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ABCC6

ATP binding cassette subfamily C member 6

The ABCC6 gene encodes the MRP6 protein, which plays a role in the transport of molecules across cell membranes and is important for preventing abnormal mineralisation in the body. The ABCC6 gene is responsible for producing the multidrug resistance-associated protein 6 (MRP6), primarily found in the liver and kidneys.

Chromosome 16p13.11 HGNC:57 Tier C
ABCC6 16p13.11 p arm q arm 16

ABCC6 is located on the short (p) arm of chromosome 16, at band 16p13.11. Arm ratio per GRCh38 - banding schematic.

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Clinical tests that include this

Carrier Screening panel
ABCC6 is 1 of 1,008 genes on this panel
Expanded carrier screening for recessive and X-linked conditions

Overview

The ABCC6 gene, or ATP binding cassette subfamily C member 6, provides the blueprint for the MRP6 protein. This protein is predominantly expressed in the liver and kidneys, with smaller amounts detected in tissues like the skin, stomach, blood vessels, and eyes. Its primary function involves transporting molecules across cell membranes, contributing to the regulation of mineralisation within the body.

What the gene does

The MRP6 protein, encoded by the ABCC6 gene, functions as a transporter, facilitating the movement of specific molecules across cellular membranes. While the exact substances it transports are not fully understood, research suggests it might be involved in releasing adenosine triphosphate (ATP) from cells. This ATP is rapidly broken down into other molecules, including pyrophosphate, which is known to help control the deposition of calcium and other minerals. Alternatively, some studies propose that MRP6 transports an unknown substance vital for ATP breakdown, which subsequently aids in preventing tissue mineralisation.

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Chromosome location

The ABCC6 gene is located on chromosome 16, specifically at band 16p13.11. This position within the human genome dictates where the gene resides and is organised.

Protein structure

The ABCC6 protein has a total length of 1503 amino acids and features several distinct domains critical for its function. It contains two ABC transmembrane type-1 domains, located at amino acids 311-593 and 947-1228, respectively. Additionally, there are two ABC transporter domains, found at amino acids 629-853 and 1265-1499. A disordered region is also present between amino acids 854-919.

Domain map · 1,503 amino acids
ABC transmembrane type-1 1 (311–593)ABC transporter 1 (629–853)ABC transmembrane type-1 2 (947–1228)ABC transporter 2 (1265–1499)ABC transmembrane type311–593ABC transmembrane type947–1228ABC transporter 21265–14991~7521,503
Domain - independent functional unit
🧬 Explore 3D structure on AlphaFold
UniProt:O95255Length:1,503 aaStructure:AlphaFold

Key variants

Variants within the ABCC6 gene can alter the function of the MRP6 protein, leading to a range of health implications. These genetic changes can affect the protein's ability to transport molecules effectively or its role in preventing mineralisation, contributing to various inherited conditions.

1,804
Total variants catalogued in ClinVar
View all on ClinVar →
300 Pathogenic / Likely pathogenic 744 Uncertain significance 679 Benign / Likely benign 81 Conflicting or other

Sample of pathogenic variants

10 pathogenic / likely-pathogenic variants from ClinVar, ranked by review status (expert-panel-reviewed first). This is a sample; recurrent founder variants in a specific population may not appear here - see the full ClinVar listing via the link above.

Variant (HGVS) Protein change Classification Evidence Associated condition
c.105del
Deletion
 p.Val37fs Pathogenic ★★☆☆ Autosomal recessive inherited pseudoxanthoma elasticum
c.1087C>T
single nucleotide variant
 p.Gln363Ter Pathogenic ★★☆☆ Autosomal recessive inherited pseudoxanthoma elasticum
c.1132C>T
single nucleotide variant
 p.Gln378Ter Pathogenic ★★☆☆ not provided
c.1255C>T
single nucleotide variant
 p.Arg419Trp Pathogenic/Likely pathogenic ★★☆☆ not provided
c.1256G>A
single nucleotide variant
 p.Arg419Gln Pathogenic/Likely pathogenic ★★☆☆ Autosomal recessive inherited pseudoxanthoma elasticum
c.1288del
Deletion
 p.Leu430fs Pathogenic/Likely pathogenic ★★☆☆ Pseudoxanthoma elasticum, forme fruste
c.1334G>A
single nucleotide variant
 p.Trp445Ter Pathogenic/Likely pathogenic ★★☆☆ ABCC6-related disorder
c.1460G>A
single nucleotide variant
 p.Arg487Gln Pathogenic/Likely pathogenic ★★☆☆ Autosomal recessive inherited pseudoxanthoma elasticum
c.1484T>A
single nucleotide variant
 p.Leu495His Pathogenic/Likely pathogenic ★★☆☆ Autosomal recessive inherited pseudoxanthoma elasticum
c.1552C>T
single nucleotide variant
 p.Arg518Ter Pathogenic ★★☆☆ Autosomal recessive inherited pseudoxanthoma elasticum

Evidence stars indicate ClinVar review status. Individual variant interpretation should always be performed by a qualified clinical laboratory - many variants remain classified as Variants of Uncertain Significance (VUS) pending more research.

Associated conditions

Pathogenic variants in the ABCC6 gene are associated with several inherited conditions, including pseudoxanthoma elasticum and generalised arterial calcification of infancy. These conditions are characterised by abnormal accumulation of calcium and other minerals in various tissues, highlighting the critical role of ABCC6 in mineral homeostasis.

No disease links recorded for this gene in our reference set.

