LAMTOR3
protein-codinglate endosomal/lysosomal adaptor, MAPK and MTOR activator 3, the group of Ragulator complex
Gene summary
This gene encodes a scaffold protein that functions in the extracellular signal-regulated kinase (ERK) cascade. The protein is localized to late endosomes by the mitogen-activated protein-binding protein-interacting protein, and binds specifically to MAP kinase kinase MAP2K1/MEK1, MAP kinase MAPK3/ERK1, and MAP kinase MAPK1/ERK2. Studies of the orthologous gene in mouse indicate that it regulates late endosomal traffic and cell proliferation. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. A pseudogene of this gene is located on the long arm of chromosome 13. [provided by RefSeq, Aug 2011]
- MAP2K1IP1
- MAPKSP1
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~16.1 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 LAMTOR3 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_021970.4. 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 | 0 | |||||
| missense | 17 | 17 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 7 | 7 | ||||
| Total | 0 | 0 | 24 | 0 | 0 | 24 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_068805.1 | 6 | MANE Select | |
| Ensembl | ENSP00000424183.1 | 6 | MANE Select | |
| RefSeq | NP_001230665.1 | 6 | Standard | |
| Ensembl | ENSP00000226522.8 | 6 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- mTOR signaling pathway - Homo sapiens (human)
- MAPK signaling pathway - Homo sapiens (human)
- EGF-Ncore
- miR-targeted genes in epithelium - TarBase
- miR-targeted genes in leukocytes - TarBase
Biological Process
- MAPK cascade
- activation of MAPKK activity
- cell cycle arrest
- regulation of macroautophagy
- positive regulation of TOR signaling
Molecular Function
- guanyl-nucleotide exchange factor activity
- protein binding
- kinase activator activity
- protein-containing complex scaffold activity
Cellular Component
- lysosomal membrane
- plasma membrane
- focal adhesion
- endosome membrane
- specific granule membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000499666
- Coding exons
- 6
- Length
- 16155
- Individuals with no LoFs
- 125274
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 2
- Defined
- 125276
- p
- 0.00000798
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.0444 | 58 | 59.0 | 0.984 | 0.00000273 | 796 |
| Missense (PolyPhen) | 12 | 13.795 | 0.8699 | 185 | ||
| Synonymous | 1.62 | 11 | 20.3 | 0.543 | 8.74e-7 | 232 |
| Loss of Function | 2.41 | 1 | 8.66 | 0.115 | 5.29e-7 | 101 |
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 | 0.000046 | 0.000046 | rare |
| European (Non-Finnish) | 0.0000089 | 0.0000088 | 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. Adapter protein that enhances the efficiency of the MAP kinase cascade facilitating the activation of MAPK2. {ECO:0000269|PubMed:20381137, ECO:0000269|PubMed:22980980}.;
Recessive Scores
- pRec
- 0.108
Intolerance Scores
- RVIS EVS
- 0.01
- RVIS percentile EVS
- 54.63
Essentials
- Essential (CRISPR)
- N
- Essential (gene trap)
- K
- Indispensability pred.
- N
- Indispensability score
- 0.114
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Low | Low | Low |
| Primary Immunodeficiency | Low | Low | Low |
| Cancer | Low | Low | Low |