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Aliases for PREPL Gene

Aliases for PREPL Gene

  • Prolyl Endopeptidase Like 2 3 5
  • Prolyl Endopeptidase-Like 2 3
  • Putative Prolyl Oligopeptidase 3
  • Prolylendopeptidase-Like 4
  • EC 3.4.21.- 4
  • KIAA0436 4
  • CMS22 3

External Ids for PREPL Gene

Previous GeneCards Identifiers for PREPL Gene

  • GC02M044458
  • GC02U900799
  • GC02M044543

Summaries for PREPL Gene

Entrez Gene Summary for PREPL Gene

  • The protein encoded by this gene belongs to the prolyl oligopeptidase subfamily of serine peptidases. Mutations in this gene have been associated with hypotonia-cystinuria syndrome, also known as the 2p21 deletion syndrome. Several alternatively spliced transcript variants encoding either the same or different isoforms have been described for this gene.[provided by RefSeq, Jan 2010]

GeneCards Summary for PREPL Gene

PREPL (Prolyl Endopeptidase Like) is a Protein Coding gene. Diseases associated with PREPL include Myasthenic Syndrome, Congenital, 22 and Hypotonia-Cystinuria Syndrome. Gene Ontology (GO) annotations related to this gene include serine-type endopeptidase activity and serine-type exopeptidase activity. An important paralog of this gene is PREP.

UniProtKB/Swiss-Prot for PREPL Gene

  • Probable serine peptidase whose precise substrate specificity remains unclear. Does not cleave peptides after a arginine or lysine residue. May play a role in the regulation of synaptic vesiscle exocytosis (PubMed:24610330).

Gene Wiki entry for PREPL Gene

Additional gene information for PREPL Gene

No data available for CIViC summary , Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for PREPL Gene

Genomics for PREPL Gene

GeneHancer (GH) Regulatory Elements for PREPL Gene

Promoters and enhancers for PREPL Gene
GeneHancer (GH) Identifier GH Type GH
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH02J044360 Promoter/Enhancer 2.1 EPDnew Ensembl ENCODE 650.7 0.0 -21 2.7 HDGF FOXA2 PKNOX1 MLX ARNT ARID4B NEUROD1 SIN3A FEZF1 DMAP1 CAMKMT PREPL THADA GC02M044085
GH02J044275 Promoter/Enhancer 1 EPDnew ENCODE 6 +84.5 84549 4.5 SP1 ATF3 REST FOSL2 HNF4A ZSCAN29 SLC3A1 PREPL GC02M044085
GH02J044267 Enhancer 0.8 Ensembl ENCODE 4.5 +93.8 93756 1.6 ATF1 ATF2 SP1 ZNF366 GLIS1 ZNF629 CREB1 ATF7 CREM ZBTB17 PREPL RPL12P19 LOC102723904 GC02M044085
GH02J044434 Enhancer 0.2 dbSUPER 4.7 -73.4 -73411 0.9 CAMKMT PREPL GC02P044396 GC02P044580 GC02M044085
GH02J044358 Enhancer 0.8 Ensembl ENCODE 0.7 +2.9 2862 0.8 SRF ZNF362 SMAD1 CBFB JUN NR2F1 DPF2 BATF ATF2 IRF4 PREPL SLC3A1 GC02M044085
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around PREPL on UCSC Golden Path with GeneCards custom track

Top Transcription factor binding sites by QIAGEN in the PREPL gene promoter:
  • Bach2
  • Pax-5
  • TBP
  • Bach1
  • STAT5A
  • FOXO4
  • E4BP4
  • Nkx2-5
  • Zic3
  • AP-4

Genomic Locations for PREPL Gene

Genomic Locations for PREPL Gene
45,582 bases
Minus strand
45,582 bases
Minus strand

Genomic View for PREPL Gene

Genes around PREPL on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
PREPL Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for PREPL Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for PREPL Gene

Proteins for PREPL Gene

  • Protein details for PREPL Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Recommended name:
    Prolyl endopeptidase-like
    Protein Accession:
    Secondary Accessions:
    • A7E2X6
    • D6W5A3
    • O43163
    • Q4J6C3
    • Q4J6C4
    • Q4ZG39
    • Q6ZMW7
    • Q96DW7

    Protein attributes for PREPL Gene

    727 amino acids
    Molecular mass:
    83927 Da
    Quaternary structure:
    • Homodimer.
    • Sequence=AAX88956.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305}; Sequence=BAA23709.1; Type=Erroneous initiation; Evidence={ECO:0000305};

    Alternative splice isoforms for PREPL Gene


neXtProt entry for PREPL Gene

Post-translational modifications for PREPL Gene

  • Ubiquitination at posLast=439439 and Lys426
  • Modification sites at PhosphoSitePlus

