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
• melorheostosis (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

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 (24 variants)
• Dermatofibrosis lenticularis disseminata (3 variants)
• Melorheostosis with osteopoikilosis (2 variants)
• LEMD3-related disorder (1 variants)
• Dermatofibrosis lenticularis disseminata, isolated (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.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			5	127	7	139
missense	1	1	290	11	2	305
nonsense	14	4	1			19
start loss			1			1
frameshift	12	4				16
inframe indel			8	1		9
splice donor/acceptor (+/-2bp)	1	3				4
splice region		1	3	6	2	12
non coding			23	31	30	84
Total	28	12	328	170	39

Variants in LEMD3

This is a list of pathogenic ClinVar variants found in the LEMD3 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
12-65169591-G-A		Dermatofibrosis lenticularis disseminata	Uncertain significance (Jan 13, 2018)
12-65169598-T-C			Uncertain significance (Nov 17, 2023)
12-65169598-T-TGGC			Uncertain significance (Jun 25, 2023)
12-65169602-G-A			Likely benign (Jan 30, 2023)
12-65169604-C-T			Uncertain significance (May 10, 2022)
12-65169605-G-A			Likely benign (Nov 30, 2022)
12-65169607-C-G			Uncertain significance (Aug 17, 2023)
12-65169609-G-A		Inborn genetic diseases	Uncertain significance (Feb 28, 2024)
12-65169609-G-C			Uncertain significance (Feb 09, 2022)
12-65169611-A-C			Likely benign (Oct 18, 2023)
12-65169611-A-G			Likely benign (Oct 24, 2022)
12-65169612-G-A			Uncertain significance (Sep 08, 2023)
12-65169613-C-T			Uncertain significance (Mar 08, 2023)
12-65169616-C-T			Uncertain significance (Apr 06, 2021)
12-65169618-G-A			Uncertain significance (Aug 24, 2023)
12-65169622-C-T			Uncertain significance (Aug 10, 2023)
12-65169624-C-T		Dermatofibrosis lenticularis disseminata	Uncertain significance (Nov 30, 2018)
12-65169625-A-C			Uncertain significance (Mar 03, 2023)
12-65169625-A-T		Dermatofibrosis lenticularis disseminata	Uncertain significance (Jan 12, 2018)
12-65169635-G-A		Dermatofibrosis lenticularis disseminata	Likely benign (Dec 09, 2023)
12-65169641-G-A			Likely benign (Jun 20, 2023)
12-65169645-C-T		Inborn genetic diseases	Uncertain significance (Jun 23, 2023)
12-65169650-C-G			Uncertain significance (Nov 01, 2022)
12-65169652-C-T			Uncertain significance (Jul 16, 2023)
12-65169660-CG-GC			Uncertain significance (Jun 04, 2023)

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
0.999	0.00123	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

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

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

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