UK clinical status

The ABCC6 gene is included in several NHS Genomic Medicine Service national test directories via PanelApp. It is rated 'green' for conditions such as DDG2P, Familial cerebral small vessel disease, Foetal anomalies (R21), Generalised arterial calcification in infancy (R384), Pseudoxanthoma elasticum (R420), and Retinal disorders (R32), indicating strong evidence for its clinical utility in these contexts.

Green-listed
High evidence · clinically actionable in NHS testing
Included in NHS GMS signed-off panels
Fetal anomalies · R21 NHS GMS → Generalised arterial calcification in infancy · R384 NHS GMS → Pseudoxanthoma elasticum · R420 NHS GMS → Retinal disorders · R32 NHS GMS → DDG2P NHS GMS →
NHS Genomic Medicine Service Jeen carrier screening

Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory

Frequently asked questions

What is the main function of the ABCC6 gene?

The ABCC6 gene provides instructions for the MRP6 protein, which transports molecules across cell membranes and helps regulate the deposition of calcium and other minerals, preventing abnormal mineralisation in tissues.

Which conditions are associated with variants in the ABCC6 gene?

Variants in the ABCC6 gene are primarily associated with pseudoxanthoma elasticum and generalised arterial calcification of infancy, both of which involve abnormal calcium accumulation.

Where is the ABCC6 protein primarily found in the body?

The MRP6 protein, encoded by the ABCC6 gene, is predominantly found in the liver and kidneys, with smaller amounts present in other tissues like the skin, stomach, blood vessels, and eyes.

References

  1. Li Q, Brodsky JL, Conlin LK. Mutations in the ABCC6 gene as a cause of generalized arterial calcification of infancy: genotypic overlap with pseudoxanthoma elasticum. The Journal of investigative dermatology. 2014. PMID: 24008425
  2. Dabisch-Ruthe M, Kuzaj P, Götting C. Pyrophosphates as a major inhibitor of matrix calcification in Pseudoxanthoma elasticum. Journal of dermatological science. 2014. PMID: 24907773
  3. Jansen RS, Duijst S, Mahakena S. ABCC6-mediated ATP secretion by the liver is the main source of the mineralization inhibitor inorganic pyrophosphate in the systemic circulation-brief report. Arteriosclerosis, thrombosis, and vascular biology. 2014. PMID: 24969777
  4. Jansen RS, Küçükosmanoglu A, de Haas M. ABCC6 prevents ectopic mineralization seen in pseudoxanthoma elasticum by inducing cellular nucleotide release. Proceedings of the National Academy of Sciences of the United States of America. 2013. PMID: 24277820
  5. Nitschke Y, Baujat G, Botschen U. Generalized arterial calcification of infancy and pseudoxanthoma elasticum can be caused by mutations in either ENPP1 or ABCC6. American journal of human genetics. 2012. PMID: 22209248
  6. Markello TC, Pak LK, St Hilaire C. Vascular pathology of medial arterial calcifications in NT5E deficiency: implications for the role of adenosine in pseudoxanthoma elasticum. Molecular genetics and metabolism. 2011. PMID: 21371928
  7. Hendig D, Schulz V, Arndt M. Role of serum fetuin-A, a major inhibitor of systemic calcification, in pseudoxanthoma elasticum. Clinical chemistry. 2006. PMID: 16384891
  8. Chassaing N, Martin L, Calvas P. Pseudoxanthoma elasticum: a clinical, pathophysiological and genetic update including 11 novel ABCC6 mutations. Journal of medical genetics. 2005. PMID: 15894595
  9. Miksch S, Lumsden A, Guenther UP. Molecular genetics of pseudoxanthoma elasticum: type and frequency of mutations in ABCC6. Human mutation. 2005. PMID: 16086317
  10. Matsuzaki Y, Nakano A, Jiang QJ. Tissue-specific expression of the ABCC6 gene. The Journal of investigative dermatology. 2005. PMID: 16297187
  11. Bercovitch L, Terry P. Pseudoxanthoma elasticum 2004. Journal of the American Academy of Dermatology. 2004. PMID: 15243491
  12. Hu X, Plomp A, Wijnholds J. ABCC6/MRP6 mutations: further insight into the molecular pathology of pseudoxanthoma elasticum. European journal of human genetics : EJHG. 2003. PMID: 12673275
  13. Hu X, Plomp AS, van Soest S. Pseudoxanthoma elasticum: a clinical, histopathological, and molecular update. Survey of ophthalmology. 2003. PMID: 12850230
  14. Iliás A, Urbán Z, Seidl TL. Loss of ATP-dependent transport activity in pseudoxanthoma elasticum-associated mutants of human ABCC6 (MRP6). The Journal of biological chemistry. 2002. PMID: 11880368
  15. Le Saux O, Beck K, Sachsinger C. A spectrum of ABCC6 mutations is responsible for pseudoxanthoma elasticum. American journal of human genetics. 2001. PMID: 11536079
  16. Bergen AA, Plomp AS, Schuurman EJ. Mutations in ABCC6 cause pseudoxanthoma elasticum. Nature genetics. 2000. PMID: 10835643
  17. Adam MP, Bick S, Mirzaa GM. Pseudoxanthoma Elasticum. 1993. PMID: 20301292
  18. Adam MP, Bick S, Mirzaa GM. Generalized Arterial Calcification of Infancy. 1993. PMID: 25392903
Educational content. This page is not medical or genetic advice, is not individually reviewed by a clinician for each reader, and should not replace a consultation with a qualified healthcare professional or genetic counsellor. If you are considering genetic testing or acting on a test result, book a consultation.
Data sources Last updated 4 October 2026. Content compiled from HGNC · MedlinePlus Genetics · ClinGen · Genomics England PanelApp · NHS National Genomic Test Directory · ClinVar · UniProt · AlphaFold .