This gene encodes a member of the rhomboid family of intramembrane serine proteases that is localized to the inner mitochondrial membrane. The encoded protein regulates mitochondrial remodeling and apoptosis through regulated substrate proteolysis. Proteolytic processing of the encoded protein results in the release of a small peptide, P-beta, which may transit to the nucleus. ... See more...

Aliases for PARL Gene

Aliases for PARL Gene

  • Presenilin Associated Rhomboid Like 2 3 5
  • Presenilins-Associated Rhomboid-Like Protein, Mitochondrial 3 4
  • EC 3.4.21.105 4 52
  • PSARL 3 4
  • Mitochondrial Intramembrane-Cleaving Protease PARL 3
  • Mitochondrial Intramembrane Cleaving Protease PARL 4
  • Presenilin Associated, Rhomboid-Like 2
  • Rhomboid 7 Homolog 1 (Drosophila) 2
  • Rhomboid 7 Homolog 1 3
  • PRO2207 3
  • PSENIP2 3
  • PSARL1 3
  • RHBDS1 3

External Ids for PARL Gene

Previous HGNC Symbols for PARL Gene

  • PSARL

Previous GeneCards Identifiers for PARL Gene

  • GC03M180317
  • GC03M184541
  • GC03M185030
  • GC03M183547
  • GC03M180956

Summaries for PARL Gene

Entrez Gene Summary for PARL Gene

  • This gene encodes a member of the rhomboid family of intramembrane serine proteases that is localized to the inner mitochondrial membrane. The encoded protein regulates mitochondrial remodeling and apoptosis through regulated substrate proteolysis. Proteolytic processing of the encoded protein results in the release of a small peptide, P-beta, which may transit to the nucleus. Mutations in this gene may be associated with Parkinson's disease. [provided by RefSeq, May 2016]

GeneCards Summary for PARL Gene

PARL (Presenilin Associated Rhomboid Like) is a Protein Coding gene. Diseases associated with PARL include Early-Onset Parkinson's Disease and Primary Angle-Closure Glaucoma. Gene Ontology (GO) annotations related to this gene include serine-type endopeptidase activity and endopeptidase activity. An important paralog of this gene is ENSG00000283765.

UniProtKB/Swiss-Prot Summary for PARL Gene

  • Required for the control of apoptosis during postnatal growth. Essential for proteolytic processing of an antiapoptotic form of OPA1 which prevents the release of mitochondrial cytochrome c in response to intrinsic apoptotic signals (By similarity). Required for the maturation of PINK1 into its 52kDa mature form after its cleavage by mitochondrial-processing peptidase (MPP) (PubMed:22354088). Promotes changes in mitochondria morphology regulated by phosphorylation of P-beta domain (PubMed:14732705, PubMed:17116872).

Gene Wiki entry for PARL Gene

Additional gene information for PARL Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for PARL Gene

Genomics for PARL Gene

GeneHancer (GH) Regulatory Elements for PARL Gene

Promoters and enhancers for PARL Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH03J183883 Promoter/Enhancer 2.1 EPDnew Ensembl ENCODE CraniofacialAtlas 513.1 +0.7 733 3.2 FOXK2 HNRNPK ZBTB40 ZNF217 EP300 CTCF SIN3A NRF1 TCF12 MYC PARL ENSG00000283765 RPSAP31 lnc-PARL-1 ALG3 EIF2B5 FAM131A POLR2H ABCC5 ENSG00000228205
GH03J183876 Promoter/Enhancer 1 EPDnew ENCODE 523.4 +7.2 7228 1.7 MYC GABPA CEBPG MAX ZNF592 SPI1 MNT HDAC2 ATF4 POLR2A PARL RF00994-710 piR-35062-003 ABCC5 MAP6D1 ALG3 ECE2 VWA5B2 MIR1224 CAMK2N2
GH03J183840 Promoter 0.3 EPDnew 525.9 +44.3 44345 0.1 PARL YEATS2 RPSAP31 piR-33614-203 lnc-MAP6D1-2 ENSG00000283765
GH03J184154 Promoter/Enhancer 2.1 EPDnew Ensembl ENCODE CraniofacialAtlas dbSUPER 22.3 -271.6 -271625 4.5 POLR2G SP1 NCOR1 TEAD4 ZFX ZNF639 ZBTB5 REST POLR2A ZBTB10 DVL3 PARL ENSG00000228205 EIF2B5 ABCF3 POLR2H ALG3 ECE2 CAMK2N2 PSMD2
GH03J184247 Promoter/Enhancer 2.1 EPDnew Ensembl ENCODE CraniofacialAtlas 13.5 -364.3 -364268 3.2 EP300 FOXK2 ZBTB40 ZNF217 CTCF SIN3A NRF1 TCF12 MYC POLR2G ALG3 ECE2 EEF1AKMT4 EEF1AKMT4-ECE2 ENSG00000228205 PARL VWA5B2 DVL3 POLR2H EIF2B5
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around PARL on UCSC Golden Path with GeneCards custom track

