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MPPE1

gene
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Also known as PGAP5Cdc1

Summary

MPPE1 (metallophosphoesterase 1, HGNC:15988) is a protein-coding gene on chromosome 18p11.21, encoding Metallophosphoesterase 1 (Q53F39). Metallophosphoesterase that catalyzes the removal of a side-chain ethanolamine-phosphate (EtNP) from the second mannose of the GPI-anchor protein intermediate.

Predicted to enable GPI anchor binding activity; GPI-mannose ethanolamine phosphate phosphodiesterase activity; and manganese ion binding activity. Involved in GPI anchor biosynthetic process. Located in Golgi apparatus and nucleoplasm.

Source: NCBI Gene 65258 — RefSeq curated summary.

At a glance

  • Clinical variants (ClinVar): 67 total — 2 pathogenic
  • MANE Select transcript: NM_023075

Identifiers

Gene identifiers

FieldValue
HGNC IDHGNC:15988
Approved symbolMPPE1
Namemetallophosphoesterase 1
Location18p11.21
Locus typegene with protein product
StatusApproved
AliasesPGAP5, Cdc1
Ensembl geneENSG00000154889
Ensembl biotypeprotein_coding
OMIM611900
Entrez65258

Gene structure

Transcript identifiers

Ensembl transcripts: 69 — 53 protein_coding, 7 protein_coding_CDS_not_defined, 5 retained_intron, 3 nonsense_mediated_decay, 1 non_stop_decay

ENST00000309976, ENST00000317235, ENST00000317251, ENST00000344987, ENST00000496196, ENST00000586204, ENST00000586364, ENST00000586844, ENST00000587381, ENST00000587724, ENST00000588072, ENST00000588103, ENST00000588186, ENST00000588191, ENST00000588939, ENST00000589267, ENST00000589731, ENST00000589829, ENST00000589859, ENST00000590302, ENST00000590501, ENST00000591667, ENST00000592180, ENST00000592306, ENST00000592331, ENST00000592447, ENST00000592755, ENST00000592894, ENST00000592977, ENST00000593001, ENST00000882028, ENST00000882029, ENST00000882030, ENST00000882031, ENST00000882032, ENST00000882033, ENST00000882034, ENST00000882035, ENST00000882036, ENST00000882037, ENST00000882038, ENST00000882039, ENST00000882040, ENST00000882041, ENST00000882042, ENST00000882043, ENST00000882044, ENST00000913098, ENST00000913099, ENST00000957382, ENST00000957383, ENST00000957384, ENST00000957385, ENST00000957386, ENST00000957387, ENST00000957388, ENST00000957389, ENST00000957390, ENST00000957391, ENST00000957392, ENST00000957393, ENST00000957394, ENST00000957395, ENST00000957396, ENST00000957397, ENST00000957398, ENST00000957399, ENST00000957400, ENST00000957401

RefSeq mRNA: 4 — MANE Select: NM_023075 NM_001242904, NM_001319154, NM_001330563, NM_023075

CCDS: CCDS11853, CCDS56054, CCDS82242

Canonical transcript exons

ENST00000588072 — 11 exons

ExonStartEnd
ENSE000012762691188649911886621
ENSE000012762761188671311886778
ENSE000012762921190620311906309
ENSE000018519871190820111908317
ENSE000029426141188262211884627
ENSE000035052431188866911888743
ENSE000035558491188691711887025
ENSE000036632061189346811893576
ENSE000036676201188567611885816
ENSE000036682591189698411897356
ENSE000037891291188938711889490

Expression profiles

Bgee: expression breadth ubiquitous, 285 present calls, max score 96.23.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 11.8085 / max 123.7697, expressed in 1801 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter IDTPM avgSamples expressed
1712247.01321757
1712254.79531685

Top tissues by expression

296 total, by Bgee expression score (0-100, higher = more expressed):

