LAMTOR2

Chr 1AR

late endosomal/lysosomal adaptor, MAPK and MTOR activator 2

Also known as: ENDAP, HSPC003, MAPBPIP, MAPKSP1AP, ROBLD3, Ragulator2, p14

The product of this gene is highly conserved with a mouse protein associated with the cytoplasmic face of late endosomes and lysosomes. The mouse protein interacts with MAPK scaffold protein 1, a component of the mitogen-activated protein kinase pathway. In humans, a mutation in this gene has been associated with a primary immunodeficiency syndrome, and suggests a role for this protein in endosomal biogenesis. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Feb 2009]

GeneReviewsOMIMResearchGenerating clinical summary…
DNmechanismARLOEUF 0.931 OMIM phenotype
Clinical SummaryLAMTOR2
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.30) despite low pLI — interpret in context.
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ClinVar Variants
44 VUS of 86 total submissions
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GeneReview available — LAMTOR2
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint?
0.93LOEUF
pLI 0.198
Z-score 1.70
OE 0.30 (0.120.93)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?
1.26Z-score
OE missense 0.57 (0.450.75)
40 obs / 69.7 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?
LoF OE?0.30 (0.120.93)
00.351.4
Missense OE?0.57 (0.450.75)
00.61.4
Synonymous OE?1.11
01.21.6
LoF obs/exp: 2 / 6.8Missense obs/exp: 40 / 69.7Syn Z: -0.45

This gene — mechanism propensity

DN
0.6647th %ile
GOF
0.5071th %ile
LOF
0.3261th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

86 submitted variants in ClinVar

Classification Summary

VUS44
Likely Benign36
Benign3
Conflicting1
44
VUS
36
Likely Benign
3
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
0
0
0
Likely Pathogenic
0
0
0
0
0
VUS
6
33
3
2
44
Likely Benign
0
0
11
25
36
Benign
0
0
2
1
3
Conflicting
1
Total633162884

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

View in ClinVar →

16 pathogenic / likely-pathogenic (of 30) ClinVar copy-number / structural variants overlap LAMTOR2 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →

Protein Context — Lollipop Plot

LAMTOR2 · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →