PIK3C3

protein-coding

phosphatidylinositol 3-kinase catalytic subunit type 3, the group of Phosphatidylinositol 3-kinase subunits|PIK3C3 complex subunits

Gene summary

Enables 1-phosphatidylinositol-3-kinase activity. Involved in several processes, including early endosome to late endosome transport; macroautophagy; and positive regulation of natural killer cell mediated cytotoxicity. Acts upstream of or within autophagy and positive regulation of protein lipidation. Located in autolysosome; late endosome; and midbody. Is active in plasma membrane. [provided by Alliance of Genome Resources, Jun 2026]

MANE transcript

NM_002647.4

Inheritance

—

ClinVar variants

U:81B:4

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.48

Max pathogenic AF

—

Genomic locus

chr18:41,955,234-42,087,830

External References & Databases

Ensembl (ENSG00000078142)

Transcript & Mutation Effects

hg38 • Region Span ~132.6 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 PIK3C3 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 61

not providedTotal: 9

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_002647.4. 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			5 clinvar	1 clinvar	2 clinvar	8
missense			69 clinvar	1 clinvar		70
nonsense						0
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)			6 clinvar			6
Total	0	0	81	2	2	85

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 51 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_002647.4	RefSeq	NP_002638.2	25	MANE Select
ENST00000262039.9	Ensembl	ENSP00000262039.3	25	MANE Select
NM_001308020.2	RefSeq	NP_001294949.1	24	Standard
ENST00000398870.7	Ensembl	ENSP00000381845.2	24	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Kaposi,s sarcoma-associated herpesvirus infection - Homo sapiens (human)
Inositol phosphate metabolism - Homo sapiens (human)
Phagosome - Homo sapiens (human)
Autophagy - animal - Homo sapiens (human)
Autophagy - other - Homo sapiens (human)

Biological Process

autophagosome assembly
protein phosphorylation
protein lipidation
endocytosis
autophagy

Molecular Function

protein kinase activity
protein binding
ATP binding
kinase activity
1-phosphatidylinositol-3-kinase activity

Cellular Component

phagophore assembly site
cytoplasm
endosome
late endosome
peroxisome

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000262039
Coding exons: 25
Length: 132624
Individuals with no LoFs: 125684
Homozygous LoFs: 0
Heterozygous LoFs: 64
Defined: 125748
p: 0.000255

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.44	325	475	0.685	0.0000248	5846
Missense (PolyPhen)		95	178.03	0.53361		2162
Synonymous	-0.517	174	166	1.05	0.00000877	1597
Loss of Function	3.55	26	54.2	0.480	0.00000268	692

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00057	0.00055	rare
Latino/Admixed American	0.000030	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00039	0.00038	rare
Finnish	0.000093	0.000092	rare
European (Non-Finnish)	0.00029	0.00029	rare
South Asian	0.00030	0.00029	rare
Other	0.00051	0.00049	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Catalytic 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 required for the abcission step in cytokinesis, probably in the context of PI3KC3-C2 (PubMed:20643123, PubMed:20208530). Involved in the transport of lysosomal enzyme precursors to lysosomes. Required for transport from early to late endosomes (By similarity). {ECO:0000250|UniProtKB:O88763, ECO:0000269|PubMed:14617358, ECO:0000269|PubMed:20208530, ECO:0000269|PubMed:20643123, ECO:0000269|PubMed:7628435, ECO:0000305}.;

Recessive Scores

pRec: 0.487

Intolerance Scores

LoFtool: 0.481
RVIS EVS: -1.35
RVIS percentile EVS: 4.56

Essentials

Essential (CRISPR): E
Essential (CRISPR2): E
Essential (gene trap): E
Indispensability pred.: E
Indispensability score: 0.999

Gene Damage Prediction

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