No data available for DME Specific Peptides for PREPL Gene

Domains & Families for PREPL Gene

Gene Families for PREPL Gene

Human Protein Atlas (HPA):
  • Disease related genes
  • Enzymes
  • Potential drug targets
  • Predicted intracellular proteins

Suggested Antigen Peptide Sequences for PREPL Gene

GenScript: Design optimal peptide antigens:

Graphical View of Domain Structure for InterPro Entry



  • Belongs to the peptidase S9A family.
  • Belongs to the peptidase S9A family.
genes like me logo Genes that share domains with PREPL: view

Function for PREPL Gene

Molecular function for PREPL Gene

UniProtKB/Swiss-Prot Function:
Probable serine peptidase whose precise substrate specificity remains unclear. Does not cleave peptides after a arginine or lysine residue. May play a role in the regulation of synaptic vesiscle exocytosis (PubMed:24610330).
UniProtKB/Swiss-Prot EnzymeRegulation:
Inhibited by PMSF and Prefabloc, as well as leupeptin at high concentrations. Partially inhibited by TPCK, a chymotrypsin inhibitor, and E64, a cysteine protease inhibitor. Not affected by 4-amidinophenyl-methanesulfonyl fluoride (APMSF), pepstatin or EDTA.

Enzyme Numbers (IUBMB) for PREPL Gene

Phenotypes From GWAS Catalog for PREPL Gene

Gene Ontology (GO) - Molecular Function for PREPL Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004252 serine-type endopeptidase activity IEA --
GO:0008233 peptidase activity IEA --
GO:0008236 serine-type peptidase activity IEA --
GO:0016787 hydrolase activity IEA --
GO:0070008 serine-type exopeptidase activity IEA --
genes like me logo Genes that share ontologies with PREPL: view
genes like me logo Genes that share phenotypes with PREPL: view

Human Phenotype Ontology for PREPL Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for PREPL Gene

MGI Knock Outs for PREPL:

Animal Model Products

  • Taconic Biosciences Mouse Models for PREPL

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for PREPL

Clone Products

No data available for Transcription Factor Targets and HOMER Transcription for PREPL Gene

Localization for PREPL Gene

Subcellular locations from UniProtKB/Swiss-Prot for PREPL Gene

Cytoplasm, cytosol.

Subcellular locations from

Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for PREPL gene
Compartment Confidence
cytosol 4
golgi apparatus 4
cytoskeleton 3
nucleus 2
mitochondrion 1

Gene Ontology (GO) - Cellular Components for PREPL Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005737 cytoplasm IEA --
GO:0005794 Golgi apparatus IBA --
GO:0005829 cytosol IEA --
GO:0005856 cytoskeleton IBA --
genes like me logo Genes that share ontologies with PREPL: view

No data available for Subcellular locations from the Human Protein Atlas (HPA) for PREPL Gene

Pathways & Interactions for PREPL Gene

SuperPathways for PREPL Gene

No Data Available

Gene Ontology (GO) - Biological Process for PREPL Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006508 proteolysis IEA --
GO:2000300 regulation of synaptic vesicle exocytosis IMP 24610330
genes like me logo Genes that share ontologies with PREPL: view

No data available for Pathways by source and SIGNOR curated interactions for PREPL Gene

Drugs & Compounds for PREPL Gene

No Compound Related Data Available

Transcripts for PREPL Gene

mRNA/cDNA for PREPL Gene

(12) REFSEQ mRNAs :
(8) Additional mRNA sequences :
(16) Ensembl transcripts including schematic representations, and UCSC links where relevant :

Unigene Clusters for PREPL Gene

Prolyl endopeptidase-like:
Representative Sequences:

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for PREPL

Clone Products

Alternative Splicing Database (ASD) splice patterns (SP) for PREPL Gene

ExUns: 1a · 1b · 1c · 1d · 1e ^ 2a · 2b · 2c · 2d ^ 3 ^ 4a · 4b · 4c ^ 5 ^ 6a · 6b ^ 7a · 7b · 7c ^ 8a · 8b ^ 9a · 9b · 9c · 9d · 9e ^
SP1: - - - - - - -
SP2: -
SP3: -
SP4: -
SP5: - - - - - - - -
SP6: - - - - - - - - -
SP7: - - - - - -
SP8: - - - - -
SP9: - - - - - - - - - - - -
SP10: - - - - - -
SP11: - - - - - - -
SP12: - - - - - - -
SP13: - - - - -
SP14: - - - - - - - -
SP15: - - - - - - - - -
SP16: - - -
SP17: - - - -
SP18: - - - - - - - -
SP19: - - - - - -
SP20: - -
SP21: -

