LAMTOR1

Chr 11

late endosomal/lysosomal adaptor, MAPK and MTOR activator 1

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

NCBI Gene: 55004 ENSG00000149357 UniProt: Q6IAA8

The LAMTOR1 protein is a key component of the Ragulator complex that anchors to lysosomal membranes and activates mTORC1 signaling in response to amino acids, while also regulating cholesterol homeostasis and endosomal trafficking. Mutations cause autosomal recessive immunodeficiency with hypopigmentation, affecting immune function and melanin production. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.557), and the condition typically presents in early childhood with recurrent infections and partial albinism.

ResearchSummary from RefSeq, UniProt

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]

ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.56

LOEUF

GOF

Mechanism· predicted

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

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?

1.27Z-score

OE missense 0.63 (0.51–0.78)

57 obs / 91.1 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.12 (0.04–0.56)

0≤0.351.4

Missense OE?0.63 (0.51–0.78)

0≤0.61.4

Synonymous OE?0.73

0≤1.21.6

LoF obs/exp: 1 / 8.5Missense obs/exp: 57 / 91.1Syn Z: 1.31

Background carrier burden — how many people carry a rare variant somewhere in LAMTOR1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 160

221 rare PASS variants

Rare truncating (LoF)

1 in 12,000

24 rare PASS variants

Rare synonymous (reference)

1 in 620

107 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for LAMTOR1. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 660	1 in 16,000
South Asian	~43k	1 in 390	≈ 1 in 20,000
Remaining (unassigned)	~30k	1 in 250	≈ 1 in 30,000
European (Finnish)	~27k	1 in 840	≈ 1 in 27,000
Admixed American	~22k	1 in 240	1 in 3,400
African / African American	~21k	1 in 190	≈ 1 in 21,000
East Asian	~20k	1 in 190	≈ 1 in 5,700
Ashkenazi Jewish	~13k	1 in 1,200	none seen
Middle Eastern	~2,884	1 in 550	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 5 coding exons well covered in gnomAD exomes and genomes.? see exons ↓