MLST8

MTOR associated protein, LST8 homolog, the group of WD repeat domain containing|MTOR complex 1|MTOR complex 2

Basic information

Region (hg38): 16:2204248-2209453

Links

ENSG00000167965 ∙ NCBI:64223 ∙ OMIM:612190 ∙ HGNC:24825 ∙ Uniprot:Q9BVC4 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the MLST8 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MLST8 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				1		1
missense			19			19
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region			1			1
non coding			9			9
Total	0	0	28	1	0

Variants in MLST8

This is a list of pathogenic ClinVar variants found in the MLST8 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
16-2206098-C-T		not specified	Uncertain significance (May 18, 2023)
16-2206383-C-T		not specified	Uncertain significance (Jul 13, 2021)
16-2206506-A-G		not specified	Uncertain significance (Dec 21, 2023)
16-2206620-C-T		not specified	Uncertain significance (Jan 16, 2025)
16-2207086-C-A		not specified	Uncertain significance (Apr 24, 2023)
16-2207226-A-G		not specified	Uncertain significance (Jul 17, 2024)
16-2207281-A-C		not specified	Uncertain significance (May 04, 2022)
16-2207282-G-C		not specified	Uncertain significance (Dec 17, 2023)
16-2207296-C-T		not specified	Uncertain significance (Mar 20, 2024)
16-2207307-G-C		not specified	Uncertain significance (Sep 10, 2024)
16-2207325-A-G		not specified	Uncertain significance (Dec 06, 2022)
16-2207344-C-A		not specified	Uncertain significance (Dec 10, 2024)
16-2208211-G-A		not specified	Uncertain significance (Jan 24, 2024)
16-2208235-C-T		not specified	Uncertain significance (Dec 22, 2024)
16-2208297-C-T		not specified	Uncertain significance (Feb 27, 2024)
16-2208303-G-A		not specified	Uncertain significance (Jan 01, 2025)
16-2208315-C-T		not specified	Uncertain significance (Nov 22, 2023)
16-2208316-G-A		not specified	Uncertain significance (Sep 26, 2024)
16-2208326-C-G		not specified	Likely benign (May 31, 2023)
16-2208479-C-T		not specified	Uncertain significance (Feb 01, 2025)
16-2208547-G-A		not specified	Uncertain significance (Nov 28, 2024)
16-2208561-C-T			Likely benign (Jan 01, 2025)
16-2208607-G-A		not specified	Uncertain significance (Jun 02, 2024)
16-2208858-A-G		not specified	Uncertain significance (Nov 08, 2024)
16-2209367-C-A		not specified	Uncertain significance (Jun 17, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
MLST8	protein_coding	protein_coding	ENST00000569417	8	5169

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00822	0.989	124784	0	29	124813	0.000116

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.38	165	223	0.739	0.0000148	2162
Missense in Polyphen		50	75.784	0.65977		731
Synonymous	-3.20	140	99.4	1.41	0.00000794	615
Loss of Function	2.64	7	19.6	0.357	0.00000111	173

