This gene encodes a secreted ligand of the TGF-beta (transforming growth factor-beta) superfamily of proteins. Ligands of this family bind various TGF-beta receptors leading to recruitment and activation of SMAD family transcription factors that regulate gene expression. The encoded preproprotein is proteolytically processed to generate the mature protein, which plays a role in... See more...

Aliases for LEFTY2 Gene

Aliases for LEFTY2 Gene

  • Left-Right Determination Factor 2 2 3 4 5
  • LEFTYA 2 3 4
  • LEFTA 2 3 4
  • Endometrial Bleeding-Associated Factor 3 4
  • Left-Right Determination Factor A 3 4
  • Transforming Growth Factor Beta-4 3 4
  • Protein Lefty-2 3 4
  • Protein Lefty-A 3 4
  • TGF-Beta-4 3 4
  • TGFB4 3 4
  • EBAF 3 4
  • Endometrial Bleeding Associated Factor (Left-Right Determination, Factor A; Transforming Growth Factor Beta Superfamily) 2
  • Transforming Growth Factor, Beta-4 (Endometrial Bleeding-Associated Factor; LEFTY A) 2
  • LEFTY2 5

External Ids for LEFTY2 Gene

Previous HGNC Symbols for LEFTY2 Gene

  • TGFB4
  • EBAF

Previous GeneCards Identifiers for LEFTY2 Gene

  • GC01M222432
  • GC01M224190
  • GC01M226126
  • GC01M196642

Summaries for LEFTY2 Gene

Entrez Gene Summary for LEFTY2 Gene

  • This gene encodes a secreted ligand of the TGF-beta (transforming growth factor-beta) superfamily of proteins. Ligands of this family bind various TGF-beta receptors leading to recruitment and activation of SMAD family transcription factors that regulate gene expression. The encoded preproprotein is proteolytically processed to generate the mature protein, which plays a role in left-right asymmetry determination of organ systems during development. The protein may also play a role in endometrial bleeding. Mutations in this gene have been associated with left-right axis malformations, particularly in the heart and lungs. Some types of infertility have been associated with dysregulated expression of this gene in the endometrium. This gene is closely linked to both a related family member and a related pseudogene. This gene encodes multiple isoforms that may undergo similar proteolytic processing. [provided by RefSeq, Aug 2016]

GeneCards Summary for LEFTY2 Gene

LEFTY2 (Left-Right Determination Factor 2) is a Protein Coding gene. Diseases associated with LEFTY2 include Visceral Heterotaxy and Complete Atrioventricular Canal. Among its related pathways are Nanog in Mammalian ESC Pluripotency and Cyclins and Cell Cycle Regulation. Gene Ontology (GO) annotations related to this gene include cytokine activity and transforming growth factor beta receptor binding. An important paralog of this gene is LEFTY1.

UniProtKB/Swiss-Prot Summary for LEFTY2 Gene

  • Required for left-right (L-R) asymmetry determination of organ systems in mammals. May play a role in endometrial bleeding.

No data available for CIViC Summary , Tocris Summary , Gene Wiki entry , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for LEFTY2 Gene

Genomics for LEFTY2 Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for LEFTY2 Gene
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around LEFTY2 on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for LEFTY2

Top Transcription factor binding sites by QIAGEN in the LEFTY2 gene promoter:
  • AP-2gamma
  • CREB
  • GCNF
  • GCNF-1
  • GCNF-2
  • Nkx2-5
  • Pax-3
  • Roaz
  • RP58

Genomic Locations for LEFTY2 Gene

Latest Assembly
chr1:225,936,598-225,941,383
(GRCh38/hg38)
Size:
4,786 bases
Orientation:
Minus strand

Previous Assembly
chr1:226,124,303-226,128,920
(GRCh37/hg19 by Entrez Gene)
Size:
4,618 bases
Orientation:
Minus strand

chr1:226,124,298-226,129,189
(GRCh37/hg19 by Ensembl)
Size:
4,892 bases
Orientation:
Minus strand

Genomic View for LEFTY2 Gene

Genes around LEFTY2 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
LEFTY2 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for LEFTY2 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for LEFTY2 Gene

Proteins for LEFTY2 Gene

  • Protein details for LEFTY2 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    O00292-LFTY2_HUMAN
    Recommended name:
    Left-right determination factor 2
    Protein Accession:
    O00292
    Secondary Accessions:
    • B3KNH4
    • B4E332
    • E9PDM4
    • O75611
    • Q5TE89
    • Q8NBQ9

