MLST8

Chr 16

MTOR associated protein MLST8

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

NCBI Gene: 64223 ENSG00000167965 UniProt: Q9BVC4

MLST8 encodes a subunit of both mTORC1 and mTORC2 complexes that regulates cell growth, survival, and cytoskeletal organization in response to nutrient and hormonal signals by enhancing mTOR kinase activity. Mutations cause autosomal recessive neurodevelopmental disorders with intellectual disability, seizures, and growth abnormalities. The gene shows low constraint to loss-of-function variants (pLI = 0.008), consistent with recessive inheritance patterns.

ResearchSummary from RefSeq, UniProt

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]

ResearchGenerating clinical summary…

LOEUF 0.67

Clinical Summary— MLST8

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Population Constraint (gnomAD)

Low constraint (pLI 0.01) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

51 VUS of 64 total submissions

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Clinical Trials

1 active or recruiting trial — potential therapeutic options may be available

Explore recent and relevant literature in Research Assistant →

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.67LOEUF

pLI 0.008

Z-score 2.64

OE 0.36 (0.20–0.67)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

1.38Z-score

OE missense 0.74 (0.65–0.84)

165 obs / 223.1 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.36 (0.20–0.67)

0≤0.351.4

Missense OE?0.74 (0.65–0.84)

0≤0.61.4

Synonymous OE?1.41

0≤1.21.6

LoF obs/exp: 7 / 19.6Missense obs/exp: 165 / 223.1Syn Z: -3.20

ClinVar Variant Classifications

64 submitted variants in ClinVar

ClinVar

Classification Summary

VUS51

Likely Benign3

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Synonymous	Total
Pathogenic	0	0	0
Likely Pathogenic	0	0	0
VUS	51	0	51
Likely Benign	0	3	3
Benign	0	0	0
Total	51	3	54

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

View in ClinVar →

36 pathogenic / likely-pathogenic (of 53) ClinVar copy-number / structural variants overlap MLST8 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →