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7 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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PPM1M
protein phosphatase, Mg2+/Mn2+ dependent 1M
Chromosome 3 · 3p21.2
NCBI Gene: 132160Ensembl: ENSG00000164088.19HGNC: HGNC:26506UniProt: Q96MI6
18PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
protein serine/threonine phosphatase activitymanganese ion bindingprotein dephosphorylationnucleuscancerneoplasmParkinson diseaseschizophrenia
✦AI Summary

PPM1M is a serine/threonine protein phosphatase belonging to the metal-dependent PPM (PP2C) family that binds manganese and magnesium ions in its catalytic center to dephosphorylate target proteins 1. As a member of the PPM1H/PPM1J/PPM1M phylogenetic class, PPM1M functions as a single-subunit enzyme with a conserved catalytic core containing metal-chelating residues 1. PPM1M exhibits substrate selectivity, preferentially dephosphorylating phosphorylated Rab12 (phosphoRab12) while also acting on phosphoRab8A and phosphoRab10 2. This activity positions PPM1M as a key regulator of the LRRK2 signaling pathway, which controls receptor trafficking through Rab GTPase phosphorylation 2. Functionally, PPM1M participates in cellular processes including control of cilia biology—PPM1M knockout leads to primary cilia loss in striatal interneurons 2. Disease relevance includes Parkinson's disease, where rare PPM1M mutations showing catalytic inactivity have been identified in patients 2. Beyond neurological disorders, PPM1M demonstrates involvement in viral pathogenesis, with PPM1M downregulation inhibiting HSV-1 replication in astrocytes 3. In cancer contexts, PPM1M expression is typically reduced in tumors versus normal tissues and correlates with patient prognosis and tumor immune infiltration patterns 4, suggesting potential immunological and prognostic significance.

Sources cited
1
PPM1M is a Ser/Thr phosphatase that binds Mn2+/Mg2+ ions, belongs to PPM1H/PPM1J/PPM1M phylogenetic class, and functions as a single-subunit enzyme with conserved catalytic core
PMID: 32650009
2
PPM1M is a phosphoRab12-preferring phosphatase that also acts on phosphoRab8A and phosphoRab10; PPM1M knockout causes primary cilia loss; rare catalytically inactive PPM1M mutations identified in Parkinson's disease patients
PMID: 40690364
3
PPM1M downregulation significantly inhibits HSV-1 replication in astrocytes, suggesting a role in viral pathogenesis
PMID: 24260274
4
PPM1M expression is higher in normal tissues than cancerous tissues and is associated with patient prognosis, immune checkpoint markers, and tumor-infiltrating immune cells
PMID: 36961170
5
PPM1M serves as an efficient substrate for phosphatase activity detection assays
PMID: 27565380
Disease Associationsⓘ20
cancerOpen Targets
0.07Suggestive
neoplasmOpen Targets
0.07Suggestive
Parkinson diseaseOpen Targets
0.07Suggestive
schizophreniaOpen Targets
0.06Suggestive
Okt4 epitope deficiencyOpen Targets
0.06Suggestive
bipolar disorderOpen Targets
0.05Suggestive
neutropenia, severe congenital, 2, autosomal dominantOpen Targets
0.04Suggestive
combined immunodeficiency with skin granulomasOpen Targets
0.04Suggestive
Abnormality of the skeletal systemOpen Targets
0.03Suggestive
AnxietyOpen Targets
0.03Suggestive
reticular dysgenesisOpen Targets
0.03Suggestive
diverticular diseaseOpen Targets
0.02Suggestive
obesityOpen Targets
0.02Suggestive
urinary bladder carcinomaOpen Targets
0.02Suggestive
lung adenocarcinomaOpen Targets
0.01Suggestive
SepsisOpen Targets
0.01Suggestive
bladder transitional cell carcinomaOpen Targets
0.01Suggestive
glioblastoma multiformeOpen Targets
0.01Suggestive
ParagangliomaOpen Targets
0.01Suggestive
pheochromocytomaOpen Targets
0.01Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
PTPN4Shared pathway100%CTDSP2Shared pathway100%PTPN18Shared pathway100%DAPP1Shared pathway100%CTDSP1Shared pathway100%PTPN5Shared pathway100%
Tissue Expression6 tissues
Lung
100%
Bone Marrow
81%
Ovary
66%
Heart
45%
Liver
23%
Brain
17%
Gene Interaction Network
Click a node to explore
PPM1MPTPN4CTDSP2PTPN18DAPP1CTDSP1PTPN5
PROTEIN STRUCTURE
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AlphaFoldAI-predicted · UniProt Q96MI6
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
1.11LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.86 [0.67–1.11]
RankingsWhere PPM1M stands among ~20K protein-coding genes
  • #14,780of 20,598
    Most Researched18
  • #11,382of 17,882
    Most Constrained (LOEUF)1.11
Genes detectedPPM1M
Sources retrieved7 papers
Response time—
📄 Sources
7▼
1
Metal-dependent Ser/Thr protein phosphatase PPM family: Evolution, structures, diseases and inhibitors.
PMID: 32650009
Pharmacol Ther · 2020
1.00
2
PPM1M, an LRRK2-counteracting, phosphoRab12-preferring phosphatase with a potential link to Parkinson's disease.
PMID: 40690364
Cell Rep · 2025
0.86
3
Phosphorylated TandeMBP: A unique protein substrate for protein phosphatase assay.
PMID: 27565380
Anal Biochem · 2016
0.71
4
Novel progressive acrodysostosis-like skeletal dysplasia, cerebellar atrophy, and ichthyosis.
PMID: 32783359
Am J Med Genet A · 2020
0.57
5
Identification of hub genes in peripheral blood mononuclear cells for the diagnosis of hepatocellular carcinoma using a weighted gene co-expression network analysis.
PMID: 32742331
Exp Ther Med · 2020
0.43