LEMD3
protein-codingLEM domain containing 3, the group of LEM domain containing
Gene summary
This locus encodes a LEM domain-containing protein. The encoded protein functions to antagonize transforming growth factor-beta signaling at the inner nuclear membrane. Two transcript variants encoding different isoforms have been found for this gene. Mutations in this gene have been associated with osteopoikilosis, Buschke-Ollendorff syndrome and melorheostosis.[provided by RefSeq, Nov 2009]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~78.8 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AD
Disease ID:MONDO:0015995
Submitter: Orphanet
Inheritance Pattern: AD
Disease ID:MONDO:0015634
Submitter: Orphanet
Inheritance Pattern: AD
Disease ID:MONDO:0008157
Submitter: PanelApp Australia
Inheritance Pattern: AD
Disease ID:MONDO:0008157
Submitter: G2P
Inheritance Pattern: AD
Disease ID:MONDO:0008157
Submitter: Genomics England PanelApp
Inheritance Pattern: AD
Disease ID:MONDO:0008157
Submitter: Labcorp Genetics (formerly Invitae)
Clinical Genomic Database (CGD)
Manifestation: Dermatologic; Musculoskeletal
Intervention: General
Rationale: 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
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to LEMD3 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_014319.5. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 6 | 214 | 5 | 225 | ||
| missense | 1 | 2 | 478 | 31 | 1 | 513 |
| nonsense | 18 | 5 | 2 | 25 | ||
| start loss | 1 | 1 | ||||
| frameshift | 29 | 15 | 44 | |||
| splice donor/acceptor (+/-2bp) | 4 | 9 | 7 | 20 | ||
| Total | 52 | 31 | 494 | 245 | 6 | 828 |
Highest pathogenic variant AF is 0.0000027402102
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_055134.2 | 13 | MANE Select | |
| Ensembl | ENSP00000308369.2 | 13 | MANE Select | |
| RefSeq | NP_001161086.1 | 13 | Standard | |
| Ensembl | ENSP00000553271.1 | 13 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Clearance of Nuclear Envelope Membranes from Chromatin
- Nuclear Envelope Breakdown
- Mitotic Prophase
- Initiation of Nuclear Envelope Reformation
- Nuclear Envelope Reassembly
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
Molecular Function
- DNA binding
- protein binding
Cellular Component
- nuclear inner membrane
- integral component of nuclear inner membrane
- membrane
- integral component of membrane
- nuclear membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000308330
- Coding exons
- 13
- Length
- 78757
- Individuals with no LoFs
- 125737
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 11
- Defined
- 125748
- p
- 0.0000437
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.260 | 485 | 469 | 1.03 | 0.0000240 | 5845 |
| Missense (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 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00018 | 0.00018 | rare |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.000054 | 0.000054 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000053 | 0.000053 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0.00016 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- 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}.;
Recessive Scores
- pRec
- 0.161
Intolerance Scores
- LoFtool
- 0.440
- RVIS EVS
- -1.15
- RVIS percentile EVS
- 6.23
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.831
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |