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Symbol LETM1 contributors: mct - updated : 09-05-2014
HGNC name leucine zipper-EF-hand containing transmembrane protein 1
HGNC id 6556
Corresponding disease
WHS Wolf-Hirschhorn syndrome
WHSCR Wolf-Hirschhorn syndrome, mild form
Location 4p16.3      Physical location : 1.813.207 - 1.857.974
Synonym name
  • Mdm38 homolog (yeast)
  • LETM1 and EF-hand domain-containing protein 1, mitochondrial
  • DNA
    TYPE functioning gene
    STRUCTURE 44.77 kb     14 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status provisional
    Map cen - D4S166 - WHSC2 - WHSC1 - D4S3327 - LETM1 - D4S98 - FGFR3 - D4S168 - D4S96 - qter
    Physical map
    PCDH18 4q31.2-q32 protocadherin 18 LOC389255 4 similar to RSTI689 LOC152687 4p16.3 hypothetical protein LOC152687 AMBN 4q21 ameloblastin, enamel matrix protein FLJ90036 4p16.3 hypothetical protein FLJ90036 LOC391611 4 similar to Zinc finger protein 208 ZNF141 4p16.3 zinc finger protein 141 (clone pHZ-44) FLJ14297 4p16.3 hypothetical protein FLJ14297 FLJ20265 4p16.3 hypothetical protein FLJ20265 PDE6B 4p16.3 phosphodiesterase 6B, cGMP-specific, rod, beta (congenital stationary night blindness 3, autosomal dominant) ATP5I 4p16.3 ATP synthase, H+ transporting, mitochondrial F0 complex, subunit e MYL5 4p16.3 myosin, light polypeptide 5, regulatory FLJ22269 4p16.3 hypothetical protein FLJ22269 RNF3 4p16.3 ring finger protein 3 CPLX1 4p16.3 complexin 1 GAK 4p16 cyclin G associated kinase MGC4618 4p16.3 hypothetical protein MGC4618 DGKQ 4p16.3 diacylglycerol kinase, theta 110kDa SLC26A1 4p16.3 solute carrier family 26 (sulfate transporter), member 1 IDUA 4p16.3 iduronidase, alpha-L- FGFRL1 4p16 fibroblast growth factor receptor-like 1 LOC285498 4p16.3 hypothetical protein LOC285498 LOC132969 4p16.3 similar to hornerin SPON2 4p16.3 spondin 2, extracellular matrix protein CTBP1 4p16 C-terminal binding protein 1 MGC21675 4p16.3 hypothetical protein MGC21675 MAEA 4p16.3 macrophage erythroblast attacher KIAA1530 4p16.3 KIAA1530 protein FLJ34443 4p16.3 hypothetical protein FLJ34443 HSPX153 4p16.3 HPX-153 homeobox LOC345375 4p16.3 similar to CG32656-PA LOC152877 4p16.3 similar to RIKEN cDNA 5430419M09 SLBP 4p16 stem-loop (histone) binding protein LOC92305 4p16.3 hypothetical protein BC009331 TACC3 4p16.3 transforming, acidic coiled-coil containing protein 3 FGFR3 4p16.3 fibroblast growth factor receptor 3 (achondroplasia, thanatophoric dwarfism) LETM1 4p16.3 leucine zipper-EF-hand containing transmembrane protein 1 WHSC1 4p16.3 Wolf-Hirschhorn syndrome candidate 1 WHSC2 4p16.3 Wolf-Hirschhorn syndrome candidate 2 LOC389195 4 hypothetical gene supported by BC038466; BC047038 FLJ37478 4p16.3 hypothetical protein FLJ37478 POLN 4p16.3 polymerase (DNA directed) nu MGC4701 4p16.3 hypothetical protein MGC4701 MXD4 4p16.3 MAX dimerization protein 4 KIAA1643 4p16.3 KIAA1643 protein LOC339985 4p16.3 hypothetical gene supported by BC010180 RNF4 4p16.3 ring finger protein 4 C4orf8 4p16.3 chromosome 4 open reading frame 8 TNIP2 4p16.3 TNFAIP3 interacting protein 2 LOC389196 4 LOC389196 SH3BP2 4p16.3 SH3-domain binding protein 2 ADD1 4p16.3 adducin 1 (alpha) TETRAN 4p16.3 tetracycline transporter-like protein C4orf9 4p16.3 chromosome 4 open reading frame 9 GPRK2L 4p16.3 G protein-coupled receptor kinase 2-like (Drosophila) HD 4p16.3 huntingtin (Huntington disease) LOC345222 4p16.3 hypothetical gene supported by BC043530 RGS12 4p16.3 regulator of G-protein signalling 12 HGFAC 4p16.3 HGF activator FLJ33718 4p16.3 hypothetical protein FLJ33718
    regionally located .
