LEFTY2 (left-right determination factor 2)

Gene

• Entrez ID: 7044
• Gene name: Left-right determination factor 2
• Gene symbol: LEFTY2
• Synonyms (NCBI Gene): EBAF, LEFTA, LEFTYA, TGFB4
• Chromosome: 1
• Chromosome location: 1q42.12
• Summary: 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

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs777139964	G>T	Likely-pathogenic	Coding sequence variant, missense variant, genic downstream transcript variant, downstream transcript variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT005557	hsa-miR-302a-3p	Immunohistochemistry, Luciferase reporter assay, Microarray, Northern blot, qRT-PCR, Western blot	21266536
MIRT005634	hsa-miR-302d-3p	Immunohistochemistry, Luciferase reporter assay, Microarray, Northern blot, qRT-PCR, Western blo	21266536
MIRT437959	hsa-miR-373-3p	Luciferase reporter assay	24709321
MIRT437959	hsa-miR-373-3p	Luciferase reporter assay	24709321
MIRT437959	hsa-miR-373-3p	Luciferase reporter assay	24709321
MIRT437959	hsa-miR-373-3p	Luciferase reporter assay	24709321
MIRT643756	hsa-miR-6736-3p	HITS-CLIP	23824327
MIRT643757	hsa-miR-4267	HITS-CLIP	23824327
MIRT643755	hsa-miR-5193	HITS-CLIP	23824327
MIRT643754	hsa-miR-660-3p	HITS-CLIP	23824327
MIRT643753	hsa-miR-4268	HITS-CLIP	23824327
MIRT643752	hsa-miR-3658	HITS-CLIP	23824327
MIRT643751	hsa-miR-7856-5p	HITS-CLIP	23824327
MIRT643756	hsa-miR-6736-3p	HITS-CLIP	23824327
MIRT643757	hsa-miR-4267	HITS-CLIP	23824327
MIRT643755	hsa-miR-5193	HITS-CLIP	23824327
MIRT643754	hsa-miR-660-3p	HITS-CLIP	23824327
MIRT643753	hsa-miR-4268	HITS-CLIP	23824327
MIRT643752	hsa-miR-3658	HITS-CLIP	23824327
MIRT643751	hsa-miR-7856-5p	HITS-CLIP	23824327
MIRT1107236	hsa-miR-24	CLIP-seq
MIRT1107237	hsa-miR-3925-3p	CLIP-seq
MIRT1107238	hsa-miR-4264	CLIP-seq
MIRT1107239	hsa-miR-4708-3p	CLIP-seq
MIRT1107240	hsa-miR-520a-5p	CLIP-seq
MIRT1107241	hsa-miR-525-5p	CLIP-seq
MIRT1107242	hsa-miR-622	CLIP-seq
MIRT1107243	hsa-miR-766	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0005125	Function	Cytokine activity	IBA
GO:0005125	Function	Cytokine activity	IEA
GO:0005160	Function	Transforming growth factor beta receptor binding	IEA
GO:0005576	Component	Extracellular region	IEA
GO:0005576	Component	Extracellular region	TAS
GO:0005615	Component	Extracellular space	IBA
GO:0005615	Component	Extracellular space	IEA
GO:0008083	Function	Growth factor activity	IEA
GO:0009948	Process	Anterior/posterior axis specification	IBA
GO:0030509	Process	BMP signaling pathway	IBA
GO:0031012	Component	Extracellular matrix	HDA	23658023
GO:0031093	Component	Platelet alpha granule lumen	TAS

Other IDs

• MIM: 601877
• HGNC: 3122
• e!Ensembl: ENSG00000143768

Protein

• UniProt ID: O00292
• Protein name: Left-right determination factor 2 (Endometrial bleeding-associated factor) (Left-right determination factor A) (Protein lefty-2) (Protein lefty-A) (Transforming growth factor beta-4) (TGF-beta-4)
• Protein function: Required for left-right (L-R) asymmetry determination of organ systems in mammals. May play a role in endometrial bleeding.
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00688	TGFb_propeptide	76 → 229	TGF-beta propeptide	Family
  PF00019	TGF_beta	262 → 353	Transforming growth factor beta like domain	Domain

• Tissue specificity: TISSUE SPECIFICITY: Mesenchymal cells of the endometrial stroma.
• Sequence:

  MWPLWLCWALWVLPLAGPGAALTEEQLLGSLLRQLQLSEVPVLDRADMEKLVIPAHVRAQ
  YVVLLRRSHGDRSRGKRFSQSFREVAGRFLASEASTHLLVFGMEQRLPPNSELVQAVLRL
  FQEPVPKAALHRHGRLSPRSAQARVTVEWLRVRDDGSNRTSLIDSRLVSVHESGWKAFDV
  TEAVNFWQQLSRPRQPLLLQVSVQREHLGPLASGAHKLVRFASQGAPAGLGEPQLELHTL
  DLRDYGAQGDCDPEAPMTEGTRCCRQEMYIDLQGMKWAKNWVLEPPGFLAYECVGTCQQP
  PEALAFNWPFLGPRQCIASETASLPMIVSIKEGGRTRPQVVSLPNMRVQKCSCASDGALV
  PRRLQP

