LEFTY1
protein-codingleft-right determination factor 1, the group of Transforming growth factor beta superfamily
Gene 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 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. This gene is closely linked to both a related family member and a related pseudogene. [provided by RefSeq, Aug 2016]
- LEFTB
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~25.1 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to LEFTY1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_020997.4. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 3 | 3 | ||||
| missense | 71 | 4 | 1 | 76 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 71 | 7 | 1 | 79 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_066277.1 | 4 | MANE Select | |
| Ensembl | ENSP00000272134.5 | 4 | MANE Select | |
| Ensembl | ENSP00000581554.1 | 3 | Standard | |
| Ensembl | ENSP00000581554.1 | 3 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- TGF-beta signaling pathway - Homo sapiens (human)
- Cell Differentiation - Index expanded
- Cell Differentiation - Index
- Differentiation Pathway
- Mesodermal Commitment Pathway
Biological Process
- negative regulation of transcription by RNA polymerase II
- heart morphogenesis
- transforming growth factor beta receptor signaling pathway
- determination of left/right symmetry
- regulation of signaling receptor activity
Molecular Function
- cytokine activity
- transforming growth factor beta receptor binding
- growth factor activity
Cellular Component
- extracellular space
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000272134
- Coding exons
- 4
- Length
- 25101
- Individuals with no LoFs
- 125675
- Homozygous LoFs
- 1
- Heterozygous LoFs
- 42
- Defined
- 125718
- p
- 0.000171
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.738 | 204 | 236 | 0.865 | 0.0000152 | 2306 |
| Missense (PolyPhen) | 56 | 62.647 | 0.89389 | 641 | ||
| Synonymous | 1.42 | 97 | 117 | 0.832 | 0.00000828 | 799 |
| Loss of Function | -0.603 | 17 | 14.5 | 1.17 | 7.78e-7 | 134 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000062 | 0.000062 | rare |
| Latino/Admixed American | 0.00035 | 0.00032 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00016 | 0.00016 | rare |
| Finnish | 0.000052 | 0.000046 | rare |
| European (Non-Finnish) | 0.00015 | 0.00015 | rare |
| South Asian | 0.00023 | 0.00023 | rare |
| Other | 0.00051 | 0.00049 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Required for left-right axis determination as a regulator of LEFTY2 and NODAL.;
Recessive Scores
- pRec
- 0.472
Intolerance Scores
- LoFtool
- 0.538
- RVIS EVS
- 1.42
- RVIS percentile EVS
- 94.86
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.197
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | High |
| Cancer | Medium | Medium | Medium |