LAMTOR1

late endosomal/lysosomal adaptor, MAPK and MTOR activator 1, the group of Ragulator complex

Basic information

Region (hg38): 11:72085894-72103297

Previous symbols: [ "C11orf59" ]

Links

ENSG00000149357 ∙ NCBI:55004 ∙ OMIM:613510 ∙ HGNC:26068 ∙ Uniprot:Q6IAA8 ∙ 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 LAMTOR1 gene.

• Inborn genetic diseases (6 variants)
• not provided (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the LAMTOR1 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			6			6
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	6	1	0

Variants in LAMTOR1

This is a list of pathogenic ClinVar variants found in the LAMTOR1 region.

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

Position	Type	Phenotype	Significance	ClinVar
11-72088058-G-A			Benign (Nov 12, 2018)
11-72088556-C-T			Likely benign (Apr 24, 2019)
11-72088622-A-C			Benign (Nov 12, 2018)
11-72088834-A-G			Likely benign (Feb 28, 2019)
11-72088919-T-C			Benign (Dec 17, 2018)
11-72089120-G-A			Likely benign (Jan 01, 2024)
11-72089135-T-C		LRTOMT-related disorder	Likely benign (Sep 22, 2023)
11-72093387-A-G			Likely benign (Dec 31, 2018)
11-72093467-G-A			Benign (Jun 16, 2018)
11-72093493-CAG-C		Rare genetic deafness	Likely pathogenic (Jun 30, 2022)
11-72093512-G-A		Autosomal recessive nonsyndromic hearing loss 63	Uncertain significance (Jan 12, 2018)
11-72093528-C-T		not specified	Conflicting classifications of pathogenicity (Oct 24, 2021)
11-72093529-G-A			Uncertain significance (Apr 24, 2019)
11-72093561-C-G		Nonsyndromic Hearing Loss, Recessive	Uncertain significance (Jun 14, 2016)
11-72093563-G-T		Autosomal recessive nonsyndromic hearing loss 63	Uncertain significance (Jan 12, 2018)
11-72093643-A-G		Autosomal recessive nonsyndromic hearing loss 63	Uncertain significance (Jan 13, 2018)
11-72093666-G-A		not specified	Benign (Nov 21, 2018)
11-72093668-C-T		not specified • Autosomal recessive nonsyndromic hearing loss 63 • LRTOMT-related disorder	Conflicting classifications of pathogenicity (Nov 01, 2023)
11-72093694-T-C		Autosomal recessive nonsyndromic hearing loss 63	Uncertain significance (Jan 12, 2018)
11-72093720-G-C			Benign (Oct 18, 2020)
11-72094686-T-TGA			Benign (Jan 28, 2019)
11-72094974-T-C			Uncertain significance (Jan 21, 2019)
11-72094988-AC-A		Autosomal recessive nonsyndromic hearing loss 63	Uncertain significance (May 25, 2020)
11-72094994-ACAGCATC-A		Autosomal recessive nonsyndromic hearing loss 63	Pathogenic (May 22, 2022)
11-72095006-G-A		Autosomal recessive nonsyndromic hearing loss 63	Uncertain significance (Jan 13, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
LAMTOR1	protein_coding	protein_coding	ENST00000278671	5	17493

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.721	0.276	125722	0	2	125724	0.00000795

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.27	57	91.1	0.626	0.00000510	1038
Missense in Polyphen		6	16.098	0.37272		227
Synonymous	1.31	27	37.1	0.727	0.00000216	315
Loss of Function	2.39	1	8.52	0.117	4.44e-7	94

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000193	0.0000176
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: As part of the Ragulator complex it is involved in amino acid sensing and activation of mTORC1, a signaling complex promoting cell growth in response to growth factors, energy levels, and amino acids. Activated by amino acids through a mechanism involving the lysosomal V-ATPase, the Ragulator functions as a guanine nucleotide exchange factor activating the small GTPases Rag. Activated Ragulator and Rag GTPases function as a scaffold recruiting mTORC1 to lysosomes where it is in turn activated. LAMTOR1 is directly responsible for anchoring the Ragulator complex to membranes. Also required for late endosomes/lysosomes biogenesis it may regulate both the recycling of receptors through endosomes and the MAPK signaling pathway through recruitment of some of its components to late endosomes. May be involved in cholesterol homeostasis regulating LDL uptake and cholesterol release from late endosomes/lysosomes. May also play a role in RHOA activation. {ECO:0000269|PubMed:19654316, ECO:0000269|PubMed:20381137, ECO:0000269|PubMed:20544018, ECO:0000269|PubMed:22980980}.
• Pathway: mTOR signaling pathway - Homo sapiens (human);Neutrophil degranulation;Signal Transduction;Gene expression (Transcription);Generic Transcription Pathway;RNA Polymerase II Transcription;mTORC1-mediated signalling;Energy dependent regulation of mTOR by LKB1-AMPK;mTOR signalling;Innate Immune System;Immune System;Fibroblast growth factor-1;TP53 Regulates Metabolic Genes;Macroautophagy;Cellular responses to external stimuli;Regulation of PTEN gene transcription;PTEN Regulation;PIP3 activates AKT signaling;Transcriptional Regulation by TP53;Intracellular signaling by second messengers (Consensus)

Recessive Scores

• pRec: 0.130

Intolerance Scores

• rvis_EVS: -0.14
• rvis_percentile_EVS: 42.88

Haploinsufficiency Scores

• pHI: 0.412
• hipred: Y
• hipred_score: 0.606
• ghis: 0.530

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: E
• gene_indispensability_pred: N
• gene_indispensability_score: 0.114

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Lamtor1
• 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); cellular phenotype

Gene ontology

• Biological process: regulation of cell growth;regulation of receptor recycling;endosome organization;lysosome organization;cell cycle arrest;regulation of cholesterol esterification;regulation of cholesterol efflux;endosomal transport;regulation of macroautophagy;positive regulation of TOR signaling;lysosome localization;cellular protein localization;cholesterol homeostasis;neutrophil degranulation;positive regulation of MAPK cascade;regulation of cholesterol import;cellular response to amino acid stimulus
• Cellular component: lysosome;lysosomal membrane;plasma membrane;late endosome membrane;azurophil granule membrane;specific granule membrane;membrane raft;extracellular exosome;Ragulator complex;ficolin-1-rich granule membrane
• Molecular function: guanyl-nucleotide exchange factor activity;protein binding;protein-containing complex scaffold activity;GTPase binding