This gene encodes a peptide hormone that binds to the Apelin receptor. The encoded protein is required for heart development in zebrafish and has been shown to maintain self-renewal of human embryonic stem cells through activation of the PI3K/AKT pathway. Experiments in human and mouse cell lines point to additional roles for the encoded protein in angiogenesis and regulation o... See more...

Aliases for APELA Gene

Aliases for APELA Gene

  • Apelin Receptor Early Endogenous Ligand 2 3 4 5
  • ELA 2 3 4
  • Protein Elabela 3 4
  • Protein Toddler 3 4
  • Ende 2 3
  • Tdl 2 3
  • ELABELA 2
  • Toddler 2
  • APELA 5
  • TDL 4

External Ids for APELA Gene

Previous GeneCards Identifiers for APELA Gene

  • GC04P165801

Summaries for APELA Gene

Entrez Gene Summary for APELA Gene

  • This gene encodes a peptide hormone that binds to the Apelin receptor. The encoded protein is required for heart development in zebrafish and has been shown to maintain self-renewal of human embryonic stem cells through activation of the PI3K/AKT pathway. Experiments in human and mouse cell lines point to additional roles for the encoded protein in angiogenesis and regulation of vascular tone. [provided by RefSeq, Jul 2016]

GeneCards Summary for APELA Gene

APELA (Apelin Receptor Early Endogenous Ligand) is a Protein Coding gene. Diseases associated with APELA include Thyroid Cancer, Nonmedullary, 1 and Vaginal Mullerian Papilloma. Gene Ontology (GO) annotations related to this gene include hormone activity and apelin receptor binding.

UniProtKB/Swiss-Prot Summary for APELA Gene

  • Endogenous ligand for the apelin receptor (APLNR) (PubMed:25639753, PubMed:28137936). Hormone required for mesendodermal differentiation, blood vessels formation and heart morphogenesis during early development and for adult cardiovascular homeostasis (PubMed:25639753, PubMed:28137936). Drives internalization of APLNR. Acts as a motogen by promoting mesendodermal cell migration during gastrulation by binding and activating APLNR. Acts as an early embryonic regulator of cellular movement with a role in migration and development of cardiac progenitor cells. May act as a chemoattractant for the activation of angioblast migration toward the embryonic midline, i.e. the position of the future vessel formation, during vasculogenesis. Positively regulates sinus venosus (SV)-derived endothelial cells migration into the developing heart to promote coronary blood vessel sprouting. Plays a role in placental vascular development; promotes placental trophoblast invasion and spiral artery remodeling in the uterus. Involved in the regulation of maternal cardiovascular homeostasis to prevent gestational hypertension and for potent cardioprotective functions during heart failure. Mediates myocardial contractility in an ERK1/2-dependent manner (By similarity).

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

Genomics for APELA Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for APELA 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
GH04J164876 Promoter/Enhancer 2 EPDnew Ensembl ENCODE CraniofacialAtlas dbSUPER 600.7 +0.7 702 2.6 STAT3 TCF12 PKNOX1 DPF2 RELB RUNX3 ZNF316 POLR2A BCL11A NBN APELA lnc-APELA-1 piR-38051-210 TRIM61
GH04J164866 Enhancer 0.8 Ensembl ENCODE dbSUPER 0.4 -9.9 -9922 2.6 IKZF2 NANOG POLR2A SP1 POU5F1 IKZF1 RNU6-668P APELA lnc-APELA-1 RF00017-4446 SMIM31
GH04J164956 Promoter/Enhancer 1.5 Ensembl ENCODE CraniofacialAtlas 0.2 +81.5 81472 4.2 SP1 ZNF629 POLR2A LARP7 GABPA ZNF143 SMAD5 NR2C1 ZNF501 GTF2F1 FAM218A TRIM60P14 ENSG00000250712 piR-35674-401 lnc-FAM218A-3 TRIM61 APELA
GH04J164977 Promoter/Enhancer 1.8 EPDnew Ensembl ENCODE CraniofacialAtlas 0.1 +100.4 100402 2 GABPA SMAD5 RCOR1 POLR2A NRF1 ELK1 CTCF RUNX3 ZBTB40 CBFB TRIM61 piR-34593-034 TRIM60P14 lnc-FAM218A-5 lnc-FAM218A-3 APELA
GH04J164884 Enhancer 0.6 dbSUPER 0.4 +7.4 7438 0.5 CTCF ZNF512 MTA1 TRIM22 ZNF512B U2AF2 SMC3 POLR2A NBN ZNF654 RNU6-668P APELA lnc-APELA-1 piR-38051-210 TRIM61
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around APELA on the GeneHancer Hub at the UCSC Golden Path

