PIK3C3

phosphatidylinositol 3-kinase catalytic subunit type 3, the group of Phosphatidylinositol 3-kinase subunits|PIK3C3 complex subunits

Basic information

Region (hg38): 18:41955234-42087830

Links

ENSG00000078142 ∙ NCBI:5289 ∙ OMIM:602609 ∙ HGNC:8974 ∙ Uniprot:Q8NEB9 ∙ 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 PIK3C3 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PIK3C3 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					2	2
missense			28	1		29
nonsense						0
start loss						0
frameshift			1			1
inframe indel						0
splice donor/acceptor (+/-2bp)			1			1
splice region			1			1
non coding					1	1
Total	0	0	30	1	3

Variants in PIK3C3

This is a list of pathogenic ClinVar variants found in the PIK3C3 region.

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

Position	Type	Phenotype	Significance	ClinVar
18-41955310-T-G		not specified	Uncertain significance (Apr 19, 2024)
18-41955311-T-C		not specified	Uncertain significance (Dec 27, 2023)
18-41955344-A-G		not specified	Uncertain significance (Mar 01, 2023)
18-41957628-A-G		not specified	Uncertain significance (Apr 04, 2024)
18-41957692-T-C		not specified	Uncertain significance (Dec 27, 2023)
18-41957718-C-G		not specified	Uncertain significance (Nov 10, 2022)
18-41957721-G-C		not specified	Uncertain significance (Mar 29, 2022)
18-41962535-A-G		not specified	Uncertain significance (Jun 23, 2023)
18-41962572-A-G		not specified	Uncertain significance (Apr 18, 2023)
18-41962580-G-A		not specified	Uncertain significance (Jun 05, 2024)
18-41962608-C-T		not specified	Uncertain significance (Nov 13, 2024)
18-41962614-C-T		not specified	Uncertain significance (Mar 15, 2024)
18-41962631-G-C		not specified	Uncertain significance (Sep 30, 2024)
18-41970334-C-T		not specified	Uncertain significance (Jul 19, 2022)
18-41970335-G-A			Uncertain significance (Jun 01, 2022)
18-41970401-C-T		not specified	Uncertain significance (Nov 12, 2024)
18-41970446-G-A		not specified	Uncertain significance (Aug 10, 2021)
18-41995940-T-G		not specified	Uncertain significance (Apr 16, 2024)
18-41996723-A-C		not specified	Uncertain significance (Aug 28, 2023)
18-42004392-C-G		not specified	Uncertain significance (Dec 15, 2023)
18-42004523-G-A			Benign (Nov 15, 2018)
18-42004523-G-T		not specified	Uncertain significance (Mar 02, 2023)
18-42004535-T-G		not specified	Uncertain significance (Nov 03, 2022)
18-42004544-G-A			Uncertain significance (Sep 25, 2019)
18-42004549-ATTAT-A			Benign (Dec 31, 2019)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PIK3C3	protein_coding	protein_coding	ENST00000262039	25	132624

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
8.42e-11	1.00	125684	0	64	125748	0.000255

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.44	325	475	0.685	0.0000248	5846
Missense in Polyphen		95	178.03	0.53361		2162
Synonymous	-0.517	174	166	1.05	0.00000877	1597
Loss of Function	3.55	26	54.2	0.480	0.00000268	692

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000600	0.000584
Ashkenazi Jewish	0.00	0.00
East Asian	0.000389	0.000381
Finnish	0.0000929	0.0000924
European (Non-Finnish)	0.000295	0.000290
Middle Eastern	0.000389	0.000381
South Asian	0.000304	0.000294
Other	0.000511	0.000489

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Catalytic subunit of the PI3K complex that mediates formation of phosphatidylinositol 3-phosphate; different complex forms are believed to play a role in multiple membrane trafficking pathways: PI3KC3-C1 is involved in initiation of autophagosomes and PI3KC3-C2 in maturation of autophagosomes and endocytosis. Involved in regulation of degradative endocytic trafficking and required for the abcission step in cytokinesis, probably in the context of PI3KC3-C2 (PubMed:20643123, PubMed:20208530). Involved in the transport of lysosomal enzyme precursors to lysosomes. Required for transport from early to late endosomes (By similarity). {ECO:0000250|UniProtKB:O88763, ECO:0000269|PubMed:14617358, ECO:0000269|PubMed:20208530, ECO:0000269|PubMed:20643123, ECO:0000269|PubMed:7628435, ECO:0000305}.
• Pathway: Kaposi,s sarcoma-associated herpesvirus infection - Homo sapiens (human);Inositol phosphate metabolism - Homo sapiens (human);Phagosome - Homo sapiens (human);Autophagy - animal - Homo sapiens (human);Autophagy - other - Homo sapiens (human);Apelin signaling pathway - Homo sapiens (human);Tuberculosis - Homo sapiens (human);Phosphatidylinositol signaling system - Homo sapiens (human);Phosphatidylinositol Phosphate Metabolism;Joubert syndrome;Inositol Metabolism;AMP-activated Protein Kinase (AMPK) Signaling;Angiopoietin Like Protein 8 Regulatory Pathway;Microglia Pathogen Phagocytosis Pathway;Insulin Signaling;Regulation of Actin Cytoskeleton;Senescence and Autophagy in Cancer;DNA Damage Response (only ATM dependent);Signal Transduction;Metabolism of lipids;Toll Like Receptor 9 (TLR9) Cascade;Toll-Like Receptors Cascades;PI3K Cascade;IRS-mediated signalling;Insulin receptor signalling cascade;Signaling by Insulin receptor;Inositol phosphate metabolism;Innate Immune System;Immune System;Metabolism;3-phosphoinositide biosynthesis;superpathway of inositol phosphate compounds;Macroautophagy;Cellular responses to external stimuli;RHO GTPases Activate NADPH Oxidases;RHO GTPase Effectors;Phosphatidylinositol phosphate metabolism;Signaling by Rho GTPases;Synthesis of PIPs at the Golgi membrane;Synthesis of PIPs at the early endosome membrane;Synthesis of PIPs at the late endosome membrane;PI Metabolism;Phospholipid metabolism;IRS-related events triggered by IGF1R;IGF1R signaling cascade;Signaling by Receptor Tyrosine Kinases;Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R) (Consensus)

Recessive Scores

• pRec: 0.487

Intolerance Scores

• loftool: 0.481
• rvis_EVS: -1.35
• rvis_percentile_EVS: 4.56

Haploinsufficiency Scores

• pHI: 0.682
• hipred: Y
• hipred_score: 0.611
• ghis: 0.666

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.999

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Pik3c3
• Phenotype: growth/size/body region phenotype; cellular phenotype; homeostasis/metabolism phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); muscle 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); normal phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); hematopoietic system phenotype; liver/biliary system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); embryo phenotype; immune system phenotype; vision/eye phenotype

Gene ontology

• Biological process: autophagosome assembly;protein phosphorylation;protein lipidation;endocytosis;autophagy;endosome organization;cell cycle;macroautophagy;protein processing;autophagy of peroxisome;regulation of cytokinesis;toll-like receptor 9 signaling pathway;protein localization to phagophore assembly site;phosphatidylinositol-3-phosphate biosynthetic process;cellular response to glucose starvation;response to leucine;early endosome to late endosome transport;phosphatidylinositol phosphorylation;phosphatidylinositol-mediated signaling;regulation of protein secretion;cell division
• Cellular component: phagophore assembly site;cytoplasm;endosome;late endosome;peroxisome;cytosol;axoneme;membrane;midbody;phagocytic vesicle membrane;phosphatidylinositol 3-kinase complex, class III, type I;phosphatidylinositol 3-kinase complex, class III, type II;phosphatidylinositol 3-kinase complex, class III;autolysosome
• Molecular function: protein kinase activity;protein binding;ATP binding;kinase activity;1-phosphatidylinositol-3-kinase activity