TissueAnatomy IDExpression scoreQuality
granulocyteCL:000009496.23gold quality
bloodUBERON:000017895.35gold quality
monocyteCL:000057694.94gold quality
leukocyteCL:000073894.94gold quality
mononuclear cellCL:000084294.92gold quality
left lobe of thyroid glandUBERON:000112094.49gold quality
right lobe of thyroid glandUBERON:000111994.43gold quality
thyroid glandUBERON:000204694.23gold quality
skin of legUBERON:000151194.08gold quality
right lungUBERON:000216794.04gold quality
metanephros cortexUBERON:001053393.80gold quality
apex of heartUBERON:000209893.79gold quality
skin of abdomenUBERON:000141693.78gold quality
body of pancreasUBERON:000115093.65gold quality
stromal cell of endometriumCL:000225593.45gold quality
calcaneal tendonUBERON:000370193.36gold quality
olfactory segment of nasal mucosaUBERON:000538693.35gold quality
cervix squamous epitheliumUBERON:000692293.19gold quality
upper lobe of left lungUBERON:000895293.16gold quality
gall bladderUBERON:000211093.07gold quality
rectumUBERON:000105292.93gold quality
small intestine Peyer’s patchUBERON:000345492.89gold quality
upper lobe of lungUBERON:000894892.80gold quality
adenohypophysisUBERON:000219692.68gold quality
descending thoracic aortaUBERON:000234592.54gold quality
spleenUBERON:000210692.47gold quality
nucleus accumbensUBERON:000188292.45gold quality
zone of skinUBERON:000001492.41gold quality
body of stomachUBERON:000116192.33gold quality
thoracic aortaUBERON:000151592.24gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

ExperimentMarker?Max mean expression
E-ANND-3yes4.42

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

28 targeting MPPE1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNAMax scoreAvg scoremiRNA target_count
HSA-MIR-513A-5P100.0069.772465
HSA-MIR-3924100.0072.092394
HSA-MIR-548C-3P99.9974.017587
HSA-MIR-6778-3P99.9667.292693
HSA-MIR-101-3P99.9475.032230
HSA-MIR-442299.7272.072908
HSA-MIR-580-3P99.6769.231841
HSA-MIR-6848-3P99.6466.49885
HSA-MIR-3682-3P99.5867.63865
HSA-MIR-427699.5667.662514
HSA-MIR-1252-3P99.5567.712862
HSA-MIR-568399.3668.592083
HSA-MIR-6843-3P99.2666.42915
HSA-MIR-1207-3P98.9966.221532
HSA-MIR-3145-3P98.8569.072031
HSA-MIR-589-5P98.7266.96927
HSA-MIR-6782-3P97.6067.75931
HSA-MIR-6748-3P97.2065.66836
HSA-MIR-3126-3P97.1766.51468
HSA-MIR-4536-3P97.0666.88175
HSA-MIR-4690-3P97.0264.72981
HSA-MIR-568597.0264.341004
HSA-MIR-7846-3P96.9265.1851
HSA-MIR-4436B-5P96.7168.371346
HSA-MIR-397696.6767.791187
HSA-MIR-6856-3P96.4766.27781
HSA-MIR-63596.0065.54687
HSA-MIR-6774-5P95.9465.18722

Literature-anchored findings (GeneRIF, showing 4)

  • cDNA cloning, genomic organization and expression of the novel human metallophosphoesterase gene MPPE1 on chromosome 18p11.2 (PMID:11978971)
  • Data demonstrate that glycosylphosphatidylinositol(GPI) glycan acts as an endoplasmic reticulum-exit signal and suggest that glycan remodeling mediated by PGAP5 regulates GPI-anchored proteins transport in the early secretory pathway. (PMID:19837036)
  • These results provide evidence of an association between a polymorphism in the MPPE1 gene and bipolar disorder. (PMID:19859903)
  • Metallophosphoesterase 1, a novel candidate gene in hepatocellular carcinoma malignancy and recurrence. (PMID:33054568)

Cross-species orthologs

5 orthologs

OrganismSymbolGene ID
danio_reriomppe1ENSDARG00000045416
mus_musculusMppe1ENSMUSG00000062526
rattus_norvegicusMppe1ENSRNOG00000018648
drosophila_melanogasterPGAP5FBGN0031997
caenorhabditis_elegansmppe-1WBGENE00015238

Protein

Protein identifiers

Metallophosphoesterase 1 — Q53F39 (reviewed: Q53F39)

Alternative names: Post-GPI attachment to proteins factor 5

All UniProt accessions (15): Q53F39, A0A075B777, A0A0A0MR93, A0A0C4DH11, K7EIQ0, K7EJU0, K7ELZ7, K7EM03, K7EQ70, K7EQ74, K7EQV4, K7ER13, K7ERI3, K7ES91, K7ESB8

UniProt curated annotations — full annotation on UniProt →

Function. Metallophosphoesterase that catalyzes the removal of a side-chain ethanolamine-phosphate (EtNP) from the second mannose of the GPI-anchor protein intermediate. Participates in the glycan remodeling steps of GPI-anchor maturation to allow an efficient transport of GPI-anchor proteins from the endoplasmic reticulum to the Golgi.

