PIK3R6

protein-coding

phosphoinositide-3-kinase regulatory subunit 6

Gene summary

Phosphoinositide 3-kinase gamma is a lipid kinase that produces the lipid second messenger phosphatidylinositol 3,4,5-trisphosphate. The kinase is composed of a catalytic subunit and one of several regulatory subunits, and is chiefly activated by G protein-coupled receptors. This gene encodes a regulatory subunit, and is distantly related to the phosphoinositide-3-kinase, regulatory subunit 5 gene which is located adjacent to this gene on chromosome 7. The orthologous protein in the mouse binds to both the catalytic subunit and to G(beta/gamma), and mediates activation of the kinase subunit downstream of G protein-coupled receptors. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2014]

Previous symbols:

C17orf38

MANE transcript

NM_001010855.4

Inheritance

—

ClinVar variants

U:118B:2

Top phenotype

—

Max pathogenic AF

—

Genomic locus

chr17:8,802,722-8,867,677

External References & Databases

Ensembl (ENSG00000276231)

Transcript & Mutation Effects

hg38 • Region Span ~65.0 kb

Loading mutation effect viewer...

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 PIK3R6 variants in ClinVar

1 Conditions Cataloged

not specifiedTotal: 109

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001010855.4. 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			2 clinvar			2
missense			112 clinvar	2 clinvar		114
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			3 clinvar			3
Total	0	0	118	2	0	120

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 32 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001010855.4	RefSeq	NP_001010855.1	19	MANE Select
ENST00000619866.5	Ensembl	ENSP00000480157.1	19	MANE Select
NM_001290211.1	RefSeq	NP_001277140.1	14	Standard
ENST00000611951.4	Ensembl	ENSP00000480685.1	3	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

PI3K-Akt signaling pathway - Homo sapiens (human)
Platelet activation - Homo sapiens (human)
Oxytocin signaling pathway - Homo sapiens (human)
Kaposi,s sarcoma-associated herpesvirus infection - Homo sapiens (human)
Adrenergic signaling in cardiomyocytes - Homo sapiens (human)

Biological Process

angiogenesis
G protein-coupled receptor signaling pathway
phosphatidylinositol 3-kinase signaling
platelet activation
regulation of natural killer cell mediated cytotoxicity

Molecular Function

protein binding
phosphatidylinositol-4,5-bisphosphate 3-kinase activity
1-phosphatidylinositol-3-kinase regulator activity

Cellular Component

cytosol
plasma membrane
phosphatidylinositol 3-kinase complex
phosphatidylinositol 3-kinase complex, class IB
membrane

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Regulatory subunit of the PI3K gamma complex. Acts as an adapter to drive activation of PIK3CG by beta-gamma G protein dimers. The PIK3CG:PIK3R6 heterodimer is much less sensitive to beta-gamma G protein dimers than PIK3CG:PIK3R5 and its membrane recruitment and beta-gamma G protein dimer-dependent activation requires HRAS bound to PIK3CG. Recruits of the PI3K gamma complex to a PDE3B:RAPGEF3 signaling complex involved in angiogenesis; signaling seems to involve RRAS. {ECO:0000269|PubMed:21393242}.;

Recessive Scores

pRec: 0.0970

Essentials

Indispensability pred.: N
Indispensability score: 0.177

Gene Damage Prediction

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