LAMTOR2

late endosomal/lysosomal adaptor, MAPK and MTOR activator 2, the group of Ragulator complex

Basic information

Region (hg38): 1:156054782-156058506

Previous symbols: [ "ROBLD3" ]

Links

ENSG00000116586 ∙ NCBI:28956 ∙ OMIM:610389 ∙ HGNC:29796 ∙ Uniprot:Q9Y2Q5 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• primary immunodeficiency syndrome due to p14 deficiency (Limited), mode of inheritance: AR
• primary immunodeficiency syndrome due to p14 deficiency (Limited), mode of inheritance: Unknown
• primary immunodeficiency syndrome due to p14 deficiency (Supportive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Immunodeficiency due to defect in MAPBP-interacting protein	AR	Allergy/Immunology/Infectious	Antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial (severe congenital neutropenia has been reported as responding to G-CSF)	Allergy/Immunology/Infectious; Dermatologic; Musculoskeletal	17195838

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the LAMTOR2 gene.

• not_provided (74 variants)
• not_specified (9 variants)
• Primary_immunodeficiency_syndrome_due_to_p14_deficiency (2 variants)
• LAMTOR2-related_disorder (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the LAMTOR2 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000014017.4. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			2	25		27
missense			32			32
nonsense			3			3
start loss						0
frameshift			4			4
splice donor/acceptor (+/-2bp)						0
Total	0	0	41	25	0

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
LAMTOR2	protein_coding	protein_coding	ENST00000368305	4	3759

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
		125744	0	4	125748	0.0000159

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.26	40	69.7	0.574	0.00000364	800
Missense in Polyphen		5	16.435	0.30422		215
Synonymous	-0.448	31	28.0	1.11	0.00000154	259
Loss of Function	1.70	2	6.77	0.295	3.79e-7	69

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000546	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.0000176	0.0000176
Middle Eastern	0.0000546	0.0000544
South Asian	0.0000327	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• 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}.
• Disease: DISEASE: Immunodeficiency due to defect in MAPBP-interacting protein (ID-MAPBPIP) [MIM:610798]: This form of primary immunodeficiency syndrome includes congenital neutropenia, partial albinism, short stature and B-cell and cytotoxic T-cell deficiency. {ECO:0000269|PubMed:17195838}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: mTOR signaling pathway - Homo sapiens (human);MAP2K and MAPK activation;Neutrophil degranulation;Signal Transduction;Gene expression (Transcription);Generic Transcription Pathway;RNA Polymerase II Transcription;mTORC1-mediated signalling;Energy dependent regulation of mTOR by LKB1-AMPK;mTOR signalling;Innate Immune System;Immune System;TP53 Regulates Metabolic Genes;Macroautophagy;Cellular responses to external stimuli;Regulation of PTEN gene transcription;RAF/MAP kinase cascade;MAPK1/MAPK3 signaling;MAPK family signaling cascades;PTEN Regulation;PIP3 activates AKT signaling;Transcriptional Regulation by TP53;Intracellular signaling by second messengers (Consensus)

Recessive Scores

• pRec: 0.0827

Intolerance Scores

• rvis_EVS: 0.04
• rvis_percentile_EVS: 56.25

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: N
• gene_indispensability_score: 0.114

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Low	Low
Primary Immunodeficiency	Medium	Low	Medium
Cancer	Low	Low	Low

Gene ontology

• Biological process: MAPK cascade;activation of MAPKK activity;regulation of cell growth;cell cycle arrest;regulation of macroautophagy;positive regulation of TOR signaling;cellular protein localization;neutrophil degranulation;cellular response to amino acid stimulus
• Cellular component: lysosomal membrane;late endosome;plasma membrane;endosome membrane;specific granule membrane;tertiary granule membrane;Ragulator complex
• Molecular function: guanyl-nucleotide exchange factor activity;protein binding;protein-containing complex scaffold activity