Subunit / interactions. Interacts with GPI-anchor proteins (via the GPI portion). Interacts with TMED10.

Subcellular location. Endoplasmic reticulum-Golgi intermediate compartment membrane.

Tissue specificity. Expressed in brain.

Cofactor. Binds 2 manganese ions per subunit.

Domain organisation. The di-lysine motif (KxKxx) acts as an endoplasmic reticulum retrieval signal.

Similarity. Belongs to the metallophosphoesterase superfamily. MPPE1 family.

Isoforms (5)

UniProt IDNamesCanonical?
Q53F39-11yes
Q53F39-22
Q53F39-33
Q53F39-44
Q53F39-55

RefSeq proteins (4): NP_001229833, NP_001306083, NP_001317492, NP_075563* (*=MANE)

Domains & families (InterPro)

IDNameType
IPR004843Calcineurin-like_PHPDomain
IPR029052Metallo-depent_PP-likeHomologous_superfamily
IPR033308PGAP5/Cdc1/Ted1Family
IPR039541MPP_MPPE1Domain

Pfam: PF00149

Catalyzed reactions (Rhea), 1 shown:

  • [protein]-C-terminal carboxyl phosphoethanolamide-GPI(deacylinositol-H8) + H2O = [protein]-C-terminal carboxyl phosphoethanolamide-GPI(deacylinositol-H7) + phosphoethanolamine + H(+) (RHEA:83747)

UniProt features (35 total): mutagenesis site 9, binding site 8, splice variant 5, sequence conflict 5, sequence variant 4, transmembrane region 2, chain 1, short sequence motif 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

ModelpLDDTFraction very-high
AF-Q53F39-F190.080.80

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (8): 303; 305; 77; 119; 119; 157; 249; 249

Mutagenesis-validated functional residues (9):

PositionPhenotype
77affects transport of gpi-anchor proteins.
79affects transport of gpi-anchor proteins.
119affects transport of gpi-anchor proteins.
157affects transport of gpi-anchor proteins.
158affects transport of gpi-anchor proteins.
249affects transport of gpi-anchor proteins.
303affects transport of gpi-anchor proteins.
305affects transport of gpi-anchor proteins.
392–394affects subcellular localization.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 189 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_BRAIN_TUMORAL_MACROPHAGE_DN, GOBP_PHOSPHOLIPID_METABOLIC_PROCESS, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, GOBP_PHOSPHATIDYLINOSITOL_METABOLIC_PROCESS, GOBP_GLYCOLIPID_BIOSYNTHETIC_PROCESS, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_VESICLE_MEDIATED_TRANSPORT, GOBP_ORGANOPHOSPHATE_BIOSYNTHETIC_PROCESS, MODULE_503, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, GOBP_PHOSPHOLIPID_BIOSYNTHETIC_PROCESS, GOBP_GLYCEROLIPID_METABOLIC_PROCESS, GOBP_PROTEIN_MATURATION, GOBP_ENDOPLASMIC_RETICULUM_TO_GOLGI_VESICLE_MEDIATED_TRANSPORT, MODULE_195

GO Biological Process (3): GPI anchor biosynthetic process (GO:0006506), endoplasmic reticulum to Golgi vesicle-mediated transport (GO:0006888), vesicle-mediated transport (GO:0016192)

GO Molecular Function (6): manganese ion binding (GO:0030145), GPI-mannose ethanolamine phosphate phosphodiesterase activity (GO:0062050), protein binding (GO:0005515), phosphoric diester hydrolase activity (GO:0008081), hydrolase activity (GO:0016787), metal ion binding (GO:0046872)

GO Cellular Component (6): nucleoplasm (GO:0005654), Golgi apparatus (GO:0005794), endoplasmic reticulum-Golgi intermediate compartment membrane (GO:0033116), endoplasmic reticulum exit site (GO:0070971), endoplasmic reticulum-Golgi intermediate compartment (GO:0005793), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

CategoryTerms
cytoplasm3
cellular anatomical structure3
intracellular membrane-bounded organelle2
GPI anchor metabolic process1
glycolipid biosynthetic process1
glycerophospholipid biosynthetic process1
GPI anchored protein biosynthesis1
intercellular transport1
intracellular transport1
Golgi vesicle transport1
transport1
cellular process1
transition metal ion binding1
phosphoric diester hydrolase activity1
binding1
phosphoric ester hydrolase activity1
catalytic activity1
cation binding1
nuclear lumen1
endomembrane system1
endoplasmic reticulum-Golgi intermediate compartment1
bounding membrane of organelle1
endoplasmic reticulum1

Protein interactions and networks

STRING

1280 interactions, top by confidence (×1000):

Protein AProtein BPartner UniProtScore
MPPE1CDC27P30260963
MPPE1BATF3Q9NR55865
MPPE1XCR1P46094864
MPPE1CLEC9AQ6UXN8852
MPPE1GNALP38405833
MPPE1CD8AP01732782
MPPE1ITGAEP38570722
MPPE1THBDP07204717
MPPE1XCL1P47992713
MPPE1IRF8Q02556697
MPPE1CD1CP29017697
MPPE1ITGAXP20702697
MPPE1SIRPAP78324690
MPPE1ITGAMP11215653
MPPE1ZBTB46Q86UZ6644

IntAct

11 interactions, top by confidence:

ABTypeScore
FLJ13057MPPE1psi-mi:“MI:0915”(physical association)0.560
MPPE1ZNF426psi-mi:“MI:0915”(physical association)0.560
MPPE1FLJ13057psi-mi:“MI:0915”(physical association)0.560
MPPE1FAM234Bpsi-mi:“MI:0914”(association)0.350
SLC39A7ESYT2psi-mi:“MI:0914”(association)0.350
SLC44A1UPK3BL1psi-mi:“MI:0914”(association)0.350
SLC4A5ESYT2psi-mi:“MI:0914”(association)0.350

BioGRID (141): MPPE1 (Two-hybrid), ZNF426 (Two-hybrid), MUCL1 (Affinity Capture-MS), EDEM1 (Affinity Capture-MS), ICAM4 (Affinity Capture-MS), TMEM186 (Affinity Capture-MS), UGT3A2 (Affinity Capture-MS), GINM1 (Affinity Capture-MS), PIGB (Affinity Capture-MS), SEMA6A (Affinity Capture-MS), TMEM59L (Affinity Capture-MS), GALNT4 (Affinity Capture-MS), DHFRL1 (Affinity Capture-MS), FZD2 (Affinity Capture-MS), ALG12 (Affinity Capture-MS)

ESM2 similar proteins: A5D6U8, O23244, O48840, O97860, P06865, P07686, P08236, P09889, P13686, P20060, P29240, P29288, P29416, P49614, P80366, Q05117, Q0V8R6, Q38924, Q53F39, Q5MAU8, Q5R5N6, Q5RC84, Q5RET5, Q5RFI5, Q641X3, Q641Z7, Q687E1, Q6AYS4, Q6TPH1, Q6ZNF0, Q8BX37, Q8H1R2, Q8S340, Q8S341, Q8VYU7, Q8VYZ2, Q93WP4, Q949Y3, Q99KR8, Q9BTY2

Diamond homologs: B1WC86, C7G3A0, D2I2M6, Q0IHA5, Q53F39, Q566Y9, Q5RET5, Q5ZK82, Q80XL7, Q95X35, Q9GMS6, Q9VLR9

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

67 variants total. Per-class counts are floors (≥ shown; pagination cap):

ClassificationCount (floor)
Pathogenic2
Likely pathogenic0
Uncertain significance51
Likely benign5
Benign0

Top pathogenic / likely-pathogenic (2)

Variant IDHGVSClassification
1706491GRCh37/hg19 18p11.22-11.21(chr18:9569601-12218695)x1Pathogenic
1706501GRCh37/hg19 18p11.32-11.21(chr18:136226-14632436)x1Pathogenic

SpliceAI

2830 predictions. Top by Δscore:

VariantEffectΔscore
18:11885829:G:Tacceptor_gain1.0000
18:11886912:CCTAC:Cdonor_loss1.0000
18:11886913:CTACC:Cdonor_loss1.0000
18:11886914:TACCT:Tdonor_loss1.0000
18:11886916:C:CAdonor_loss1.0000
18:11886916:CCT:Cdonor_gain1.0000
18:11887021:CAAAG:Cacceptor_gain1.0000
18:11887026:C:CCacceptor_gain1.0000
18:11889380:TACTT:Tdonor_loss1.0000
18:11889381:ACTTA:Adonor_loss1.0000
18:11889382:CT:Cdonor_loss1.0000
18:11889383:TTA:Tdonor_loss1.0000
18:11889384:TAC:Tdonor_loss1.0000
18:11889385:A:ACdonor_gain1.0000
18:11889385:ACT:Adonor_gain1.0000
18:11889385:ACTCA:Adonor_loss1.0000
18:11889386:C:CAdonor_gain1.0000
18:11889386:CT:Cdonor_gain1.0000
18:11889386:CTC:Cdonor_gain1.0000
18:11889486:CAGGC:Cacceptor_gain1.0000
18:11889487:AGGCC:Aacceptor_loss1.0000
18:11889488:GGCCT:Gacceptor_loss1.0000
18:11889489:GCCTG:Gacceptor_loss1.0000
18:11889491:C:CCacceptor_gain1.0000
18:11889491:CTGA:Cacceptor_loss1.0000
18:11889492:T:Aacceptor_loss1.0000
18:11893486:C:Adonor_gain1.0000
18:11893576:CCT:Cacceptor_gain1.0000
18:11893585:C:CTacceptor_gain1.0000
18:11893586:A:Tacceptor_gain1.0000

