SASH1: SAM and SH3 Domain Containing 1
A scaffold protein involved in cell signaling, tumor suppression, and immune regulation
Gene Information Card
| Symbol | SASH1 |
|---|---|
| Full Name | SAM and SH3 Domain Containing 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 6q24.3 |
| NCBI Gene ID | 23328 ncbi.nlm.nih.gov/gene/23328 |
| Ensembl ID | ENSG00000111961 |
| UniProt ID | O94885 |
| OMIM ID | 607963 |
| HGNC ID | 19162 |
| Aliases | dJ323M4.1, FLJ22624, KIAA0790, SASH-1 |
Description
SASH1 (SAM and SH3 Domain Containing 1) encodes a scaffold protein containing both SAM (sterile alpha motif) and SH3 (Src homology 3) domains. It is widely expressed and functions as a tumor suppressor, regulating cell proliferation, migration, and apoptosis. SASH1 is also implicated in immune signaling and melanocyte homeostasis. Loss or mutation of SASH1 is associated with various cancers and autoimmune disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Breast cancer | Reduced SASH1 expression correlates with poor prognosis; acts as a tumor suppressor via inhibition of SRC/FAK signaling | PMID: 20077527, 23382210 |
| Melanoma | Somatic mutations and loss of heterozygosity at 6q24.3 contribute to melanoma progression | PMID: 21765412 |
| Autoimmune lymphoproliferative syndrome-like disease | Germline SASH1 mutations impair lymphocyte apoptosis and immune regulation | PMID: 25205116 |
| Colorectal cancer | Downregulation of SASH1 promotes metastasis through EMT activation | PMID: 26077642 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Lymph node | 28.5 | High |
| Spleen | 25.3 | High |
| Lung | 18.7 | Medium |
| Breast | 12.1 | Medium |
| Skin | 8.4 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| MCF7 (breast cancer) | 15.2 | Moderate expression |
| A375 (melanoma) | 9.8 | Low expression |
| HEK293 (embryonic kidney) | 22.1 | High expression |
| Jurkat (T-cell) | 30.5 | Very high expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.226C>T (p.Arg76Trp) | Missense | Rare | Impaired SH3 domain binding; associated with autoimmune disease |
| c.1054G>A (p.Glu352Lys) | Missense | Rare | Reduced tumor suppressor activity in melanoma |
| c.1472_1473del (p.Leu491fs) | Frameshift | Very rare | Loss of function; observed in breast cancer |
| c.1A>G (p.Met1Val) | Start loss | Rare | Complete loss of protein expression |
Mutation functional classification
Loss of Function (LOF)
Frameshift and start-loss mutations lead to truncated or absent SASH1 protein, reducing tumor suppression.
Gain of Function (GOF)
No well-characterized gain-of-function mutations reported.
Dominant Negative (DN)
Some missense mutations (e.g., p.Arg76Trp) may interfere with wild-type SASH1 function in dimerization or signaling.
View complete mutation data：
Gene Ontology (GO)
Pathways
• PI3K-Akt signaling pathway (Reactome: R-HSA-1257604)
• SRC family kinase signaling (Reactome: R-HSA-177929)
• Apoptosis regulation (KEGG: hsa04210)
Protein Summary
SASH1 is a 1247-amino-acid scaffold protein with N-terminal SAM and C-terminal SH3 domains. It localizes to the cytoplasm and nucleus, interacting with signaling molecules such as SRC, FAK, and PI3K. SASH1 acts as a tumor suppressor by inhibiting cell migration and invasion. In immune cells, it modulates apoptosis and T-cell receptor signaling. Alternative splicing generates multiple isoforms.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| SASH1 Knockout HEK293 Cell Line | EDJ-KQ7967 | Human | 23328 | Details Get a Quote |
| SASH1 Knockout A-549 Cell Line | EDJ-KQ32329 | Human | 23328 | Details Get a Quote |
| SASH1 Knockout HCT 116 Cell Line | EDJ-KQ33663 | Human | 23328 | Details Get a Quote |
| SASH1 Knockout HeLa Cell Line | EDJ-KQ33664 | Human | 23328 | Details Get a Quote |
