LAMP2
  • 3
    Haplo
    Score
  • 0
    Triplo
    Score

Gene Facts External Data Attribution

HGNC Symbol
LAMP2 (HGNC:6501) HGNC Entrez Ensembl OMIM UCSC Uniprot GeneReviews LOVD LSDB ClinVar
HGNC Name
lysosomal associated membrane protein 2
Gene type
protein-coding gene
Locus type
gene with protein product
Previous symbols
No previous names found
Alias symbols
CD107b
%HI
54.6(Read more about the DECIPHER Haploinsufficiency Index)
pLI
0.27(Read more about gnomAD pLI score)
LOEUF
0.64(Read more about gnomAD LOEUF score)
Cytoband
Xq24
Genomic Coordinates
GRCh37/hg19: chrX:119560003-119603204 NCBI Ensembl UCSC
GRCh38/hg38: chrX:120426148-120469349 NCBI Ensembl UCSC
MANE Select Transcript
NM_002294.3 ENST00000200639.9 (Read more about MANE Select)
Function
Lysosomal membrane glycoprotein which plays an important role in lysosome biogenesis, lysosomal pH regulation and autophagy (PubMed:8662539, PubMed:11082038, PubMed:18644871, PubMed:24880125, PubMed:27628032, PubMed:36586411, PubMed:37390818). Acts as an important regulator of lysosomal lumen pH regulation by acting as a direct inhibitor of the proton channel TMEM175, facilitating lysosomal acidification for optimal hydrolase activity (PubMed:37390818). Plays an important role in chaperone-media... (Source: Uniprot)

Dosage Sensitivity Summary (Gene)

Dosage ID:
ISCA-17531
ClinGen Curation ID:
CCID:007389
Curation Status:
Complete
Issue Type:
Dosage Curation - Gene
Haploinsufficiency:
Sufficient Evidence for Haploinsufficiency (3)
Read full report...
Triplosensitivity:
No Evidence for Triplosensitivity (0)
Read full report...
Last Evaluated:
02/09/2021

Haploinsufficiency (HI) Score Details

HI Score:
3
HI Evidence Strength:
Sufficient Evidence for Haploinsufficiency (Disclaimer)
HI Disease:
HI Evidence:
  • PUBMED: 20173215
    Yang (2010): A report of three male patients with Danon disease who had intragenic deletions in LAMP2. Parental studies were not available for two patients and one deletion was found to be de novo.
  • PUBMED: 19588270
    Regelsberg (2009): A report of a male patient with Danon disease who had a de novo frameshift mutation in LAMP2.
  • PUBMED: 19057086
    Dougu (2009): A report of a frameshift mutation in LAMP2 found in a boy with Danon disease as well as his mother and two sisters who have cardiomyopathy. The authors also provide a table listing multiple loss-of-function mutations that had been reported previously.
  • PUBMED: 27145725
    Sugie et al (2016) describe a 15 year old girl with Danon disease who presented with early onset of hypertrophic cardiomyopathy and mild intellectual disability. She had a de novo novel mutation, c.749C > A (p.Ser250X), in the LAMP2 gene, and her muscles showed decreased LAMP‐2 expression. There are also many more reports of de novo and maternally inherited loss of function LAMP2 variants in the literature associated with Danon disease.
  • PUBMED: 10972294
    Nishino et al. (2000) report ten unrelated patients with Danon disease and variants in LAMP2, including nonsense, frameshift, and exon-skipping variants. At least 6 of these variants were demonstrated to result in complete LAMP-2 deficiency by Western blot analysis on frozen skeletal muscle specimens from the patients.
  • PUBMED: 16565504
    Fanin et al. (2006) report three "novel families...with unreported LAMP2 gene null [variants] and LAMP-2 protein deficiency in skeletal and myocardial muscle, leukocytes, and fibroblasts." While there was a reported family history of Danon disease in all three families, only one family, Family 3 had multiple family members tested, and was able to demonstrate 3 segregations of the variant amongst affected individuals.
HI Evidence Comments:
Loss of function mutations in LAMP2 cause Danon disease in males (OMIM 300257). Danon disease is a multisystem condition with predominant involvement of the heart, skeletal muscles, and retina, with overlying cognitive dysfunction. The clinical features in females are broader and more variable. Females are more likely to have dilated cardiomyopathy, with a smaller proportion requiring heart transplantation compared to affected males. Cardiac conduction abnormalities, skeletal muscle weakness, mild cognitive impairment, and pigmentary retinopathy are variably seen in affected females.
NOTE:

The loss-of-function and triplosensitivity ratings for genes on the X chromosome are made in the context of a male genome to account for the effects of hemizygous duplications or nullizygous deletions. In contrast, disruption of some genes on the X chromosome causes male lethality and the ratings of dosage sensitivity instead take into account the phenotype in female individuals. Factors that may affect the severity of phenotypes associated with X-linked disorders include the presence of variable copies of the X chromosome (i.e. 47,XXY or 45,X) and skewed X-inactivation in females.

Triplosensitivity (TS) Score Details

TS Score:
0
TS Evidence Strength:
No Evidence for Triplosensitivity (Disclaimer)
NOTE:

The loss-of-function and triplosensitivity ratings for genes on the X chromosome are made in the context of a male genome to account for the effects of hemizygous duplications or nullizygous deletions. In contrast, disruption of some genes on the X chromosome causes male lethality and the ratings of dosage sensitivity instead take into account the phenotype in female individuals. Factors that may affect the severity of phenotypes associated with X-linked disorders include the presence of variable copies of the X chromosome (i.e. 47,XXY or 45,X) and skewed X-inactivation in females.

Genomic View

Select assembly: (NC_000023.10) (NC_000023.11)