AlphaMissense

2601 scored. Top likely-pathogenic:

VariantProtein changeam_pathogenicity
18:11885709:A:CS325R0.998
18:11885709:A:TS325R0.998
18:11885711:T:GS325R0.998
18:11893502:T:AD119V0.998
18:11887007:G:CS196R0.997
18:11887007:G:TS196R0.997
18:11887009:T:GS196R0.997
18:11893502:T:GD119A0.997
18:11893505:C:AG118V0.997
18:11885724:G:CS320R0.996
18:11885724:G:TS320R0.996
18:11885726:T:GS320R0.996
18:11885781:A:CS301R0.996
18:11885781:A:TS301R0.996
18:11885783:T:GS301R0.996
18:11889408:T:GH158P0.996
18:11889410:G:CN157K0.996
18:11889410:G:TN157K0.996
18:11893506:C:AG118W0.996
18:11885708:A:GW326R0.995
18:11885708:A:TW326R0.995
18:11885716:G:AS323F0.995
18:11889395:G:CF162L0.995
18:11889395:G:TF162L0.995
18:11889397:A:GF162L0.995
18:11889409:G:CH158D0.995
18:11893501:A:CD119E0.995
18:11893501:A:TD119E0.995
18:11893502:T:CD119G0.995
18:11893503:C:GD119H0.995

dbSNP variants (sampled 300 via entrez): RS1000089062 (18:11887927 G>A), RS1000339085 (18:11908365 G>A), RS1000367963 (18:11882415 C>T), RS1000534954 (18:11892521 T>G), RS1000580401 (18:11902934 C>T), RS1000580595 (18:11890339 C>T), RS1000642385 (18:11898489 T>C), RS1000694690 (18:11896539 A>G), RS1000776593 (18:11898269 G>A), RS1000970907 (18:11901497 C>T), RS1000992177 (18:11892138 G>A), RS1001198713 (18:11895458 C>A), RS1001251067 (18:11895243 A>G), RS1001422272 (18:11906623 G>A,C), RS1001499676 (18:11895842 G>T)

Disease associations

OMIM: gene MIM:611900 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

24 total (human), top 24 by PubMed support.

ChemicalActions (top 5)PubMed papers
Cyclosporineincreases expression, decreases expression2
aristolochic acid Iincreases expression1
triphenyl phosphateaffects expression1
bisphenol Aaffects cotreatment, increases expression1
abrinedecreases expression1
jinfukangaffects cotreatment, increases expression1
Acetaminophendecreases expression1
Benzo(a)pyrenedecreases methylation1
Cisplatinaffects cotreatment, increases expression1
Copperincreases expression, affects binding1
Dexamethasoneaffects cotreatment, increases expression1
Disulfiramaffects binding, increases expression1
Doxorubicinincreases expression1
Indomethacinaffects cotreatment, increases expression1
Leadaffects expression1
Methyl Methanesulfonateincreases expression1
Silicon Dioxidedecreases expression1
Tobacco Smoke Pollutiondecreases expression1
Valproic Acidincreases expression1
1-Methyl-3-isobutylxanthineaffects cotreatment, increases expression1
Okadaic Aciddecreases expression1
Copper Sulfatedecreases expression1
Lactic Aciddecreases expression1
tert-Butylhydroperoxideincreases expression1

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.

No linked Atlas pages yet — the cross-entity mesh grows as the corpus expands.

About this page

Generated deterministically by Sugi Atlas from primary biomedical databases via BioBTree. Every record on this page traces to a primary source.

Generated
Atlas version
v1.1.4
BioBTree
v2.0.2

Sources 74

This page pulls from 74 datasets indexed by BioBTree:

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