GENE REFERENCE / HGNC:3356

ENPP1

ectonucleotide pyrophosphatase/phosphodiesterase 1

protein-coding gene6q23.2Gene information

What does this gene do?

The ENPP1 gene provides instructions for making a protein that helps break down a molecule called adenosine triphosphate (ATP). Specifically, the ENPP1 protein breaks down ATP that is found outside of cells (extracellular). Extracellular ATP is quickly broken down into other molecules called adenosine monophosphate (AMP) and pyrophosphate. Pyrophosphate is important for preventing the accumulation of abnormal deposits of calcium (calcification) and other minerals (mineralization) in the body.

The ENPP1 protein also plays a role in the cell signaling that occurs in response to the hormone insulin. Part of the ENPP1 protein, called the SMB2 domain, interacts with the insulin receptor, which is a protein that binds to insulin and initiates cell signaling. Insulin plays many roles in the body. It helps regulate levels of blood glucose (also called blood sugar) by controlling how much glucose passes from the bloodstream into cells to be used as energy. Insulin is also important for the maintenance of the outer layer of skin (the epidermis). It helps control the transport of the pigment melanin from the cells that produce it (melanocytes) to epidermal cells called keratinocytes. Insulin is also involved in the development of keratinocytes.

Source: MedlinePlus, National Library of Medicine. Source publication: 2026-03-19. Source review: 2026-03.

ClinGen reviews

ClinGen reviews the evidence linking a particular gene to a condition. Each rating below describes the strength of that link. It does not classify a variant in your DNA file.

Condition	Inheritance	Evidence
arterial calcification, generalized, of infancy, 1MONDO:0008817 · Evaluated 2025-11-23	Autosomal recessive	DefinitiveSyndromic Disorders Gene Curation Expert Panel
hypopigmentation-punctate palmoplantar keratoderma syndromeMONDO:0014227 · Evaluated 2022-06-17	Autosomal dominant	LimitedSyndromic Disorders Gene Curation Expert Panel

ClinVar records

These numbers show what has been submitted to ClinVar. They cannot tell you how likely you are to have a condition.

Submitted alleles: 1,001
Submissions for variants in or overlapping this gene: 1,679
Submissions explicitly reporting this gene: 1,613
Alleles reported pathogenic / likely pathogenic: 103
VariationIDs with uncertain significance: 433
VariationIDs with conflicting classifications: 60

The rows count different things: alleles, submissions or VariationIDs. Their categories can overlap, so do not add them together. Pathogenic/likely pathogenic counts exclude structural variants that merely overlap a gene. A dash in the source means “not reported,” not zero.

NCBI produces the gene-summary file each week using counts recorded at the start of the month. The numbers may differ from those on the live ClinVar website. Read the field definitions ↗

View this gene in ClinVar ↗

YOUR DNA FILE

Can your DNA file tell you about ENPP1?

From a DNA test kit (such as 23andMe, AncestryDNA or MyHeritage). These kits check a fixed list of about 600,000 to 700,000 positions across your whole genome. ClinVar lists 103 alleles in ENPP1 reported as pathogenic or likely pathogenic. A kit checks only some of these positions, and often none of them.

From whole genome sequencing (a VCF file). Sequencing reads most of your genome. Your file lists the places where your DNA differs from the reference genome. Some regions are hard to sequence, including parts of some genes that have near-identical copies elsewhere, and a VCF file does not record which positions were read well.

If a variant is not in your file, that does not mean you don’t have it.

What BioDecode checks

BioDecode compares every variant in your file with ClinVar, on your own computer. For each match, it shows the ClinVar classification, the review status and the condition it was reported for. Your file is not uploaded.

A ClinVar classification applies to one particular variant and the condition it was reported for. It does not tell you about other variants in ENPP1.

BioDecode cannot fill gaps in your test, diagnose a condition or replace clinical testing.

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