LPP
protein-codingLIM domain containing preferred translocation partner in lipoma, the group of MicroRNA protein coding host genes|Zyxin family
Gene summary
This gene encodes a member of a subfamily of LIM domain proteins that are characterized by an N-terminal proline-rich region and three C-terminal LIM domains. The encoded protein localizes to the cell periphery in focal adhesions and may be involved in cell-cell adhesion and cell motility. This protein also shuttles through the nucleus and may function as a transcriptional co-activator. This gene is located at the junction of certain disease-related chromosomal translocations, which result in the expression of chimeric proteins that may promote tumor growth. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2014]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~737.4 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to LPP variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001375462.1. 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 | 4 | 7 | 4 | 15 | ||
| missense | 108 | 8 | 4 | 120 | ||
| nonsense | 1 | 1 | 2 | |||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 4 | 4 | ||||
| Total | 0 | 1 | 117 | 15 | 8 | 141 |
Highest pathogenic variant AF is 0.00006381819
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001362391.1 | 9 | MANE Select | |
| Ensembl | ENSP00000478901.1 | 9 | MANE Select | |
| RefSeq | NP_001161143.1 | 9 | Standard | |
| RefSeq | NP_001161144.1 | 9 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| lpp | Danio rerio | Structure: whole organism Quality: decreased length abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- EGFR1
- Stabilization and expansion of the E-cadherin adherens junction
Biological Process
- cell adhesion
- biological_process
Molecular Function
- protein binding
- metal ion binding
Cellular Component
- nucleus
- cytosol
- plasma membrane
- focal adhesion
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000312675
- Coding exons
- 9
- Length
- 737389
- Individuals with no LoFs
- 125715
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 33
- Defined
- 125748
- p
- 0.000131
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -1.50 | 441 | 361 | 1.22 | 0.0000197 | 3923 |
| Missense (PolyPhen) | 165 | 167.66 | 0.98412 | 1777 | ||
| Synonymous | -1.97 | 165 | 136 | 1.21 | 0.00000761 | 1277 |
| Loss of Function | 3.33 | 9 | 28.1 | 0.321 | 0.00000159 | 318 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000062 | 0.000062 | rare |
| Latino/Admixed American | 0.00020 | 0.00020 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.000054 | 0.000054 | rare |
| Finnish | 0.000047 | 0.000046 | rare |
| European (Non-Finnish) | 0.00017 | 0.00017 | rare |
| South Asian | 0.00013 | 0.00013 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: May play a structural role at sites of cell adhesion in maintaining cell shape and motility. In addition to these structural functions, it may also be implicated in signaling events and activation of gene transcription. May be involved in signal transduction from cell adhesion sites to the nucleus allowing successful integration of signals arising from soluble factors and cell-cell adhesion sites. Also suggested to serve as a scaffold protein upon which distinct protein complexes are assembled in the cytoplasm and in the nucleus. {ECO:0000269|PubMed:10637295, ECO:0000269|Ref.2}.;
- Disease
- DISEASE: Note=A chromosomal aberration involving LPP is associated with pulmonary chondroid hamartomas. Translocation t(3;12)(q27- q28;q14-q15) with HMGA2 is detected in pulmonary chondroid hamartomas.; DISEASE: Note=A chromosomal aberration involving LPP is associated with parosteal lipomas. Translocation t(3;12)(q28;q14) with HMGA2 is also shown in one parosteal lipoma.; DISEASE: Note=A chromosomal aberration involving LPP is associated with acute monoblastic leukemia. Translocation t(3;11)(q28;q23) with KMT2A/MLL1 is associated with acute monoblastic leukemia.;
Recessive Scores
- pRec
- 0.159
Intolerance Scores
- LoFtool
- 0.294
- RVIS EVS
- 1.05
- RVIS percentile EVS
- 91.37
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.848
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |