PIK3C2A

phosphatidylinositol-4-phosphate 3-kinase catalytic subunit type 2 alpha, the group of Phosphatidylinositol 3-kinase subunits

Basic information

Region (hg38): 11:17077730-17207986

Links

ENSG00000011405 ∙ NCBI:5286 ∙ OMIM:603601 ∙ HGNC:8971 ∙ Uniprot:O00443 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• oculocerebrodental syndrome (Strong), mode of inheritance: AR
• oculocerebrodental syndrome (Supportive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Oculoskeletodental syndrome	AR	Audiologic/Otolaryngologic; Ophthalmologic	Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development; The condition can include secondary glaucoma, and awareness may allow prompt diagnosis and management	Audiologic/Otolaryngologic; Craniofacial; Endocrine; Musculoskeletal; Neurologic; Ophthalmologic	31034465

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PIK3C2A gene.

• not_provided (419 variants)
• not_specified (198 variants)
• PIK3C2A-related_disorder (17 variants)
• Oculocerebrodental_syndrome (10 variants)
• Short_stature (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PIK3C2A gene is commonly pathogenic or not. These statistics are base on transcript: NM_000002645.4. Only rare variants are included in the table.

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.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			6	122	12	140
missense	1		277	20	6	304
nonsense	10	2	2			14
start loss						0
frameshift	8	2				10
splice donor/acceptor (+/-2bp)	1	4	8			13
Total	20	8	293	142	18

Highest pathogenic variant AF is 0.000009774701

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PIK3C2A	protein_coding	protein_coding	ENST00000265970	32	130254

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
		125696	0	50	125746	0.000199

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.30	749	856	0.875	0.0000422	11066
Missense in Polyphen		233	351.06	0.66371		4629
Synonymous	1.31	267	296	0.903	0.0000145	3174
Loss of Function	6.59	23	90.7	0.254	0.00000512	1094

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000212	0.000212
Ashkenazi Jewish	0.0000992	0.0000992
East Asian	0.0000544	0.0000544
Finnish	0.0000927	0.0000924
European (Non-Finnish)	0.000327	0.000325
Middle Eastern	0.0000544	0.0000544
South Asian	0.000133	0.000131
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Generates phosphatidylinositol 3-phosphate (PtdIns3P) and phosphatidylinositol 3,4-bisphosphate (PtdIns(3,4)P2) that act as second messengers. Has a role in several intracellular trafficking events. Functions in insulin signaling and secretion. Required for translocation of the glucose transporter SLC2A4/GLUT4 to the plasma membrane and glucose uptake in response to insulin- mediated RHOQ activation. Regulates insulin secretion through two different mechanisms: involved in glucose-induced insulin secretion downstream of insulin receptor in a pathway that involves AKT1 activation and TBC1D4/AS160 phosphorylation, and participates in the late step of insulin granule exocytosis probably in insulin granule fusion. Synthesizes PtdIns3P in response to insulin signaling. Functions in clathrin-coated endocytic vesicle formation and distribution. Regulates dynamin- independent endocytosis, probably by recruiting EEA1 to internalizing vesicles. In neurosecretory cells synthesizes PtdIns3P on large dense core vesicles. Participates in calcium induced contraction of vascular smooth muscle by regulating myosin light chain (MLC) phosphorylation through a mechanism involving Rho kinase-dependent phosphorylation of the MLCP-regulatory subunit MYPT1. May play a role in the EGF signaling cascade. May be involved in mitosis and UV-induced damage response. Required for maintenance of normal renal structure and function by supporting normal podocyte function. {ECO:0000269|PubMed:10766823, ECO:0000269|PubMed:10805725, ECO:0000269|PubMed:11239472, ECO:0000269|PubMed:12719431, ECO:0000269|PubMed:16215232, ECO:0000269|PubMed:21081650, ECO:0000269|PubMed:9337861}.
• Pathway: Inositol phosphate metabolism - Homo sapiens (human);Phosphatidylinositol signaling system - Homo sapiens (human);Proton Pump Inhibitor Pathway, Pharmacodynamics;Anti-diabetic Drug Potassium Channel Inhibitors Pathway, Pharmacodynamics;Sorafenib Pharmacodynamics;VEGF Signaling Pathway;Phosphatidylinositol Phosphate Metabolism;Joubert syndrome;Signaling Pathways in Glioblastoma;Integrated Lung Cancer Pathway;Angiopoietin Like Protein 8 Regulatory Pathway;Focal Adhesion-PI3K-Akt-mTOR-signaling pathway;Microglia Pathogen Phagocytosis Pathway;Insulin Signaling;Regulation of Actin Cytoskeleton;DNA Damage Response (only ATM dependent);Golgi Associated Vesicle Biogenesis;Clathrin derived vesicle budding;trans-Golgi Network Vesicle Budding;Vesicle-mediated transport;Membrane Trafficking;Metabolism of lipids;Inositol phosphate metabolism;Metabolism;3-phosphoinositide biosynthesis;superpathway of inositol phosphate compounds;Phosphatidylinositol phosphate metabolism;Clathrin-mediated endocytosis;Synthesis of PIPs at the Golgi membrane;Synthesis of PIPs at the early endosome membrane;Synthesis of PIPs at the plasma membrane;Synthesis of PIPs at the late endosome membrane;PI Metabolism;Phospholipid metabolism;Integrins in angiogenesis (Consensus)

Recessive Scores

• pRec: 0.636

Intolerance Scores

• loftool: 0.657
• rvis_EVS: -1.48
• rvis_percentile_EVS: 3.72

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.988

Gene Damage Prediction

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

Zebrafish Information Network

• Gene name: pik3c2a
• Affected structure: intersegmental vessel
• Phenotype tag: abnormal
• Phenotype quality: process quality

Gene ontology

• Biological process: phosphatidylinositol biosynthetic process;exocytosis;endocytosis;epidermal growth factor receptor signaling pathway;insulin receptor signaling pathway;phosphatidylinositol 3-kinase signaling;vascular smooth muscle contraction;cell migration;phosphatidylinositol-3-phosphate biosynthetic process;phosphatidylinositol phosphorylation;platelet-derived growth factor receptor signaling pathway;phosphatidylinositol-mediated signaling;clathrin coat assembly;membrane organization;positive regulation of cell migration involved in sprouting angiogenesis
• Cellular component: nucleus;cytoplasm;Golgi apparatus;cytosol;plasma membrane;phosphatidylinositol 3-kinase complex;membrane;clathrin-coated vesicle;vesicle;extracellular exosome
• Molecular function: ATP binding;1-phosphatidylinositol-3-kinase activity;phosphatidylinositol 3-kinase activity;1-phosphatidylinositol-4-phosphate 3-kinase activity;phosphatidylinositol binding