    Protein attributes for LEFTY2 Gene

    Size:
    366 amino acids
    Molecular mass:
    40920 Da
    Quaternary structure:
    No Data Available
    SequenceCaution:
    • Sequence=AAB53269.1; Type=Miscellaneous discrepancy; Note=Authors have revised their sequence, but have not submitted the revised DNA sequence.; Evidence={ECO:0000305};

    Alternative splice isoforms for LEFTY2 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for LEFTY2 Gene

Post-translational modifications for LEFTY2 Gene

  • The processing of the protein may also occur at the second R-X-X-R site located at AA 132-135. Processing appears to be regulated in a cell-type specific manner.
  • Glycosylation at Asn158
  • Modification sites at PhosphoSitePlus

Other Protein References for LEFTY2 Gene

No data available for DME Specific Peptides for LEFTY2 Gene

Domains & Families for LEFTY2 Gene

Gene Families for LEFTY2 Gene

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

Protein Domains for LEFTY2 Gene

InterPro:
Blocks:
  • Transforming growth factor beta (TGFb), N-terminal
  • Transforming growth factor beta (TGFb)
  • Transforming growth factor beta 4 precursor signature

Suggested Antigen Peptide Sequences for LEFTY2 Gene

GenScript: Design optimal peptide antigens:
  • Transforming growth factor beta-4 (LFTY2_HUMAN)

Graphical View of Domain Structure for InterPro Entry

O00292

UniProtKB/Swiss-Prot:

LFTY2_HUMAN :
  • Belongs to the TGF-beta family.
Family:
  • Belongs to the TGF-beta family.
genes like me logo Genes that share domains with LEFTY2: view

Function for LEFTY2 Gene

Molecular function for LEFTY2 Gene

UniProtKB/Swiss-Prot Function:
Required for left-right (L-R) asymmetry determination of organ systems in mammals. May play a role in endometrial bleeding.

LifeMap Function Summary for LEFTY2 Gene

LEFTY2 as growth factor is involved in stem cell differentiation protocols towards the derivation of the following cells:

Phenotypes From GWAS Catalog for LEFTY2 Gene

Gene Ontology (GO) - Molecular Function for LEFTY2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005125 cytokine activity IBA 21873635
GO:0005160 transforming growth factor beta receptor binding IEA --
GO:0008083 growth factor activity IEA --
genes like me logo Genes that share ontologies with LEFTY2: view
genes like me logo Genes that share phenotypes with LEFTY2: view

Animal Models for LEFTY2 Gene

MGI Knock Outs for LEFTY2:

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for LEFTY2

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for LEFTY2 Gene

Localization for LEFTY2 Gene

Subcellular locations from UniProtKB/Swiss-Prot for LEFTY2 Gene

Secreted.

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 LEFTY2 gene
Compartment Confidence
extracellular 5
cytoskeleton 2
nucleus 2
plasma membrane 1
mitochondrion 1
cytosol 1
lysosome 0

Gene Ontology (GO) - Cellular Components for LEFTY2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005576 extracellular region TAS --
GO:0005615 extracellular space IBA 21873635
GO:0031093 platelet alpha granule lumen TAS --
GO:0062023 collagen-containing extracellular matrix HDA 23658023
genes like me logo Genes that share ontologies with LEFTY2: view

No data available for Subcellular locations from the Human Protein Atlas (HPA) for LEFTY2 Gene

Pathways & Interactions for LEFTY2 Gene

PathCards logo

SuperPathways for LEFTY2 Gene

SuperPathway Contained pathways
1 Apoptotic Pathways in Synovial Fibroblasts
.85
.85
.84
.84
.74
.72
.66
.65
.64
.62
.61
.60
.57
.57
2 GPCR Pathway
.73
.73
.62
.59
.58
.58
.55
3 ERK Signaling
.61
.61
.58
.51
.49
4 Nanog in Mammalian ESC Pluripotency
.61
.61
.59
.48
5 Activation of cAMP-Dependent PKA
.77
.77
.71
.56
genes like me logo Genes that share pathways with LEFTY2: view

Pathways by source for LEFTY2 Gene

1 GeneGo (Thomson Reuters) pathway for LEFTY2 Gene
  • Development Role of Activin A in cell differentiation and proliferation
67 Qiagen pathways for LEFTY2 Gene
  • 14-3-3 Induced Intracellular Signaling
  • Actin-Based Motility by Rho Family GTPases
  • Activation of cAMP-Dependent PKA
  • Activation of PKA through GPCR
  • Activation of PKC through GPCR
1 GeneTex pathway for LEFTY2 Gene

SIGNOR curated interactions for LEFTY2 Gene

Is activated by:

Gene Ontology (GO) - Biological Process for LEFTY2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0002576 platelet degranulation TAS --
GO:0007165 signal transduction IEA --
GO:0007179 transforming growth factor beta receptor signaling pathway TAS 9153275
GO:0007275 multicellular organism development TAS,IEA --
GO:0010862 positive regulation of pathway-restricted SMAD protein phosphorylation IBA 21873635
genes like me logo Genes that share ontologies with LEFTY2: view

Drugs & Compounds for LEFTY2 Gene

(4) Drugs for LEFTY2 Gene - From: Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials

(1) Additional Compounds for LEFTY2 Gene - From: Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
genes like me logo Genes that share compounds with LEFTY2: view

Transcripts for LEFTY2 Gene

mRNA/cDNA for LEFTY2 Gene

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

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for LEFTY2

Alternative Splicing Database (ASD) splice patterns (SP) for LEFTY2 Gene

No ASD Table

Relevant External Links for LEFTY2 Gene

GeneLoc Exon Structure for
LEFTY2

Expression for LEFTY2 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for LEFTY2 Gene

mRNA differential expression in normal tissues according to GTEx for LEFTY2 Gene

This gene is overexpressed in Uterus (x20.0), Ovary (x9.0), and Artery - Aorta (x4.6).

Protein differential expression in normal tissues from HIPED for LEFTY2 Gene

This gene is overexpressed in Uterus (63.1).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB and MOPED for LEFTY2 Gene



Protein tissue co-expression partners for LEFTY2 Gene

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for LEFTY2

SOURCE GeneReport for Unigene cluster for LEFTY2 Gene:

Hs.520187

mRNA Expression by UniProt/SwissProt for LEFTY2 Gene:

O00292-LFTY2_HUMAN
Tissue specificity: Mesenchymal cells of the endometrial stroma.

Evidence on tissue expression from TISSUES for LEFTY2 Gene

  • Heart(2)
genes like me logo Genes that share expression patterns with LEFTY2: view

Primer products for research

No data available for Phenotype-based relationships between genes and organs from Gene ORGANizer for LEFTY2 Gene

Orthologs for LEFTY2 Gene

This gene was present in the common ancestor of chordates.

Orthologs for LEFTY2 Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia LEFTY2 29 30
  • 99.18 (n)
OneToOne
Cow
(Bos Taurus)
Mammalia LEFTY2 29
  • 88.25 (n)
-- 30
  • 83 (a)
ManyToMany
-- 30
  • 82 (a)
ManyToMany
Dog
(Canis familiaris)
Mammalia LEFTY2 29
  • 85.43 (n)
-- 30
  • 80 (a)
OneToMany
Mouse
(Mus musculus)
Mammalia Lefty2 29 16 30
  • 83.33 (n)
ManyToMany
Lefty1 30
  • 80 (a)
ManyToMany
Rat
(Rattus norvegicus)
Mammalia Lefty2 29
  • 82.41 (n)
Oppossum
(Monodelphis domestica)
Mammalia -- 30
  • 54 (a)
OneToMany
Platypus
(Ornithorhynchus anatinus)
Mammalia -- 30
  • 42 (a)
OneToMany
Chicken
(Gallus gallus)
Aves LEFTY2 30
  • 39 (a)
OneToMany
Lizard
(Anolis carolinensis)
Reptilia -- 30
  • 42 (a)
OneToMany
Zebrafish
(Danio rerio)
Actinopterygii lft2 30
  • 36 (a)
ManyToMany
lft1 30
  • 36 (a)
ManyToMany
Sea Squirt
(Ciona savignyi)
Ascidiacea CSA.2199 30
  • 29 (a)
OneToMany
Species where no ortholog for LEFTY2 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium 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)
  • Baker's yeast (Saccharomyces cerevisiae)
  • 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)
  • Fruit Fly (Drosophila melanogaster)
  • 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 (Oryza sativa)
  • Rice Blast Fungus (Magnaporthe grisea)
  • Schistosome Parasite (Schistosoma mansoni)
  • Sea Anemone (Nematostella vectensis)
  • Sea Vase (Ciona intestinalis)
  • 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)
  • Tropical Clawed Frog (Silurana tropicalis)
  • Wheat (Triticum aestivum)
  • Worm (Caenorhabditis elegans)

Evolution for LEFTY2 Gene

ENSEMBL:
Gene Tree for LEFTY2 (if available)
TreeFam:
Gene Tree for LEFTY2 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for LEFTY2: view image
Alliance of Genome Resources:
Additional Orthologs for LEFTY2

