PIK3R4
protein-codingphosphoinositide-3-kinase regulatory subunit 4, the group of WD repeat domain containing|PIK3C3 complex subunits|Armadillo like helical domain containing
Gene summary
Predicted to enable protein serine/threonine kinase activity. Involved in several processes, including autophagosome maturation; early endosome to late endosome transport; and phosphatidylinositol 3-kinase/protein kinase B signal transduction. Located in late endosome. [provided by Alliance of Genome Resources, Jun 2026]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~67.9 kbGenCC 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 PIK3R4 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_014602.3. 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 | 1 | 3 | |||
| missense | 161 | 3 | 3 | 167 | ||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 6 | 6 | ||||
| Total | 0 | 0 | 168 | 5 | 4 | 177 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_055417.1 | 19 | MANE Select | |
| Ensembl | ENSP00000349205.3 | 19 | MANE Select | |
| Ensembl | ENSP00000424274.1 | 3 | Standard | |
| Ensembl | ENSP00000427302.1 | 4 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| pik3r4 | Danio rerio | Structure: whole organism Quality: curved abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Autophagy - animal - Homo sapiens (human)
- Autophagy - other - Homo sapiens (human)
- Apelin signaling pathway - Homo sapiens (human)
- Phosphatidylinositol Phosphate Metabolism
- Joubert syndrome
Biological Process
- protein phosphorylation
- protein targeting to vacuole
- macroautophagy
- autophagy of peroxisome
- regulation of cytokinesis
Molecular Function
- protein kinase activity
- protein serine/threonine kinase activity
- protein binding
- ATP binding
- 1-phosphatidylinositol-3-kinase activity
Cellular Component
- late endosome
- autophagosome
- cytosol
- axoneme
- microtubule cytoskeleton
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000356763
- Coding exons
- 19
- Length
- 67895
- Individuals with no LoFs
- 125711
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 37
- Defined
- 125748
- p
- 0.000147
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 2.48 | 548 | 737 | 0.743 | 0.0000391 | 8953 |
| Missense (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 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00018 | 0.00012 | rare |
| Latino/Admixed American | 0.00015 | 0.00012 | rare |
| Ashkenazi Jewish | 0.000099 | 0.000099 | rare |
| East Asian | 0.00011 | 0.00011 | rare |
| Finnish | 0.00014 | 0.00014 | rare |
| European (Non-Finnish) | 0.00019 | 0.00018 | rare |
| South Asian | 0.00014 | 0.00013 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- 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}.;
Intolerance Scores
- LoFtool
- 0.548
- RVIS EVS
- -1.13
- RVIS percentile EVS
- 6.56
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- S
- Essential (gene trap)
- E
- Indispensability pred.
- E
- Indispensability score
- 0.964
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |