PPM1A

protein phosphatase, Mg2+/Mn2+ dependent 1A, the group of Protein phosphatases, Mg2+/Mn2+ dependent

Basic information

Region (hg38): 14:60245751-60299087

Links

ENSG00000100614 ∙ NCBI:5494 ∙ OMIM:606108 ∙ HGNC:9275 ∙ Uniprot:P35813 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PPM1A gene.

• Inborn genetic diseases (13 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PPM1A gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous						0
missense			13			13
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	13	0	0

Variants in PPM1A

This is a list of pathogenic ClinVar variants found in the PPM1A region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
14-60282686-C-G		not specified	Uncertain significance (Dec 15, 2023)
14-60282753-G-A		not specified	Uncertain significance (May 09, 2023)
14-60282771-G-A		not specified	Uncertain significance (May 04, 2022)
14-60282774-A-T		not specified	Uncertain significance (Aug 04, 2023)
14-60282858-C-T		not specified	Uncertain significance (Mar 06, 2023)
14-60282940-C-G		not specified	Uncertain significance (Nov 08, 2022)
14-60283044-T-C		not specified	Uncertain significance (Jan 08, 2024)
14-60283168-G-C		not specified	Uncertain significance (Apr 25, 2022)
14-60283326-A-G		not specified	Uncertain significance (Feb 11, 2022)
14-60283390-A-T		not specified	Uncertain significance (Dec 13, 2021)
14-60283391-G-A		not specified	Uncertain significance (Dec 06, 2022)
14-60283488-A-G		not specified	Uncertain significance (Aug 26, 2022)
14-60283489-T-G		not specified	Uncertain significance (Sep 22, 2022)
14-60285682-C-T		not specified	Uncertain significance (May 26, 2022)
14-60285710-G-T		not specified	Uncertain significance (Sep 27, 2021)
14-60285731-C-G		not specified	Uncertain significance (Jun 28, 2022)
14-60291404-G-A		not specified	Uncertain significance (Dec 13, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PPM1A	protein_coding	protein_coding	ENST00000325642	6	53336

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.998	0.00166	124833	0	1	124834	0.00000401

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.58	127	239	0.531	0.0000119	3023
Missense in Polyphen		6	81.403	0.073708		1011
Synonymous	0.418	80	84.9	0.942	0.00000448	816
Loss of Function	4.00	0	18.7	0.00	0.00000103	258

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00000883	0.00000883
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Enzyme with a broad specificity. Negatively regulates TGF-beta signaling through dephosphorylating SMAD2 and SMAD3, resulting in their dissociation from SMAD4, nuclear export of the SMADs and termination of the TGF-beta-mediated signaling. Dephosphorylates PRKAA1 and PRKAA2. Plays an important role in the termination of TNF-alpha-mediated NF-kappa-B activation through dephosphorylating and inactivating IKBKB/IKKB. {ECO:0000269|PubMed:16751101, ECO:0000269|PubMed:18930133}.
• Pathway: MAPK signaling pathway - Homo sapiens (human);TGF-Ncore;TGF-beta Signaling Pathway;MAPK Signaling Pathway;Signal Transduction;Gene expression (Transcription);Generic Transcription Pathway;RNA Polymerase II Transcription;Energy dependent regulation of mTOR by LKB1-AMPK;mTOR signalling;Downregulation of SMAD2/3:SMAD4 transcriptional activity;TGF_beta_Receptor;Transcriptional activity of SMAD2/SMAD3:SMAD4 heterotrimer;BMP receptor signaling;Signaling by TGF-beta Receptor Complex;Signaling by TGF-beta family members;Regulation of cytoplasmic and nuclear SMAD2/3 signaling (Consensus)

Recessive Scores

• pRec: 0.240

Intolerance Scores

• loftool: 0.288
• rvis_EVS: -0.36
• rvis_percentile_EVS: 28.63

Haploinsufficiency Scores

• pHI: 0.994
• hipred: Y
• hipred_score: 0.794
• ghis: 0.646

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.990

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Ppm1a
• Phenotype: hearing/vestibular/ear phenotype; skeleton phenotype; immune system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); homeostasis/metabolism phenotype; cellular phenotype

Gene ontology

• Biological process: negative regulation of transcription by RNA polymerase II;protein dephosphorylation;N-terminal protein myristoylation;cell cycle arrest;negative regulation of SMAD protein complex assembly;dephosphorylation;negative regulation of transforming growth factor beta receptor signaling pathway;negative regulation of BMP signaling pathway;peptidyl-threonine dephosphorylation;positive regulation of I-kappaB kinase/NF-kappaB signaling;negative regulation of I-kappaB kinase/NF-kappaB signaling;positive regulation of transcription, DNA-templated;positive regulation of protein export from nucleus;cellular response to transforming growth factor beta stimulus;positive regulation of canonical Wnt signaling pathway;negative regulation of NIK/NF-kappaB signaling
• Cellular component: nucleus;nucleoplasm;cytosol;plasma membrane;membrane
• Molecular function: magnesium ion binding;protein serine/threonine phosphatase activity;magnesium-dependent protein serine/threonine phosphatase activity;protein binding;manganese ion binding;calmodulin-dependent protein phosphatase activity;R-SMAD binding