PICALM
PICALM (Phosphatidylinositol-binding clathrin assembly protein) is a gene whose normal job is to hold cell growth in check. The public catalogues list it as a tumour suppressor and a fusion partner, and it is called a cancer driver by mutation analysis of patient cohorts. Tied to Thyroid cancer and Papillary thyroid cancer.
Overview
Cytoplasmic adapter protein that plays a critical role in clathrin-mediated endocytosis which is important in processes such as internalisation of cell receptors, synaptic transmission or removal of apoptotic cells. Recruits AP-2 and attaches clathrin triskelions to the cytoplasmic side of plasma membrane leading to clathrin-coated vesicles (CCVs) assembly. Furthermore, regulates clathrin-coated vesicle size and maturation by directly sensing and driving membrane curvature.
IntOGen calls it a driver in 1 cohort (0 activating, 1 loss-of-function), covering Well-Differentiated Thyroid Cancer.
- Target · the protein and the cell it sits on
- Drug · antibody, small molecule, cell or radioligand
- Effect · signal, damage or kill
In plain words · PICALM (Phosphatidylinositol-binding clathrin assembly protein) is a gene whose normal job is to hold cell growth in check. The public catalogues list it as a tumour suppressor and a fusion partner, and it is called a cancer driver by mutation analysis of patient cohorts. Tied to Thyroid cancer and Papillary thyroid cancer.
- 1 · What it is
PICALM (Phosphatidylinositol-binding clathrin assembly protein) is a gene whose normal job is to hold cell growth in check. The public catalogues list it as a tumour suppressor and a fusion partner, and it is called a cancer driver by mutation analysis of patient cohorts. Tied to Thyroid cancer and Papillary thyroid cancer.
- 2 · What goes wrong in cancer
Cytoplasmic adapter protein that plays a critical role in clathrin-mediated endocytosis which is important in processes such as internalisation of cell receptors, synaptic transmission or removal of apoptotic cells.
- 3 · How drugs use it
No product in this corpus aims at PICALM yet. Because the protein is lost rather than overactive, drugs either restore its function or exploit the weakness its loss leaves (synthetic lethality).
External identifiers
Sources: HGNC HGNC:15514 (approved symbol, name, aliases, locus and cross-references (hgnc_complete_set.txt)); UniProt Q13492 (protein name, function text, keywords and locations (REST API)); IntOGen PICALM (driver in 1 cohort (Act 0, LoF 1); Compendium_Cancer_Genes.tsv release 20240920, CC0 1.0)
Biology
Cytoplasmic adapter protein that plays a critical role in clathrin-mediated endocytosis which is important in processes such as internalisation of cell receptors, synaptic transmission or removal of apoptotic cells. Recruits AP-2 and attaches clathrin triskelions to the cytoplasmic side of plasma membrane leading to clathrin-coated vesicles (CCVs) assembly. Furthermore, regulates clathrin-coated vesicle size and maturation by directly sensing and driving membrane curvature. In addition to binding to clathrin, mediates the endocytosis of small R-SNARES (Soluble NSF Attachment Protein REceptors) between plasma membranes and endosomes including VAMP2, VAMP3, VAMP4, VAMP7 or VAMP8. In turn, PICALM-dependent SNARE endocytosis is required for the formation and maturation of autophagic precursors. Modulates thereby autophagy and the turnover of autophagy substrates such as MAPT/TAU or amyloid precursor protein cleaved C-terminal fragment (APP-CTF). Location: Cell membrane; Membrane, clathrin-coated pit; Golgi apparatus; Cytoplasmic vesicle, clathrin-coated vesicle (UniProt). Locus 11q14.2 (HGNC).
- Thyroid cancer: IntOGen driver in 1 cohort (WDTC)
- Papillary thyroid cancer: IntOGen driver in 1 cohort (WDTC)
Notes
top- Written by scripts/fetch-cancer-genes.ts from CIViC, Open Targets, IntOGen, HGNC and UniProt; the function text is UniProt's, condensed and in UK spelling. Roles: IntOGen calls it a loss-of-function (LoF) driver in 1 cohort; UniProt disease notes describe a translocation or gene fusion involving the gene. Evidence tier "cohort-driver" is the strongest of those signals.
- Prevalence not recorded: none of the sources gives a positivity rate.
Latest papers
topQuery for this target: (TITLE:"PICALM" OR ABSTRACT:"PICALM" OR TITLE:"phosphatidylinositol binding clathrin assembly protein" OR ABSTRACT:"phosphatidylinositol binding clathrin assembly protein" OR TITLE:"Phosphatidylinositol-binding clathrin assembly protein" OR ABSTRACT:"Phosphatidylinositol-binding clathrin assembly protein") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about PICALM, not a curated reading list.
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