PICALM
protein-codingphosphatidylinositol binding clathrin assembly protein
Gene summary
This gene encodes a clathrin assembly protein, which recruits clathrin and adaptor protein complex 2 (AP2) to cell membranes at sites of coated-pit formation and clathrin-vesicle assembly. The protein may be required to determine the amount of membrane to be recycled, possibly by regulating the size of the clathrin cage. The protein is involved in AP2-dependent clathrin-mediated endocytosis at the neuromuscular junction. A chromosomal translocation t(10;11)(p13;q14) leading to the fusion of this gene and the MLLT10 gene is found in acute lymphoblastic leukemia, acute myeloid leukemia and malignant lymphomas. The polymorphisms of this gene are associated with the risk of Alzheimer disease. Multiple alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2011]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~112.7 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 PICALM variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_007166.4. 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 | 4 | 6 | |||
| missense | 68 | 2 | 70 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 7 | 7 | ||||
| Total | 0 | 0 | 75 | 4 | 4 | 83 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_009097.2 | 20 | MANE Select | |
| Ensembl | ENSP00000377015.3 | 20 | MANE Select | |
| RefSeq | NP_001008660.1 | 20 | Standard | |
| RefSeq | NP_001193875.1 | 20 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- miR-targeted genes in adipocytes - TarBase
- miR-targeted genes in epithelium - TarBase
- miR-targeted genes in lymphocytes - TarBase
- miR-targeted genes in muscle cell - TarBase
- miR-targeted genes in squamous cell - TarBase
Biological Process
- endocytosis
- receptor-mediated endocytosis
- vesicle budding from membrane
- axonogenesis
- learning or memory
Molecular Function
- SNARE binding
- amyloid-beta binding
- protein binding
- 1-phosphatidylinositol binding
- phosphatidylinositol-4,5-bisphosphate binding
Cellular Component
- nucleus
- early endosome
- Golgi apparatus
- cytosol
- plasma membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000393346
- Coding exons
- 20
- Length
- 112198
- Individuals with no LoFs
- 125728
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 19
- Defined
- 125747
- p
- 0.0000756
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.45 | 258 | 333 | 0.776 | 0.0000152 | 4268 |
| Missense (PolyPhen) | 51 | 81.072 | 0.62907 | 1058 | ||
| Synonymous | -0.668 | 122 | 113 | 1.08 | 0.00000515 | 1256 |
| Loss of Function | 4.85 | 3 | 33.1 | 0.0905 | 0.00000140 | 444 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000062 | 0.000062 | rare |
| Latino/Admixed American | 0.000089 | 0.000058 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0.00014 | 0.00014 | rare |
| European (Non-Finnish) | 0.00012 | 0.00011 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Assembly protein recruiting clathrin and adapter protein complex 2 (AP2) to cell membranes at sites of coated-pit formation and clathrin-vesicle assembly. May be required to determine the amount of membrane to be recycled, possibly by regulating the size of the clathrin cage. Involved in AP2-dependent clathrin-mediated endocytosis at the neuromuscular junction. {ECO:0000269|PubMed:10436022}.;
Recessive Scores
- pRec
- 0.130
Intolerance Scores
- LoFtool
- 0.618
- RVIS EVS
- -0.49
- RVIS percentile EVS
- 22.51
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.883
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |