LAMTOR4

Chr 7

late endosomal/lysosomal adaptor, MAPK and MTOR activator 4

Also known as: C7orf59

NCBI Gene: 389541ENSG00000188186UniProt: Q0VGL1

Contributes to guanyl-nucleotide exchange factor activity and molecular adaptor activity. Involved in several processes, including cellular response to amino acid stimulus; positive regulation of TORC1 signaling; and protein localization to lysosome. Located in lysosome. Part of FNIP-folliculin RagC/D GAP and Ragulator complex. Is active in lysosomal membrane. [provided by Alliance of Genome Resources, Jul 2025]

0
ClinVar variants
0
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— LAMTOR4
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
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.
1.63LOEUF
pLI 0.004
Z-score 0.52
OE 0.75 (0.37–1.63)
Tolerant

Highly tolerant — LoF variants common in population

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.
0.27Z-score
OE missense 0.90 (0.71–1.14)
49 obs / 54.6 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.0.75 (0.37–1.63)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.90 (0.71–1.14)
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.1.14
0≤1.21.6
LoF obs/exp: 4 / 5.3Missense obs/exp: 49 / 54.6Syn Z: -0.54

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

LAMTOR4 · 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
Aberrant hyper-expression of the RNA binding protein GIGYF2 in endothelial cells modulates vascular aging and function.
Niu F et al.·Redox Biol
2023
Elevated LAMTOR4 Expression Is Associated with Lethal Prostate Cancer and Its Knockdown Decreases Cell Proliferation, Invasion, and Migration In Vitro.
Gamallat Y et al.·Int J Mol Sci
2024
Heterogeneity of late endosome/lysosomes shown by multiplexed DNA-PAINT imaging.
Bond C et al.·J Cell Biol
2025
The Absence of Intra-Tumoral Tertiary Lymphoid Structures is Associated with a Worse Prognosis and mTOR Signaling Activation in Hepatocellular Carcinoma with Liver Transplantation: A Multicenter Retrospective Study.
Li J et al.·Adv Sci (Weinh)
2024
C7orf59/LAMTOR4 phosphorylation and structural flexibility modulate Ragulator assembly.
Rasheed N et al.·FEBS Open Bio
2019
Quantitative genetic screening reveals a Ragulator-FLCN feedback loop that regulates the mTORC1 pathway.
De Zan E et al.·Sci Signal
2020
The coding and non-coding transcriptional landscape of subependymal giant cell astrocytomas.
Bongaarts A et al.·Brain
2020
Distinct Synaptic Vesicle Proteomic Signatures Associated with Pre- and Post-Natal Oxycodone-Exposure.
Odegaard KE et al.·Cells
2022
AKT-mTORC1 reactivation is the dominant resistance driver for PI3Kβ/AKT inhibitors in PTEN-null breast cancer and can be overcome by combining with Mcl-1 inhibitors.
Dunn S et al.·Oncogene
2022
Lysosomal TMEM9-LAMTOR4-controlled mTOR signaling integrity is required for mammary tumorigenesis.
Zhang S et al.·Cancer Commun (Lond)
2023
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC

No open access results found

Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

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External Resources

Links to major genomics databases and tools