PIK3C2B

protein-coding

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

Gene summary

The protein encoded by this gene belongs to the phosphoinositide 3-kinase (PI3K) family. PI3-kinases play roles in signaling pathways involved in cell proliferation, oncogenic transformation, cell survival, cell migration, and intracellular protein trafficking. This protein contains a lipid kinase catalytic domain as well as a C-terminal C2 domain, a characteristic of class II PI3-kinases. C2 domains act as calcium-dependent phospholipid binding motifs that mediate translocation of proteins to membranes, and may also mediate protein-protein interactions. The PI3-kinase activity of this protein is sensitive to low nanomolar levels of the inhibitor wortmanin. The C2 domain of this protein was shown to bind phospholipids but not Ca2+, which suggests that this enzyme may function in a calcium-independent manner. [provided by RefSeq, Jul 2008]

MANE transcript

NM_001377334.1

Inheritance

ClinVar variants

U:214B:55

Top phenotype

PIK3C2B-related disorder

gnomAD constraint

pLI —, LoF o/e 0.18

Max pathogenic AF

—

Genomic locus

chr1:204,422,628-204,494,805

External References & Databases

Ensembl (ENSG00000133056)

Transcript & Mutation Effects

hg38 • Region Span ~72.2 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

familial partial epilepsyMODERATE

Inheritance Pattern: AD

Disease ID:MONDO:0017704

Submitter: PanelApp Australia

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to PIK3C2B variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 190

PIK3C2B-related disorderTotal: 63

not providedTotal: 22

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001377334.1. 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			4 clinvar	21 clinvar	10 clinvar	35
missense			197 clinvar	21 clinvar	3 clinvar	221
nonsense			1 clinvar			1
start loss						0
frameshift			3 clinvar			3
splice donor/acceptor (+/-2bp)			9 clinvar			9
Total	0	0	214	42	13	269

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 14 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001377334.1	RefSeq	NP_001364263.1	32	MANE Select
ENST00000684373.1	Ensembl	ENSP00000507222.1	32	MANE Select
NM_001377335.1	RefSeq	NP_001364264.1	33	Standard
NM_002646.4	RefSeq	NP_002637.3	32	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Inositol phosphate metabolism - Homo sapiens (human)
Phosphatidylinositol signaling system - Homo sapiens (human)
Proton Pump Inhibitor Pathway, Pharmacodynamics
Sorafenib Pharmacodynamics
VEGF Signaling Pathway

Biological Process

biological_process
cellular response to starvation
phosphatidylinositol 3-kinase signaling
cell migration
phosphatidylinositol-3-phosphate biosynthetic process

Molecular Function

lipid kinase activity
protein binding
ATP binding
1-phosphatidylinositol-3-kinase activity
1-phosphatidylinositol-4-phosphate 3-kinase activity

Cellular Component

nucleoplasm
cytoplasm
endoplasmic reticulum
cytosol
plasma membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000367187
Coding exons: 32
Length: 72097
Individuals with no LoFs: 125712
Homozygous LoFs: 0
Heterozygous LoFs: 36
Defined: 125748
p: 0.000143

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.55	749	972	0.770	0.0000601	10645
Missense (PolyPhen)		287	425.99	0.67373		4619
Synonymous	1.67	350	392	0.893	0.0000228	3290
Loss of Function	6.91	15	82.8	0.181	0.00000464	906

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00018	0.00018	rare
Latino/Admixed American	0.000058	0.000058	rare
Ashkenazi Jewish	0.00010	0.000099	rare
East Asian	0.00011	0.00011	rare
Finnish	0.000092	0.000092	rare
European (Non-Finnish)	0.00017	0.00017	rare
South Asian	0.00014	0.00013	rare
Other	0.00049	0.00049	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Phosphorylates PtdIns and PtdIns4P with a preference for PtdIns. Does not phosphorylate PtdIns(4,5)P2. May be involved in EGF and PDGF signaling cascades. {ECO:0000269|PubMed:10805725}.;

Recessive Scores

pRec: 0.245

Intolerance Scores

LoFtool: 0.455
RVIS EVS: 0.45
RVIS percentile EVS: 77.93

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.988

Gene Damage Prediction

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