LCP1
protein-codinglymphocyte cytosolic protein 1, the group of EF-hand domain containing
Gene summary
Plastins are a family of actin-binding proteins that are conserved throughout eukaryote evolution and expressed in most tissues of higher eukaryotes. In humans, two ubiquitous plastin isoforms (L and T) have been identified. Plastin 1 (otherwise known as Fimbrin) is a third distinct plastin isoform which is specifically expressed at high levels in the small intestine. The L isoform is expressed only in hemopoietic cell lineages, while the T isoform has been found in all other normal cells of solid tissues that have replicative potential (fibroblasts, endothelial cells, epithelial cells, melanocytes, etc.). However, L-plastin has been found in many types of malignant human cells of non-hemopoietic origin suggesting that its expression is induced accompanying tumorigenesis in solid tissues. [provided by RefSeq, Jul 2008]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~86.0 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AD
Disease ID:MONDO:0000159
Submitter: PanelApp Australia
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to LCP1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_002298.5. 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 | 2 | 2 | ||||
| missense | 61 | 1 | 2 | 64 | ||
| nonsense | 1 | 1 | ||||
| start loss | 1 | 1 | ||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 3 | 3 | ||||
| Total | 1 | 0 | 67 | 1 | 2 | 71 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_002289.2 | 15 | MANE Select | |
| Ensembl | ENSP00000315757.2 | 15 | MANE Select | |
| Ensembl | ENSP00000381581.1 | 15 | Standard | |
| Ensembl | ENSP00000408052.1 | 6 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| lcp1 | Danio rerio | Structure: whole organism Quality: viability abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Gene and protein expression by JAK-STAT signaling after Interleukin-12 stimulation
Biological Process
- T cell activation involved in immune response
- protein kinase A signaling
- cell migration
- extracellular matrix disassembly
- animal organ regeneration
Molecular Function
- actin binding
- integrin binding
- calcium ion binding
- identical protein binding
- actin filament binding
Cellular Component
- stress fiber
- ruffle
- phagocytic cup
- podosome
- extracellular space
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000398576
- Coding exons
- 15
- Length
- 85952
- Individuals with no LoFs
- 125735
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 13
- Defined
- 125748
- p
- 0.0000517
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.72 | 247 | 335 | 0.736 | 0.0000166 | 4158 |
| Missense (PolyPhen) | 46 | 101.85 | 0.45165 | 1327 | ||
| Synonymous | 1.16 | 112 | 129 | 0.870 | 0.00000680 | 1181 |
| Loss of Function | 4.19 | 7 | 33.0 | 0.212 | 0.00000170 | 398 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00018 | 0.00018 | rare |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0.000099 | 0.000099 | rare |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000062 | 0.000062 | rare |
| South Asian | 0.000033 | 0.000033 | rare |
| Other | 0.00016 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Actin-binding protein (PubMed:16636079, PubMed:17294403, PubMed:28493397). Plays a role in the activation of T-cells in response to costimulation through TCR/CD3 and CD2 or CD28 (PubMed:17294403). Modulates the cell surface expression of IL2RA/CD25 and CD69 (PubMed:17294403). {ECO:0000269|PubMed:16636079, ECO:0000269|PubMed:17294403, ECO:0000269|PubMed:28493397}.;
- Disease
- DISEASE: Note=Chromosomal aberrations involving LCP1 is a cause of B-cell non-Hodgkin lymphomas (B-cell NHL). Translocation t(3;13)(q27;q14), with BCL6. {ECO:0000269|PubMed:10469447}.; DISEASE: Note=Defects in LCP1 has been found in a patient with isolated coloboma, a defect of the eye characterized by the absence of ocular structures due to abnormal morphogenesis of the optic cup and stalk, and the fusion of the fetal fissure (optic fissure). Isolated colobomas may be associated with an abnormally small eye (microphthalmia) or small cornea. {ECO:0000269|PubMed:28493397}.;
Recessive Scores
- pRec
- 0.288
Intolerance Scores
- LoFtool
- 0.0867
- RVIS EVS
- 0.11
- RVIS percentile EVS
- 61.91
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.907
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |