MPPE1
protein-codingmetallophosphoesterase 1
Gene summary
Predicted to enable GPI-mannose ethanolamine phosphate phosphodiesterase activity and manganese ion binding activity. Involved in GPI anchor biosynthetic process. Located in Golgi apparatus. [provided by Alliance of Genome Resources, Jun 2026]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~25.7 kbGenCC 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 MPPE1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_023075.6. 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 | 0 | |||||
| missense | 69 | 6 | 75 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 2 | 2 | ||||
| Total | 0 | 0 | 71 | 6 | 0 | 77 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_075563.3 | 9 | MANE Select | |
| Ensembl | ENSP00000465894.1 | 9 | MANE Select | |
| RefSeq | NP_001229833.1 | 7 | Standard | |
| RefSeq | NP_001306083.1 | 7 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- GPI anchor biosynthetic process
- endoplasmic reticulum to Golgi vesicle-mediated transport
Molecular Function
- protein binding
- phosphoric diester hydrolase activity
- manganese ion binding
- GPI anchor binding
Cellular Component
- nucleoplasm
- endoplasmic reticulum
- endoplasmic reticulum-Golgi intermediate compartment
- Golgi apparatus
- cis-Golgi network
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000588072
- Coding exons
- 9
- Length
- 26602
- Individuals with no LoFs
- 125548
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 200
- Defined
- 125748
- p
- 0.000796
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.352 | 210 | 225 | 0.934 | 0.0000133 | 2588 |
| Missense (PolyPhen) | 74 | 82.213 | 0.9001 | 998 | ||
| Synonymous | -0.0502 | 90 | 89.4 | 1.01 | 0.00000572 | 769 |
| Loss of Function | 0.855 | 16 | 20.1 | 0.794 | 0.00000112 | 222 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00031 | 0.00031 | rare |
| Latino/Admixed American | 0.0016 | 0.0016 | notable |
| Ashkenazi Jewish | 0.0031 | 0.0030 | notable |
| East Asian | 0.00039 | 0.00038 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.00022 | 0.00022 | rare |
| South Asian | 0.0024 | 0.0024 | notable |
| Other | 0.00085 | 0.00081 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Metallophosphoesterase required for transport of GPI- anchor proteins from the endoplasmic reticulum to the Golgi. Acts in lipid remodeling steps of GPI-anchor maturation by mediating the removal of a side-chain ethanolamine-phosphate (EtNP) from the second Man (Man2) of the GPI intermediate, an essential step for efficient transport of GPI-anchor proteins. {ECO:0000269|PubMed:19837036}.;
Recessive Scores
- pRec
- 0.0830
Intolerance Scores
- LoFtool
- 0.925
- RVIS EVS
- 0.4
- RVIS percentile EVS
- 76.36
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.236
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |