MLST8

Chr 16

MTOR associated protein MLST8

Also known as: GBL, GbetaL, LST8, POP3, WAT1

NCBI Gene: 64223ENSG00000167965UniProt: Q9BVC4

Enables protein serine/threonine kinase activator activity and protein-macromolecule adaptor activity. Involved in TOR signaling; positive regulation of TOR signaling; and regulation of actin cytoskeleton organization. Part of TORC1 complex; TORC2 complex; and serine/threonine protein kinase complex. [provided by Alliance of Genome Resources, Jul 2025]

106
ClinVar variants
36
Pathogenic / LP
0.01
pLI score
1
Active trials
Clinical Summary— MLST8
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.01) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
36 Pathogenic / Likely Pathogenic· 67 VUS of 106 total submissions
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.67LOEUF
pLI 0.008
Z-score 2.64
OE 0.36 (0.20–0.67)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
1.38Z-score
OE missense 0.74 (0.65–0.84)
165 obs / 223.1 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.36 (0.20–0.67)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.74 (0.65–0.84)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.41
0≤1.21.6
LoF obs/exp: 7 / 19.6Missense obs/exp: 165 / 223.1Syn Z: -3.20

ClinVar Variant Classifications

106 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic34
Likely Pathogenic2
VUS67
Likely Benign3
34
Pathogenic
2
Likely Pathogenic
67
VUS
3
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
34
0
34
Likely Pathogenic
0
0
2
0
2
VUS
0
51
16
0
67
Likely Benign
0
0
0
3
3
Benign
0
0
0
0
0
Total051523106

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

MLST8 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Lipotoxicity-induced STING1 activation stimulates MTORC1 and restricts hepatic lipophagy.
Liu K et al.·Autophagy
2022
CDK1/FBXW7 facilitates degradation and ubiquitination of MLST8 to inhibit progression of renal cell carcinoma.
Zhang E et al.·Cancer Sci
2022
Enhanced mLST8 Expression Correlates with Tumor Progression in Hepatocellular Carcinoma.
Yu XN et al.·Ann Surg Oncol
2020
Bioactive peptide inhibits acute myeloid leukemia cell proliferation by downregulating ALKBH5-mediated m(6)A demethylation of EIF4EBP1 and MLST8 mRNA.
Zhang L et al.·Cell Oncol (Dordr)
2022
Targeted Inhibition of Rictor/mTORC2 in Cancer Treatment: A New Era after Rapamycin.
Zou Z et al.·Curr Cancer Drug Targets
2016Review
Identification and targeting of novel CDK9 complexes in acute myeloid leukemia.
Beauchamp EM et al.·Blood
2019
Interactome-transcriptome analysis discovers signatures complementary to GWAS Loci of Type 2 Diabetes.
Li JW et al.·Sci Rep
2016Meta-analysis
Pre-clinical activity of combined LSD1 and mTORC1 inhibition in MLL-translocated acute myeloid leukaemia.
Deb G et al.·Leukemia
2020
MELK promotes Endometrial carcinoma progression via activating mTOR signaling pathway.
Xu Q et al.·EBioMedicine
2020
Cytoplasmic and nuclear distribution of the protein complexes mTORC1 and mTORC2: rapamycin triggers dephosphorylation and delocalization of the mTORC2 components rictor and sin1.
Rosner M et al.·Hum Mol Genet
2008
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Myeloproliferative NeoplasmSecondary Leukemia

MultiOmic characteriZation of Acute Myeloid Leukemia Evolving From myelopRoliferative Neoplasm to Identify New Targeted Therapeutic Strategies

NOT YET RECRUITING
NCT06022341Phase NAUniversity Hospital, AngersStarted 2023-10-15
Multiomic characterizationIn vitro drug screening

External Resources

Links to major genomics databases and tools