MLST8

Chr 16

MTOR associated protein MLST8

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

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.

OMIMResearchSummary from RefSeq, UniProt
LOEUF 0.67
Clinical SummaryMLST8
Population Constraint (gnomAD)
Low constraint (pLI 0.01) — loss-of-function variants are relatively tolerated in the population.
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ClinVar Variants
36 unique Pathogenic / Likely Pathogenic· 67 VUS of 117 total submissions
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Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.67LOEUF
pLI 0.008
Z-score 2.64
OE 0.36 (0.200.67)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
1.38Z-score
OE missense 0.74 (0.650.84)
165 obs / 223.1 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.36 (0.200.67)
00.351.4
Missense OE0.74 (0.650.84)
00.61.4
Synonymous OE1.41
01.21.6
LoF obs/exp: 7 / 19.6Missense obs/exp: 165 / 223.1Syn Z: -3.20

ClinVar Variant Classifications

117 submitted variants in 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.

3D Protein StructureAlphaFold
Clinical Literature
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