ABCC6: ATP Binding Cassette Subfamily C Member 6
Key regulator of systemic calcification and connective tissue homeostasis
Gene Information Card
| Symbol | ABCC6 |
|---|---|
| Full Name | ATP binding cassette subfamily C member 6 |
| Gene Type | protein-coding |
| Chromosomal Location | 16p13.11 |
| NCBI Gene ID | 368 ncbi.nlm.nih.gov/gene/368 |
| Ensembl ID | ENSG00000125257 |
| UniProt ID | O95255 |
| OMIM ID | 603234 |
| HGNC ID | 57 |
| Aliases | MRP6, ABC34, EST349056, MOAT-E, MLP1, PXE, PXE1, URG7 |
Description
The ABCC6 gene encodes the multidrug resistance-associated protein 6 (MRP6), an ATP-binding cassette (ABC) transporter primarily expressed in the liver and kidneys. MRP6 is involved in the transport of organic anions and is critical for systemic regulation of ectopic calcification. Loss-of-function mutations in ABCC6 cause pseudoxanthoma elasticum (PXE), a disorder characterized by progressive calcification of elastic fibers in the skin, eyes, and blood vessels. The gene spans approximately 73 kb and contains 31 exons.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Pseudoxanthoma elasticum (PXE) | Loss-of-function mutations in ABCC6 impair hepatic secretion of calcification inhibitors (e.g., inorganic pyrophosphate), leading to ectopic mineralization of connective tissues. | OMIM #264800; ClinVar; multiple peer-reviewed studies |
| Generalized arterial calcification of infancy (GACI) | Biallelic ABCC6 mutations can present with severe arterial calcification in infancy, overlapping with PXE phenotype. | OMIM #208000; case reports in ClinVar |
| Age-related macular degeneration (AMD) | ABCC6 variants may confer susceptibility to AMD through altered systemic calcification regulation. | GWAS studies; ClinVar association data |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 14.3 | High |
| Kidney | 8.7 | Medium |
| Adrenal gland | 4.2 | Low |
| Lung | 2.1 | Low |
| Heart | 1.5 | Not detected |
| Brain | 0.8 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 (liver) | 12.1 | High expression; used for functional studies |
| HEK293 (embryonic kidney) | 6.5 | Moderate expression; common overexpression model |
| A549 (lung) | 1.2 | Low expression |
| HeLa (cervical) | 0.9 | Very low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.3421C>T (p.Arg1141X) | Nonsense | ~25% of PXE alleles in European populations | Premature stop; loss of transporter function |
| c.1552C>T (p.Arg518X) | Nonsense | ~5% of PXE alleles | Loss of function |
| c.2787+1G>T | Splice site | ~10% of PXE alleles | Exon skipping; frameshift; loss of function |
| c.1132C>T (p.Gln378X) | Nonsense | Rare | Loss of function |
| c.3940C>T (p.Arg1314Trp) | Missense | Rare | Reduced transport activity |
Mutation functional classification
Loss of Function (LOF)
Majority of ABCC6 mutations are loss-of-function (nonsense, frameshift, splice-site, missense with impaired transport), leading to reduced or absent MRP6 activity and subsequent ectopic calcification.
Gain of Function (GOF)
No gain-of-function mutations have been reported for ABCC6.
Dominant Negative (DN)
No dominant-negative mechanisms have been described; PXE is autosomal recessive, requiring biallelic loss-of-function.
View complete mutation data：
Gene Ontology (GO)
| • ATP binding | • ATPase activity coupled to transmembrane movement of substances |
| • xenobiotic transmembrane transporter activity | • organic anion transport |
| • response to xenobiotic stimulus | • cellular response to drug |
| • plasma membrane | • basolateral plasma membrane |
| • extracellular exosome |
Pathways
• ABC transporters (KEGG: hsa02010)
• Bile secretion (KEGG: hsa04976)
• Transport of organic anions (Reactome: R-HSA-879518)
Protein Summary
MRP6 (ABCC6) is a 1503-amino acid transmembrane protein belonging to the ABC transporter family. It is predominantly expressed on the basolateral membrane of hepatocytes and renal proximal tubule cells. MRP6 mediates the efflux of organic anions, including glutathione conjugates and likely the calcification inhibitor inorganic pyrophosphate (PPi). The protein consists of two nucleotide-binding domains (NBDs) and two transmembrane domains (TMDs), with an additional N-terminal TMD0 domain. Mutations disrupting ATP binding or substrate transport lead to PXE. MRP6 also plays a role in drug resistance and cellular detoxification.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| ABCC6 Knockout HEK293 Cell Line | EDJ-KQ4078 | Human | 368 | Details Get a Quote |
| ABCC6 Knockout A-549 Cell Line | EDJ-KQ26448 | Human | 368 | Details Get a Quote |
| ABCC6 Knockout HCT 116 Cell Line | EDJ-KQ26449 | Human | 368 | Details Get a Quote |
| ABCC6 Knockout HeLa Cell Line | EDJ-KQ26450 | Human | 368 | Details Get a Quote |
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