LEMD3
  • 3
    Haplo
    Score
  • 0
    Triplo
    Score

Gene Facts External Data Attribution

HGNC Symbol
LEMD3 (HGNC:28887) HGNC Entrez Ensembl OMIM UCSC Uniprot GeneReviews LOVD LSDB ClinVar
HGNC Name
LEM domain containing 3
Gene type
protein-coding gene
Locus type
gene with protein product
Previous symbols
No previous names found
Alias symbols
MAN1
%HI
36.92(Read more about the DECIPHER Haploinsufficiency Index)
pLI
0.4(Read more about gnomAD pLI score)
LOEUF
0.59(Read more about gnomAD LOEUF score)
Cytoband
12q14.3
Genomic Coordinates
GRCh37/hg19: chr12:65563363-65642135 NCBI Ensembl UCSC
GRCh38/hg38: chr12:65169583-65248355 NCBI Ensembl UCSC
MANE Select Transcript
NM_014319.5 ENST00000308330.3 (Read more about MANE Select)
Function
Can function as a specific repressor of TGF-beta, activin, and BMP signaling through its interaction with the R-SMAD proteins. Antagonizes TGF-beta-induced cell proliferation arrest. {ECO:0000269|PubMed:15601644, ECO:0000269|PubMed:15647271}. (Source: Uniprot)

Dosage Sensitivity Summary (Gene)

Dosage ID:
ISCA-35665
ClinGen Curation ID:
CCID:007396
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:
10/19/2020

Haploinsufficiency (HI) Score Details

HI Score:
3
HI Evidence Strength:
Sufficient Evidence for Haploinsufficiency (Disclaimer)
HI Disease:
HI Evidence:
  • PUBMED: 15489854
    Hellemans et al. (2004): Describes loss-of-function variants identified in three families with variable expressivity for osteopoikilosis, Buschke-Ollendorf syndrome, and melorheostosis, as well as in three unrelated individuals with osteopoikilosis. Two nonsense variants were reported, along with three frameshift variants and one splice-site variant that results in exon 6 skipping and a frameshift were reported; all were believed to result in loss-of-function. The reported variants in the 3 families were shown to segregate with all affected relatives in each kindred (>7 segregations across all 3 families). Of note, the paper also reports a case of an individual with osteopoikilosis, microcephaly, ectopic kidneys, and learning disabilities who was found to have a microdeletion enccompassing LEMD3 as well as a number of other genes.
  • PUBMED: 17087626
    Mumm et al. (2007): Describes 4 additional variants, including one nonsense variant (L478X) in a 3 generation family with osteopoikilosis, another nonsense variant (R655X) in a family with osteopoikilosis and melorheostosis, another nonsense (Y441X) variant in a family with Buschke-Ollendorf syndrome and lastly a 2 base insertion resulting in a frameshift in a family with Buschke-Ollendorf syndrome.
  • PUBMED: 19438932
    Zhang et al. (2009): Describes a W855X variant described in a boy with Buschke-Ollendorf syndrome that was inherited from his father with osteopoikilosis.
HI Evidence Comments:
Loss-of-function variants in LEMD3 are associated with osteopoikilosis, Buschke-Ollendorf syndrome, and melorheostosis with many more publications beyond those presented here supporting haploinsufficiency for LEMD3. Variable expressivity has been reported, with members of the same family exhibiting each of these different phenotypes. To date, variants in LEMD3 have not been observed in individuals with isolated melorheostosis (see Gnoli et al. 2019 PMID: 31129707).

Triplosensitivity (TS) Score Details

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

Genomic View

Select assembly: (NC_000012.11) (NC_000012.12)