GENE REFERENCE / HGNC:9277

PPM1D

protein phosphatase, Mg2+/Mn2+ dependent 1D

protein-coding gene17q23.3Gene information

What does this gene do?

The PPM1D gene provides instructions for making an enzyme called protein phosphatase 1D. This enzyme plays an essential role in cell division, immune cell development, gene expression, and the process by which cells create energy from food (metabolism). This enzyme is present in many of the body's tissues, including the developing brain.

Protein phosphatase 1D belongs to a group of enzymes known as the PP2C phosphatases, which help regulate cell development in response to environmental stress. The PP2C phosphatases turn on (activate) after attaching (binding) to charged molecules (ions) of manganese or magnesium. The activated enzyme can then regulate the activity of other proteins by removing a cluster of oxygen and phosphorous atoms (phosphate group) from that protein. This regulation helps repair DNA damage and return the cell to its normal state.

Protein phosphatase 1D specifically regulates tumor suppressors, such as tumor protein p53. Tumor suppressors are proteins that keep cells from growing and dividing too fast or in an uncontrolled way. By stopping cells with damaged DNA from dividing, tumor suppressors help prevent the development of tumors. Protein phosphatase 1D turns off proteins such as tumor protein p53 when they are no longer needed, which allows cells to continue growing and dividing.

Protein phosphatase 1D is also thought to play a role in regulating areas of tightly packed DNA called heterochromatin. Because gene expression is lower when DNA is tightly packed than when DNA is loosely packed, protein phosphatase 1D helps to turn off (silence) regions of DNA that are not needed.

Source: MedlinePlus, National Library of Medicine. Source publication: 2025-03-17. Source review: 2025-03.

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
syndromic intellectual disabilityMONDO:0000508 · Evaluated 2022-02-15	Autosomal dominant	DefinitiveIntellectual Disability and Autism 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: 463
Submissions for variants in or overlapping this gene: 643
Submissions explicitly reporting this gene: 594
Alleles reported pathogenic / likely pathogenic: 76
VariationIDs with uncertain significance: 171
VariationIDs with conflicting classifications: 26

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 PPM1D?

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 76 alleles in PPM1D 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 PPM1D.

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

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