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

Genomic Locations for APELA Gene

Genomic Locations for APELA Gene
chr4:164,877,023-164,899,063
(GRCh38/hg38)
Size:
22,041 bases
Orientation:
Plus strand
chr4:165,798,156-165,820,117
(GRCh37/hg19)
Size:
21,962 bases
Orientation:
Plus strand

Genomic View for APELA Gene

Genes around APELA on UCSC Golden Path with GeneCards custom track

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

RefSeq DNA sequence for APELA Gene

Proteins for APELA Gene

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

    Protein Symbol:
    P0DMC3-ELA_HUMAN
    Recommended name:
    Apelin receptor early endogenous ligand
    Protein Accession:
    P0DMC3

    Protein attributes for APELA Gene

    Size:
    54 amino acids
    Molecular mass:
    6622 Da
    Quaternary structure:
    • Interacts with APLNR (PubMed:24316148).

neXtProt entry for APELA Gene

Post-translational modifications for APELA Gene

  • Glycosylation at Asn27

Other Protein References for APELA Gene

No data available for DME Specific Peptides for APELA Gene

Domains & Families for APELA Gene

Gene Families for APELA Gene

HGNC:
Human Protein Atlas (HPA):
  • Predicted secreted proteins

Protein Domains for APELA Gene

ProtoNet:

Graphical View of Domain Structure for InterPro Entry

P0DMC3

UniProtKB/Swiss-Prot:

ELA_HUMAN :
  • Belongs to the Elabela/Toddler family.
Family:
  • Belongs to the Elabela/Toddler family.
genes like me logo Genes that share domains with APELA: view

No data available for Suggested Antigen Peptide Sequences for APELA Gene

Function for APELA Gene

Molecular function for APELA Gene

UniProtKB/Swiss-Prot Function:
Endogenous ligand for the apelin receptor (APLNR) (PubMed:25639753, PubMed:28137936). Hormone required for mesendodermal differentiation, blood vessels formation and heart morphogenesis during early development and for adult cardiovascular homeostasis (PubMed:25639753, PubMed:28137936). Drives internalization of APLNR. Acts as a motogen by promoting mesendodermal cell migration during gastrulation by binding and activating APLNR. Acts as an early embryonic regulator of cellular movement with a role in migration and development of cardiac progenitor cells. May act as a chemoattractant for the activation of angioblast migration toward the embryonic midline, i.e. the position of the future vessel formation, during vasculogenesis. Positively regulates sinus venosus (SV)-derived endothelial cells migration into the developing heart to promote coronary blood vessel sprouting. Plays a role in placental vascular development; promotes placental trophoblast invasion and spiral artery remodeling in the uterus. Involved in the regulation of maternal cardiovascular homeostasis to prevent gestational hypertension and for potent cardioprotective functions during heart failure. Mediates myocardial contractility in an ERK1/2-dependent manner (By similarity).

Phenotypes From GWAS Catalog for APELA Gene

Gene Ontology (GO) - Molecular Function for APELA Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005179 hormone activity ISS --
GO:0031704 apelin receptor binding ISS --
genes like me logo Genes that share ontologies with APELA: view

No data available for Enzyme Numbers (IUBMB) , Phenotypes , Human Phenotype Ontology , Animal Models , miRNA , Transcription Factor Targets and HOMER Transcription for APELA Gene

Localization for APELA Gene

Subcellular locations from UniProtKB/Swiss-Prot for APELA Gene

Secreted. Secreted, extracellular space. Note=Found in blood plasma (PubMed:28137936). Found in serum of pregnant mice, peaking at midgestation; indicating a maternal and zygotic origin of circulating APELA during pregnancy (By similarity). {ECO:0000250 UniProtKB:P0DMC4}.

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

Gene Ontology (GO) - Cellular Components for APELA Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005576 extracellular region IEA,IDA 24316148
GO:0005615 extracellular space ISS --
GO:0016020 membrane IEA --
GO:0016021 integral component of membrane IEA --
genes like me logo Genes that share ontologies with APELA: view

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

Pathways & Interactions for APELA Gene

PathCards logo

SuperPathways for APELA Gene

No Data Available

Interacting Proteins for APELA Gene

Gene Ontology (GO) - Biological Process for APELA Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001525 angiogenesis IEA --
GO:0001570 vasculogenesis ISS --
GO:0007275 multicellular organism development IEA --
GO:0007369 gastrulation IEA --
GO:0007492 endoderm development ISS --
genes like me logo Genes that share ontologies with APELA: view

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

Drugs & Compounds for APELA Gene

No Compound Related Data Available

Transcripts for APELA Gene

mRNA/cDNA for APELA Gene

1 REFSEQ mRNAs :
3 NCBI additional mRNA sequence :
5 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

Inhibitory RNA Products

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

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

No ASD Table

Relevant External Links for APELA Gene

GeneLoc Exon Structure for
APELA

Expression for APELA Gene

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

mRNA differential expression in normal tissues according to GTEx for APELA Gene

This gene is overexpressed in Prostate (x7.4) and Skin - Not Sun Exposed (Suprapubic) (x4.8).