ExUns: 10a · 10b · 10c · 10d · 10e ^ 11 ^ 12 ^ 13 ^ 14 ^ 15a · 15b ^ 16 ^ 17a · 17b ^ 18a · 18b · 18c
SP1: -
SP2: -
SP3: - -
SP4: - -

Relevant External Links for PREPL Gene

GeneLoc Exon Structure for
ECgene alternative splicing isoforms for

Expression for PREPL Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and CGAP SAGE for PREPL Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

Protein differential expression in normal tissues from HIPED for PREPL Gene

This gene is overexpressed in Frontal cortex (33.0), Fetal Brain (8.4), and Spinal cord (7.1).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for PREPL Gene

Protein tissue co-expression partners for PREPL Gene

- Elite partner

NURSA nuclear receptor signaling pathways regulating expression of PREPL Gene:


SOURCE GeneReport for Unigene cluster for PREPL Gene:


mRNA Expression by UniProt/SwissProt for PREPL Gene:

Tissue specificity: Widely expressed. Expressed at higher level in brain, skeletal muscle, heart and kidney. Expressed at the endplates in the neuromuscular junction (PubMed:24610330).

Evidence on tissue expression from TISSUES for PREPL Gene

  • Nervous system(5)
  • Bone(4)
  • Kidney(2.5)
  • Skin(2.5)
  • Muscle(2.1)
  • Heart(2)

Phenotype-based relationships between genes and organs from Gene ORGANizer for PREPL Gene

Germ Layers:
  • ectoderm
  • endoderm
  • mesoderm
  • cardiovascular
  • digestive
  • endocrine
  • integumentary
  • nervous
  • reproductive
  • respiratory
  • skeletal muscle
  • skeleton
  • urinary
Head and neck:
  • brain
  • cerebellum
  • chin
  • ear
  • eye
  • eyelid
  • face
  • forehead
  • head
  • jaw
  • larynx
  • lip
  • mandible
  • maxilla
  • mouth
  • neck
  • nose
  • outer ear
  • pharynx
  • pituitary gland
  • skull
  • vocal cord
  • breast
  • heart
  • lung
  • intestine
  • kidney
  • large intestine
  • small intestine
  • stomach
  • ovary
  • penis
  • prostate
  • testicle
  • ureter
  • urinary bladder
  • uterus
  • vagina
  • vulva
  • blood vessel
  • hair
  • peripheral nerve
  • peripheral nervous system
  • skin
genes like me logo Genes that share expression patterns with PREPL: view

No data available for mRNA differential expression in normal tissues for PREPL Gene

Orthologs for PREPL Gene

This gene was present in the common ancestor of eukaryotes.

Orthologs for PREPL Gene

Organism Taxonomy Gene Similarity Type Details
(Pan troglodytes)
Mammalia PREPL 34 33
  • 99.68 (n)
(Canis familiaris)
Mammalia PREPL 34 33
  • 93.96 (n)
(Bos Taurus)
Mammalia PREPL 34 33
  • 90.97 (n)
(Mus musculus)
Mammalia Prepl 16 34 33
  • 86.53 (n)
(Rattus norvegicus)
Mammalia Prepl 33
  • 86.24 (n)
(Monodelphis domestica)
Mammalia PREPL 34
  • 54 (a)
(Ornithorhynchus anatinus)
Mammalia PREPL 34
  • 38 (a)
(Gallus gallus)
Aves PREPL 34 33
  • 64.56 (n)
(Anolis carolinensis)
Reptilia PREPL 34
  • 47 (a)
tropical clawed frog
(Silurana tropicalis)
Amphibia prepl 33
  • 59.12 (n)
(Danio rerio)
Actinopterygii prepl 34 33
  • 53.49 (n)
fruit fly
(Drosophila melanogaster)
Insecta CG5355 34
  • 17 (a)
CG2528 34
  • 16 (a)
baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes IMA1 36
thale cress
(Arabidopsis thaliana)
eudicotyledons AT1G69020 33
  • 44.58 (n)
(Oryza sativa)
Liliopsida Os09g0475700 33
  • 45.61 (n)
Species where no ortholog for PREPL was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea squirt (Ciona intestinalis)
  • sea squirt (Ciona savignyi)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)
  • worm (Caenorhabditis elegans)

Evolution for PREPL Gene

Gene Tree for PREPL (if available)
Gene Tree for PREPL (if available)
Evolutionary constrained regions (ECRs) for PREPL: view image

