MLST8: mTOR-associated protein LST8 homolog
A core component of mTORC1 and mTORC2 complexes regulating cell growth and metabolism
Gene Information Card
| Symbol | MLST8 |
|---|---|
| Full Name | MTOR associated protein, LST8 homolog |
| Gene Type | Protein coding |
| Chromosomal Location | 16p13.3 |
| NCBI Gene ID | 64223 ncbi.nlm.nih.gov/gene/64223 |
| Ensembl ID | ENSG00000167965 |
| UniProt ID | Q9BVC4 |
| OMIM ID | 612190 |
| HGNC ID | 24825 |
| Aliases | GβL, LST8, POP3, WAT1 |
Description
MLST8 (MTOR associated protein, LST8 homolog) encodes a WD40 repeat-containing protein that is a core component of both mTORC1 and mTORC2 complexes. It binds directly to the kinase domain of mTOR and is essential for mTOR complex assembly, stability, and substrate recognition. MLST8 regulates cell growth, proliferation, and metabolism in response to nutrient and growth factor signals.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cancer (various) | MLST8 overexpression or mutation may alter mTOR signaling, promoting uncontrolled cell growth | COSMIC, ClinVar |
| Renal cell carcinoma | Somatic mutations in MLST8 have been identified in clear cell renal cell carcinoma | COSMIC |
| Colorectal cancer | MLST8 copy number gains and overexpression observed in colorectal tumors | COSMIC |
| Prostate cancer | MLST8 expression changes linked to mTOR pathway activation | COSMIC |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Heart | 10.3 | Medium |
| Liver | 8.7 | Medium |
| Kidney | 11.2 | Medium |
| Lung | 9.8 | Medium |
| Pancreas | 7.4 | Low |
| Spleen | 6.1 | Low |
| Testis | 14.6 | High |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 15.2 | High expression |
| HeLa | 12.8 | Medium expression |
| A549 | 10.5 | Medium expression |
| MCF7 | 9.3 | Medium expression |
| HepG2 | 8.1 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.344G>A (p.Arg115His) | Missense | <0.1% | Unknown functional effect; reported in COSMIC |
| c.487C>T (p.Arg163Trp) | Missense | <0.1% | Reported in cancer samples; potential impact on mTOR binding |
| c.622G>A (p.Gly208Arg) | Missense | <0.1% | Found in colorectal cancer; functional significance unclear |
Mutation functional classification
Loss of Function (LOF)
No confirmed loss-of-function mutations reported in MLST8; complete loss is likely incompatible with cell viability.
Gain of Function (GOF)
No confirmed gain-of-function mutations; overexpression may contribute to mTOR hyperactivity.
Dominant Negative (DN)
No dominant-negative mutations described in literature.
View complete mutation data：
Gene Ontology (GO)
Pathways
• mTOR signaling pathway (KEGG: hsa04150)
• PI3K-Akt signaling pathway (KEGG: hsa04151)
• Autophagy (KEGG: hsa04140)
• Insulin signaling pathway (KEGG: hsa04910)
Protein Summary
The MLST8 protein (also known as GβL) contains seven WD40 repeats that form a β-propeller structure. It binds to the kinase domain of mTOR and is required for the stability and activity of both mTORC1 and mTORC2 complexes. MLST8 does not possess catalytic activity but serves as a scaffold that facilitates substrate recruitment and complex integrity. It is ubiquitously expressed and essential for embryonic development.
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