GeneBe

LEMD3

LEM domain containing 3, the group of LEM domain containing

Basic information

Region (hg38): 12:65169583-65248355

Links

ENSG00000174106 ∙ NCBI:23592 ∙ OMIM:607844 ∙ HGNC:28887 ∙ Uniprot:Q9Y2U8 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

  • Buschke-Ollendorff syndrome (Definitive), mode of inheritance: AD
  • Buschke-Ollendorff syndrome (Strong), mode of inheritance: AD
  • melorheostosis with osteopoikilosis (Supportive), mode of inheritance: AD
  • Buschke-Ollendorff syndrome (Supportive), mode of inheritance: AD
  • isolated osteopoikilosis (Supportive), mode of inheritance: AD
  • Buschke-Ollendorff syndrome (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Buschke-Ollendorff syndromeADGeneralGenetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testingDermatologic; Musculoskeletal12749062; 15489854; 17223882; 17087626; 19438932; 20618940; 20732851; 21985280

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the LEMD3 gene.

  • not_provided (667 variants)
  • Inborn_genetic_diseases (109 variants)
  • Dermatofibrosis_lenticularis_disseminata (69 variants)
  • LEMD3-related_disorder (13 variants)
  • not_specified (7 variants)
  • Osteopoikilosis (2 variants)
  • Melorheostosis_with_osteopoikilosis (2 variants)
  • Dermatofibrosis_lenticularis_disseminata,_isolated (2 variants)
  • Gorham-Stout_disease (1 variants)
  • Intellectual_disability (1 variants)
  • See_cases (1 variants)
  • OSTEOPOIKILOSIS_WITH_OR_WITHOUT_MELORHEOSTOSIS (1 variants)
  • Cerebral_arteriovenous_malformation (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the LEMD3 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000014319.5. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

EffectPLPVUSLBBSum
synonymous
3
clinvar
170
clinvar
7
clinvar
 180
missense
2
clinvar
1
clinvar
390
clinvar
27
clinvar
2
clinvar
 422
nonsense
18
clinvar
4
clinvar
 22
start loss
1
 1
frameshift
21
clinvar
6
clinvar
1
clinvar
 28
splice donor/acceptor (+/-2bp)
4
clinvar
5
clinvar
 9
Total 45 16 395 197 9

Highest pathogenic variant AF is 0.00000274021

Loading clinvar variants...

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
LEMD3protein_codingprotein_codingENST00000308330 1378757
pLI Probability
LOF Intolerant 		pRec Probability
LOF Recessive 		Individuals with
no LOFs 		Individuals with
Homozygous LOFs 		Individuals with
Heterozygous LOFs 		Defined p
0.9990.001231257370111257480.0000437
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense-0.2604854691.030.00002405845
Missense in Polyphen149188.440.790722349
Synonymous-1.221991781.120.000009101848
Loss of Function5.25541.50.1200.00000227489

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.0001850.000185
Ashkenazi Jewish0.000.00
East Asian0.00005440.0000544
Finnish0.000.00
European (Non-Finnish)0.00005290.0000527
Middle Eastern0.00005440.0000544
South Asian0.000.00
Other0.0001640.000163

dbNSFP

Source: dbNSFP

Function
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}.;
Pathway
Clearance of Nuclear Envelope Membranes from Chromatin;Nuclear Envelope Breakdown;Mitotic Prophase;Initiation of Nuclear Envelope Reformation;Nuclear Envelope Reassembly;Mitotic Anaphase;Mitotic Metaphase and Anaphase;M Phase;Cell Cycle;Cell Cycle, Mitotic (Consensus)

Recessive Scores

pRec
0.161

Intolerance Scores

loftool
0.440
rvis_EVS
-1.15
rvis_percentile_EVS
6.23

Haploinsufficiency Scores

pHI
0.487
hipred
Y
hipred_score
0.816
ghis
0.658

Essentials

essential_gene_CRISPR
N
essential_gene_CRISPR2
N
essential_gene_gene_trap
N
gene_indispensability_pred
E
gene_indispensability_score
0.831

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium

Mouse Genome Informatics

Gene name
Lemd3
Phenotype
cellular phenotype; embryo phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan);

Gene ontology

Biological process
angiogenesis;nuclear envelope organization;negative regulation of transforming growth factor beta receptor signaling pathway;negative regulation of BMP signaling pathway;negative regulation of activin receptor signaling pathway;regulation of intracellular signal transduction
Cellular component
nuclear inner membrane;integral component of nuclear inner membrane;membrane;integral component of membrane;nuclear membrane
Molecular function
DNA binding;protein binding