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

mRNA Expression by UniProt/SwissProt for APELA Gene:

P0DMC3-ELA_HUMAN
Tissue specificity: Expressed in the intima of blood vessels (PubMed:28137936). Expressed in endothelial cells in blood vessels in the heart and lung (PubMed:28137936). Expressed in cytotrophoblasts and syncytiotrophoblasts of first-trimester placental tissue and term placentas (at protein level) (PubMed:28663440). Not detected in smooth muscle cells or cardiomyocytes (at protein level) (PubMed:28137936). Expressed in kidney (PubMed:25639753). Expressed in blood vessels (PubMed:28137936). Expressed in embryonic (ESCs) and induced (iPSCs) pluripotent stem cells (PubMed:25639753). Most highly expressed in undifferentiated embryonic stem cell and is rapidly down-regulated during differentiation (PubMed:24316148).

Evidence on tissue expression from TISSUES for APELA Gene

  • Skin(2.9)
  • Nervous system(2.7)
  • Blood(2.5)
  • Heart(2.2)
  • Bone(2.1)
  • Muscle(2.1)
  • Urine(2.1)
genes like me logo Genes that share expression patterns with APELA: view

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

Orthologs for APELA Gene

Evolution for APELA Gene

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

No data available for Orthologs for APELA Gene

Paralogs for APELA Gene

No data available for Paralogs for APELA Gene

Variants for APELA Gene

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

SNP ID Clinical significance and condition Chr 04 pos Variation AA Info Type
718276 Likely Benign: not provided 164,877,355(+) T/C SYNONYMOUS_VARIANT
769296 Likely Benign: not provided 164,879,002(+) T/C SYNONYMOUS_VARIANT

Additional dbSNP identifiers (rs#s) for APELA Gene

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

Variant ID Type Subtype PubMed ID
esv2674138 CNV deletion 23128226
esv2759299 CNV gain 17122850
esv2760864 CNV gain 21179565
esv3603007 CNV gain 21293372
esv3603008 CNV loss 21293372
nsv1019150 CNV gain 25217958
nsv528320 CNV loss 19592680
nsv528686 CNV gain 19592680
nsv596037 CNV gain 21841781

Additional Variant Information for APELA Gene

SNPedia medical, phenotypic, and genealogical associations of SNPs for
APELA

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot and Variation tolerance for APELA Gene

Disorders for APELA Gene

MalaCards: The human disease database

(33) MalaCards diseases for APELA Gene - From: LncRNADisease and DISEASES

Disorder Aliases PubMed IDs
thyroid cancer, nonmedullary, 1
  • nmtc1
vaginal mullerian papilloma
  • vaginal muellerian papilloma
factitious disorder
  • munchausen syndrome
munchausen by proxy
  • munchausen syndrome by proxy
urethral false passage
- elite association - COSMIC cancer census association via MalaCards
Search APELA in MalaCards View complete list of genes associated with diseases
genes like me logo Genes that share disorders with APELA: view

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

Publications for APELA Gene

  1. ELABELA: a hormone essential for heart development signals via the apelin receptor. (PMID: 24316148) Chng SC … Reversade B (Developmental cell 2013) 2 3 4
  2. ELABELA deficiency promotes preeclampsia and cardiovascular malformations in mice. (PMID: 28663440) Ho L … Reversade B (Science (New York, N.Y.) 2017) 3 4
  3. Elabela/Toddler Is an Endogenous Agonist of the Apelin APJ Receptor in the Adult Cardiovascular System, and Exogenous Administration of the Peptide Compensates for the Downregulation of Its Expression in Pulmonary Arterial Hypertension. (PMID: 28137936) Yang P … Davenport AP (Circulation 2017) 3 4
  4. Elabela-apelin receptor signaling pathway is functional in mammalian systems. (PMID: 25639753) Wang Z … Gong DW (Scientific reports 2015) 3 4
  5. Toddler: an embryonic signal that promotes cell movement via Apelin receptors. (PMID: 24407481) Pauli A … Schier AF (Science (New York, N.Y.) 2014) 2 3

Products for APELA Gene

Sources for APELA Gene