Paralogs for LEFTY2 Gene

(1) SIMAP similar genes for LEFTY2 Gene using alignment to 1 proteins:

  • LFTY2_HUMAN

Pseudogenes.org Pseudogenes for LEFTY2 Gene

genes like me logo Genes that share paralogs with LEFTY2: view

Variants for LEFTY2 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for LEFTY2 Gene

SNP ID Clinical significance and condition Chr 01 pos Variation AA Info Type
1005254 Uncertain Significance: Left-right axis malformations 225,939,500(-) G/C
NM_003240.5(LEFTY2):c.598C>G (p.Gln200Glu)
MISSENSE
1017089 Uncertain Significance: Left-right axis malformations 225,937,752(-) A/G
NM_003240.5(LEFTY2):c.790T>C (p.Cys264Arg)
MISSENSE
1038741 Uncertain Significance: Left-right axis malformations 225,939,853(-) C/T
NM_003240.5(LEFTY2):c.400G>A (p.Gly134Arg)
MISSENSE
1044618 Uncertain Significance: Left-right axis malformations 225,941,017(-) C/T
NM_003240.5(LEFTY2):c.124G>A (p.Val42Ile)
MISSENSE
847148 Uncertain Significance: Left-right axis malformations 225,937,590(-) C/T
NM_003240.5(LEFTY2):c.952G>A (p.Ala318Thr)
MISSENSE

dbSNP identifiers (rs#s) for variants without ClinVar clinical significance for LEFTY2 Gene

All consequence types are included: molecular consequences (e.g. missense, synonymous), and location-based (e.g. intron, upstream).

Structural Variations from Database of Genomic Variants (DGV) for LEFTY2 Gene

Variant ID Type Subtype PubMed ID
esv2762223 CNV gain 21179565
nsv524126 CNV gain 19592680
nsv549267 CNV loss 21841781
nsv945329 CNV duplication 23825009

Variation tolerance for LEFTY2 Gene

Residual Variation Intolerance Score: 35.4% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 4.72; 66.30% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for LEFTY2 Gene

Human Gene Mutation Database (HGMD)
LEFTY2
SNPedia medical, phenotypic, and genealogical associations of SNPs for
LEFTY2
Leiden Open Variation Database (LOVD)
LEFTY2

SNP Genotyping and Copy Number Assays for research

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for LEFTY2 Gene

Disorders for LEFTY2 Gene

MalaCards: The human disease database

(19) MalaCards diseases for LEFTY2 Gene - From: ORP, COP, and GCD

- elite association - COSMIC cancer census association via MalaCards

UniProtKB/Swiss-Prot

LFTY2_HUMAN
  • Left-right axis malformations (LRAM) [MIM:601877]: The defect includes left pulmonary isomerism, with cardiac anomalies characterized by complete atrioventricular canal defect and hypoplastic left ventricle, and interrupted inferior vena cava. {ECO:0000269 PubMed:10053005}. Note=The disease is caused by variants affecting the gene represented in this entry.

Additional Disease Information for LEFTY2

Human Genome Epidemiology Navigator
(HuGE)
Atlas
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
Open Targets Platform
Open Targets Platform
genes like me logo Genes that share disorders with LEFTY2: view

No data available for Genatlas for LEFTY2 Gene

Publications for LEFTY2 Gene

  1. Detection of ebaf, a novel human gene of the transforming growth factor beta superfamily association of gene expression with endometrial bleeding. (PMID: 9153275) Kothapalli R … Tabibzadeh S (The Journal of clinical investigation 1997) 2 3 4 22
  2. A large-scale candidate gene association study of age at menarche and age at natural menopause. (PMID: 20734064) He C … Hunter DJ (Human genetics 2010) 3 40
  3. Maternal genes and facial clefts in offspring: a comprehensive search for genetic associations in two population-based cleft studies from Scandinavia. (PMID: 20634891) Jugessur A … Murray JC (PloS one 2010) 3 40
  4. Regulation of matrix metalloproteinase-9/gelatinase B expression and activation by ovarian steroids and LEFTY-A/endometrial bleeding-associated factor in the human endometrium. (PMID: 15536155) Cornet PB … Henriet P (The Journal of clinical endocrinology and metabolism 2005) 3 22
  5. Signal sequence and keyword trap in silico for selection of full-length human cDNAs encoding secretion or membrane proteins from oligo-capped cDNA libraries. (PMID: 16303743) Otsuki T … Isogai T (DNA research : an international journal for rapid publication of reports on genes and genomes 2005) 3 4

Products for LEFTY2 Gene

Sources for LEFTY2 Gene