LAMTOR1

Chr 11

late endosomal/lysosomal adaptor, MAPK and MTOR activator 1

Also known as: C11orf59, PDRO, Ragulator1, p18, p27RF-Rho

NCBI Gene: 55004ENSG00000149357UniProt: Q6IAA8

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. Part of FNIP-folliculin RagC/D GAP. Is active in Ragulator complex and lysosomal membrane. [provided by Alliance of Genome Resources, Apr 2025]

33
ClinVar variants
8
Pathogenic / LP
0.72
pLI score
0
Active trials
Clinical Summary— LAMTOR1
⚡
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.72) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
8 Pathogenic / Likely Pathogenic· 24 VUS of 33 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.56LOEUF
pLI 0.721
Z-score 2.39
OE 0.12 (0.04–0.56)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
1.27Z-score
OE missense 0.63 (0.51–0.78)
57 obs / 91.1 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.12 (0.04–0.56)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.63 (0.51–0.78)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.73
0≤1.21.6
LoF obs/exp: 1 / 8.5Missense obs/exp: 57 / 91.1Syn Z: 1.31

ClinVar Variant Classifications

33 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic8
VUS24
Likely Benign1
8
Pathogenic
24
VUS
1
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
8
0
8
Likely Pathogenic
0
0
0
0
0
VUS
0
19
5
0
24
Likely Benign
0
0
0
1
1
Benign
0
0
0
0
0
Total01913133

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

LAMTOR1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
LAMTOR1 decreased exosomal PD-L1 to enhance immunotherapy efficacy in non-small cell lung cancer.
Wu B et al.·Mol Cancer
2024
N-myristoyltransferase-1 deficiency blocks myristoylation of LAMTOR1 and inhibits bladder cancer progression.
Sun Y et al.·Cancer Lett
2022
Regulation of LAMTOR1 by oxidative stress in retinal pigment epithelium: Implications for age-related macular degeneration pathogenesis.
Cai J et al.·Exp Eye Res
2024
Patient-Driven Discovery, Therapeutic Targeting, and Post-Clinical Validation of a Novel AKT1 Fusion-Driven Cancer.
Slotkin EK et al.·Cancer Discov
2019Case report
Identification of prostate cancer biomarkers in urinary exosomes.
Øverbye A et al.·Oncotarget
2015
Exosomal proteins as prostate cancer biomarkers in urine: From mass spectrometry discovery to immunoassay-based validation.
Wang L et al.·Eur J Pharm Sci
2017
Gene biomarker discovery at different stages of Alzheimer using gene co-expression network approach.
Soleimani Zakeri NS et al.·Sci Rep
2020
"Benign" Metastasizing Fibrous Histiocytoma Harboring PRKCD Gene Fusions With Malignant Clinical Course.
Wang CI et al.·Genes Chromosomes Cancer
2025Case report
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools