PPME1

protein-coding

protein phosphatase methylesterase 1, the group of Abhydrolase domain containing|Protein phosphatase 2 modulatory subunits

Gene summary

This gene encodes a protein phosphatase methylesterase localized to the nucleus. The encoded protein acts on the protein phosphatase-2A catalytic subunit and supports the ERK pathway through dephosphorylation of regulatory proteins. It plays a role in malignant glioma progression. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2012]

MANE transcript

NM_016147.3

Inheritance

—

ClinVar variants

U:39B:2

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.04

Max pathogenic AF

—

Genomic locus

chr11:74,171,267-74,254,703

External References & Databases

Ensembl (ENSG00000214517)

Transcript & Mutation Effects

hg38 • Region Span ~83.4 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to PPME1 variants in ClinVar

1 Conditions Cataloged

not specifiedTotal: 29

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_016147.3. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			2 clinvar	1 clinvar		3
missense			34 clinvar	1 clinvar		35
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	39	2	0	41

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 41 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_016147.3	RefSeq	NP_057231.1	14	MANE Select
ENST00000328257.13	Ensembl	ENSP00000329867.8	14	MANE Select
NM_001271593.2	RefSeq	NP_001258522.1	14	Standard
ENST00000398427.6	Ensembl	ENSP00000381461.4	14	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Cyclin A/B1/B2 associated events during G2/M transition
G2/M Transition
Mitotic G2-G2/M phases
Cell Cycle
Cell Cycle, Mitotic

Biological Process

G2/M transition of mitotic cell cycle
protein demethylation
negative regulation of phosphoprotein phosphatase activity

Molecular Function

protein phosphatase inhibitor activity
protein binding
protein phosphatase regulator activity
protein kinase binding
protein phosphatase binding

Cellular Component

nucleoplasm

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000328257
Coding exons: 14
Length: 83605
Individuals with no LoFs: 124557
Homozygous LoFs: 0
Heterozygous LoFs: 3
Defined: 124560
p: 0.0000120

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.75	139	210	0.661	0.0000106	2525
Missense (PolyPhen)		21	74.094	0.28342		885
Synonymous	1.92	47	67.0	0.701	0.00000305	720
Loss of Function	4.40	1	24.5	0.0408	0.00000133	280

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0.00010	0.000099	rare
East Asian	0	0.0	absent
Finnish	0.000047	0.000046	rare
European (Non-Finnish)	0.0000096	0.0000088	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Demethylates proteins that have been reversibly carboxymethylated. Demethylates PPP2CB (in vitro) and PPP2CA. Binding to PPP2CA displaces the manganese ion and inactivates the enzyme. {ECO:0000269|PubMed:10318862}.;

Intolerance Scores

RVIS EVS: -0.1
RVIS percentile EVS: 46.49

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): E
Indispensability pred.: E
Indispensability score: 0.989

Gene Damage Prediction

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