LYL1 Gene - Lymphoblastic Leukemia Associated Hematopoiesis Regulator
Comprehensive genomic and functional analysis of LYL1, a basic helix-loop-helix transcription factor implicated in T-cell acute lymphoblastic leukemia and hematopoietic development.
Gene Information Card
| Symbol | LYL1 |
|---|---|
| Full Name | lymphoblastic leukemia associated 1 |
| Gene Type | protein-coding |
| Chromosomal Location | 19p13.13 |
| NCBI Gene ID | 4066 ncbi.nlm.nih.gov/gene/4066 |
| Ensembl ID | ENSG00000104903 |
| UniProt ID | P12980 |
| OMIM ID | 151440 |
| HGNC ID | 6731 |
| Aliases | bHLHa18, TAL-1-related, TAL1R |
Description
LYL1 (lymphoblastic leukemia associated 1) encodes a basic helix-loop-helix (bHLH) transcription factor that plays a critical role in hematopoiesis, particularly in the development of erythroid and megakaryocytic lineages. It is frequently dysregulated in T-cell acute lymphoblastic leukemia (T-ALL) through chromosomal translocations or aberrant expression. LYL1 forms heterodimers with E-proteins (e.g., TCF3/E2A) to regulate target gene transcription involved in cell proliferation and differentiation.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| T-cell acute lymphoblastic leukemia (T-ALL) | LYL1 is activated by chromosomal translocations (e.g., t(7;19)(q35;p13)) that place it under the control of T-cell receptor enhancers, leading to aberrant expression and blockade of T-cell differentiation. | PMID: 1902990; COSMIC; ClinVar |
| Acute myeloid leukemia (AML) | Overexpression of LYL1 has been reported in AML subtypes, potentially contributing to leukemogenesis by disrupting normal hematopoietic differentiation. | PMID: 10655559; COSMIC |
| Hematopoietic disorders | Dysregulation of LYL1 expression may impair erythroid/megakaryocyte development, though direct disease associations are less defined. | OMIM: 151440 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Bone marrow | 12.5 | Medium |
| Spleen | 8.3 | Low |
| Thymus | 6.1 | Low |
| Lung | 2.4 | Not detected |
| Heart | 1.1 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| K562 (erythroleukemia) | 45.2 | High expression; used as model for erythroid differentiation |
| Jurkat (T-cell leukemia) | 32.8 | High expression; relevant to T-ALL |
| HEK293 (embryonic kidney) | 1.5 | Low/background expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1A>G (p.Met1?) | missense | <0.1% | Potential loss of start codon; uncertain significance |
| c.200C>T (p.Pro67Leu) | missense | <0.1% | Rare variant; no functional data |
| t(7;19)(q35;p13) | translocation | rare in T-ALL | Fusion with TCRB enhancer; drives LYL1 overexpression |
Mutation functional classification
Loss of Function (LOF)
No confirmed loss-of-function mutations reported in disease; experimental knockdown in cell lines impairs erythroid differentiation.
Gain of Function (GOF)
Chromosomal translocations leading to overexpression in T-ALL represent a gain-of-function mechanism.
Dominant Negative (DN)
Not described for LYL1; dominant-negative effects are hypothesized for certain bHLH mutants but not validated.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Hematopoietic stem cell differentiation (Reactome: R-HSA-9616222)
• Transcriptional regulation by bHLH factors (KEGG: hsa04350)
• T-cell receptor signaling in T-ALL (KEGG: hsa05202)
Protein Summary
LYL1 is a 280-amino acid bHLH transcription factor that localizes to the nucleus and binds E-box DNA sequences (CANNTG) as a heterodimer with E-proteins. It is essential for primitive and definitive hematopoiesis, particularly erythroid and megakaryocyte lineage commitment. In cancer, aberrant LYL1 expression blocks T-cell differentiation, contributing to leukemogenesis. The protein contains a conserved bHLH domain (residues 109-160) required for DNA binding and dimerization.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| LYL1 Knockout HEK293 Cell Line | EDJ-KQ2530 | Human | 4066 | Details Get a Quote |
| LYL1 Knockout HCT 116 Cell Line | EDJ-KQ23155 | Human | 4066 | Details Get a Quote |
| LYL1 Knockout HeLa Cell Line | EDJ-KQ53818 | Human | 4066 | Details Get a Quote |
| LYL1 Knockout A-549 Cell Line | EDJ-KQ62298 | Human | 4066 | Details Get a Quote |
