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)
Haploinsufficiency (HI) Score Details
- Danon disease Monarch
-
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.
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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.
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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.
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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.
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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.
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
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.