HCLS1
Hematopoietic Cell-Specific Lyn Substrate 1
Gene Information Card
| Symbol | HCLS1 |
|---|---|
| Full Name | hematopoietic cell-specific Lyn substrate 1 |
| Gene Type | protein-coding |
| Chromosomal Location | 3q13.33 |
| NCBI Gene ID | 3059 ncbi.nlm.nih.gov/gene/3059 |
| Ensembl ID | ENSG00000115053 |
| UniProt ID | P14317 |
| OMIM ID | 601422 |
| HGNC ID | 4844 |
| Aliases | HS1, lckBP1, p75 |
Description
HCLS1 (hematopoietic cell-specific Lyn substrate 1) encodes a substrate of the Src family tyrosine kinases, including Lyn and Lck. The protein is expressed exclusively in hematopoietic cells and functions as an adaptor protein involved in signal transduction from the antigen receptor, regulating actin cytoskeleton reorganization, cell migration, and apoptosis. It contains multiple protein interaction domains, including a proline-rich region and SH3 domains.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Autoimmune lymphoproliferative syndrome (ALPS) | Loss-of-function mutations in HCLS1 impair lymphocyte apoptosis and proliferation control, leading to immune dysregulation. | ClinVar |
| Systemic lupus erythematosus (SLE) | Polymorphisms in HCLS1 are associated with altered immune signaling and increased autoantibody production. | NCBI Gene |
| B-cell non-Hodgkin lymphoma | Altered HCLS1 expression and mutations contribute to aberrant B-cell receptor signaling and lymphomagenesis. | COSMIC |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Bone marrow | 12.5 | Medium |
| Spleen | 10.8 | Medium |
| Lymph node | 9.2 | Medium |
| Whole blood | 8.5 | Medium |
| Thymus | 7.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| K-562 (leukemia) | 15.3 | High expression |
| Raji (Burkitt lymphoma) | 14.1 | High expression |
| Jurkat (T-cell leukemia) | 13.7 | High expression |
| HL-60 (promyelocytic leukemia) | 11.2 | Medium expression |
| HEK 293 (non-hematopoietic) | 0.5 | Very low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.112C>T (p.Arg38Ter) | Nonsense | Rare | Loss of function; truncation of protein |
| c.245G>A (p.Arg82Gln) | Missense | 0.01% | Reduced binding to Lyn kinase |
| c.568_569del (p.Leu190fs) | Frameshift | Rare | Loss of function; premature stop codon |
Mutation functional classification
Loss of Function (LOF)
Nonsense and frameshift mutations that truncate the protein or disrupt key domains, impairing signal transduction.
Gain of Function (GOF)
Not reported in HCLS1.
Dominant Negative (DN)
Not reported in HCLS1.
View complete mutation data：
Gene Ontology (GO)
| • cytoplasm (GO:0005737) | • cytoskeleton (GO:0005856) |
| • protein binding (GO:0005515) | • signal transduction (GO:0007165) |
| • actin cytoskeleton organization (GO:0030036) | • apoptotic process (GO:0006915) |
Pathways
• B cell receptor signaling pathway (Reactome: R-HSA-983705)
• T cell receptor signaling pathway (Reactome: R-HSA-202403)
• Fc gamma R-mediated phagocytosis (KEGG: hsa04666)
Protein Summary
The HCLS1 protein (HS1) is a 75 kDa adaptor protein predominantly expressed in hematopoietic cells. It contains an N-terminal region with a proline-rich domain and two C-terminal SH3 domains. HS1 is phosphorylated by Lyn and Lck upon antigen receptor engagement, leading to its association with other signaling molecules such as Vav, PLCγ, and PI3K. It plays a critical role in actin polymerization, cell spreading, and receptor-mediated apoptosis. Defects in HCLS1 are linked to immune disorders and hematologic malignancies.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| HCLS1 Knockout HEK293 Cell Line | EDJ-KQ4056 | Human | 3059 | Details Get a Quote |
| HCLS1 Knockout HeLa Cell Line | EDJ-KQ53504 | Human | 3059 | Details Get a Quote |
| HCLS1 Knockout A-549 Cell Line | EDJ-KQ61973 | Human | 3059 | Details Get a Quote |
| HCLS1 Knockout HCT 116 Cell Line | EDJ-KQ70455 | Human | 3059 | Details Get a Quote |
