Laboratory for Molecular Diagnostics
Center for Nephrology and Metabolic Disorders

Ectonucleotide pyrophosphatase/phosphodiesterase 1

The gene ENPP1 encodes a transmembrane glycoprotein that cleaved various phosphodiesterbounds. Mutations are responsible for autosomal recessive hypophosphatemic rickets type 2 and for also recessive general calcification of infancy type 1. Also it is a risk gene for obesity and insulin resistance.

Genetests:

Clinic Method Carrier testing
Turnaround 5 days
Specimen type genomic DNA
Clinic Method Genomic sequencing of the entire coding region
Turnaround 25 days
Specimen type genomic DNA
Clinic Method Massive parallel sequencing
Turnaround 25 days
Specimen type genomic DNA

Related Diseases:

Autosomal recessive hypophosphatemic rickets type 2
ENPP1
Insulin resistance
CIDEC
Diabetes mellitus with insulin resistance and acanthosis nigricans
INSR
ENPP1
IRS1
IRS2
PPARG
Generalized arterial calcification of infancy 1
ENPP1
Susceptibility to obesity
ADRB2
ADRB3
CARTPT
ENPP1
GHRL
PPARGC1B
SDC3
UCP1

References:

1.

Abate N et al. (2003) Genetic polymorphism PC-1 K121Q and ethnic susceptibility to insulin resistance.

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2.

Nakamura I et al. (1999) Association of the human NPPS gene with ossification of the posterior longitudinal ligament of the spine (OPLL).

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3.

Pizzuti A et al. (1999) A polymorphism (K121Q) of the human glycoprotein PC-1 gene coding region is strongly associated with insulin resistance.

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4.

Maddux BA et al. (2000) Membrane glycoprotein PC-1 inhibition of insulin receptor function occurs via direct interaction with the receptor alpha-subunit.

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5.

Rutsch F et al. (2001) PC-1 nucleoside triphosphate pyrophosphohydrolase deficiency in idiopathic infantile arterial calcification.

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6.

Frittitta L et al. (2001) The Q121 PC-1 variant and obesity have additive and independent effects in causing insulin resistance.

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7.

Koshizuka Y et al. (2002) Nucleotide pyrophosphatase gene polymorphism associated with ossification of the posterior longitudinal ligament of the spine.

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8.

Rutsch F et al. (2003) Mutations in ENPP1 are associated with 'idiopathic' infantile arterial calcification.

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9.

Buckley MF et al. (1992) Plasma cell membrane glycoprotein gene Pca-1 (alkaline phosphodiesterase I) is linked to the proto-oncogene Myb on mouse chromosome 10.

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10.

Meyre D et al. (2004) A genome-wide scan for childhood obesity-associated traits in French families shows significant linkage on chromosome 6q22.31-q23.2.

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11.

Hamaguchi K et al. (2004) The PC-1 Q121 allele is exceptionally prevalent in the Dominican Republic and is associated with type 2 diabetes.

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12.

Kubaszek A et al. (2004) The association of the K121Q polymorphism of the plasma cell glycoprotein-1 gene with type 2 diabetes and hypertension depends on size at birth.

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13.

Dong H et al. (2005) Increased hepatic levels of the insulin receptor inhibitor, PC-1/NPP1, induce insulin resistance and glucose intolerance.

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14.

Meyre D et al. (2005) Variants of ENPP1 are associated with childhood and adult obesity and increase the risk of glucose intolerance and type 2 diabetes.

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15.

Rebbe NF et al. (1991) Identification of nucleotide pyrophosphatase/alkaline phosphodiesterase I activity associated with the mouse plasma cell differentiation antigen PC-1.

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16.

Keshavarz P et al. (2006) No evidence for association of the ENPP1 (PC-1) K121Q variant with risk of type 2 diabetes in a Japanese population.

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17.

Horikoshi T et al. (2006) A large-scale genetic association study of ossification of the posterior longitudinal ligament of the spine.

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18.

Böttcher Y et al. (2006) ENPP1 variants and haplotypes predispose to early onset obesity and impaired glucose and insulin metabolism in German obese children.

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19.

Dlamini N et al. (2009) Generalized arterial calcification of infancy: phenotypic spectrum among three siblings including one case without obvious arterial calcifications.

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20.

Levy-Litan V et al. (2010) Autosomal-recessive hypophosphatemic rickets is associated with an inactivation mutation in the ENPP1 gene.

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21.

Lorenz-Depiereux B et al. (2010) Loss-of-function ENPP1 mutations cause both generalized arterial calcification of infancy and autosomal-recessive hypophosphatemic rickets.

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22.

Buckley MF et al. (1990) Plasma cell membrane glycoprotein PC-1. cDNA cloning of the human molecule, amino acid sequence, and chromosomal location.

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23.

van Driel IR et al. (1987) Plasma cell membrane glycoprotein PC-1. Primary structure deduced from cDNA clones.

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24.

Harahap AR et al. (1988) Distribution of the murine plasma cell antigen PC-1 in non-lymphoid tissues.

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25.

Takahashi T et al. (1970) Surface alloantigens of plasma cells.

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26.

Sakaguchi AY et al. (1984) Chromosome assignments of four mouse cellular homologs of sarcoma and leukemia virus oncogenes.

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27.

Kahn CR et al. (1995) Diabetes. Causes of insulin resistance.

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28.

Maddux BA et al. (1995) Membrane glycoprotein PC-1 and insulin resistance in non-insulin-dependent diabetes mellitus.

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29.

Huang R et al. (1994) Expression of the murine plasma cell nucleotide pyrophosphohydrolase PC-1 is shared by human liver, bone, and cartilage cells. Regulation of PC-1 expression in osteosarcoma cells by transforming growth factor-beta.

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30.

Okawa A et al. (1998) Mutation in Npps in a mouse model of ossification of the posterior longitudinal ligament of the spine.

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Update: Sept. 26, 2018