LAMTOR1
protein-codinglate endosomal/lysosomal adaptor, MAPK and MTOR activator 1, the group of Ragulator complex
Gene summary
Enables GTPase binding activity and protein-membrane adaptor activity. Contributes to guanyl-nucleotide exchange factor activity and molecular adaptor activity. Involved in several processes, including cholesterol homeostasis; positive regulation of TORC1 signaling; and regulation of cholesterol transport. Located in lysosome and plasma membrane. Part of FNIP-folliculin RagC/D GAP. Is active in Ragulator complex and lysosomal membrane. [provided by Alliance of Genome Resources, Jun 2026]
- C11orf59
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~17.4 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to LAMTOR1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_017907.3. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 1 | 1 | ||||
| missense | 21 | 21 | ||||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 23 | 1 | 0 | 24 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_060377.1 | 5 | MANE Select | |
| Ensembl | ENSP00000278671.5 | 5 | MANE Select | |
| Ensembl | ENSP00000445170.1 | 4 | Standard | |
| Ensembl | ENSP00000445170.1 | 4 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- mTOR signaling pathway - Homo sapiens (human)
- Neutrophil degranulation
- Signal Transduction
- Gene expression (Transcription)
- Generic Transcription Pathway
Biological Process
- regulation of cell growth
- regulation of receptor recycling
- endosome organization
- lysosome organization
- cell cycle arrest
Molecular Function
- guanyl-nucleotide exchange factor activity
- protein binding
- protein-containing complex scaffold activity
- GTPase binding
Cellular Component
- lysosome
- lysosomal membrane
- plasma membrane
- late endosome membrane
- azurophil granule membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000278671
- Coding exons
- 5
- Length
- 17493
- Individuals with no LoFs
- 125722
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 2
- Defined
- 125724
- p
- 0.00000795
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.27 | 57 | 91.1 | 0.626 | 0.00000510 | 1038 |
| Missense (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 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000019 | 0.000018 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- 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}.;
Recessive Scores
- pRec
- 0.130
Intolerance Scores
- RVIS EVS
- -0.14
- RVIS percentile EVS
- 42.88
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- S
- Essential (gene trap)
- E
- Indispensability pred.
- N
- Indispensability score
- 0.114
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |