PICALM

phosphatidylinositol binding clathrin assembly protein

Basic information

Region (hg38): 11:85957174-86069882

Links

ENSG00000073921 ∙ NCBI:8301 ∙ OMIM:603025 ∙ HGNC:15514 ∙ Uniprot:Q13492 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PICALM gene.

• not provided (40 variants)
• Inborn genetic diseases (13 variants)
• not specified (3 variants)
• Marfanoid habitus and intellectual disability (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PICALM gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				1	6	7
missense			12	1		13
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)			1			1
splice region				1	2	3
non coding					30	30
Total	0	0	13	2	36

Variants in PICALM

This is a list of pathogenic ClinVar variants found in the PICALM region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
11-85959342-CAA-C			Benign (Nov 12, 2018)
11-85974531-C-T			Benign (Nov 12, 2018)
11-85975053-T-G			Benign (Nov 12, 2018)
11-85975108-A-T			Benign (Jun 19, 2021)
11-85978392-T-C			Benign (Nov 12, 2018)
11-85981018-A-G			Benign (Nov 12, 2018)
11-85981131-T-C		PICALM-related disorder	Likely benign (Feb 22, 2019)
11-85981138-A-C		not specified • PICALM-related disorder	Benign (Oct 17, 2019)
11-85981138-A-T			Benign (Dec 31, 2019)
11-85981150-G-A			Benign (Dec 31, 2019)
11-85981157-G-T		not specified	Uncertain significance (Aug 30, 2022)
11-85981299-A-C			Benign (Nov 12, 2018)
11-85981910-G-T		not specified	Uncertain significance (Jan 29, 2024)
11-85981922-C-T		not specified	Likely benign (Mar 21, 2023)
11-85982310-C-T			Benign (Nov 12, 2018)
11-85983565-A-G			Benign (Nov 12, 2018)
11-85983935-C-A		not specified	Uncertain significance (Jun 09, 2022)
11-85983980-A-G			Likely benign (Jun 06, 2018)
11-85990283-T-C		not specified	Uncertain significance (May 24, 2023)
11-85990327-C-G		not specified	Uncertain significance (Feb 23, 2023)
11-85990355-T-C		not specified	Uncertain significance (Jan 08, 2024)
11-85990358-G-C		not specified	Uncertain significance (Feb 06, 2024)
11-85990394-A-C		not specified	Uncertain significance (Jun 29, 2023)
11-85990579-T-C			Benign (Nov 12, 2018)
11-85990698-T-C			Benign (Nov 12, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PICALM	protein_coding	protein_coding	ENST00000393346	20	112198

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.999	0.00104	125728	0	19	125747	0.0000756

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.45	258	333	0.776	0.0000152	4268
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000151	0.000150
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.000139	0.000139
European (Non-Finnish)	0.000115	0.000114
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• 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}.
• Pathway: 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;Golgi Associated Vesicle Biogenesis;Clathrin derived vesicle budding;trans-Golgi Network Vesicle Budding;Vesicle-mediated transport;endocytotic role of ndk phosphins and dynamin;Membrane Trafficking;Clathrin-mediated endocytosis;Cargo recognition for clathrin-mediated endocytosis (Consensus)

Recessive Scores

• pRec: 0.130

Intolerance Scores

• loftool: 0.618
• rvis_EVS: -0.49
• rvis_percentile_EVS: 22.51

Haploinsufficiency Scores

• pHI: 0.978
• hipred: Y
• hipred_score: 0.595
• ghis: 0.624

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.883

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Picalm
• Phenotype: immune system phenotype; pigmentation phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); hematopoietic system phenotype; liver/biliary system phenotype; embryo phenotype; cellular phenotype; homeostasis/metabolism phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); growth/size/body region phenotype

Gene ontology

• Biological process: endocytosis;receptor-mediated endocytosis;vesicle budding from membrane;axonogenesis;learning or memory;cell population proliferation;negative regulation of gene expression;synaptic vesicle budding from presynaptic endocytic zone membrane;synaptic vesicle maturation;vesicle-mediated transport;endosomal transport;hemopoiesis;regulation of endocytosis;receptor internalization;regulation of protein localization;vesicle cargo loading;positive regulation of GTPase activity;transcytosis;positive regulation of transcription, DNA-templated;negative regulation of receptor-mediated endocytosis;clathrin coat assembly;synaptic vesicle endocytosis;dendrite morphogenesis;iron ion homeostasis;membrane organization;protein-containing complex assembly;clathrin-dependent endocytosis;modulation of age-related behavioral decline;regulation of vesicle size;membrane bending;iron ion import across plasma membrane;amyloid-beta clearance by transcytosis;positive regulation of neuron death;regulation of amyloid-beta formation;positive regulation of amyloid-beta formation;regulation of aspartic-type endopeptidase activity involved in amyloid precursor protein catabolic process;positive regulation of aspartic-type endopeptidase activity involved in amyloid precursor protein catabolic process;negative regulation of metalloendopeptidase activity involved in amyloid precursor protein catabolic process;negative regulation of protein localization to plasma membrane;negative regulation of protein localization to cell surface;positive regulation of clathrin-dependent endocytosis
• Cellular component: nucleus;early endosome;Golgi apparatus;cytosol;plasma membrane;clathrin-coated pit;synaptic vesicle;cell surface;membrane;AP-2 adaptor complex;clathrin coat of coated pit;clathrin-coated vesicle;intrinsic component of membrane;vesicle;presynaptic membrane;neuronal cell body;intracellular membrane-bounded organelle;postsynaptic membrane;clathrin-coated endocytic vesicle;perinuclear region of cytoplasm;endosome to plasma membrane transport vesicle;neurofibrillary tangle;extrinsic component of presynaptic endocytic zone membrane
• Molecular function: SNARE binding;amyloid-beta binding;protein binding;1-phosphatidylinositol binding;phosphatidylinositol-4,5-bisphosphate binding;Rab GTPase binding;clathrin binding;clathrin heavy chain binding;cadherin binding;tau protein binding;low-density lipoprotein particle receptor binding