PIK3C2G

protein-coding

phosphatidylinositol-4-phosphate 3-kinase catalytic subunit type 2 gamma, 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. This gene may play a role in several diseases, including type II diabetes. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2014]

MANE transcript

NM_001288772.2

Inheritance

—

ClinVar variants

P:2U:178B:12

Top phenotype

Premature coronary artery atherosclerosis

gnomAD constraint

pLI —, LoF o/e 0.92

Max pathogenic AF

—

Genomic locus

chr12:18,242,961-18,648,416

External References & Databases

Ensembl (ENSG00000139144)

Transcript & Mutation Effects

hg38 • Region Span ~405.5 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to PIK3C2G variants in ClinVar

5 Conditions Cataloged

not specifiedTotal: 173

not providedTotal: 13

Premature coronary artery atherosclerosisTotal: 1

Esophageal atresia/tracheoesophageal fistulaTotal: 1

Familial hypercholesterolemiaTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001288772.2. 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	2 clinvar		6
missense			169 clinvar	9 clinvar		178
nonsense			1 clinvar			1
start loss						0
frameshift		1 clinvar				1
splice donor/acceptor (+/-2bp)		1 clinvar	4 clinvar	1 clinvar		6
Total	0	2	178	12	0	192

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 38 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001288772.2	RefSeq	NP_001275701.1	32	MANE Select
ENST00000538779.6	Ensembl	ENSP00000445381.1	32	MANE Select
NM_001288774.2	RefSeq	NP_001275703.1	32	Standard
NM_004570.6	RefSeq	NP_004561.3	31	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)
Signaling Pathways in Glioblastoma
Angiopoietin Like Protein 8 Regulatory Pathway
Insulin Signaling

Biological Process

chemotaxis
phosphatidylinositol 3-kinase signaling
cell migration
phosphatidylinositol-3-phosphate biosynthetic process
viral RNA genome replication

Molecular Function

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

Cellular Component

cytoplasm
cytosol
plasma membrane
phosphatidylinositol 3-kinase complex
membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000433979
Coding exons: 31
Length: 400801
Individuals with no LoFs: 123648
Homozygous LoFs: 2
Heterozygous LoFs: 1005
Defined: 124655
p: 0.00405

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.973	757	685	1.10	0.0000331	9542
Missense (PolyPhen)		241	209.35	1.1512		3058
Synonymous	-0.177	248	244	1.01	0.0000125	2566
Loss of Function	0.605	63	68.4	0.921	0.00000315	937

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0042	0.0039	notable
Latino/Admixed American	0.0026	0.0023	notable
Ashkenazi Jewish	0.00011	0.000099	rare
East Asian	0.0092	0.0092	notable
Finnish	0.0032	0.0029	notable
European (Non-Finnish)	0.0052	0.0045	notable
South Asian	0.0040	0.0035	notable
Other	0.0042	0.0038	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Generates phosphatidylinositol 3-phosphate (PtdIns3P) and phosphatidylinositol 3,4-bisphosphate (PtdIns(3,4)P2) that act as second messengers. May play a role in SDF1A-stimulated chemotaxis (By similarity). {ECO:0000250}.;

Recessive Scores

pRec: 0.199

Intolerance Scores

LoFtool: 0.704
RVIS EVS: 0.64
RVIS percentile EVS: 83.79

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Indispensability pred.: E
Indispensability score: 0.653

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	High	High	High
Primary Immunodeficiency	High	High	High
Cancer	High	High	High