPLETED	Intravitreal Ranibizumab (Lucentis®) in the Treatment of Non-leaking Macular Cysts in Retinal Dystrophy
NCT04068207	PHASE2	COMPLETED	Minocycline Treatment in Retinitis Pigmentosa
NCT04945772	PHASE2	COMPLETED	Efficacy and Safety of MCO-010 Optogenetic Therapy in Adults With Retinitis Pigmentosa [RESTORE]
NCT01373476	PHASE2	COMPLETED	Multicentre, Randomized, Controlled Trial of Qideng Mingmu Capsule in The Treatment of Diabetic Retinopathy
NCT01793090	PHASE2	COMPLETED	EPI-743 in Cobalamin C Defect: Effects on Visual and Neurological Impairment
NCT00430326	PHASE2	COMPLETED	Juvista (Avotermin) in Scars Following Varicose Vein Removal
NCT00442364	PHASE2	COMPLETED	Safety Study of Varisolve® Procedure for Treatment of Varicose Veins in Patients With Right-to-left Cardiac Shunt
NCT00928421	PHASE2	COMPLETED	An Open-label, Single-dose Pilot Study to Evaluate Varisolve® (Polidocanol Endovenous Microfoam (PEM)) 0.125% [0.2%] for Varicose Veins
NCT02139085	PHASE2	UNKNOWN	Great Saphenous Vein Electrocoagulation
NCT04203043	PHASE2	UNKNOWN	The Prevstain Trial
NCT05734196	PHASE1	RECRUITING	The ENERGY Study: Evaluation of Safety and Tolerability of INZ-701 in Infants With ENPP1 Deficiency or ABCC6 Deficiency
NCT05902962	PHASE1	COMPLETED	SAD of IVT VP-001 in PRPF31 Mutation-Associated Retinal Dystrophy Subjects
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