PIK3R4

phosphoinositide-3-kinase regulatory subunit 4, the group of WD repeat domain containing|PIK3C3 complex subunits|Armadillo like helical domain containing

Basic information

Region (hg38): 3:130678933-130746829

Links

ENSG00000196455 ∙ NCBI:30849 ∙ OMIM:602610 ∙ HGNC:8982 ∙ Uniprot:Q99570 ∙ 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 PIK3R4 gene.

• Inborn genetic diseases (29 variants)
• not provided (12 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PIK3R4 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	1	3
missense			31	2	3	36
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region					1	1
non coding					1	1
Total	0	0	31	4	5

Variants in PIK3R4

This is a list of pathogenic ClinVar variants found in the PIK3R4 region.

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

Position	Type	Phenotype	Significance	ClinVar
3-130679332-C-T		not specified	Uncertain significance (May 16, 2022)
3-130679353-T-C		not specified	Uncertain significance (May 27, 2022)
3-130679418-G-A		not specified	Uncertain significance (Nov 28, 2023)
3-130680647-T-C		not specified	Uncertain significance (Nov 07, 2022)
3-130680701-G-C			Uncertain significance (Jan 01, 2023)
3-130680708-C-A		not specified	Uncertain significance (Dec 14, 2021)
3-130681528-A-C			Uncertain significance (Dec 17, 2021)
3-130681584-C-A		not specified	Uncertain significance (Aug 02, 2021)
3-130684266-C-A		not specified	Uncertain significance (Dec 28, 2023)
3-130684280-G-A		not specified	Uncertain significance (Nov 15, 2023)
3-130684283-T-C		not specified	Uncertain significance (Jun 23, 2023)
3-130686267-T-A		not specified	Uncertain significance (Oct 20, 2023)
3-130686282-A-G		not specified	Uncertain significance (Jun 12, 2023)
3-130686388-C-T		not specified	Uncertain significance (Sep 22, 2022)
3-130686401-G-A			Likely benign (Oct 10, 2018)
3-130690557-C-G		not specified	Uncertain significance (Nov 03, 2023)
3-130690589-T-A		not specified	Uncertain significance (Nov 08, 2022)
3-130690595-C-A		not specified	Uncertain significance (Apr 15, 2022)
3-130690650-T-C			Benign (Nov 05, 2018)
3-130703748-T-A			Likely benign (Dec 31, 2019)
3-130703796-C-T		not specified	Uncertain significance (Jul 14, 2021)
3-130703835-C-T		not specified	Uncertain significance (Jan 19, 2022)
3-130703882-C-T		not specified	Uncertain significance (Jan 08, 2024)
3-130705564-G-T		not specified	Uncertain significance (Jun 13, 2023)
3-130705638-C-T		not specified	Uncertain significance (Aug 02, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PIK3R4	protein_coding	protein_coding	ENST00000356763	19	67895

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0245	0.975	125711	0	37	125748	0.000147

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.48	548	737	0.743	0.0000391	8953
Missense in Polyphen		149	258.04	0.57743		3052
Synonymous	0.172	254	258	0.986	0.0000134	2624
Loss of Function	5.43	16	62.3	0.257	0.00000344	729

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000334	0.000272
Ashkenazi Jewish	0.0000993	0.0000992
East Asian	0.000109	0.000109
Finnish	0.000139	0.000139
European (Non-Finnish)	0.000187	0.000185
Middle Eastern	0.000109	0.000109
South Asian	0.000135	0.000131
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Regulatory 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 cytokinesis, probably in the context of PI3KC3-C2 (PubMed:20643123). {ECO:0000269|PubMed:20643123}.
• Pathway: Autophagy - animal - Homo sapiens (human);Autophagy - other - Homo sapiens (human);Apelin signaling pathway - Homo sapiens (human);Phosphatidylinositol Phosphate Metabolism;Joubert syndrome;Inositol Metabolism;Angiopoietin Like Protein 8 Regulatory Pathway;Focal Adhesion-PI3K-Akt-mTOR-signaling pathway;Insulin Signaling;Regulation of Actin Cytoskeleton;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;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;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)

Intolerance Scores

• loftool: 0.548
• rvis_EVS: -1.13
• rvis_percentile_EVS: 6.56

Haploinsufficiency Scores

• pHI: 0.861
• hipred: Y
• hipred_score: 0.624
• ghis: 0.636

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.964

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Pik3r4
• Phenotype: immune system phenotype; normal 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); cellular phenotype; homeostasis/metabolism phenotype; muscle phenotype

Zebrafish Information Network

• Gene name: pik3r4
• Affected structure: whole organism
• Phenotype tag: abnormal
• Phenotype quality: curved

Gene ontology

• Biological process: protein phosphorylation;protein targeting to vacuole;macroautophagy;autophagy of peroxisome;regulation of cytokinesis;receptor catabolic process;toll-like receptor 9 signaling pathway;phosphatidylinositol-3-phosphate biosynthetic process;cellular response to glucose starvation;positive regulation of phosphatidylinositol 3-kinase activity;late endosome to vacuole transport
• Cellular component: late endosome;autophagosome;cytosol;axoneme;microtubule cytoskeleton;membrane;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;intracellular membrane-bounded organelle;nucleus-vacuole junction
• Molecular function: protein kinase activity;protein serine/threonine kinase activity;protein binding;ATP binding;1-phosphatidylinositol-3-kinase activity