• Sequence length: 366

Pathways

KEGG:

TGF-beta signaling pathway
Signaling pathways regulating pluripotency of stem cells

Reactome:

Platelet degranulation

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
CENTRAL NERVOUS SYSTEM CANCER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CONGENITAL HEART DEFECTS	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CONGENITAL HEART DISEASE	—	ClinGen, Disgenet ClinGen, Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
GLIOBLASTOMA MULTIFORME	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
GLIOMA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HETEROTAXY SYNDROME	—	CTD, Disgenet CTD, Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Left-right axis malformations	Uncertain significance; Likely benign; Benign; Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
LEFTY2-related disorder	Uncertain significance; Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
TETRALOGY OF FALLOT	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Visceral heterotaxy	Uncertain significance	ClinVar CTD	★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Adenocarcinoma	Adenocarcinoma	BEFREE	9230066		★☆☆☆☆ Found in Text Mining only
Alzheimer Disease	Alzheimer disease	Pubtator	40244244	Associate	★☆☆☆☆ Found in Text Mining only
Asplenia Syndrome	Asplenia	CTD_human_DG	10053005		★☆☆☆☆ Found in Text Mining only
Ciliopathies	Ciliopathies	GENOMICS_ENGLAND_DG			★☆☆☆☆ Found in Text Mining only
Coronary heart disease	Coronary Heart Disease	BEFREE	25111179		★☆☆☆☆ Found in Text Mining only
Double Outlet Right Ventricle	Double outlet right ventricle	Pubtator	23899608	Inhibit	★☆☆☆☆ Found in Text Mining only
Endometrial Carcinoma	Endometrial carcinoma	BEFREE	29845221		★☆☆☆☆ Found in Text Mining only
Endometrial Neoplasms	Endometrial neoplasm	Pubtator	19874624, 29845221	Inhibit	★☆☆☆☆ Found in Text Mining only
Endometrial Neoplasms	Endometrial neoplasm	Pubtator	27497669, 32236143	Associate	★☆☆☆☆ Found in Text Mining only
Endometriosis	Endometriosis	BEFREE	10902804		★☆☆☆☆ Found in Text Mining only
Glaucoma	Glaucoma	Pubtator	27293372	Associate	★☆☆☆☆ Found in Text Mining only
Glioma	Glioma	Pubtator	36124685	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Heart Diseases	Heart disease	Pubtator	23899608	Associate	★☆☆☆☆ Found in Text Mining only
Heart Septal Defects Ventricular	Congenital heart septal defect	Pubtator	23899608	Associate	★☆☆☆☆ Found in Text Mining only
Heterotaxy Syndrome	Heterotaxia	GENOMICS_ENGLAND_DG	10053005		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Heterotaxy Syndrome	Heterotaxia	CTD_human_DG	10053005		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Left Atrial Isomerism	Left atrial isomerism	CTD_human_DG	10053005		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of endometrium	Endometrial Cancer	BEFREE	29845221		★☆☆☆☆ Found in Text Mining only
Multiple congenital anomalies	Multiple Congenital Anomalies	CTD_human_DG	10053005		★☆☆☆☆ Found in Text Mining only
Neoplasms	Neoplasms	BEFREE	29845221, 9230066		★☆☆☆☆ Found in Text Mining only
Polysplenia Syndrome	Polysplenia	CTD_human_DG	10053005		★☆☆☆☆ Found in Text Mining only
Proteus Syndrome	Proteus Syndrome	BEFREE	11471152		★☆☆☆☆ Found in Text Mining only
Retinoblastoma	Retinoblastoma	Pubtator	30401983	Associate	★☆☆☆☆ Found in Text Mining only
Right Atrial Isomerism	Atrial Isomerism	CTD_human_DG	10053005		★☆☆☆☆ Found in Text Mining only
Situs ambiguous	Situs ambiguus	ORPHANET_DG			★☆☆☆☆ Found in Text Mining only
Situs ambiguus	Situs ambiguus	CTD_human_DG	10053005		★☆☆☆☆ Found in Text Mining only
Situs ambiguus	Situs ambiguus	ORPHANET_DG			★☆☆☆☆ Found in Text Mining only
Uterine Diseases	Uterine polyp	Pubtator	32236143, 9153275	Associate	★☆☆☆☆ Found in Text Mining only
Ventricular Septal Defects	Ventricular septal defect	BEFREE	23899608		★☆☆☆☆ Found in Text Mining only