    TRANSCRIPTS type messenger
    text four different transcript resulting from alternative polydenylation (Endele 1999)
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    14 - 5462 - 739 - 2007 17606466
    Type ubiquitous
       expressed in (based on citations)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    blood / hematopoieticthymus   highly
    Digestivesalivary gland   highly
    Reproductivefemale systembreastmammary gland highly
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Connectiveadipose  highly
    SystemCellPubmedSpeciesStageRna symbol
    Cardiovascularendothelial cell Homo sapiens
    cell lineage
    cell lines
    at STAGE
  • N terminal extracellular domain, with mitochondrial targeting sequences
  • a transmembrane segment (TM1),two EF-hand calcium Ca2 + binding sites
  • a C terminal leucine-zipper and phosphorylation sites
  • secondary structure an alpha helical domain forming a coiled coil
    interspecies ortholog to murine Letm1
    homolog to C.elegans F58G11.1b
    ortholog to yeast YOL027
    homolog to to yeast Mdm38
  • EF-hand family of calcium-binding proteins
  • CATEGORY receptor membrane
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,organelle,endoplasmic reticulum
  • in the inner mitochondrial membrane
  • reside in the ER membrane
  • basic FUNCTION
  • may be involved in Ca(2+) signaling and/or homeostasis
  • playing a role in mitochondrial morphology
  • encoding factors involved in both K+ homeostasis and organelle volume control
  • regulates the volume of the mitochondrial matrix
  • binding partner for THEM4 that may play an important role in mitochondrial fragmentation via OPA1-cleavage
  • serves as an anchor protein for complex formation with the mitochondrial ribosome and regulates mitochondrial biogenesis
  • plays an essential role in mitochondrial K+ homeostasis by mediating the mitochondrial K+/H+ exchange that is of prime importance for organelle-volume control
  • acts as an anchor protein and associates with mitochondrial ribosome protein L36
  • served as an anchor protein for complex formation between mitochondria and ribosome, and regulated mitochondrial biogenesis
  • mitochondrial Ca2+/H+ antiporter that achieved mitochondrial Ca2+ sequestration at small Ca2+ increases
  • LETM1 and UCP2/3 independently contribute to two distinct, mitochondrial Ca2+ uptake pathways in intact endothelial cells
  • its activity is essential for ER Ca(2+) uptake
  • SLC8B1 but not LETM1, mediates Ca(2+) extrusion from mitochondria
    signaling signal transduction
    a component
    small molecule metal binding,
  • Ca2+
  • protein
    cell & other
    Other regulated by BCS1L (stimulates the assembly of the LETM1 complex)
    corresponding disease(s) WHS , WHSCR
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional   deletion    
    in most patients with the Wolf-Hirschhorn syndrome exhibiting seizures and putative contributor to the phenotype, but preserved in those without seizures
    tumoral     --over  
    significantly increased in multiple human cancer tissues compared with normals
    Variant & Polymorphism
    Candidate gene for seizures in Wolf-Hirschhorn syndrome
    Therapy target
    adenovirus-mediated LETM1 may provide a useful target for designing lung tumor prevention and treatment