Paralogs for PREPL Gene

Paralogs for PREPL Gene

genes like me logo Genes that share paralogs with PREPL: view

Variants for PREPL Gene

Sequence variations from dbSNP and Humsavar for PREPL Gene

SNP ID Clin Chr 02 pos Variation AA Info Type
rs1057523690 pathogenic, Myasthenic syndrome, congenital, 22 44,339,309(-) AA/A coding_sequence_variant, frameshift
rs111438719 likely-benign, Myasthenic syndrome, congenital, 22 44,323,296(-) T/C coding_sequence_variant, missense_variant
rs113272276 benign, Myasthenic syndrome, congenital, 22 44,339,162(-) T/C coding_sequence_variant, synonymous_variant
rs121912693 pathogenic, Cystinuria 44,320,614(-) T/C 3_prime_UTR_variant
rs121912695 pathogenic, Cystinuria 44,320,536(-) C/G/T 3_prime_UTR_variant

Structural Variations from Database of Genomic Variants (DGV) for PREPL Gene

Variant ID Type Subtype PubMed ID
dgv3798n100 CNV loss 25217958
dgv3799n100 CNV loss 25217958
dgv6837n54 CNV loss 21841781
dgv6838n54 CNV loss 21841781
esv2538552 OTHER inversion 19546169
esv2762539 CNV loss 21179565
esv3575237 CNV gain 25503493
esv3590555 CNV gain 21293372
esv3892026 CNV loss 25118596
nsv1006405 CNV loss 25217958
nsv1011655 CNV loss 25217958
nsv457196 CNV gain 19166990
nsv521399 CNV loss 19592680
nsv581691 CNV gain 21841781
nsv581692 CNV loss 21841781
nsv581695 CNV gain 21841781
nsv581698 CNV loss 21841781
nsv833947 CNV gain 17160897

Variation tolerance for PREPL Gene

Residual Variation Intolerance Score: 22.9% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 3.59; 56.27% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for PREPL Gene

Human Gene Mutation Database (HGMD)
SNPedia medical, phenotypic, and genealogical associations of SNPs for

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for PREPL Gene

Disorders for PREPL Gene

MalaCards: The human disease database

(6) MalaCards diseases for PREPL Gene - From: HGMD, OMIM, ClinVar, GTR, Orphanet, DISEASES, and GeneCards

Disorder Aliases PubMed IDs
myasthenic syndrome, congenital, 22
  • cms22
hypotonia-cystinuria syndrome
  • cystinuria with mitochondrial disease
  • csnu
2p21 microdeletion syndrome without cystinuria
  • del(2)(p21) without cystinuria
- elite association - COSMIC cancer census association via MalaCards
Search PREPL in MalaCards View complete list of genes associated with diseases


  • Hypotonia-cystinuria syndrome (HCS) [MIM:606407]: Characterized generalized hypotonia at birth, nephrolithiasis, growth hormone deficiency, minor facial dysmorphism, failure to thrive, followed by hyperphagia and rapid weight gain in late childhood. {ECO:0000269 PubMed:16385448}. Note=The gene represented in this entry is involved in disease pathogenesis. Hypotonia-cystinuria syndrome is a contiguous gene syndrome caused by a homozygous deletion on chromosome 2p21 that disrupts the gene represented in this entry and SLC3A1.
  • Myasthenic syndrome, congenital, 22 (CMS22) [MIM:616224]: A form of congenital myasthenic syndrome, a group of disorders characterized by failure of neuromuscular transmission, including pre-synaptic, synaptic, and post-synaptic disorders that are not of autoimmune origin. Clinical features include easy fatigability and muscle weakness. CMS22 is an autosomal recessive form characterized by neonatal hypotonia. {ECO:0000269 PubMed:24610330}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Additional Disease Information for PREPL

genes like me logo Genes that share disorders with PREPL: view

No data available for Genatlas for PREPL Gene

Publications for PREPL Gene

  1. PREPL deficiency with or without cystinuria causes a novel myasthenic syndrome. (PMID: 24610330) Régal L … Engel AG (Neurology 2014) 2 3 4 58
  2. Deletion of PREPL, a gene encoding a putative serine oligopeptidase, in patients with hypotonia-cystinuria syndrome. (PMID: 16385448) Jaeken J … Matthijs G (American journal of human genetics 2006) 3 4 22 58
  3. The 2p21 deletion syndrome: characterization of the transcription content. (PMID: 15913950) Parvari R … Hershkovitz E (Genomics 2005) 3 4 58
  4. The PREPL A protein, a new member of the prolyl oligopeptidase family, lacking catalytic activity. (PMID: 16143824) Szeltner Z … Polgár L (Cellular and molecular life sciences : CMLS 2005) 3 4 58
  5. A recessive contiguous gene deletion of chromosome 2p16 associated with cystinuria and a mitochondrial disease. (PMID: 11524703) Parvari R … Hershkovitz E (American journal of human genetics 2001) 2 3 58

Products for PREPL Gene

Sources for PREPL Gene

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