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for PARL

Top Transcription factor binding sites by QIAGEN in the PARL gene promoter:
  • C/EBPalpha
  • CUTL1
  • FOXD1
  • GR
  • GR-alpha
  • GR-beta
  • HNF-4alpha1
  • HNF-4alpha2
  • TGIF
  • Zic3

Genomic Locations for PARL Gene

Genomic Locations for PARL Gene
chr3:183,826,488-183,884,933
(GRCh38/hg38)
Size:
58,446 bases
Orientation:
Minus strand
chr3:183,547,173-183,602,721
(GRCh37/hg19)
Size:
55,549 bases
Orientation:
Minus strand

Genomic View for PARL Gene

Genes around PARL on UCSC Golden Path with GeneCards custom track

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

RefSeq DNA sequence for PARL Gene

Proteins for PARL Gene

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

    Protein Symbol:
    Q9H300-PARL_HUMAN
    Recommended name:
    Presenilins-associated rhomboid-like protein, mitochondrial
    Protein Accession:
    Q9H300
    Secondary Accessions:
    • Q96CQ4
    • Q9BTJ6
    • Q9P1E3

    Protein attributes for PARL Gene

    Size:
    379 amino acids
    Molecular mass:
    42190 Da
    Quaternary structure:
    • Interacts with PSEN1 and PSEN2. Binds OPA1.

    Alternative splice isoforms for PARL Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for PARL Gene

Selected DME Specific Peptides for PARL Gene

Q9H300:
  • FFDHAAHLGGALFG
  • RKEINKWWN
  • SIVNILGQEQF
  • IMTVLAAVCTKIPE
  • RTMIRYFTSNPASKVLCSPMLLSTFSHFSLFHMAANMYV
  • LSDGQRTVTGIIAAN
  • FTVGFTGC
  • YGHELIW
  • GPSLGASG

Post-translational modifications for PARL Gene

  • P-beta is proteolytically processed (beta-cleavage) in a PARL-dependent manner. The cleavage is inhibited when residues Ser-65, Thr-69 and Ser-70 are all phosphorylated.
  • Ubiquitination at Lys75, Lys136, and Lys362
  • Modification sites at PhosphoSitePlus

Domains & Families for PARL Gene

Gene Families for PARL Gene

HGNC:
Human Protein Atlas (HPA):
  • Enzymes
  • Predicted intracellular proteins
  • Predicted membrane proteins
  • Transporters

Protein Domains for PARL Gene

Blocks:
  • Rhomboid-like protein
InterPro:
ProtoNet:

Suggested Antigen Peptide Sequences for PARL Gene

GenScript: Design optimal peptide antigens:
  • Mitochondrial intramembrane cleaving protease PARL (PARL_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q9H300

UniProtKB/Swiss-Prot:

PARL_HUMAN :
  • Belongs to the peptidase S54 family.
Family:
  • Belongs to the peptidase S54 family.
genes like me logo Genes that share domains with PARL: view

Function for PARL Gene

Molecular function for PARL Gene

UniProtKB/Swiss-Prot Function:
Required for the control of apoptosis during postnatal growth. Essential for proteolytic processing of an antiapoptotic form of OPA1 which prevents the release of mitochondrial cytochrome c in response to intrinsic apoptotic signals (By similarity). Required for the maturation of PINK1 into its 52kDa mature form after its cleavage by mitochondrial-processing peptidase (MPP) (PubMed:22354088). Promotes changes in mitochondria morphology regulated by phosphorylation of P-beta domain (PubMed:14732705, PubMed:17116872).
UniProtKB/Swiss-Prot CatalyticActivity:
Reaction=Cleaves type-1 transmembrane domains using a catalytic dyad composed of serine and histidine that are contributed by different transmembrane domains.; EC=3.4.21.105; Evidence=. ;.