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.000101	0.0000993
East Asian	0.000167	0.000167
Finnish	0.000338	0.000325
European (Non-Finnish)	0.000142	0.000141
Middle Eastern	0.000167	0.000167
South Asian	0.0000654	0.0000654
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Subunit of both mTORC1 and mTORC2, which regulates cell growth and survival in response to nutrient and hormonal signals. mTORC1 is activated in response to growth factors or amino acids. Growth factor-stimulated mTORC1 activation involves a AKT1- mediated phosphorylation of TSC1-TSC2, which leads to the activation of the RHEB GTPase that potently activates the protein kinase activity of mTORC1. Amino acid-signaling to mTORC1 requires its relocalization to the lysosomes mediated by the Ragulator complex and the Rag GTPases. Activated mTORC1 up-regulates protein synthesis by phosphorylating key regulators of mRNA translation and ribosome synthesis. mTORC1 phosphorylates EIF4EBP1 and releases it from inhibiting the elongation initiation factor 4E (eiF4E). mTORC1 phosphorylates and activates S6K1 at 'Thr-389', which then promotes protein synthesis by phosphorylating PDCD4 and targeting it for degradation. Within mTORC1, LST8 interacts directly with MTOR and enhances its kinase activity. In nutrient- poor conditions, stabilizes the MTOR-RPTOR interaction and favors RPTOR-mediated inhibition of MTOR activity. mTORC2 is also activated by growth factors, but seems to be nutrient-insensitive. mTORC2 seems to function upstream of Rho GTPases to regulate the actin cytoskeleton, probably by activating one or more Rho-type guanine nucleotide exchange factors. mTORC2 promotes the serum- induced formation of stress-fibers or F-actin. mTORC2 plays a critical role in AKT1 'Ser-473' phosphorylation, which may facilitate the phosphorylation of the activation loop of AKT1 on 'Thr-308' by PDK1 which is a prerequisite for full activation. mTORC2 regulates the phosphorylation of SGK1 at 'Ser-422'. mTORC2 also modulates the phosphorylation of PRKCA on 'Ser-657'. {ECO:0000269|PubMed:12718876, ECO:0000269|PubMed:15467718}.
• Pathway: PI3K-Akt signaling pathway - Homo sapiens (human);mTOR signaling pathway - Homo sapiens (human);Autophagy - animal - Homo sapiens (human);Autophagy - other - Homo sapiens (human);Thermogenesis - Homo sapiens (human);Regulation of toll-like receptor signaling pathway;Target Of Rapamycin (TOR) Signaling;VEGFA-VEGFR2 Signaling Pathway;Angiopoietin Like Protein 8 Regulatory Pathway;Focal Adhesion-PI3K-Akt-mTOR-signaling pathway;Steatosis AOP;Pathways in clear cell renal cell carcinoma;PI3K-Akt Signaling Pathway;Interferon type I signaling pathways;Senescence and Autophagy in Cancer;Disease;Signal Transduction;Gene expression (Transcription);HSF1-dependent transactivation;VEGFA-VEGFR2 Pathway;Generic Transcription Pathway;CD28 dependent PI3K/Akt signaling;Cellular responses to stress;CD28 co-stimulation;Costimulation by the CD28 family;RNA Polymerase II Transcription;mTORC1-mediated signalling;Energy dependent regulation of mTOR by LKB1-AMPK;mTOR signalling;Immune System;Adaptive Immune System;insulin Mam;TP53 Regulates Metabolic Genes;Macroautophagy;Cellular responses to external stimuli;CXCR4-mediated signaling events;ErbB1 downstream signaling;Regulation of PTEN gene transcription;Regulation of TP53 Degradation;Regulation of TP53 Expression and Degradation;PTEN Regulation;PIP3 activates AKT signaling;Cellular response to heat stress;Regulation of TP53 Activity;Transcriptional Regulation by TP53;Signaling by VEGF;Constitutive Signaling by AKT1 E17K in Cancer;PI3K/AKT Signaling in Cancer;Signaling by Receptor Tyrosine Kinases;Intracellular signaling by second messengers;mTOR signaling pathway;Diseases of signal transduction;Signaling events mediated by Hepatocyte Growth Factor Receptor (c-Met);CXCR3-mediated signaling events;Class I PI3K signaling events mediated by Akt;LKB1 signaling events;VEGFR2 mediated vascular permeability;insulin (Consensus)

Intolerance Scores

• loftool: 0.429
• rvis_EVS: -0.45
• rvis_percentile_EVS: 24.19

Haploinsufficiency Scores

• hipred: Y
• hipred_score: 0.783
• ghis: 0.597

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.848

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Mlst8
• Phenotype: embryo phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); growth/size/body region phenotype

Gene ontology

• Biological process: cell cycle arrest;regulation of macroautophagy;positive regulation of actin filament polymerization;TOR signaling;positive regulation of TOR signaling;activation of protein kinase B activity;regulation of actin cytoskeleton organization;TORC1 signaling;regulation of GTPase activity;positive regulation of peptidyl-tyrosine phosphorylation;positive regulation of protein serine/threonine kinase activity;regulation of cellular response to heat
• Cellular component: nucleoplasm;cytoplasm;cytosol;TORC1 complex;TORC2 complex
• Molecular function: protein binding;protein serine/threonine kinase activator activity