LETM1
  • 0
    Haplo
    Score
  • 0
    Triplo
    Score

Gene Facts External Data Attribution

HGNC Symbol
LETM1 (HGNC:6556) HGNC Entrez Ensembl OMIM UCSC Uniprot GeneReviews LOVD LSDB ClinVar
HGNC Name
leucine zipper and EF-hand containing transmembrane protein 1
Gene type
protein-coding gene
Locus type
gene with protein product
Previous symbols
No previous names found
Alias symbols
SLC55A1, Mdm38
%HI
63.78(Read more about the DECIPHER Haploinsufficiency Index)
pLI
0(Read more about gnomAD pLI score)
LOEUF
0.88(Read more about gnomAD LOEUF score)
Cytoband
4p16.3
Genomic Coordinates
GRCh37/hg19: chr4:1813206-1857883 NCBI Ensembl UCSC
GRCh38/hg38: chr4:1811479-1856156 NCBI Ensembl UCSC
MANE Select Transcript
NM_012318.3 ENST00000302787.3 (Read more about MANE Select)
Function
Plays an important role in maintenance of mitochondrial morphology and in mediating either calcium or potassium/proton antiport (PubMed:18628306, PubMed:19797662, PubMed:24898248, PubMed:24344246, PubMed:29123128, PubMed:32139798, PubMed:36321428, PubMed:36055214). Mediates proton-dependent calcium efflux from mitochondrion (PubMed:19797662, PubMed:24344246, PubMed:29123128). Functions also as an electroneutral mitochondrial proton/potassium exchanger (PubMed:24898248, PubMed:36055214, PubMed:36... (Source: Uniprot)

Dosage Sensitivity Summary (Gene)

Dosage ID:
ISCA-17077
ClinGen Curation ID:
CCID:007398
Curation Status:
Complete
Issue Type:
Dosage Curation - Gene
Haploinsufficiency:
No Evidence for Haploinsufficiency (0)
Read full report...
Triplosensitivity:
No Evidence for Triplosensitivity (0)
Read full report...
Related Links:
Last Evaluated:
02/03/2012

Haploinsufficiency (HI) Score Details

HI Score:
0
HI Evidence Strength:
No Evidence for Haploinsufficiency (Disclaimer)
HI Disease:
HI Evidence Comments:
LETM1 is typically deleted as part of the Wolf-Hirschhorn syndrome. Though it is believed to be one of the critical dosage-sensitive genes contributing to the Wolf-Hirschhorn phenotype, particularly the development of seizures (see PMIDs 10486213, 17696124), there are no reports demonstrating that loss of function mutations in LETM1 alone cause a specific phenotype in humans. Furthermore, there are some patients with larger deletions encompassing LETM1 that do no develop siezures. Within the paper PMID:21729882, there is a single patient with a focal deletion of 54kb involving LETM1. The patient did not exhibit features of Wolf-Hirschhorn syndrome (including facial features), but rather presented at one year of age with microtia, renal agenesis, Duane anomaly, and a congenital heart defect. Parental studies were not described and seizures were not mentioned, but at the age of presentation may not be ruled-out. Also note the phenoytpe of this patient is different enough from those with larger deletions that are associated with Wolf-Hirschhorn syndrome, that it is possible the LETM1 deletion is not related to the phenotype of this patient. It is important to note that, though the current ISCA Haploinsufficiency rating for specific LETM1 is 0, deletions involving the larger Wolf-Hirschhorn region have a haploinsufficiency rating of 3. Given the expected critical role in WHS syndrome, any deletion involving LETM1 should be considered carefuly for pathogenicity, particularly when seizures are present.

Triplosensitivity (TS) Score Details

TS Score:
0
TS Evidence Strength:
No Evidence for Triplosensitivity (Disclaimer)
TS Evidence Comments:
Duplications encompassing LETM1 (along with other genes) have been reported in association with intellectual disability and congenital anomalies (PMID:21815251; PMID:20197130). No reports have been found, however, linking duplications involving only the LETM1 gene to specific phenotypes in humans.

Genomic View

Select assembly: (NC_000004.11) (NC_000004.12)