Enzyme Numbers (IUBMB) for PARL Gene

Phenotypes From GWAS Catalog for PARL Gene

Gene Ontology (GO) - Molecular Function for PARL Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004175 endopeptidase activity IMP 21426348
GO:0004252 serine-type endopeptidase activity IBA,IEA 21873635
GO:0005515 protein binding IPI 21138942
GO:0008233 peptidase activity IEA --
GO:0008236 serine-type peptidase activity IEA --
genes like me logo Genes that share ontologies with PARL: view
genes like me logo Genes that share phenotypes with PARL: view

Animal Models for PARL Gene

MGI Knock Outs for PARL:
  • Parl Parl<tm1.1Bdes>
  • Parl Parl<tm1a(EUCOMM)Hmgu>

Animal Model Products

  • Taconic Biosciences Mouse Models for PARL

CRISPR Products

Inhibitory RNA Products

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

Clone Products

  • Addgene plasmids for PARL
  • Addgene plasmids for PARL

No data available for Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for PARL Gene

Localization for PARL Gene

Subcellular locations from UniProtKB/Swiss-Prot for PARL Gene

Mitochondrion inner membrane; Multi-pass membrane protein.
[P-beta]: Nucleus. Note=Translocated into the nucleus by an unknown mechanism (PubMed:17116872). {ECO:0000269 PubMed:17116872}.

Subcellular locations from

COMPARTMENTS
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 PARL gene
Compartment Confidence
mitochondrion 5
nucleus 4
peroxisome 2
endoplasmic reticulum 2
cytosol 2
lysosome 2
plasma membrane 1
extracellular 1
cytoskeleton 1
endosome 1
golgi apparatus 1

Subcellular locations from the

Human Protein Atlas (HPA)

Gene Ontology (GO) - Cellular Components for PARL Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005634 nucleus IEA --
GO:0005739 mitochondrion IBA 21873635
GO:0005743 mitochondrial inner membrane TAS 21426348
GO:0016020 membrane IEA --
GO:0016021 integral component of membrane IEA --
genes like me logo Genes that share ontologies with PARL: view

Pathways & Interactions for PARL Gene

PathCards logo

SuperPathways for PARL Gene

No Data Available

Gene Ontology (GO) - Biological Process for PARL Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006508 proteolysis IMP,IEA 21426348
GO:0006851 mitochondrial calcium ion transmembrane transport TAS --
GO:0010821 regulation of mitochondrion organization IMP 21355049
GO:0030162 regulation of proteolysis IGI 21355049
GO:0033619 membrane protein proteolysis TAS 24522549
genes like me logo Genes that share ontologies with PARL: view

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

Drugs & Compounds for PARL Gene

No Compound Related Data Available

Transcripts for PARL Gene

mRNA/cDNA for PARL Gene

6 REFSEQ mRNAs :
7 NCBI additional mRNA sequence :
13 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Inhibitory RNA Products

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

Clone Products

  • Addgene plasmids for PARL
  • Addgene plasmids for PARL

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

ExUns: 1a · 1b · 1c ^ 2a · 2b ^ 3 ^ 4 ^ 5a · 5b · 5c ^ 6a · 6b · 6c ^ 7a · 7b ^ 8 ^ 9a · 9b ^ 10 ^ 11a · 11b
SP1: - - -
SP2: - - - - -
SP3: - - - - - -
SP4: - -
SP5: - -
SP6: - - - -
SP7: - - - -
SP8:
SP9: - - -

Relevant External Links for PARL Gene

GeneLoc Exon Structure for
PARL

Expression for PARL Gene

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

Protein differential expression in normal tissues from HIPED for PARL Gene

This gene is overexpressed in Nasal epithelium (57.6).

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



Transcriptomic regulation report from SPP (The Signaling Pathways Project) for PARL

SOURCE GeneReport for Unigene cluster for PARL Gene:

Hs.478469

Evidence on tissue expression from TISSUES for PARL Gene

  • Lung(4.4)
  • Nervous system(3.3)
genes like me logo Genes that share expression patterns with PARL: view

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery , mRNA differential expression in normal tissues , Protein tissue co-expression partners , mRNA Expression by UniProt/SwissProt and Phenotype-based relationships between genes and organs from Gene ORGANizer for PARL Gene

Orthologs for PARL Gene

This gene was present in the common ancestor of animals and fungi.

