LAMTOR4

protein-coding

late endosomal/lysosomal adaptor, MAPK and MTOR activator 4, the group of Ragulator complex

Gene summary

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]

Previous symbols:

C7orf59

MANE transcript

NM_001008395.4

Inheritance

—

ClinVar variants

U:21B:2

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.75

Max pathogenic AF

—

Genomic locus

chr7:100,148,912-100,155,944

External References & Databases

Ensembl (ENSG00000188186)

Transcript & Mutation Effects

hg38 • Region Span ~7.0 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to LAMTOR4 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 19

not providedTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001008395.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous					2 clinvar	2
missense			19 clinvar			19
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	21	0	2	23

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 43 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001008395.4	RefSeq	NP_001008396.1	4	MANE Select
ENST00000341942.10	Ensembl	ENSP00000343118.5	4	MANE Select
NM_001318236.2	RefSeq	NP_001305165.1	4	Standard
NM_001318237.2	RefSeq	NP_001305166.1	3	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

mTOR signaling pathway - Homo sapiens (human)
Signal Transduction
Gene expression (Transcription)
Generic Transcription Pathway
RNA Polymerase II Transcription

Biological Process

cell cycle arrest
regulation of cell size
regulation of macroautophagy
positive regulation of TOR signaling
protein localization to lysosome

Molecular Function

guanyl-nucleotide exchange factor activity
protein binding
protein-containing complex scaffold activity

Cellular Component

lysosome
lysosomal membrane
intracellular membrane-bounded organelle
Ragulator complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000341942
Coding exons: 4
Length: 7038
Individuals with no LoFs: 125739
Homozygous LoFs: 0
Heterozygous LoFs: 9
Defined: 125748
p: 0.0000358

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.268	49	54.6	0.898	0.00000306	606
Missense (PolyPhen)		8	12.506	0.63971		160
Synonymous	-0.544	27	23.6	1.14	0.00000121	216
Loss of Function	0.524	4	5.30	0.755	2.26e-7	56

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.000053	0.000053	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

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. {ECO:0000269|PubMed:22980980}.;

Recessive Scores

pRec: 0.107

Intolerance Scores

RVIS EVS: -0.05
RVIS percentile EVS: 49.39

Essentials

Essential (CRISPR): E
Essential (CRISPR2): S
Essential (gene trap): N

Gene Damage Prediction

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