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 (Strong), 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 (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Buschke-Ollendorff syndrome	AD	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Dermatologic; Musculoskeletal	12749062; 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 (782 variants)
• Inborn_genetic_diseases (126 variants)
• Dermatofibrosis_lenticularis_disseminata (70 variants)
• LEMD3-related_disorder (13 variants)
• not_specified (7 variants)
• Osteopoikilosis (2 variants)
• Melorheostosis_with_osteopoikilosis (2 variants)
• Multiple_monogenic_benign_skin_tumours (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.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			6	199	7	212
missense	2	1	457	28	2	490
nonsense	19	4	1			24
start loss			1			1
frameshift	27	7	2			36
splice donor/acceptor (+/-2bp)	4	6	5			15
Total	52	18	472	227	9

Highest pathogenic variant AF is 0.0000027402102

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
LEMD3	protein_coding	protein_coding	ENST00000308330	13	78757

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
		125737	0	11	125748	0.0000437

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.260	485	469	1.03	0.0000240	5845
Missense in Polyphen		149	188.44	0.79072		2349
Synonymous	-1.22	199	178	1.12	0.00000910	1848
Loss of Function	5.25	5	41.5	0.120	0.00000227	489

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000185	0.000185
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000544	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.0000529	0.0000527
Middle Eastern	0.0000544	0.0000544
South Asian	0.00	0.00
Other	0.000164	0.000163

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

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

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

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