Orthologs for PARL Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia PARL 31 30
  • 99.82 (n)
OneToOne
dog
(Canis familiaris)
Mammalia PARL 31 30
  • 93.05 (n)
OneToOne
cow
(Bos Taurus)
Mammalia PARL 31 30
  • 92.57 (n)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia -- 31
  • 91 (a)
OneToMany
-- 31
  • 70 (a)
OneToMany
mouse
(Mus musculus)
Mammalia Parl 17 31 30
  • 87.09 (n)
rat
(Rattus norvegicus)
Mammalia Parl 30
  • 85.5 (n)
oppossum
(Monodelphis domestica)
Mammalia PARL 31
  • 84 (a)
OneToOne
chicken
(Gallus gallus)
Aves PARL 31 30
  • 71.91 (n)
OneToOne
lizard
(Anolis carolinensis)
Reptilia PARL 31
  • 66 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia parl 30
  • 69.38 (n)
Str.16379 30
African clawed frog
(Xenopus laevis)
Amphibia Xl.4319 30
zebrafish
(Danio rerio)
Actinopterygii PARL (1 of 2) 31
  • 67 (a)
OneToMany
LOC792889 30
  • 64.86 (n)
parla 31
  • 54 (a)
OneToMany
Dr.337 30
rainbow trout
(Oncorhynchus mykiss)
Actinopterygii Omy.4994 30
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP002626 30
  • 52.69 (n)
fruit fly
(Drosophila melanogaster)
Insecta rho-7 31 32 30
  • 52.19 (n)
OneToOne
worm
(Caenorhabditis elegans)
Secernentea rom-5 31
  • 35 (a)
OneToOne
baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes PCP1 33 31
  • 23 (a)
fission yeast
(Schizosaccharomyces pombe)
Schizosaccharomycetes SPBC13E7.11 30
  • 47.55 (n)
sea squirt
(Ciona savignyi)
Ascidiacea CSA.8594 31
  • 25 (a)
OneToOne
Species where no ortholog for PARL was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • 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)
  • 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)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)

Evolution for PARL Gene

ENSEMBL:
Gene Tree for PARL (if available)
TreeFam:
Gene Tree for PARL (if available)
Aminode:
Evolutionary constrained regions (ECRs) for PARL: view image

Paralogs for PARL Gene

Paralogs for PARL Gene

Pseudogenes.org Pseudogenes for PARL Gene

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

Variants for PARL Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for PARL Gene

SNP ID Clinical significance and condition Chr 03 pos Variation AA Info Type
718072 Likely Benign: not provided 183,884,724(-) G/A NON_CODING_TRANSCRIPT_VARIANT,SYNONYMOUS_VARIANT
755321 Likely Benign: not provided 183,884,817(-) G/A NON_CODING_TRANSCRIPT_VARIANT,SYNONYMOUS_VARIANT
rs571537271 Uncertain Significance: not provided 183,867,956(-) C/T MISSENSE_VARIANT,NON_CODING_TRANSCRIPT_VARIANT
rs3732581 - p.Val262Leu
rs4912470 - p.Ala137Gly

Additional dbSNP identifiers (rs#s) for PARL Gene

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

Variant ID Type Subtype PubMed ID
esv2512102 CNV insertion 19546169
esv3598932 CNV loss 21293372
esv3598933 CNV gain 21293372
nsv520163 CNV gain 19592680
nsv592656 CNV gain 21841781
nsv820085 CNV loss 19587683

Variation tolerance for PARL Gene

Residual Variation Intolerance Score: 65.9% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 11.16; 92.35% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for PARL Gene

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

SNP Genotyping and Copy Number Assay Products

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

Disorders for PARL Gene

MalaCards: The human disease database

(9) MalaCards diseases for PARL Gene - From: DISEASES and GeneCards

Disorder Aliases PubMed IDs
early-onset parkinson's disease
  • early-onset parkinson disease
primary angle-closure glaucoma
  • primary angle closure glaucoma
inflammatory mfh
  • xanthosarcoma
3-methylglutaconic aciduria, type iii
  • mgca3
spastic paraplegia 7, autosomal recessive
  • spg7
- elite association - COSMIC cancer census association via MalaCards
Search PARL in MalaCards View complete list of genes associated with diseases

Additional Disease Information for PARL

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
genes like me logo Genes that share disorders with PARL: view

No data available for UniProtKB/Swiss-Prot and Genatlas for PARL Gene

Publications for PARL Gene

  1. Evaluation of nine candidate genes in patients with normal tension glaucoma: a case control study. (PMID: 19754948) Wolf C … Weisschuh N (BMC medical genetics 2009) 3 23 41 54
  2. Phosphorylation and cleavage of presenilin-associated rhomboid-like protein (PARL) promotes changes in mitochondrial morphology. (PMID: 17116872) Jeyaraju DV … Pellegrini L (Proceedings of the National Academy of Sciences of the United States of America 2006) 3 4 23 54
  3. Genetic variants in nuclear-encoded mitochondrial genes influence AIDS progression. (PMID: 20877624) Hendrickson SL … O'Brien SJ (PloS one 2010) 3 41 54
  4. No association between the SNPs (rs3749446 and rs1402000) in the PARL gene and LHON in Chinese patients with m.11778G>A. (PMID: 20711738) Zhang AM … Yao YG (Human genetics 2010) 3 41 54
  5. Genetic variation in PARL influences mitochondrial content. (PMID: 19862556) Curran JE … Kissebah AH (Human genetics 2010) 3 23 54

Products for PARL Gene

Sources for PARL Gene