PPM1H Gene

HGNC Family	Phosphatases
Name	protein phosphatase, Mg2+/Mn2+ dependent, 1H
Description	Enables identical protein binding activity and phosphoprotein phosphatase activity. Predicted to be involved in signal transduction. Located in cytoplasm and nucleoplasm. [provided by Alliance of Genome Resources, Mar 2025]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nPPM1H is a metal‐dependent serine/threonine phosphatase that plays multifaceted roles by counterbalancing phosphorylation‐dependent signaling in diverse cellular settings. In the context of neurodegeneration, PPM1H directly dephosphorylates Rab GTPases that have been hyperphosphorylated by the pathogenic kinase LRRK2. This dephosphorylation restores proper vesicular trafficking and autophagosome transport, with appropriate subcellular localization (including at the Golgi and near mother centrioles) being crucial for efficient substrate targeting."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn oncological studies, PPM1H has emerged as a key modulator of tumor cell behavior. In HER2‐positive breast cancer, for instance, PPM1H dephosphorylates the tumor suppressor p27 at threonine 187, preventing its proteasomal degradation and thereby modulating sensitivity to trastuzumab. Similarly, in colon adenocarcinoma, elevated PPM1H levels and its interaction with the proliferation‐linked factor CSE1L suggest a role in controlling cell cycle progression and apoptosis. In pancreatic cancer cells, reduced expression or silencing of PPM1H triggers epithelial–mesenchymal transition (EMT), which in turn promotes cell invasion, metastasis, and proliferation. Moreover, in non‐small cell lung cancer, higher PPM1H expression correlates with increased proliferation markers and an unfavorable prognosis, underscoring its importance as a potential prognostic factor."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "4", "end_ref": "7"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its roles in neurological and oncological processes, PPM1H also critically regulates growth factor signaling pathways. It acts as a specific cytoplasmic phosphatase for phosphorylated Smad1/5/8, thereby attenuating Bone Morphogenetic Protein (BMP) signal transduction and subsequent gene transcription. By dephosphorylating these transcription factors, PPM1H serves as a gatekeeper that prevents excessive BMP signaling and mesenchymal differentiation under normal physiological conditions, while also offering a potential target for therapeutic modulation in developmental disorders and disease states."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Kerryn Berndsen, Pawel Lis, Wondwossen M Yeshaw, et al. "}, {"type": "b", "children": [{"type": "t", "text": "PPM1H phosphatase counteracts LRRK2 signaling by selectively dephosphorylating Rab proteins."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Elife (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.7554/eLife.50416"}], "href": "https://doi.org/10.7554/eLife.50416"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31663853"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31663853"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Dan Dou, Erin M Smith, Chantell S Evans, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Regulatory imbalance between LRRK2 kinase, PPM1H phosphatase, and ARF6 GTPase disrupts the axonal transport of autophagosomes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Rep (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.celrep.2023.112448"}], "href": "https://doi.org/10.1016/j.celrep.2023.112448"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "37133994"}], "href": "https://pubmed.ncbi.nlm.nih.gov/37133994"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Wondwossen M Yeshaw, Ayan Adhikari, Claire Y Chiang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Localization of PPM1H phosphatase tunes Parkinson's disease-linked LRRK2 kinase-mediated Rab GTPase phosphorylation and ciliogenesis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.2315171120"}], "href": "https://doi.org/10.1073/pnas.2315171120"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "37889931"}], "href": "https://pubmed.ncbi.nlm.nih.gov/37889931"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Takeyuki Sugiura, Yoshie Noguchi, Kayo Sakurai, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Protein phosphatase 1H, overexpressed in colon adenocarcinoma, is associated with CSE1L."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Biol Ther (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4161/cbt.7.2.5302"}], "href": "https://doi.org/10.4161/cbt.7.2.5302"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18059182"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18059182"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Si Tuen Lee-Hoeflich, Thinh Q Pham, Don Dowbenko, et al. "}, {"type": "b", "children": [{"type": "t", "text": "PPM1H is a p27 phosphatase implicated in trastuzumab resistance."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Discov (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1158/2159-8290.CD-11-0062"}], "href": "https://doi.org/10.1158/2159-8290.CD-11-0062"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22586611"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22586611"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Han Zhu, Hua Qin, De-Min Li, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Effect of PPM1H on malignant phenotype of human pancreatic cancer cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncol Rep (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3892/or.2016.5065"}], "href": "https://doi.org/10.3892/or.2016.5065"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27599670"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27599670"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Wen-Qi Zhang, Jian-Nan Gao, Xiang-Lei Chen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "PPM1H is an independent prognostic biomarker of non-small cell lung cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neoplasma (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4149/neo_2021_201117N1238"}], "href": "https://doi.org/10.4149/neo_2021_201117N1238"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33847131"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33847131"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Tao Shen, Chuang Sun, Zhengmao Zhang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Specific control of BMP signaling and mesenchymal differentiation by cytoplasmic phosphatase PPM1H."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Res (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/cr.2014.48"}], "href": "https://doi.org/10.1038/cr.2014.48"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24732009"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24732009"}]}]}]}
Synonyms	ARHCL1, NERPP-2C, URCC2
Proteins	PPM1H_HUMAN
NCBI Gene ID	57460
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

PPM1H has 7,588 functional associations with biological entities spanning 9 categories (molecular profile, organism, chemical, functional term, phrase or reference, disease, phenotype or trait, structural feature, cell line, cell type or tissue, gene, protein or microRNA, sequence feature) extracted from 112 datasets.

Click the + buttons to view associations for PPM1H from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

PPM1H Gene

Functional Associations

Please acknowledge the Harmonizome in your publications by citing the following reference(s):

	Dataset	Summary
	Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of PPM1H gene relative to other tissues from the Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles	tissues with high or low expression of PPM1H gene relative to other tissues from the Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles	tissue samples with high or low expression of PPM1H gene relative to other tissue samples from the Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray	tissue samples with high or low expression of PPM1H gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq	tissue samples with high or low expression of PPM1H gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq dataset.
	Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of PPM1H gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	BioGPS Cell Line Gene Expression Profiles	cell lines with high or low expression of PPM1H gene relative to other cell lines from the BioGPS Cell Line Gene Expression Profiles dataset.
	BioGPS Human Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of PPM1H gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset.
	BioGPS Mouse Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of PPM1H gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset.
	Carcinogenome Chemical Perturbation Carcinogenicity Signatures	small molecule perturbations changing expression of PPM1H gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of PPM1H gene relative to other cell lines from the CCLE Cell Line Gene CNV Profiles dataset.
	CCLE Cell Line Gene Expression Profiles	cell lines with high or low expression of PPM1H gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with PPM1H protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with PPM1H gene from the CellMarker Gene-Cell Type Associations dataset.
	ChEA Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of PPM1H gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of PPM1H gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets dataset.
	ChEA Transcription Factor Targets 2022	transcription factors binding the promoter of PPM1H gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	CM4AI U2OS Cell Map Protein Localization Assemblies	assemblies containing PPM1H protein from integrated AP-MS and IF data from the CM4AI U2OS Cell Map Protein Localization Assemblies dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of PPM1H gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with PPM1H protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025	cellular components co-occuring with PPM1H protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with PPM1H gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with PPM1H gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with PPM1H gene/protein from the curated CTD Gene-Disease Associations dataset.
	dbGAP Gene-Trait Associations	traits associated with PPM1H gene in GWAS and other genetic association datasets from the dbGAP Gene-Trait Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of PPM1H protein relative to other small molecule perturbations from the DeepCoverMOA Drug Mechanisms of Action dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by PPM1H gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores	diseases associated with PPM1H gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with PPM1H gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores 2025	diseases co-occuring with PPM1H gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores 2025 dataset.
	DisGeNET Gene-Disease Associations	diseases associated with PPM1H gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with PPM1H gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at PPM1H gene from the ENCODE Histone Modification Site Profiles dataset.
	ENCODE Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of PPM1H gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of PPM1H gene in ChIP-seq datasets from the ENCODE Transcription Factor Targets dataset.
	ESCAPE Omics Signatures of Genes and Proteins for Stem Cells	PubMedIDs of publications reporting gene signatures containing PPM1H from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD Gene-Disease Associations	diseases associated with PPM1H gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.
	GDSC Cell Line Gene Expression Profiles	cell lines with high or low expression of PPM1H gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset.
	GeneRIF Biological Term Annotations	biological terms co-occuring with PPM1H gene in literature-supported statements describing functions of genes from the GeneRIF Biological Term Annotations dataset.
	GeneSigDB Published Gene Signatures	PubMedIDs of publications reporting gene signatures containing PPM1H from the GeneSigDB Published Gene Signatures dataset.