ABCC6
- Known as:
- ABCC6
- Catalog number:
- 000912A
- Product Quantity:
- 250ul
- Category:
- -
- Supplier:
- ABM
- Gene target:
- ABCC6
Related genes to: ABCC6
- Gene:
- ABCC6 NIH gene
- Name:
- ATP binding cassette subfamily C member 6
- Previous symbol:
- ARA, PXE
- Synonyms:
- MRP6, EST349056, MLP1, URG7
- Chromosome:
- 16p13.11
- Locus Type:
- gene with protein product
- Date approved:
- 1997-10-27
- Date modifiied:
- 2019-04-23
Related products to: ABCC6
Related articles to: ABCC6
- Pseudoxanthoma elasticum (PXE) is a rare inherited disorder characterized by progressive ectopic calcification of soft connective tissues, including skin, arteries, and eyes, leading to significant morbidity. PXE results from loss of functional ABCC6, a liver specific ATP efflux conduit. Reduced ATP release into the circulation limits its conversion into AMP and the mineralization inhibitor pyrophosphate (PPi). Consequently, low plasma PPi levels drive ectopic calcification in PXE. Although oral PPi supplementation can inhibit ectopic calcification in Abcc6/ mice, impractically high doses are needed, due to its rapid hydrolysis in the gastrointestinal tract. Here, we evaluated phosphocitrate, an exceedingly more potent mineralization inhibitor, in vitro and in Abcc6/ mice. In ATDC5 cells, 1 μM phosphocitrate significantly inhibited mineralization following induction, comparable to approximately tenfold higher concentrations of PPi. In vivo, daily intraperitoneal administration of phosphocitrate (4.7 μmol/kg bw) markedly reduced calcification in muzzle skin and kidneys, whereas an at least fivefold higher dose of PPi was needed to achieve a similar effect. Oral administration required substantially higher doses of both compounds (~2.4 mmol/kg bw), but PC remained more effective than PPi at inhibiting soft tissue calcification in Abcc6/ mice. Importantly, unlike PPi, oral phosphocitrate did not adversely affect skeletal strength or stiffness, even at supraphysiological doses. In summary, phosphocitrate is a more potent inhibitor of ectopic calcification than PPi in Abcc6/ mice. While optimization of oral delivery remains necessary, its increased potency supports the potential of alternative administration routes, including subcutaneous delivery, as a practical therapeutic strategy for PXE. - Source: PubMed
Publication date: 2026/07/16
Rajpar IbtesamShao ChristinaNg CelinaNiaziorimi FatemehBeiriger JacobTurhanen Petrivan de Wetering Koen - Cerebral small vessel diseases (CSVDs) are a group of disorders affecting the small arteries, veins, and capillaries supplying the white matter and deep grey matter structures. They are the most common form of cerebrovascular disease, accounting for approximately half of vascular dementia cases and 20% of stroke incidence. Whilst genetic testing is a routine diagnostic tool for monogenic CSVDs, less than 20% of patients have a causal variant in known CSVD genes. We performed whole exome sequencing on 117 patients suspected of monogenic CSVD who previously tested negative for pathogenic variants in seven well-characterised CSVD genes (NOTCH3, HTRA1, COL4A1, COL4A2, TREX1, GLA, and FOXC1). Targeted analysis was conducted on known and associated CSVD genes, as well as candidate genes which cause conditions with overlapping symptomology to CSVD. Burden analysis focussing on rare, functional variants was used to identify novel associations when compared against a cohort of 1035 non-neurological controls. We identified 18 suspected disease-causing variants across nine CSVD-associated genes and a significant burden of both rare and rare, likely disease-causing heterozygous variants in ABCC6. Two genes from stroke and neurodegenerative disease gene panels also possessed a significant burden of rare, likely disease-causing variants, MYH11 (adjusted P = 1 × 10) and NOTCH1 (adjusted P = 1 × 10). We further identified novel associations for seven genes (COL7A1, HMCN1, LAMA1, MMP9, TENM4, TNC, TTN) with monogenic CSVD in this cohort. Our findings implicate several genes as potentially causal of monogenic CSVD, highlighting the need for more extensive genetic screening in suspected CSVD cases, and functional characterisation of implicated variants to determine their mechanistic role in CSVD pathogenesis. - Source: PubMed
Publication date: 2026/07/21
Guyler Solomon KAlfayyadh Mohammed MMaksemous NevenLea Rodney ASmith Robert ASutherland Heidi GGriffiths Lyn R - - Source: PubMed
Publication date: 2026/07/15
Benchluch AshleyPereira AustinBallios Brian G - Inorganic pyrophosphate (PPi) is a key inhibitor of ectopic calcification, yet transcriptional regulation of genes controlling its systemic production and degradation (ABCC6, ALPL, ANKH, and ENPP1) remains poorly understood. We hypothesized that PPi homeostasis is regulated by an evolutionarily conserved transcription factor (TF) network. Promoter motif analysis combined with ATAC-seq revealed conserved enrichment of TF binding sites, including FOXA1, HNF4A, and SREBF1, across mouse and human orthologues. Bulk and single-cell RNA-seq together with RT-qPCR analyses in wild-type and Abcc6 mice showed hepatocytes as major cell type expressing the most relevant genes maintaining PPi homeostasis. Further inference analysis identifies a conserved transcriptional program that regulates systemic PPi balance across mice and humans. Functionally, mice showed an age-dependent inverse correlation between plasma PPi and serum alkaline phosphatase (AP) activity, strongest during early life. Abcc6 mice displayed persistently reduced but gradually increasing PPi levels and altered Pi/PPi ratios during aging. In humans, plasma PPi correlated inversely with AP activity and positively with Pi in both controls and ABCC6-deficient pseudoxanthoma elasticum patients. Together, these findings support a conserved TF-associated regulatory program linking PPi homeostasis gene expression with circulating mineralization-related factors across physiological and pathological states. - Source: PubMed
Publication date: 2026/07/10
Tamatey VirgilVárhegyi MartinBlaha BenceVan Wynsberghe JudithLion LonaAhmadi ZahiraJuhász DénesBata EmeseTóth Dániel MártonMuazu MuhyiddeenNagy Anikó IlonaMartinez-Jimenez Celia PVanakker OlivierArányi TamásSzeri Flóra - Small effective population size and the disproportionately large use of few genetically superior bulls in artificial insemination lead to extensive runs of homozygosity and an increased risk of homozygosity for deleterious alleles in domestic cattle, which may cause inbreeding depression. The adverse effects of inbreeding on phenotypic performance are well established, but the genetic variants contributing to inbreeding depression remain largely unknown. This study aimed to analyse the impacts of inbreeding on stature (measured as height at the sacral bone) in a cohort of 15,306 Brown Swiss (BS) cows that have imputed genotypes at 20 million sequence variants and stature measurements as height at the sacral bone. - Source: PubMed
Publication date: 2026/06/28
He QiongyuDeuber JessicaSeefried Franz RPausch HubertKadri Naveen Kumar