PPM1D protein phosphatase, Mg2+/Mn2+ dependent 1D [Homo sapiens (human)] - Gene

Summary

Official Symbol: PPM1Dprovided by HGNC
Official Full Name: protein phosphatase, Mg2+/Mn2+ dependent 1Dprovided by HGNC
Primary source: HGNC:HGNC:9277
See related: Ensembl:ENSG00000170836 MIM:605100; AllianceGenome:HGNC:9277
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: JDVS; WIP1; IDDGIP; PP2C-DELTA
Summary: The protein encoded by this gene is a member of the PP2C family of Ser/Thr protein phosphatases. PP2C family members are known to be negative regulators of cell stress response pathways. The expression of this gene is induced in a p53-dependent manner in response to various environmental stresses. While being induced by tumor suppressor protein TP53/p53, this phosphatase negatively regulates the activity of p38 MAP kinase, MAPK/p38, through which it reduces the phosphorylation of p53, and in turn suppresses p53-mediated transcription and apoptosis. This phosphatase thus mediates a feedback regulation of p38-p53 signaling that contributes to growth inhibition and the suppression of stress induced apoptosis. This gene is located in a chromosomal region known to be amplified in breast cancer. The amplification of this gene has been detected in both breast cancer cell line and primary breast tumors, which suggests a role of this gene in cancer development. [provided by RefSeq, Jul 2008]
Expression: Ubiquitous expression in testis (RPKM 7.0), ovary (RPKM 5.5) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 17q23.2

Exon count:: 8

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	17	NC_000017.11 (60600193..60666280)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	17	NC_060941.1 (61468992..61535104)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	17	NC_000017.10 (58677554..58743641)

Chromosome 17 - NC_000017.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

PPM1D activity promotes cellular transformation by preventing senescence and cell death.
Title: PPM1D activity promotes cellular transformation by preventing senescence and cell death.
SOD1 is a synthetic-lethal target in PPM1D-mutant leukemia cells.
Title: SOD1 is a synthetic-lethal target in PPM1D-mutant leukemia cells.
PPM1D activity promotes the replication stress caused by cyclin E1 overexpression.
Title: PPM1D activity promotes the replication stress caused by cyclin E1 overexpression.
Low-Frequency PPM1D Gene Mutations Affect Treatment Response to CD19-Targeted CAR T-Cell Therapy in Large B-Cell Lymphoma.
Title: Low-Frequency PPM1D Gene Mutations Affect Treatment Response to CD19-Targeted CAR T-Cell Therapy in Large B-Cell Lymphoma.
PPM1D modulates hematopoietic cell fitness and response to DNA damage and is a therapeutic target in myeloid malignancy.
Title: PPM1D modulates hematopoietic cell fitness and response to DNA damage and is a therapeutic target in myeloid malignancy.
A Case Study on PPM1D and 9 Other Shared Germline Alterations in a Family.
Title: A Case Study on PPM1D and 9 Other Shared Germline Alterations in a Family.
Jansen-de Vries syndrome: Expansion of the PPM1D clinical and phenotypic spectrum in 34 families.
Title: Jansen-de Vries syndrome: Expansion of the PPM1D clinical and phenotypic spectrum in 34 families.
Lipid Droplet Formation Is Regulated by Ser/Thr Phosphatase PPM1D via Dephosphorylation of Perilipin 1.
Title: Lipid Droplet Formation Is Regulated by Ser/Thr Phosphatase PPM1D via Dephosphorylation of Perilipin 1.
PPM1D in Solid and Hematologic Malignancies: Friend and Foe?
Title: PPM1D in Solid and Hematologic Malignancies: Friend and Foe?
Allosteric inhibition of PPM1D serine/threonine phosphatase via an altered conformational state.
Title: Allosteric inhibition of PPM1D serine/threonine phosphatase via an altered conformational state.

Submit: New GeneRIF Correction See all GeneRIFs (150)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Familial cancer of breast MedGen: C0346153 OMIM: 114480 GeneReviews: BRCA1- and BRCA2-Associated Hereditary Breast and Ovarian Cancer	not available
Intellectual developmental disorder with gastrointestinal difficulties and high pain threshold MedGen: C4479517 OMIM: 617450 GeneReviews: Not available	not available

Copy number response

Description
Copy number response Triplosensitivity No evidence available (Last evaluated 2023-03-28) ClinGen Genome Curation Page Haploinsufficency No evidence available (Last evaluated 2023-03-28) ClinGen Genome Curation PagePubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

RH102472 (e-PCR)
- UniSTS:96806

SHGC-53722 (e-PCR)
- UniSTS:35888

D8S2279 (e-PCR)
- UniSTS:473907

Ppm1d (e-PCR), detects polymorphism
- UniSTS:506691

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables metal ion binding	IEA Inferred from Electronic Annotation more info
enables mitogen-activated protein kinase binding	IBA Inferred from Biological aspect of Ancestor more info
enables mitogen-activated protein kinase binding	IPI Inferred from Physical Interaction more info	PubMed
enables myosin phosphatase activity	IEA Inferred from Electronic Annotation more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein serine/threonine kinase activity	TAS Traceable Author Statement more info
enables protein serine/threonine phosphatase activity	IBA Inferred from Biological aspect of Ancestor more info
enables protein serine/threonine phosphatase activity	IDA Inferred from Direct Assay more info	PubMed

Process	Evidence Code	Pubs
involved_in DNA damage response, signal transduction by p53 class mediator	IEA Inferred from Electronic Annotation more info
involved_in DNA methylation-dependent heterochromatin formation	ISS Inferred from Sequence or Structural Similarity more info
involved_in G2/M transition of mitotic cell cycle	IEA Inferred from Electronic Annotation more info
involved_in cellular response to starvation	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of cell population proliferation	TAS Traceable Author Statement more info	PubMed
involved_in negative regulation of gene expression, epigenetic	IBA Inferred from Biological aspect of Ancestor more info
involved_in negative regulation of gene expression, epigenetic	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in peptidyl-threonine dephosphorylation	IDA Inferred from Direct Assay more info	PubMed
involved_in protein dephosphorylation	TAS Traceable Author Statement more info	PubMed
involved_in regulation of intracellular signal transduction	IBA Inferred from Biological aspect of Ancestor more info
involved_in regulation of transcription initiation by RNA polymerase II	TAS Traceable Author Statement more info
involved_in response to bacterium	IEA Inferred from Electronic Annotation more info
involved_in response to radiation	TAS Traceable Author Statement more info	PubMed

Component	Evidence Code	Pubs
is_active_in cytosol	IBA Inferred from Biological aspect of Ancestor more info
located_in cytosol	IDA Inferred from Direct Assay more info	PubMed
located_in nucleolus	IDA Inferred from Direct Assay more info
located_in nucleoplasm	IDA Inferred from Direct Assay more info
located_in nucleoplasm	TAS Traceable Author Statement more info
is_active_in nucleus	IBA Inferred from Biological aspect of Ancestor more info
located_in nucleus	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: protein phosphatase 1D

Names: protein phosphatase Wip1; wild-type p53-induced phosphatase 1

NP_003611.1

EC 3.1.3.16

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.