LAMP2

lysosomal associated membrane protein 2, the group of CD molecules|Lysosome associated membrane proteins

Basic information

Region (hg38): X:120426147-120469365

Links

ENSG00000005893 ∙ NCBI:3920 ∙ OMIM:309060 ∙ HGNC:6501 ∙ Uniprot:P13473 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Danon disease (Definitive), mode of inheritance: XLR
• Danon disease (Strong), mode of inheritance: XL
• Danon disease (Supportive), mode of inheritance: XL
• Danon disease (Definitive), mode of inheritance: XL
• Danon disease (Definitive), mode of inheritance: XL
• Danon disease (Strong), mode of inheritance: XL
• Danon disease (Definitive), mode of inheritance: XL

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Danon disease	XL	Cardiovascular	Surveillance (eg, with EKG and electrocardiogram) and medical management can help decrease morbidity related to cardiomyopathy and arrhythmias; Heart transplant has been suggested to be the only truly effective treatment	Biochemical; Cardiovascular; Musculoskeletal; Neurologic	6450334; 3806120; 3057987; 8504498; 7919972; 10972294; 12084876; 15253947; 15673802; 15889279; 15792868; 15907287; 17899313; 19318653; 21161685; 21816855; 22074992; 22365987; 22541782; 22750798
Males typically display mental retardation and other recognizable features, but females may be affected with cardiomyopathy and arrhthymias

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the LAMP2 gene.

• Danon disease (471 variants)
• not provided (179 variants)
• Cardiovascular phenotype (108 variants)
• not specified (85 variants)
• Hypertrophic cardiomyopathy (70 variants)
• Cardiomyopathy (23 variants)
• History of neurodevelopmental disorder (7 variants)
• Primary dilated cardiomyopathy (4 variants)
• Primary familial hypertrophic cardiomyopathy (4 variants)
• Danon disease;Cardiomyopathy (4 variants)
• Danon disease;Hypertrophic cardiomyopathy (2 variants)
• Inborn genetic diseases (2 variants)
• Intellectual disability (2 variants)
• Hypertrophic cardiomyopathy;Danon disease (1 variants)
• Trifascicular block on electrocardiogram (1 variants)
• Isolated Noncompaction of the Ventricular Myocardium (1 variants)
• Primary dilated cardiomyopathy;Danon disease (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the LAMP2 gene is commonly pathogenic or not.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			3	73	2	78
missense	2		171	13	2	188
nonsense	29	4			1	34
start loss		2	1			3
frameshift	34	9	1			44
inframe indel			1	1		2
splice donor/acceptor (+/-2bp)	9	7	3			19
splice region	3	1	11	19	2	36
non coding			41	82	29	152
Total	74	22	221	169	34

Variants in LAMP2

This is a list of pathogenic ClinVar variants found in the LAMP2 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
X-120426151-T-C		Hypertrophic cardiomyopathy • Danon disease	Uncertain significance (Oct 26, 2021)
X-120426275-T-A		Hypertrophic cardiomyopathy • Danon disease	Benign/Likely benign (Jan 13, 2018)
X-120426285-T-C		Danon disease • Hypertrophic cardiomyopathy	Benign/Likely benign (Jan 12, 2018)
X-120426359-TC-T		Hypertrophic cardiomyopathy • Danon disease	Conflicting classifications of pathogenicity (Dec 01, 2022)
X-120426362-T-C		Danon disease • Hypertrophic cardiomyopathy	Conflicting classifications of pathogenicity (Nov 01, 2022)
X-120426465-T-C		Hypertrophic cardiomyopathy • Danon disease	Uncertain significance (Jan 12, 2018)
X-120426560-T-A		Hypertrophic cardiomyopathy • Danon disease	Uncertain significance (Jan 12, 2018)
X-120426566-T-C		Danon disease	Conflicting classifications of pathogenicity (Feb 01, 2023)
X-120426652-G-A		Hypertrophic cardiomyopathy • Danon disease	Benign/Likely benign (Jan 13, 2018)
X-120426659-T-C		Danon disease	Uncertain significance (Jan 13, 2018)
X-120426744-T-C		Danon disease • Hypertrophic cardiomyopathy	Benign/Likely benign (Jan 13, 2018)
X-120426761-T-C		Danon disease • Hypertrophic cardiomyopathy	Benign/Likely benign (Jan 12, 2018)
X-120427317-C-A		Danon disease	Uncertain significance (Jan 13, 2018)
X-120427319-G-A		Danon disease	Uncertain significance (Jan 13, 2018)
X-120427634-A-G		Hypertrophic cardiomyopathy • Danon disease	Uncertain significance (Jul 23, 2021)
X-120427636-A-G		Hypertrophic cardiomyopathy • Danon disease	Conflicting classifications of pathogenicity (Jan 13, 2018)
X-120427646-G-T		Hypertrophic cardiomyopathy • Danon disease	Uncertain significance (Jan 13, 2018)
X-120427740-T-C		Danon disease	Benign (Jan 12, 2018)
X-120427760-A-C		Danon disease	Uncertain significance (Jan 13, 2018)
X-120427829-T-C		Danon disease	Benign (Jan 13, 2018)
X-120427835-G-A		Danon disease	Uncertain significance (Jul 28, 2021)
X-120427852-GAAC-G		Danon disease • Hypertrophic cardiomyopathy	Likely benign (May 20, 2021)
X-120427864-C-A		Danon disease	Benign/Likely benign (May 13, 2021)
X-120427871-A-G		Danon disease	Benign (Jan 13, 2018)
X-120427910-A-G		Danon disease	Uncertain significance (Jan 13, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
LAMP2	protein_coding	protein_coding	ENST00000434600	9	41539

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.267	0.728	125723	1	4	125728	0.0000199

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.840	116	144	0.803	0.00000998	2690
Missense in Polyphen		21	35.744	0.5875		717
Synonymous	1.06	43	52.8	0.815	0.00000356	818
Loss of Function	2.42	3	12.1	0.248	8.34e-7	231

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.000184	0.000109
Finnish	0.00	0.00
European (Non-Finnish)	0.0000244	0.0000176
Middle Eastern	0.000184	0.000109
South Asian	0.0000524	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Plays an important role in chaperone-mediated autophagy, a process that mediates lysosomal degradation of proteins in response to various stresses and as part of the normal turnover of proteins with a long biological half-live (PubMed:8662539, PubMed:11082038, PubMed:18644871, PubMed:24880125, PubMed:27628032). Functions by binding target proteins, such as GAPDH and MLLT11, and targeting them for lysosomal degradation (PubMed:8662539, PubMed:11082038, PubMed:18644871, PubMed:24880125). Plays a role in lysosomal protein degradation in response to starvation (By similarity). Required for the fusion of autophagosomes with lysosomes during autophagy (PubMed:27628032). Cells that lack LAMP2 express normal levels of VAMP8, but fail to accumulate STX17 on autophagosomes, which is the most likely explanation for the lack of fusion between autophagosomes and lysosomes (PubMed:27628032). Required for normal degradation of the contents of autophagosomes (PubMed:27628032). Required for efficient MHCII-mediated presentation of exogenous antigens via its function in lysosomal protein degradation; antigenic peptides generated by proteases in the endosomal/lysosomal compartment are captured by nascent MHCII subunits (PubMed:20518820). Is not required for efficient MHCII-mediated presentation of endogenous antigens (PubMed:20518820). {ECO:0000250|UniProtKB:P17046, ECO:0000269|PubMed:11082038, ECO:0000269|PubMed:18644871, ECO:0000269|PubMed:20518820, ECO:0000269|PubMed:24880125, ECO:0000269|PubMed:27628032, ECO:0000269|PubMed:8662539}.
• Disease: DISEASE: Danon disease (DAND) [MIM:300257]: DAND is a lysosomal glycogen storage disease characterized by the clinical triad of cardiomyopathy, vacuolar myopathy and mental retardation. It is often associated with an accumulation of glycogen in muscle and lysosomes. {ECO:0000269|PubMed:15673802, ECO:0000269|PubMed:15907287}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Phagosome - Homo sapiens (human);Autophagy - animal - Homo sapiens (human);Lysosome - Homo sapiens (human);Tuberculosis - Homo sapiens (human);Senescence and Autophagy in Cancer;Neutrophil degranulation;Innate Immune System;Immune System;Platelet degranulation ;Response to elevated platelet cytosolic Ca2+;Platelet activation, signaling and aggregation;Hemostasis (Consensus)

Recessive Scores

• pRec: 0.618

Intolerance Scores

• rvis_EVS: 0.11
• rvis_percentile_EVS: 61.73

Haploinsufficiency Scores

• pHI: 0.499
• hipred: N
• hipred_score: 0.372
• ghis: 0.502

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.150

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Lamp2
• Phenotype: nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); skeleton phenotype; immune system phenotype; liver/biliary system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); hematopoietic system phenotype; growth/size/body region phenotype; reproductive system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); craniofacial phenotype; muscle phenotype; homeostasis/metabolism phenotype; cellular phenotype; endocrine/exocrine gland phenotype

Gene ontology

• Biological process: platelet degranulation;protein targeting;cellular response to starvation;protein import;regulation of protein stability;neutrophil degranulation;muscle cell cellular homeostasis;protein stabilization;chaperone-mediated autophagy;protein targeting to lysosome involved in chaperone-mediated autophagy;autophagosome maturation;lysosomal protein catabolic process
• Cellular component: extracellular space;lysosome;lysosomal membrane;late endosome;plasma membrane;membrane;phagocytic vesicle membrane;platelet dense granule membrane;late endosome membrane;azurophil granule membrane;lysosomal lumen;autolysosome;membrane raft;extracellular exosome;integral component of autophagosome membrane;membrane microdomain;ficolin-1-rich granule membrane;lysosomal matrix
• Molecular function: protein binding;enzyme binding;protein domain specific binding